Elephant's foot (Elephantopus scaber L)

[Rich66]

(Cox2, VEGF, apoptosis, stronger than Paclitaxel?)



Br J Pharmacol. 2010 Jan 25. [Epub ahead of print]
Deoxyelephantopin, a novel multifunctional agent, suppresses mammary tumour growth and lung metastasis and doubles survival time in mice.

Huang CC, Lo CP, Chiu CY, Shyur LF.
Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.
Background and purpose: Elephantopus scaber L. (Asteraceae) is a traditional herbal medicine with anti-cancer effects. We evaluated the in vitro and in vivo efficacy of a major sesquiterpene lactone constituent of E. scaber, deoxyelephantopin (DET), against mammary adenocarcinoma and the underlying molecular mechanism. Experimental approach: A variety of cellular assays, immunoblotting and immunohistochemistry, as well as both orthotopic and metastatic TS/A tumour models in BALB/c mice, were used. Test mice were pretreated and post-treated with DET or paclitaxel and mammary tumour growth evaluated. Key results: DET (Pretreatment with DET was more effective than paclitaxel, for profound suppression of orthotopic tumour growth (99% vs. 68% reduction in tumour size) and lung metastasis of TS/A cells (82% vs. 63% reduction in metastatic pulmonary foci) and prolonged median survival time (56 vs. 37 days, P < 0.01) in mice. The levels of cyclooxygenase-2 and vascular endothelial growth factor in metastatic lung tissues of TS/A-bearing mice were attenuated by DET. Conclusions and implications: Our data provide evidence for the suppression of mammary adenocarcinoma by DET with several mechanisms and suggest that DET has potential as a chemopreventive agent for breast cancer.

PMID: 20105176 [PubMed - as supplied by publisher]

LINK ANTITUMOR ACTIVITIES OF THE FOUR SESQUITERPENE LACTONES FROM ELEPHANTOPUS SCABER L.

G. Xu^{1, 2}, Q. Liang³, Z. Gong^{1, *}, W. Yu⁴, S. He⁵, L. Xi^6
1Center for New Drug Research & Development, College of Life Science,
Nanjing Normal University, Nanjing, China
²Molecular and Medical Biology Laboratory, College of Life Science,
Nanjing Normal University, Nanjing, China
³Nanjing University of Traditional Chinese Medicine, Nanjing, China
⁴Department of Pathophysiology Medical School of Southeast University, Nanjing, China
⁵Department of Biochemical Pharmaceutics, China Pharmaceutical University, Nanjing, China
⁶Department of Pharmacology, China Pharmaceutical University, Nanjing, China
Abstract. Aim: To evaluate antitumor activity of sesquiterpene lactones (scabertopin (ES-2), isoscabertopin (ES-3), deoxyelephantopin (ES-4), isodeoxyelephantopin (ES-5)) isolated from Elephantopus scaber L. in vitro and in vivo. Methods: SMMC-7721, Caco-2 and HeLa cell lines were treated with ES-2,3,4,5. Cell viability was determined by MTT assay. Agarose gel electrophoresis was used to detect DNA fragmentation. To evaluate in vivo antitumor activity of ES-4, experimental murine tumor model was used. Results: It was shown that ES-2, ES-4, ES-5 exhibited significant antitumor effect in vitro in a concentration-dependent manner. However, the effect of ES-3 on the growth of tested cell lines was relatively weak. In HeLa cells exposed to ES-4 for 48 h, morphological changes and DNA ladder pattern evidencing on apoptosis were detected. ES-4 revealed in vivo antitumor activity. Conclusion: Antitumor activity of studied sesquiterpene lactones may be due, at least in part, to induction of apoptosis in vitro. ES-4 possesses also antitumor activity in vivo.
Key Words: Elephantopus scaber L., sesquiterpene lactones, antitumor activity.
Language:



J Proteome Res. 2010 Jan;9(1):237-53.
Differential proteomic profiling identifies novel molecular targets of paclitaxel and phytoagent deoxyelephantopin against mammary adenocarcinoma cells.

Lee WL, Wen TN, Shiau JY, Shyur LF.
Molecular and Biological Agricultural Sciences Program, Taiwan International Graduate Program, Taiwan, ROC.
A major germacranolide sesquiterpene lactone, deoxyelephantopin, identified from Elephantopus scaber L. (known as "Didancao" in Chinese medicine) showed significant antitumor growth and antimetastatic effect on murine mammary adenocarcinoma TS/A cells in vitro and in vivo in mice. Deoxyelephantopin exhibited a superior effect to that of the paclitaxel in prolonging median survival time of tumor-bearing animals in our recent study. To investigate the molecular mechanisms underlying the difference in efficacy between deoxyelephantopin and paclitaxel, we used 2-D DIGE and LC-ESI-MS/MS to profile proteins differentially expressed in the nucleus and cytoplasm of TS/A cells and used the MetaCore database to determine the functional protein networks affected by both treatments. Deoxyelephantopin and paclitaxel treatment produced regulation of molecules involved in proteolysis and calcium ion transport, suggesting the possible effects of both drugs on proteasome and endoplasmic reticulum machinery in TS/A cells. Western blot analysis of marker proteins (e.g., PDI, GRP78, TXND5, caspase-12, caspase-3 and PARP) further verified that induction of endoplasmic reticulum stress was associated with apoptosis induced by both deoxyelephantopin and paclitaxel, but only deoxyelephantopin inhibited proteasomal proteolysis in TS/A cells. The novel effects on targeting ER machinery and suppressing proteasome activity suggest the great potential of deoxyelephantopin for mammary cancer therapy.

PMID: 19894775 [PubMed - in process]



Phytomedicine. 2009 Mar;16(2-3):252-7. Epub 2008 Aug 6.
A novel steroid from Elephantopus scaber L. an ethnomedicinal plant with antidiabetic activity.

Daisy P, Jasmine R, Ignacimuthu S, Murugan E.
Department of Biotechnology, Holy Cross College, Tiruchirappalli 620002, India.
Acetone extract of Elephantopus scaber, an ethnomedicnal plant, reduced the blood glucose levels in streptozotocin-induced diabetic rats significantly. Acute toxicity studies revealed the non-toxic nature of the crude extract. Fractionation of the acetone extract yielded a new steroid, 28Nor-22(R)Witha 2,6,23-trienolide. Biological testing of the compound demonstrated a significant antidiabetic activity by reducing the elevated blood glucose levels and restoring the insulin levels in streptozotocin-induced diabetic rats. This compound can be a useful candidate to treat diabetes.

PMID: 18693100 [PubMed - indexed for MEDLINE]



J Asian Nat Prod Res. 2008 May-Jun;10(5-6):403-7.
A new elemanolide sesquiterpene lactone from Elephantopus scaber.

Liang QL, Min ZD, Tang YP.
Department of Medicinal Chemistry, Nanjing University of Chinese Medicine, Nanjing, China.
A new elemanolide sesquiterpene lactone, named elescaberin (1), together with two known compounds, namely, isodeoxyelephantopin (2) and deoxyelephantopin (3), was isolated from the whole plant of Elephantopus scaber. The structure of 1 was elucidated on the basis of spectroscopic analysis. All three compounds exhibited significant inhibitory activities against human SMMC-7721 liver cancer cells in vitro (IC(50) 8.18-14.08 micromol/l).

PMID: 18464077 [PubMed - indexed for MEDLINE]

SOURCES

Yao Xue Xue Bao. 1996;31(7):543-53.
Authentication of the Chinese drug "ku-di-dan" (herba elephantopi) and its substitutes using random-primed polymerase chain reaction (PCR).

Cao H, But PP, Shaw PC.
Department of Biology, Chinese University of Hong Kong, Shatin, N. T., Hong Kong.
DNA fingerprinting and polymorphism among the Chinese drug "Ku-Di-Dan" and its substitutes were demonstrated with arbitrarily primed polymerase chain reaction (AP-PCR) and random amplified polymorphic DNA (RAPD). Distinctive, reproducible genomic fingerprints from DNA of the Chinese drug Ku-Di-Dan and 9 species of Compositae were generated with six long (18-24 mer) and one short (10 mer) random-chosen primers with PCR. Ku-Di-Dan samples can be distinguished according to the banding patterns of their amplified DNA on agarose gels. Results showed that AP-PCR and RAPD fingerprints of the commercial samples of Ku-Di-Dan retailed in Fujian, Taiwan, Hong Kong and Macau markets are identical with that of Elephantopus scaber L. The relatedness of Ku-Di-Dan among 9 plants may also be estimated by the Similarity Indexes values of the genomic DNA fingerprints.

PMID: 9772698 [PubMed - indexed for MEDLINE]






J Ethnopharmacol. 1995 Feb;45(2):113-23.
The evaluation of hepatoprotective effects of Taiwan folk medicine 'teng-khia-u'.

Lin CC, Tsai CC, Yen MH.
Graduate Institute of Natural Products of Kaohsiung Medical College, Taiwan, ROC.
'Teng-khia-u' is a folk medicine of Taiwan, derived from the entire plants of Elephantopus scaber L., E. mollis H.B.K. and Pseudoelephantopus spicatus (Juss.) Rohr. The hepatoprotective effects of water extracts of these three plants against beta-D-galactosamine (D-GalN)- and acetaminophen (APAP)-induced acute hepatic damage were determined in rats. The results indicated that the serum glutamate-oxalate-transaminase (sGOT) and the serum glutamate-pyruvate-transaminase (sGPT) levels caused by D-GalN and APAP decreased after treatment with crude extracts of 'teng-khia-u' (P < 0.005). The pathological changes of hepatic lesions, caused by D-GalN and APAP, improved following treatment with the drug extracts mentioned above.

PMID: 7776660 [PubMed - indexed for MEDLINE]





http://en.wikipedia.org/wiki/Elephantopus

Elephantopus is a genus of at least twelve species of perennials in the daisy family. Several species are native to the southeastern United States,^[3] and at least one is native to India and the Himalayas.^[4]

E. scaber is a traditional medicine^[5] and other species, including E. mollis^[6] and E. carolinianus,^[7] have also been investigated for medicinal properties. E. scaber contains elephantopin which is a germacranolide sesquiterpene lactone containing two lactone rings and an epoxide functional group, and it has shown to have an antitumour activity.^[8]



Elephantopus tomentosus in the United States

1. ^ "187d. Asteraceae Martinov tribe Vernonieae Cassini". Flora of North America. http://www.efloras.org/florataxon.as...taxon_id=20545.
2. ^ "29. Elephantopus Linnaeus". Flora of North America. http://www.efloras.org/florataxon.as...axon_id=111427.
3. ^ "Elephantopus L.". USDA PLANTS. http://plants.usda.gov/java/profile?symbol=ELEPH.
4. ^ Press, J.R., Shrestha, K.K. & Sutton, D.A.. "Elephantopus L.". Annotated Checklist of the Flowering Plants of Nepal. http://www.efloras.org/florataxon.as...axon_id=111427. Retrieved 2009-06-15.
5. ^ Poli, A; Nicolau, M; Simoes, Cm; Nicolau, Rm; Zanin, M (Aug 1992). "Preliminary pharmacologic evaluation of crude whole plant extracts of Elephantopus scaber. Part I: in vivo studies". Journal of ethnopharmacology 37 (1): 71–6. ISSN 0378-8741. PMID 1453704.
6. ^ Tabopda, Tk; Liu, J; Ngadjui, Bt; Luu, B (Apr 2007). "Cytotoxic triterpene and sesquiterpene lactones from Elephantopus mollis and induction of apoptosis in neuroblastoma cells". Planta medica 73 (4): 376–80. doi:10.1055/s-2007-967132. ISSN 0032-0943. PMID 17366372.
7. ^ Lee, Kh; Cowherd, Cm; Wolo, Mt (Sep 1975). "Antitumor agents. XV: Deoxyelephantopin, an antitumor principle from Elephantopus carolinianus Willd". Journal of pharmaceutical sciences 64 (9): 1572–3. ISSN 0022-3549. PMID 1185584.
8. ^ "Antitumor activity of elephantopus scaber linn against dalton's ascitis lymphoma", Indian Journal of Pharmaceutical Sciences 64 (1): 71-3, 2002 Jan-Feb