Research progress on signaling pathways related to the treatment of non-alcoholic fatty liver disease with traditional Chinese medicine
Non alcoholic fatty liver disease (NAFLD) is a liver cell steatosis disease mainly characterized by large bubbles, which occurs without excessive alcohol consumption or liver damage. Its incidence continues to increase and shows a trend of younger onset. According to the severity of pathological development, NAFLD can be divided into four stages: simple fatty liver, fatty hepatitis, fatty liver fibrosis, and fatty liver cirrhosis. High energy diet, obesity, genetic susceptibility, genetic polymorphism, cytokines, and dysbiosis of gut microbiota are the main causes of NAFLD. The theory of “second strike” can partially reveal the mechanism of NAFLD. Insulin resistance (IR) leads to a large accumulation of adipocytes in liver tissue, which is the first strike in the pathogenesis of NAFLD. The cytotoxic reactions that occur on this basis, including oxidative stress and inflammatory reactions, become the second strike in the pathogenesis of NAFLD, ultimately leading to liver fibrosis. With the continuous deepening of modern research, the “multiple strikes” theory provides a more accurate explanation for the pathogenesis of NAFLD. This theory believes that cytokine and endoplasmic reticulum induced steatosis and inflammatory response are the basis of NAFLD pathogenesis, and IR, lipid accumulation, bile acids, genetic polymorphism, etc. are the main factors that induce NAFLD. Both of the above theories believe that the key to the formation and development of NAFLD lies in abnormal lipid metabolism and inflammatory response. Therefore, studying the fundamental mechanism of abnormal liver lipid metabolism and inflammation formation is the focus of NAFLD treatment.
As of now, there is no specific treatment for NAFLD. Modern medicine mainly attempts to improve insulin resistance, reduce liver fatty acid levels, improve oxidative stress and endoplasmic reticulum stress. The types of drugs mainly include insulin sensitizers, antioxidants, cell protectants, tumor necrosis factor alpha (TNF – α) inhibitors, etc. But for NAFLD, especially for patients who develop liver fibrosis, the efficacy of these drugs still needs further research. Traditional Chinese medicine points out from the perspectives of “fat people have more phlegm and dampness” and “fat people have more qi deficiency” that the essence of NAFLD is mostly based on the deficiency of the root and the deficiency of the spleen and liver, and the stagnation of dampness, phlegm, and blood stasis. The common syndrome types can be divided into dampness and turbidity resistance, damp heat accumulation, liver depression and spleen deficiency, and phlegm blood stasis. The treatment methods mainly focus on soothing the liver and spleen, resolving phlegm and dampness, clearing heat and dampness, and promoting blood circulation and removing blood stasis. NAFLD is a chronic disease with a long and persistent course. Traditional Chinese Medicine (TCM) has developed its own system for the prevention and treatment of NAFLD, based on the principles of “treating diseases with the root cause”, “putting people first”, and “treating based on syndrome differentiation”. A large number of experiments have shown that the original advantage of traditional Chinese medicine in treating NAFLD through multi-target and multi pathway therapy is excellent efficacy and universal applicability. This article summarizes the common signaling pathways of traditional Chinese medicine in the treatment of NAFLD in terms of lipid metabolism and inflammatory response, providing theoretical basis for clinical treatment and experimental research.

In summary, lipid metabolism and inflammatory response are two important targets for traditional Chinese medicine treatment of NAFLD. Traditional Chinese medicine reduces lipid deposition by mediating signaling pathways such as FXR, PPAR α, G protein, and regulating bile acid metabolism. It also reduces inflammatory response and oxidative stress by mediating signaling pathways such as NF – κ B, Nrf2, Th17/Treg, JNK, ultimately preventing and treating the progression of NAFLD (see Table 1 for details). In addition, most traditional Chinese medicine and compound formulas have the effects of clearing heat, soothing the liver, removing blood stasis, dispelling dampness, and nourishing the body, which is consistent with the etiology and pathogenesis of NAFLD in traditional Chinese medicine. Traditional Chinese medicine provides comprehensive treatment for NAFLD from a holistic, multi-dimensional, and multi-target perspective, and its efficacy and safety have also been widely recognized.
But the author found through literature search that traditional Chinese medicine treatment for NAFLD also has many shortcomings. Firstly, in the study of formula therapy for NAFLD, it often reflects the comprehensive effects of various drugs, with complex influencing factors, unclear specific active ingredients and mechanisms of action, and a lack of in-depth mechanism research. Secondly, some signaling pathways involved in the treatment of NAFLD with traditional Chinese medicine lack exploratory research and authoritative theoretical support, and basic experimental research and subsequent clinical application research are relatively insufficient. Once again, traditional Chinese medicine involves multiple signaling pathways in the treatment of NAFLD, and each pathway does not function independently. The multiplicity of signaling pathways and whether there are antagonistic and synergistic relationships between them, as well as whether there are other influencing factors and related pathways, are still issues that we need to explore. Therefore, more scholars need to conduct in-depth research on their targets and mechanisms to provide technical and theoretical support for future clinical medication.