Zhuifeng tougu capsules inhibit the TLR4/MyD88/NF-κB signaling pathway and alleviate knee osteoarthritis: In vitro and in vivo experiments
Background: Knee osteoarthritis (KOA), a chronic degenerative disease, is mainly characterized by destruction of articular cartilage and inflammatory reactions. At present, there is a lack of economical and effective clinical treatment. Zhuifeng Tougu (ZFTG) capsules have been clinically approved fo...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.951860/full |
| _version_ | 1798000955405369344 |
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| author | Xiaotong Xu Xiaotong Xu Naping Li Yongrong Wu Ke Yan Yilin Mi Nanxing Yi Xuyi Tan Gaoyan Kuang Gaoyan Kuang Min Lu |
| author_facet | Xiaotong Xu Xiaotong Xu Naping Li Yongrong Wu Ke Yan Yilin Mi Nanxing Yi Xuyi Tan Gaoyan Kuang Gaoyan Kuang Min Lu |
| author_sort | Xiaotong Xu |
| collection | DOAJ |
| description | Background: Knee osteoarthritis (KOA), a chronic degenerative disease, is mainly characterized by destruction of articular cartilage and inflammatory reactions. At present, there is a lack of economical and effective clinical treatment. Zhuifeng Tougu (ZFTG) capsules have been clinically approved for treatment of OA as they relieve joint pain and inflammatory manifestations. However, the mechanism of ZFTG in KOA remains unknown.Purpose: This study aimed to investigate the effect of ZFTG on the TLR4/MyD88/NF-κB signaling pathway and its therapeutic effect on rabbits with KOA.Study design:In vivo, we established a rabbit KOA model using the modified Videman method. In vitro, we treated chondrocytes with IL-1β to induce a pro-inflammatory phenotype and then intervened with different concentrations of ZFTG. Levels of IL-1β, IL-6, TNF-α, and IFN-γ were assessed with histological observations and ELISA data. The effect of ZFTG on the viability of chondrocytes was detected using a Cell Counting Kit-8 and flow cytometry. The protein and mRNA expressions of TLR2, TLR4, MyD88, and NF-κB were detected using Western blot and RT-qPCR and immunofluorescence observation of NF-κB p65 protein expression, respectively, to investigate the mechanism of ZFTG in inhibiting inflammatory injury of rabbit articular chondrocytes and alleviating cartilage degeneration.Results: The TLR4/MyD88/NF-κB signaling pathway in rabbits with KOA was inhibited, and the levels of IL-1β, IL-6, TNF-α, and IFN-γ in blood and cell were significantly downregulated, consistent with histological results. Both the protein and mRNA expressions of TLR2, TLR4, MyD88, NF-κB, and NF-κB p65 proteins in that nucleus decreased in the ZFTG groups. Moreover, ZFTG promotes the survival of chondrocytes and inhibits the apoptosis of inflammatory chondrocytes.Conclusion: ZFTG alleviates the degeneration of rabbit knee joint cartilage, inhibits the apoptosis of inflammatory chondrocytes, and promotes the survival of chondrocytes. The underlying mechanism may be inhibition of the TLR4/MyD88/NF-kB signaling pathway and secretion of inflammatory factors. |
| first_indexed | 2024-04-11T11:28:28Z |
| format | Article |
| id | doaj.art-b66c479b9e154eff9ca160d708881f2a |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-11T11:28:28Z |
| publishDate | 2022-09-01 |
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| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-b66c479b9e154eff9ca160d708881f2a2022-12-22T04:26:12ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-09-011310.3389/fphar.2022.951860951860Zhuifeng tougu capsules inhibit the TLR4/MyD88/NF-κB signaling pathway and alleviate knee osteoarthritis: In vitro and in vivo experimentsXiaotong Xu0Xiaotong Xu1Naping Li2Yongrong Wu3Ke Yan4Yilin Mi5Nanxing Yi6Xuyi Tan7Gaoyan Kuang8Gaoyan Kuang9Min Lu10Department of Orthopedic Surgery, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, ChinaGraduate School, Hunan University of Chinese Medicine, Changsha, Hunan, ChinaDepartment of Orthopedic Surgery, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, ChinaSchool of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, ChinaDepartment of Orthopedic Surgery, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, ChinaGraduate School, Hunan University of Chinese Medicine, Changsha, Hunan, ChinaGraduate School, Hunan University of Chinese Medicine, Changsha, Hunan, ChinaDepartment of Orthopedic Surgery, Affiliated Hospital of Hunan Academy of Chinese Medical Science, Changsha, Hunan, ChinaDepartment of Orthopedic Surgery, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, ChinaPostdoctoral Research Workstation, Hinye Pharmaceutical Co., Ltd., Changsha, Hunan, ChinaDepartment of Orthopedic Surgery, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, ChinaBackground: Knee osteoarthritis (KOA), a chronic degenerative disease, is mainly characterized by destruction of articular cartilage and inflammatory reactions. At present, there is a lack of economical and effective clinical treatment. Zhuifeng Tougu (ZFTG) capsules have been clinically approved for treatment of OA as they relieve joint pain and inflammatory manifestations. However, the mechanism of ZFTG in KOA remains unknown.Purpose: This study aimed to investigate the effect of ZFTG on the TLR4/MyD88/NF-κB signaling pathway and its therapeutic effect on rabbits with KOA.Study design:In vivo, we established a rabbit KOA model using the modified Videman method. In vitro, we treated chondrocytes with IL-1β to induce a pro-inflammatory phenotype and then intervened with different concentrations of ZFTG. Levels of IL-1β, IL-6, TNF-α, and IFN-γ were assessed with histological observations and ELISA data. The effect of ZFTG on the viability of chondrocytes was detected using a Cell Counting Kit-8 and flow cytometry. The protein and mRNA expressions of TLR2, TLR4, MyD88, and NF-κB were detected using Western blot and RT-qPCR and immunofluorescence observation of NF-κB p65 protein expression, respectively, to investigate the mechanism of ZFTG in inhibiting inflammatory injury of rabbit articular chondrocytes and alleviating cartilage degeneration.Results: The TLR4/MyD88/NF-κB signaling pathway in rabbits with KOA was inhibited, and the levels of IL-1β, IL-6, TNF-α, and IFN-γ in blood and cell were significantly downregulated, consistent with histological results. Both the protein and mRNA expressions of TLR2, TLR4, MyD88, NF-κB, and NF-κB p65 proteins in that nucleus decreased in the ZFTG groups. Moreover, ZFTG promotes the survival of chondrocytes and inhibits the apoptosis of inflammatory chondrocytes.Conclusion: ZFTG alleviates the degeneration of rabbit knee joint cartilage, inhibits the apoptosis of inflammatory chondrocytes, and promotes the survival of chondrocytes. The underlying mechanism may be inhibition of the TLR4/MyD88/NF-kB signaling pathway and secretion of inflammatory factors.https://www.frontiersin.org/articles/10.3389/fphar.2022.951860/fullZhuifeng tougu capsulesTLR4NF-κBknee osteoarthritisinflammatory factorsinnate immune |
| spellingShingle | Xiaotong Xu Xiaotong Xu Naping Li Yongrong Wu Ke Yan Yilin Mi Nanxing Yi Xuyi Tan Gaoyan Kuang Gaoyan Kuang Min Lu Zhuifeng tougu capsules inhibit the TLR4/MyD88/NF-κB signaling pathway and alleviate knee osteoarthritis: In vitro and in vivo experiments Frontiers in Pharmacology Zhuifeng tougu capsules TLR4 NF-κB knee osteoarthritis inflammatory factors innate immune |
| title | Zhuifeng tougu capsules inhibit the TLR4/MyD88/NF-κB signaling pathway and alleviate knee osteoarthritis: In vitro and in vivo experiments |
| title_full | Zhuifeng tougu capsules inhibit the TLR4/MyD88/NF-κB signaling pathway and alleviate knee osteoarthritis: In vitro and in vivo experiments |
| title_fullStr | Zhuifeng tougu capsules inhibit the TLR4/MyD88/NF-κB signaling pathway and alleviate knee osteoarthritis: In vitro and in vivo experiments |
| title_full_unstemmed | Zhuifeng tougu capsules inhibit the TLR4/MyD88/NF-κB signaling pathway and alleviate knee osteoarthritis: In vitro and in vivo experiments |
| title_short | Zhuifeng tougu capsules inhibit the TLR4/MyD88/NF-κB signaling pathway and alleviate knee osteoarthritis: In vitro and in vivo experiments |
| title_sort | zhuifeng tougu capsules inhibit the tlr4 myd88 nf κb signaling pathway and alleviate knee osteoarthritis in vitro and in vivo experiments |
| topic | Zhuifeng tougu capsules TLR4 NF-κB knee osteoarthritis inflammatory factors innate immune |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.951860/full |
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