Int. J. Mol. Sci. 2011, 12, 4550-4573; doi:10.3390/ijms12074550 OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 www.mdpi.com/journal/ijms Review Bioactivities from Marine Algae of the Genus Gracilaria Cynthia Layse F. de Almeida, Heloina de S. Falcão, Gedson R. de M. Lima, Camila de A. Montenegro, Narlize S. Lira, Petrônio F. de Athayde-Filho, Luis C. Rodrigues, Maria de Fátima V. de Souza, José M. Barbosa-Filho and Leônia M. Batista * Department of Pharmaceutical Sciences, Laboratory of Pharmaceutical Technology, Federal University of Paraiba, João Pessoa, PB 58051-900, Brazil; E-Mails:
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[email protected]; Tel.: +55-83-32167003; Fax: +55-83-32167502. Received: 16 May 2011; in revised form: 26 June 2011 / Accepted: 5 July 2011 / Published: 15 July 2011 Abstract: Seaweeds are an important source of bioactive metabolites for the pharmaceutical industry in drug development. Many of these compounds are used to treat diseases like cancer, acquired immune-deficiency syndrome (AIDS), inflammation, pain, arthritis, as well as viral, bacterial, and fungal infections. This paper offers a survey of the literature for Gracilaria algae extracts with biological activity, and identifies avenues for future research. Nineteen species of this genus that were tested for antibacterial, antiviral, antifungal, antihypertensive, cytotoxic, spermicidal, embriotoxic, and anti-inflammatory activities are cited from the 121 references consulted. Keywords: Gracilaria; macroalgae; seaweed; biological activity; natural product; review 1. Introduction The ocean environment contains over 80% of world’s plant and animal species [1] and with more than 150,000 seaweeds found in the intertidal zones and tropical waters of the oceans, it is a primary source of natural products [2]. Int. J. Mol. Sci. 2011, 12 4551 Seaweeds are floating and submerged plants of shallow marine meadows. They have salt tolerance because the osmolarity of cytoplasm is adjusted to match the osmolarity of the seawater so that desiccation does not occur. They lack true stems, roots and leaves; however, they possess a blade that is leaf like, a stipe that is stem like, and a holdfast that resembles roots like terrestrial plants. Seaweeds contain photosynthetic pigments and use sunlight to produce food and oxygen from carbon dioxide, and the water [3]. Marine macroalgae are important ecologically and commercially to many regions of the world, especially in Asian countries such as China, Japan and Korea [4]. They are a valuable food resource which contains low calories, and they are rich in vitamins, minerals, proteins, polysaccharides, steroids and dietary fibers [5–7]. Since as early as 3000 BC, they were also considered important as traditional remedies [4]. The Japanese and Chinese use brown algae in the treatment of hyperthyroidism and other glandular disorders [8–11]. The unsaturated lipids afford protection against cardiovascular pathogens [12]. Seaweeds have been one of the richest and most promising sources of bioactive primary and secondary metabolites [13] and their discovery has significantly expanded in the past three decades [4,14,15]. The algae synthetize a variety of compounds such as carotenoids, terpenoids, xanthophylls, chlorophyll, vitamins, saturated and polyunsaturated fatty acids, amino acids, acetogenins, antioxidants such as polyphenols, alkaloids, halogenated compounds and polysaccharides such as agar, carrageenan, proteoglycans, alginate, laminaran, rhamnan sulfate, galactosyl glycerol and fucoidan [16–25]. These compounds probably have diverse simultaneous functions for the seaweeds and can act as allelopathic, antimicrobial, antifouling, and herbivore deterrents, or as ultraviolet-screening agents [26]. They are also used by the pharmaceutical industry in drug development to treat diseases like cancer, acquired immune-deficiency syndrome (AIDS), inflammation, pain, arthritis, infection for virus, bacteria and fungus [27]. Currently, algae represent about 9% of biomedical compounds obtained from the sea [28]. Compounds with cytostatic, antiviral, antihelmintic, antifungal and antibacterial activities have been detected in green, brown and red algae [29,30]. The algae produce pure forms of the fatty acids found in human milk that appear to be building blocks for mental and visual development [31] and have been extensively screened for syntheses of new drugs [32,33]. During the 1970s, Ryther and collaborators evaluated numerous species of red, green and brown macroalgae for their potential growth rates and dry weight yields [34]. They demonstrated that the genus Gracilaria was the most attractive candidate because of its ability to achieve high yields and while producing commercially valuable extracts [35]. Gracilaria Greville genus (Gracilariales, Rhodophyta) is a macroalgae group with more than 300 species of which 160 have been accepted taxonomically. These are usually red, green or greenish brown with a three-phase cycle and can be found in tropical and subtropical seas [36,37]. The Gracilaria species are important for the industrial and biotechnological uses because they have phycocolloids, the main source of agar α-(1,4)-3,6-anhydro-L-galactose and β-(1,3)-D-galactose with little esterification in cell wall [2,38]. Among the carbohydrates, agar and other polysaccharides are present in G. confervoides [39], G. dura [40], G. chilensi and G. secundata [41,42]. 65]. So in this study we reviewed the literature related to bioactivities for Gracilaria algae. prostaglandin A2. antihypertensive. leukotriene B4 and phytol [61–63]. antioxidant. Mol. linoleic acid. asiatica reported the diterpenes cis and trans-phytol [63]. and the eicosanoids which are derivatives C20 polyunsaturated fatty acid (PUFA) metabolism through oxidative pathways that originate mainly from arachidonic acid and eicosapentaenoic acids. many researchers have focused on natural sources for new molecules with algae among the targets of these studies. and spasmolytic effects in gastrointestinal tract (Table 1).45]. cytotoxic. confervoides [64. Studies with G. G. longa [70]. andersoniana showed the following isolates: oleic acid. coronopifolia. coronopifolia respectively [50–52]. as well as G. dura [50]. gamma linolenic acid [58]. crassa [49. the precursors of prostaglandins (PGs) [44. known as “ogonori” poisoning in Japan [48]. longa [48. Lipids are abundant in this genus being mainly prostaglandins [49]. Other constituents are also containedin this genus such as proteins r-phycoerythrin from G.66]. poriferastene 8 [50]. 12 4552 These algae also produce important bioactive metabolites like the primary compound with antibiotic activity acrylic acid [43]. and polycavernoside A2 and A3 isolated from G.5-α:24(S)-ethyl [52]. asiatica [45]. The search for new effective medicines remains a challenge for scientists. with 49% of substances isolated from natural sources followed by semi-synthetic derivatives or synthesized molecules taking the structures of natural origin as models [29]. 5-dehydro avenasterol. longa also has a variety of compounds like alpha linolenic acid. .Int. Species such as G. spermicidal. For this reason the plants and their derivatives are major sources of all drugs. G. Results and Discussion In this review. cholestane-3-β-5-diol. polycavernoside B. Phytochemical studies with extracts from fresh thallus of G. myristic acid. According to Newman et al. cholesterol. antiprotozoa. antibacterial. poriferast-5-ene-3-β-7-β-diol [51] and poriferast-5-ene-3-β-7-α-diol [51] were identified in G. 3-beta-7-alpha-diol-poriferast-5-ene and 5-alpha-poriferast-9(11)-en-3-beta-ol are isolated from G. A variety of lactones are present in Gracilaria from the Pacific Ocean. salicornia [67] and G. PGF2 and 15-keto-PGE2 were respectively isolated from G. desmosterol and 5-alpha-24(S)-ethyl-cholestane-3-beta-6-beta-diol [60]. antifungal. Therefore around the world. steroids.47]. lichenoids and G. anti-inflammatory. verrucosa contains PGA2 that appears to be responsible for a gastrointestinal disorder. J. crassa and G. affecting about 30% of pharmaceutical market [71]. 877 new molecules were introduced into the market. longa [68]. between the years 1981 and 2002. only 19 of them had their extracts and fractions chemically tested for toxicity. polycavernoside B2. antiviral. such as cholesterol and clinoasterol are present in G. glycolipids [59]. analgesic. lichenoids contain PGE2 [46. among the 160 species of Gracilaria already identified taxonomically. 2. such as aplysiatoxin isolated from G. antiimplantation. Sci. (2003). asiatica and G. chilensis [69] and proteoglycan from G. gigartinine from G. fucosterol. 2011. prostaglandin E2. dura. Other steroids such as 3-beta-hydroxy-poriferast-5-en-7-one. The possibility of finding new molecules from natural products is immeasurable.53–57] and G. CHCl3 Ext.Agardh Gracilaria domingensis (Kützing) Sonder ex Dickie Gracilaria edulis (S.p. (1:1) EtOH-H2O Ext. J. organism.Int.G.2 mg/animal-i.2 µg/mL Result 4553 Inactive [72] Inactive [72] Active [48] Active [65] Active [73] Active [74] Active [49] Active [75] Active [76] Inactive [77] Equivocal [78] Equivocal [78] Inactive [78] . 95% EtOH Ext. dose or route of administration Cytotoxic activity-cell culture-10.-200 μg/mL Toxicity effect (death)-human adult-oral Toxicity assessment-mouse-DL50 0.p. Plant 90% EtOH Ext.Silva Part used FzDTh FTh Gracilaria chorda (Holmes) Gracilaria coronopifolia (J. Mol. CCl4 Ext. Botanical Name Studies of toxicity Gracilaria bursa-pastoris (S.Gmelin) P. 12 Table 1.C.G. Hexane Ext. 90% EtOH Ext. Bioassays models. Sci. or CHCl3 Ext.0 µg/mL Toxicity assessment-mouse-1. H2O Ext.2 µg/mL Cytotoxic activity-culture cell (LEUK P 388)-ED 50 32.Agardh) J. Bioactivities of marine algae of the Gracilaria genus. Plant 50% EtOH-H2O Ext.Gmelin) P.Silva Gracilaria foliifera (Forsskål) Borgesen Gracilaria textorii (Suringar) De Toni FsO FTh Th DO DTh SDTh DEP FzDO FsTh Type of extract H2O Ext.0 µg/mL Cytotoxic activity-cell culture-10. Agardh) Gracilaria corticata (J.825 mg/kg-i.C. Cytotoxic activity-cell culture-dose: dry weight of plant Cytotoxic activity-cell culture (CA 9 KB) Cytotoxic activity-culture cell (LEUK P 388)-ED 50 > 100 µg/mL Cytotoxic activity-culture cell (LEUK P 388)-ED 50 22. 2011. Toxic effect-human adult-oral Toxicity assessment-mouse-DL50 1000 mg/kg-ip Cytotoxity-Artemia salina L. MeOH Ext. Int.p. Sci. 90% EtOH Ext. Embryotoxic effect-pregnant rat-1. Cont. J. Botanical Name Gracilaria verrucosa (Hudson) Papenfuss Part used DO FzDO FO Type of extract H2O Ext.Agardh SDTh 90% EtOH Ext. Cytotoxic activity-cell culture (CA 9 KB) Cytotoxic activity-cell culture (CA 9 KB)-10.0 µg/mL Cytotoxic activity-cell culture (CA 9 KB)-1. MeOH Ext. H2O Ext. 12 Table 1.C. (1:1) CHCl3MeOH Ext.G.0 µg/mL Cytotoxic activity-cell culture (LEUK P 388-P 3)-10. Mol. and 95% EtOH Ext. DTh SDTh (1:1) MeOHCH2Cl2 Ext.Agardh SDTh Gracilaria edulis (S.0 % Inactive [80] Inactive [75] Inactive [75] .0 µg/µL Result Active [48] 4554 Inactive [77] Inactive [79] Equivocal [79] Inactive [72] FTh Effects on the nervous system Gracilaria corticata J. 2011. Bioassays models. Autonomic effects-dog-50 mg/kg-iv CNS effects-mouse Analgesic activity-mouse Anticonvulsant activity-mouse Autonomic effects-dog-50 mg/kg-iv CNS effects-mouse Analgesic activity-mouse Anticonvulsant activity-mouse CNS effects-mouse Inactive [75] Inactive [75] Inactive [75] Inactive [75] Inactive [75] Inactive [75] Inactive [75] Inactive [75] Inactive [75] Gracilaria verrucosa (Hudson) Papenfuss Contraception activity Gracilaria corticata J. 30% EtOH Ext.Gmelin) P.2 mg/animal-i.Silva SDTh 90% EtOH Ext. organism. dose or route of administration Toxicity assessment-mouse-1.0 mg/kg Spermicidal effect-rat-2.0 mg/kg-intragastric Antiimplantation effect-pregnant rat-100. 90% EtOH Ext. Gmelin) P. 12 Table 1. Bioassays models. EP H2O Ext.5 mg/animal-gastric intubation Active [48] Active [48] . Platelet aggregation inhibition (adenosine diphosphate.0% Result 4555 Inactive [75] Inactive [75] Inactive [75] SDTh 90% EtOH Ext. Mouse-0. DTh Polysaccharide fraction 90% EtOH Ext. Botanical Name Gracilaria edulis (S. Antiinflammatory activity-rat-intragastric Radical scavenging effect (DPPH radicals)-IC50 480.p.0 mg/animal-i.Int.0 µg Oxygen radical formation induction-mouse-4.0% Spermicidal effect-rat-2.0 mg/animal-i. MeOH Ext.C. Mol.p. dose or route of administration Antiimplantation effect-pregnant rat-100. Inactive [81] Inactive [81] Active [82] Active [82] Inactive [75] Active [83] Active [82] SDTh Antioxidant activity Gracilaria verrucosa (Hudson) Papenfuss Plant DTh Gastrointestinal effects Gracilaria chorda (Holmes) Gracilaria verrucosa (Hudson) Papenfuss FsO DO Mouse-0. Cont. Polysaccharide fraction H2O Ext.0 mg/kg Spermicidal effect-rat-2. 2011.0 mg/animal-i.Silva Gracilaria verrucosa (Hudson) Papenfuss Anti-inflammatory activity Gracilaria textorii (Suringar) De Toni Gracilaria verrucosa (Hudson) Papenfuss Part used SDTh Type of extract 90% EtOH Ext. organism.0 µg/mL Venotonic activity (platelet aggregating factor stimulation)-100. J.p.5 mg/loop-i. arachidonic acid or collagen stimulation)-100.0 µg/mL Immunostimulant activity-mouse-4. Sci.p. Phagocytosis stimulation-mouse-4.G. H2O Ext.5 mg/animal-gastric intubation and dose 0. Botanical Name Cardiovascular effects Gracilaria corticata (J.0 µg/mL Cyclic AMP phosphodiesterase inhibition Lipase inhibition Cyclic AMP phosphodiesterase inhibition Inactive [81] Inactive [77] Equivocal [88] Inactive [77] .G. 12 Table 1. 90% EtOH Ext. Rat-250 mg/kg – intragastric Rat-250. Mol. 90%EtOH Ext.Gmelin) P.G. MeOH Ext. or MeOH Ext. H2O Ext.Int. 90% EtOH Ext. Bioassays models.Agardh) J. CHCl3 Ext.Silva Anti-enzymes activity Gracilaria arcuata (Zanardini) Gracilaria corticata (J. EtOAc Ext. H2O Ext. SDTh SDTh 90% EtOH Ext. PET Ether Ext. dose or route of administration Cardiovascular effects-dog-50 mg/kg-iv Cardiovascular effects-dog-50 mg/kg-iv Diuretic activity-rat-intragastric Antihypertensive activity-rat-iv Antihypertensive activity-rat-iv Cardiovascular effects-dog-50 mg/kg-iv Result 4556 Inactive [75] Inactive [75] Active [75] Active [84] Active [85] Inactive [75] EP FsTh SDTh H2O Ext. organism.Agardh Gracilaria edulis (S.Agardh) J.Agardh Gracilaria textorii (Suringar) De Toni Gracilaria verrucosa (Hudson) Papenfuss Part used SDTh SDTh Type of extract 90% EtOH Ext.33 mg/mL Penicillinase inhibition-1.C. J.C. 2011.Gmelin) P. Cont.Silva Gracilaria lichenoides (Greville) Gracilaria verrucosa (Hudson) Papenfuss Hypoglycemic activity Gracilaria corticata J. Tyrosinase inhibition-0.. Sci.0 mg/kg – intragastric Inactive [75] Inactive [75] DTh DO EP FzDO FzDO MeOH Ext.0 µg/units Inactive [86] Inactive [87] Aldose reductase inhibition-10. MeOH Ext.Agardh Gracilaria edulis (S. C. Escherichia coli-MIC >200 µg/mL Active [89] Inactive [89] Gracilaria corticata (J. Pseudomonas aeruginosa. Shigella sonnei Agar plate-Bacillus subtilis.Agardh) J. CHCl3 Ext. 90% EtOH Ext.C.0 mg/mL Agar plate-Staphylococcus aureus. Agar plate-Staphylococcus aureus-5.Gmelin) P. Streptococcus pyogenes50.0 mg/kg-iv Result 4557 Inactive [75] Inactive [75] Inactive [75] SDTh SDTh 90% EtOH Ext. Salmonella paratyphi B. Botanical Name Respiratory effects Gracilaria corticata (J.G. dose or route of administration Respiratory depressant-dog-50 mg/kg-iv Respiratory depressant-dog-50 mg/kg-iv Respiratory depressant-dog-50.Int. 90% EtOH Ext. Agar plate-Escherichia coli. Spasmolytic activity-guinea pig Negative chronotropic effect-dog-50.0 mg/mL Agar plate-Proteus vulgaris. Escherichia coli. Aspergillus fumigates.G.Gmelin) P. Staphylococcus aureus. Inactive [90] SDTh 90% EtOH Ext. Salmonella paratyphi A. Streptococcus viridans Agar plate-Klebsiella pneumonia.Agardh) J. 90% EtOH Ext.Silva Antibacterial activity Gracilaria cervicornis (Turner) J. organism. MeOH Ext. Bacillus megaterium.0 mg/kg-iv Inactive [75] Inactive [75] DEP 95% EtOH Ext. Staphylococcus aureus. J. Mol.Agardh) J. 2011. Cont. Bioassays models. Escherichia coli.Agardh Part used SDTh SDTh SDTh Type of extract 90% EtOH Ext.. Streptococcus faecalis Inactive [91] Active [91] Inactive [75] . or MeOH Ext.Agardh Gracilaria edulis (S. Candida albicans.Agardh Gracilaria edulis (S. Sci.Silva Gracilaria verrucosa (Hudson) Papenfuss Spasmolytic activity Gracilaria corticata (J.Agardh DO FsO PET Ether Ext. 12 Table 1. Pseudomonas aeruginosa. Inactive [92] Active [92] Inactive [92] Active [92] Inactive [75] Inactive [91] Gracilaria edulis (S. Staphylococcus aureus. or EtOH Ext. 2011. MeOH Ext. Acetone Ext. Shigella sonnei. Bioassays models. Micrococcus imfimus. 90% EtOH Ext. Bacteriophage T 4. Staphylococcus aureus Agar plate-Escherichia coli. Staphylococcus aureus Agar plate-Mycobacterium smegmatis Agar plate -Staphylococcus aureus Agar plate-Streptococcus faecalis. 12 Table 1. Streptococcus viridans.0 µg/µL Antiphage activity-agar plate-Bacteriophage T 1. Mol. Pseudomonas aeruginosa.Int. Klebsiella pneumoniae Agar plate-Bacillus subtilis. or Acetone Ext. Active [91] Active [92] Inactive [92] Active [93] Inactive [93] Inactive [94] Inactive [95] Gracilaria verrucosa (Hudson) Papenfuss FTh Th . Staphylococcus aureus Agar plate-Mycobacterium smegmatis Agar plate-Escherichia coli. J.Gmelin) P.50 µg/mL Result Active [92] 4558 DO 95% EtOH Ext. Salmonella paratyphi B Agar plate-Bacillus megaterium Agar plate-Escherichia coli. Staphylococcus aureus. CHCl3 Ext. Botanical Name Gracilaria debilis (Forsskål) Borgesen Gracilaria domingensis (Kützing) Sonder ex Dickie Part used DO Type of extract 95% EtOH Ext. ** 70% EtOH Ext. Bacteriophage MS 2. Streptococcus faecalis. Staphylococcus aureus Agar plate-Mycobacterium smegmatis Agar plate-Escherichia coli.Silva Gracilaria pygmea (Borgesen) SDTh FsO Gracilaria sjoestedii (Kylin) Gracilaria tikvahiae McLachlan DO DEP 95% EtOH Ext. organism.G. or Ether Ext. dose or route of administration Agar plate-Escherichia coli. 95% EtOH Ext. Escherichia coli. Cont. Salmonella paratyphi A.C. Bacteriophage T 2. Bacteriophage T 7. Bacteriophage PHI-CHI 174-0. Pseudomonas atlantica-40. Sci. Pseudomonas aeruginosa Agar plate-Vibrio marinofulvis. G.05 mg/mL Cell culture-Ranikhet Virus Inactive [96] Equivocal [73] Inactive [73] Inactive [75] SDTh . Penicillium funiculosum Agar plate-Sporotrichum schenckii.Silva Gracilaria pygmea (Borgesen) Gracilaria sjoestedii (Kylin) Gracilaria tikvahiae McLachlan Antiviral activity Gracilaria bursa-pastoris (S. Candida albicans.Int. Botanical Name Antifungal activity Gracilaria corticata (J. CHCl3 Ext. and Acetone Ext.C. Candida albicans. 12 Table 1.05 mg/mL Cell culture-Ranikhet and Vaccinia Virus-0. Mol.Agardh Part used FsO SDTh Gracilaria debilis (Forsskål) Borgesen Gracilaria domingensis (Kützing) Sonder ex Dickie Gracilaria edulis (S.Gmelin) P. 90% EtOH Ext. Trichophyton mentagrophytes. Trichophyton mentagrophytes. Aspergillus fumigates Agar plate-Candida albicans Agar plate-Neurospora crassa Agar plate-Candida albicans. 2011. 90% EtOH Ext. Aspergillus fumigates Agar plate-Aspergillus niger. Alternaria solani. 90% EtOH Ext.Gmelin) P. Sci.Agardh DO Type of extract MeOH Ext. MeOH Ext. FzDTh Th Cell culture-Herpes simplex 1 and HIV Virus Cell culture-Semlicki-forest Virus-0.G. organism. 95% EtOH Ext. Neurospora crassa Agar plate-Candida albicans Agar plate-Sporotrichum schenckii.C.Silva Gracilaria corticata (J.Agardh) J. 95% EtOH Ext. dose or route of administration Agar plate-Aspergillus niger. and EtOH Ext. Cont. Fusarium solani.Agardh) J. ** 50% EtOH-H2O Ext. J. Penicillium funiculosum Agar plate-Candida albicans Agar plate-Neurospora crassa Agar plate-Candida albicans Result 4559 Inactive [91] Inactive [75] Active [92] Inactive [92] Active [92] Inactive [92] Inactive [75] Inactive [91] Active [92] Inactive [92] Active [93] DO SDTh FsO DO DEP 95% EtOH Ext. Bioassays models. Cryptococcun neoformans. Alternaria solani. Fusarium solani. Cryptococcus neoformans. Ether Ext. Gmelin) SDTh 90% EtOH Ext. EP = Entire plant. A. Agar plate-Helianthus tuberosus-dose: dry weight of plant Active [76] Greville Gracilaria foliifera (Forsskål) DEP H2O Ext. Plasmodium berghei Inactive [75] J. MeOH Ext. FO = Frozen organism.0 µg/mL Cell culture-Virus sindbis-200. 12 Table 1. MeOH Ext.Int. Agar plate-Entamoeba histolytica. . H2O Ext. DTh = Dried thallus. FTh = Frozen thallus. FzDO = Freeze dried organism. Agar plate-Helianthus tuberosus-dose: dry weight of plant Active [76] Borgesen Gracilaria verrucosa (Hudson) DEP 95% EtOH Ext. FzDTh = Freeze Dried thallus. ** = Not stated. Agar plate-Entamoeba histolytica. PET Ether). Inactive [77] Papenfuss Antiprotozoal activity Gracilaria corticata (J. dose or route of administration Cell culture-Semlicki-forest and Ranikhet Virus Cell culture-Herpes simplex 1 Virus-400. ** MeOH Ext.Silva Allelophatic activity Gracilaria compressa (C. J.C. Botanical Name Gracilaria edulis (S. Bioassays models. Agar plate-Helianthus tuberosus-dose: dry weight of plant Active [76] Papenfuss Legend: DEP = Dried entire plant.G. Th = Thallus.Agardh Gracilaria edulis (S. 2011. Cont. Abbott) Gracilaria species Gracilaria textorii (Suringar) De Toni Part used SDTh DO FzDTh FzDO Th Fresh Th FzDO Type of extract 90% EtOH Ext.Agardh) DEP 95% EtOH Ext.G. Plasmodium berghei Inactive [75] P.C. DO = Dried organism. FsTh = Fresh thallus. organism. Sci.Agardh) SDTh 90% EtOH Ext. FsO = Fresh organism.Silva Gracilaria pacifica (I.0 μg/mL Cell culture-Herpes simplex 1 and HIV Virus Cell culture-Herpes simplex 1 Virus Cell culture-HIV Virus-MIC > 1000 µg/mL Epstein-Barr virus early antigen activation inhibition (telocidin b-4 induced Epstein-Barr virus induced activation)-4. SDTh = Shade dried thallus.Gmelin) P.0 µg/mL Cell culture-Herpes simplex 1 Virus Result 4560 Inactive [75] Inactive [97] Active [97] Inactive [96] Inactive [77] Inactive [98] ** [99] Gracilaria verrucosa (Hudson) MeOH Ext. Mol. foliifera. radiation. the macroalgae are industrially used as a source of hydrocolloids agar. Australia and Guam have recently become interested in the study of algae and diverse marine species. 2011. . metal ions and other chemically fundamental components. verrucosa at a dose of 1. 2. coronopifolia and G. domingensis had LC50 of 200 μg/mL against A. lauric and myristic acids [103]. France and Greece. manauealide A. Carbohydrate. lipids were indentified. foliifera showed toxicity in humans when treated with oral dose and cytotoxicity studies [75. Figure 1. In western countries like Venezuela. salina [74]. In this seaweed. This fact is justified by the extensive coastlines and marine biodiversity and is influenced by several factors for the development of these species. A 90% ethanol extract of G.Int. [106]. There is currently a tendency to substitute the use of laboratory animals in toxicological tests with alternative methods to reduce their numbers in experiments.2 mg/animal showed toxicity to mice [48]. agar [101]. However. manauealide B [64]. palmitoleic. extract studies with ethanol/water draw up from dried entire plant of G. or refine the existing methodology in order to minimize pain and stress [105]. bursa-pastoris (10. according to Table 1. USA and Canada. heparin [97]. edulis were also toxic to humans [65. which was isolated steroid cholest-4-en-3-one [107]. manauealide C [102]. edulis. oleic.76].0 µg/mL). chloroform and methanol extracts from G. carrageenan and alginate [100]. The consumption of algae has increased in European countries in recent decades with 15 to 20 species of algae being marketed in Italy. aqueous extract from G. coronopifolia and G. Another method to evaluate toxicity is determining cytotoxic activity. Structure of the compounds found in G. In this context aqueous extract from dried thallus of G. textorii.49] (See Table 1). Mol. salinity. steroids and alkaloids malyngamide [104] were found in these species (Figure 1). such as temperature. G. palmitic. verrucosa were not toxic in cell culture. A rapid and effective alternative to realize primary toxicity and biological action screening of compounds is the estimation of the 50% lethal concentration (LC50) through brine shrimp assay using Artemia salina L.1. 12 4561 These biological studies were mainly developed in Japan and Brazil. and ethanol extract from G. Carrageenan has been found to be useful in ulcer therapy and alginates are known to prolong the period of activity of certain drugs [8–11]. J. Sci. Studies of Toxicity In France. G. 85]. 90% Ethanol extracts from G. and did not show analgesic or anticonvulsant activities for mice [75] (Table 1).2. 90% ethanol extracts from G.83]. 12 4562 such as PGFα [84. verrucosa at a dose of 4. Figure 2.80]. choline-phosphatidyl [58. Higher doses produced significant post-coital contraceptive activity due to enhanced pre-implantation without any marked side effects. Mol. Methanol extract and polysaccharide fractions from G. and carbohydrates. These findings indicate that red marine algae are a potential source for post-coital contraceptive drugs [80]. Contraception Activity The researchers have also investigated new molecules with anticonceptive action. verrucosa were also antioxidant [82. verrucosa did not cause central or periphery effects for mice or dogs (50 mg/kg). ethanol-phosphatidyl [58]. the post-coital contraceptive action of marine seaweeds was also evaluated in animals. ethanolamine-phosphatidyl [58]. corticata was orally administered at 500 or 1000 mg/kg/day to female rats from day 1 to day 7 of their pregnancies. 2. corticata. edulis showed 100% inhibition of sperm motility and this effect was related to disruption of the plasma membrane by spermicidal compounds [3] (Table 1). edulis and G. J. Aqueous extract from . 2. Ethanol extracts from shade dried thallus of G. edulis (100 mg/kg) and G. Effects on the Nervous System Studies related to nervous system are important to understanding and treat complex degenerative and behavioral diseases. Polysaccharide fractions from G.4. verrucosa were inactive in spermicidal bioassays [75]. corticata were inactivated before the antiimplantation effect when they tested in pregnant rats [75. Extracts from G.108]. Structure composed of species of Gracilaria tested in cytotoxicity. glycerol. edulis and G. Anti-Inflammatory and Antioxidant Activities The anti-inflammatory activity of seaweeds has been studied.Int.3. 2. Methanol: methylene chloride (1:1) extract from G.0 mg/animal were orally and intraperitoneally administered to mice and showed immunopotentiating activity stimulating phagocytosis [82]. Sci. G. floridoside [109]. 2011. such as agar [110–113] (Figure 2). Staphylococcus aureus. lichenoides and others species contain PGE2 [47. Shigella dysenteriae.119] (Figure 4). Yet it was inactive for Sporotrichum schenckii. Candida albicans and Cryptococcus neoformans [75]. β-cryptoxanthin and β-carotene) [118] and carbohydrates [84. textorii. Figure 3. J.6. Cardiovascular Effects 90% Ethanol extracts from G.5 mg/animal controlled gastrointestinal disorders in mice [48] (Table 1). corticata.7. G. verrucosa algae or fresh G. edulis extract than S. Structure of the compounds found in G. G. arachidonic acid or collagen [81]. Mol. 5-alpha-poriferastane. asiatica. Aqueous extract from G. hypotension.85. Tyrosinase inhibition was not induced by methanol extract from G. edulis showed diuretic activity [75]. arcuata [86] and aqueous extract from G. edulis and G. smooth muscle dilatation. 2. Salmonella paratyphi. G.85]. carotenoids. chorda. was negligable on aldose reductase [83] (Table 1). Gastrointestinal Effects Aqueous extract from dried G. that have physiological effects including hyperthermia. 10 µg/mL.115] (Table 1). pyrimidine 2-amino-4-carboxy. 90 % ethanol extract from G. 2011. Antibiotic Activity Extracts or ingredients from various algae have shown antibacterial activity in vitro against gram-positive and gram-negative bacteria [117]. The agar disc diffusion method for antibacterial susceptibility was used for evaluation and 6 mm discs were impregnated with 20 µL of the extracts and placed in inoculated Muller Hinton agar. non-alkaloid nitrogen heterocycle [90]. aureus extract [12]. textorii at a dose of 100 µg/mL did not inhibit platelet aggregation induced by adenosine diphosphate. Pseudomonas aeruginosa and Klebsiella pneumonia (Table 1). . 5-alpha-3-beta-6-beta-diol [51] and gigatinine [85] (Figure 3).Int. verrucosa showed no cardiovascular effects in dogs (50 mg/kg) [75]. We observed higher activity for G. lichenoides was administered intravenously in rats and it was antihypertensive [84]. verrucosa and G. 2. G. Sci.5. Shigella bodii. hyperalgesia and gastric secretion inhibition [114. 12 4563 G. the chemical compounds isolated from the species were steroids (carotenoids. 3-beta-6-alpha-diol poriferastane. edulis (Gmelin) Silva was tested against bacterial strains of Vibrio cholera. Antibacterial activity from chloroform extract of G. 2. verrucosa. In the present investigation. steroids. chorda algae at a dose of 0. resulting from zeaxanthin and antheraxanthin [116]. Chloroform. edulis. Petroleum ether. debilisi. Figure 5. or Penicillium funiculosum [91]. ether and methanol extracts from G. 12 Figure 4. Ethanol extract from G. coli and S. ethanol extract from G. sjoestedii showed antibacterial activity against E. aureus at a concentration of 5. Fusarium solani. domigensis and G. cholest-7-en-3-β-ol and brassicasterol) [52] (Figure 6). 4564 Mahasneh et al. The growth of Neurospora crassa was not inhibited by extracts from G. tikvahiae were inactive [93]. aureus. stearic lipids and capric acids were isolated [121] (Figure 5). Chemical structure of the steroids isolated from G. debilis showed antibacterial activity against S. debilis. Bacillus megaterium. Structure of compounds found in species of Gracilaria with antifungal activity. domingensis. palmitic acid and steroids (stigmasterol. G. domigensis was active against Mycobacterium smegmatis and Neurospora crassa [92]. aureus and Streptococcus viridians [91].0 mg/mL [89]. campesterol. Sci. Methanol extract from fresh G. Figure 6. corticata was active against Bacillus subtilis. aureus but was inactive against Mycobacterium smegmatis [92]. Ethanol extracts from G. 95% ethanol extract from whole dried G. S. corticata and G. Alternaria solani. Mol. . Ethanol extracts from G. J.0 µg/units proved to be inactive on the inhibition of penicillinase enzyme [87]. polysaccharide CT-1 [122]. Structure of the steroids isolated from G. G. domingensis and G. 2011. pygmea did not inhibit the growth of Aspergillus niger. cervicornis algae was active against S. From this specie. domigensis has as chemical constituents. chloroform and methanol extracts from this seaweed at a concentration of 1. sjoestedii were active against Candida albicans shown by agar plate method [92]. (1995) demonstrated activity of organic extracts from algae against multi-resistant bacteria to antibiotics [120]. sjoestedii and G. G. sitosterol.Int. The search was carried out using data banks such as. J. Figure 7. 2011.8. Granin BP and citrullinyl-arginine proteins were isolated from these extracts [123.124]. 90 % ethanol extract from G. simplex 1 when tested at a concentration of 400 µg/mL. However. bursa-pastoris and Gracilaria sp were inactive against the Herpes simplex 1 virus (HSV) and the human immunodeficiency virus (HIV) when evaluated in cell cultures [96]. SciFinder Scholar. pacifica at a concentration of 200. 12 Figure 6. Extracts and compounds obtained from Gracilaria sp with anti-HIV activity are also active against other retroviruses such as HSV. corticata and G. 4565 Some studies highlighting antiparasitic activity of seaweeds also were verified. the pharmacodynamic mechanisms of the antiretroviral activity are still unknown because bioactive compounds from seaweed poorly investigated [9] (Table 1) (Figure 7). Material and Methods In this article. AlgaeBase. Structure of a compound found in Gracilaria sp and G. Cont. 2. Pubmed and NAPRALERT (acronym for Natural Products ALERT-University of Illinois in Chicago. Biological Abstracts. bursa-pastoris.Int.0 µg/mL was active against Sindbis virus. USA). but was not effective against H. Mol. edulis were tested against Entamoeba histolytica and Plasmodium berghei and were not active [75]. . Methanol extract from dried G. Sci. HN H2N O NH O O R2 Citrullinylarginine R1 NH NH NH C NH R3 3. some reports about bioactivity of Gracilaria algae were reviewed in the specialized literature published up to January 2011. Antivirial Activity Extracts from G. X. Ito. 2.or. Food Rev.R. efficacy and quality of the end products. pp.J. Ravikumar. Darcy-Vrillon. R. 1–14. Int. 2011. Acknowledgments The authors thank CNPq/CAPES/PRONEX-FAPESQ-PB-Brazil for financial support. Appl. In addition. 54. 16. J. respectively. Conclusions 4566 Algae are abundant in the oceans and represent a rich source of as yet unknown secondary metabolites. A. J. there is a great need for toxicological. 2006.Int. It is important to taxonomically classify and standardize extractions. Phycol. 4. 123–146. Drugs 2004. 2. Smit. Nutritional aspects of the developing use of marine macroalgae for the human food industry. 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