Inhibition of tanshinone IIA on renin activity protected against osteoporosis in diabetic mice

CONTEXT: Salvia miltiorrhiza Bge. (Labiatae) (SMB) is applied clinically for management of diabetic osteoporosis in China, and research results has suggested its potential action on renin–angiotensin system (RAS). OBJECTIVE: This study screens and explores naturally occurring bioactive constituents from the root of SMB acting on renin activity and evaluates its osteoprotective efficacy in diabetic mice. MATERIALS AND METHODS: Human embryonic kidney (HEK) 293 cells, engineered to express human renin, were used as an in vitro model to identify bioactive compound, tanshinone IIA, inhibiting renin activity. The C57BL/6 mice (n = 10 in each group) with diabetes induced by streptozotocin (STZ) were intraperitoneally injected with tanshinone IIA (10 and 30 mg/kg). The mice without STZ treatment and the diabetic mice treated with aliskiren were used as non-diabetic control and positive control, respectively. RESULTS: Tanshinone IIA was found to display inhibitory effects on renin activity of HEK-293 cells; moreover, it down-regulated protein expression of ANG II in human renin-expressed HEK-293 cells. Treatment of diabetic mice with tanshinone IIA with both doses could significantly decrease ANG II level in serum (from 16.56 ± 1.70 to 10.86 ± 0.68 and 9.14 ± 1.31 pg/mL) and reduce ANG II expression in bone, consequently improving trabecular bone mineral density and micro-structure of proximal tibial end and increasing trabecular bone area of distal femoral end in diabetic mice. CONCLUSIONS: This study revealed beneficial effects of tanshinone IIA on bone of diabetic mice, and potentially suggested the application of Salvia miltiorrhiza in the treatment of osteoporosis and drug development of tanshinone IIA as a renin inhibitor.