System pharmacology analysis to decipher the effect and mechanism of active ingredients combination from Duhuo Jisheng decoction on osteoarthritis in rats

Zheng, Senwang; Zhou, Bo; Hou, Ajiao; Zhang, Jiaxu; Yu, Huan; Kuang, Hai‐Xue; Jiang, Hai; Yang, Lin

doi:10.1016/j.jep.2023.116679

Cited by 4 publications

(3 citation statements)

References 35 publications

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“…Studies have shown that DHJSD inhibits the production of inflammatory factors, including interleukins and matrix metalloproteinases (MMPs) [ 33 , 34 ]. However, there is a lack of detailed research on the mechanism via which DHJSD in protects articular cartilage in KOA.…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, zinc is an essential cofactor for a variety of matrix metalloproteinases and is involved in the metabolic homeostasis of cartilage matrix [35,36]. Moreover, previous studies have found that DHJSD can decrease zinc levels in chondrocytes and inhibit the expression of MMP-13 and other proteins [19,33]. In addition, autophagy has been found to be closely related to intracellular zinc homeostasis [16][17][18].…”

Section: Plos Onementioning

confidence: 99%

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Duhuo Jisheng Decoction regulates intracellular zinc homeostasis by enhancing autophagy via PTEN/Akt/mTOR pathway to improve knee cartilage degeneration

Wang,

Zhou,

Gao

et al. 2024

PLoS ONE

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Background Articular cartilage and cartilage matrix degradation are key pathological changes occurring in the early stage of knee osteoarthritis (KOA). However, currently, there are limited strategies for early prevention and treatment of KOA. Duhuo Jisheng Decoction (DHJSD) is a formula quoted in Bei Ji Qian jin Yao Fang, which was compiled by Sun Simiao in the Tang Dynasty of China. As a complementary therapy, it is widely used to treat early-stage KOA in China; however, its mechanism has not been completely elucidated. Objective This study investigated the potential role of DHJSD in preventing cartilage degradation and the underlying mechanism. Methods A rat model of KOA model was established via the Hulth method. Subsequently, 25 rats were randomized into sham (saline), model control (saline), high-DHJSD (1.9g/mL of DHJSD), medium-DHJSD (1.2g/mL of DHJSD), and low-DHJSD groups (0.6g/mL of DHJSD). After 4 weeks of treatment, all rats were sacrificed and the severity of the cartilage degeneration was evaluated by a series of histological methods. The autophagosome was observed using transmission electron microscopy, and the related functional proteins were detected by the western blotting and real-time polymerase chain reaction. Next, the mechanism by which DHJSD improves knee cartilage degeneration was further clarified the in vitro by gene silencing technology combined with a series of functional experiments. The proteins levels of PTEN, Akt, p-Akt, mTOR, and p-mTOR, as well as the marker proteins of autophagy and apoptosis were determined. Zinc levels in chondrocytes were determined using inductively coupled plasma mass spectrometry. Results Histopathological staining revealed that DHJSD had a protective effect on the cartilage. DHJSD increased autophagosome synthesis and the expression of autophagy proteins LC3 and Beclin-1 in chondrocytes. Moreover, it reduced the phosphorylation levels of Akt and mTOR and the levels of zinc, MMP-13, Bax, and Bcl-2. Following PTEN silencing, this DHJSD-mediated reduction in Akt and mTOR phosphorylation and Bax, Bcl-2, and zinc levels were further decreased; in addition, DHJSD-mediated increase in LC3 and Beclin-1 levels was decreased. Conclusion DHJSD inhibits the Akt/mTOR signaling pathway by targeting PTEN to promote autophagy in chondrocytes, which may help reduce MMP-13 production by regulating zinc levels in chondrocytes.

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Section: Resultsmentioning

confidence: 99%

Section: Plos Onementioning

confidence: 99%

Duhuo Jisheng Decoction regulates intracellular zinc homeostasis by enhancing autophagy via PTEN/Akt/mTOR pathway to improve knee cartilage degeneration

Wang,

Zhou,

Gao

et al. 2024

PLoS ONE

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“…Lei's formula (LSF) is derived from Lei's medical treatise "Treatise on Chronic Diseases" and has been widely utilized in OA treatment. LSF includes the Chinese medicinal pair Duhuo-Qianghuo, known for their anti-inflammatory and analgesic effects, as demonstrated in previous studies [24][25][26][27][28]. Table 1 summarizes the herbs present in LSF.…”

Section: Introductionmentioning

confidence: 99%

Lei’s formula attenuates osteoarthritis mediated by suppression of chondrocyte senescence via the mTOR axis: in vitro and in vivo experiments

Zhou,

Li,

Zhuang

et al. 2024

Aging

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Lei’s formula (LSF), a traditional Chinese herbal remedy, is recognized for its remarkable clinical effectiveness in treating osteoarthritis (OA). Despite its therapeutic potential, the exact molecular mechanisms underlying LSF’s action in OA have remained enigmatic. Existing research has shed light on the role of the mTOR signaling pathway in promoting chondrocyte senescence, a central factor in OA-related cartilage degeneration. Consequently, targeting mTOR to mitigate chondrocyte senescence presents a promising avenue for OA treatment. The primary objective of this study is to establish LSF’s chondroprotective potential and confirm its anti-osteoarthritic efficacy through mTOR inhibition. In vivo assessments using an OA mouse model reveal substantial articular cartilage degeneration. However, LSF serves as an effective guardian of articular cartilage, evidenced by reduced subchondral osteosclerosis, increased cartilage thickness, improved surface smoothness, decreased OARSI scores, elevated expression of cartilage anabolic markers (Col2 and Aggrecan), reduced expression of catabolic markers (Adamts5 and MMP13), increased expression of the chondrocyte hypertrophy marker (Col10), and decreased expression of chondrocyte senescence markers (P16 and P21). In vitro findings demonstrate that LSF shields chondrocytes from H 2 O 2 -induced apoptosis, inhibits senescence, enhances chondrocyte differentiation, promotes the synthesis of type II collagen and proteoglycans, and reduces cartilage degradation. Mechanistically, LSF suppresses chondrocyte senescence through the mTOR axis, orchestrating the equilibrium between chondrocyte anabolism and catabolism, ultimately leading to reduced apoptosis and decelerated OA cartilage degradation. LSF holds significant promise as a therapeutic approach for OA treatment, offering new insights into potential treatments for this prevalent age-related condition.

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Systematic insight into the dual COX-2/5-LOX inhibitory mechanism of Duhuo Jisheng decoction for treatment of osteoarthritis based on in silico and bioassay

Zhang,

Li,

Liu

et al. 2025

Journal of Ethnopharmacology

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System pharmacology analysis to decipher the effect and mechanism of active ingredients combination from Duhuo Jisheng decoction on osteoarthritis in rats

Cited by 4 publications

References 35 publications

Duhuo Jisheng Decoction regulates intracellular zinc homeostasis by enhancing autophagy via PTEN/Akt/mTOR pathway to improve knee cartilage degeneration

Duhuo Jisheng Decoction regulates intracellular zinc homeostasis by enhancing autophagy via PTEN/Akt/mTOR pathway to improve knee cartilage degeneration

Lei’s formula attenuates osteoarthritis mediated by suppression of chondrocyte senescence via the mTOR axis: in vitro and in vivo experiments

Systematic insight into the dual COX-2/5-LOX inhibitory mechanism of Duhuo Jisheng decoction for treatment of osteoarthritis based on in silico and bioassay

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