Total Flavonoids of Rhizoma Drynariae Restore the MMP/TIMP Balance in Models of Osteoarthritis by Inhibiting the Activation of the NF-<math xmlns="http://www.w3.org/1998/Math/MathML" id="M1">
                     <mi>κ</mi>
                     <mi>B</mi>
                  </math> and PI3K/AKT Pathways

Evidence-Based Complementary and Alternative Medicine

Yang

et al. 2022

Objective. The extent, range, and nature of available research in the field of herbal therapies for osteoarthritis (OA) have not been systematically analyzed. This study aimed to map the literature available on herbal therapies for OA and identify global hotspots and trends in this field. Methods. Studies on herbal therapies for OA published between 2004 and 2022 were searched from the Web of Science Core Collection. Microsoft Excel, SPSS Statistics, and CiteSpace software were used to analyze and visualize the quantity and citations of publications, and the research hotspots and trends in research on herbal therapies for OA. Results. A total of 1649 publications mainly from 76 countries/regions and 270 institutions were included in this study. From 2004 to 2022, there is an upward trend in the publications of herbal therapies for OA. China ranked first in the number of publications (n = 568, 34.45%), followed by the USA (n = 353, 21.41%), South Korea (n = 187, 11.34%), Germany (n = 85, 5.15%), and England (n = 79, 4.79%). Kyung Hee University (n = 46), Xianxiang Liu (n = 25), and Evidence-Based Complementary and Alternative Medicine (n = 74) were the most prolific affiliation, author, and journal, respectively. Felson DT (n = 185) and Arthritis and Rheumatism (n = 1173) held the record for the most cited papers by an author and journal, respectively. Currently, the hot keywords in the field of herbal therapies for OA include knee OA, traditional Chinese medicine (TCM), differentiation, rosa canina, inflammation, oxidative stress, stem cell, and regenerative medicine. The emerging research trends in herbal therapies for OA are herbal medicinal product, chronic knee pain, mesenchymal stem cell, and clinical pharmacology. Conclusions. Research on herbal therapies for OA is flourishing, but communication among countries/regions should be strengthened. Current research on herbal therapies for OA mainly focuses on knee OA, TCM, differentiation, rosa canina, inflammation, oxidative stress, stem cell, and regenerative medicine. The research frontiers are herbal medicinal product, chronic knee pain, mesenchymal stem cell, and clinical pharmacology.

Section: Discussionmentioning

confidence: 99%

Research on Herbal Therapies for Osteoarthritis in 2004–2022: A Web of Science-Based Cross-Sectional Bibliometric Analysis

Song

Evidence-Based Complementary and Alternative Medicine

Yang

et al. 2022

“…The knee OA was established in the Hulth model group and the the CBWE treated group by the Hulth method under isoflurane anesthesia, the surgical carried out as previously described [ 33 ]. Rats in the blank control group were only anesthetized and cut the epidermis without destroying the joint structure.…”

Section: Methodsmentioning

confidence: 99%

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

Evidence-Based Complementary and Alternative Medicine

Wang

et al. 2022

Self Cite

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.

“…The specific methods of the validation experiments, including cell culture, MTS assay, RNA isolation, PCR, ELISA, western blotting, and immunofluorescence, are shown in our previous research [ 11 ]. The mitochondrial membrane potential (Δ ψ m) was measured by flow cytometry (BD FACSCanto II, USA) using the mitochondrial membrane potential detection JC-1 kit according to the manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

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

Liu

Evidence-Based Complementary and Alternative Medicine

et al. 2021

Self Cite

Rhizoma Drynariae has been widely used for the treatment of osteoarthritis (OA), but its potential targets and molecular mechanisms remain to be further explored. Targets of Rhizoma Drynariae and OA were predicted by relevant databases, and a protein-protein interaction (PPI) network was constructed to identify key targets. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed to obtain related pathways and then select significant pathways associated with OA. The OA chondrocyte model was established by inflammatory factor-induced SW1353 chondrocytes, and molecular docking was conducted to verify the above theoretical prediction. The results showed that a total of 86 Rhizoma Drynariae-OA interaction targets were identified, among which IL-6 and AKT1 were the key targets in the PPI network. Luteolin was the most critical component of Rhizoma Drynariae. KEGG results indicated that the effects of Rhizoma Drynariae on OA are associated with the PI3K/AKT, TNF, IL-17, apoptosis, and HIF-1 signaling pathway. The PI3K/AKT pathway can activate the downstream NF-κB pathway and further regulate the transcription and expression of downstream IL-6, IL-17, HIF-1α, Bax, and TNF, suggesting that the PI3K/AKT/NF-κB pathway is the critical pathway in the treatment of OA with Rhizoma Drynariae. Active components of Rhizoma Drynariae and key proteins of the PI3K/AKT/NF-κB signaling pathway were subjected to molecular docking, whose results showed that luteolin and IKK-α played a critical role. In vitro experiments indicated that both aqueous extracts of Rhizoma Drynariae (AERD) and luteolin inhibited the expression of IL-6 and HIF-1α and suppressed the activation of PI3K/AKT/NF-κB, IL-17, and TNF pathways. The measurement of mitochondrial membrane potential (Δψm) indicated that AERD and luteolin can decrease the LPS-induced early apoptotic cells. Luteolin had a more prominent inhibitory effect than AERD in the abovementioned in vitro experiments. In conclusion, the therapeutic mechanism of Rhizoma Drynariae against OA may be closely related to the inhibition of the PI3K/AKT/NF-κB pathway and downstream pathways, and luteolin plays a vital role in the treatment.