RETRACTED ARTICLE: Asiatic acid attenuates pre-neoplastic lesions, oxidative stress, biotransforming enzymes and histopathological alterations in 1,2-dimethylhydrazine-induced experimental rat colon carcinogenesis

Abstract

Asiatic acid (AA), a pentacyclic triterpenoid, derived from the tropical medicinal plant Centella asiatica is known to exhibit numerous pharmacological properties. We hypothesized that AA will have chemopreventive potential against 1,2-dimethylhydrazine (DMH)-induced experimental colon carcinogenesis in male Wistar rats. Rats were arbitrarily divided into six groups. Group I rats were processed as control. Group II rats received AA (8 mg/kg b.w., p.o.) and groups III-VI rats received subcutaneous injections of DMH (20 mg/kg b.w.) once a week, for the first four weeks. In addition, groups IV-VI rats received AA at the doses of 2, 4 and 8 mg/kg b.w., respectively, for 16 weeks. Our results discovered that supplementation with AA to the DMH-exposed rats significantly decreased the incidence of polyps and Aberrant crypt foci (ACF) as compared to the DMH-alone-exposed rats. Moreover, in the AA-supplemented DMH-exposed rats, we ascertained increased activities of the antioxidants and decreased levels of lipid peroxidation (LPO) in the liver and circulation and enhanced levels of both LPO and antioxidants in the colon, which were altered in the DMH-alone-exposed rats. Furthermore, we also observed altered activities of vitamins C and E and biotransforming enzymes in DMH-alone-exposed rats, which were reversed on AA supplementation. All the observations were supported by our histological findings. Thus, we can conclude that, AA could be used as an effective chemopreventive agent against DMH-induced colon carcinogenesis.

Therapeutic Potential of Centella asiatica and Its Triterpenes: A Review

“…It also has a certain therapeutic effect on gastrointestinal tumors. Three mechanisms are reported in the studies: asiatic acid can reduce the level of pro-apoptotic factors (B-cell lymphoma 2(Bcl-2) ↑, Bcl-2-associated X protein(Bax) ↓, caspase-3 ↓), and related inflammation factors (TGF-β1 ↓, TNF-α ↓, IL-6 ↓, IL-1β ↓), and increase the level of anti-oxidative stress factors (SOD ↑, GSH-Px ↑, CAT ↑, GST ↑, GSH ↑) ( Xiao et al, 2017 ; Siddique et al, 2017 ; Wei et al, 2018 .). The study on madecassoside found that it could ameliorate drug-induced acute liver failure by reducing inflammation (TNF-α ↓, IL-1β ↓, IL-6 ↓, iNOS ↓, COX-2 ↓) and oxidative stress (SOD ↑, CAT ↑, GPx ↑, Nrf2 ↑, HO-1 ↑) ( Wang W. et al, 2018 ).…”

Orientin, a flavanoid, mitigates 1, 2 dimethylhydrazine-induced colorectal lesions in Wistar rats fed a high-fat diet

“…DMH was dissolved in1mM EDTA just ahead of use and the pH adjusted to 6.5 with 1 mM NaOH to make sure the stability of carcinogen. Animals were given subcutaneous injections of DMH at a dose of 20 mg/kg body weight for 4 consecutive weeks of the total experimental period [ 28 , 29 ].…”

Pharmacological Properties, Molecular Mechanisms, and Pharmaceutical Development of Asiatic Acid: A Pentacyclic Triterpenoid of Therapeutic Promise

“…AA reduced polyps and aberrant crypt foci and salvaged colonic tissues following reduction in lipid peroxidation and restoration of antioxidant defense in the colon. In another study, the protective mechanism in colon cancer was demonstrated by virtue of anti-inflammatory, antiproliferative, and pro-apoptotic properties of AA (Siddique et al, 2017 ). AA improved disease activity indices, decreased phase I metabolic enzymes and improved phase II metabolic enzymes and mucin in colon cancer in rats induced by DMH.…”