Chemical Constituents of Plants from the Genus Blumea

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REVIEW Chemical Constituents of Plants from the Genus Blumea by Ming Chen a ), Hui-Zi Jin a ), Wei-Dong Zhang* a ) b ), Shi-Kai Yan a ), and Yun-Heng Shen b ) a )Department of Chemistry and Bioactivity of Traditional Chinese Medicine, School of Pharmacy, Shanghai Jiaotong University, 800 DongChuan Road, 200240, Shanghai, P.R. China b )Department of Natural Product Chemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, 200433 Shanghai, P. R. China (phone: þ 86-21-25070386; fax: 86-21-25070386; e-mail: [email protected]) Contents 1. Introduction 2. Chemical Constituents 2.1. Flavonoids 2.2. Monoterpenes 2.3. Sesquiterpenes 2.4. Acetylenic Thiophenes 2.5. Triterpenoids 2.6. Xanthenes 2.7. Diterpenes 2.8. Essential Oils 3. Biological Activities 3.1. Essential Oils 3.2. Crude Extracts and Compounds 3.2.1. Free Radical-Scavenging Activity 3.2.2. Enhanced Percutaneous Penetration Activity 3.2.3. Hepatoprotective Effects 3.2.4. Antitumor Activity 3.2.5. Antifungal Effects 4. Concluding Remarks 1. Introduction. Blumea is a genus with ca. 80 species mainly found in tropical and subtropical Asia, Africa, and Oceania. Thirty species of them are distributed in the southern provinces of China. Among them, Blumea balsamifera DC and B. riparia DC are used as traditional herbal medicines. B. balsamifera, called (Dafengai), has been reported to possess stomachic, expectorant, antispasmodic, and sudorific properties. Its leaves and roots are used as a crude drug for beriberi, menorrhagia, leucorrhoea, lumbago, rheumatism, and a variety of ailments [1] [2]. B. riparia is used as folk medicines in Guangxi for puerperal metrorrhagia, puerperal edema, and barrenness [3]. Recently, much attention has been paid to Blumea genus and their chemical constituents because of their multifaceted activities. Extensive studies of Blumea genus CHEMISTRY & BIODIVERSITY – Vol. 6 (2009) 809 # 2009 Verlag Helvetica Chimica Acta AG, Zɒrich

Transcript of Chemical Constituents of Plants from the Genus Blumea

REVIEW

Chemical Constituents of Plants from the Genus Blumea

by Ming Chena), Hui-Zi Jina), Wei-Dong Zhang*a)b), Shi-Kai Yana), and Yun-Heng Shenb)

a) Department of Chemistry and Bioactivity of Traditional Chinese Medicine, School of Pharmacy,Shanghai Jiaotong University, 800 DongChuan Road, 200240, Shanghai, P. R. China

b) Department of Natural Product Chemistry, School of Pharmacy, Second Military Medical University,325 Guohe Road, 200433 Shanghai, P. R. China

(phone: þ86-21-25070386; fax: 86-21-25070386; e-mail: [email protected])

Contents

1. Introduction2. Chemical Constituents

2.1. Flavonoids2.2. Monoterpenes2.3. Sesquiterpenes2.4. Acetylenic Thiophenes2.5. Triterpenoids2.6. Xanthenes2.7. Diterpenes2.8. Essential Oils

3. Biological Activities3.1. Essential Oils3.2. Crude Extracts and Compounds

3.2.1. Free Radical-Scavenging Activity3.2.2. Enhanced Percutaneous Penetration Activity3.2.3. Hepatoprotective Effects3.2.4. Antitumor Activity3.2.5. Antifungal Effects

4. Concluding Remarks

1. Introduction. – Blumea is a genus with ca. 80 species mainly found in tropical andsubtropical Asia, Africa, and Oceania. Thirty species of them are distributed in thesouthern provinces of China. Among them, Blumea balsamifera DC and B. riparia DCare used as traditional herbal medicines. B. balsamifera, called �Dafengai�, has beenreported to possess stomachic, expectorant, antispasmodic, and sudorific properties. Itsleaves and roots are used as a crude drug for beriberi, menorrhagia, leucorrhoea,lumbago, rheumatism, and a variety of ailments [1] [2]. B. riparia is used as folkmedicines in Guangxi for puerperal metrorrhagia, puerperal edema, and barrenness[3]. Recently, much attention has been paid to Blumea genus and their chemicalconstituents because of their multifaceted activities. Extensive studies of Blumea genus

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have led to the identification of several compounds. In this review, we summarize thephytochemical progress and list the compounds isolated from the genus Blumea overthe past decades, including the biological activities of this genus.

2. Chemical Constituents. – Since 1900s, more than 70 constituents have beenisolated from the genus Blumea, including flavonoids, monoterpenes, sesquiterpenes,acetylenic thiophenes, triterpenoids, xanthenes, diterpenes, and essential oils [4– 30].Their structures are shown below, and their names and the corresponding plant sourcesare collected in the Table.

2.1. Flavonoids. Flavonoids are the major components of this genus. Flavonoids 1 –29 were isolated from the genus Blumea [4– 13]. Five flavones, 1 –5, were isolated fromB. malcomii. Two trimethoxyflavones, 6 and 7, were isolated from B. lacera. Fourflavonones, 8 – 11, and 22– 25 and 27– 29 were isolated from B. balsamifera. Compounds12– 21 and 26 were isolated from B. riparia.

2.2. Monoterpenes. Thirteen monoterpenes (30 –42) were isolated from the genusBlumea [5] [9] [14 – 20]. (�)-Borneol (30) was isolated from B. balsamifera. 31 and 36–38 from B. lacera, 32 and 33 from B. wightiana, 34 and 35 from B. malcomii, and 39 – 42from B. riparia were isolated

2.3. Sesquiterpenes. Nineteen sesquiterpenes, 43– 61, were isolated from the genusBlumea [21– 24]. Seven eudesmadienones, 44, 45, 50, 54, and 56– 58, were isolated fromB. densiflora. Five eudesmenes, 46– 49 and 59, and compound 43 were isolated from B.alata. Blumealactones A– C (51– 53, resp.), and 60 and 61 were isolated from B.balsamifera. 2-Himachalene-7,12-diol (55) was isolated from B. gariepina.

2.4. Acetylenic Thiophenes. Five acetylenic thiophenes, 62 – 66, were isolated fromthe genus [25] [26]. Compound 62 was isolated from B. amplectens, and compounds 63–66 were isolated from B. oblique.

2.5. Triterpenoids. Three triterpenoids, 67– 69, were isolated from this genus[19] [28]. Compound 67 was isolated from B. lacera, and compounds 68 and 69 wereisolated from B. balsamifera.

2.6. Xanthenes. Only one xanthene, blumeaxanthene (70), was isolated from B.riparia [27].

2.7. Diterpenes. Only one diterpene, austroinulin (71), was isolated from B.glomerata [31].

2.8. Essential Oils. Components of the essential oil extracted from B. riparia wereanalyzed by GC/MS. Ninetyeight compounds were separated, and 57 of them wereidentified, which included hexadecanoic acid, a-cadinol, etc. [30].

3. Biological Activities. – 3.1. Essential Oils. The essential oil of B. membranaceaproduced a marked and long-lasting fall in blood pressure in anaesthetized dogs,exerted a direct depressant action on frog heart, and spasmolytic effect on rabbit ileum.It also depressed the conditioned avoidance response, adversely affected performance,and potentiated the pentobarbitone-induced hypnosis in rats [32]. The essential oilfrom B. membranacea showed significant antifungal activity by the filter-paper-diskmethod. Extracts with different dilutions of the oil (0.5 – 100%) indicated thatCladosporium cladosporioides was the most sensitive of the tested strains. In contrast,Fusarium oxysporium was completely resistant to the oil [33]. In addition, Gupta et al.

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Table. Chemical Constituents from the Genus Blumea

No. Compound name Source Ref.

Flavonoids1 2’,5’,6-Trihydroxy-3,5,7-trimethoxyflavone B. malcomii [4]2 5’,6-Dihydroxy-2’,3,5,7-trimethoxyflavone B. malcomii [4]3 6-Hydroxy-2’,3,5,5’,7-pentamethoxyflavone B. malcomii [4]4 6-Hydroxy-3,4’,5,7-tetramethoxyflavone B. malcomii [4]5 5-Hydroxy-3,4’,6,7-tetramethoxyflavone B. malcomii [4]6 4’,5-Dihydroxy-3’,6,7-trimethoxyflavone B. lacera [5]7 3,4’,5-Trihydroxy-3’,6,7-trimethoxyflavone B. lacera [5]8 2’,3,5-Trihydroxy-5’,7-dimethoxyflavanone B. balsamifera [6]9 3,3’,5,7-Tetrahydroxy-4’-methoxyflavanone B. balsamifera [7]

10 3,4’,5-Trihydroxy-3’,7-dimethoxyflavanone B. balsamifera [8]11 3,3’,5-Trihydroxy-4’,7-dimethoxyflavanone B. balsamifera [7]12 Tricin B. riparia [9]13 Apigenin B. riparia [9]14 Luteolin B. riparia [9]15 Tricin 7-O-b-d-glucopyranoside B. riparia [9]16 Apigenin 7-O-b-d-glucopyranoside B. riparia [9]17 Luteolin 7-O-b-d-glucopyranoside B. riparia [9]18 3,3’,5-Trihydroxy-4’,7-dimethoxyflavone B. riparia [10]19 3,3’,4’,5-Tetrahydroxy-7-methoxyflavone B. riparia [10]20 Quercetin B. riparia [10]21 5-Hydroxy-3,3’,4’,7-tetramethoxyflavone B..riparia [10]22 Tamarixetin B. balsamifera [11]23 Rhamnetin B. balsamifera [11]24 Luteolin-7-methyl ether B. balsamifera [11]25 Velutin B. balsamifera [12]26 Nepitrin B. riparia [9]27 Blumeatin B. balsamifera [11]28 3’,5,5’,7-Tetrahydroxyflavanone B. balsamifera [11]29 3-O-7’’-Biluteolin B. balsamifera [13]

Monoterpenes30 (�)-Borneol B. balsamifera [14]31 (þ)-Fenchone B. lacera [15]32 5-Hydroxy-7’-tigloyloxy-p-menth-1(6)-en-2-one B. wightiana [16]33 7’-Ethoxy-5-hydroxy-p-menth-1(6)-en-2-one B. wightiana [16]34 (�)-Carvomenthone B. malcomii, B. eriantha [17]35 p-Menth-1-en-6-one B. malcomii [18]36 a-Pinene 7b-O-b-d-2’,6’-diacetylglucopyranoside B. lacera [5]37 2-Isoprenyl-5-isopropylphenol 4-O-b-d-xylopyranoside B. lacera [19]38 1-(4-Angeloyloxy-3-methoxyphenyl)-3-

(angeloyloxy)prop-1-eneB. lacera [20]

39 Protocatechuic acid B. riparia [9]40 Protocatechuic acid methyl ester B. riparia [9]41 Caffeic acid B. riparia [9]42 Caffeic acid methyl ester B. riparia [9]

Sesquiterpenes43 7b,8b : 8a,12-Diepoxyeremophil-11(13)-ene B. alata [21]44 1-Hydroxy-3-(2-methylpropanoyl)eudesma-

4(15),11(13)-dien-12,8-olideB. densiflora [22]

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Table (cont.)

No. Compound name Source Ref.

45 1-Hydroxy-3-(2-methylbutanoyl)eudesma-4(15),11(13)-dien-12,8-olide

B. densiflora [22]

46 3-Angeloyl-4-hydroxy-7b,11-epoxyeudesman-8-one B. alata [21]47 4-Acetyl-3-angeloyl-7b,11-epoxyeudesman-8-one B. alata [21]48 3-(2,3-Epoxy-2-methylbutanoyl)-4-hydroxy-7b,11-

epoxyeudesman-8-oneB. alata [21]

49 4-Acetyl-3-(2,3-epoxy-2-methylbutanoyl)-7b,11-epoxyeudesman-8-one

B. alata [21]

50 1-Hydroxy-3-O-(2-methylbutanoyl)-2-oxoeudesma-3,11(13)-dien-12,8-olide

B. densiflora [22]

51 Blumealactone A B. balsamifera [23]52 Blumealactone B B. balsamifera [23]53 Blumealactone C B. balsamifera [23]54 1,3-Dihydroxy-2-(2-methylbutanoyl)eudesma-

4(15),11(13)-dien-12,8-olideB. densiflora [22]

55 2-Himachalene-7,12-diol B. gariepina [21]56 1,3-Diacetyl-2-(2-methylbutanoyl)eudesma-

4(15),11(13)-dien-12,8-olideB. densiflora [22]

57 1,2-Dihydroxy-3-(2-methylbutanoyl)eudesma-4(15),11(13)-dien-12,8-olide

B. densiflora [22]

58 1-Acetyl-2-hydroxy-3-(2-methylbutanoyl)eudesma-4(15),11(13)-dien-12,8-olide

B. densiflora [22]

59 4-Acetoxy-3-(angeloyloxy)-11-hydroperoxyeudesm-6-en-8-one

B. alata [21]

60 2-Methylbut-2-enoic acid (3aR,4S,5R,7R,8aS)-decahydro-3a,4-dihydroxy-4-methyl-7-(1-methylethyl)-1-methylidene-8-oxoazulen-5-yl ester

B. balsamifera [24]

61 2,3-Dimethyloxiranecarboxylic acid (1R,3R,5E,10S)-10-hydroxy-6,10-dimethyl-3-(1-methylethyl)-4,9-dioxocyclodec-5-en-1-yl ester

B. balsamifera [24]

Acetylenic thiophenes62 Amplectol B. amplectens [25]63 5-(But-3-en-1-ynyl)-5’-[(3-methylbutanoyloxy)-

methyl]-2,2’-bithiopheneB. obliqua [26]

64 4-(5’-Methyl-[2,2’-bithiophen]-5-yl)but-3-ynyl3-methylbutanoate

B. obliqua [26]

65 2-Hydroxy-4-(5’-methyl-[2,2’-bithiophen]-5-yl)but-3-ynyl3-methylbutanoate

B. obliqua [26]

66 5’,5’’-Methylenebis[5-(but-3-en-1-ynyl)-2,2’-bithiophene] B. obliqua [26]

Triterpenoids67 b-Sitosterol B. balsamifera [30]68 Stigmasterol B. balsamifera [30]69 19a-Hydroxyurs-12-ene-24,28-dioate

3-O-b-d-xylopyranosideB. lacera [19]

Xanthenes70 Blumeaxanthene B. riparia [27]

Diterpenes71 Austroinulin B. glomerata [31]

confirmed that the essential oils of B. lacera and B. malcomii increased the insecticidalactivity of pyrethrum, as determined by knockdown activity and toxicity againsthouseflies (Musca domestica) [34].

3.2. Crude Extracts and Compounds. 3.2.1. Free Radical-Scavenging Activity. Inpreliminary investigations, the free radical-scavenging activities of petroleum ether,CHCl3, and MeOH extracts, and flavonoids of B. balsamifera leaves on nonenzymati-cally (phenazine methosulfate/NADH) generated superoxide radicals were evaluated.The results showed that the MeOH extract exhibited higher radical-scavenging activitythan the other two extracts. The superoxide radical-scavenging capacity of flavonoids asdetermined decreased in the order quercetin (20)> luteolin (14)>3’,5,5’,7-tetrahy-droxyflavanone (28)>blumeatin (27)> rhamnetin (23)> tamarixetin (22)> luteolin-7-methyl ether (24)>dihydroquercetin-4’-methyl ether>dihydroquercetin-4’,7-dimethylether [11] [12].

3.2.2. Enhanced Percutaneous Penetration Activity. (�)-Borneol (30) isolated fromB. balsamifera was an effective percutaneous penetration enhancer [35]. The essentialoils camphor and 1-menthol isolated from B. balsamifera also enhanced thepercutaneous absorption of nicotinamide, and their enhancement effect was similar[36].

3.2.3. Hepatoprotective Effects. Zhao et al. reported that blumeatin (27) possessedantioxidant property that protected monkey�s hepatocytes and hepatic subcellularorganelle against injuries induced by FeSO4 or CCl4 [37].

3.2.4. Antitumor Activity. It was reported that 3,3’,5,7-tetrahydroxy-4’-methoxy-flavanone (9) isolated from B. balsamifera exhibited the most striking synergism withTRAIL (a novel anticancer agent), which could induce apoptosis in many transformedcells but not in normal cells [38]. Oxiranecarboxylic acid ester 61 isolated from B.balsamifera also proved to be weakly cytotoxic against Jurkat human T-cell leukemiacells [24]. Blumealactones A, B, and C (51 –53, resp.) isolated from B. balsamiferaexhibited antitumor activities against Yoshida sarcoma cells in tissue culture [23]. In2004, it was reported that austroinulin (71) from B. glometata exhibited a cell cycle-inhibition effect at the G1 stage at the concentration of 15.2 mg/ml (47.2 mm) [31].

3.2.5. Antifungal Effects. Two acetylenic thiophenes, 63 and 64, isolated from B.obliqua showed antifungal activity against Epidermophyton floccosum and Pleurotusostreatus [29]. 4’,5-Dihydroxy-3’,6,7-trimethoxyflavone (6), 3,4’,5-trihydroxy-3’,6,7-trimethoxyflavone (7), and a-pinene 7b-O-b-d-2’,6’-diacetylglucopyranoside (36)showed moderate activities against Candida albicans, low activities against Trichophy-ton mentagrophytes, and both 7 and 36 exhibited low activities against Escherichia coli,Pseudomonas aeruginosa, and Staphylococcus aureus [5].

4. Concluding Remarks. – The genus Blumea includes ca. 80 species, and some ofthem have been used as traditional herbal medicines. B. balsamifera had been used inChina long years ago. The chemical investigation on these Blumea species has revealedthat many components from this genus exhibit significant bioactivities. Nevertheless,there are still many Blumea species that have received no or only little attention. In thefuture, much more phytochemical and biological studies should be carried out on thisgenus.

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The work was supported by the Program for Changjiang Scholars and Innovative Research Team inUniversity (PCSIRT), NCET Foundation, NSFC (C03050201), National 863 Program (2006AA02Z338),and, in part, by the Scientific Foundation of Shanghai, China (07DZ19728, 06DZ19717, 06DZ19005).

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