Guizhi Shaoyao Zhimu granules attenuate bone destruction in mice with collagen-induced arthritis by promoting mitophagy of osteoclast precursors to inhibit osteoclastogenesis

Yao, Huan; Xiang, Li; Huang, Yucheng; Tan, Jin; Shen, Yongmei; Li, Fangqiong; Geng, Funeng; Liu, Weiwei; Li, Xueping; Gao, Yongxiang

doi:10.1016/j.phymed.2023.154967

Cited by 15 publications

(2 citation statements)

References 40 publications

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“…The rats with successful induction of CIA were randomly divided into five groups (n = 10): the Model group (Model), JTQBG low-dose group (JTQBG-L), JTQBG medium-dose group (JTQBG-M), JTQBG high-dose group (JTQBG-H), and positive control MTX group (MTX). The animal dose in our study was converted based on the body surface area (BSA) normalization method, as was reported by the previous studies (Xu, et al, 2002;Yao et al, 2023). From day 7 to day 42, rats in the JTQBG groups (JTQBG-L, JTQBG-M and JTQBG-H) were orally administered JTQBG at concentrations of 1.25 g/kg, 2.5 g/kg, and 5 g/kg, respectively, once a day, and in the MTX group, MTX (1 mg/kg) was administered once a week.…”

Section: Cia Establishment and Treatmentmentioning

confidence: 99%

The protective effect of traditional Chinese medicine Jinteng Qingbi granules on rats with rheumatoid arthritis

Wan,

Sun,

Yang

et al. 2024

Front. Pharmacol.

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Introduction: Jinteng Qingbi granules (JTQBG), a traditional Chinese medicine formulation, are widely used for the treatment of rheumatoid arthritis (RA) due to their satisfactory therapeutic efficacy. However, the underlying mechanism of action remains unclear. This study aims to investigate the protective effects of JTQBG against RA and elucidates its potential molecular mechanisms.Methods: A collagen-induced arthritis (CIA) rat model was utilized, and JTQBG (1.25, 2.5, 5 g/kg/day) or methotrexate (MTX, 1 mg/kg/week) was orally administered. The rats’ weight, arthritis index (AI), and paw volume were measured weekly. Synovial hyperplasia of the joints was detected using a small animal ultrasound imaging system. Joint destruction was assessed using an X-ray imaging system. Histopathological examinations were performed using hematoxylin-eosin (H&E), Saffron-O and fast green staining. Serum inflammatory cytokines were detected using ELISA. Furthermore, 4D label-free quantitative proteomics of synovial tissues and non-targeted metabolomics of blood serum were conducted to analyze the molecular mechanisms.Results: JTQBG exerted a significant therapeutic effect on CIA rats by reducing inflammatory cell infiltration, synovial hyperplasia, cartilage erosion, and bone destruction. It also decreased the spleen index, inhibited hyperplasia of the white pulp, and decreased the serum levels of IL-1β and IL-18. Proteomics analysis identified 367 differentially expressed proteins (DEPs) between the Model and Normal groups, and 71 DEPs between the JTQBG and Model groups. These DEPs were significantly enriched in the NF-κB pathway. 11 DEPs were significantly reversed after treatment with JTQBG. Western blot results further validated the expression levels of Nfkb1, Pdk1, and Pecam1, and analyzed the expression levels of p-IKK, p-IκBα, and IκBα. The therapeutic efficacy of JTQBG was partly attributed to the suppression of the NF-κB pathway in synovial tissues. Serum metabolomics identified 17 potential biomarkers for JTQBG treatment of CIA rats, which were closely related to Alanine, aspartate and glutamate metabolism, Tryptophan metabolism, Ascorbate and aldarate metabolism, Arginine metabolism, and Inositol phosphate metabolism.Conclusion: Our findings demonstrated that JTQBG was effective against RA by alleviating synovial inflammation, synovial hyperplasia, and joint destruction. The anti-RA properties of JTQBG were likely attributed to the inhibition of the NF-κB pathway and the regulation of serum metabolite disorders.

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Section: Cia Establishment and Treatmentmentioning

confidence: 99%

The protective effect of traditional Chinese medicine Jinteng Qingbi granules on rats with rheumatoid arthritis

Wan,

Sun,

Yang

et al. 2024

Front. Pharmacol.

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“…However, a study by Yao et al found that Guizhi Shaoyao decoction, an herbal formula, promoted mitophagy in osteoclasts through PINK1/Parkin signaling, resulting in the inhibition of osteoclast differentiation. When PINK1 expression in osteoclasts was reduced, the inhibitory effect of Guizhi Shaoyao on osteoclastogenesis was eliminated [ 248 ]. Regulation of mitophagy levels can impact macrophage inflammatory phenotypes.…”

Section: The Mrc and Mitophagy In Bone Metabolismmentioning

confidence: 99%

The Emerging Role of the Mitochondrial Respiratory Chain in Skeletal Aging

Tao,

Zhu,

Xia

et al. 2023

Aging and disease

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Maintenance of mitochondrial homeostasis is crucial for ensuring healthy mitochondria and normal cellular function. This process is primarily responsible for regulating processes that include mitochondrial OXPHOS, which generates ATP, as well as mitochondrial oxidative stress, apoptosis, calcium homeostasis, and mitophagy. Bone mesenchymal stem cells express factors that aid in bone formation and vascular growth. Positive regulation of hematopoietic stem cells in the bone marrow affects the differentiation of osteoclasts. Furthermore, the metabolic regulation of cells that play fundamental roles in various regions of the bone, as well as interactions within the bone microenvironment, actively participates in regulating bone integrity and aging. The maintenance of cellular homeostasis is dependent on the regulation of intracellular organelles, thus understanding the impact of mitochondrial functional changes on overall bone metabolism is crucially important. Recent studies have revealed that mitochondrial homeostasis can lead to morphological and functional abnormalities in senescent cells, particularly in the context of bone diseases. Mitochondrial dysfunction in skeletal diseases results in abnormal metabolism of bone-associated cells and a secondary dysregulated microenvironment within bone tissue. This imbalance in the oxidative system and immune disruption in the bone microenvironment ultimately leads to bone dysplasia. In this review, we examine the latest developments in mitochondrial respiratory chain regulation and its impacts on maintenance of bone health. Specifically, we explored whether enhancing mitochondrial function can reduce the occurrence of bone cell deterioration and improve bone metabolism. These findings offer prospects for developing bone remodeling biology strategies to treat age-related degenerative diseases.

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Targeting Mitophagy as a Potential Therapeutic Approach for Age‐Related Bone Diseases

Zhang,

Li,

Zhang

et al. 2024

Advanced Therapeutics

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Accumulating evidence has suggested a strong correlation between age‐related bone diseases and abnormal metabolism of bone microenvironment‐related cells, including mesenchymal stem cells (MSCs), osteoblasts, osteoclasts, osteocytes, and chondrocytes. Mitochondrial dysfunction significantly impacts cell metabolism and initiates the development and progress of numerous age‐related bone diseases. Mitochondrial autophagy or mitophagy, a process that selectively removes damaged or dysfunctional mitochondria, is closely associated with maintaining mitochondrial quality control and homeostasis. Recent studies indicate a decisive regulatory role of mitophagy in age‐related bone diseases, thereby pointing toward the potential for manipulating mitophagy levels as a new treatment paradigm. Based on the importance and novelty of mitophagy, the present review offers an overview of the pathways involved in mitophagy and meticulously examines its function in age‐related bone diseases. Various treatment methods targeting mitophagy are also discussed, mainly including biomaterials with mitophagy‐modulatory capabilities, “old drugs in a new bottle” (e.g., Metformin, Rapamycin), natural compounds, endogenous factors, and stem cell‐based therapies. In conclusion, these innovative approaches uncover mitophagy‐related signals, pathways, and mechanisms, and may shed light on mitophagy‐targeting treatments for age‐related bone diseases in the future.

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Guizhi Shaoyao Zhimu granules attenuate bone destruction in mice with collagen-induced arthritis by promoting mitophagy of osteoclast precursors to inhibit osteoclastogenesis

Cited by 15 publications

References 40 publications

The protective effect of traditional Chinese medicine Jinteng Qingbi granules on rats with rheumatoid arthritis

The protective effect of traditional Chinese medicine Jinteng Qingbi granules on rats with rheumatoid arthritis

The Emerging Role of the Mitochondrial Respiratory Chain in Skeletal Aging

Targeting Mitophagy as a Potential Therapeutic Approach for Age‐Related Bone Diseases

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