Protective effect of centella triterpene saponins against cyclophosphamide-induced immune and hepatic system dysfunction
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ORIGINAL PAPER
Protective effect of centella triterpene saponins against cyclophosphamide-induced immune and hepatic system dysfunction in rats: its possible mechanisms of action Pragathi Duggina & Chandra Mouli Kalla & Seshadri Reddy Varikasuvu & Suman Bukke & Vijaya Tartte Received: 14 November 2014 / Accepted: 3 July 2015 # University of Navarra 2015
Abstract This study was designed to investigate the protective effects of the centella triterpene saponins (EXT) on cyclophosphamide (CYP)-induced hepatotoxicity and immunosuppression in rats. The phytochemical profile of EXT was analyzed for centella saponins by using high-performance liquid chromatographic (HPLC). Therapeutic efficacy of EXT (250 mg/kg/day p.o) on hematological profile of blood, liver function markers, and cytokine profiles in CYP (10 mg/kg/day p.o)-treated rats. In addition, weights of immune organs
Pragathi Duggina and Chandra Mouli Kalla contributed equally to this work. P. Duggina Department of Biotechnology, Sri Venkateswara University, Tirupati, Andhra Pradesh, India C. M. Kalla Department of Biotechnology, Vikrama Simhapuri University, Nellore, Andhra Pradesh, India S. R. Varikasuvu Department of Biochemistry, BPS Govt Medical College for Women, Sonepat, Haryana, India S. Bukke Department of Biochemistry, Sri Venkateswara University, Tirupati, Andhra Pradesh, India V. Tartte (*) Department of Botany, Sri Venkateswara University, Tirupati, Andhra Pradesh, India e-mail: [email protected]
(spleen and thymus) and histopathological changes in the liver, intestine, and spleen were also evaluated. The active principles in EXT were identified as madecassoside, asiaticoside, and asiatic acid by HPLC analysis. Upon administration of EXT, enhanced levels of glutamate pyruvate transaminase, alkaline phosphatase, and lipid peroxidation were found reduced while the levels of reduced glutathione and hematological parameters and relative weights of immune organs were restored to normal in CYP-treated rats. The hepatic mRNA level of TNF-α, which was increased during CYP administration, was significantly decreased by the EXT treatment. The decreased levels of mRNA expression of other cytokines like IFN-γ, IL-2, GM-CSF, after CYP treatment, were also found elevated upon administration of the EXT. Histopathological examination of the intestine, liver, and spleen indicated that the extract could attenuate the CYPinduced hepatic and immune organ damage. These results indicated that EXT modulated the immune and hepatic system function of rats against CYPinduced immunosuppression and hepatotoxicity by restoring the cytokine production, antioxidant system, and multiorgan injury. Thus, triterpene saponins may provide protective and/or therapeutic alternative against the immune-mediated liver diseases. Keywords Asiatic acid . Asiaticoside . Cyclophosphamide . Hepatotoxicity . Immunosuppression . Madecassoside
P. Duggina et al.
Introduction The immune system is the body’s defense against microbes and foreign antigens. It is involved in the etiology as well as
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