1.Mechanism of NAFLD-associated Intestinal Barrier Damage and Traditional Chinese Medicine Intervention Strategies Based on "Turbid Pathogenic Factors Entering the Blood" Theory
Haoyang QIN ; Lei LUO ; Mengge LI ; Xueqian KONG ; Fanghua ZHANG ; Zhongqin DANG ; Zhibo DANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):277-287
Intestinal barrier damage is a prominent feature of non-alcoholic fatty liver disease (NAFLD) and serves as a critical factor driving the progression from simple fatty liver to non-alcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. The "turbid pathogenic factors entering the blood" theory integrates classical traditional Chinese medicine (TCM) principles with contemporary disease evolution trends and research findings. It posits that endogenous turbid pathogenic factors within the body infiltrate the blood vessels, leading to impure and viscous blood quality, thereby triggering various diseases. Based on this theory, this article elucidated the pathogenic mechanism of NAFLD-associated intestinal barrier damage. It argued that in NAFLD, the liver loses its dredging function, and the spleen becomes obstructed and dysfunctional. Moreover, essential nutrients fail to be properly transformed, resulting in the internal generation of turbid pathogenic factors. This subsequently initiates a series of pathological changes, namely, "infiltration of phlegm-turbidity into the blood, eroding the intestinal mucosa", "infiltration of glucose-turbidity into the blood, macerating and eroding the intestinal mucosa", "infiltration of heat-turbidity into the blood, scorching and eroding the intestinal mucosa", and "infiltration of stasis-turbidity into the blood, stagnating and eroding the intestinal mucosa", ultimately causing intestinal barrier damage. Furthermore, guided by the "turbid pathogenic factors entering the blood" theory, this article explored TCM intervention strategies: employing medicinals targeting the liver meridian to address the root cause and reduce the generation and deposition of turbid pathogenic factors in the liver, administering blood-system medicinals to clear the blood and purge turbidity, thereby intercepting the progression of the disease mechanism, and applying tonifying medicinals to bolster healthy Qi and defend against turbid invasion, allowing the damaged intestinal mucosa to gradually heal. This article presented novel theoretical and medicinal perspectives for analyzing NAFLD-associated intestinal barrier damage based on the "turbid pathogenic factors entering the blood" theory, aiming to provide new entry points and broader horizons for related research and clinical practice.
2.Traditional Chinese Medicine for Hepatocellular Carcinoma Treatment Based on NF-κB Signaling Pathway: A Review
Ren YANG ; Mengge LI ; Zhibo DANG ; Biaobiao GUO ; Shilong LIU ; Zhongqin DANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):327-335
Hepatocellular carcinoma (HCC), the predominant subtype of primary liver cancer, ranks among the top in both incidence and mortality rates of malignant tumors in China. In its early stages, the disease may present with subtle or nonspecific symptoms, often leading to poor clinical prognosis and low patient survival rates, which makes it a significant public health concern. The pathogenesis is associated with multiple factors, including hepatitis virus infection, alcohol consumption, obesity, drug-induced liver injury, and immune disorders, which may interact synergistically to promote disease development. Currently, mainstream therapeutic approaches for HCC in modern medicine encompass surgical resection, liver transplantation, radiofrequency ablation, radiotherapy, and chemotherapy, but they all have certain limitations, such as large side effects and poor prognosis, imposing substantial psychological distress and financial strain on affected individuals. With a rich historical background in hepatic malignancy management, traditional Chinese medicine offers therapeutic benefits characterized by multi-targeted mechanisms, multi-level regulation, minimal adverse effects, and reduced likelihood of disease recurrence. It can not only enhance the curative effect, but also reduce the side effects of radiotherapy, chemotherapy, and surgery. Thus, it has attracted widespread attention. Extensive research has demonstrated that traditional Chinese medicine exhibits significant antitumor properties, along with notable anti-inflammatory and oxidative stress-reducing capabilities, and its mechanism may be related to the regulation of nuclear factor-kappa B (NF-κB) signaling pathway, which can affect multiple stages of hepatocarcinogenesis, such as cell proliferation, invasion, metastasis, and apoptosis. The mechanism of NF-κB signaling pathway in traditional Chinese medicine for HCC treatment has emerged as one of the pivotal research directions in current oncology studies. Based on the existing research foundation, a systematic literature review method was adopted to retrieve and analyze relevant Chinese and English literature in recent years. Integrating the molecular regulatory mechanisms of the NF-κB signaling pathway and its pivotal role in HCC pathogenesis and progression helped further explore the latest research advances in traditional Chinese medicine interventions targeting this pathway for HCC treatment. This approach may provide novel theoretical foundations and translational strategies for the prevention and management of HCC using traditional Chinese medicine.
3.Mechanism of total salvianolic acid improving myeloid macrophage infiltration in liver cancer bearing mice by regulating TLR4/MyD88/NF-κB pathway
Yunan DU ; Zhibo DANG ; Xiqian ZHANG ; Gaofeng TAN ; Honglin LI ; Yunfei JIA
Chinese Journal of Immunology 2025;41(11):2624-2630
Objective:To investigate the impacts of total salvianolic acid(TSA)on macrophage polarization and mesenchymal macrophage infiltration in liver cancer bearing mice by regulating the Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB)pathway.Methods:Mice were randomly separated into liver cancer group,TSA low concentra-tion group,TSA medium concentration group,TSA high concentration group,TSA high concentration+TLR4 inhibitor(TAK242)group and control group,with 12 mice in each group.Except for control group,mice in all other groups were injected subcutaneously into the right axilla to construct liver cancer models by intraperitoneal transmission of third-generation H22 cell suspension.After suc-cessful modeling,administration was carried out once a day for 2 weeks.Changes in tumor weight,tumor volume,spleen index and thymus index were detected.Immunofluorescence was applied to detect proportions of CD86 and CD206 positive cells in tumor tissue.ELISA was applied to detect levels of inducible nitric oxide synthase(iNOS),IL-6 and IL-10 in tumor tissues.Flow cytometry was ap-plied to detect proportion of CD11b+F4/80+in tumor tissue.Western blot was applied to detect TLR4,p-NF-κB P65 and MyD88 pro-teins in tumor tissue.The life quality and survival rate of mice were observed.Results:Compared with control group,spleen index,thymus index,proportion of CD86 positive cells in tumor tissue,levels of iNOS and IL-6,and expressions of TLR4,p-NF-κB P65 and MyD88 proteins were reduced in liver cancer group,while proportion of CD206 positive cells and level of IL-10 in tumor tissue were increased(P<0.05).Compared with liver cancer group,tumor weight and volume of mice in TSA low,medium,high concentration groups were decreased,while survival rate,spleen index,thymus index,proportion of CD86 positive cells in tumor tissue,levels of iNOS and IL-6,and expressions of TLR4,p-NF-κB P65 and MyD88 proteins were increased,proportion of CD206 positive cells,level of IL-10,and proportion of CD11b+F4/80+in tumor tissue decreased(P<0.05).TAK242 reversed the effects of high concentration TSA on macrophage polarization and myeloid macrophage infiltration in liver cancer bearing mice.Conclusion:TSA may promote M1 polari-zation of macrophages in liver cancer bearing mice and inhibit myeloid macrophage infiltration by activating the TLR4/MyD88/NF-κB pathway.
4.Mechanism of total salvianolic acid improving myeloid macrophage infiltration in liver cancer bearing mice by regulating TLR4/MyD88/NF-κB pathway
Yunan DU ; Zhibo DANG ; Xiqian ZHANG ; Gaofeng TAN ; Honglin LI ; Yunfei JIA
Chinese Journal of Immunology 2025;41(11):2624-2630
Objective:To investigate the impacts of total salvianolic acid(TSA)on macrophage polarization and mesenchymal macrophage infiltration in liver cancer bearing mice by regulating the Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB)pathway.Methods:Mice were randomly separated into liver cancer group,TSA low concentra-tion group,TSA medium concentration group,TSA high concentration group,TSA high concentration+TLR4 inhibitor(TAK242)group and control group,with 12 mice in each group.Except for control group,mice in all other groups were injected subcutaneously into the right axilla to construct liver cancer models by intraperitoneal transmission of third-generation H22 cell suspension.After suc-cessful modeling,administration was carried out once a day for 2 weeks.Changes in tumor weight,tumor volume,spleen index and thymus index were detected.Immunofluorescence was applied to detect proportions of CD86 and CD206 positive cells in tumor tissue.ELISA was applied to detect levels of inducible nitric oxide synthase(iNOS),IL-6 and IL-10 in tumor tissues.Flow cytometry was ap-plied to detect proportion of CD11b+F4/80+in tumor tissue.Western blot was applied to detect TLR4,p-NF-κB P65 and MyD88 pro-teins in tumor tissue.The life quality and survival rate of mice were observed.Results:Compared with control group,spleen index,thymus index,proportion of CD86 positive cells in tumor tissue,levels of iNOS and IL-6,and expressions of TLR4,p-NF-κB P65 and MyD88 proteins were reduced in liver cancer group,while proportion of CD206 positive cells and level of IL-10 in tumor tissue were increased(P<0.05).Compared with liver cancer group,tumor weight and volume of mice in TSA low,medium,high concentration groups were decreased,while survival rate,spleen index,thymus index,proportion of CD86 positive cells in tumor tissue,levels of iNOS and IL-6,and expressions of TLR4,p-NF-κB P65 and MyD88 proteins were increased,proportion of CD206 positive cells,level of IL-10,and proportion of CD11b+F4/80+in tumor tissue decreased(P<0.05).TAK242 reversed the effects of high concentration TSA on macrophage polarization and myeloid macrophage infiltration in liver cancer bearing mice.Conclusion:TSA may promote M1 polari-zation of macrophages in liver cancer bearing mice and inhibit myeloid macrophage infiltration by activating the TLR4/MyD88/NF-κB pathway.
5.Nucleos(t)ide Analogues for Reducing Hepatocellular Carcinoma in Chronic Hepatitis B Patients: A Systematic Review and Meta-Analysis
Xinhui WANG ; Xiaoli LIU ; Zhibo DANG ; Lihua YU ; Yuyong JIANG ; Xianbo WANG ; Zhiyun YANG
Gut and Liver 2020;14(2):232-247
Background/Aims:
Studies have shown that nucleos(t)ide analogue (NA) treatment can reduce the risk of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients, but it is unclear which NA is most effective. We performed a meta-analysis and systematic review comparing the efficacies of NAs in CHB patients.
Methods:
We searched literature databases for randomized controlled trials (RCTs) and observational studies that analyzed the hepatic biochemical response, virological response, seroconversion rate, drug resistance rate, and HCC incidence rate in CHB patients treated with NAs. Meta-analyses were performed with RevMan and Stata/SE software.
Results:
Twelve cohort studies and one RCT were selected, in which entecavir (ETV), lamivudine (LAM), telbivudine (LdT), and/or tenofovir disoproxil fumarate (TDF) were evaluated in CHB patients. The meta-analysis showed that ETV was superior to LAM with regard to the HCC incidence (p<0.001), biochemical response (p=0.001), virological response (p=0.02), and drug resistance (p<0.001), and ETV was superior to LdT with regard to the virological response (p<0.001) and drug resistance (p<0.001). We found no significant difference between ETV and TDF with regard to the HCC incidence (p=0.08), biochemical response (p=0.39), virological response (p=0.31), serological conversion (p=0.38), or drug resistance (p=0.95). NA-treated patients with pre-existing cirrhosis had a 5.49 times greater incidence of HCC than those without cirrhosis (p<0.001).
Conclusions
ETV or TDF should be used for long-term first-line monotherapy in CHB patients according to the current guidelines. Standardized protocols are needed for future studies of ETV and TDF to facilitate conclusive comparisons. Patients with cirrhosis are at significantly elevated risk for HCC, despite the benefits of NA treatment.
6.Therapeutic Effect of Wenwei Zhitong Granules Combined with Acupoint Moxibustion for Spleen-stomach Deficiency-cold Ulcer Disease
Hongxia WANG ; Zhibo DANG ; Zhongqin DANG ; Xian LI ; Gelin XU ; Jinhua SHI
Journal of Guangzhou University of Traditional Chinese Medicine 2015;(3):434-436,440
Objective To observe the therapeutic effect of Wenwei Zhitong Granules ( WZG) combined with acupoint moxibustion for spleen-stomach deficiency-cold ulcer disease. Methods A total of 120 cases of spleen-stomach deficiency-cold ulcer disease were evenly randomized into treatment group and control group. Both groups were given conventional treatment with western medicine plus oral use of WZG, and the treatment group was given acupoint moxibustion additionally. The treatment lasted for 8 weeks. The therapeutic effect on gastroscopy and on relieving stomachache, and the adverse reaction were observed. Results ( 1) The total effective rate showed by gastroscopy was 95.00% in the treatment group and was 85.00% in the control group, the difference being significant (P<0.05). (2) Total effective rate for relieving stomachache was 98.33% in the treatment group and was 88.33% in the control group, the difference being significant ( P<0.05). ( 3) During the treatment, both groups had 2 cases of adverse reaction of nausea, poor appetite and loose stool after oral use of Clarithromycin and Amoxicillin, and then the adverse reaction disappeared after two weeks. No other reverse action was found. Conclusion WZG combined with acupoint moxibustion is effective, convenient and safe for the treatment of spleen-stomach deficiency-cold ulcer disease by promoting the healing of ulcer and relieving stomachache.

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