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Medicinal and Aromatic Plant Science and Biotechnology ©2007 Global Science Books Clerodendrum and Heathcare: An Overview Neeta Shrivastava* • Tejas Patel B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, S. G. Highway, Thaltej, Ahmedabad - 380054, Gujarat, India Corresponding author: * neetashrivastava_perd@yahoo.co.in ABSTRACT The genus Clerodendrum L. (Family: Lamiaceae) is very widely distributed in tropical and subtropical regions of the world. More than five hundred species of the genus are identified till now, which includes small trees, shrubs and herbs. Ethno-medical importance of various species of Clerodendrum genus has been reported in various indigenous systems of medicines and as folk medicines. The genus is being used as medicines specifically in Indian, Chinese, Thai, Korean, Japanese systems of medicine for the treatment of various lifethreatening diseases such as syphilis, typhoid, cancer, jaundice and hypertension. Few species of the genus like Clerodendrum inerme, C. thomosonae, C. indicum, and C. speciosum are ornamental and being cultivated for aesthetic purposes. The powder/paste form and the various extracts of root, stem and leaves are reported to be used as medicine for the treatment of asthma, pyreticosis, cataract, malaria, and diseases of blood, skin and lung. To prove these ethno-medical claims, some of these species are being extensively studied for their biological activities using various animal models. Along with biological studies, isolation and identification studies of chemical constituents and its correlation with the biological activities of the genus has also been studied. The major chemical components reported from the genus are phenolics, steroids, di- and triterpenes, flavonoids, volatile oils, etc. This review mainly covers the extent of work done on biological activities of various Clerodendrum species such as C. trichotomum, C. bungei, C. chinense, C. colebrookianum, C. inerme, C. phlomidis, C. petasites, C. grayi, C. indicum, C. serratum, C. campbellii, C. calamitosum and C. cyrtophyllum that can be used both in conventional therapy or as replacement therapies for the treatment of various diseases. _____________________________________________________________________________________________________________ Keywords: ethnomedical, phytochemistry, anti-inflammatory, antimicrobial, antimalarial, antioxidant, antidiabetic, polyphyletic, paraphyletic Abbreviations: AGC, apigenin-7-O-ȕ-D-glucoside; GSH, glutathione; MDA, malondialdehyde; PGE2, prostaglandin E2; XO, xanthine oxidase CONTENTS INTRODUCTION...................................................................................................................................................................................... 142 ETHNOMEDICAL USES.......................................................................................................................................................................... 146 PHYTOCHEMISTRY................................................................................................................................................................................ 146 BIOLOGICAL ACTIVITIES ..................................................................................................................................................................... 147 Anti-inflammatory activities.................................................................................................................................................................. 147 Antimicrobial activites .......................................................................................................................................................................... 147 Antimalarial activities............................................................................................................................................................................ 148 Antioxidant activities............................................................................................................................................................................. 148 Other biological activities of Clerodendrum genus ............................................................................................................................... 148 SUMMARY ............................................................................................................................................................................................... 148 ACKNOWLEDGEMENT ......................................................................................................................................................................... 149 REFERENCES........................................................................................................................................................................................... 149 _____________________________________________________________________________________________________________ INTRODUCTION The genus Clerodendrum L. [Family Lamiaceae (Verbenaceae)] is very widely distributed in tropical and subtropical regions of the world and is comprised of small trees, shrubs and herbs. The first description of the genus was given by Linnaeus in 1753, with identification of C. infortunatum. After a decade later in 1763 Adanson changed the Latin name "Clerodendrum" to its Greek form "Clerodendron"; in Greek Klero means chance and dendron means tree i.e. chance tree which means the tree which does not bring good luck like Clerodendron infortunatum or the tree which brings good luck like C. fortunatum. Later on after a span of about two centuries in 1942 Moldenke readopted the Latinized name 'Clerodendrum', which is now commonly used by taxonomists for the classification and description of the genus and species (Moldenke 1985; Rueda 1993; Hsiao and Lin 1995; Steane et al. 1999). Clerodendrum is a very Received: 4 January, 2007. Accepted: 22 January, 2007. large and diverse genus and till now five hundred and eighty species of the genus have been identified and are widely distributed in Asia, Australia, Africa and America (Table 1). A high degree of morphological and cytological variation (from 2n=24 to 2n=184) amongst the species, suggesting the paraphyletic or polyphyletic origin of the genus. Molecular systematic studies based on cloroplast and nuclear DNA also indicate polyphyletic origin of the genus (Steane et al. 1999). Owing to morphological variations like length of the corolla tube, size of leaves, and type of inflorescence some authors have classified the genus into two major subgenera, Clerodendrum and Cyclonema (Steane et al. 1999) while others have classified it into five subgenera and each subgenus is again subdivided into many sections (Moldenke 1985). Similarly many species of the genus have been described by more than one author and hence are denoted in the literature with the name of different authors e.g. C. floribundum Hort. and C. floribundum R.Br., C. foetidum Bunge Invited Review Medicinal and Aromatic Plant Science and Biotechnology 1(1), 142-150 ©2007 Global Science Books Table 1 List of various species from the genus Clerodendrum. * Species described by more than one author. C. cernuum Wall.ex Steud. C. foetidum Bunge* C. acerbiana Benth. & Hook.f. C. chamaeriphes Wernham C. formicarum Gurke C. aculeatum (L.) Schlecht.* C. citrinum Ridley C. formosanum Maxim. C. acuminatum Wall. C. coccineum D.Dietr.* C. fortunatum Buch.-Ham.ex Wall.* C. adenocalyx Dop C. cochinchinense Dop C. fortunei Hemsl. C. adenophysum H.Hallier C. colebrookianum Walp. C. fragrans Vent.* C. affine Griff. C. commersonii Spreng. C. francavilleanum Buchinger ex C. africanum Moldenke C. condensatum Miq. Berthold Thomas C. aggregatum Gurke C. confusum H.Hallier C. friesii K.Schum. C. alatum Gurke C. congense Baker* C. f.rutectorum S.Moore C. albiflos H.J.Lam C. congestum Guerke C. fugitans Wernham C. amicorum Seem. C. conglobatum Baker C. fuscum Gurke. C. amplifolium S.Moore C. consors S.Moore C. galeatum Balf.f. C. amplius Hance C. corbisieri De Wild. C. garrettianum Craib C. anafense Britton & P.Wils. C. gaudichaudii Dop C. angolense Guerke C. cordatum D.Don C. geoffrayi Dop C. angustifolium Salisb.* C. cordifolium A.Rich. C. giletii Wildem. & Th.Dur. C. apayaoense Quisumb. C. coriaceum Poir.* C. glaberrimum Hayata C. arenarium Baker C. coromandelianum Spreng. C. glabratum Guerke C. arthur-gordoni Horne ex Baker C. costaricense Standley C. glabrum E.Mey. C. assurgens K.Schum. C. costatum R.Br. C. glandulosum Colebr.ex Wall. C. attenuatum De Wild.* C. costulatum K.Schum. C. glandulosum Lindl. C. aucubifolium Hemsl. C. cruentum Lindl. C. glaucum Wall.ex Steud. C. aurantiacum Baker C. cubensis Schau. C. globuliflorum Berthold Thomas C. aurantium G.Don C. culinare Sesse & Moc. C. godefroyi Kuntze C. × speciosum Teijsm. & Binn. C. cumingianum Schau. C. goossensi De Wild. C. bakeri Gurke C. cuneatum Guerke* C. gordoni Baker C. balfouri Hort. C. cuneifolium Baker C. gossweileri Exell C. barbafelis H.Hallier C. cunninghamii Benth. C. grandicalyx E.A.Bruce C. baronianum Oliver C. curranii Elmer C. grandiflorum Schau. C. barteri Baker C. curtisii N.E.Br. C. grandifolium Gurke* C. baumii Guerke C. cuspidatum Turcz. C. gratum Kurz* C. bequaerti De Wild C. cyrtophyllum Turcz C. greyi Baker C. bernieri Briq. C. darrisii Leveille C. griffithianum C.B.Clarke C. bethuneanum Low C. deflexum Wall. C. guerkii Baker C. bingaense S.Moore C. dekindtii Guerke C. haematocalyx Hance C. bipindense Guerke C. dembianense Chiov. C. haematolasium H.Hallier C. blancoanum Villar C. densiflorum Griff. C. hahnianum Dop C. blancoi Naves ex Villar C. dentatum Wall. C. hainanense Hand.-Mazz. C. blumeanum Schau. C. depauperatum Wall.ex Steud. C. harmandianum Dop C. bodinierii Leveille C. dependens Aug.DC. C. harnierianum Schweinf. C. bolivianum Rusby C. dicolor Vatke C. hastato-oblongum C.B.Clarke C. botryoides Baker C. diepenhorstii Miq. C. hastatum Lindl. C. botryoides K.Schum. C. dinklagei Gurke C. helianthemifolium Wall.ex Steud. C. brachyanthum Schau. C. discolor Becc. C. hemiderma F.Muell.ex Benth. C. brachypus Urb. C. disparifolium Blume C. henryi P'ei C. lerodendrum bracteatum Wall. C. divar. catum Jack* C. herbaceum Wall. C. bracteosum Kostel. C. diversifolium Vahl C. brassii Beer & H.J.Lam C. dubium De Wild. C. heterophyllum C. brazzavillense A.Cheval. C. duckei Moldenke C. hettae H.Hallier C. hexagonum De Wild C. dumale Baker C. breviflorum Ridl. C. hexangulatum Berthold Thomas C. dumale K.Schum. C. brookeanum W.W.Smith C. hildebrandtii Vatke C. dusenii Guerke C. brunfelsiiflorum H.Hallier C. hircinum Schau. C. eketense Wernham C. brunsvigioides Baker C. hirsutum G.Don* C. ekmani Moldenke C. buchananii Herb.Roxb.ex Wall. C. hispidum M.R.Henderson C. elberti H.Hallier C. buchholzii Gurke C. hockii De Wild. C. elegans Manetti ex Lem. C. buchneri Gurke C. holstii Guerke ex Baker* C. ellipticum Zipp.ex Span. C. buettneri Gurke C. holtzei F.Muell. C. elliptifolium Merrill C. bukobense Gurke C. horsfieldii Miq. C. elmeri Merrill C. bungei Steud. C. huegelii Hort.ex Regel C. emarginatum Briq. C. buruanum Miq. C. humile Chiov. C. emirnense Boj.ex Hook. C. buxifolium Spreng. C. hysteranthum Baker C. epiphyticum Standley C. cabrae De Wild. C. illustre N.E.Br. C. caeruleum N.E.Br. C. erectum De Wild. C. impensum Berthold Thomas C. caesium Guerke C. eriophyllum Gurke C. imperialis Carr. C. calamistratum Hort.Belg.ex Lem. C. eriosiphon Schau. C. inaequipetiolatum Good C. calamitosum Linn. C. esquirolii Leveille* C. incisum Klotzsch C. calcicola Britton C. eucalycinum Oliver C. indeniense A.Cheval. C. calycinum Turcz. C. eupatorioides Baker C. indicum Druce* C. camagueyense Britton & P.Wils. C. euryphyllum Mildbr. C. inerme Gaertn.* C. canescens Wall. C. excavatum De Wild. C. infortunatum Dennst.* C. capense D.Don ex Steud.* C. fallax Lindl. C. ingratum K.Schum. & Lauterb. C. capitatum Hook.* C. fargesii Dode C. intermedium Berthold Thomas* C. capsulare Blanco C. farinosum Wall. C. involucratum Vatke C. cardiophyllum F.Muell. C. fasciculatum Berthold Thomas C. ixoraeflorum Hazsk. C. carnosulum Baker C. fastigiatum H.J.Lam C. jackianum Wall. C. castaneaefolium Klotzsch C. ferrugineum Turcz. C. japonicum Mak.* C. castaneifolium Hook. & Arn. C. finetii Dop C. javanicum Spreng.* C. catalpifolium H.Hallier C. fischeri Gurke ex Engl. C. johnstoni Oliver C. caulambum Exell C. fistulosum Becc.* C. kaempferi Fisch.ex Morr. C. cauliflorum De Wild.* C. flavum Merrill C. kalaotoense H.J.Lam C. cavaleriei Leveille C. fleuryi A.Chevalier C. kalbreyeri Baker C. cephalanthum Oliver C. floribundum Hort.* 143 C. kampotense Dop C. kanichi Wildem. C. katangensis Wildem. C. kentrocaule Baker C. kinabaluense Stapf C. kirkii Baker C. kissakense Guerke C. klemmei Elmer C. koshunense Hayata C. kwangtungense Hand.-Mazz. C. laciniatum Balf.f. C. laevifolium Blume C. lanceolatum F.Muell. C. lanceolatum Gurke. C. lanceoliferum S.Moore C. lanessanii Dop C. lankawiense King & Gamble C. lanuginosum Blume C. lasiocephalum C.B.Clarke C. laxicymosum De Wild. C. laxiflorum Baker C. lecomtei Dop C. lehuntei Horne ex Baker C. lelyi Hutchinson C. leucophloeum Balf.f. C. leucosceptrum D.Don C. leveillei Fedde ex Leveille C. ligustrinum C. lindawianum Lauterb. C. lindemuthianum Vatke C. lindenianum A.Eich. C. lindleyi Decne.ex Planch. C. linnaei F.Muell.* C. lividum Lindl. C. lloydianum Craib C. lobbii C.B.Clarke C. longicolle G.F.W.Mey. C. longiflorum Decne. C. longilimbum P'ei C. longipetiolatum Gurke* C. longisepalum Dop C. longituba Valeton C. longitubum Wildem. & Th.Dur. C. luembense De Wild. C. lujaei Wildem. & Th.Dur. C. lupakense S.Moore C. luzoniense Merrill C. mabesae Merrill C. macradenium Miq. C. macrocalycinum Baker C. macrocalyx De Wild.* C. macrophyllum Blume* C. macrosiphon Hook.f.* C. macrostachyum Baker* C. macrostegium Schau. C. madaeera Voigt C. magnificum Warb. C. magnoliaefolium Baker C. makanjanum H.Winkler C. mandarinorum Diels C. manetti Vis. C. mannii Baker C. margaritense Moldenke C. matudae Standley C. medium R.Br. C. megasepalum Baker C. melanocrater Gurke C. membranifolium H.J.Lam C. mexicanum T.S.Brandegee C. meyeri-johannis Mildbraed C. micans Gurke C. microcalyx Ridley C. microphyllum Berthold Thomas C. mildbraedii Berthold Thomas C. minahassae Teijsm. & Binn. C. mindorense Merrill C. minutiflorum Baker C. mirabile Baker C. mite Vatke C. moldenkeanum Standley C. molle H.B. & K.* C. montanum Berthold Thomas Clerodendron and healthcare. Shrivastava and Patel Table 1 (cont.) * Species described by more than one author. C. schultzei Mildbr. C. morigono Chiov. C. poggei Gurke C. schweinfurthii Gurke C. mossambicense Klotzsch C. polyanthum Guerke C. scopiferum Miq. C. moupinense Franch. C. polycephalum Baker C. semiserratum Wall. C. muenzneri Berthold Thomas C. populneum Beer & H.J.Lam C. multibracteatum Merrill C. porphyrocalyx K.Schum. & Lauterb. C. sereti De Wild. C. multiflorum G.Don C. powellii Benth. & Hook.f.ex Drake C. sericeum Wall. C. serotinum Carr.* C. myrianthum Mildbr. C. preslii Elmer C. serratum Moon* C. myricoides Gurke* C. preussii Gurke. C. sieboldii Kuntze C. myrmecophila Ridl. C. prittwitzii Berthold Thomas C. silvaeanum Henriques C. natalense Gurke C. puberulum Merrill C. silvestre Berthold Thomas C. navesianum Vidal C. pubescens Lindl. C. silvicola Guerke. C. nereifolium Wall. C. pubescens Walp. C. simile H.H.W.Pearson* C. neumayeri Vatke C. pulchrum Fawc. C. simplex G.Don C. nhatrangense Dop C. pulverulentum Engl. C. singalense Miq. C. nipense Urb. C. pumilum Ridley C. singwanum Berthold Thomas C. noiroti A.Chevalier C. pumilum Spreng. C. sinuatum Hook. C. nutans Jack* C. pusillum Guerke C. siphonanthus C. nyctaginifolium Good C. putre Schau. C. somalense Chiov. C. obanense Wernham C. pygmaeum Merrill C. speciosissimum Hort.Angl.ex C. obovatum Walp. C. pynaertii De Wild. Schau. C. obtusidens Miq. C. pyramidale Andr. C. odoratum D.Don C. quadrangulatum Berthold Thomas C. speciosum Guerke* C. spicatum Thunb. C. ohwii Kanehira & Hatusima C. quadriloculare Merrill C. spinescens Gurke C. orbiculare Baker C. ramosissimum Baker C. spinosum Spreng. C. oreadum S.Moore C. reflexum H.H.W.Pearson C. splendens A.Cheval.* C. ornatum Wall. C. rehmannii Guerke C. splendidum Wall. C. ovale Klotzsch C. rhytidophyllum K.Schum. C. squamatum Vahl C. ovalifolium A.Gray* C. ridleyi King & Gamble C. squiresii Merrill C. ovatum Poir.* C. riedelii Oliver C. stenanthum Klotzsch C. oxysepalum Miq. C. ringoeti De Wild. C. palmatolobatum Dop C. robecchii Chiov. C. streptocaulon Hutchinson & C. paniculatum Linn. C. robinsonii Dop Dalziel C. papuanum Scheff. C. robustum Klotzsch C. strictum Baker C. parvitubulatum Berthold Thomas C. roseum Poit. C. stuhlmanni Gurke C. pearsoni Moldenke C. rotundifolium Oliver C. subpandurifolium Kuntze C. peekelii Markgraf C. rubellum Baker C. subpeltatum Wernham C. penduliflorum Wall. C. rumphianum Bull C. subreniforme Guerke C. pentagonum Hance C. rumphianum De Vriese C. subscaposum Hemsl. C. petasites S.Moore C. rusbyi Moldenke C. suffruticosum Guerke C. petunioides Baker C. sagittatum Wall. C. swynnertonii S.Moore C. philippinense Elmer C. sagraei Schau. C. sylvaticum Briq. C. philippinum Schau. C. syringaefolium Baker C. sahelangii Koord.ex Bakh. C. phlebodes C.H.Wright C. talbotii Wernham C. sanguineum K.Schum. C. phlomoides Hort.Ital.ex DC.* C. tanganyikense Baker C. sansibarense Gurke C. phyllomega Steud. C. tatomense Dop C. sarawakanum H.J.Lam C. picardae Urb. C. teaguei Hutchinson C. savanorum De Wild. C. pierreanum Dop C. ternatum Schinz C. scandens Beauv.* C. pilosum H.H.W.Pearson C. ternifolium Baker* C. scheffleri Guerke* C. pithecobium Standley & Steyerm. C. schlechteri Guerke C. tessmanni Moldenke C. pittieri Moldenke ex Standley C. thomasii Moldenke C. schliebenii Mildbr. C. thonneri Guerke C. schmidtii C.B.Clarke C. pleiosciadium Gurke C. thyrsoideum Baker* C. tomentellum Hutchinson & Dalziel C. tomentosum R.Br. C. tonkinense Dop C. toxicarium Baker* C. tracyanum F.Muell.ex Benth C. transvaalense Berthold Thomas C. tricholobum Guerke C. trichotomum Thunb.* C. triflorum Vis. C. trifoliatum Steud. C. triphyllum H.H.W.Pearson C. triplinerve Rolfe C. tuberculatum A.Rich. C. ubanghense A.Chevalier C. ugandense Prain C. ulei Hayek C. ulugurense Guerke C. umbellatum Poir. C. umbratile King & Gamble C. uncinatum Schinz C. urticifolium Wall. C. utakwense Wernham C. validipes S.Moore C. vanoverberghii Merril C. vanprukii Craib C. var. ifolium De Wild. C. var. um Berthold Thomas C. velutinum A.Chevalier C. velutinum Berthold Thomas* C. venosum Wall. C. verrucosum Splitg.ex De Vriese C. versteegi Pulle C. verticillatum D.Don C. vestitum Wall.ex Steud. C. villosum Blume C. violaceum Guerke* C. viscosum Vent. C. volubile Beauv. C. weinlandii K.Schum.ex H.J.Lam C. welwitschii Gurke C. wenzelii Merrill C. whitfieldii Seem.* C. wildemanianum Exell C. williamsii Elmer C. wilmsii Guerke C. yakusimense Nakai C. yatschuense H.Winkler C. yaundense Guerke C. yunnanense Hu C. zambesiacum Baker Table 2 A few species of the Clerodendrum genus described by many authors. C. floribundum Hort. C. infortunatum Dennst. C. aculeatum (L.) Schlecht. C. floribundum R.Br. C. infortunatum Gaertn. C. aculeatum Griseb. C. foetidum Bunge C. infortunatum Linn. C. angustifolium Salisb. C. foetidum D.Don C. intermedium Berthold Thomas C. angustifolium Spreng. C. foetidum Hort.Par.ex Planch. C. intermedium Cham. C. attenuatum De Wild. C. fortunatum Buch.-Ham.ex Wall. C. japonicum Mak. C. attenuatum R.Br. C. fortunatum Linn. C. japonicum Sweet C. capense D.Don ex Steud. C. javanicum Spreng. C. capense Eckl. & Zeyh.ex Schau. C. fragrans Vent. C. fragrans Willd. C. javanicum Walp. C. capitatum Hook. C. glandulosum Colebr.ex Wall. C. linnaei F.Muell. C. capitatum Schum & Thou. C. glandulosum Lindl. C. linnaei Thw. C. cauliflorum De Wild. C. grandiflorum Schau. C. cauliflorum Vatke C. macrocalyx De Wild. C. grandifolium Gurke C. coccineum D.Dietr. C. macrocalyx H.J.Lam C. grandifolium Salisb. C. coccineum H.J.Lam C. macrophyllum Blume C. gratum Kurz C. congense Baker C. macrophyllum Sims C. gratum Wall. C. congense Engl. C. molle H.B. & K. C. hirsutum G.Don C. coriaceum Poir. C. molle Jack C. hirsutum H.H.W.Pearson C. coriaceum R.Br. C. myricoides Gurke C. holstii Guerke ex Baker C. divar. catum Jack C. myricoides R.Br. & Vatke C. divar. catum Sieb. & Zucc. C. nutans Jack C. holstii Gurke. C. fistulosum Becc. C. nutans Wall. C. indicum Druce C. fistulosum Bower C. ovalifolium A.Gray C. indicum Kuntze C. ovalifolium Bakh. C. ovalifolium Engl. C. ovatum Poir. C. ovatum R.Br C. scandens Beauv. C. scandens Druce C. scandens Linn.ex Jackson C. scheffleri Guerke C. schifferi A.Cheval. C. serratum Moon C. serratum Spreng. C. simile H.H.W.Pearson C. simile Merrill C. ternifolium D.Don C. ternifolium H.B. & K. C. thyrsoideum Baker C. thyrsoideum Guerke C. toxicarium Baker C. toxicarium Baker ex Gurke C. velutinum A.Chevalier C. velutinum Berthold Thomas C. velutinum Wall. and C. foetidum D. Don, C. lanceolatum F. Muell. and C. lanceolatum Gurke, etc.; some more examples are cited in Table 2 (Rueda 1993; Hsiao and Lin 1995; Steane et al. 1999). Conclusive remarks on the origin and classification of the genus are still lacking and a thorough revision of the classification of this genus supported by molecular systematics has been suggested by some researchers (Steane et al. 1999, 2004). 144 Medicinal and Aromatic Plant Science and Biotechnology 1(1), 142-150 ©2007 Global Science Books OH HO HO OH OH O O O O H OCH2CH3 H3CO O OH HO OH 5-O-ethylclerodendricin O O HO Hispudilin HO OH Iridiod diglucoside HOH2CH2C CH2CH2OH O Bungein H CN HO OH COOH HO O Colebrin OH OH O O 1(R) Lucumin O H OH HO O OH O HO O O O O O OH OH HO COOH Clerodermic acid O H3 C OCH3 Jionoside D HO HO O OH CN OH OH HO O OH O OH 2(R) Prunasin HO OH OH O O Uncinatone OH RO O Apigenin O OCH3 OH R = Gluc. acid (6-OMe) O Acacetin-7-O-methylglucuronate Clerosterol HOOC O OR''' RO COOH R'O CH3O CH3O OR'' Neolignan I Neolignan III R R', R" R''' = -CH2- R R' = CH3, R" R'" = -CH2- HO Serratagenic acid Neolignan II R R' = -CH2-, R" R'" = CH3 O HO O O OH O O OH HO H3C OH O HO OH HOOC Verbacoside OH HO HO HO OH O O OH HO OH O Scutellarin Fig. 1 Some of the major chemical constituents of Clerodendrum genus. 145 Clerodendron and healthcare. Shrivastava and Patel calamitosum was used as a medicine for the treatment of kidney, gall and bladder stones. This plant is also reported to have diuretic and antibacterial properties (Cheng et al. 2001). In the Chinese system of medicine C. bungei is used for the treatment of headaches, dizziness, furuncles and hysteroptosis (Zhou et al. 1982; Yang et al. 2002). In India, fruits of C. petasites are used to produce sterility, while in China the plant is used as medicine for malaria (Hazekamp et al. 2001; Panthong et al. 2003). Leaves of C. buchholzii are reported in African pharmacopeia for treatment of furunculosis, echymosis and gastritis (Nyegue et al. 2005). Other then their therapeutic use, some of the species of the genus such as C. inerme, C. thomosonae, C. indicum and C. speciosum are also cultivated and used as ornamental plants. The genus is taxonomically characterized by its entire or toothed, oppositely arranged leaves, terete stems, terminally or axillary cymose inflorescence, hypogynous bisexual flowers, persistent calyx, cylindrical corolla tube with spreading 5-lobed at the top, exerted stamens, short bifided stigma, imperfectly 4-celled ovary, exalbumenous seeds and endocarp separating into 4 stony pyrenes (Kirtikar and Basu 1991; Hsiao et al. 1995; Steane et al. 1999). Resembling its taxonomic diversity, the genus exhibits a wide spectrum of folk and indigenous medicinal uses. Research is advancing towards scientific validation of classical therapeutic claims of the genus. In the present review we have focused on the medicinal and health care aspects of the genus. We have also included the work done on the phytochemical constituent responsible or believed to be responsible for the therapeutic properties of various species belong to the genus (Fig. 1). PHYTOCHEMISTRY ETHNOMEDICAL USES A number of species from this genus were documented to be used as folk medicine by various tribes in Asian and African continents (Table 3). Many species of the genus have also been documented in traditional systems of medicine practiced in countries like India, China, Korea, Thailand and Japan. Roots and leaf extracts of C. indicum, C. phlomidis, C. serratum, C. trichotomum, C. chinense and C. petasites have been used for the treatment of rheumatism, asthma and other inflammatory diseases (Anonymous 1992; Hazekamp et al. 2001; Kang et al. 2003; Panthong et al. 2003; Choi et al. 2004; Sungwook et al. 2004; Kanchanapoom et al. 2005). Plant species such as C. indicum and C. inerme were used to treat coughs, serofulous infection, buboes problem, venereal infections, skin diseases and as a vermifuge, febrifuge and also to treat Beriberi disease (Anonymous 1992; Rehman et al. 1997; Kanchanapoom et al. 2001). It was also reported that tribals use C. inerme as an antidote of poisoning from fish, crabs and toads (Rehman et al. 1997; Kanchanapoom et al. 2001; Pandey et al. 2003). C. phlomidis, C. colebrookianum, C. calamitosum and C. trichotomum have been reported to have antidiabetic, antihypertensive and sedative properties (Singh et al. 1980; Chaturvedi et al. 1984; Khan et al. 1996; Cheng et al. 2001; Kang et al. 2003; Chae et al. 2004; Choi et al. 2004). C. cyrtophyllum and C. chinense were used for the treatment of fever, jaundice, typhoid and syphilis (Cheng et al. 2001; Kanchanapoom et al. 2005). Roots, leaves and fresh juice of leaves of C. infortunatum were used in eliminating ascarids and tumors, and also as a laxative (Anonymous 1992). C. phlomidis has been used as an astringent and also in the treatment of gonorrhea (Rani et al. 1999; Murugesan et al. 2001). The roots of C. serratum have been claimed to be used in dyspepsia, seeds in dropsy and leaves as a febrifuge and in cephalagia and ophthalmia (Anonymous 1992). C. As mentioned earlier the genus Clerodendrum is reported in various indigenous systems of medicine throughout the world for the treatment of various diseases. Efforts have been made by various researchers to isolate and identify biologically active principle and other major chemical constituents from various species of the genus. Research reports on the genus denote that the major class of chemical constituents present in the Clerodendrum genus are steroids such as ȕ-sitosterol, Ȗ-sitosterol octacosanol, clerosterol, bungein A, acteoside, betulinic acid, clerosterol 3-O-E-Dglucopyranoside, colebrin A-E, campesterol, 4Į-methylsterol, cholesta-5-22-25-trien-3-ȕ-ol, 24-ȕ-cholesta-5-22-25trine, cholestanol, 24-methyl-22-dihydrocholestanol, 24-ȕ22-25-bis-dehydrocholesterol, 24-Į-methyl-22-dehydrocholesterol, 24-ȕ-methyl-22-dehydrocholesterol, 24-ethyl22-dehydrocholesterol, 24-ethylcholesterol, 22-dehydroclerosterol, 24-methyllathosterol, 24-ȕ-ethyl-25-dehydrolathosterol, (24S)-ethylcholesta-5-22-25-triene-3ȕ-ol have been isolated from various Clerodendron species such as C. inerme, C. phlomidis, C. infortunatum, C. paniculatum, C. cyrtophyllum, C. fragrans, C. splendens, C. campbellii and C. splendens (Bolger et al. 1970; Abdul-Alim 1971; Joshi et al. 1979; Sinha et al. 1980; Singh and Singhi 1981; Sinha et al. 1982; Hsu et al. 1983; Singh and Prakash 1983; Singh and Singhi 1983; Pinto and Nes 1985; Rempler and Hunkler 1986; Akihisa et al. 1989; Att-Ur-Rehman et al. 1997; Goswami et al. 1996; Yang et al. 2000; Kanchanapoom et al. 2001; Yang et al. 2002; Gao et al. 2003a, 2003b; Pandey et al. 2003; Kanchanapoom et al. 2005; Lee et al. 2006). Another class of constituents are terpenes which include: monoterpenes, diterpenes, triterpenes, iridoids and sesquiterpenes. Terpenes such as D-amyrin, ȕ-amyrin, caryoptin, 3-epicaryoptin, 16-hydroxy epicaryoptin, clerodendrin A, B and C, clerodin, clerodermic acid, cleroinermin, friedelin, gramisterol, iridoids (inerminoside A, B, C and D, melittaside, monomelittoside, sammangaoside, ugandoside, 8-O-acetylmioporoside), obtusifoliol, oleanolic acid, royleanone, dehydroroyleanone, sesquiterpene (sammangaoside A, Table 3 A few species of Clerodendrum genus and their distribution in the world. Scientific Name Synonym Distribution India, Sri Lanka, South East Asian countries, Australia, Pacific Islands C. inerme Gaertn. India C. multiforum Burm. f. C. phlomidis Linn. f. India C. serratum Spreng. The Philippines C. infortunatum Linn. India C. indicum (Linn) Kuntze C. siphonanthus R. Br. China C. commersonii Spreng. Southern Africa C. glabrum E. Mey. Southern Africa C. triphyllum R. Br. China, Korea, Japan C. trichotomum China C. bungei Stued. Indonesia, Taiwan C. calamitosum L. Taiwan C. cyrtophyllum Turez. Tropical regions of Asia C. fragrans (Vent.) Willd. C. chinense (Osb.) Mabberley India, South Asian countries C. colebrookianum South Africa C. myricoides India, Malaysia, Sri Lanka, Vietnam, Southern China C. petasites S. Moore Queensland, Australia C. philippinum Schauer Southern Africa C. heterophyllum R. Br. & Thb. 146 Medicinal and Aromatic Plant Science and Biotechnology 1(1), 142-150 ©2007 Global Science Books B) clerodendrin A, uncinatone, Mi saponins-A, friedelanone, lupeol, betulinic acid, royleanone and dehydroroyleanone, and betulin have till now been isolated from various Clerodendron species such as C. inerme, C. phlomidis, C. paniculatum, C. colebrookianum, C. wildii, C. uncinatum, C. mandarinorum, C. thomsonae, C. fragrans, C. ugandense, C. chinense (Joshi et al. 1979; Sharma and Singh 1979; Singh et al. 1981; Sinha et al. 1981; Seth et al. 1982; Singh and Prakash 1983; Achari et al. 1990; Raha et al. 1991; Achari et al. 1992; Rao et al. 1993; Calis et al. 1994; El-Shamy et al. 1996; Kawai et al. 1998; Hazekamp 2001; Kanchanapoom et al. 2001; Yang et al. 2002; Kumari et al. 2003; Chae et al. 2004; Dorsaz et al. 2004; Nishida et al. 2004; Min et al. 2005). Flavonoids are another class of compounds which are mainly present in Clerodendron speices and they are also responsible for few biological activities. The major flavonoids present are cynaroside, 5-hydroxy-4’-7-dimethoxy methyl flavone, kaempferol, salvigenin, 4-methyl scutellarein, 5,7,4 O-trihydroxyflavone, apigenin, luteolin, acacetin-7-O-glucuronide, hispidulin, 2’-4-4’trihydroxy-6’methyl chalcone, 7-hydroxy flavone, luteolin, naringin-4’-O-Į-glucopyranoside, pectolinarigenin, cirsimaritin, cirsimaritin-4’glucoside, quercetin-3-methyl ether which were isolated from C. inerme, C. phlomidis, C. petasites, C. trichotomum, C. mandarinorum, and C. infortunatum (Vendatham et al. 1977; Seth et al. 1982; Raha et al. 1989; Achari et al. 1990; Raha et al. 1991; Roy and Pandey 1994, 1995; Roy et al. 1995 ; El-Shamy et al. 1996; Anam 1997, 1999). There are also other chemical constituents present which include volatile constituents such as 5-O-ethylcleroindicin D, linalool, benzyl acetate and benzyl benzoate, which have been isolated from C. canescens, C. cyrtophyllum, C. inerme and C. philippinum (Yang et al. 2002; Nyegue et al. 2004; Wong and Tan 2005). Other chemical constituent includes cyanogenic glycosides such as lucumin and prunasin which were isolated from C. grayi (Miller et al. 2006). Phenolic compounds like ȕ-benzyl alcohol, ȕ-benzyl alcohol-D-glucoside, neolignan, darendoside-B, phenyl propanoids like (isovarbascoside, verbascoside, leucosceptoside), vanillic acid, anisic acid, para-hydroxy benzoic acid, gallic acid have been reported in C. inerme, C. bungei and C. dauricum (Liu and Fu 1980; Gabriele and Rimpler 1981; Zhou et al. 1982; Gabriele et al. 1983; Sakurai and Kato 1983; Calis et al. 1994); D-mannitol from C. serratum (Garg and Verma 2006). Carbohydrates like glucose, fructose, sucrose are been reported in C. mandarinorum and C. inerme. Other constituents such as ribosome-inactivating protein, salidroside, jinoside-D, acetoside have been isolated from C. inerme (Olivieri et al. 1996), while trichotomoside, cytotoxic pheophorbides and cleromyrin-I have been isolated from C. trichotomum, C. calamitosum and C. cyrtophyllum (Bashwira et al. 1989; Cheng et al. 2001; Chae et al. 2006). BIOLOGICAL ACTIVITIES The genus Clerodendrum contains many plant species that are being used in various health care systems for the treatment of various disorders including life-threatening diseases. To validate traditional claims associated with the genus many studies are being carried out using various animal models and in vitro assays. These studies showed that the different species of the genus possess potent anti-inflammatory, antidiabetic, antimalarial, antiviral, antihypertensive, hypolipidemic and antioxidant activities and have potential to be developed as potent remedial agents from natural resources. Some major activities are described below. Anti-inflammatory activities Inflammation is a very complex pathophysiological process involving a variety of biomoleucles responsible for causing it such as leucocytes, macrophages, mast cells, platelets and lymphocytes by releasing eicosanoids and nitric oxide. Pro147 inflammatory cytokines such as TNF- and IL-1 are also responsible for various inflammatory conditions. Many species of the genus Clerodendrum showed potent anti-inflammatory activity. C. phlomidis was reported for significantly decreasing paw oedemas induced by carrageenan in rats at a dose of 1g/kg (Surendrakumar 1988). Similarly C. petasites was reported to show moderate anti-inflammatory activity in the acute phase of inflammation in rats. The ED50 values of the experiment were reported to be 2.34 mg/ear and 420.41 mg/kg in rats (Panthong et al. 2003), it has been suggested by the authors that the anti-inflammatory activity of the plant extract could be due to the inhibition of prostaglandin synthesis by the extract. The anti-inflammatory activity of C. trichotomum leaves were checked in rat, mice and Raw 264.7 macrophage cells using experimental models with 1 mg/kg solution of 30% and 60% methanolic extracts of leaves. Experimental results concluded that inhibition by methanolic extract was comparable to that of the positive control in an acute inflammation model, while in the chronic model the extract showed 10% higher activity than the positive control. It also suppressed the levels of prostaglandin E2 (PGE2) in RAW 264.7 macrophage cells (Choi et al. 2004). A phenyl propanoid glycoside 'acetoside' isolated from C. trichotomum also showed anti-inflammatory activity by inhibiting the release of histamine, arachidonic acid and prostaglandin E2 in RBL 2H3 cells. The mechanism identified for the inhibition of histamine release was related to calcium concentration (Lee et al. 2006). Xanthine oxidase (XO) is the enzyme responsible for the formation of uric acid from the purines hypoxanthine and xanthine, and is responsible for the medical condition, gout. Gout is caused by the deposition of uric acid in the joints leading to painful inflammation. Purified hydroalcoholic extracts of leaves and branches of C. floribundum showed 84% inhibition of XO activity (Sweeney et al. 2001). Results of the experiment indicate the potential of the plant species to be developed as a remedy for XO-induced diseases. Flavonoid glycosides of C. inerme showed modulation in calcium transport in isolated inflamed rat liver and thereby showed reduction in inflammation. The results obtained in the experiment were comparable with indomethacine used as a positive control (Somasundram and Sadique 1986). The alcoholic extract of roots of C. serratum showed a significant anti-inflammatory activity in carrageenan and also in the cotton pellet model in experimental mice, rats and rabbits (Narayanan et al. 1999). Antimicrobial activites Antiinfective compounds from natural resources are of great interest as the existing drugs are getting less effective due to increased tolerance of microorganisms. A number of species from the genus Clerodendrum were documented in ancient texts for their antimicrobial action. To validate these claims, research work was carried out with various Gram positive and Gram negative bacterial strains and also with fungal and viral pathogens. Dried, aerial parts of C. inerme showed potent antiviral activity against Hepatitis B virus with an ED50 value of 16 μg/ml (Mehdi et al. 1997). Essential oil obtained from leaves of the plant showed antifungal activity against variety of fungal species such as Alternaria species, Aspergillus species, Cladosporium herbarum, Cunnimghamella echinulata, Helminthosporium saccharii, Microsporum gypseum, Mucor mucedo, Penicillium digitatum, Rhizopus nigricans, Trichophyton rubrum and Trichothecium roseum (Sharma and Singh 1979). Alcoholic extracts of leaves and flowers of C. inerme also exhibited antibacterial activity against Escherichia coli and Staphylococcus aureus (George and Pandalai 1949). Pectolinarigenin and chalcone glucoside isolated from leaf of C. phlomidis showed antifungal activity (Roy et al. 1995). Two phenyl propanoid glycosides (acteoside and acteoside isomer) isolated from C. trichotomum showed potent Clerodendron and healthcare. Shrivastava and Patel inhibition of HIV-1 integrase with IC50 values of 7.8 ± 3.6 and 13.7 ± 6.0 μM (Kim et al. 2001). A new hydroquinone diterpenoid was isolated from C. uncinatum and was strongly fungi toxic to the spores of Cladosporium cucumerinum (Dorsaz et al. 2004). Hexane extracts of C. colebrookianum at concentrations of 1000 and 2000 ppm showed strong antibacterial activities against various Gram positive and Gram negative pathogens such as S. aureus, Staphylococcus haemolyticus, E. coli, Pseudomonas aeruginosa (Misra et al. 1995). Two flavonoids from roots of C. infortunatum, cabruvin and quercetin, showed strong antifungal activity. The former showed activity against Alternaria carthami and Helminthosporin oryzae, the latter against Alternaria alternate and Fusarium lini at concentrations of 200, 500 and 1000 mg/ml (Roy et al. 1996). Mi-saponin-A, a triterpenoid saponin isolated from the roots of C. wildii, showed potent antifungal activity against Cladosporium cucumerinum (Toyoto et al. 1990). ing reflux oesophagitis and gastritis and may therefore be a promising drug for their treatment (Min et al. 2005). In present lifestyles where stress has taken an unwanted important position leading to excess production of free radicals these natural remedies will prove a support to our biological system to balance metabolism. Other biological activities of Clerodendrum genus Antimalarial activities In various ancient literatures related to healthcare Clerodendrum have been reported for its antimalarial activities because of the presence of a bitter principle. Studies with different parasites support these ancient claims. The alcoholic extract of C. phlomidis showed antimalarial activity against Plasmodium falciparum with an IC50 value of 48 μg/ml (Simonsen et al. 2001). Another Indian species, C. inerme also inhibited the growth of larvae of Ades aegypti, Culex quinquefasciatus and Culex pipiens at 80 and 100 ppm concentration of petroleum ether and ether extracts (Gayar and Shazll 1968; Kalyanasundaram and Das 1985). C. myricoides a species from Southern Africa was also tested positive for its antimalarial activity against both sensitive and resistant strains of P. falciparum with IC50< 30 μg/ml (Muregi et al. 2004), it also showed 31.7% suppression in parasitaemia against cloroquine tolerant strain of Plasmodium berghei NK65 (Muregi et al. 2007). These plants may be useful as a source for novel anti-plasmodial drugs/compounds from natural origin. Antioxidant activities Antioxidant compounds are responsible for scavenging free radicals, which are produced during normal metabolism or during adverse conditions that can be harmful to biological systems and leading to death of an organism. Species like C. inerme have been used as antioxidant drugs in various indigenous systems of medicines (Masuda et al. 1999). Organic and aqueous extracts of C. colebrookianum showed significant inhibition of lipid peroxidation in vitro and in vivo induced by FeSO4-ascorbate in rats. Aqueous extracts showed strongest inhibitory activity over organic extracts. This lends scientific support to the therapeutic use of the plant leaves claimed in tribal medicine (Rajlakshmi et al. 2003). Isoacteoside, trichotomoside and jionoside D, three compounds isolated from C. trichotomum, when tested showed significant scavenging activity of intracellular reactive oxygen species produced by hydrogen peroxide suggesting their antioxidant properties (Chae et al. 2004, 2005, 2006). Apigenin-7-O-ȕ-D-glucuronopyranoside (AGC), isolated from C. trichotomum leaves decreased the volume of gastric juice and increased the gastric pH in a dose-dependent manner, decreasing the number of gastric lesions. A malondialdehyde (MDA) level, which is the end product of lipid peroxidation, was also decreased by AGC (i.d. 3 mg/kg), which increased significantly after the induction of reflux oesophagitis. The MDA levels did not decrease when either apigenin or omeprazole were used as a control suggesting that AGC has an antioxidative mechanism to reduce gastric lesions. Apigenin glucuronopyranoside also decreased mucosal glutathione (GSH) levels significantly suggesting that AGC possesses free radical scavenging activity. So it can be concluded that AGC is more potent in inhibit148 Other major biological activites reported for this genus are antihypertensive, antitumor, antidiabetic, antihyperlipidemic, larvicidal, antidiarrhoel activities. Organic extracts of C. inerme showed strong uterine stimulant activity when tested in female rats and rabbits (Sharaf et al. 1969), and also showed strong antihemolytic activity in human adults at 0.02-2.0 mg/ml, with inhibition of phospholipase at 0.05-1.5 mg/ml (Somasundaram and Sidique 1986). The methanolic extract of C. multiflorum leaves showed antidiarrhoeal activity against castor oil-induced diarrhoea, PGE2-induced enteropooling and caused reduction in gastrointestinal motility in rats (Rani et al. 1999), while leaf juice at 0.1% showed anthelmentic activity against Ascaris lumbricoides, Phreitima posthuma and Taenia solium (Garg and Sidique 1992). Two compounds, isoacteoside and jionoside D isolated from C. trichotomum also reduced the levels of apoptotic cells induced by the action of hydrogen peroxide (Chae et al. 2004, 2005). C. bungei showed antitumor activity in hepatic cells of mice at a dose of 100 g/kg (Shi et al. 1993). CNS-related activities were also observed in C. phlomidis showing tranquillizing, CNS depressant, muscle relaxant and psychopharmacological effects in experimental mice and rats (Murugesan et al. 2001). C. mandarinorum root extracts showed strong binding with opiate, adenosine-1, -2adrenergic, 5HT-1, 5HT-2, dopamine-2, histamine-1, GABA (A), and GABA (B) receptors. Isolated compounds of these plants showed weak binding with these recepters suggesting its synergestic effect (Zhu et al. 1996). C. inerme extracts showed hypotensive effects in dogs at 50 mg/kg (Bhakuni et al. 1969). A decoction of the entire C. phlomidis plant has been reported to have antidiabetic activity. A dose of 1 g/kg showed antidiabetic effects in epinephrine and alloxan induced hyperglycemia in rats and it also showed antihyperglycemic activity in human adults at a dose of 15-30 g/day (Chaturvedi et al. 1984). Organic and crude extracts of C. colebrookianum significantly lowered the serum lipid profile in rats suggesting that it has cardioprotective potential (Devi and Sharma 2004). The methanolic extract of C. phlomidis and leaf extracts of C. inerme showed antispasmodic activity in mouse (200 mg/kg; Murugesan et al. 2001) and guinea pigs (2 mg/ml; Cox et al. 1989). Ethanolic extract (2.25-9.0 mg/ml) of C. petasites evaluated for spasmolytic activity in guinea-pigs showed spasmolysis on tracheal smooth muscles; it also relaxed the smooth muscle which was contracted by exposure to histamine. The activity of smooth muscle relaxation was attributed to hispidulin (flavonoid) with an EC50 (3.0 ± 0.8 * 10-5 M) suggesting hispidulin has anti-inflammatory activity (Hazekamp 2001). Dichloromethane leaf extracts of C. myricoides indicated antimutagenic properties against Salmonella typhimurium TA98 and TA100 bacterial strains (Reid et al. 2006). No adverse effects of the genus have been reported in the literature until now. Various species of the genus like C. infortunatum, C. serratum, C. phlomidis have been reported to be safe in the prescribed dosage in traditional system of medicines (Anynomous 1; Sharma PV 2001). SUMMARY The genus Clerodendrum has been cited in many indigenous systems of health care for the treatment of variety of disorders. A few species extensively used as folk medicines for years have been investigated for their chemical constituents and biological activity to confirm these traditional claims. The genus is reported to have activities against a wide spec- Medicinal and Aromatic Plant Science and Biotechnology 1(1), 142-150 ©2007 Global Science Books trum of disorders which includes many life-threatening diseases like HIV. Still there are many species of the genus having a potential towards many disorders in their unexplored fold. clerodendron inerme L. growing in Egypt. 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