Abstract
Rehmanniae Radix Praeparata (RR, named as Shudihuang in traditional Chinese medicine), the steamed roots of Rehmannia glutinosa Libosch (Scrophulariaceae), has been demonstrated to have anti-diabetic and anti-osteoporotic activities. This study aimed to explore the protective effect and underlying mechanism of RR on diabetes-induced bone loss. It was found that RR regulated the alkaline phosphatase activity and osteocalcin level, enhanced bone mineral density, and improved the bone microarchitecture in diabetic rats. The catalpol (CAT), acteoside (ACT), and echinacoside (ECH) from RR increased the proliferation and differentiation of osteoblastic MC3T3-E1 cells injured by high glucose and promoted the production of IGF-1 and expression of related proteins in BMP and IGF-1/PI3K/mammalian target of rapamycin complex 1 (mTOR) signaling pathways. The verifying tests of inhibitors of BMP pathway (noggin) and IGF-1/PI3K/mTOR pathway (picropodophyllin) and molecular docking of IGF-1R further indicated that CAT, ACT, and ECH extracted from RR enhanced bone formation by regulating IGF-1/PI3K/mTOR signaling pathways. These findings suggest that RR may prove to be a promising candidate drug for the prevention and treatment of diabetes-induced osteoporosis.
Highlights
Diabetes mellitus (DM) and osteoporosis are common diseases with increasing prevalence in the aging population [1]
The aim of the present study was to observe the protective effects of Radix praeparata (RR) against bone loss in a diabetic rat model induced by STZ combined with high fat and high glucose diet, clarify the effects of active components in RR on MC3T3-E1 osteoblasts damaged by high glucose, and explore the underlying action mechanisms of these active constituents in RR in regulating bone formation through the Insulin-like growth factors (IGFs)-1/PI3K/mammalian target of rapamycin complex 1 (mTOR) pathways
The body weight in the model groups was significantly lower than that in the CON group, while there was no significant difference in body weight between the model groups and alendronate sodium treatment (ALE), metformin treatment (MET), and RR treatment groups
Summary
Diabetes mellitus (DM) and osteoporosis are common diseases with increasing prevalence in the aging population [1]. Bone loss or osteoporosis induced by DM, known as diabetic osteoporosis (DOP), is characterized by poor bone healing and regeneration, and increased risk of bone fractures [3]. Accumulating evidence has shown that the risk of osteoporotic fractures is significantly increased in both type 1 (T1)DM and type 2 (T2)DM patients [4]. The treatment costs of bone fractures in diabetic patients are increased due to prolonged wound healing and other complications. With the sharp increase in diabetic populations, diabetic osteoporosis, which often causes more pains and increased risk of fractures for DM patients, has become a clinical challenge that needs to be addressed.
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