Puerarin alleviates osteoporosis in the ovariectomy-induced mice by suppressing osteoclastogenesis via inhibition of TRAF6/ROS-dependent MAPK/NF-κB signaling pathways

Xiao, Long; Zhong, Mengdan; Huang, Yu; Zhu, Jie; Tang, Wenkai; Li, Danyong; Shi, Jiandong; Lu, Aiqing; Yang, Huilin; Geng, Dechun; Li, Hong; Wang, Zhirong

doi:10.18632/aging.103976

Cited by 113 publications

(87 citation statements)

References 65 publications

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“…In summary, the need to determine related specific targets and targeted drugs/chemotherapies for the treatment of ALI is urgent. Puerarin is a flavonoid component isolated from Pueraria lobata widely known as Gegen in traditional Chinese medicine and has been clinically used for its protection against inflammation, oxidative stress, and mitochondrial dysfunction (Wang et al, 2016;Zeng et al, 2018;Xiao et al, 2020). Previous research has found that puerarin plays a significantly regulator role in various diseases, including liver damage (Peng et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Puerarin Prevents Acute Liver Injury via Inhibiting Inflammatory Responses and ZEB2 Expression

Yang

Fang

et al. 2021

Front. Pharmacol.

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Puerarin, an isoflavone component extracted from herb radix puerariae, is widely used in China in the treatment of immune diseases and inflammation. Previous studies have demonstrated that puerarin prevented acute lung injury by regulating inflammatory responses. However, the effect of puerarin on acute liver injury (ALI) was unclear. The purpose of this study was to explore the beneficial effects of puerarin when applied to ALI. We found that puerarin inhibited liver injury and inflammatory cell infiltration in lipopolysaccharide (LPS)/D-galactose (D-Gal)-induced acute liver failure and the liver pro-inflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) in liver tissues with ALI and LPS-induced L-02 cells but upregulated the expression level of zinc finger E-box-binding homeobox 2 (ZEB2). Significantly, the results of this study showed that the inhibition of liver pro-inflammatory cytokine (IL-1β, IL-6, and TNF-α) production in LPS-induced L-02 cells was caused by ZEB2 overexpression. However, knocking down ZEB2 promoted LPS-mediated secretion of liver pro-inflammatory cytokines in L-02 cells. Additional experiments showed that puerarin inhibited the activation of the NF-κB signaling pathway by elevating ZEB2 expression in L-02 cells. In summary, puerarin most likely prevented activation of the pro-inflammatory factors and reduced LPS/D-Gal-induced liver injury by enhancing the ZEB2 expression level and, consequently, blocking activation of the NF-κB signaling pathway in the liver.

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Section: Discussionmentioning

confidence: 99%

Puerarin Prevents Acute Liver Injury via Inhibiting Inflammatory Responses and ZEB2 Expression

Yang

Fang

et al. 2021

Front. Pharmacol.

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“…Osteoporosis has always been a research hotspot in orthopedics and other related fields. There are many methods to obtain animal models of osteoporosis, such as surgical induction [ 40 ] (removal of bilateral ovaries/testes), drug induction [ 41 ] (adrenocortical hormone and other drugs), loss induction, diet induction [ 42 ] (low calcium diet), gene knockout [ 43 ] (knockout of the OPG gene), and spontaneous degeneration. The molding time is generally about 2 months.…”

Section: Discussionmentioning

confidence: 99%

QiangGuYin Modulates the OPG/RANKL/RANK Pathway by Increasing Secretin Levels during Treatment of Primary Type I Osteoporosis

Cui

Wen-hua

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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QiangGuYin (QGY) is a common Traditional Chinese medicine prescription for the treatment of osteoporosis. Previous clinical studies have found that QGY effectively improves bone mineral density (BMD) in postmenopausal women, but its underlying mechanism remains unclear. The osteoprotegerin (OPG)/receptor activator of nuclear factor kappa B ligand (RANKL)/receptor activator of nuclear factor kappa B (RANK) pathway is a classic pathway involved in osteoporosis. Secretin levels are a serum marker of osteoporosis, but their effect on the OPG/RANKL/RANK pathway has not been reported. Hence, we investigated the relationship between the OPG/RANKL/RANK pathway and secretin and further revealed the mechanism underlying the effect of QGY in the treatment of osteoporosis. Mice were divided into secretin knockdown, secretin overexpression, and corresponding control groups. Micro-computed tomography was used to detect BMD in different groups, and the results show that QGY significantly improved BMD in mice of the secretin knockdown group. To further verify this, the serum levels of OPG, RANKL, RANK, and secretin were measured by enzyme-linked immunosorbent assays, and femur levels of OPG, RANKL, RANK, and secretin were evaluated by real-time quantitative PCR and western blotting. The results show that the expression of OPG was inhibited and that of RANKL and RANK was increased in mice from the secretin knockdown group, whereas the expression of OPG was upregulated and that of RANKL and RANK was downregulated after QGY intervention. Therefore, QGY inhibited bone resorption by promoting the expression of secretin and modulating the OPG/RANKL/RANK pathway. In addition to the effect of QGY, we also revealed the general regulatory effect of secretin on the OPG/RANKL/RANK pathway. We conclude that QGY modulates the OPG/RANKL/RANK pathway by increasing secretin levels during treatment of primary type I osteoporosis. This work provides a theoretical basis for the clinical use of QGY in the treatment of osteoporosis.

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“…SOG repressed the induction of osteoclast speci c genes RANKL stimulation up-regulates osteoclast-related genes, which regulats the differentiation, maturation, and function of osteoclasts. NFATc1, a master transcription factors for osteoclastogenesis, regulats the expression of osteoclast speci c genes 17 . To investigate the impacts of SOG on osteoclast-related genes, we used RT-PCR to examine the mRNA expression of these genes, including NFATc1, c-Fos, CTSK, TRAP, DC-STAMP.…”

Section: Sog Inhibited Rankl-induced Osteoclast Formationmentioning

confidence: 99%

Sec-O-glucosylhamaudol Inhibits RANKL-induced Osteoclastogenesis Via Repressing 5-LO and AKT/GSK3β Signaling

Cao

Zhou

Chen

et al. 2021

Preprint

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BackgroundOsteoclast excessive activation was closely related to bone diseases such as osteoporosis and rheumatoid arthritis. Sec-O-glucosylhamaudol (SOG), an active flavonoid compound derived from the root of divaricate Saposhnikovia, was reported to exhibit analgesic, anti-inflammatory and high 5-lipoxygenase (5-LO) inhibitory effects. However, its effect on osteoclastogenesis and bone resorption remained unclear.MethodsOsteoclast formation, bone resorption pit area formation and F-actin ring formation were examined by TRAP staining, modified Vonkonsa staining and immunofluorescence, respectively. RT-Realtime PCR assay and western blot analysis were performed. siRNA transfection was conducted to silence the expression of 5-LO in cells. LPS-induced bone-loss mice model was prepared and the left and right femurs were collected for Micro-CT and histomorphometric analysis, respectively.ResultsSOG markedly attenuated RANKL-induced osteoclastogenesis through decreasing TRAP activity, F-actin ring formation and bone resorption with reduction of mRNA levels of osteoclastogenesis marker genes such as TRAP, CTSK and DC-STAMP. Our results further indicated that SOG markedly reduced the induction of key transcription factors NFATc1 and c-Fos at both mRNA and protein levels during osteoclastogenesis. In addition, SOG treatment did not alter the transient phosphorylation of NF-κB p65 subunit and MAPKs (p38, ERK1/2 and JNK), AKT and GSK3β by RANKL. Interestingly, our results showed that SOG significantly inhibited the phosphorylation of AKT and GSK3β at middle-late stage of osteoclastogenesis, but did not alter calcineurin catalytic subunit PP2B-Aα expression. GSK3β inhibitor SB415286 could partly reverse inhibition of osteoclastogenesis by SOG. 5-LO knockdown at BMMs also markedly reduced RANKL-induced osteoclastogenesis. In consistent with in vitro results，SOG could significantly improve bone destruction in LPS-induced mice model.ConclusionsSOG attenuated formation and function of osteoclast through suppressing AKT-mediated GSK3β inactivation, and 5-LO catalytic activity. Moreover, SOG prevented LPS-induced bone loss in mice through inhibiting osteoclastogenesis. Taken together, this study provided the evidence that SOG may have a potential therapeutic effect on osteoclast-related bone lysis disease.

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Puerarin alleviates osteoporosis in the ovariectomy-induced mice by suppressing osteoclastogenesis via inhibition of TRAF6/ROS-dependent MAPK/NF-κB signaling pathways

Cited by 113 publications

References 65 publications

Puerarin Prevents Acute Liver Injury via Inhibiting Inflammatory Responses and ZEB2 Expression

Puerarin Prevents Acute Liver Injury via Inhibiting Inflammatory Responses and ZEB2 Expression

QiangGuYin Modulates the OPG/RANKL/RANK Pathway by Increasing Secretin Levels during Treatment of Primary Type I Osteoporosis

Sec-O-glucosylhamaudol Inhibits RANKL-induced Osteoclastogenesis Via Repressing 5-LO and AKT/GSK3β Signaling

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