Sirt1/Foxo Axis Plays a Crucial Role in the Mechanisms of Therapeutic Effects of Erzhi Pill in Ovariectomized Rats

Liang, Wenna; Li, Xihai; Li, Guanhui; Hu, Liu; Ding, Shanshan; Kang, Jie; Shen, Jianying; Li, Candong; Asakawa, Tetsuya

doi:10.1155/2018/9210490

Cited by 6 publications

(4 citation statements)

References 37 publications

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“…At the same time, Liang W et al claimed that the SIRT1/FoxO3a axis is a potential target for osteoporosis treatment, which suggests that the SIRT1/FoxO3a contributes to orthopedic diseases [ 41 ]. Consistent with the above research, this article revealed that miR-30b-5p bound to SIRT1 and repressed its expression, and overexpressing miR-30b-5p inactivated SIRT1 and FoxO3a.…”

Section: Discussionmentioning

confidence: 99%

NF-κB inducible miR-30b-5p aggravates joint pain and loss of articular cartilage via targeting SIRT1-FoxO3a-mediated NLRP3 inflammasome

Zhang

Shi

et al. 2021

Aging

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MicroRNAs (miRNAs) contribute to osteoarthritis (OA) development. Nevertheless, the function and mechanism of miR-30b-5p in OA are unclear. In the present article, we gauged the miR-30b-5p level in OA patients and analyzed its correlation with OA stages. Then, we conducted in-vivo and in-vitro gain-of-function assays to determine the function of miR-30b-5p, silent information regulator 2 homolog 1 (SIRT1) and Fox. Cell counting Kit-8 (CCK-8) assay, BrdU assay and flow cytometry were utilized to gauge cell viability and apoptosis of human chondrocyte (HC-A). The targeting association between miR-30b-5p and SIRT1 was validated through the dual-luciferase reporter assay and RNA immunoprecipitation (RIP) experiment. The results signified that miR-30b-5p was up-regulated in OA patients, OA rats and interleukin-1β (IL-1β)-induced chondrocytes. The higher miR-30b-5p expression brought about progressive stages of OA patients and enhanced levels of pro-inflammatory mediators in the synovial fluid. Functionally, overexpressing miR-30b-5p hampered cell viability, aggravated chondrocyte apoptosis and NLRP3 inflammasome activation induced by IL-1β, while down-regulating miR-30b-5p exerted the reverse effects. The in-vivo experiment exhibited that down-regulating miR-30b-5p improved joint pain and loss of articular cartilage in the rats with restrained inflammation and NLRP3 inflammasome activation. Mechanistically, miR-30b-5p targeted the 3’-non-translated region (3’UTR) of SIRT1, and miR-30b-5p was inducible with NF-κB phosphorylation enhancement. Overexpressing SIRT1 or inhibiting NF-κB relieved miR-30b-5p-induced apoptosis and NLRP3 inflammasome activation by promoting FoxO3a, while down-regulating SIRT1 or FoxO3a reversed miR-30b-5p-in-induced anti-inflammatory and apoptosis-suppressive effects. Collectively, NF-κB-induced miR-30b-5p modulates chondrocyte apoptosis and OA progression by regulating the SIRT1-FoxO3a-mediated NLRP3 inflammasome.

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Section: Discussionmentioning

confidence: 99%

NF-κB inducible miR-30b-5p aggravates joint pain and loss of articular cartilage via targeting SIRT1-FoxO3a-mediated NLRP3 inflammasome

Zhang

Shi

et al. 2021

Aging

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“…Erzhi Pill (EZP), a Chinese Pharmacopeia-listed herbal preparation composed of Ecliptae Herba (Mohanlian, MHL) and Fructus Ligustri Lucidi (Nvzhenzi, NZZ), has been widely applied in the long-term clinical management of post-menopausal symptoms and osteoporosis. 6 In vivo studies have shown that EZP has anti-OP effect on ovariectomized rat model and glucocorticoid-induced osteoporosis (GIOP) rat model, 7 , 8 and shows effects for bone metabolism regulation and alleviation of post-menopausal symptoms in women. 9 , 10 However, due to the complexity of the ingredients of traditional Chinese medicine (TCM) prescription and the limits of existing research methods, its effective constituents, the rationality of herbal combination and the pharmacological mechanisms of promoting bone formation, inhibiting bone absorption and improving bone quality have not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

Predicting and Exploring the Mechanisms of Erzhi Pill in Prevention and Treatment of Osteoporosis Based on Network Pharmacology and Zebrafish Experiments

Zhong

Chen

et al. 2021

DDDT

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Background Erzhi Pill (EZP), a traditional Chinese medicine (TCM) prescription, has been widely applied to improve bone metabolism and treat osteoporosis (OP) in China. However, its effective constituents and mechanisms remain unclear. Methods By combining network pharmacology and zebrafish experiments, an integrative method was employed to address this problem. Firstly, the disease targets of OP were collected from two public gene databases. Secondly, the active compounds and drug targets of EZP were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP). Thirdly, a drug-target-disease interaction network was constructed, and the key active components were identified by analyzing the topological characteristics of the network. Finally, these predicted results were tested by zebrafish experiments and compared with those from the literature. Specifically, quercetin as an important representative active component of EZP was applied to wild type and transgenic zebrafish larvae to assess its effects on skull mineralization and osteoplastic differentiation. Results Our study identified 72 active compounds, 220 targets and 166 signaling pathways probably involved in the prevention and treatment of OP by EZP, wherein quercetin, apigenin, daidzein, luteolin, ursolic acid and kaempferol could be the key compounds, while PI3K-Akt signaling pathway, TNF signaling pathway and IL-17 signaling pathway could be the key signaling pathways. The experiments indicated that quercetin attenuated both the decrease of skull mineralization and the inhibition of skull osteoplastic differentiation in zebrafish larvae trigged by dexamethasone. Conclusion Our study not only investigated potentially effective constituents and mechanisms of EZP in the prevention and treatment of OP, but also provided a reference for the in-depth research, development and application of TCM.

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“…One study showed that EZP had potential anti-OP effects by preventing the degradation of the alveolar trabecular microarchitecture and alveolar bone loss in ovariectomized rats through activation of the Wnt3a/low-density lipoprotein receptor-related protein 5 (LRP5)/b-catenin signaling pathway (Sun et al, 2014). A study by Liang et al found that EZP played a therapeutic role in an ovariectomized rat model by improving bone metabolism disorder, bone morphology, bone mineral density (BMD) and bone biomechanics and that the underlying mechanism was related to the Sirt1/Foxo signal (Liang et al, 2018). In addition, an in vitro study found that EZP-containing serum could inhibit the proliferation and differentiation of OCs from RAW264.7 cells induced by RANKL (Zhang et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Synergistic Effects of Erzhi Pill Combined With Methotrexate on Osteoblasts Mediated via the Wnt1/LRP5/β-Catenin Signaling Pathway in Collagen-Induced Arthritis Rats

Fan

et al. 2020

Front. Pharmacol.

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Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by chronic synovitis, bone erosion, and bone loss. Erzhi Pill (EZP), a classic Chinese patent medicine, is often used to treat osteoporosis and shows a capacity for bone metabolism regulation. Methotrexate (MTX), an essential drug for RA treatment, has been reported to inhibit generalized bone loss in RA patients. However, the combined therapeutic effects and mechanism of EZP and MTX in RA have not been fully elucidated. The aim of this study was to investigate the synergistic effect of EZP and MTX on RA and to explore the underlying mechanism through network pharmacological prediction and experimental verification. Chemical compounds of EZP, human target proteins of EZP and MTX, and RA-related human genes were identified in the Encyclopedia of Traditional Chinese Medicine database, PubChem database, and NCBI database, respectively. The molecular network of EZP and MTX in RA was generated and analyzed with Ingenuity Pathway Analysis software according to the datasets. Then, MTX monotherapy, EZP monotherapy, and combined MTX and EZP therapy were administered to collageninduced arthritis rats, followed by assessment of pathological score, bone damage, bone alkaline phosphatases (BALP), and tartrate-resistant acid phosphatase (TRACP), and of gene levels related to the Wnt1/LRP5/b-catenin pathway according to network pharmacological analysis. Finally, serum samples from MTX-, EZP-and MTX+EZPtreated rats were used to treat the rat osteoblast (OB)-like UMR-106 cell line to evaluate gene levels related to Wnt1/LRP5/b-catenin. Network pharmacological analysis showed that the Wnt/b-catenin signaling pathway was the top signaling pathway shared among MTX, EZP, and RA. The results from in vivo experiments

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Sirt1/Foxo Axis Plays a Crucial Role in the Mechanisms of Therapeutic Effects of Erzhi Pill in Ovariectomized Rats

Cited by 6 publications

References 37 publications

NF-κB inducible miR-30b-5p aggravates joint pain and loss of articular cartilage via targeting SIRT1-FoxO3a-mediated NLRP3 inflammasome

NF-κB inducible miR-30b-5p aggravates joint pain and loss of articular cartilage via targeting SIRT1-FoxO3a-mediated NLRP3 inflammasome

Predicting and Exploring the Mechanisms of Erzhi Pill in Prevention and Treatment of Osteoporosis Based on Network Pharmacology and Zebrafish Experiments

Synergistic Effects of Erzhi Pill Combined With Methotrexate on Osteoblasts Mediated via the Wnt1/LRP5/β-Catenin Signaling Pathway in Collagen-Induced Arthritis Rats

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