Cytotoxic sesquiterpene lactones from the leaves of Vernonia guineensis Benth. (Asteraceae)
Graphical abstract
Introduction
Vernonia guineensis Benth. (Asteraceae) is a variable species with three varieties (var. guineensis, var. cameroonica, and var. procera) recognized in the West African region. They are herbaceous with strong erect stems from a perennial woody rootstock, 1.70 m high, distributed across the region from Mali to Western Cameroon, and across central Africa from Cameroon to Sudan (Burkill, 1985). Vernonia guineensis Benth. is a widely used medicinal plant in West Africa and particularly in Cameroon (Tchinda et al., 2002, Focho et al., 2009, Noumi, 2010). Whole carrot-like tubers and powders derived therefrom, packaged in 10–20 g sachets, are sold by herbalists in the open market. Claimed medicinal uses include adaptogenic properties to combat stress and as a stimulant (Toyang et al., 2012). The plant is also used as an anthelmintic, an aphrodisiac, an antidote and to treat malaria and jaundice (Iwu, 1993, Jiofack et al., 2010).
On the phytochemistry and biological activity of V. guineensis, early isolation work on this plant was carried out by Toubiana et al. (1975) who isolated two compounds called Vernodalin and vernolepin. These compounds have also been isolated from other members of the Vernonia genus including V. amygdalina and have been reported to be responsible for the antibacterial activity related to the use of this species by chimpanzees (Jisaka et al., 1993). Tchinda et al., 2002, Tchinda et al., 2003 reported the isolation of stigmastane derivatives and sucrose ester type compounds from the roots, with one of the stigmastanes showing anti-trypanocidal activity. Recent studies resulted in the isolation of a sucrose ester from the roots with antiprostate cancer activity (Toyang et al., 2012) and a stigmastane steroid with antimicrobial activity (Donfack et al., 2012).
The diagnosis of new cancer cases remains on the rise worldwide, and there is a need for the continuous search for new anticancer agents (Parkin et al., 2008, Ferlay et al., 2010). Based on the preliminary cytotoxicity activity observed with the root extract of V. guineensis (Toyang et al., 2012a), the leaves were evaluated and found to be even more potent than the roots. Bioactivity guided fractionation of the leaf extract afforded a germacranolide and an elemanolide with cytotoxic and clonogenic activity which are reported herein.
Section snippets
Plant material collection
The leaves of V. guineensis Benth. Var. cameroonica were harvested from young plants at Baicham, Boyo, Division of the North West Region of Cameroon in 2009. A voucher specimen was authenticated at the Limbe Botanic Garden, South West Region Cameroon and deposited at the Limbe Botanic Garden Herbarium with reference no.: SCA 12431.
Extraction and isolation
The powder of V. guineensis leaves (1.5 kg) was extracted with 10 L of acetone 2× for 24 h and filtered using a Buchner funnel and Whatman no.1 filter paper. The marc
Activity guided isolation
The acetone extract obtained as described above was found to be active (IC50 6.24 μg/mL) against the PC-3 prostate cancer cell line which was used for the bioactivity guided fractionation. The extract (50 g) was absorbed onto Celite and then fractionated over a silica gel column, eluting with a gradient of n-hexane–ethyl acetate. Sixteen fractions were obtained and pooled on the basis of TLC analysis to seven main fractions. Fraction #4 (11 g) obtained with n-hexane/ethyl acetate (1:1) was active
Discussion
The sesquiterpene lactones, Vernopicrin (1) and Vernomelitensin (2) were isolated for the first time from V. guineensis in this study, to the best of our knowledge, and show cytotoxicity against a range of cancer cell lines. Sesquiterpene lactones are commonly found amongst plants of the Asteraceae family (Merfort, 2011). At least 34 sesquiterpene lactones from the Vernonia genus have been reported to possess anticancer and other biological activities including antimalarial, antibiotic,
Conclusion
The present paper reports the isolation of two cytotoxic sesquiterpene lactones from V. guineensis. The cytotoxicity demonstrated by the crude extract and isolated sesquiterpenes against cancer cell lines supports the medicinal potential of V. guineensis. The anti-proliferation activity and dose dependent anticlonogenic activity suggests that the identified sesquiterpenes could be potential leads for development into antitumor compounds. The in-vivo efficacy studies of Vernopicrin and
Acknowledgment
The authors are grateful to Alosyius N. Toyang, Yua Eric and Therese Toyeng for assisting with the collection and processing of the plant material. The technical support of the Translational Core, Greenebaum Cancer Center at the University of Maryland School of Medicine; a NCI Comprehensive Cancer Center are acknowledged.
References (31)
- et al.
Sesquiterpene lactones from Vernonia scorpioides and their in vitro cytotoxicity
Phytochemistry
(2010) - et al.
Stigmatane derivatives from the root extract of Vernonia guineensis and their antimicrobial activity
Phytochemistry Letters
(2012) - et al.
Estimates of cancer incidence and mortality in Europe in 2008
European Journal of Cancer
(2010) - et al.
Sesquiterpene lactones from Centaurea tweediei
Biochemical Systematics and Ecology
(2001) - et al.
Insect antifeedant elemanolide lactones from Vernonia amygdalina
Phytochemistry
(1983) - et al.
What made sesquiterpene lactones reach cancer clinical trials
Drug Discovery Today
(2010) - et al.
Antimalarials from nature
Bioorganic and Medicinal Chemistry
(2009) - et al.
Ent-kaurane glycosides and sesquiterpene lactones of the hirsutinolide type from Vernonia triflosculosa
Phytochemistry
(2006) - et al.
Use of Vernonia amygdalina by wild chimpanzee: possible roles of its bitter and related constituents
Physiology and Behavior
(1994) - et al.
Sesquiterpenes from Centaurea aspera
Phytochemistry
(2005)
WST-1-based cell cytotoxicity assay as a substitute for MTT-based assay for rapid detection of toxigenic Bacillus species using CHO cell line
Journal of Microbiological Methods
Cancer in indigenous Africans: burden, distribution, and trends
The Lancet Oncology
Two new elemanolides from Onopordon leptolepis
Phytochemistry
Vernoguinosterol and vernoguinoside, trypanocidal stigmastane derivatives from Vernonia guineensis (Asteraceae)
Phytochemistry
Stigmatane derivatives and isovaleryl sucrose esters from Vernonia guineensis (Asteraceace)
Phytochemistry
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