Active Components Of Traditional Chinese Medicine in The Treatment Of Knee Osteoarthritis Ⅱ
Oct 12, 2024
2.2 PI3K/AKT/NF-κB signaling pathway
2 2.1 Mullein isoflavones
Shi et al. [41] found that after acting on KOA mice, mullein down-regulated the expression of IL-6, TNF-α, iNOS and COX-2, inhibited the occurrence of cartilage inflammation, and at the same time, down-regulated PI3K/Akt and NFκB. Signaling pathway-related markers are used to regulate the activation of NF-κB and PI3K/AKT signaling pathways to prevent and treat the occurrence of KOA, inhibit IL-1β-induced apoptosis of mouse chondrocytes, and exert chondroprotective effects.
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2 2.2 Chichoric acid
Experiments by Qu et al. [10] showed that chicoric acid can improve KOA by inhibiting the NF-κB and PI3K/AKT signaling pathways, enhancing the activation of the Nrf2/HO-1 pathway, thereby counteracting the activation of NF-κB. It significantly down-regulates the expression of NO, PGE2, iNOS, COX-2, IL-1β, IL-6 and IL-12 and relieves inflammation. In addition, in terms of cartilage metabolism, ECM degradation is attenuated by up-regulating the expression of collagen II and aggrecan and down-regulating the expression of MMP. In terms of cell apoptosis, by up-regulating Bcl-2 levels, down-regulating Bax and ROS levels and activating Nrf2/ HO-1 pathway to inhibit chondrocyte apoptosis. It shows that chicoric acid can prevent and treat the occurrence of KOA by regulating NFκB and PI3K/AKT signaling pathways.
2 2.3 Purpurin
He et al. [42] experimentally demonstrated that in vitro, procytein effectively reversed the excessive secretion of pro-inflammatory factors, such as PGE2, IL-6, TNF-α, COX-2, NO and iNOS, alleviated inflammation, and also It can inhibit ECM apoptosis by reducing the secretion of ADAMTS and MMP, reduce chondrocyte damage, inhibit abnormal excitation of the PI3K/AKT/NF-κB axis, and reduce serum inflammatory factor levels in OA mice in vivo. Improved the destruction of articular cartilage, indicating that procytedin prevents and treats KOA by mediating the PI3K/AKT/NFκB signaling pathway.
2 2.4 Glycyrrhizin
Jiang et al. [43] experimentally confirmed that glycyrrhizin inhibits the growth of human OA chondrocytes in vitro.
The phosphorylation of PI3K/AKT/NF-κB downregulates the expression of NO, PGE2, TNF-α, IL-6, COX-2, iNOs, MMP3, MMP13, and ADAMTS5, inhibits the occurrence of inflammation, and in vivo, glycyrrhizin In OA mice, it reversed cartilage destruction.
2 2.5 Aloe glycoside
Zhang et al. [44] experimentally demonstrated that aloin inhibits the activation of the PI3K/Akt/NF-κB signaling pathway to improve the progression of OA. In vitro, aloin inhibits the expression of TNF-α, IL-6, iNOS, and COX-2. Reduce inflammation, reduce ECM degradation and increase cartilage protection.
2 2.6 Maltol
Lu et al. [45] experimentally demonstrated that when maltol acts on human cartilage tissue, maltol significantly inhibits the phosphorylation of AKT, PI3K and p65 and upregulates the expression of IκBα. In terms of inflammation, it inhibits inflammatory factors induced by IL-1β. and the expression of cytokines (PGE2, NO, IL-6, TNF-α). In terms of cartilage metabolism, maltol downregulates the expression of ADAMTS-5 and MMP13, inhibits the degradation of aggrecan and collagen II to prevent the degradation of ECM, The above proves that maltol can inhibit the occurrence of KOA through the PI3K/AKT/NF-κB signaling pathway.
2 2.7 Maslinic acid
Chen et al. [46] experimentally demonstrated that in vitro, maslinic acid acts on chondrocytes to inactivate the PI3K/AKT/NF-κB pathway and exhibits anti-inflammatory effects. Maslinic acid reduces NO, PGE2, IL-6, iNOS, and COX- 2. Expression of TNF-α. In addition, maslinic acid also inhibits ECM degradation by down-regulating the expression levels of ADAMTS5 and MMP13 in chondrocytes. In vivo experiments found that cartilage damage in OA mice was significantly attenuated.
2 2.8 Ginsenoside-Rb1
Hossain et al. [40] experimentally demonstrated that ginsenoside-Rb1 acts in an OA rabbit model and inhibits the NF-κB signaling pathway by inhibiting the activation of the PI3K/Akt signaling pathway and resists the occurrence of KOA. After application of ginsenoside-Rb1, MMPs, The expression of TNF-α, caspase-3, and bax decreased, and the expression of chondrocytes, proteoglycans, and collagen increased, effectively promoting the generation of chondrocytes, thereby playing a role in preventing and treating KOA.
From the above results, it can be seen that the PI3K/Akt/NF-κB signaling pathway plays a significant role in the pathogenesis and prevention of KOA. A large number of experimental studies have proven the important role of many traditional Chinese medicine monomers in the prevention and treatment of KOA, thus providing a basis for research and development. Provide theoretical basis for drugs that are more effective, more characteristic of traditional Chinese medicine, and have significant curative effects.
2.3 Other NF-κB related signaling pathways
Qiu et al. [14] experimentally demonstrated that exosomes from mesenchymal stem cells (MSCS) treated with curcumin can restore the activity of chondrocytes, inhibit apoptosis to a certain extent, and reduce the mRNA expression of NF-kB. Up-regulated the expression of miR-124 and miR-143, mainly by reducing DNA methylation of their promoters. Wild-type miR-143 significantly inhibited the fluorescence of NF-kB 3'UTR. curcumin inhibits the expression of NF-kB, thus curcumin may prevent and treat KOA by regulating the miR-124/NF-kB and miR-143 pathways.
Lu et al. [47] experimentally demonstrated that chrysophanol reduces the inflammatory response in OA mice by inhibiting the activation of the Nrf2/NF-κB signaling pathway, inhibits the degradation of articular cartilage in vivo, and downregulates ADAMTS-4 and MMP13 in OA mice. , COX-2 and iNOS expression, inhibit the generation of inflammatory response and reduce the degradation of ECM. This plays a role in protecting cartilage and effectively delays the occurrence of KOA.
Wang et al. [48] experimentally demonstrated that safflower yellow acts on chondrocytes of OA rats, inhibits the expression of TNF-α, reduces the protein levels of MMP-13, COX-2, and PGE2, and inhibits the inflammatory response and inflammation of chondrocytes. degradation. Safflower yellow also inhibits TNF-α-induced activation of NF-κB by promoting the phosphorylation of AMPK. Effectively prevent and treat the occurrence of KOA by regulating the AMPK/NF-κB signaling pathway.
Wang et al. [49] found that icariin acted on OA mice and neutralized the activation of IKK (IKK phosphorylation), phosphorylation of IkB and NF-κB, and expression of HIF-2α. It inhibited inflammatory damage by inhibiting the nuclear translocation of NF-κB and the expression of two key targets of the NF-κB/HIF-2α signaling pathway, MMP9 and ADAMTS5. Icariin can regulate the NF-κB/HIF-2α signaling pathway to prevent and treat the occurrence of KOA.
From the above content, we can see that many NF-κB-related pathways, such as miR-124/NF-kB signaling pathway, Nrf2/NF-κB signaling pathway, AMPK/NF-κB signaling pathway, NF-κB/HIF-2α signaling pathway, and many pathways not mentioned (Pin1/NF-κB signaling pathway, LR4/Syk/NF-κB signaling pathway, HMGB1-RAGE/TLR4-NF-κB/AKT pathway) can inhibit the production of inflammatory response, protect cartilage, and prevent the occurrence of KOA. With the advancement of technology, we can start from the above pathways for research in the future, which will enable us to more fully understand the pathogenesis of KOA, thereby developing more effective and reliable traditional Chinese medicines to start from the above targets and provide a more reasonable theoretical basis.
3 Summary and outlook
In summary, NF-κB-related signaling pathways play a key role in regulating inflammatory factors, inhibiting ECM degradation, participating in chondrocyte metabolism, and maintaining bone homeostasis. Therefore, regulating the NF-κB-related signaling pathway can significantly improve the pathological changes and clinical symptoms of KOA and effectively prevent and treat KOA. Currently, the drugs used clinically for the treatment of KOA are mainly non-steroidal anti-inflammatory drugs, such as diclofenac sodium, naproxen, etoricoxib tablets, etc. However, previous studies have found that these drugs include gastrointestinal damage, kidney damage, Many adverse reactions, including liver damage and other diseases. In addition, the price of these drugs is relatively high and patients have poor tolerance. The incidence of KOA is increasing year by year. Therefore, it is a general trend to develop drugs that are low-priced, have few side effects, are easily tolerated by patients, and are highly accepted by patients to prevent and treat KOA. As an important part of China's traditional medicine, traditional Chinese medicine has been in clinical practice for thousands of years. It has the significant advantages of stable curative effect, low toxic and side effects, multi-target and multi-pathway coordination. With the modern development of traditional Chinese medicine, the extraction of traditional Chinese medicine Drugs and related Chinese patent medicines have been fully explored, and the use of Chinese medicine to treat chronic diseases such as KOA has broad prospects and is of great significance.
According to the clinical characteristics of KOA, it can be classified into the categories of "knee paralysis", "bone paralysis" and "paralysis disease". At this stage, many experts are guided by the thinking of "syndrome differentiation and treatment and holistic concept" of traditional Chinese medicine, combined with modern science and technology. Continuous summarization of experience and exploration in experiments and clinical trials have confirmed the effectiveness of traditional Chinese medicine in regulating NFκB-related signaling pathways in the treatment of KOA, and also explained the mechanism of action as much as possible. However, there are still some shortcomings in the current modern research on the prevention and treatment of KOA with traditional Chinese medicine. Many classic prescriptions still lack strong theoretical and practical support in the prevention and treatment of KOA. There are still many ethical and clinical drug aspects to apply in clinical practice. There are many factors, which have led to shortcomings in the research and development of traditional Chinese medicine in our country. Therefore, in the future, we should continue to make full use of modern research methods to further clarify the mechanism and mechanism of action of traditional Chinese medicine in preventing and treating KOA, promote the large-scale use of traditional Chinese medicine, and use this to develop Traditional Chinese medicine drugs with better efficacy and clearer mechanisms. To promote the development of traditional Chinese medicine, we must pay attention to innovation and apply innovative thinking to continuously inherit and carry forward traditional Chinese medicine.
Table 1 Summary of the intervention of Chinese herbal extracts in NF-κB signaling pathway for prevention and treatment of KOA
Test Panel Results
Reference:
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