International Journal of Research in Pharmaceutical and Biomedical SciencesISSN: 2229-3701 __________________________________________Review Paper Jiao Gu Lan (Gynostemma pentaphyllum): The Chinese Rasayan- Current Research Scenario R. N. Mishra*, Dharnidhar Joshi Sagar Institute of Pharmaceutical Sciences, Sagar (M.P.) India- 470228 ABSTRACT Jiaogulan (Gynostemma Pentaphyllum) is age old herb in traditional Chinese herbology. It has been widely researched. It is true Rasayan (Rejuvenator / Antiaging ) herb as it is immunomodulator, adaptogen, antioxidant, anti-cancer, neuroprotective, nootropic and hepatoprotective. The only one Rasayan therapeutic activity about which there was no research reference is aphrodisiac. Key words Jiaogulan, Gynostemma Pentaphyllum, Rasayan, Anti aging, Anti oxidant, Immunomodulator INTRODUCTION The Rasayan branch of Ayurveda deals specifically with and Rasayan herbs and formulations that bestows upon the user, the longevity with age stabilization and retaining youth for longer.1 Order: Cucurbitales Family: Cucurbitaceae Subfamily: Zanonioideae Gomphogyninae Genus: Gynostemma Species: G. pentaphyllum Subtribe: From the rasayan treatment, one attains longevity, memory, intelligence, freedom from disorders, youthful age, excellence of luster, complexion and voice, oratory, optimum strength of physique and sense organs, respectability and brilliance. It means the attaining the excellent Rasa etc. These antiaging attributes will also incorporate being Adaptogen, Antioxidant and Immunomodulator 1.2 Scientific Classification: Kingdom: Plantae 1.3 Names in different languages: Western languages such as English and German commonly refer to the plant as jiaogulan. Other names include.2 ___________________________________ *Address for correspondence: E-mail:
[email protected] Chinese: xiancao (仙草, literally "immortal grass"; more accurately "herb of immortality") English: five-leaf ginseng, poor man's ginseng, miracle grass, fairy herb, sweet tea vine, gospel herb, Southern Ginseng Japanese: amachazuru (kanji: 甘茶蔓; hiragana: あまちゃずる; literally 甘いamai=sweet, tasty 茶 cha=tea, 蔓 zuru=vine, creeping plant) Korean language: dungkulcha (덩굴차) or dolwe (돌외) Vol. 2(4) Oct - Dec 2011 www.ijrpbsonline.com 1483 International Journal of Research in Pharmaceutical and Biomedical Sciences Latin: Gynostemma pentaphyllum or Vitis pentaphyllum Taiwanese: sencauw Tay language: zan tong Thai: jiaogulan (เจียวกูหลาน) Vietnamese: giảo cổ lam or bổ đắng (bổ= nutritious, đắng=bitter) Portuguese: cipó-doce 1.4 Jiao gu lan in classical Chinese texts: Although jiaogulan grows in many Asian countries, there does not seem to be any early historical documentation in existence other than in China. Jiaogulan is pronounced “jow-goo-lan”. Gynostemma pentaphyllum is known as Jiaogulan (Chinese: 绞股蓝 "twisting-vine-orchid"3) in China. The plant was first described in 1406 CE by Zhu Xiao, who presented a description and sketch in the book Materia Medica for Famine as a survival food rather than a medicinal herb.4 The earliest record of jiaogulan's use as a drug comes from herbalist Li Shi-Zhen's book Compendium of Meteria Medica published in 1578, identifying jiaogulan for treating various ailments such as hematuria, edema in the pharynx and neck, tumors, and trauma. While Li Shi-Zhen had confused jiaogulan with an analogous herb Wulianmei, in 1848 Wu Qi-Jun rectified this confusion in Textual Investigation of Herbal Plants, which also added more information on medicinal usage.5 Jiaogulan’s traditional use has not been widespread in China. It was used as a folk herb in the local areas where it grew wild. Jiaogulan grows mostly in the mountainous regions of southern China, far from the central part of China, an area which has long been known as the “ancient domain of China”. This central area of China is where the classical system that we call traditional Chinese medicine (TCM) evolved. For this reason, jiaogulan is not included in the standard pharmacopoeia of the TCM system, and therefore has not had as widespread use as TCM herbs. However, an experienced TCM practitioner in China has analyzed jiaogulan and described its qualities in terms of traditional Chinese medicine, as “sweet, slightly bitter, neutral, warm, enhancing ‘Yin’ and supporting ‘Yang’”, and suggested that “it would be used to increase the resistance to infection and for anti-inflammation.” Jiaogulan has been used by the people in the mountainous regions of Southern China as an energizing agent. They would take it as a tea before work to increase endurance and strength, and after work to relieve fatigue. It has also been taken for general health and has been recognized as a rejuvenating elixir. People also used it for treating common colds and other infectious diseases. Vol. 2(4) Oct - Dec 2011 ISSN: 2229-3701 Hence, the local Chinese people called jiaogulan, xiancao the “Immortality Herb,” and described it thus: “Like ginseng but better than ginseng.” Another story states that in a village near Fanjing Mountain in Guizhou province, the inhabitants would drink jiaogulan tea instead of the more common green tea and as a result many people there were living to 100 years of age. The modern history of jiaogulan: In 1972 the Research Group of Combined Traditional Chinese-Western Medicine of Qu Jing in Yunnan province did a study on the therapeutic effect of jiaogulan in 537 cases of chronic tracheobronchitis. This was the first report of medicinal usage of jiaogulan in modern Chinese medical literature.6Jiaogulan has since been included in the more recent Dictionary of Chinese Materia Medica, where it describes the traditional uses for jiaogulan as a medicine. There it is indicated for antiinflammation, detoxification, cough remedy, as an expectorant and as a chronic bronchitis remedy.7Other traditional uses as a medicine have been anecdotally said to be for heart palpitation and for fatigue syndromes. In Japan, jiaogulan is called Amachazuru8 “Amacha” means “sweet” in Japanese, referring to the sweet component prevalent in the plant, “cha” means tea, and “zuru” means “vine”. The name perfectly describes the jiaogulan plant, which grows as a climbing vine and produces a sweet tea from its leaves. Amachazuru has been recognized in Japan since the late 1970s, and its description and uses are included in the Japanese Colour Encyclopedia of Medicinal Herbs. Among other things, it is stated there: “Because of the sweet taste of the leaves, it has been used as a mountain vegetable” 9, similar to its use during the Ming Dynasty mentioned previously. Perhaps one of the more significant revelations about jiaogulan came about in Japan in the mid1970s. Previously unknown as a medicinal herb, jiaogulan’s discovery in Japan came about like many of the world’s great discoveries, partially through the hard labor of a dedicated scientist, and partially by accident. In the 1960s there was a trend amongst some research scientists to find an alternative sweetener to sugar. Although saccharin was in use for many years, they were still pursuing other sugar alternatives. In Japan, the government had prohibited the use of sodium cyclamate, a recently discovered artificial sweetener. Dr. Osama Tanaka, in the Dept. of Medicine of Hiroshima University, analyzing Amachzuru, found chemical compounds contained in amachazuru that are identical to some of the compounds found in Panax ginseng. He announced his findings at the twentywww.ijrpbsonline.com 1484 as well as a sugar alternative. Various pharmacological and therapeutic effects of jiaogulan were investigated and proven by tests on animals and human beings. nevertheless having been tested on mammals. and when mixed with water and shaken. This was borne out by subsequent studies on humans. From the time of the Qin Dynasty (221 B. Tsunematsu Takemoto. Jiaogulan would Vol. there was no further investigation of the herb for its sweetness. His interest of study was in a Chinese fruit. Shicuan and other southern provinces). and they have been continuing up to the present.ijrpbsonline. The plant is dioecious. sparked by the results of a nationwide population census taken in the 1970s. was seeking natural treatments for cancer and other ailments arising from stress. a melon of the Cucurbitaceae (cucumber or gourd) family. but their efforts were always fruitless.12 Upon analyzing the amachazuru himself. which they simply numbered 1-82. or amachazuru.19 Because of the significant results of the census taken in China during the 1970’s. 1. Surveys of the resources of jiaogulan in various portions of China have been made and cultivation techniques investigated. to enhance endurance. Throughout the 1980s. Perhaps. Although the Japanese findings were significant. an herb in the same family as the fruit he was studying and became very interested in studying it. whereas Panax ginseng has been found to have up to 28 saponins. Dr. In Panax ginseng the saponins are called ginsenosides. 2(4) Oct . they contain the same major components: saponins.13 Over the next ten years he and his group of researchers identified and named eighty-two saponins from amachazuru. Nearly 300 scientific papers on jiaogulan or its saponins have been published in respected journals. Another Japanese scientist. the research significantly slowed in Japan. whose specialty was herb medicine research.17 and a third showed the herb’s ability (adaptogenic) to prevent the unpleasant side effects of dexamethasone (hormone treatmen)18 These studies used mice as subjects. They saw that amachazuru increased the activity and strength of mice in a swimming test.11 He learned of the research being done with amachazuru. showing the herb’s ability to improve endurance. However.16 Another study on mice showed the herb’s effectiveness as a neoplasm or tumor inhibitor. perennial vine native to China.). in an apparently insignificant perennial weed. as well as provide many other healthpromoting benefits.com 1485 . interest in jiaogulan by Chinese researchers was growing rapidly. Takemoto. in studies. many research studies on jiaogulan were undertaken in China. but also for its medicinal uses. and because it was growing wild in the fields and mountains. the Emperors of ancient China would send various envoys overseas to search for the “elixir of life”. After death of Dr. a substance that has the unique quality of dissolving both in water and oil. While the plant grows abundantly and is harvested from the wild. The census revealed that. and information about the herb has been formally collected and published in the modern Dictionary of Chinese Materia Medica. Takemoto discovered that it contained four kinds of saponins exactly like those in Panax ginseng and seventeen other kinds of saponins very similar to those in Panax ginseng. Takemoto. at Hiroshima.International Journal of Research in Pharmaceutical and Biomedical Sciences third Meeting of the Japanese Society of Pharmacognosy in 1976. Dr. right in his native country. performed studies which isolated and identified eighty-two saponins. growing in their own homeland. It is reputed as the “precious fruit of longevity” and as a popular Chinese medicine. Cancer incidence was extremely low among the inhabitants as well. in small regions in the south central portion of China (some villages of Guangxi. the “elixir” has been found by descendants of the Emperors.18 Jiaogulan has been recognized and accepted by ever-increasing numbers of Chinese people. inhibit tumors and help protect the cellular immunity in humans. Dr. and then the boom of scientific interest in jiaogulan (amachazuru) in Japan during the 1980s. Since the compounds in amachazuru were found to be similar to those in Panax ginseng. an inexpensive and readily available health panacea.20. it carries male and female flowers on separate plants. Scientists from the Chinese Academy of Medical Science in Beijing and other institutions began to research these regions and discovered that the people living there were regularly drinking a tea made from the herb jiaogulan. in jiaogulan. Japan. Tonics and recipes made of jiaogulan have been developed and are being used in Chinese medical institutions. they were a significant marker for the herb’s possible effectiveness on humans. Takemoto thought that he had possibly found.14 Although these two plants are not related. it has been brought under cultivation and tissue culture has been achieved. along with his staff. Dr. they were only the beginning of the extensive research that would be done on amachazuru.8 Botany: Gynostemma pentaphyllum is a climbing.Dec 2011 ISSN: 2229-3701 prove. they are called gypenosides.10 As it turned out. 21. and parts of southeast Asia. that is.15 In 1984 they performed three experiments that began to demonstrate amachazuru’s many healthsupporting and medicinal qualities. botanical name Momordica grosvenori. will foam up. 22 www.C. high rates of people per capita were living to 100 years of age. known not only for its sweetness. Japan. which is considered unusual in plants. 27. Investigation as a potential sweetening agent stimulated chemical investigations in Japan. Those areas with unusual longevity (many people over 100) and low cancer rates all had only one thing in common. gypenoside 4 is identical to ginsenoside Rb3. have been isolated from the leaves.9 g/kg IP has also been reported. published studies to justify this dose are lacking. compressum Chen and Liang have yielded dammarane saponins related to the gypenosides. 36. 43 have also been identified. 2 DOSAGE The adaptogenic use of jiaogulan is standardized on an extract containing 85% gypenosides. and Vol. 32. four of the 85 saponins (called Gypenosides) in this herb are identical to those of Ginseng. however.23 1. They all drank Jiao gu Ian tea on a regular basis. It is an oriental medicinal herb for heat clearing. Control group received orally 10 ml kg(-1) day(-1). R3 = glucose. Specifically. rhamnose. LD50 for the oral route could not be determined. xylose).com 1486 .34 The content of saponins is comparable to that of ginseng roots. 1. and gypenoside 12 is identical to ginsenoside F2. Its properties are said to have been investigated when a Chinese census revealed a large number of elderly people in the province reported using the plant. Jiao gu Ian is an adaptogenic herb (normalizes body functions) and an antioxidant. 28. but about four times as concentrated. Many of the other gypenosides are closely related structurally to the ginsenosides and include the 6′-malonyl derivatives characteristic of ginseng. and Korea.5 Traditional properties and products: The jiaogulan plant has a history of folk use in the Guizhou province in China. 29 . gypenoside 8 is identical to ginsenoside Rd. 33 Several of these saponins are identical to those found in ginseng. 37. Today. Other constituents reported from Gynostemma pentaphyllum include sterols with the ergostane.8 g/kg IP. Others are converted into Ginseng saponins but other saponins are unique to this herb.41 and yixingensin42.1LD50 The LD50 in mice for the aqueous extract has been reported as 2.44 In fact. General Structure of Dammarane-Type Gypenosides. 30 . ombuoside.25. The related species G.45 3. detoxification and expectorant for relieving cough in southern China.ijrpbsonline. 2(4) Oct .46 A third study of two different extracts found an LD50 of 1 to 2 g/kg IP in mice.31.45 Another study found an oral LD50 of 49 g/kg for the crude extract with no organ toxicity at 4 g/kg daily for 90 days.Dec 2011 ISSN: 2229-3701 stigmastane skeletons. 38.35. Commercialization and scientific study of the leaves have been promoted by provincial Chinese authorities. with a daily dose of 60 to 180 mg gypenosides recommended.40 The flavonoid glycosides rutin. and the discovery that several ginseng saponins occur in the leaves has prompted aggressive promotion of the product as a substitute for ginseng. In the southern Chinese mountains where the herb grows it is preferred to Ginseng. The extract was orally www. 39 with several examples containing an acetylenic functionality.47 A rat LD50 of 1. Since the 16th century. gypenoside 3 is identical to ginsenoside Rb1. wide variation in the amount and nature of gypenosides has made production of a product standardized with specific gypenosides somewhat problematic. gypenosides 1-82. Thailand and Japan. cholestane. and is also available as an alcohol extract and in capsule or pill form. it is commonly used for a variety of ailments in China. However. The reasons for this variation have been investigated but have not been fully elucidated.24 Jiaogulan is most often consumed as an herbal tea. Jiaogulan has been referred to in Chinese medical texts and the herb of immortality. Ginseng has about 25 saponins.2Chronictoxicity: The effect of water extract of Gynostemma pentaphyllum was evaluated on 6-month chronic toxicity in Wistar rats. 3 TOXICITY / SAFETY 3. India. Chinese scientists surveyed demographics all over China to determine longevity and cancer rates. Most current products are standardized on total saponin content. principally by Takemoto's group. Gypenoside consists of both the hydrophobic sapogenin part and the hydrophilic sugar part in the molecule (where R1 and R2 = glucose. However.9 Chemical constituents: A large series of dammarane triterpene saponins. 26.International Journal of Research in Pharmaceutical and Biomedical Sciences Adulteration by Cayratia japonica has been noted. from agricultural areas. five days a week for 4 weeks. However. through T cell functions. Rats were divided into groups and treated with drinking water (control).49 3.com 1487 . 150. rate of special Ea-RFC formation and percentage of NK cell activity had been employed for the study as experimental indices. In addition. but these effects could not be found with the same Cd level contamination in GP herbal tea. however. GPH) G. This study indicated that high Cd contamination in drinking water alone had suppressive effects on T cell functions.05 mg/L).1. The aim of this study was to determine whether long-term oral administration of G. However. both GP-LCd. galacturonic acid (4. 0. After the treatments.50 4 PHARMACOLOGICAL AND CLINICAL PROPERTIES 4.006 mg/L).1Water-soluble polysaccharide from Gynostemma pentaphyllum herb tea (PSGP) was isolated by hot-water extraction and ethanol precipitation.2%). high CdCl2 in drinking water (HCd. reactive oxygen species.Dec 2011 ISSN: 2229-3701 preliminary immunomodulating activity of PSGP were investigated both in vitro and in vivo. both the normal healthy mice and the mice with immunity impairment due to Cyclophosphamide (Cy) management as experimental models.75 g/kg (low dose. Capillary zone electrophoresis analysis showed that PSGP was a typical nonstarch heteropolysaccharide. especially cadmium (Cd). The last group served as the recovery group. The chemical components and Vol. Weight of immune organs. The objective of this study is to evaluate the immunomodulatory effects of Cd contaminated in GP herbal tea and inorganic Cd on rat splenocytes.International Journal of Research in Pharmaceutical and Biomedical Sciences given to the five treatment groups at the doses of 6. pentaphyllum at the given doses did not produce any significant toxic effect in rats during 6-month period of the treatment. The cytokine levels or antibodies in BALF. The airway hyperresponsiveness (AHR) and eosinophilia in bronchoalveolar lavage fluid (BALF) were examined. It is evident that PSGP is a very important ingredient responsible for at least in part the immunomodulating activity of G.48 3.5 μg/mL PWM-induced B cell proliferation. jiaogulan does not show toxicity.006 mg/L Cd (GP-LCd) for 6 months. 750 and 750 mg kg(-1) day(-1) for 24 weeks. it is concluded that the extract of G.1%). Both high and low dose extracts reduced AHR. these parameters tended to decrease slightly in LCd. this herbal tea can be contaminated with some heavy metals. The results of the study exhibited: (1) The total saponin of Gynostemma pentaphylla could markedly act against the www. GP herbal tea containing 0. pentaphyllum attenuated airway inflammation in OVA-sensitized mice.1 Immunomodulation: 4. and glucuronic acid (1. and GP herbal tea containing 0.3 The specimen of the total saponin for this experimental study was extracted from Gynostemma pentaphylla growing in Suining county in Hunan province.51 4. HCd-treated rats had 4-fold higher Cd accumulations than GP-HCd-treated rats.9%). 2(4) Oct .3 Unlike most plants of the Cucurbitaceae family. rhamnose (7. 0. These results show that long-term orally administered G. serum OVA-IgE. pentaphyllum herb tea. Cd accumulation in organs and blood was detected by using a graphite furnace atomic absorption spectrophotometer. Cd accumulation in liver and kidney in the HCd group also increased significantly. and GP-HCd groups.ijrpbsonline. was also significantly inhibited by HCd as compared to the control group. pentaphyllum extract reduced allergic reactions in OVA-sensitized mice. Therefore.9%). with 1 μg/mL Con A and PHA-P. There were no significant changes in total leucocyte and lymphocyte counts. In spleen.5%). GPL) or 5 g/kg (high dose. which may affect human health.05 mg/L Cd (GP-HCd) for 4 months. xylose (3. while GP-HCd had no effects. The results showed that the extract did not produce any significant dose-related changes.and LCdtreated rats had a slight increase in Con Astimulated splenocyte proliferation. content of anti-SRBC hemolysin. arabinose (10. 30.7%).52 4.4 Gynostemma pentaphyllum Makino (GP) is a herbal tea widely grown in Southeast Asia.1.2%). This immunostimulating activity of PSGP was further demonstrated by its inhibition on the proliferation of human colon carcinoma HT-29 and SW-116 cells incubated with the supernatant of PSGP-stimulated macrophage culture. serum and spleen cell culture supernatants were also determined.2 Their previous report demonstrated that the oral administration of short-term high dose Gynostemma pentaphyllum extract (5 g/kg per day for 7days) decreased allergic reactions in ovalbumin (OVA)-sensitized mice. GP-LCd. and Th2-associated cytokine levels in spleen cell supernatants and BALF in OVAsensitized mice. PSGP could significantly stimulate peritoneal macrophages to release nitric oxide. The HCd group (ex vivo) significantly produced suppressive effects on T cell mitogen-induced splenocyte proliferation.1. and tumor necrosis factor-alpha in a dose-dependent manner. followed by galactose (18. with glucose being the main component monosaccharide (23.7%). pentaphyllum extract. low CdCl2 in drinking water (LCd. 0. OVA-sensitized mice were fed with 1. mannose (3. Mice were sensitized and challenged with normal saline or OVA. increasing mitochondrial enzyme activity in vascular www. After the treatment. The objective of this study is to evaluate the immunomodulatory effects of Cd contaminated in GP herbal tea and inorganic Cd on rat splenocytes. Furthermore. GP herbal tea containing 0. high CdCl 2 in drinking water (HCd.01).53 4. The extract was intraperitoneally injected into mice for 5 consecutive days. and GP herbal tea containing 0.006 mg/L Cd (GP-LCd) for 6 months.05 mg/L Cd (GP-HCd) for 4 months. Cd accumulation in organs and blood was detected by using a graphite furnace atomic absorption spectrophotometer.5 Gynostemma pentaphyllum Makino (GP) is a herbal tea widely grown in Southeast Asia. the injection of the extract enhanced the production of all antibodies from LPS-activated spleen cells. The above description indicates that the total saponin of Gynostemma pentaphylla is a better immunomodulator. This study indicated that high Cd contamination in drinking water alone had suppressive effects on T cell functions. However. The HCd group (ex vivo) significantly produced suppressive effects on T cell mitogen-induced splenocyte proliferation. saponins of Gynostemma pentaphyllum.61 4. was also significantly inhibited by HCd as compared to the control group. In addition. pentaphyllum total plant extracts on immune cells was evaluated in this study. this herbal tea can be contaminated with some heavy metals.6 An extract of Gynostemma inhibited the growth of a rectal adenocarcinoma cell line.2 Adaptogenic activity: 4. The production of antibodies from B cells or cytokines from T cells was determined mainly with ELISA.59 Gypenosides protected against cyclophosphamide-induced bone marrow and spermatozoal mutagenesis when given orally at 40 to 160 mg/kg to mice. more cytokines were secreted from Con A-stimulated splenocytes of G.and LCd-treated rats had a slight increase in Con A-stimulated splenocyte proliferation. which may affect human health. 58 Crude gypenosides also had activity versus S-180 cells both in vitro and in vivo.1. It was also found that GP protected biomembranes from oxidative injury by reversing the decreased membrane fluidity of liver microsomes and mitochondria. After the treatments. content of hemolysin. and GP-HCd groups.ijrpbsonline.006 mg/L).5 mug/mL PWM-induced B cell proliferation.05 mg/L).1 The action of gypenosides (GP.60 Similar treatments enhanced immune function in another report. 0. both GPLCd. HCd-treated rats had 4-fold higher Cd accumulations than GP-HCd-treated rats. 2(4) Oct .com 1488 . In addition to the serum levels. liver microsomes and vascular endothelial cells. Our results suggest that the extract of G. serum IgA and IgG1 were also increased when received the extract at the doses of 0. forming rate of EaRFC and unequivocally elevating NK cell activity. a Chinese medicinal herb) as an antioxidant was studied using various models of oxidant stress in phagocytes. Calu 1.54 4.57 Both callus and field grown Gynostemma increased the lifespan of mice bearing Ehrlich's ascites carcinoma. GP-LCd. especially cadmium (Cd). There were no significant changes in total leucocyte and lymphocyte counts. Rats were divided into groups and treated with drinking water (control). In Vol. showing a variant recovery in mice treated by Cy in weight of the immune organs.50 g/kg/day. and 592/9 carcinoma cells more potently (1 to 10 mg/L) than Hela and Colo 205 cells. (2) The total saponin showed a definite of bidirective immunomodulatory action in normal healthy mice.05 or 0. 0. Astragalus membranaceus etc. (3) The total saponin had actions to prevent from fatigue and to tolerate hypoxia under usual atmospheric pressure.4 Gynostemma pentaphyllum is a popular herbal tea in China and some Asian countries.International Journal of Research in Pharmaceutical and Biomedical Sciences immunity inhibition due to Cy management in the experimental animals. The modulatory function of G.Dec 2011 ISSN: 2229-3701 spleen. Moreover. serum IgM and IgG2a were significantly enhanced and showed dose-dependent effect.55 4. through T cell functions. these parameters tended to decrease slightly in LCd. seems to be like the actions of some Chinese drugs. from agricultural areas. however. pentaphyllumtreated mice. An increase of lipid peroxidation induced by Fe2+/cysteine. low CdCl 2 in drinking water (LCd.1. Cd accumulation in liver and kidney in the HCd group also increased significantly. ascorbate/NADPH or hydrogen peroxide in liver microsomes and vascular endothelial cells was inhibited by GP. while GP-HCd had no effects. with 1 mug/mL Con A and PHA-P.2. However.7 Cancer patients given jiaogulan granules after chemotherapy showed improved immune function by several endpoints.1. by significant difference in comparison with the Cy control groups (P less than 0. for example.56 while total gypenosides inhibited growth of A549. an effect attributed to immune enhancement. pentaphyllum might promote immune responses through the activation of T and B cells.1. The results show that GP decreased superoxide anion and hydrogen peroxide content in human neutrophils and diminished chemiluminescent oxidative burst triggered by zymosan in human monocytes and murine macrophages.01). recovering the immune indices to normal value from either originally lower or higher than the medium figure.62 4. Panax ginseng. but these effects could not be found with the same Cd level contamination in GP herbal tea. by significant difference in comparison with the Cy control groups (P less than 0.05-0.05-0. 0. 4. GP2 had the highest total saponin content of 132. SOD is one of the body‘s most important antioxidants and studies show that charting SOD levels in various animal species is a reliable indicator of their longevity. GP1 had the highest antiproliferative activity at 3.2 GP1 had the highest antiproliferative activity at 3. the immune system. saponin. and anti-inflammatory effects. pentaphyllum for improving human health.Dec 2011 ISSN: 2229-3701 dependently strong inhibition on IL-6 and Ptgs2 mRNA expression and weak inhibition on TNF-α mRNA expression.4. and flavonoid contents and in their rutin and quercetin concentrations.3 mg of gallic acid equiv/g in GP1 with 50% acetone as the extraction solvent. Rat microsome studies also have found similar effects for crude gypenosides. Trials in humans have shown that SOD levels returned to youthful levels after taking 20 mg of Gypenosides (active principle) daily for one month. 75% ethanol. and the greatest total phenolic content was 44. In addition. endothelial cell. and liver microsome systems.67 4. The 100% ethanol extracts also showed doseVol.3. Extracts (50% acetone. The results from this study will be used to promote the application of G. and other biological functions. antiproliferative.2 mg equiv/mL concentration in HT-29 human colon cancer cells. These extracts also differed in their scavenging capacity against DPPH and hydroxyl radicals. and enhanced tolerance to anoxia. pentaphyllum for improving human health.6 mg/g with 100% ethanol as the extraction solvent.3 mg of gallic acid equiv/g in GP1 with 50% acetone as the extraction solvent. T lymphocytes and natural killer cells and that it acts as a tumor inhibitor.70 4.3.3.3 Five Gynostemma pentaphyllum (GP) samples were investigated and compared for their chemical compositions and their antioxidant. Jiaogulan also has the remarkable property of increasing endogenous SOD (Superoxide Dismutase) in the body.5 Chen67 found an increased tolerance to fatigue in forced swimming and hanging models in mice. saponin.International Journal of Research in Pharmaceutical and Biomedical Sciences endothelial cells and decreasing intracellular lactate dehydrogenase leakage from these cells.1 An antioxidant effect of gypenosides was reported in phagocyte.68Further study by the same group69 explored these effects in vascular endothelial cells injured by hydrogen peroxide.5 mg of rutin equiv/g in GP4.2. 4. GP2 had the highest total saponin content of 132. The 100% ethanol extracts also showed dosedependently strong inhibition on IL-6 and Ptgs2 mRNA expression and weak inhibition on TNF-α mRNA expression. GP1 had the highest antiproliferative activity at 3.3 Antioxidant activity: 4.66 4.6 mg/g with 100% ethanol as the extraction solvent. and flavonoid contents and in their rutin and quercetin concentrations. The extensive antioxidant effect of GP may be valuable to the prevention and treatment of various diseases such as atherosclerosis.2. which is an herb reputed to help the body to maintain optimal homeostasis64 by balancing endocrine hormones.72 4. although they all showed significant radical scavenging capacity.74 www.4 Jiaogulan is also believed to be useful in combination with codonopsis for jet lag and altitude sickness.65 .74 4.3.ijrpbsonline. antiproliferative.4 Jiaogulan has been shown in tests to lower the amount of superoxide radical and hydrogen peroxide in certain white blood cells.com 1489 . and 100% ethanol) of the five GP samples (GP1-5) differed in their total phenolic.4Anticancer 4. improving stamina and endurance.62 4. In addition. Studies have found it increases the activities of macrophages. The highest level of total flavonoids was 63. These extracts also differed in their scavenging capacity against DPPH and hydroxyl radicals.71 4.5 mg of rutin equiv/g in GP4.2 mg equiv/mL concentration in HT-29 human colon cancer cells. which is a powerful endogenous cellular antioxidant. The results from this study will be used to promote the application of G.3.2.4. The highest level of total flavonoids was 63. although they all showed significant radical scavenging capacity. and 100% ethanol) of the five GP samples (GP1-5) differed in their total phenolic. liver disease and inflammation. along with potentiation of pentobarbital hypnosis. the nervous system. and the greatest total phenolic content was 44. 75% ethanol.2 Jiaogulan is known as an adaptogen.2 mg equiv/mL concentration in HT-29 human colon cancer cells.3 Adaptogenic effects include regulating blood pressure and the immune system.1 Cancer patients given jiaogulan granules after chemotherapy showed improved immune function by several endpoints.63 4. an excellent indicator of antioxidant activity.2. and anti-inflammatory effects.73 4.5 Five Gynostemma pentaphyllum (GP) samples were investigated and compared for their chemical compositions and their antioxidant.2 Jiaogulan has been found to increase superoxide dismutase (SOD). Extracts (50% acetone. 2(4) Oct . 2amino-3-methylimidazo 4.80 4. 2(4) Oct . was developed to evaluate their antiproliferative effects on the hepatoma cell Hep3B. 5-f. However. imidazole (GIu-P-2). 2'. wt/wt) was used to elute carotenoid with 2% ethanol in ethyl acetate and chlorophyll with 50% ethanol in acetone. and evaluate their antiproliferation effect on hepatoma cell Hep3B. 2-aminodipyrido 1. All these findings suggest that the apoptosis of PC-3 cells may proceed through the intrinsic mitochondria pathway. The western blot assay indicated Vol. with the cell cycle being arrested at G0/G1 phase for all the treatments. 2'. cyclin A and B. imidazole (Glu-P-1).and kaempferolglycosides. proapoptotic proteins Bad and Bax.with the IC50 being 39. pentaphyllum as raw material.3 both fractions induced an arrest of PC-3 cell cycle at both S and G2/M phase. followed by eluting flavonoids and saponins with ethanol-water (30:70.77 Crude gypenosides also had activity versus S-180 cells both in vitro and in vivo.ijrpbsonline. followed by HPLC-MS-MS analysis. pentaphyllum was extracted with ethanol. Additionally. Mutagenicity of aflatoxin B1 (AFB1).7 The hot water extract of the herbal tea.82 4. pyrene (Ba. and β-carotene as well as epoxy-containing carotenoids.4 A preparative column chromatographic method was developed to isolate flavonoids and saponins from Gynostemma pentaphyllum. 3-amino-1methyl-5H-pyrido 4.75 while total gypenosides inhibited growth of A549. v/v) and 100% ethanol. Additionally. 2-amino-6-methyldipyrido 1. with both early and late apoptotic cell population showing a dosedependent rise. in an open-column containing 5 g of Cosmosil 75C(18)-OPN. the inhibition effect followed a dose-dependent increase for all the sample treatments. 2-a: 3'. was not found to be mutagenic in Salmonella mutation assay with or without metabolic activation. with the standards rutin and ginsenoside Rb(3) being used for comparison.) Makino on prostate cancer cell PC-3.83 4. respectively. Gynostemma pentaphyllum Makino.International Journal of Research in Pharmaceutical and Biomedical Sciences 4. α-carotene.4. However.P) was inhibited by the extract of Gynostemma pentaphyllum Makino in a dosedependent manner. but no effect was found on the mutagenic activity of 2-(2-Furyl)-3-(5-nitro-2furyl) acrylamide (AF-2).3 An extract of Gynostemma inhibited the growth of a rectal adenocarcinoma cell line. quinoline (IQ) and Benzo a. For all treatments.4.76 Both callus and field grown Gynostemma increased the lifespan of mice bearing Ehrlich's ascites carcinoma. the extract had both DT-diaphorase inducing activity in the murine hepatoma (Hepa1c1c7) cell line and antimutagenic properties towards chemical-induced mutation in Salmonella typhimurium strains TA98 and TA100. 4-dimethyl5H-pyrido 4. with Hep3B cells undergoing necrosis or apoptosis. and 592/9 carcinoma cells more potently (1 to 10 mg/L) than Hela and Colo 205 cells.5 The objectives of this study were to investigate the antiproliferation and apoptosis mechanism of saponin and flavonoid fractions from Gynostemma pentaphyllum (Thunb. Calu 1. Both fractions were more effective against Hep3B cells than the standards rutin and ginsenoside Rb(3). respectively. Based on MTT assay. while the chlorophyll fraction consisted of chlorophylls a and b and their derivatives.3 and 33. the cell cycle was arrested in the G₀/G₁ phase. After high-performance liquid chromatography-mass spectrometry analysis. the saponin and flavonoid fraction were comparably effective in inhibiting growth of PC-3 cells. 3-b. while in saponin fraction. the carotenoid fraction was composed of all-trans. Both flavonoid and saponin fractions were isolated by a column chromatographic method with cosmosil 75C¬18OPN as adsorbent and elution solvents of ethanolwater (30:70. the extract enhanced the mutagenicity induced by 2- www. An open column containing 70 g of magnesium oxide-diatomaceous earth (1:2. The result of this study may be used as a basis for possible phytopreparations in the future with G. a traditional Chinese herb.4. The flavonoid fraction was mainly composed of quercetin.5. Initially the powdered G.4. as well as the anti-apoptotic proteins Bcl-2 and Bcl-xl.Dec 2011 ISSN: 2229-3701 that the incorporation of flavonoid or saponin fraction could modulate the expression of G2 and M checkpoint regulators. 2-amino-1. indole (Trp-P-2). 3-d.and cis-isomers of lutein. an effect attributed to immune enhancement. Both carotenoid and chlorophyll fractions as well as lutein and chlorophyll a standards at 50-100 μg/mL were effective against Hep3B cells with a dosedependent response with the following order: carotenoid fraction > chlorophyll fraction > lutein > chlorophyll a.6 A preparative column chromatographic method for isolation of carotenoids and chlorophylls from Gynostemma pentaphyllum. g/mL. and then subjected to HPLC-MS analysis.81 4. 2-a: 3'.78 Gypenosides protected against cyclophosphamide-induced bone marrow and spermatozoal mutagenesis when given orally at 40 to 160 mg/kg to mice.com 1490 . The expression of the caspase-3 and its activated downstream substrate effectors. a Chinese Medicinal herb.4. indole (Trp-P-1). 3-b. v/v) for the former and 100% ethanol for the latter. 3-d.79 Similar treatments enhanced immune function in another report. DFF45 and poly (ADP-ribose) polymerase-1 (PARP-1) was also increased and followed a dose-dependent manner. both ginsenoside Rb(3) and ginsenoside Rd dominated. The effects of Gyp were dose and time dependent. morphological changes.5 Neuroprotective activities: 4. However. and N-methyl-N-nitro-Nnitrosoguanidine (MNNG). and reduce the activation of inflammatory astrocytes. We used a rat model of chronic cerebral hypoperfusion to investigate the protective effects of GP on the cortex and hippocampal CA1 region and the underlying mechanisms for its inhibition of cognitive decline. the saponin extract derived from the Gynostemma pentaphyllum Makino. Experimental design. The results from comet assay revealed that the incubation of SAS cells with Gyp led to a longer DNA migration smear (comet tail) when compared with control and this effect was dose-dependent. decrease lipid peroxide products and oxidative DNA damage. The results from real-time PCR analysis indicated that treatment of SAS cells with 180 mug/ml of Gyp for 24 h led to a decrease in 14-3-3sigma. viability. In immature neural cells. reactive oxygen species (ROS) production. ATF6-α. respectively.85 4. -8. a Chinese medical plant.International Journal of Research in Pharmaceutical and Biomedical Sciences aminoanthracene (2AA). DNA-dependent serine/threonine protein kinase (DNAPK).86 4. and confocal laser microscopy was used to examine the translocation of proteins in cells.4. Antioxidative capability was measured biochemically. Gyp has been shown to induce cell cycle arrest and apoptosis in many human cancer cell lines. and stimulated release of cytochrome c. 4. DNA fragmentation.5. ataxia-telangiectasia and Rad3-related (ATR) and breast cancer gene 1 (BRCA1) mRNA expression. there is no available information to address the effects of Gyp on DNA damage and DNA repair-associated gene expression in human oral cancer cells.05). Rats receiving 200 mg/kg GP had better spatial learning and memory than saline-treated rats. Agglutinin receptors in the two groups were different significantly. a widely reputed medicinal plant in China. cell cycle distribution. GP may have therapeutic potential for the treatment of dementia induced by chronic cerebral hypoperfusion and further evaluation is warranted.4. The levels of GADD153. AIF (apoptosis-inducing factor). resulting in ER (endoplasmic reticular) stress in WEHI-3 cells. GRP78.87 Vol. and spatial learning and memory were assessed using the Morris water maze. glutamate cytotoxicity is known to be mediated by the inhibition of cystine uptake.5. we investigated whether Gyp induced DNA damage and DNA repair gene expression in human oral cancer SAS cells. intracellular Ca(2+) determination.Dec 2011 ISSN: 2229-3701 4. increased Ca(2+) levels. cell cycle distribution. Western blotting was used to examine levels of apoptosis-associated proteins. The depletion of GSH impairs www. However. Recently. Therefore.84 4. Activated astrocytes were assessed by immunohistochemical staining and western blotting with GFAP antibodies.9 Gypenosides (Gyp) are the major components of Gynostemma pentaphyllum Makino. Gyp increased levels of the proapoptotic protein Bax.89 4. 1023 Recipe is effective in treating hyperplasia. leading to depletion of intracellular glutathione (GSH). and induction of apoptosis in human oral cancer SAS cells and the determination of murine SAS xenograft model in vivo. caspase-3. Gyp promoted the production of reactive oxygen species. sub-G1 phase (apoptosis). and the level of mitochondrial membrane potential (ΔΨ(m)). Daily doses of 100 and 200 mg/kg GP were orally administered to adult male Sprague-Dawley rats for 61 days after inducing cerebral hypoperfusion experimentally. and Endo G (endonuclease G) from mitochondria. reduced levels of the antiapoptotic proteins Bcl-2. These observations may explain the cell death caused by Gyp in SAS cells. The levels of lipid peroxidation and oxidative DNA damage were assessed by immunohistochemical staining for 4hydroxynonenal and 8-hydroxy-2'-deoxyguanosine. and can prevent its cancer transformation. ataxia telangiectasia mutated (ATM). Taken together.10 The rate of cancer transformation in 1023 Recipe treated group was lower than that in the control group without treatment (P<0.com 1491 . The mechanism may be that 1023 Recipe can induce precancerous lesions to differentiate into normal tissues. and -9 activity.8 Gypenosides (Gyp) are the major components of Gynostemma pentaphyllum Makino.4. Flow cytometry was used to quantify the percentage of viable cells. Moreover.11 Gyp inhibited the growth of WEHI-3 cells. These effects were associated with the induction of G0/G1 arrest. and ATF4-α were increased by Gyp. and increased sub-G1 phase. 2(4) Oct .1 Gypenosides (GP).ijrpbsonline.2 Gypenosides (GPs) were tested for their ability to protect primary cultures of immature cortical cells against oxidative glutamate toxicity. GP 200 mg/kg/day were found to markedly enhance antioxidant abilities. has been reported to have some neuroprotective effects. p53. and induced the depolarization of the mitochondrial membrane potential. The authors investigated the effects of Gyp on cell morphology. Gyp induced DNA damage and inhibited DNA repair-associated gene expressions in human oral cancer SAS cells in vitro. Oral consumption of Gyp increased the survival rate of mice injected with WEHI-3 cells used as a mouse model of leukemia.4. GP 100 mg/kg had no significant effects. The results from flow cytometric assay indicated that Gyp-induced cytotoxic effects led to a decrease in the percentage of viable SAS cells. 3. TN-2 (10. p.0%.91 4.3 Oxidative injury has been implicated in the etiology of Parkinson's disease (PD). Furthermore. 2(4) Oct . have shown antioxidative effects in vitro. Gypenosides (GPs). which are saponins with various bioactivities. loss of tyrosine hydrolase (TH)-immunopositive neurons and degeneration of TH-immunopositive neurites.International Journal of Research in Pharmaceutical and Biomedical Sciences cellular antioxidant defenses resulting in oxidative stress and cell death. These results strongly indicate the possible therapeutic potential of GP as an antioxidant in PD.5. It was found that GPs pretreatment.2% to 67. The neuroprotective effect of GP may be attributed to increased antioxidation. leading to a decrease in glutamate-induced apoptosis. and 40 mg/kg. 82. we conclude that GPs protect cortical cells by multiple antioxidative actions via enhancing intracellular GSH. These results suggest that GP-EX might be helpful in the prevention of Parkinson's disease. GP-EX administration (10 and 30 mg/kg) also recovered the levels of dopamine. cotreatment or posttreatment significantly and dose-dependently attenuated MPP(+)-induced oxidative damage. GPs lowered the consumption of GSH through decreased accumulation of intracellular peroxides. GP-EX at the given doses did not produce any sign of toxicity such as weight loss.ijrpbsonline. The novel role of GPs implies their remarkable preventative and therapeutic potential in treatment of neurological diseases involving glutamate and oxidative stress.5.1%.2%.3%. the preventive effect of GPs was more potential than its therapeutical effect. an oral administration of herbal ethanol extracts from Gynostemma pentaphyllum (GP-EX) (10 mg/kg and 30 mg/kg) starting on day 3 post-lesion for 28 days markedly ameliorated the reduction of THimmunopositive neurons induced by 6hydroxydopamine-lesioned rat brain from 40.1% and 67. Thus. homovanillic acid and norepinephrine in postlesion striatum to 64. TN-2 inhibited memory and learning deficits in scopolamine treated mice in the passive avoidance test. and the protein expressions of brain-derived neurotrophic factor (BDNF). GPs was investigated for its neuroprotective effects on the 1-methyl-4phenylpyridinium ion (MPP(+))-induced oxidative injury of dopaminergic neurons in primary nigral culture. respectively.5 Oxidative injury has been implicated in the aetiology of Parkinson's disease (PD) and gypenosides (GP). as manifested by significantly increased glutathione content and enhanced superoxide dismutase activity in the substantia nigra.7%. loss of nigral dopaminergic neurons and motor dysfunction.5. the neuroprotective effect of GPs may be attributed to GPs-induced strengthened antioxidation as manifested by significantly increased glutathione content and enhanced activity of glutathione peroxidase. leading to an increase in the intracellular GSH content.4% and 75. Most importantly.90 4. catalyze and superoxide dismutase in nigral culture. and Morris water maze tests.o.8% in the substantia nigra. However. 20.92 4. 47. cAMP element binding protein (CREB).93 4.6 The memory-enhancing effects of TN-2 were evaluated using passive avoidance. reduction of dopamine uptake. 3.4 6-Hydroxydopamine administration for 28 days (8 microg/2 microL) reduced the number of tyrosine hydroxylase (TH)-immunopositive Vol. which resulted in oxidative stress. diarrhea and vomiting in rats during the 28 day treatment period and four gypenoside derivatives.9% and 89. Results show that GPs significantly upregulated mRNAs encoding gammaglutamylcysteine synthetase (gamma-GCS) and glutathione reductase (GR) and enhanced their activities for GSH synthesis as well as recycle. We found that pretreatment with GPs (100-400 microg/ml) significantly protected cells from glutamate-induced cell death. suppressing glutamate-induced cytosolic Ca(2+) elevation and blocking glutamate-induced apoptosis. gypenoside XLV and gypenoside LXXIV were identified from GP-EX. homovanillic acid and norepinephrine levels were reduced to 19.Dec 2011 ISSN: 2229-3701 neurons to 40. GPs were also found to prevent lipid peroxidation and reduce the influx of Ca(2+) which routinely follows glutamate oxidative challenge. 3. has various bioactivities. Y-maze. and p-CREB were determined by immunoblotting. gynosaponin TN-1. However. 77.2% of the control group. the saponins extract derived from the Gynostemma pentaphyllum. Acute administration of MPTP led to decreased glutathione content and reduced superoxide dismutase activity in the substantia nigra of the mice.2% in the substantia nigra compared to the intact contralateral side. The neuroprotective effects of GPs are specific for dopaminergic neurons and it may have therapeutic potential in the treatment of PD. Dopamine.1% and 65. gynosaponin TN-2. It was therefore of interest to investigate whether GPs protect cortical cells against glutamateinduced oxidative injury through preventing GSH depletion.4dihydroxyphenylacetic acid.6% and 90.4-dihydroxyphenylacetic acid.com 1492 . In this study.5.1% and 89. GPs treatment significantly blocked glutamate-induced decrease in levels of Bcl-2 and increase in Bax.4% in the striatum of 6hydroxydopamine-lesioned rats compared to the control group. Co-treatment with GP attenuated all the injuries induced by MPTP in a dose-dependent manner.6tetrahydropyridine (MPTP)-induced mouse model of PD.) significantly inhibited memory and learning deficits in the www.2. The present study was designed to evaluate the effect of GP on a 1-methyl-4-phenyl-1. and 88. 52. 1 g/kg P407 induced plasma triglyceride (25 fold). respectively) and total cholesterol levels (10% and 44%. family Cucurbitaceae).103 4. compared to 46% for ginseng and 93% for Indapamide (a hypertension medication).7.5 A second study in mice and rats given 200 mg/kg PO of the crude saponin demonstrated lower total cholesterol (TC) and VLDL but increased HDL/LDL.ijrpbsonline. with a 2-fold increase at ~10 μg/ml.6. Based on these findings.7 Preliminary studies indicate Gynostemma isolated triterpine glycosides lower cholesterol. a dose response was not demonstrated.6.2 In a double-blind study. 96% and 78%.96 4.05). a major constituent of GYNOSTEMMA PENTAPHYLLUM Makino (GP.101 4.4 Administration of an aqueous extract of the whole plant to rats in over 12 weeks resulted in a reduction in serum levels of total cholesterol and beta-lipoproteins. when combined with other herbs.3 Oral administration of a gynostemma decoction in combination with Nelumbo nucifera and Crataegus cuneata was found to lower triglycerides and cholesterol in rats and quail.6. Similar results were obtained with atorvastatin (75 mg/kg for 4 days). it reversed the P407 inhibition of LPL activity in a concentrationdependent manner. however.6 Cholesterol lowering activity (antihyperlipidemic): 4.6. G-74 potently reversed memory impairment caused by scopolamine. After acute (4 days) and chronic (12 days) oral administration the gypenoside extract (250 mg/kg) reduced triglyceride (53% and 85%. cholesterol and nitrite in acute hyperlipidemia.6 A clinical study of hyperlipoproteinemic subjects also found a decrease in TC with increased HDL/TC at a dose of 10 mg given 3 times daily for Vol.Dec 2011 ISSN: 2229-3701 30 days. and LDL while raising HDL levels. respectively). and exhibited significant memoryenhancing effects on the Y-maze test and the Morris water maze test.4 The hot water extract of Gynostemma pentaphyllum was found to activate platelet www. increasing heart stroke volume. G-74 might improve learning deficits. However. keeping blood pressure in a normal range. has beneficial effects on cardiovascular system.International Journal of Research in Pharmaceutical and Biomedical Sciences passive avoidance test by 40%. triglycerides. 102A study of 105 patients confirmed these effects.7. except that LDL cholesterol was reduced (17%) and HDL cholesterol increased.7.6.6.7 Gypenoside LXXIV (G-74). was isolated and its memoryenhancing effects were investigated in scopolamine-treated mice in passive-avoidance and Morris water maze tests. without affecting arterial pressure.95 4.94 4. and cardiac output while reducing the heart rate.7.1 Numerous clinical studies in Chinese medical literature have shown that jiagolan lowers serum cholesterol. 50% of lipoprotein lipase (LPL) plasma activity was inhibited by ~20 μM P407.99 4.The adaptogenic nature of gypenosides have been found lower hypertension and raise hypotension. No significant effects on LDL or HDL cholesterol were observed. Laboratory tests demonstrate that jiaogulan stimulates the release of nitric oxide. These studies examine anti-hyperlipidemic effects of gypenosides.05) and increased the scopolamine-shortened swimming time within the platform quadrant (p < 0. 108 4. high density lipoprotein cholesterol (HDL) (1.105 4. causing blood vessels to relax. coronary flow.5.97 4.107. with reported effectiveness rates ranging from 67% to 93%. The gypenosides reduced nitrite ~80%.106 4.com 1493 . total cholesterol (6 fold).100 4. 2(4) Oct .6 fold).6.5. TN-2 may ameliorate memory and learning deficits by activating the CREB-BDNF pathway. TN-2 also markedly increased BNDF expression and activated the transcription factor CREB in the hippocampi of scopolamine-treated mice. These studies demonstrate efficacy of Gynostemma pentaphyllum in lowering triglyceride.1 Blood pressure. low density lipoprotein cholesterol (LDL) (7 fold).2 Jiagolan lowers serum cholesterol. gypenosides administered to with Grade II hypertension showed 82% effectiveness in reducing hypertension.3 Cardiovascular functions: Animal studies as well as clinical testing on humans suggest that jiaogulan.104 4.98 4. Gynostemma had no effect on LL.7 Cardio and cerebrovascular effects: 4. The results suggest further investigations of Gynostemma gypenosides are warranted to examine the mechanisms of this activity.8 Experimental senility in mice induced by Dgalactose was attenuated by intraperitoneal (IP) injection of Gynostemma aqueous extract. G-74 also significantly shortened the scopolamineprolonged escape latencies in the Morris water maze test (p < 0. and nitrite (8 fold). this is one proposed mechanism by which jiaogulan reduces high blood pressure. respectively. animals were provided a standard AIN-76 diet (normal control) with rosiglitazone (0.8.7 mm glucose.com 1494 . or adverse effects regarding kidney and liver parameters or gastrointestinal function. and glycosylated hemoglobin (HbA(1C)) were measured before.International Journal of Research in Pharmaceutical and Biomedical Sciences aggregation.8. Dose-dependent insulin-releasing activities at 3. cholesterol-lowering. β-cell sensitivity to phanoside is higher at 16.0+/-1. 6 g daily.117 4. and reduced blood pressure while slightly increasing cardiac output. immunopotentiating. solid phase extraction/separation. We have shown by NMR and mass spectrometry that this active compound is a novel saponin. Interestingly. decrease coronary. a gypenoside. We have isolated one active compound by ethanol extraction. Phanoside is a dammarane-type saponin.-β-dglycopyranosyl(1→3). body measurements.5 Da.8 Antidiabetes activity: 4.8. The GPE and www.01%. has been reported to affect numerous activities resulting in antitumor. wt/wt).3 mm glucose.2 mmol/l in the control group (p<0. and several rounds of reverse phase high pressure liquid chromatography. which we have named phanoside (21. and safe approach.20-.2 It has shown potential as a hypoglycemic treatment to reduce blood glucose.7 mm glucose levels were determined for the racemic mixture containing all four stereoisomers. and peripheral blood vessel resistance.6+/-2. cortisol levels. and blood pressure were not different between the groups. and thereby provides a basis for a novel.7. Phanoside at 500 μm stimulates insulin release in vitro 10-fold at 3. pentaphyllum ethanol extract (GPE) of the plant leaves (0. We have also found that the stereoisomers are interconvertible. and after the treatment.Dec 2011 ISSN: 2229-3701 at 3.1+/-3.115 4. This study shows a prompt improvement of glycemia and insulin sensitivity. and hypoglycemic effects. a Southeast Asian herb.ijrpbsonline. phanoside (40 and 80 mg/ml) improved glucose tolerance and enhanced plasma insulin levels at hyperglycemia.6 In rabbits.109 4.4 The aim of the study was to investigate the antidiabetic effect of the traditional Vietnamese herb Gynostemma pentaphyllum in 24 drug-naïve type 2 diabetic patients.114 4. 2 μm glibenclamide stimulates insulin release only 2-fold.7 mm than Vol.116 4. distribution in nbutyl alcohol/water. using Gynostemma pentaphyllum tea. In addition. insulin levels.5 Gypenosides inhibited platelet aggregation in another study.8. containing standardized concentrations of gypenosides. wt/wt) or two different doses of G. After 12-week treatment. At these glucose levels. HbA(1C) levels after 12 weeks decreased approximately 2% units in the Gynostemma pentaphyllum group compared to 0. with a molecular mass of 914.21-trihydroxydammar-24-ene3-O-(α-d-rhamnopyranosyl(1→2). effective. and lower heart rate in dogs.3 and 16. Oral glucose tolerance tests were performed every four weeks. However. dilated blood vessels. The plasma insulin concentrations of the GPEsupplemented mice were significantly elevated compared to the control group.01). although insulin responses were significantly increased by phanoside below 125 μm only at high glucose levels. Change in Homeostasis Model Assessment-Insulin Resistance between baseline and twelfth week indicated that insulin resistance decreased significantly in the Gynostemma pentaphyllum group (-2.7.23-epoxy-.005%.7.8 Crude gypenosides protected against cerebral ischemic damage in a rabbit model. Also when given orally to rats.3β-. the blood glucose levels of the high-dose GPE. There were no hypoglycemias. 2(4) Oct .05). lipid profiles. to treat type 2 diabetic patients.3 mm glucose and potentiates the release almost 4-fold at 16. For 5 weeks.0025% and 0. increased stroke volume.7.5 This study was conducted to evaluate the antihyperglycemic effect of an extract of Gynostemma pentaphyllum Makino. Fasting plasma glucose.3) in the control group (p<0. antioxidant.8 mmol/l in the Gynostemma pentaphyllum tea group as compared to a decrease of 0. crude gypenosides decreased heart rate.2% unit in the controls (p<0.8.7 Purified gypenosides 5 and 10 were found to lower systolic and diastolic blood pressure. raise coronary flow.001). during twelve weeks and received information regarding diet and exercise.and rosiglitazone-supplemented groups were significantly lower than that of the control group. After the experimental period.111 4.3 Extracts from Gynostemma pentaphyllum Makino (Cucurbitaceae). in C57BL/KSJ-db/db mice. glucagon.0) compared with that (+1. each of which were found to stimulate insulin release from isolated rat pancreatic islets. fasting plasma glucose levels totally decreased to an extent of 3.1 Gynostemma pentaphyllum tea has been used in a Randomized Controlled Trial to treat type 2 diabetic patients.113 4.110 4.112 4. and four stereoisomers differing in configurations at positions 21 and 23 were identified. All patients were randomized to authenticated Gynostemma pentaphyllum tea or placebo tea. the active principle was not elucidated. during. brain.1+/-3.-β-d-lyxopyranoside)). 121 4. In this study. 2(4) Oct . the ratios of glucokinase/glucose-6-phosphatase activities in the high-dose GPE.1 In the present study. pH or acidity output. thus indicating a lack of anti-secretory effect. The results suggest further investigations of Gynostemma gypenosides are warranted to examine the mechanisms of this phytoprotective activity.9 GIT and kidney protection: 4.10 Hepatoprotective activity: 4. In the evaluation of effects on hepatic glucose metabolism. gastric wall mucus and hexosamine content were markedly preserved by GPB pretreatment. However.120 4. These results suggest that the supplementation of high-dose GPE (0. Our results suggest that A. Our previous studies showed that these crude drugs exert antiinflammatory activity and hepatoprotective activity against CC14-induced liver damage. gross necrosis in the centribular area. These studies demonstrate the efficacy of Gynostemma pentaphyllum in lowering gastrointestinal damage induced by indomethacin. pH or acidity output.119 4. In ethanol-induced ulcerated rats. kidney toxicity was evident after indomethacin and in animals pretreated with indomethacin plus G. sinusoidal congestion. In the renal system. significantly inhibited gastric ulcer formation induced by indomethacin. but not the intraperitoneal glucose tolerance test. hypertension and cancer in Taiwan. The present study was undertaken to evaluate a G.01%) in the diet lowers the blood glucose level by altering the hepatic glucose metabolic enzyme activities. Acute oral administration of the gypenoside extract (200 mg/kg) significantly reduced gastric and intestinal toxicity induced by indomethacin as measured by ulceration. HCl/EtOH and water-immersion restraint stress in rats.10. On acetaminophen-intoxicated model. caecal haemoglobin and plasma haptoglobin. In histological observation. The plant's principal saponin components are structurally similar to those found in ginseng plants and this similarity is assumed to be responsible for the claimed activities.9. Oral administration of the GPB at 200 and 400 Vol. formosanus and G.and rosiglitazone-supplemented groups were prominently higher than that of the control group.9. In pylorusligated rats. the phytoprotective effects of gypenosides from Gynostemma pentaphyllum throughout the gastrointestinal tract and kidney were examined in indomethacin-treated rats. In pylorus-ligated rats.Dec 2011 ISSN: 2229-3701 mg/kg body wt.9. pentaphyllum butanol fraction (GPB) for its anti-gastric ulcer activity using experimental models. HCl/EtOH and waterimmersion restraint stress in rats. The histology of the pancreatic islets revealed that the insulin-positive β-cell numbers were higher in the high-dose GPE. pentaphyllum then indomethacin. Oral administration of the GPB at 200 and 400 mg/kg body wt. The findings indicate that the butanol fraction of G.2 GIT protection: Gynostemma pentaphyllum is an oriental medicinal herb reputed to have broadspectrum activities. pentaphyllum-treated animals. pentaphyllum possesses gastroprotective potential related to the preservation of gastric mucus synthesis and secretion. The present study was undertaken to evaluate a G. pentaphyllum possesses gastroprotective potential related to the preservation of gastric mucus synthesis and secretion. pentaphyllum butanol fraction (GPB) for its antigastric ulcer activity using experimental models. pentaphyllum with an increase in urinary N-acetyl-betaglucosaminidase and a decrease in urinary sodium and chloride electrolyte output.3 Antigastric ulcer activity: Gynostemma pentaphyllum is an oriental medicinal herb reputed to have broad-spectrum activities. pretreatment with the GPB had no effect on gastric volume. pretreatment with the GPB had no effect on gastric volume. The plant's principal saponin components are structurally similar to those found in ginseng plants and this similarity is assumed to be responsible for the claimed activities.1 Anoectochilus formosanus Hay and Gynostemma pentaphyllum Makino are popular folk medicines that have been used for treating hepatitis. a significant increase in urinary microprotein in indomethacin-treated animals was not present in indomethacin plus G. In ethanol-induced ulcerated rats.ijrpbsonline. the antioxidant effect of these crude drugs and their hepatoprotective activity on acetaminophen-induced liver injury in rat was evaluated.com 1495 . The findings indicate that the butanol fraction of G. pentaphyllum do have antioxidant effects.and rosiglitazone-supplemented groups than in the control group. Indomethacin induced gastric and intestinal damage as well as renal toxicity after a single toxicological dose (10 mg/kg) in rats. A significant decrease in small intestinal lactose fermenting enterobacteria was evident in animals treated with indomethacin and those pre-treated with G.118 4. thus indicating a lack of anti-secretory effect. significantly inhibited gastric ulcer formation induced by indomethacin. gastric wall mucus and hexosamine content were markedly preserved by GPB pretreatment. infiltration of the lymphocytes and www. the increased levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) by acetaminophen administration were reduced by treatment with these two herbs.International Journal of Research in Pharmaceutical and Biomedical Sciences rosiglitazone treatments profoundly affected the intraperitoneal insulin tolerance test compared to the control group. Our results suggest that G. the effect of A. Methanol extract (100 and 300 mg/kg) and water extract (300 and 500 mg/kg) of A formosanus and water extract (100.13 Exercise induced fatigue: 4. pentaphyllum extracts might be beneficial for asthma airway inflammation through the suppression of Th2 activity.) caused a similar protective effect in both experimental models used.5. G. pentaphyllum extracts significantly attenuated airway hyperresponsiveness (AHR) and inhibited eosinophil infiltration in mice in both models. Th1-biased immune responses caused by G.7 mg kg(-1).1 The bronchodilatory activity of the aqueous extract of Gynostemma pentaphyllum Makino leaves was investigated in anaesthetized guineapigs and compared with two of its isolated gypenosides (III and VIII). the Vol. Forty-eight mice were studied by being divided into three group (n = 16 per group) included the normal control group (NC). a common herbal tea in China. the chemopreventive role of Gyp in human lung cancer (A549) cells in vitro was evaluated by studying the regulation of the cell cycle and apoptosis. caspase-3 and caspase-9. pentaphyllum (2.ijrpbsonline. In conclusion. 5 or 10 mg kg(-1)) decreased bronchial resistance in basal conditions and significantly (P < 0. 2(4) Oct . i.v. pentaphyllum is biphasic. pentaphyllum might have the potential to relieve asthmatic symptoms. Decreased Th2-type cytokines and increased IFN-gamma were detected in the cultures of OVA-activated splenocytes from treated mice. BALB/c mice were sensitized with intraperitoneal injection and challenged 3 times with OVA inhalation (IH) (the IH3 model). In this study.) and VIII (0. the low dose GGP group (LG) and the high dose GGP group (HG).122 4.1 The increasing incidence of asthma in developing countries emphasizes the importance of identifying more effective treatments that have low cost. This increase may be the major factor by which Gyp caused GO/G1 arrest in the examined cells.13. formosanus methanol extract resulted in serious hepatic injury. G. and loss of cell boundaries and ballooning degeneration were reduced with herbal treatment. Since the Th2 cytokines are the major mediators in the pathogenesis of asthma.124 4.) Makino (Cucurbitaceae).11. The GGP groups were first administered different doses of GGP (50 and 100 mg/kg). Investigation of the cyclin-dependent protein kinase inhibitors by Western blotting showed that p16. Serum OVA-specific antibodies were also reduced with the treatment. but down-regulation of the Bcl-2 levels. We hypothesized that oral administration of G.com 1496 .125 4. i.12 Allergy asthma: 4. pentaphyllum extracts might suppress Th2 cytokine-induced airway inflammation responses in ovalbumin (OVA)-sensitive mice. GGP may have beneficial www. Gypenosides III (0.12.123 4. has been used to treat lung inflammation. In the IH5 model. pentaphyllum was orally administered for 7 consecutive days before the end of the OVA challenge. The results showed that the intravenous administration of the decoction of G. Furthermore.3 mg kg(-1). However.2 Hepatoprotective and anticancer: Gynostemma pentaphyllum Makino is known in Asia for its effect on the treatment of hepatitis and cardiovascular diseases. however. This study confirmed the validity of the traditional use of this plant in the treatment of asthma and other respiratory disorders. Gyp appears to exert its anticancer properties by inducing GO/GI-phase arrest and apoptosis via activation of caspase-3 in human lung A549 cancer cells. 300 and 500 mg/kg) of G. the extract antagonized (80% inhibition) the bronchoconstrictor response induced by the antigen in sensitized guinea-pigs. Gypenosides (Gyp) are the major components extracted from Gynostemma pentaphyllum Makino. Flow cytometric assay and gel electrophoresis of DNA fragmentation also confirmed that Gyp induced apoptosis in the A549 cells.1 This study was designed to determine the effect of Gypenosides from Gynostemma Pentaphyllum (GGP) on exercise-induced fatigue in mice. The GGP groups showed a significant increase in swimming time to exhaustion as compared to the control group. formosanus and G. p27 and p53 proteins were increased with the increasing time of incubation with Gyp in the A549 cells. Blood lactate concentration of the GGP groups was significantly lower and blood glucose concentration of the GGP groups was significantly higher than that in the NC group. 2 more OVA challenges were administered to mimic the encounter with an allergen after drug treatment. Taken together. However.11 Bronchodilatory activity: 4.01) reduced (68% inhibition) the bronchoconstrictor action of histamine. the molecular mechanism underlying the Gyp-induced cell cycle arrest and apoptotic process is unclear. p21. Our data demonstrated that Gyp-induced apoptotic cell death was accompanied by upregulation of Bax. pentaphyllum enhanced the recovery of liver injury while treatment with 500 mg/kg of A. while the NC group were force administered 1% arboxymethylcellulose for 28 days.v.International Journal of Research in Pharmaceutical and Biomedical Sciences Kupffer cells around the hepatic central vein. Gyp induced GO/G1 arrest and apoptosis in the human lung cancer A549 cells. Gynostemma pentaphyllum (Thunb.10.Dec 2011 ISSN: 2229-3701 duration and the intensity of the action was less than that of the extract containing corresponding quantities of gypenosides III and VIII. "Investigation of the plant jiaogulan and its analogous herb. Jpn. “Studies of the constituents of Gynostemma pentaphyllum Makino. “Abstracts of Papers. effectively delay the lowering of glucose in the blood. 1998. et al. Paul. “Abstracts of Papers. 11. Shloka 7-8 2.-Amachazuru. CA: Torchlight Publishing. Dictionary of Chinese Materia Medica Vol2. Two glycosides of a novel dammarane alcohol from Gynostemma pentaphyllum. Structures of gypenosides. 8. Dictionary of Chinese materia Medica Vol 2. “Saponins of Gynostemma pentaphyllum as neoplasm inhibitors. Cheng JG et al (1990). Pharmacognosy of Gynostemma pentaphyllum and Cayratia japonica.com 1497 . Nagai. Shanghai Science and Technological Publishing House. ed. Takemoto. et al. Jialiu Liu (2003).” Yakugakuzasshi. Masahiro. Studies on the constituents of Cucurbitaceae plants. p. 3. Yutaka Nakano Shobo 1984. Bergner.” Kokai Tokkyo Koho. Arichi. March 4.1989 25. et al. 23. Nov.immortalitea. nootropic and hepatoprotective.” Kokai Tokkyo Koho. et al. 2005. Y. 1987. Wulianmei". Qu.ijrpbsonline. Takemoto T. Jing and combined research group of Traditional Chinese/Western Medicine. Chinese. The only one Rasayan therapeutic activity about which we did not get research reference is aphrodisiac. 1985. adaptogen. The Healing Power of Ginseng. Yutaka Nakano Shobo 1984. On the saponin constituents of Gynostemma www. Vol.http://www.Dec 2011 ISSN: 2229-3701 13. Blumert. Chinese. Jpn. 107 15. 1st. Michael. 17. CONCLUSION: Jiaogulan (Gynostemma Pentaphyllum) is true Rasayan (Rejuvenator / Antiaging ) herb as it is immunomodulator. Other Names for Jiaogulan. et al. Studies on the constituents of Gynostemma pentaphyllum Makino. Journal of Chinese Medicinal Materials. 103:173. 19. et al. Section 6 Chikitsasthanam. Wu. antioxidant. 22. 20. K. 1998 Chaukhambha Orientalia Varanasi.c om/othernames. Prima Publishing. pp. (ed). 60(105): 627.. 1985. 29(3):779–83 26.. Jpn.International Journal of Research in Pharmaceutical and Biomedical Sciences effects on exercise-induced fatigue. Health Before You Know It. 12. et al.2005. anti-cancer.Eng. et al. 24. Charak Samhita. 1983. Nov. Yakugaku Zasshi. I. (4):22–25. Takemoto. Jialiu Liu (2003). (2): 24 7. 1987. et al. 1983. 1976: 37. Shanghai. Tsunematsu. Chem Pharm Bull. 2(4) Oct .” Kokai Tokkyo Koho. Nagai. 4. Jpn. 27. 1989. et al. “Saponins of Gynostemma pentaphyllum as tonics. Blumert. “Studies on the constituents of Cucurbitaceae plants. Shanghai. 1983. “Prevention of glucocorticoid side effects by saponins of Gynostemma pentaphyllum. Jpn. Zhong Cao Yao 21 (9): 424. Color Encyclopedia of Medicinal Herbs. Yakugaku Zasshi. 9. 1972. Tsunematsu. 60(105): 626. Shigeru. 6.G. et al. et al. Jiaogulan: China's "Immortality" Herb. Michael. 1976: 37. Studies on the constituents of Gynostemma pentaphyllum Makino. Guangxi Ribao (Guangxi Daily Newspaper). Arichi. 14(6):335–36. 12. Shanghai Science and Technological Publishing House. Structures of gypenosides. et al. Health Before You Know It. 5. Wu. Chinese. XVIII. Jpn.Eng. “Study of the therapeutic effects of Chinese herb. Liu X.jiaogulan in 537 cases of chronic tracheo-bronchitis. Takemoto T. et al. I. Qtr 1. Arichi. Shigeru.” Zhong Chao Yao Tong Xun (Bulletin of Chinese Herbs and Medicines). 1996. Takemoto T. 12(6):8–10. p. I-XIV.126 5. Jiaogulan: China's "Immortality" Herb. Badger. Kazuo. 1981. CA: Torchlight Publishing. 1989. XVXXI. 103(10):1015–23. (ed).1088. neuroprotective. Yoshikawa.htm. Tissue culture and plantlet regeneration of Gynostemma pentaphyllum. 1985. Y. Zhang ZH. Jpn. Chinese. 21. On the Saponin constituents of Gynostemma pentaphyllum Makino (13)” Yakugaku Zasshi. Megalli et al. Badger.-Amachazuru. Jpn.” The 23rd Meeting of the Japanese Society of Pharmacognosy. China J Chinese Materia Medica. and prevent the increase in lactate. Zhongyaocai. pp. 21. As Jiaogulan REFERENCE 1. 1972. Wu M. Takemoto. 1088. Immoralitea.” The 23rd Meeting of the Japanese Society of Pharmacognosy. 18. XI.. Nagai M.G. pp 3-4. GGP Supplementation can extend the swimming time for the mice. Kuwahara et al. ed. Izawa. et al. 1st. 103(2): 173-185. Masahiro. 28. Shigeru. II. Structures of Gypenosides IXIV. Tsunematsu. Propagation of Gynostemma pentaphyllum by tissue culture. 1998: 458 10. 14. et al. Chapter 1. et al.. Yunnan. 107: 361-366 16.. 60(105): 625. et al. 1998. Gycomoside I: a new dammarane saponin from Gynostemma compressum. Rd. Studies on the constituents of Cucurbitaceae plants. Ruan Y. Yakugaku Zasshi.75(6):539-51 49. `Sumitra Suntararuks. 107(5):361. XIV. 1987. 2004 Sep. Yoshikawa K. Ding S. 24. Chinese Tradit Patent Med. Bansiddhi J. Yakugaku Zasshi. 35. Vol.9(11). et al. Yakugaku Zasshi. Choi HS. Liu X. Akihisa T. On the saponin constituents of Gynostemma pentaphyllum Makino. 2008. Luksamee Worasuttayangkurn. et al. a sterol from Gynostemma pentaphyllum. et al. 1989. 34. et al. Kim SH.. 1984. www. et al. 1989. Phytochemistry. 1987. Agric. 1986. Dammarance-type glycosides from Gynostemma pentaphyllum. 39. Akihisa T. 1990. On the saponin constituents of Gynostemma pentaphyllum Makino. Kuwahara M. 14α-dimethyl-5αergosta-7. 11(8):27–29. Akihisa T. Isolation and identification of flavonoids from Gynostemma yixingense. XV. 69-70. et al. Chronic toxicity of Gynostemma pentaphyllum. Liou CJ. Park MS. 2(4) Oct . Phytochemistry. Shen JJ.56(16):6905-9. pentaphyllum Makino. XVI. Antistress action of Gynostemma pentaphyllum. Phytochemistry. 1990 Feb.Isolation and characterization of immunostimulatory polysaccharide from an herb tea. XVII. Kuo ML. 2008 Aug 27. Zhiwu Xuebao. et al. pp 9305–9311 51.24(28)trien-3β-ol from Phaseolus vulgaris and Gynostemma pentaphyllum. 32. 1993. Chivapat S. 1986. 20(4):51–53. Mitrijit O. China J of Chinese Materia Medica. 47. 1994. Chen J. 1989. 29(5):1647–51. 33. 27(9):2931–33.com 1498 . 45. Zhao Y. 1997. 50. et al. Yukagaku. a sterol from Gynostemma pentaphyllum. 1989..28(4):1271–73. Epub 2008 Jul 18. Journal of New Chinese Medicine. Chinese Tradit Patent Med. 44(4):667.1989. Akihisa T. Food Chem. Yang Y. Yoshikawa K. 37(8):659– 62. 373. . 104(11):1155–62. Nuchanart Rangkadilok. Phadungpat S. et al. a new sterol from Gynostemma pentaphyllum. J Agric Food Chem. Zhang C. 1988. Studies on the constituents of Cucurbitaceae plants. 107(4):262–67. 37. "Neuroprotective effects of herbal ethanol extracts from Gynostemma pentaphyllum in the 6hydroxydopamine-lesioned rat model of Parkinson's disease" (PDF). Pharmacological studies on the total saponin of Gynostemma pentaphyllum from Guangxi. PMID:20558230 53. 24. Studies on the constituents of Cucurbitaceae plants. Planta Med. et al. 48.10(2):96-8. XII. Lee MK (2010). et al. et al. Fitoterapia. 54:606–10. Isolation and identification of flavonoids glycosides and organic acids from Gynostemma pentaphyllum. 1987. 1988.ijrpbsonline. 36. 46. 36(3):239. 1989. 42. 1984. Studies on the constituents of Cucurbitaceae plants. Studies on the constituents of Cucurbitaceae plants. Zhong Xi Yi Jie He Za Zhi.International Journal of Research in Pharmaceutical and Biomedical Sciences 29. 56 (19). et al. Attawish A. 44. On the saponin constituents of Gynostemma pentaphyllum Makino. 40. 52. Chaorai B. Yoshikawa K. Further evidence that marine sterols are not unique. Hu L.24–Dimethyl-5α-cholest8–en–3β-ol. Fang Z. Takemoto T. 37(1):135–39. 43. Long-term oral administration of Gynostemma pentaphyllum extract attenuates airway inflammation and Th2 cell activities in ovalbumin-sensitized mice. Yakugaku Zasshi. et al. and malonylgypenoside V. Chavalittumrong P. Huang WC. 14α-methyl-5α-ergosta9(11). Hwang BY. 106(9):758–63. Phytochemistry. 30. Takemoto T. et al. Molecules 15 (4): 2814–24. On the saponin constituents of Gynostemma pentaphyllum Makino. Si J. Sumontha Nookabkaew and Jutamaad Satayavivad. J.24(28)-dien-3β-ol. 1988.Dec 2011 ISSN: 2229-3701 41. 4α. et al. Dammarane saponins of Gynostemma pentaphyllum Makino and the isolation of malonylginsenosides-Rb1. 31. Isolation of acetylenic sterols from a higher plant. Yang X. OrgChem. 11(1):31–32. Akihisa T. Immunomodulatory action of the total saponin of Gynostemma pentaphylla. Yakugaku Zasshi. 26(8):2412–13. Akihisa T. Yang X. Xu L.. 106(8):664–70. Yang RC. Techadamrongsin Y. 14(11):676– 78. Chemical and pharmacological studies on Gynostemma pentaphyllum. (24R)-and (24S)-14αmethyl-5α-ergost-9(11)-en 3β-ols from Gynostemma pentaphyllum. 104(10):1043–49.24–Dimethyl-5αcholestan-3β-ol. et al. 38. Chem Pharm Bull. Lee CK. Phytochemistry. et al. Gynostemma pentaphyllum Makino. et al. Yakugaku Zasshi. Nattaporn Yoopan. Li R. On the saponin constituents of Gynostemma pentaphyllum Makino. Zhou H. et al. Modern Applied Pharmacy. and Anti-inflammatory Properties. et al. Nookabkaew S. Whent M. 63. J Agric Food Chem.International Journal of Research in Pharmaceutical and Biomedical Sciences 54. Liu W. Andrew Gamble. 77. Wang Y. Slavin M. Zhejiang Journal of Traditional Chinese Medicine. Phytother Res 1993. 65. Yu LL.. 58. 79. 80.. 1994. et al. Immunological effects of Gynostemma pentaphyllum in mice. Chemical Composition of Five Commercial Gynostemma pentaphyllum Samples and Their Radical Scavenging. Chen P.. Journal of Xi'an Medical University. 1993. Chinese Tradit Patent Med. 75. Lutterodt H.ijrpbsonline. Blackford J. 3rd Edition. Chinese Pharm Bull. Huang H. Zhao Y. Chinese Pharmacol Bull. 74. J Agric Food Chem. Worasuttayangkurn L. 1991. et al. Jin M. Lutterodt H. Wang Z. Effects of gypenosides on mutagenesis induced by cyclophosphamide in mice. Yu LL. 78. Suppression effects of gypenosides on cultured human carcinoma cells. Cancer Biother. Suntararuks S. vascular endothelial cells. 72. Immunological effects of Gynostemma pentaphyllum in mice.. Bensky. ISSN: 2229-3701 microsomes. Journal of Xi'an Medical University. 1992. Effects of extract of Gynostemma pentaphyllum on human rectal adenocarcinoma cell. Immunological effects of jiaogulan granule in 19 cancer patients. Protective effect of gypenosides against oxidative stress in phagocytes. 76. Steven Maimes (2007). Modern Applied Pharmacy.8(3):263-72 64. Whent M. Chemical Composition of Five Commercial Gynostemma pentaphyllum Samples and Their Radical Scavenging. Blackford J. 10(6):457–59 Tong K. Chen J. Chen P. Jiangsu Journal of Traditional Chinese Medicine. Erich Stöger (September 2004). David Winston. Drugs. et al. Dan. 8(3):263–272. 57. Chemical Composition of Five Commercial Gynostemma pentaphyllum Samples and Their Radical Scavenging. 15(4):346–48. Jiao L. 1994. (4):184–86. Tong K. 61. and liver Vol. Slavin M. and Anti-inflammatory Properties. Liu. Tumor. 10(6):246– 49. 1989. Liu H. et al. 2010 Oct 12. et al. Rangkadilok N. Slavin M. 8(5):286. 2007 May. Blackford J. Huang H. Effects of gypenosides on mutagenesis induced by cyclophosphamide in mice. 7(5):341–44. Zhao Y. 7(4):299–304. 24(10):449. Zhong Guo yi Yao Xue Bao 7 (2): 99. 2(4) Oct . et al. Zhao Y. 62. Wang S. et al.. Immunomodulatory effects of cadmium and Gynostemma pentaphyllum herbal tea on rat splenocyte proliferation.com". Yu LL. Chen P. Wang TT.com. et al. Lutterodt H.Extract of Gynostemma pentaphyllum enhanced the production of antibodies and cytokines in mice. Adaptogens: Herbs for Strength.. J Agric Food Chem. Inhibitory effect of Gynostemma pentaphyllum on Ehrlich's ascites carcinoma. Protective effect of gypenosides against oxidative stress in phagocytes. Huang H. Zhou H. Antistress action of Gynostemma pentaphyllum. et al. Li L. 1994. vascular endothelial cells and liver microsomes. Antiproliferative. 70. 10(6):246– 49.drugs. 60. Inhibitory effect of Gynostemma pentaphyllum on Ehrlich's ascites carcinoma. Wang TT. 15(4):346–48.56(19):930511 56. Wang J. 1989. http://www. et al. "Complete Jiaogulan information from Drugs. Chinese J Integrated Tradit Western Med. Yakugaku Zasshi. Stamina. 2008 Oct 8. et al. "Therapeutic effect of jiaogulan on leukopenia due to irradiation and chemotherapy".. Wang Y.Dec 2011 69. 1990. 1988.html 66. 2010 Oct 12 Xie Z. Effects of extract of Gynostemma pentaphyllum on human rectal adenocarcinoma cell. Tumor. Chinese J Integrated Tradit Western Med. Whent M.. 73. Cancer Biother. Suppression effects of gypenosides on cultured human carcinoma cells. Wang Y. Protection of vascular endothelial cells from hydrogen peroxide-induced oxidant injury by gypenosides saponins of Gynostemma pentaphyllum. Liu W. et al (1992). Wang S. Wang Z. Yoopan N. 9(2):49–52 Liu H. Jiangsu www. Eastland Press 67.127(5):889-96 55. 2010 Oct 12 Jin M. Liu W. Protective effects of gypenosides on rat hepatic lipid peroxidation and membrane fluidity damage: in vitro studies. 59. 1993 Fall. Li L. et al. J Agric Food Chem. Wang Y. 68.com 1499 . Antineoplastic action of gypenosides. et al. Lau BH. Xie Z.com/npp/jiaogulan.. and Anti-inflammatory Properties. 1992. Li L. Healing Arts Press. et al. Chinese Pharmacol Bull. et al. 11(1):31–32. Steven Clavey. 9(2):49–52. 10(6):457–59. 1988. Chinese Herbal Medicine: Materia Medica. 1989. Wang TT. Antineoplastic action of gypenosides. Xie Z. 71. and Stress Relief. Antiproliferative. Li L. Antiproliferative. Satayavivad J. 1990. 8(5):286. Wang S. 1994. Zhou H. 93. Gypenosides protect primary cultures of rat cortical cells against oxidative neurotoxicity.18(1):2-10.15(4):2814-24. Chueh FS. 10(5):4–6.. Chung JG. 2011 Sep 11. 85. 10(1):8–9.22(7):633-44 90. China Medical University.Antimutagenicity and DT-diaphorase inducing activity of Gynostemma pentaphyllum Makino extract. Lu KW. Kim DH. 96. Kuo HI.Gypenoside LXXIV ameliorates scopolamine-induced learning deficit in mice. Lin CL. Lu JF. Wang P. Lin LJ. Gao GD. Chinese Tradit Patent Med. Niu L. Kim SH. Lu KW. Wang XL. 11(5):29– 30. Effects of Gynostemma pentaphyllum extract on T-lymphocyte and lipid metabolism in rats. 2005 Aug. Gao GD. Yan ZQ. Lin JJ. Gao GD. Li WX. Xin H. Lin ML. J Med Invest. Kim HJ.2(4):281-4 Hsu HY. Zhao L. Lu KW. J Int Med Res. 82. Traditional Chinese medicine in treatment of hyperlipidaemia. 2010 May-Jun. Jia D. Lai TY. Chen BH. Deng JP. Brain Res Bull. et al.. 101. Chung JG. et al. 2010 Oct 30. 89. Chen B H.Dec 2011 ISSN: 2229-3701 activation. et al. Chen ZL. 2011 Apr 12. Effects of the total saponin of Gynostemma pentaphyllum on lipoproteins.. Cao W. Lu PJ. Chou ST. Kongtawelert P. Weng JR. Vinitketkumnuen U. Wood WG. Jiaogulan: China's "Immortality" Herb. Yu CS. 99. Gao L. Chen XL. 97. Hwang BY. Lai TY. Michael. Behav Pharmacol. 2006 Aug 2. CA: Torchlight Publishing. Li WX.ijrpbsonline. Weng SW. Joh EH. Liu BL. Yang JS. Yi Z (May 1995). Neuroprotective effects of herbal ethanol extracts from Gynostemma pentaphyllum in the 6-hydroxydopaminelesioned rat model of Parkinson's disease. Ma YS. Preparation of carotenoids and chlorophylls from Gynostemma pentaphyllum (Thunb. Wang XL. Leechanachai P. Chinese Tradit Herbal Drugs.1102(1):163-74. Guangxi Med J. Antilipemic effect Gynostemma pentaphyllum in patients. Li J. Wu RS. Geng W. Wang JS. 95. 2010 Apr 16...38(3):1084-92. J Ethnopharmacol. Antiproliferation Effect and Apoptosis Mechanism of Prostate Cancer Cell PC-3 by Flavonoids and Saponins Prepared from Gynostemma pentaphyllum Tsai YC. J Ethnopharmacol. Journal of Traditional Chinese Medicine. Blumert. et al. Lin HY. Planta Med. Badger. Brain Res. p.. Lee CK. Chen BH. Lee MK. et al. Yang JW. Zhang GL. Weng SW. Guan YQ. Yang JH. Phytomedicine. Ma YS.International Journal of Research in Pharmaceutical and Biomedical Sciences 81. 88. Fujian Medical Journal. Hu X.24(3):287-91... Epub 2010 Oct 14 Kulwat C..52(3-4):145-50. 2004 Jul. 2(4) Oct . Chen SS. www. Integr Cancer Ther. J Med Food. Guo XD. Xong JR.134(3):1010-3. Chung JG. Guo XD. Preparative chromatography of flavonoids and saponins in Gynostemma pentaphyllum and their antiproliferation effect on hepatoma cell.. Gao L. Wu WB.Neuroprotective effect of gypenosides against oxidative injury in the substantia nigra of a mouse model of Parkinson's disease. In Vivo. J Ethnopharmacol 46 (2): 125–9. Wang X. Chen YY. "Traditional Chinese medicine in treatment of hyperlipidaemia". 98.. 1988.. Park MS. Ma LT. 2010 May. Liu J. 2011 Oct. 2010 Dec 15.Gypenosides Suppress Growth of Human Oral Cancer SAS Cells In Vitro and in a Murine Xenograft Model: The Role of Apoptosis Mediated by Caspase-Dependent and Caspase-Independent Pathways.. Zhao ZW.83(5):266-71 92. Effect of Chinese herbal medicine 1023 Recipe in blocking cancer transformation of experimental precancerous lesion and its mechanism. 20(4):172–73. Wu KC.. Choi HS. . Xu F. 84.. 100. Niu L. 83. . 87. 2010 May-Jun. la Cour B. Kim DH. Lertprasertsuke N. Zhu Q. Joh EH. Yang JS.J Agric Food Chem. Gypenosides causes DNA damage and inhibits expression of DNA repair genes of human oral cancer SAS cells.76(8):793-5. An experimental study on the antileukemia effects of gypenosides in vitro and in vivo. 94. Shang L. Gypenosides protects dopaminergic neurons in primary culture against MPP(+)-induced oxidative injury. 1989. Gao L.Gypenoside TN-2 ameliorates scopolamine-induced learning deficit in mice. Tsai YC. 2011 Jun 10. 86..) Makino and their antiproliferation effect on hepatoma cell. 1988. Hong SW.. 102.13(6):1431-42. 1989. Jia D..com 1500 . Zhong Xi Yi Jie He Xue Bao.. Anti-aging actions of Gynostemma pentaphyllum and its compound formula. Wang BH. 1995. 42. La Cour B. (4):184–86. 2010 Dec. Feng Y. 46:125–29. 1989. Taichung.Gypenosides improve cognitive impairment induced by chronic cerebral hypoperfusion in rats by suppressing oxidative stress and astrocytic Vol. Epub 2006 Jun 27 91. Chen JC. Tang NY.. Taiwan. Wang P. Molecules. Chen X. Epub 2010 Oct 30 Cheng TC. Jialiu Liu (2003). Mølgaard P. Chen JC. Yang JS. Chen JC. Dai H. Seon-Min Jeon. Hormone & Metabolic Research 42 (5): 353–7.. Phanoside. Lin HJ. Journal of Guiyang Medical College 18 (4): 261. 116. Myers PR (1999-10-03). 2010 May. 1985. Chen L. Hoa NK. Jiyoung Yeo. 2008. Palumbo DR. 110. Comparison between the effects of gypenosides and ginsenosides on cardiac function and hemodynamics in dogs.. December 2008. Bronchodilatory effects of the aqueous extract of Gynostemma pentaphyllum and gypenosides III and VIII in anaesthetized guinea-pigs. C. . Yeh CC. 2(4) Oct . Ostenson CG (April 2009).Chen. Amornlerdpison D. J Pharm Pharmaceut Sci 8(3):507-515. Phan DV. Liu KC. 108. 4(1):54–57. Zhou. Chiu TH. GH et al (1996). Ostenson CG (May 2010). Li Y.. Thang P. 121. Phytomedicine. Huang PC. Phytother Res. Kuo ML. 33(12):5568–71. LF et al (1990). et al.com 1501 .Antioxidant and hepatoprotective effects of Anoectochilus formosanus and Gynostemma pentaphyllum. "Comparison between the effects of gypenosieds and ginsegnosides on cardiac function and hemodynamics in dogs". Chem Pharm Bull. 112. D. www. 2000. Chung JG.21(6):523-30 120. Liou CJ. Zhou H. Phan DV. Treatment of hyperlipidemia with Gynostemma pentaphyllum Jiaogulan. 107. Fugen Aktan. Phan DV. et al. 11(4): 709-716. Steimle JA. 111. Lin CC.. Chinese J Pharmacol Toxicol. Chinese J Pharmacol Toxicol. Thang P.0148. from the Plant Gynostemma pentaphyllum. 123. Rujjanawate C. Hesse C. Yang RC.. Mi-Kyung Lee. Lin JM. Yang JS. Chinese J Pharmacol Toxicol 4 (1): 17–20. Basil D. Davies NM. Phytopreventative effects of Gynostemma pentaphyllum against acute Indomethacininduced gastrointestinal and renal toxicity in rats. Hans Jörnvall. Takagi J. Circosta C. Amornlerdpison. 2008 Mar-Apr. In Vivo. Huang WC. 1992. Guizhou Medical Journal 20: 19–26. Roufogalis BD. Roufogalis. et al. Gypenosides induced G0/G1 arrest via inhibition of cyclin E and induction of apoptosis via activation of caspases-3 and -9 in human lung cancer A549 cells. Shen JJ. 1990.A Novel Insulinreleasing Substance. J Pharm Pharmacol. Åke Norberg. 106.Gynostemma pentaphyllum decreases allergic reactions in a murine asthmatic model. Horm Metab Res.Antidiabetic effect of Gynostemma pentaphyllum tea in randomly assigned type 2 diabetic patients. The anti-gastric ulcer effect of Gynostemma pentaphyllum Makino. 118. Chen GW. Lu. Chen JC. doi:10. Am J Chin Med. et al. 22(2):215-21. Effects of total gypenosides on heart function and blood pressure of rabbits. Li ML. Hebok Song and Myung-Sook Choi. Huyen VT. Wang Z. De Pasquale R. 114. Neal M. 1991. 4(1):17–20. Hoa NK. Kanjanapothi. Rannar Sillard and Claes-Göran Östenson.. Epub 2010 Mar 8.Tanner MA. Thuan ND. Lu KW. Young-Jin Kang. A new platelet aggregation factor from Gynostemma pentaphyllum Makino. Ning-Ya et al (1993). D. Samer Megalli.ijrpbsonline. Acta Academiae Medicinae Shandong. Huyen VT.28(1):87-96. 115. Bu X. Wu J. Dao Van Phan∥. The anti-gastric ulcer effect of Gynostemma pentaphyllum Makino. and cAMP level in rabbits. "Comparative study on anti-hypertensive effect of Gypenosides. Protective effect of gypenoside on acute incomplete cerebral ischemia in rabbits. Phytopreventative Anti-Hyperlipidemic Effects Of Gynostemma Pentaphyllum In Rats. Chinese J Pharmacol Toxicol.57(8):1053-8 125. Hoa NK. Kanjanapothi D. Nitric Oxide 3 (5): 359–65. 2005 105.. "Screening of the hypoglycemic effect of eight Vietnamese Vol. Chen YS.42(5):353-7. Nguyen Khanh Hoa.2007. 6(3):204–06. 117. 113. Effects of gypenosides on platelet aggregation. Journal of Medicinal Food. 109. release. 8(5):259–60. 2004 Jul. 1990. Razmovski-Naumovski V. 104. Am J Chin Med.11(5):4315.36(3):579-92. "Antidiabetic effect of Gynostemma pentaphyllum tea in randomly assigned type 2 diabetic patients". Duke CC. et al. 2005 Aug. Un Ju Jung.Dec 2011 ISSN: 2229-3701 herbal drugs". 119. et al. Ginseng and Indapamide in patients with essential hypertension". Hunan Med J. Edvards Liepinsh.International Journal of Research in Pharmaceutical and Biomedical Sciences 103. 124. Davies. Rujjanawate .. Occhiuto F. Methods & Findings in Experimental & Clinical Pharmacology 31 (3): 165–9. 28(3):34–36. Available online 30 June 2004 122. Ostenson CG. 1990. "Effects of gypenosides-containing tonic on the pulmonary function in exercise workload". Lu HF. "The direct release of nitric oxide by gypenosides derived from the herb Gynostemma pentaphyllum". Nguyen Duy Thuan. 2007 Jun.1089/jmf. Dec 2011 www. 18 April. pp.com 1502 . 5(8). Ke-ji Tang2. Yong-jiang Ding1*. 2010 Vol.International Journal of Research in Pharmaceutical and Biomedical Sciences ISSN: 2229-3701 126. Feng-lin Li3 and Qing-lan Hu4. African Journal of Agricultural Research Vol. 707711.ijrpbsonline. 2(4) Oct . Effects of Gypenosides from Gynostemma pentaphyllum supplementation on exerciseinduced fatigue in mice.