Abstract
Madecassoside (MA), a triterpenoid saponin isolated from C. asitica, exerts various pharmacological activity including antioxidative and antinflammatory. Doxorubicin (DOX), a common chemotherapeutic drug, has been reported to induce numerous toxic side effects including renal-toxicity. We hypothesized that MA administration may decrease renal-toxicity caused by DOX. In this study, we investigated this hypothesis by introducing MA and DOX into the culture of Human Proximal Tubule Cells HK-2 and mice model. Our in vivo study demonstrated that MA (12 mg/kg), treatment for two weeks attenuated DOX-induced renal injury via protecting renal function, recovering antioxidant enzyme activity, inhibiting Bax, p-ERK1/2, NF-κB p65, iNOS expression and increasing Bcl-2 expression. Similar findings were obtained in our in vitro studies with treatment of DOX and/or MA. Further studies with application of iNOS inhibitor and ERK1/2 kinase inhibitor indicated that the inhibitory effects of MA on DOX-induced apoptosis and inflammation might be mediated by the suppression of the activation of cleaved caspase-3, ERK1/2 pathways, NF-κB p65 and NO production. These results suggest that MA is a promising protective agent for DOX-induced renal toxicity and can be a potential candidate to protect against renal toxicity in DOX-treated cancer patients.
Highlights
Centella asiatica (Umbelliferae), growing in tropical swampy areas, is an annual herbaceous plant used for treating renal disease in traditional Chinese medicine
Our results indicate that the inhibitory effects of MA on DOX-induced apoptosis and inflammation might be mediated by the suppression of the activation of cleaved caspase-3, ERK1/2 pathways, NF-κ B p65 and Nitric oxide (NO) production
After one week treatment, DOX treatment led to severe reduction of body weight compared to non-treatment control group, while the addition of MA rescued the DOX induced body loss (Fig. 2A)
Summary
Centella asiatica (Umbelliferae), growing in tropical swampy areas, is an annual herbaceous plant used for treating renal disease in traditional Chinese medicine. MA was found to be effective in decreasing oxidative stress and enhancing the activities of antioxidative enzymes in various disease models[3,4,5,6]. DOX has highly potent cytotoxicity to induce Human Proximal Tubule Cells HK-2 cells apoptosis by significantly changing caspase activities[13]. MA has shown anti-inflammatory and anti-oxidant effects in multiple disease models, whether it could inhibit DOX-induced cell apoptosis has not been examined. Our results indicate that MA administration can significantly attenuate DOX-induced HK-2 cell apoptosis. Our results indicate that the inhibitory effects of MA on DOX-induced apoptosis and inflammation might be mediated by the suppression of the activation of cleaved caspase-3, ERK1/2 pathways, NF-κ B p65 and Nitric oxide (NO) production. Our results support the application of MA as a protective agent in chemotherapy medicine optimization and practice
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
