Sesquiterpenoids and Flavonoids from the Aerial Parts of Tithonia diversifolia and Their Cytotoxic Activity

Abstract

Tithonia diversifolia (HEMSL.) A. GRAY (Compositae) is native to Mexico and also grows in parts of Africa, Australia, Asia, and other countries of North America, and is commonly called Mexican sunflower or tree marigold.1) An extract of T. diversifolia has been traditionally used for the treatment of diabetes, diarrhea, menstrual pain, malaria, hematomas, hepatitis, hepatomas, and wound healing. 2-5)Pharmacological studies of Tithonia diversifolia showed that it has anti-diabetic, 6,7) anti-malarial, 8) anti-inflammatory, 9) analgesic, 9) and cancer chemopreventive 10) activity, some of which account for the folkloric claims of this medicinal plant. Several sesquiterpenoids were isolated from T. diversifolia.1,10,11) As part of our systematic survey of bioactive compounds from higher plants, we have now conducted a detailed phytochemical screening of the 80% EtOH extract of T. diversifolia using a cytotoxicity-guided fractionation method, which has resulted in the isolation of twelve sesquiterpenoids (1-12), including three new ones (4, 10, 12), and three known flavonoids (13)(14)(15). This paper deals with the structural identification and determination of the sesquiterpenoids and flavonoids, and with their cytotoxic activity. Results and DiscussionThe dried aerial parts of T. diversifolia were extracted with hot 80% EtOH. The concentrated 80% EtOH extract, which showed cytotoxic activity against HL-60 cells with an IC 50 value of 4.10 mg/ml, was passed through a porous-polymer polystyrene resin (Diaion HP-20) column, and successively eluted with 30% MeOH, EtOH, and EtOAc. The EtOH eluate fraction exhibited cytotoxic activity against HL-60 cells (IC 50 1.03 mg/ml), and was repeatedly subjected to column chromatography on silica gel, octadecylsilanized (ODS) silica gel, Sephadex LH-20, and reversed phase HPLC, giving compounds 1 (8.4 mg), 2 (11.3 mg), 3 (118 mg), 4 (744 mg), 5 (112 mg), 6 (8.7 mg), 7 (67.9 mg), 8 (90.7 mg), 9 (245 mg), 10 (14.0 mg), 11 (24.2 mg), 12 (19.0 mg), 13 (18.8 mg), 14 (60.8 mg), and 15 (6.6 mg).Compounds 1-3, 5-9, 11, and 13-15 were identified as tirotundin (1), 12) tirotundin 3-O-methyl ether (2), 13) tagitinin A (3), 14) tagitinin C (5), 12) deacetylviguiestin (6), 15) tagitinin F (7), 12) 1b-methoxydiversifolin (8), 1) 1b-methoxydiversifolin 3-O-methyl ether (9), 1) 4b,10a-dihydroxy-3-oxo-8b-isobutyroyloxyguaia-11(13)-en-6,12-olide (11), 16) luteolin (13), 16) nepetin (14), 16) and hispidulin (15) Hachioji, Tokyo 192-0392, Japan: b Hiro International Co., Ltd.; 2-16-5 Shibuya, Shibuya-ku, Tokyo 150-0002, Japan: and c Division of Molecular Pharmacology, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research; 3-10-6 Ariake, Koto-ku, Tokyo 135-8550, Japan. Received April 26, 2007; accepted May 15, 2007 Cytotoxicity-guided fractionation of the 80% EtOH extract of Tithonia diversifolia has resulted in the isolation of twelve sesquiterpenoids (1-12), including three new ones (4, 10, 12), and three known flavonoids (13-15). The structures of the new compounds were deter...

Toxicity studies of Tithonia diversifolia A. Gray (Asteraceae) in rats

“…Depression in the blood profile after the adminis- tration of the plants extracts suggests that the plant extracts may have cytolytic or cytotoxic effects. It has documented that some of the components of the crude extracts have cytotoxic effects (Kuroda et al, 2007), but these may not include marrow stoma dysfunction or damage as seen with other known cytotoxic drugs like cytosine arabinoside (Ben-Ishay and Barak, 2001) since the rate of recovery of the red blood cell line was quicker.…”

“…A previous study found that isolated compounds showed cytotoxic activity against HL-60 leukemia cells (Kuroda et al, 2007). The cancer growth inhibitory property of the extract was further examined using a disease-oriented panel composed of 39 human cancer cell lines in the Japanese Foundation for Cancer Research by the same group.…”

Chlorogenic acids from Tithonia diversifolia demonstrate better anti-inflammatory effect than indomethacin and its sesquiterpene lactones

“…T. diversifolia has been exhaustively studied 0378-8741/$ -see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.jep.2011.04.067 and possesses several biological activities including the following: anti-inflammatory, analgesic, antimalarial, antiviral, antidiabetic, antidiarrhoeal and antimicrobial, among others (Cos et al, 2002;Owoyele et al, 2004;Kuroda et al, 2007). Besides these numerous, documented biological activities, this plant is important due to its substantial use within traditional medicine in several countries (Frei et al, 1998;Heinrich et al, 1998;Játem-Lásser et al, 1998).…”

Microbial transformation of the sesquiterpene lactone tagitinin C by the fungus Aspergillus terreus

“…Similar results were found while using peripheral blood mononuclear cells, where 1 and 2 also presented cytotoxic effects, thus indicating nonselective toxicity. It has previously been shown that 1 has cytotoxic activity against HL-60 cells [19], but its activity has not yet been compared with that of the derivative 2. In the same work, compound 1b was isolated from T. diversifolia as a natural compound and was found to be approximately 10 times more active than 1.…”

“…Gray, Asteraceae) [2]. It shows cytotoxic [19], anti-inflammatory [33], and antifeedant activities [2], and thus is a promising compound for further research into its mechanisms of action in different targets. T. diversifolia, the source of 1, is used in folk medicine in many countries [8,14] and has anti-inflammatory and antimalarial properties [8].…”