Shenjinhuoxue Mixture Attenuates Inflammation, Pain, and Cartilage Degeneration by Inhibiting TLR-4 and NF-κB Activation in Rats with Osteoarthritis: A Synergistic Combination of Multitarget Active Phytochemicals
Osteoarthritis (OA), a highly prevalent chronic joint disease, involves a complex network of inflammatory mediators that not only triggers pain and cartilage degeneration but also accelerates disease progression. Traditional Chinese medicinal shenjinhuoxue mixture (SHM) shows anti-inflammatory and a...
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2021
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oai:doaj.org-article:138e4686af364c5eb71a46c415d2177d2021-11-15T01:19:44ZShenjinhuoxue Mixture Attenuates Inflammation, Pain, and Cartilage Degeneration by Inhibiting TLR-4 and NF-κB Activation in Rats with Osteoarthritis: A Synergistic Combination of Multitarget Active Phytochemicals1942-099410.1155/2021/4190098https://doaj.org/article/138e4686af364c5eb71a46c415d2177d2021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/4190098https://doaj.org/toc/1942-0994Osteoarthritis (OA), a highly prevalent chronic joint disease, involves a complex network of inflammatory mediators that not only triggers pain and cartilage degeneration but also accelerates disease progression. Traditional Chinese medicinal shenjinhuoxue mixture (SHM) shows anti-inflammatory and analgesic effects against OA with remarkable clinical efficacy. This study explored the mechanism underlying anti-OA properties of SHM and evaluated its efficacy and safety via in vivo experiments. Through network pharmacology and published literature, we identified the key active phytochemicals in SHM, including β-sitosterol, oleanolic acid, licochalcone A, quercetin, isorhamnetin, kaempferol, morusin, lupeol, and pinocembrin; the pivotal targets of which are TLR-4 and NF-κB, eliciting anti-OA activity. These phytochemicals can enter the active pockets of TLR-4 and NF-κB with docking score≤−3.86 kcal/mol, as shown in molecular docking models. By using surface plasmon resonance assay, licochalcone A and oleanolic acid were found to have good TLR-4-binding affinity. In OA rats, oral SHM at mid and high doses (8.72 g/kg and 26.2 g/kg) over 6 weeks significantly alleviated mechanical and thermal hyperalgesia (P<0.0001). Accordingly, the expression of inflammatory mediators (TLR-4, interleukin (IL-) 1 receptor-associated kinase 1 (IRAK1), NF-κB-p65, tumor necrosis factor (TNF-) α, IL-6, and IL-1β), receptor activator of the NF-κB ligand (RANKL), and transient receptor potential vanilloid 1 (TRPV1) in the synovial and cartilage tissue of OA rats was significantly decreased (P<0.05). Moreover, pathological observation illustrated amelioration of cartilage degeneration and joint injury. In chronic toxicity experiment of rats, SHM at 60 mg/kg demonstrated the safety. SHM had an anti-inflammatory effect through a synergistic combination of active phytochemicals to attenuate pain and cartilage degeneration by inhibiting TLR-4 and NF-κB activation. This study provided the experimental foundation for the development of SHM into a more effective dosage form or new drugs for OA treatment.Xiaoqin MaChenxia HaoZhaokang ZhangHuiting JiangWeixia ZhangJingjing HuangXiaofei ChenWanhua YangHindawi LimitedarticleCytologyQH573-671ENOxidative Medicine and Cellular Longevity, Vol 2021 (2021) |
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Cytology QH573-671 |
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Cytology QH573-671 Xiaoqin Ma Chenxia Hao Zhaokang Zhang Huiting Jiang Weixia Zhang Jingjing Huang Xiaofei Chen Wanhua Yang Shenjinhuoxue Mixture Attenuates Inflammation, Pain, and Cartilage Degeneration by Inhibiting TLR-4 and NF-κB Activation in Rats with Osteoarthritis: A Synergistic Combination of Multitarget Active Phytochemicals |
| description |
Osteoarthritis (OA), a highly prevalent chronic joint disease, involves a complex network of inflammatory mediators that not only triggers pain and cartilage degeneration but also accelerates disease progression. Traditional Chinese medicinal shenjinhuoxue mixture (SHM) shows anti-inflammatory and analgesic effects against OA with remarkable clinical efficacy. This study explored the mechanism underlying anti-OA properties of SHM and evaluated its efficacy and safety via in vivo experiments. Through network pharmacology and published literature, we identified the key active phytochemicals in SHM, including β-sitosterol, oleanolic acid, licochalcone A, quercetin, isorhamnetin, kaempferol, morusin, lupeol, and pinocembrin; the pivotal targets of which are TLR-4 and NF-κB, eliciting anti-OA activity. These phytochemicals can enter the active pockets of TLR-4 and NF-κB with docking score≤−3.86 kcal/mol, as shown in molecular docking models. By using surface plasmon resonance assay, licochalcone A and oleanolic acid were found to have good TLR-4-binding affinity. In OA rats, oral SHM at mid and high doses (8.72 g/kg and 26.2 g/kg) over 6 weeks significantly alleviated mechanical and thermal hyperalgesia (P<0.0001). Accordingly, the expression of inflammatory mediators (TLR-4, interleukin (IL-) 1 receptor-associated kinase 1 (IRAK1), NF-κB-p65, tumor necrosis factor (TNF-) α, IL-6, and IL-1β), receptor activator of the NF-κB ligand (RANKL), and transient receptor potential vanilloid 1 (TRPV1) in the synovial and cartilage tissue of OA rats was significantly decreased (P<0.05). Moreover, pathological observation illustrated amelioration of cartilage degeneration and joint injury. In chronic toxicity experiment of rats, SHM at 60 mg/kg demonstrated the safety. SHM had an anti-inflammatory effect through a synergistic combination of active phytochemicals to attenuate pain and cartilage degeneration by inhibiting TLR-4 and NF-κB activation. This study provided the experimental foundation for the development of SHM into a more effective dosage form or new drugs for OA treatment. |
| format |
article |
| author |
Xiaoqin Ma Chenxia Hao Zhaokang Zhang Huiting Jiang Weixia Zhang Jingjing Huang Xiaofei Chen Wanhua Yang |
| author_facet |
Xiaoqin Ma Chenxia Hao Zhaokang Zhang Huiting Jiang Weixia Zhang Jingjing Huang Xiaofei Chen Wanhua Yang |
| author_sort |
Xiaoqin Ma |
| title |
Shenjinhuoxue Mixture Attenuates Inflammation, Pain, and Cartilage Degeneration by Inhibiting TLR-4 and NF-κB Activation in Rats with Osteoarthritis: A Synergistic Combination of Multitarget Active Phytochemicals |
| title_short |
Shenjinhuoxue Mixture Attenuates Inflammation, Pain, and Cartilage Degeneration by Inhibiting TLR-4 and NF-κB Activation in Rats with Osteoarthritis: A Synergistic Combination of Multitarget Active Phytochemicals |
| title_full |
Shenjinhuoxue Mixture Attenuates Inflammation, Pain, and Cartilage Degeneration by Inhibiting TLR-4 and NF-κB Activation in Rats with Osteoarthritis: A Synergistic Combination of Multitarget Active Phytochemicals |
| title_fullStr |
Shenjinhuoxue Mixture Attenuates Inflammation, Pain, and Cartilage Degeneration by Inhibiting TLR-4 and NF-κB Activation in Rats with Osteoarthritis: A Synergistic Combination of Multitarget Active Phytochemicals |
| title_full_unstemmed |
Shenjinhuoxue Mixture Attenuates Inflammation, Pain, and Cartilage Degeneration by Inhibiting TLR-4 and NF-κB Activation in Rats with Osteoarthritis: A Synergistic Combination of Multitarget Active Phytochemicals |
| title_sort |
shenjinhuoxue mixture attenuates inflammation, pain, and cartilage degeneration by inhibiting tlr-4 and nf-κb activation in rats with osteoarthritis: a synergistic combination of multitarget active phytochemicals |
| publisher |
Hindawi Limited |
| publishDate |
2021 |
| url |
https://doaj.org/article/138e4686af364c5eb71a46c415d2177d |
| work_keys_str_mv |
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| _version_ |
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