Chebulagic acid, a COX–LOX dual inhibitor isolated from the fruits of Terminalia chebula

详细信息    查看全文

• 作者：D. Bharat Reddy ; T.C.M. Reddy ; G. Jyotsna ; Satish Sharan ; Nalini Priya ; V. Lakshmipathi ; Pallu Reddanna
• 关键词：Terminalia chebula Retz. ; Chebulagic acid ; COX– ; LOX dual inhibitor ; Anti-oxidant ; Apoptosis
• 刊名：Journal of Ethnopharmacology
• 出版年：2009
• 出版时间：30 July 2009
• 年：2009
• 卷：124
• 期：3
• 页码：506-512
• 全文大小：600 K

文摘

Ethnopharmacological relevance

Terminalia chebula has an esteemed origin in Indian mythology; its fruits are used to treat many diseases such as digestive, diabetes, colic pain, chronic cough, sore throat, asthma, etc.

Aim of the study

The water or ethanolic extracts of the fruits were reported to have anti-oxidant, anti-inflammatory, anti-cancer and radio-protector properties. The present study is to isolate and identify the compounds that inhibit COX and 5-LOX, the key enzymes involved in inflammation and carcinogenesis.

Materials and methods

The ethanolic extract of the fruits was fractionated by RP-HPLC and fractions were tested for enzyme inhibition activity against COX and 5-LOX. One of the fractionated compounds showed potent dual inhibition against COX and 5-LOX. It was identified as chebulagic acid by LC–MS, NMR and IR analyses. The chebulagic acid was also tested for anti-proliferative activity.

Results

Chebulagic acid showed potent COX–LOX dual inhibition activity with IC₅₀ values of 15 ± 0.288, 0.92 ± 0.011 and 2.1 ± 0.057 μM for COX-1, COX-2 and 5-LOX respectively. It also showed anti-proliferative activity against HCT-15, COLO-205, MDA-MB-231, DU-145 and K562 cell lines. Further mechanistic studies on COLO-205 cells revealed induction of apoptosis by chebulagic acid.

Conclusions

Chebulagic acid, a COX-2 and 5-LOX dual inhibitor isolated from the fruits of Terminalia chebula, induces apoptosis in COLO-205 cells.