Perception on Marine Natural Products from Brown Algae and Its Pharmacological Review

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PERCEPTION ON MARINE NATURAL PRODUCTS FROM BROWN ALGAE AND ITS PHARMACOLOGICAL REVIEW

Harini. R*1, Selvakumari. E1, Gopal. V1, Arumugam. M2

1. Department of Pharmacognosy, College of Pharmacy, Mother Theresa Post Graduate & Research Institute of health sciences, Puducherry-605006, India. 2. Centre of Advanced Study in Marine Biology, Faculty of Marine Sciences, Annamalai University, Parangipettai- 608502, Cuddalore Dt., Tamilnadu, India.

Abstract : Marine natural product is an untapped resource for new drug development. The complex marine metabolites of novel chemical structure with its targeted mechanism of action for various diseases and disorders will prompt the chemist for the synthesis of active pharmaceutical ingredients leads to the discovery of new lead molecules from marine source. The algae play a very important role because of its immense distribution which has to be focused in the research for discovering new chemical entity in therapy. In addition the phytoconstitutents reported in brown algae with special importance to fucoidan, fucoxanthin and phlorotannins are elaborately discussed along with its pharmacological action. The data mining on the brown algae address phytochemical information to the researcher to develop a lead molecule with potent pharmacophore for different disease and disorders. This review focus the compilation of the complex marine metabolites and the therapeutic uses of brown algae belongs to phaeophyceae

IndexTerms - Fucoidan, Fucoxanthin, Phlorotannins, Brown algae.

I. INTRODUCTION

Marine flora and fauna play an important role as a source of lead molecules. The oceans cover more than 70% of the earth’s surface contains over 2, 00,000 invertebrates and algal species. The oceans contain 5 billion species in about 30 phyla. Because of the diversities of marine organisms and habitats, the marine natural products has a wide range of chemical metabolites including terpenes, shikimates, polyketides, acetogenins, peptides, alkaloids, pigments and polyphenols. Marine natural product is an untapped resource for new drug development. In addition, the complex marine metabolites of novel chemical structure with its targeted mechanism of action for various diseases and disorders will prompt the chemist for the synthesis of active pharmaceutical ingredients leads to the discovery of new lead molecules from marine source. The algae play a very important role because of its immense distribution which has to be focused in the research for discovering new chemical entity in therapy. Generally the marine algae are classified into four types namely Cyanophyceae- Blue green algae, Rhodophyceae- Red algae, Chlorophyceae- Green algae and Phaeophyceae- Brown algae. This review focus the compilation of the complex marine metabolites and the therapeutic uses of brown algae belongs to phaeophyceae.

II. TAXONOMY

The taxonomical hierarchy of brown algae is given table 1

Class: Phaeophyceae (Silberfeld et al, 2014, Guiry et al, 2009)

Table: 1 Taxonomy of Brown algae

SUBCLASS ORDER FAMILY

Discosporsangiophycidae Discosporangiales Choristocarpaceae, Discosporangiaceae

Ishigeophycidae Ishigeales Ishigeaceae, Petrodermataceae Dictyotales Dictyotaceae Onslowiales Onslowiaceae Dictyotophycidae Sphacelariales Cladostephaceae, Lithodermataceae, Phaeostrophiaceae, Sphacelariaceae, Sphacelodermaceae, Stypocaulaceae Syrinsgodermatales Syringodermataceae Fucophycidae Ascoseirales Ascoseiraceae Asterocladales Asterocladaceae JETIR2002357 Journal of Emerging Technologies and Innovative Research (JETIR) www.jetir.org 1011

Desmarestiales Arthrocladiaceae, Desmarestiaceae Ectocarpales Acinetosporaceae, Adenocystaceae, Chordariaceae, Ectocarpaceae, Petrospongiaceae, Scytosiphonaceae Fucales Bifurcariopsidaceae, Durvillaeaceae, Fucaceae, Himanthaliaceae,Hormosiraceae, Notheiaceae, Sargassaceae, Seirococcaceae, Xiphophoraceae

Laminariales Agaraceae, Akkesiphycaceae, Alariaceae, Aureophycaceae, Laminariaceae, Lessoniaceae, Pseudochordaceae, Chordaceae Nemodermatales Nemodermataceae

Phaeosiphoniellales Phaeosiphoniellaceae

Ralfsiales Mesosporaceae, Neoralfsiaceae, Ralfsiaceae

Scytothamnales Asteronemataceae, Bachelotiaceae, Splachnidiaceae Sporochnales Sporochnaceae

Tilopteridales Cutleriaceae, Halosiphonaceae, Phyllariaceae, Stschapoviaceae, Tilopteridaceae

The complex phytometabolite reported in brown algae are an acid derivative alginic acid, fucoidan polysaccharide from cellulose. An inorganic salt is in calcified form aragonite needle. Chlorophyll a photosynthetic pigment, carotenoids, chlorophyll c, fucoxanthin a carotenoid from plastids and phlorotannins a polyphenol compound reported in various genous of brown algae. The chemical structure given in the table 2

Table 2: Phytoconstitutent reported in Brown algae (Lee, 2008, Claire et al, 1990)

S.No PLANT PART CHEMICAL SUBCLASS CONSTITUENT

Acid

Alginic acid 1 Cellulose

Polysaccharide

Fucoidan

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2 Calcified form along with Inorganic salts plant cells

Aragonite Needles

3 Photosynthetic pigment Chlorophyll

Chlorophyll a

4 Plastids Chlorophyll Chlorophyll c

Carotenoids Fucoxanthin

5 Tannins Phlorotannins Structure elaboratory given in table 5

III. COMPLEX MARINE METABOLITES

The complex metabolites such as fucoidan, fucoxanthin and phlorotannins have greater pharmacological significance. These complex marine metabolites with its pharmacological activity reported in various genus of brown algae is elaborately disused in table 3, 4 and 6.

FUCOIDAN

Fucoidan, an extra cellular matrix of brown algae which is chemically a fucose enriched sulphated polysaccharide (Damonte et al, 2004). – n number of 1-fucose units has been bonded to sulphate groups or uronic acids in fucoidans by α-1-2

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© 2020 JETIR February 2020, Volume 7, Issue 2 www.jetir.org (ISSN-2349-5162) and α-1-4 bonds (Sakai et al, 2003).The structure of fucoidan differs from species to species and hence possess different pharmacological action (A.Cumashi et al, 2007; L.Chevolot et al, 2001; T.Teruya et al, 2007).

Table: 3 Pharmacological studies of Fucoidan reported in the various genus of Brown algae

ACTIVITY SEAWEED REFERENCE Anti-cancer Cladosiphon navae Zhang et al, 2013, Cladosiphon okamuranus Nagamine et al, 2009, Fucoidan Kasai et al,2015

Anti-viral Kjellmaniella crassifolia Wang et al,2017

Anti-hepatitis Fucus evanescens Kujnetsova et al, 2017, Fucus vesiculosus Li, H.F et al,2017

Anti-HIV Sargassum swartzii Dinesh et al, 2016, Sargassum mcclure Thanh.T.T et al, 2015 Sargassum polycystum Turbinara ornate

Anti-diabetic Fucus vesiculosus Shan et al, 2016, Cheng

Sargassum fusiforme et al, 2019

Anti-coagulant Lessonia vadosa Chandia et al,2008, Wang Lonicera japonica et al, 2010

Veterinary medicine Cladosiphon okamuranus Trejo-Avila et al, 2014 FUCOXANTHIN

Carotenoids are the natural pigments which mainly comprises of two subclasses namely non-polar hydrocarbon and polar compounds. The non-polar hydrocarbon is called carotene and polar compounds as xanthophyll (G.Van Poppel et al, 1997and S.K.Das et al, 2005). Fucoxanthin comes under the category xanthophylls which is chemically an allenic band and a 5, 6- monoepoxide (A.Asai et al, 2004). Generally Fucoxanthins are isolated from brown algae (A.Asai et al, 2004) but diatoms (Bacillariophyta) are also one of the choices for its isolation (C.Ishikawa et al, 2008).It has been reported that the composition of fucoxanthin differs from species to species (Tsukui et al, 2007) and the major metabolites of fucoxanthin are Fucoxanthinol and amarouciaxanthin A (Asai et al, 2004).

Table: 4 Pharmacological studies of Fucoxanthin reported in the various genuses of Brown algae

ACTIVITY SEAWEED REFERENCE Fucoxanthin Anti-tumor Lonicera japonica Swadesh et al, 2008, Masashi et al, 1999, Kim et al, 2010, Ishikawa et Undaria pinnatifida al, 2008

Ishige okamurae

Anti-obesity effect Undaria pinnatifida Megumi et al, 2010, Masashi et al, 2010

Anti-diabetic Undaria pinnatifida Hayato et al, 2007, Hosokawa et al, 2009

Anti-inflammatory Sargassum siliquastrum Hea et al, 2008, Kim et Ishige okamurae al, 2010, Sakai et al, Undaria pinnatifida 2009, Sakai et al, 2011 JETIR2002357 Journal of Emerging Technologies and Innovative Research (JETIR) www.jetir.org 1014

Skin Protective effect Sargassum siliquastrum Heo et al, 2009, Laminaria japonica Shimoda et al, 2010, Undaria pinnatidida Urikura et al, 2011

Anti-angiogenic effect Undaria pinnatidida Sugawara et al, 2006

Cerebro vascular Undaria pinnatidida Ikeda et al, 2003 Protective effect

Bone protective effect Laminaria japonica Das et al, 2010

Ocular protective effect Hijikia fusiformis Shiratori et al,2005 Undaria pinnatifida Sargassum fulvellum

Anti-malarial effect Sargassum Afolayan et al, 2008 heterophyllum

PHLOROTANNINS

Polyphenolic compounds are the secondary metabolites which are present in both terrestrial as well as in aquatic environments and possess numerous pharmacological actions (Shibata et al, 2002; Susanto et al, 2009). Tannins are the poyphenolic compounds which exist as phlorotannins in marine mainly in brown algae. Phlorotannins are formed by polymerization of phloroglucinol whose structure is less complex when compared to terrestrial tannins (Glombitza and Hauperich, 1997; Kang et al, 2007; Koivikko et al,2005; Wang et al, 2008).

Table: 5 Structure of Phlorotannins reported in the various genus of brown algae

CONSTITUTENT CHEMICAL STRUCTURE REPORTED IN BROWN SEAWEED Phloroglucinol

Ecklonia cava

Eckol

E.cava, Eisenia Bicyclis

Fucodiphloroethol G

E. cava

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Phlorofucofuroeckol A

E. cava, E.stolonifera, E.kurome

Phlorofucofuroeckol B

E. bicyclis

7-Phloroeckol

E.cava, E. stolinifera

Triphloroethol A

E. cava

6,6-Bieckol -*

E. cava, ishigeokamurae

Dieckol

E. stolinifera

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2-Phloroeckol

E. stolinifera

6,8-Bieckol

E. bicyclis

8,8-Bieckol

E. bicyclis

Table: 6 Pharmacological studies of phlorotannins reported in the various genus of Brown algae.

ACTIVITY SEAWEED REFERENCE Phlorotannins Anti-fungal Ecklonia stolonifera Choi et al, 2008

Anti-allergic Eisenia arborea Sugiura et al, 2007

Anti-cancer Ecklonia cava Kong et al, 2009

Anti-diabetic Ecklonia cava Lee et al, 2009, Lee

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Ishige foliaceae et al, 2011

Anti- Neuroinflammatory Ecklonia cava Weisiger et al, 1973, Kiningham et al, 1999

Anti-HIV Ecklonia cava Finnie et al, 1985 Ishige okamurae Farber et al, 1973

Anti-oxidant Sargassum Matsubara et al, 2004, Kjellamanianum McLellan et al, 1992, Sargassum siliquastrum Bae 2011, Shibata et Ecklonia stolonifera al, 2008 Ecklonia maxima

Anti-hypertensive Ecklonia cava Athukorala et al, 2005 Ecklonia stolonifera Pelvetia siliqousa Hizikia fusiforme Undaria pinnatifida

Radio protective Ecklonia cava Kim, 2010

Plant growth regulating Ecklonia maxima Kang et al, 2004

Anti-arousal Ecklonia cava Bellows et al, 1991, Yeo et al, 2012

Anti-chlolinesterase Ecklonia stolonifera Yoon et al,2009

Tyrosinase inhibition Ecklonia cava Kiminori , 2004

Anti-coagulant Sargassum thunbergii Shibata et al, 2008

Bone tissue regenerator Ecklonia cava Yeo et al, 2012

The various species of Sargassum is intensively screened pharmacologically. Table 7 shows the detailed compilation of different species of Sargassum. The active metabolite and its various pharmacological screening method.

Table: 7 Pharmacological studies on the various species of sargassum genus

ACTIVITY SEAWEED ACTIVE METHOD REFERENCE METABOLITE Anti-oxidant S.fulvellum Sulphate polysaccharide NO scavenging, DPPH Kim et al, 2007 scavenging

S.hemiphyllum Total phenolic DPPH scavenging, Hwang et al, 2010 compound Superoxide anion scavenging

S.thunbergii Tetraprenyltoluquinol, DPPH scavenging Seo et al, 2006 Sargothunbergol Seo et al, 2007

S.siliquastrum Sargachromanols DPPH scavenging, Jung et al, 2008 Superoxide sacvenging Lim et al, 2002

S.micracanthum Plastiquinones DPPH scavenging, Iwashim et al, 2005 Deoxyribose scavenging, Mori et al, 2005 Hydroxy radical Chandini et al, 2008, scavenging Park et al, 2005

Cholinesterase S.sagamianum Farnesylacetone Acetylcholinesterase Ryu et al, 2003 inhibitory derivative, inhibitory activity, Choi et al, 2007 JETIR2002357 Journal of Emerging Technologies and Innovative Research (JETIR) www.jetir.org 1018

Plastoquinones Butyrylcholinesterase Natarajan et al, 2010 inhibitory activity

Neuroprotective S.fulvellum Pheophylin A Ina et al, 2007 activity Nerve growth factor

Trang et al, 2005 S.macrocarpum Sargaquinoic acid Kamei et al, 2003 Tsang et al, 2004

Anti-Cancer S.oligocystum Polysaccharide Hep G2 cells Chenx et al, 2012

S.pallidum Polysaccharide A549 cells, MGC 803 Ye et al, 2008 cells

S.swartzii Meroterpenoids Ca CO-2 cells, T47 cells Khanani et al, 2010

S.turtile Hydroy sargaquinone P-388 Lymphocytic Numata et al, 1992 Sargasals I and II leukemia cells fraction

S.latifolium Polysaccharide E3 Lymphoblastic, leukemia Gamal-Eldeen et al, 1301 cells 2009

Anti-pyretic, S.wightii - Carrageenan induced Dar et al, 2007 Analgesic and Anti- edema Kang et al, 2008 inflammatory activities Hwang et al, 2011 S.fulvellum - Mouse ear edema

S.thunbergii - Yeast induced pyrexia, Kang et al, 2008,Hong Tail flick test, Phorbol et al, 2011 myristate acetate induced inflammation

S.swartzii - Acetic acid induced writhing, Hot plate induced pain models, Carragenan and peritonitis model, Amiant induced granuloma in mice

S.hemiphyllum Fucoidan Invitro and in vivo anti Hwang et al, 2011 inflammatory

Hepatoprotective S.polycystum - Acetaminophen induced Raghavendran et al, activity toxic hepatitis 2005

S.wightii Sulphate polysaccharide Cyclosporine A induced oxidative liver injury Josephine A et al, 2008

Anti viral activity S.micracanthum Plastoquinones Cytomegalo virus, Iwashima et al, 2005 Measles virus Zhu et al, 2004 S.patens Sulphated Acyclovir sensitive and polysaccharide resistant stains of Herpes virus type 1 Lee et al, 2011 S.trichophyllum Fucoidan Herpes simplex virus type

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2 Sinha et al, 2010

S.tenerrimum Fucoidan, Guluronic Herpes simplex virus type acid rich alginate 1

Anti-coagulant S.fulvellum Polysaccharide De Zoysa et al, 2008 activity Activated partial thromboplastin time Athukorala et al, 2007 S.borneri -

Immunomodulatory S.ilicifolium Terpenes,Steroids Stimulation of Chemotatic Chandraraj et al, 2010 activity and Phagocytic, Intracellular killing of human neutrophils

S.hemiphyllum - Cell proliferation, IgM Wu et al, 2009 secretion, Phagocytosis in HB4C5 cells and J774 cell lines

Fibrinolytic activity S.Fluvellum 1-()-palmitoyl-2-()- Pro-U-PA and Wu et al, 2007 oleoyl-3-()-(α-D- Plasminogen glucopyranosyl)-lycerol, 1-()-myristoyl-2-()- oleoyl_3_()-(α-D- glucopyranosyl)-glycerol

Diabetes and S.yezoense Sargaquinoic acid PPARs α/γ Kin et al, 2008 dyslipidemia treatment Sargahydroquinoic acid

Anti-ulcer S.polycystum - Maintance of acidity of Raghavendran et al, gastric juice, Gastric 2004 mucosal injury improvement

Skin whitenning S.polycystum - Tyrosinase and melanin Cha et al, 2011 activity S.silquastrum - production inhibition Chan et al, 2011

IV. CONCLUSION

It is concluded that the marine natural products is complex structure which is an untapped resources for new drug development. The biomolecules such as fucoidan, fucoxanthin and phlorotannins have wide pharmacological action due to its complex unique structure. This review article will address a key for the researcher to develop a lead molecule with potent pharmacophore for different diseases and disorders for benefit of suffering mankind.

V. ACKNOWLEDGMENT

We thank Dr. S. Kanchana, Senior Research Fellowship, Centre of Advanced Study in Marine Biology, Faculty of Marine Sciences, Annamalai University,Parangipettai, Cuddalore, Tamilnadu, India for her kind help and support.

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