1.Effect of Xibining Formula (膝痹宁) on Knee Cartilage Tissue Damage and the cGAS-STING Signaling Pathway in Knee Osteoarthritis Model Mice
Houyu FU ; Xiaochen LI ; Zijian GONG ; Lishi JIE ; Jiangyu LIU ; Yingqi CHEN ; Peimin WANG
Journal of Traditional Chinese Medicine 2025;66(12):1257-1264
ObjectiveTo investigate the possible mechanism of action of Xibining Formula (膝痹宁) for cartilage damage in knee osteoarthritis (KOA) through the cyclic guanosine-adenosine monophosphate synthase (cGAS)- stimulator of interferon genes (STING) signaling pathway. MethodsFifty C57BL/6J mice were randomly divided into five groups (10 per group), sham operation group, KOA model group, low-dose Xibining Formula group, high-dose Xibining Formula group, and high-dose Xibining Formula + agonist group. The KOA models were constructed using the destabilization of the medial meniscus (DMM) method in all groups but the sham surgery group. Two weeks after surgery, the low- and high-dose Xibining Formula groups were administered Xibining Formula at doses of 3.58 g/(kg·d) and 14.32 g/(kg·d) respectively via gavage. The high-dose Xibining Formula + agonist group received 14.32 g/(kg·d) of Xibining Formula via gavage followed by an intraperitoneal injection of Vadimezan (DMXAA) at 25 mg/kg. The sham surgery group and the KOA model group mice were given an equivalent volume of normal saline at 5 ml/(kg·d) via gavage, once daily for four consecutive weeks. Serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) were measured by ELISA; pathological changes in cartilage tissue were observed using hematoxylin-eosin (HE) staining and Safranin O-Fast Green staining. Pathological changes were scored according to the Mankin scoring system; the levels of cartilage tissue matrix regulation-related indicators such as matrix metalloproteinase 3 (MMP3), matrix metalloproteinase 13 (MMP13), a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS), type-Ⅱ collagen (CⅡ) and aggregated proteoglycan (Aggrecan), and also cGAS-STING pathway-related protein and mRNA expression levels were detected by Western blot and qPCR methods. ResultsCompared with the sham surgery group, the KOA model group showed severe cartilage edge destruction, significantly increased Mankin scores, significantly decreased protein and mRNA expression levels of COLⅡ and Aggrecan, and significantly increased protein and mRNA expression levels of cGAS, STING, MMP3, MMP13, and ADAMTS5 (P<0.01). Compared with the control group, serum level of IL-6, IL-1β, TNF-α in all the intervented groups decreased (P<0.01), while compared with high-dose Xibining Formula group, level of IL-6, IL-1β, and TNF-α in low-dose Xibining Formula group and high-dose Xibining Formula + agonist group increased (P<0.01). Compared with the KOA model group, all the intervention groups exhibited alleviated cartilage pathological changes, signi-ficantly reduced Mankin scores, significantly increased protein and mRNA expression levels of COLⅡ and Aggrecan, and significantly decreased protein and mRNA expression levels of cGAS, STING, MMP3, MMP13, and ADAMTS5 (P<0.01). Compared with high-dose Xibining Formula group, high-dose Xibining Formula + agonist group showed cartilage edge destruction, significantly increased Mankin scores, significantly decreased protein and mRNA expression levels of COLⅡ and Aggrecan, and increased protein and mRNA expression levels of cGAS, STING, MMP3, MMP13, and ADAMTS5 (P<0.01). ConclusionXibining Formula may improve KOA cartilage damage by inhibiting the cGAS-STING signaling pathway, decreasing matrix degradation-related proteins, and elevating matrix composition-related proteins.
2.Research Progress on Antitumor Effect of AMPK/mTOR Signaling Pathway Regulated by Traditional Chinese Medicine
Xiafei ZHENG ; Dongdong LI ; Peimin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):268-276
With the increasing incidence and mortality of malignant tumors year by year, the prevention and treatment of malignant tumors has become a hot field of research. Although the existing anti-tumor treatment methods such as surgery, radiotherapy, chemotherapy, immunity and targeting have achieved some results, there are also obvious shortcomings, which are not conducive to the improvement of patients' quality of life and long-term treatment. Therefore, seeking a new efficient and safe treatment has become a hot topic of concern for many oncologists. adenosine monophosphate activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR) signaling pathway can participate in intracellular energy metabolism and affect the pathogenesis and outcome of tumors through multiple mechanisms. It is widely mentioned in the occurrence and development of many tumors. The activity level of this pathway is closely related to the abnormal proliferation and invasion of tumor cells, and is considered as an important pathway for anti-tumor therapy research. The anti-tumor treatment of traditional Chinese medicine(TCM) has significant advantages such as syndrome differentiation and treatment and sample consideration. The study found that flavonoids, alkaloids, polyphenols, saponins and other active components of traditional Chinese medicine, as well as the traditional Chinese medicine compound Xiangbei San, Yiqi Fuzheng Jiedu decoction, Yiqi Fuzheng prescription, etc can activate the AMPK/ mTOR signaling pathway by regulating the expression of AMPK/mTOR signaling pathway and upstream and downstream proteins, thereby inducing tumor cell autophagy and apoptosis, inhibiting tumor angiogenesis and epithelial mesenchymal transformation, regulating aerobic glycolysis and energy metabolism, and reversing drug resistance to exert anti-tumor effects. In this paper, by summarizing the research achievements of TCM anti-tumor in recent years, the specific mechanism of action of TCM regulating AMPK/ mTOR signaling pathway against tumor was discussed, aiming to provide ideas and references for the research and development of anti-tumor new drugs.
3.TCM Treatment of Lung Cancer Based on AMPK Signaling Pathway: A Review
Chengzhi WANG ; Yifan LIU ; Zhenyao YANG ; Wenjun LI ; Xiaoqing ZHANG ; Dongdong LI ; Peimin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):291-298
As a common malignant tumor of the respiratory system, the incidence and mortality of lung cancer are still rising year by year. Its pathogenesis is complex, the prognosis is poor, and it seriously affects human physical and mental health. Although existing Western medical treatments can inhibit tumor growth to a certain extent and relieve patients' painful symptoms, problems such as postoperative recurrence and metastasis, numerous adverse reactions, and the tendency to develop drug resistance make the overall therapeutic effect unsatisfactory. Therefore, it is urgent to seek more efficient and safer treatments. Adenosine monophosphate-activated protein kinase (AMPK) signaling pathway can regulate the growth, differentiation, apoptosis, and autophagy of lung cancer cells, and is extensively involved in the occurrence and development of lung cancer, thus being regarded as an important target for anti-lung cancer therapy. Traditional Chinese medicine (TCM) exerts anti-lung cancer effects through multiple pathways, mechanisms, and targets, with advantages such as preventing postoperative recurrence and metastasis, alleviating the adverse reactions of radiotherapy and chemotherapy, and improving quality of life. TCM has therefore become a key approach in current anti-lung cancer treatment. Studies have found that active components of Chinese medicine, including flavonoids, saponins, polyphenols, and terpenes, as well as Chinese medicine compound prescriptions such as Guiqi Yiyuan extract, Qingzao Jiufei decoction, and Yiqi Fuzheng formula, have significant regulatory effects on AMPK and its interacting signaling pathways. These effects include inducing autophagy and apoptosis of lung cancer cells, modulating macrophage polarization, inhibiting epithelial-mesenchymal transition, reversing drug resistance, and blocking the cell cycle, thereby exerting anti-lung cancer activity. This article reviews and summarizes recent studies on the anti-lung cancer effects of TCM, and discusses the mechanisms by which TCM regulates the AMPK signaling pathway in the treatment of lung cancer, with the aim of providing ideas and references for the development of new clinical anti-lung cancer drugs.
4.TCM Treatment of Lung Cancer Based on AMPK Signaling Pathway: A Review
Chengzhi WANG ; Yifan LIU ; Zhenyao YANG ; Wenjun LI ; Xiaoqing ZHANG ; Dongdong LI ; Peimin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):291-298
As a common malignant tumor of the respiratory system, the incidence and mortality of lung cancer are still rising year by year. Its pathogenesis is complex, the prognosis is poor, and it seriously affects human physical and mental health. Although existing Western medical treatments can inhibit tumor growth to a certain extent and relieve patients' painful symptoms, problems such as postoperative recurrence and metastasis, numerous adverse reactions, and the tendency to develop drug resistance make the overall therapeutic effect unsatisfactory. Therefore, it is urgent to seek more efficient and safer treatments. Adenosine monophosphate-activated protein kinase (AMPK) signaling pathway can regulate the growth, differentiation, apoptosis, and autophagy of lung cancer cells, and is extensively involved in the occurrence and development of lung cancer, thus being regarded as an important target for anti-lung cancer therapy. Traditional Chinese medicine (TCM) exerts anti-lung cancer effects through multiple pathways, mechanisms, and targets, with advantages such as preventing postoperative recurrence and metastasis, alleviating the adverse reactions of radiotherapy and chemotherapy, and improving quality of life. TCM has therefore become a key approach in current anti-lung cancer treatment. Studies have found that active components of Chinese medicine, including flavonoids, saponins, polyphenols, and terpenes, as well as Chinese medicine compound prescriptions such as Guiqi Yiyuan extract, Qingzao Jiufei decoction, and Yiqi Fuzheng formula, have significant regulatory effects on AMPK and its interacting signaling pathways. These effects include inducing autophagy and apoptosis of lung cancer cells, modulating macrophage polarization, inhibiting epithelial-mesenchymal transition, reversing drug resistance, and blocking the cell cycle, thereby exerting anti-lung cancer activity. This article reviews and summarizes recent studies on the anti-lung cancer effects of TCM, and discusses the mechanisms by which TCM regulates the AMPK signaling pathway in the treatment of lung cancer, with the aim of providing ideas and references for the development of new clinical anti-lung cancer drugs.
5.Mechanism of Xibining Ⅱ Combined with ADSC-Exos in Improving Knee Osteoarthritis by Regulating Mitochondrial Autophagy
Junfeng KANG ; Lishi JIE ; Houyu FU ; Taiyang LIAO ; Lei SHI ; Zishan SU ; Likai YU ; Yibao WEI ; Deren LIU ; Di TIAN ; Jun MAO ; Peimin WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(11):111-119
ObjectiveTo observe the effects of Xibining (XBN) and adipose stem cell exosome (ADSC-Exos) in the cases of separate or joint application on cartilage degeneration and mitochondrial autophagy and explore its mechanism of action to improve knee osteoarthritis (KOA). MethodSD rats were divided into a sham operation group (sham group), a model group, an ADSC-Exos group (Exos group), an XBN group, and an ADSC-Exos+XBN group (Exos+XBN group). KOA model was established by using anterior cruciate ligament transection (ACLT). The pain sensitivity status of rats was evaluated, and the degeneration degree of the knee joint and cartilage tissue was detected by Micro-CT and pathological staining. The expression of p62 and LC3B was observed by immunofluorescence, and the serum levels of TNF-α, IL-1β, IL-6, and IL-15 in rats were detected by ELISA. The Western blot was used to detect the protein expression levels of MMP-3, MMP-13, ADAMTS5, ColⅡ, TIMP, ACAN, PINK1, Parkin, p62, and LC3A/B. ResultCompared with the sham group, rats in the model group showed decreased cold-stimulated foot-shrinkage thresholds and mechanical pain sensitivity thresholds, varying degrees of abrasion and loss of cartilage tissue, degeneration of cartilage tissue, elevated serum IL-1β, IL-6, IL-15, and TNF-α levels (P<0.01), and increased protein expression of MMP-3, MMP-13, and ADAMTS5 in cartilage tissue. In addition, the protein expression of ColⅡ, TIMP1, and ACAN was decreased (P<0.01). Compared with the model group, rats in each treatment group showed higher cold-stimulated foot-shrinkage thresholds and mechanical pain sensitivity thresholds, reduced cartilage tissue degeneration, lower serum levels of IL-1β, IL-6, IL-15, and TNF-α (P<0.05,P<0.01), decreased protein expression of MMP-3, MMP-13, and ADAMTS5, and higher protein expression of Cold, TIMP1, and ACAN in cartilage tissue (P<0.05,P<0.01). Moreover, the changes were the most obvious in the Exos+XBN group. ConclusionBoth ADSCs-Exos and XBN can increase the level of mitochondrial autophagy in chondrocytes and delay cartilage tissue degeneration by promoting the expression of the PINK1/Parkin signaling pathway, and the combination of the two can enhance the therapeutic effect.
6.Mechanism of Small Molecules of Traditional Chinese Medicine Targeting Tumor-associated Macrophages in Gastrointestinal Tumors: A Review
Yumeng CAI ; Xiaoqing ZHANG ; Gelei ZHAO ; Shan ZHANG ; Peimin LIU ; Dongdong LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(21):271-278
Tumor-associated macrophages (TAMs), as the main immune cells in the human body, are key factors in maintaining the homeostasis of the tumor microenvironment. With high plasticity, they can polarize into the classically activated (M1) macrophages or alternatively activated (M2) macrophages under different conditions. M1 macrophages can inhibit tumor growth by phagocytosis, and M2 can inhibit the immune microenvironment to promote tumorigenesis and immune escape. Small molecules of traditional Chinese medicine have been widely studied in gastrointestinal tumors. These small molecules exert anti-tumor activity by enhancing TAM activity and promoting the polarization of macrophages. Targeted intervention in TAMs with these molecules has the potential to inhibit the development of gastrointestinal tumors. This article summarizes the research status and significance of small molecules of traditional Chinese medicine targeting TAMs against gastrointestinal tumors, aiming to provide reference for the future studies in this field.
7.Research progress of pyroptosis in tumor immunity
Yuting HAN ; Dongdong LI ; Peimin LIU
Chinese Journal of Immunology 2024;40(11):2421-2426
Pyroptosis,as the main mechanism of host defense,is the key link between innate immunity and adaptive immunity.Pyroptosis is accompanied by membrane rupture,and the cells release a large number of inflammatory mediators,which recruit inflam-matory cells and activate the inflammatory response.Tumor immunotherapy utilizes the natural defense mechanism of the host to ad-minister certain immunomodulators,antibodies or stimulation-adjusted immune cells to obtain stronger anti-tumor effects.Recent stud-ies have shown that pyroptosis has a positive regulatory effect on tumor immunotherapy,including immune checkpoint inhibitors and chimeric antigen receptor T-cell immunotherapy,etc.In this paper,based on the published experimental studies,the mechanism of pyroptosis and its correlation with tumor immunotherapy.In this paper,based on the published experimental studies,the mechanism of cellular apoptosis in tumor immunity is elucidated on the basis of the mechanism of apoptosis and the correlation between tumor im-munotherapy,in order to provide new ideas for the basic and clinical research of malignant tumors.
8.Optimization of the extraction technology for the raw drugs of Sanse powder gel paste
Mingqing FENG ; Nan YANG ; Yuan FANG ; Taiyang LIAO ; Peimin WANG ; Zixiu LIU
China Pharmacy 2023;34(23):2841-2847
OBJECTIVE To optimize the extraction technology for the raw drugs of Sanse powder gel paste. METHODS SD rats were divided into blank group, model group, traditional technology group, water extraction group and ethanol extraction group, with 5 rats in each group. Anterior cruciate ligament transection was used to construct knee osteoarthritis model, and the pharmacodynamic effects of different extraction methods on arthritic rats were investigated. Analgesic experiments were conducted using cold and hot pain thresholds and pain mediators calcitonin gene-related peptide (CGRP), cyclooxygenase-2 (COX-2), substance P (SP), and prostaglandin E2 (PGE2) contents as indicators. HE staining was performed on the synovial membrane of rats to observe the degree of synovial cell proliferation, inflammatory infiltration and vascular invasion, and anti-inflammatory experiments were conducted using protein and mRNA expressions of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and IL-6 as indicators. The analgesic and anti-inflammatory effects were compared among those groups. In the orthogonal test, ethanol dosage, extraction time and extraction times were used as evaluation factors, and the contents of casticin, strychnine and toxiferine were taken as evaluation indicators; comprehensive score was calculated. The validation experiments were carried out after optimizing the extraction technology of the raw drugs of Sanse powder gel paste. RESULTS Compared with the model group, the cold and heat pain thresholds of drug administration groups (except for the traditional technology group) were all increased significantly (P<0.05), while the contents of pain (No.Y2021rc02) mediators CGRP, COX-2, SP and PGE2 were all decreased significantly (P<0.05). HE staining showed that inflammatory cell infiltration, fibrosis and collagen deposition were 炎。E-mail:liuzixiu3221@126.com decreased in the administration groups; a small amount of capillary proliferation could be found; the protein and mRNA expressions of inflammatory factors such as IL-1β, IL-6 and TNF-α were decreased significantly in synovial tissue of rats in administration groups (P<0.05). Compared with the traditional technology group, most indicators of the ethanol extraction group were significantly reduced (P<0.05), and only heat pain threshold and mRNA expression of IL-6 in rats were decreased significantly in the water extraction group (P<0.05). The optimal extraction technology of the raw drugs of Sanse powder gel paste included suitable dose of Sanse powder, 8-fold 55% ethanol, heating reflux extraction for 90 minutes, extracting twice. The results of 3 times of verification experiments showed that the average contents of casticin, strychnine and toxiferine were 0.007%, 0.092%, and 0.214%, respectively; RSD were all less than 5%. CONCLUSIONS The optimized extraction technology for the raw drugs of Sanse powder gel paste is stable and feasible, which can improve the efficacy of the preparation.
9.LC-MS Combined with Network Pharmacology to Explore the Mechanism of “Wenyujin Rhizoma Concisum-Angelicae Sinensis Radix” Essential Oil in the Treatment of Knee Osteoarthritis
FENG Mingqing ; LIAO Taiyang ; YANG Nan ; FANG Yuan ; WANG Peimin ; LIU Zixiu
Chinese Journal of Modern Applied Pharmacy 2023;40(17):2403-2413
OBJECTIVE To extract the essential oil of “Wenyujin Rhizoma Concisum-Angelica Sinensis Radix”, and to qualitatively analyze the chemical composition of the extracted essential oil by LC-MS. Network pharmacology was used to explore the mechanism of the essential oil acting on knee osteoarthritis(KOA). METHODS The essential oil of “Wenyujin Rhizoma Concisum-Angelicae Sinensis Radix” was extracted by steam distillation, the components of the essential oil were analyzed by LC-MS. PubChem, Swiss Target Prediction, GeneCards, DAVID and other databases were used to predict disease targets and pathways of active component in prevention and treatment of KOA. The key genes were analyzed by Gene ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. Cytoscape was used to construct a visual network map of “active component-disease targets”. AutoDock and Pymol were used to verify the molecular docking between the target with the highest degree target and the active components. RESULTS A total of 59 compounds were identified in the “Wenyujin Rhizoma Concisum-Angelicae Sinensis Radix” essential oil, and the main components were curzerenone, isocurcumenol, ligustilide, etc. Through network pharmacology, 28 potential targets of essential oil acting on KOA were screened, including CTSK, PTGS1, PTGS2 and ESR1, etc. KEGG enrichment analysis predicted that “Wenyujin Rhizoma Concisum-Angelicae Sinensis Radix” essential oil mainly targeted TNF signaling pathway, osteoclast differentiation, IL-17 signaling pathway, relaxin signaling pathway, MAPK signaling pathway to treat KOA. The results of molecular docking showed that the screened active components and their corresponding target proteins had positive binding activity. CONCLUSION LC-MS combined with network pharmacology is used to preliminaries explore the main active components and the potential targets and mechanism of action of “Wenyujin Rhizoma Concisum-Angelicae Sinensis Radix” essential oil in the intervention of KOA, providing ideas for the further study of “Wenyujin Rhizoma Concisum-Angelicae Sinensis Radix” essential oil.
10.Determination of individualized PEEP during lung-protective ventilation in patients undergoing general anesthesia: comparison of pulmonary electrical impedance tomography and dynamic lung compliance
Jinlu LI ; Xuemei WU ; Hong XIE ; Jiang ZHU ; Peimin CHEN ; Hairui LIU
Chinese Journal of Anesthesiology 2021;41(1):72-75
Objective:To compare the efficacy of individualized PEEP determined by lung electrical impedance tomography (EIT) and dynamic lung compliance (Cdyn) during lung-protective ventilation strategies in the patients undergoing general anesthesia.Methods:Sixty patients of both sexes, aged 18-64 yr, of American Society of Anesthesiologists physical status Ⅰor Ⅱ, with body mass index of 18.5-28.0 kg/m 2, undergoing elective surgery with general anesthesia and endotracheal intubation in the Second Affiliated Hospital of Soochow University, were selected.Lung-protective ventilation strategy was applied in supine position after general anesthesia.The peak value of PEEP did not exceed 10 cmH 2O, with an increment/decrement of 2 cmH 2O for titration.The corresponding Cdyn value and lung EIT data were collected during titration.The patients were divided into 2 groups ( n=30 each) using a random number table method: titration first increased and then decreased group (group A) and titration first decreased and then increased group (group B). The determination method of individualized PEEP: Cdyn method was the PEEP corresponding to the maximum Cdyn value; EIT method was obtained through PV500 PC software analysis.The level and success rate of individualized PEEP determined by the Cdyn and EIT methods were compared, and the ICC consistency analysis of the determined individualized PEEP was performed. Results:Compared with the Cdyn method, the success rate of individualized PEEP determined by EIT method was significantly increased, and the level of individualized PEEP was decreased in the two group ( P<0.05). In group A, the individualized PEEP titrated by the EIT and Cdyn methods showed good agreement (the ICC value of the increment-Cdyn and increment-EIT methods was 0.761, P<0.05; the ICC value of the decrement-Cdyn and decrement-EIT methods was 0.763, P<0.05). In group B, the individualized PEEP titrated by the EIT and Cdyn methods showed good agreement (the ICC value of the increment-Cdyn and increment-EIT methods was 0.809, P<0.05; the ICC value of the decrement-Cdyn and decrement-EIT methods was 0.797, P<0.05). Conclusion:The agreement between the individualized PEEP determined by lung EIT method and Cdyn method during lung-protective ventilation is good in the patients undergoing general anesthesia, and the success rate of EIT method is higher, and the level of individualized PEEP is lower.


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