Abstract

Pueraria tuberosa (Roxb. ex Willd.) DC., known as Indian Kudzu belongs to family Fabaceae and it is solicited as "Rasayana" drugs in Ayurveda. In the present study, we analyzed the efficacy of an ethyl acetate fraction from the tuber extract of Pueraria tuberosa (fraction rich in antioxidant compounds, FRAC) against menopausal osteoporosis, and breast and ovarian cancer cells. The FRAC from Pueraria tuberosa was characterized for its phenolic composition (total phenolic and flavonoid amount). Antioxidant property (in vitro assays) of the FRAC was also carried out followed by the analysis of the FRAC for its antiosteoporotic and anticancer potentials. The antiosteoporotic activity of FRAC was investigated in ovariectomy-induced osteoporosis in rats. The cytotoxicity effect was determined in breast and ovarian cancer cells. Gas chromatography/mass spectrometry (GC/MS) analysis of the FRAC was performed to determine its various phytoconstituents. Docking analysis was performed to verify the interaction of bioactive molecules with estrogen receptors (ERs). The FRAC significantly improved various biomechanical and biochemical parameters in a dose-dependent manner in the ovariectomized rats. FRAC also controlled the increased body weight and decreased uterus weight following ovariectomy in rats. Histopathology of the femur demonstrated the restoration of typical bone structure and trabecular width in ovariectomized animals after treatment with FRAC and raloxifene. The FRAC also exhibited in vitro cytotoxicity in the breast (MCF-7 and MDA-MB-231) and ovarian (SKOV-3) cancer cells. Furthermore, genistein and daidzein exhibited a high affinity towards both estrogen receptors (α and β) in the docking study revealing the probable mechanism of the antiosteoporotic activity. GC/MS analysis confirmed the presence of other bioactive molecules such as stigmasterol, β-sitosterol, and stigmasta-3,5-dien-7-one. The FRAC from Pueraria tuberosa has potential for treatment of menopausal osteoporosis. Also, the FRAC possesses anticancer activity.

Highlights

  • The World Health Organization (WHO) defines osteoporosis as a decrease of bone mineral density (BMD) more than 2.5 standard deviations of the standard reference for BMD in young healthy women [1]

  • We have reported the presence of genistein and daidzein in the fraction rich in antioxidant compounds of Pueraria tuberosa [31]

  • Part of the protective effect of fraction rich in antioxidant compounds (FRAC) might be attributed to its antioxidant potential as bone loss in osteoporosis could be due to the generation of reactive oxygen species/oxidative stress along with other factors

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Summary

Introduction

The World Health Organization (WHO) defines osteoporosis as a decrease of bone mineral density (BMD) more than 2.5 standard deviations of the standard reference for BMD in young healthy women [1]. Osteoporosis deteriorates BMD, and bone architectural structure The cause of osteoporosis is variation in bone-forming (osteoblastic) and bone-resorbing (osteoclastic) cell function [3]. A decrease in the level of estrogen is the key contributing feature for menopausal osteoporosis (MO) in women. Oxidative stress can reduce the life span of osteoblasts by inhibiting osteoblastic differentiation and promoting bone resorption by boosting the development and activity of osteoclasts, causing osteoporosis. In MO, the activated osteoclasts produce reactive oxygen species like superoxides and a rise in the malondialdehyde level in blood. These oxidative stresses contribute to bone loss in osteoporosis [4]. Antioxidants can be useful in the management of MO by normalizing the altered osteoblastic and osteoclastic functions [10]

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