Aqueous Extract of Salvia miltiorrhiza Bunge-Radix Puerariae Herb Pair Attenuates Osteoporosis in Ovariectomized Rats Through Suppressing Osteoclast Differentiation

Abstract

Traditional herb pair Salvia miltiorrhiza Bunge-Radix Puerariae (DG) owns various biological activities including anti-inflammatory and anti-oxidative stress. Oxidative stress is one high-risk factor for osteoporosis, then effect of DG on osteoporosis and underlying mechanisms was explored both in vivo and in vitro. Firstly, the predication from network pharmacology hinted that DG has the potential for ameliorating osteoporosis. Consistent with predication, DG significantly restored bone loss and deficiency of type II collagen, decreased TRAP and Cathepsin K positive areas in femur. Meanwhile it improved important characteristics of microarchitectural deterioration of tissue, reduced the numbers of NFATc1-positive osteoclast in the vertebra as well as decreased the serum osteoclast-specific cytokine RANKL and OPG release in OVX rats exhibiting its protective effect against osteoporosis. In vitro, DG noticeably decreased osteoclastic-special marker protein expressions of RANK, c-Fos and NFATc1. Furthermore, autophagy pathway p62/LC3B, ROS production and NF-κB were all activated by RANKL stimulation and blocked by DG pretreatment. Moreover, autophagy inhibitors, ROS scavenger, Ca2+ chelator and NF-κB inhibitor remarkably suppressed c-Fos and NFATc1 expressions. Taken together, DG may ameliorate osteoporosis by regulating osteoclast differentiation mediated by autophagy and oxidative stress. This study provided a mechanistic basis for DG treating osteoporosis and offered a safe dose for DG in preventing and improving bone diseases.

Orcinol Glucoside Improves Senile Osteoporosis through Attenuating Oxidative Stress and Autophagy of Osteoclast via Activating Nrf2/Keap1 and mTOR Signaling Pathway

“…Increasing evidence displays that autophagy dysregulation results in alteration of osteoclast function and increased bone loss [ 10 ]. Under oxidative stress, autophagy is activated [ 11 ] and accompanied by an unusual increase in osteoclast differentiation and bone resorption [ 12 ]. Thus, the interplay between oxidative stress and autophagy plays a crucial role in cellular homeostasis and the survival of osteoclast.…”

Dehydromiltirone inhibits osteoclast differentiation in RAW264.7 and bone marrow macrophages by modulating MAPK and NF-κB activity

“…The traditional Chinese medicine s, Salvia miltiorrhiza Bge and Salvia przewalskii Maxim have been widely used to treat osteoporosis and other related diseases in the clinic. Other active ingredients have also been demonstrated to inhibit osteoporosis by blocking osteoclast production or promoting osteoblast growth ( Guo et al, 2014 ; He et al, 2019 ; Ekeuku et al, 2021 ; Qin et al, 2021 ; Qu et al, 2021 ). DHT, a diterpenoid quinone found in the traditional Chinese medicines, Salvia miltiorrhiza Bge and Salvia przewalskii Maxim , has been widely used to prevent liver injury by modifying the MAPK and NF-κB signaling pathways, reducing neuroinflammatory responses, and inhibiting platelet aggregation.…”

Anti-osteoporosis effects and regulatory mechanism of Lindera aggregata based on network pharmacology and experimental validation

“…Osteoporosis (OP) is a metabolic and systemic skeletal disease characterized by increased bone resorption and reduced bone mineral density, which results in increased bone fragility and fracture risk. 1,2 It seriously affects the health and quality of life of the elderly due to its high incidence and disability rate. 3 OP has become a public health issue of universal concern with the inevitable ageing of population.…”

“…6 Many studies have reported that excessive bone resorption is the key point of OP, and osteoclast is considered to be the most important target for treating OP. 1,7,8 Currently, the drugs for preventing and curing OP mainly include anabolic agents, anti-catabolic agents, and supplements, such as vitamin K2, calcium, and strontium. 9 However, these drugs have disadvantages such as serious adverse effects and poor efficacy.…”