Antitubercular Activity of Triterpenoids from Asteraceae Flowers

Abstract

The flowers of Chrysanthemum morifolium RAMAT. and related chrysanthemum plants (Asteraceae) are used as a Chinese natural medicine. Florists Chrysanthemum Flower (Ju Hua) is prescribed for anti-inflammatory, analgesic, and antipyretic purposes and for the treatment of eye disease in Chinese traditional preparations. 1) In the course of our studies on bioactive principles of natural medicines and medicinal foodstuffs, we found that the triterpene alcohols isolated from the non-saponifiable lipid (NSL) fraction of the extract of chrysanthemum (C. morifolium RAMAT. var. sinense MAKINO forma esculentum MAKINO; Japanese name: Ryourigiku) and other Asteraceae plants (pot marigold, cosmos, sunflower, burdock, etc.) possess remarkable anti-inflammatory activity on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema in mice, [2][3][4][5] inhibitory effects on trypsin and chymotrypsin, 6) anti-tumor promoting effects, [7][8][9] and cytotoxic activity against human cancer cell lines. 7) Various types of triterpenoids from plants have recently been reported to exhibit antitubercular activity. 10,11) In this paper, we describe the antitubercular activity against Mycobacterium tuberculosis of twenty-nine 3-hydroxy triterpenoids: twentyeight (1-16, 18-29) were isolated from the NSL fraction of the extract of chrysanthemum flowers and one (17) was chemically derived from compound 16. MATERIALS AND METHODSChemicals Twenty-seven triterpenoids (1-16, 18-26, 28, 29) (Chart 1) were isolated from the NSL fraction of the methanol extract of chrysanthemum flowers.2,3,5) Triterpenoid 27, which had previously been isolated from the extract of sunflower pollen, 12) was isolated from the NSL fraction of the methanol extract of chrysanthemum flower, 13) and triterpenoid 17 was prepared from 16 by oxidation with CrO 3 -pyridine followed by NaBH 4 reduction of the oxidation product. 14)Determination of Antitubercular Activity Antitubercular activity of compounds in DMSO was determined against Mycobacterium tuberculosis H 37 Rv (ATCC 27294) in Middlebrook 7H12 medium using the Microplate Alamar Blue Assay (MABA) as previously described.15) The MIC is defined as the lowest concentration effecting a reduction in fluorescence of 90% relative to controls.Cytotoxicity Assay Toxicity against Vero cells (ATCC CCL-81) was determined as described earlier.16) After 72 h exposure, cell viability was measured using the CellTiter 96 aqueous non-radioactive cell proliferation assay. The IC 50 is defined as the reciprocal dilution resulting in 50% inhibition of the Vero cells. RESULTS AND DISCUSSIONThe MIC values of 1-29 against M. tuberculosis are shown in Table 1. Among the compounds tested, fifteen of them: five taraxastanes (2, 4-7), two oleananes (9, 11), two ursanes (13, 15), two lupanes (17, 18), two cycloartanes (22, 24), one tirucallane (27), and one dammarane (29), exhibited activity with MIC values of 4-64 mg/ml, among which maniladiol (9; MIC 4 mg/ml) and 3-epilupeol (17; 4 mg/ml) followed by 4,5a-epoxyhelianol (27; 6 mg/ml) showed the ...

Cytotoxic activity and chemical constituents ofAnthemis mirheydari

“…The 50% inhibitory dose (ID 50 ) values were reported to be 0.3 and 0.4 mg/ear for 1 and 2, respectively . The same research group described the anti-tubercular activity of 1 and 2 against Mycobacterium tuberculosis with the MIC values of 64 and464 mg/mL, respectively (Akihisa et al 2005). As for the anticancer activity of compound 1, it has shown cytotoxicity against PC3 (human prostate cancer) (IC 50 15.8 mg/mL) and HT-29 (human colon cancer) (IC 50 38.3 mg/mL) (Boutaghane et al 2013), and MCF-7 (breast cancer) (IC 50 53.3 mM) cells (Lee et al 2010) in previous studies; however, in another study on KB (human nasopharyngeal carcinoma) and P388 (murine leukaemia) cells, no anticancer effect was observed for this compound (Villarreal et al 1994).…”

Formation of Triterpenoids throughout Olea europaea Fruit Ontogeny

“…Over 100 different carbon skeletons are known and further oxidative modifications and glycosylations generate even more diversity [1][2][3]. Despite the increasing interest in the wide range of biological properties of plant triterpenoids and their derivatives for human health [4][5][6][7], their roles and functions in planta still remain poorly understood. Sterols and non-steroidal triterpenoids are synthesized via the cytoplasmic acetate/mevalonate pathway and share common biosynthetic precursors up to (3S)-2,3-oxidosqualene (OS) [8,9].…”

Antitubercular Activity and Inhibitory Effect on Epstein-Barr Virus Activation of Sterols and Polyisoprenepolyols from an Edible Mushroom, Hypsizigus marmoreus

“…4) Hypsiziprenols are the possible biosynthetic precursors of gymnopilins, bitter principles of H. marmoreus. 4) In the course of our studies on the bioactive principles of natural medicines and foodstuffs, 5,6) we evaluated the constituents of H. marmoreus for their antitubercular activity 7) as well as their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). 5,6) In this paper, we describe the antitubercular activity against Mycobacterium tuberculosis of seven sterols (1-7) and eight polyisoprenepolyols, hypsiziprenols (8)(9)(10)(11)(12)(13)(14)(15), and inhibitory effects on the induction of EBV-EA by the TPA of seven sterols (1-7) and three hypsiziprenols (8, 10, 12) isolated from the non-saponifiable lipid (NSL) fraction of the extract of H. marmoreus.…”