Tanshinone prevents alveolar bone loss in ovariectomized osteoporosis rats by up-regulating phosphoglycerate dehydrogenase

Cai

Yang

et al. 2020

Pharmaceutical Biology

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 ¼ 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.

Section: Discussionsupporting

confidence: 59%

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

Cai

Yang

et al. 2020

Pharmaceutical Biology

“…In our present study, we chose a rat model induced by OVX to mimic postmenopausal women with alveolar high-turnover bone loss. These patients usually feature high bone resorption and bone formation processes [ 32 , 33 ]. Our 3-D bone microstructure modeling revealed many parameters, e.g., Tb.Th, BV/TV, BS, Tb.N, Tb.Pf, Tb.Sp, as well as SMI were significantly changed.…”

Section: Discussionmentioning

confidence: 99%

A circRNA-miRNA-mRNA network plays a role in the protective effect of diosgenin on alveolar bone loss in ovariectomized rats

BMC Complement Med Ther

Yue

Wang

et al. 2020

Background The present study aimed to assess the perturbation in circular RNA (circRNA)/mRNA expression profiles and a circRNA-miRNA-mRNA coexpression network involved in the potential protective effect of diosgenin (DIO) on alveolar bone loss in rats subjected to ovariectomy (OVX). Methods The Wistar rats (female) manipulated with sham operation were classified as the SHAM group and the grouping of OVX rats administered with DIO, estradiol valerate or vehicle for 12 weeks was DIO group, EV group and OVX group respectively. Following treatments, the plasmatic levels of osteocalcin and tumor necrosis factor-alpha and the microstructure of alveolar bone were assayed. Based on microarray analyses, we identified differentially expressed (DE) circRNAs and mRNAs in alveolar bone of rats in both OVX and DIO group. The DE circRNAs and DE mRNAs involved in the bone metabolism pathway validated by RT-qPCR were considered key circRNAs/mRNAs. On the basis of these key circRNAs/mRNAs, we predicted the overlapping relative miRNAs of key circRNAs/mRNAs, and a circRNA-miRNA-mRNA network was built. Results DIO showed an anti-osteopenic effect on the rat alveolar bone loss induced by OVX. In total, we found 10 DE circRNAs (6 downregulated and 4 upregulated) and 614 DE mRNAs (314 downregulated and 300 upregulated) in samples of the DIO group compared with those of the OVX group. However, only one circRNA (rno_circRNA_016717) and seven mRNAs ( Sfrp1 , Csf1 , Il1rl1 , Nfatc4 , Tnfrsf1a , Pik3c2g , and Wnt9b ) were validated by qRT-PCR and therefore considered key circRNA/mRNAs. According to these key circRNA/mRNAs and overlapping predicted miRNAs, a coexpression network was constructed. After network analysis, one circRNA-miRNA-mRNA axis (circRNA_016717/miR-501-5p/ Sfrp1 ) was identified. Conclusion The mechanism of DIO inhibiting alveolar bone loss after OVX is possibly relevant to the simultaneous inhibition of osteogenesis and osteoclastogenesis by mediating the expression of important molecules in the Wnt, PI3K, RANK/RANKL or osteoclastogenic cytokine pathways. The circRNA_016717/miR-501-5p/ Sfrp1 axis may play important roles in these processes.

“…Tanshinone (10 mg/kg for a period of 21 days, i.v.) was also able to upregulate phosphoglycerate dehydrogenase and to thereby suppress OVX-induced osteoporosis and BMSC senescence ( 77 ). Tanshinone can alleviate the adverse effects of Dex treatment and consequence cellular injuries such as caspase-9-dependent apoptosis, increased cytosolic cytochrome c and Nox levels, and increased ROS generation ( 75 ).…”

Section: The Impact Of Herbal Medicines On Glucocorticoid- Induced Osteoporosismentioning

confidence: 99%

The Use of Herbal Medicines for the Prevention of Glucocorticoid-Induced Osteoporosis

Ying

et al. 2021

Front. Endocrinol.

Glucocorticoids are drugs that are widely used to suppress inflammation and the activation of the immune system. However, the prolonged use or at high doses of glucocorticoid can result in adverse side effects including osteoporosis, bone loss, and an increased risk of fracture. A number of compounds derived from natural plant sources have been reported to exert anti-inflammatory activity by interacting with the glucocorticoid receptor (GR), likely owing to their chemical similarity to glucocorticoids, or by regulating GR, without a concomitant risk of treatment-related side effects such as osteoporosis. Other herbal compounds can counteract the pathogenic processes underlying glucocorticoid-induced osteoporosis (GIOP) by regulating homeostatic bone metabolic processes. Herein, we systematically searched the PubMed, Embase, and Cochrane library databases to identify articles discussing such compounds published as of May 01, 2021. Compounds reported to exert anti-inflammatory glucocorticoid-like activity without inducing GIOP include escin, ginsenosides, and glycyrrhizic acid, while compounds reported to alleviate GIOP by improving osteoblast function or modulating steroid hormone synthesis include tanshinol and icariin.