Prediction of Rhizoma Drynariae Targets in the Treatment of Osteoarthritis Based on Network Pharmacology and Experimental Verification

Chen, Guang-Yao; Liu, Xiaoyu; Chen, Jiaqi; Yu, Xin-bo; Luo, Jing; Yan, Zeran; Tao, Qing-Wen

doi:10.1155/2021/5233462

Cited by 4 publications

(6 citation statements)

References 40 publications

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“…JC-1 has been widely used to detect mitochondrial membrane potential as a fluorescent probe [ 32 , 33 ]. The JC-1 dye accumulates in mitochondria in a potential-dependent manner, which is usually indicated by a shift in fluorescence emission from green (535 nm) to red (595 nm).…”

Section: Discussionmentioning

confidence: 99%

“…is suggests that the GBT recipe can promote chondroprotection by inhibiting the expression of MMP-13 in inflammatory chondrocytes. JC-1 has been widely used to detect mitochondrial membrane potential as a fluorescent probe [32,33]. e JC-1 dye accumulates in mitochondria in a potential-dependent manner, which is usually indicated by a shift in fluorescence emission from green (535 nm) to red (595 nm).…”

Section: Discussionmentioning

confidence: 99%

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Chondroprotective Effects of Gubitong Recipe via Inhibiting Excessive Mitophagy of Chondrocytes

Chen

Zhou

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objective. Osteoarthritis (OA) is the most common degenerative joint disorder and a leading cause of disability. A previous randomized controlled trial has shown that Gubitong (GBT) recipe can improve OA-related symptoms and articular function without noticeable side effects. However, the underlying mechanisms remain unclear. This study aims to explore the therapeutic mechanisms of the GBT recipe for OA through in vivo and in vitro experiments. Methods. Rats of the OA model were established by Hulth surgery and intervened with the GBT recipe and then were subjected to pathological assessment of the cartilage. Matrix metalloproteinase 13 (MMP-13) expression in cartilage tissues was assessed by immunohistochemical staining. Chondrocytes were isolated from sucking rats and stimulated with LPS to establish an in vitro model. After intervened by water extraction of the GBT recipe, the fluorescent signal of Mtphagy Dye and mitochondrial membrane potential (Δψm) were detected to determine the states of mitophagy and mitochondrial dynamics of chondrocytes in vitro, respectively. Western blot test was used to detect levels of proteins related to catabolism of the cartilage matrix, mitophagy, and PI3K/AKT pathway. Results. In in vivo experiments, the GBT recipe can effectively inhibit the cartilage degeneration of chondrocytes in OA rats, as well as markedly suppress the expression of MMP-13. In vitro experiments on LPS-induced chondrocytes exhibited increase in mitochondrial depolarization and excessive mitophagy, and the GBT recipe can alleviate these changes. LPS-stimulated chondrocytes showed increases in MMP-13, PINK1, and Parkin in cell lysates and LC3II/LC3I ratio in the mitochondrial fraction, and the GBT recipe can inhibit these increases in a dose-dependent manner. Moreover, the GBT recipe can attenuate the abnormal activation of PI3K/AKT pathway induced by LPS. Conclusion. The GBT recipe exhibits chondroprotective effects through inhibiting excessive mitophagy of chondrocytes, which may be associated with its inhibitory effect on the abnormal activation of PI3K/AKT pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Chondroprotective Effects of Gubitong Recipe via Inhibiting Excessive Mitophagy of Chondrocytes

Chen

Zhou

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…16,17 Various flavonoids extracted from plants, such as quercetin, luteolin and kaempferol, are considered candidates for disease-modifying anti-OA drugs by virtue of their anti-inflammatory and chondroprotective effects. [18][19][20][21][22] Rhizoma Drynariae is the dried rhizome of Davallia mariesii T. Moore ex Baker, which has been applied in traditional Chinese medicine for thousands of years to treat joint pain, and flavonoids are the main active ingredients in Rhizoma Drynariae. 20 In previous clinical studies, it was demonstrated that oral administration of total flavonoids from Rhizoma Drynariae (TFRD) could improve Lequesne and Visual Analogue Scale (VAS) score for joint pain in patients with OA, while it could exhibit a good safety profile.…”

Section: Introductionmentioning

confidence: 99%

“…[18][19][20][21][22] Rhizoma Drynariae is the dried rhizome of Davallia mariesii T. Moore ex Baker, which has been applied in traditional Chinese medicine for thousands of years to treat joint pain, and flavonoids are the main active ingredients in Rhizoma Drynariae. 20 In previous clinical studies, it was demonstrated that oral administration of total flavonoids from Rhizoma Drynariae (TFRD) could improve Lequesne and Visual Analogue Scale (VAS) score for joint pain in patients with OA, while it could exhibit a good safety profile. 23,24 In our earlier in vitro studies, it was proved that TFRD is able to regulate the imbalance of MMPs/TIMPs caused by inflammatory factors, thus exerting a chondroprotective effect.…”

Section: Introductionmentioning

confidence: 99%

Total Flavonoids of Rhizoma Drynariae Treat Osteoarthritis by Inhibiting Arachidonic Acid Metabolites Through AMPK/NFκB Pathway

Chen,

Liu,

Yan

et al. 2023

JIR

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Previous clinical studies have found that total flavonoids of Rhizoma Drynariae (TFRD) have a good therapeutic effect on osteoarthritis (OA), but its therapeutic mechanism needs further research. Methods: OA rat model was established by Hulth method and was intervened by TFRD. Pathological assessments were conducted to assess the protective effect of TFRD on cartilage. Serum metabolomics and network pharmacology were detected to predict the mechanism of TFRD treating OA. In further experiments, molecular biology experiment was carried out to confirm the predicted mechanisms in vivo and in vitro. Results: TFRD can effectively reduce chondrocyte apoptosis and cartilage degeneration in OA model rats. Serum metabolomics revealed that the intervention effect may be closely related to arachidonic acid metabolism pathway. Network pharmacologic prediction showed that COX-2 was the key target of TFRD in treating OA, and its mechanism might be related with NFκB, apoptosis, AMPK and arachidonic acid metabolism pathway. In vivo experiments indicated that TFRD can inhibit the abnormal expression of COX-2 mRNA in OA model rats. In the in vitro studies, the expression of COX-2 mRNA and protein increased, AMPK phosphorylation was inhibited, and NFκB signaling pathway was activated in IL-1β-induced chondrocytes, and these changes can be reversed by TFRD. After the activation of AMPK signaling pathway or the block-down of NFκB signaling pathway, the effect of TFRD on COX-2 mRNA expression was significantly weakened. Conclusion: TFRD can inhibit COX-2-mediated arachidonic acid metabolites, and its mechanism is closely related to AMPK/NFκB pathway, which may be a key mechanism in the treatment of OA.

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“…rough network pharmacology, researchers have revealed the mechanism of traditional Chinese medicine in the treatment of a series of rheumatic diseases such as rheumatoid arthritis, systemic lupus erythematosus, and osteoarthritis [23][24][25]. is study aimed to investigate the potential mechanisms of Cibotium barometz in the treatment of OA by network pharmacology and verify them through in vitro and in vivo experiments.…”

Section: Introductionmentioning

confidence: 99%

Network Pharmacology-Based Strategy to Investigate the Mechanisms of Cibotium barometz in Treating Osteoarthritis

Chen

Wang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Cibotium barometz is a representative tonifying kidney drug and is widely used for osteoarthritis (OA) in traditional Chinese medicine. However, its regulatory mechanisms in treating OA remain to be sufficiently investigated. The main chemical components of Cibotium barometz were screened through the TCMID database and the corresponding targets were acquired through SwissTargetPrediction. The OA-related targets were obtained from the OMIM, Genecards, Genebank, TTD, and DisGeNET databases. The prediction of key targets and pathways of Cibotium barometz in the treatment of OA was achieved by constructing a compounds-targets network and performing KEGG enrichment analysis. The OA model rats were established by the Hulth method and used to explore the protective effect of Cibotium barometz via cartilage pathological assessment. In vitro models of OA were built by the proinflammatory factor interleukin-1β (IL-1β) induced SW1353 cells and used to validate the mechanisms predicted by network pharmacology. Network pharmacology results suggested that the therapeutic effects of Cibotium barometz were closely related to matrix metalloproteinase (MMP)-1, 3, 13 and inflammation-related gene COX2, which are regulated by the NFκB pathway. In vivo experiments revealed that Cibotium barometz could effectively restrain cartilage from degeneration and inhibit the mRNA expression of MMP-1, MMP-3, MMP-13, and COX2 in cartilage. In vitro experiments indicated that Cibotium barometz water extract (CBWE) could significantly inhibit the expression of MMP-1, MMP-3, MMP-13, and PGE2 in IL-1β-induced SW1353 cells and markedly prevent the translocation of NFκB p65 from the cytoplasm to the nuclei and decrease its phosphorylation level. After small-interfering RNA (siRNA) was used to suppress the synthesis of NFκB p65 to block NFκB signaling pathway, the ability of CBWE to inhibit MMP-1, MMP-3, MMP-13, and PGE2 was greatly reduced. Cibotium barometz has a chondroprotective effect on OA by inhibiting the response to inflammation and substrate degradation, and the related mechanism is associated with the inhibition of the NFκB pathway.

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Prediction of Rhizoma Drynariae Targets in the Treatment of Osteoarthritis Based on Network Pharmacology and Experimental Verification

Cited by 4 publications

References 40 publications

Chondroprotective Effects of Gubitong Recipe via Inhibiting Excessive Mitophagy of Chondrocytes

Chondroprotective Effects of Gubitong Recipe via Inhibiting Excessive Mitophagy of Chondrocytes

Total Flavonoids of Rhizoma Drynariae Treat Osteoarthritis by Inhibiting Arachidonic Acid Metabolites Through AMPK/NFκB Pathway

Network Pharmacology-Based Strategy to Investigate the Mechanisms of Cibotium barometz in Treating Osteoarthritis

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