1.Mechanism of Action of Kaixinsan in Ameliorating Alzheimer's Disease
Xiaoming HE ; Xiaotong WANG ; Dongyu MIN ; Xinxin WANG ; Meijia CHENG ; Yongming LIU ; Yetao JU ; Yali YANG ; Changbin YUAN ; Changyang YU ; Li ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):20-29
ObjectiveTo investigate the mechanism of action of Kaixinsan in the treatment of Alzheimer's disease (AD) based on network pharmacology, molecular docking, and animal experimental validation. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and the Encyclopedia of Traditional Chinese Medicine(ETCM) databases were used to obtain the active ingredients and targets of Kaixinsan. GeneCards, Online Mendelian Inheritance in Man(OMIM), TTD, PharmGKB, and DrugBank databases were used to obtain the relevant targets of AD. The intersection (common targets) of the active ingredient targets of Kaixinsan and the relevant targets of AD was taken, and the network interaction analysis of the common targets was carried out in the STRING database to construct a protein-protein interaction(PPI) network. The CytoNCA plugin within Cytoscape was used to screen out the core targets, and the Metascape platform was used to perform gene ontology(GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis. The “drug-active ingredient-target” interaction network was constructed with the help of Cytoscape 3.8.2, and AutoDock Vina was used for molecular docking. Scopolamine (SCOP) was utilized for modeling and injected intraperitoneally once daily. Thirty-two male C57/BL6 mice were randomly divided into blank control (CON) group (0.9% NaCl, n=8), model (SCOP) group (3 mg·kg-1·d-1, n=8), positive control group (3 mg·kg-1·d-1 of SCOP+3 mg·kg-1·d-1 of Donepezil, n=8), and Kaixinsan group (3 mg·kg-1·d-1 of SCOP+6.5 g·kg-1·d-1 of Kaixinsan, n=8). Mice in each group were administered with 0.9% NaCl, Kaixinsan, or Donepezil by gavage twice a day for 14 days. Morris water maze experiment was used to observe the learning memory ability of mice. Hematoxylin-eosin (HE) staining method was used to observe the pathological changes in the CA1 area of the mouse hippocampus. Enzyme linked immunosorbent assay(ELISA) was used to determine the serum acetylcholine (ACh) and acetylcholinesterase (AChE) contents of mice. Western blot method was used to detect the protein expression levels of signal transducer and activator of transcription 3(STAT3) and nuclear transcription factor(NF)-κB p65 in the hippocampus of mice. ResultsA total of 73 active ingredients of Kaixinsan were obtained, and 578 potential targets (common targets) of Kaixinsan for the treatment of AD were screened out. Key active ingredients included kaempferol, gijugliflozin, etc.. Potential core targets were STAT3, NF-κB p65, et al. GO functional enrichment analysis obtained 3 124 biological functions, 254 cellular building blocks, and 461 molecular functions. KEGG pathway enrichment obtained 248 pathways, mainly involving cancer-related pathways, TRP pathway, cyclic adenosine monophosphate(cAMP) pathway, and NF-κB pathway. Molecular docking showed that the binding of the key active ingredients to the target targets was more stable. Morris water maze experiment indicated that Kaixinsan could improve the learning memory ability of SCOP-induced mice. HE staining and ELISA results showed that Kaixinsan had an ameliorating effect on central nerve injury in mice. Western blot test indicated that Kaixinsan had a down-regulating effect on the levels of NF-κB p65 phosphorylation and STAT3 phosphorylation in the hippocampal tissue of mice in the SCOP model. ConclusionKaixinsan can improve the cognitive impairment function in SCOP model mice and may reduce hippocampal neuronal damage and thus play a therapeutic role in the treatment of AD by regulating NF-κB p65, STAT3, and other targets involved in the NF-κB signaling pathway.
2.The level of HBV cccDNA in liver tissue and its clinical significance in patients in the convalescence stage of hepatitis B virus-related acute-on-chronic liver failure
Zhekai CAI ; Long XU ; Wenli LIU ; Yingqun XIAO ; Qingmei ZHONG ; Wei ZHANG ; Min WU
Journal of Clinical Hepatology 2025;41(1):57-62
ObjectiveTo investigate the expression level of HBV cccDNA in patients in the convalescence stage of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) and its correlation with HBV markers and liver histopathological changes. MethodsA total of 30 patients in the convalescence stage of HBV-ACL who were hospitalized in The Ninth Hospital of Nanchang from January 2015 to October 2023 were enrolled as liver failure group, and 9 patients with chronic hepatitis B (CHB), matched for sex and age, were enrolled as control group. The content of HBV cccDNA in liver tissue was measured, and its correlation with clinical data and laboratory markers was analyzed. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and a one-way analysis of variance or the Kruskal-Wallis H test was used for comparison between multiple groups; the Fisher’s exact test was used for comparison of categorical data between groups. A Spearman correlation analysis was performed. ResultsThe liver failure group had a significantly lower content of HBV cccDNA in liver tissue than the control group (-0.92±0.70 log10 copies/cell vs -0.13±0.91 log10 copies/cell, t=2.761, P=0.009). In the liver failure group, there was no significant difference in the content of HBV cccDNA in liver tissue between the HBeAg-positive patients and the HBeAg-negative patients (P>0.05); there was no significant difference in the content of HBV cccDNA in liver tissue between the patients with different grades (G0-G2, G3, and G4) of liver inflammatory activity (P>0.05); there was no significant difference in the content of HBV cccDNA in liver tissue between the patients with different stages (S0-S2, S3, and S4) of liver fibrosis (P>0.05); there was no significant difference in the content of HBV cccDNA in liver tissue between the patients with negative HBV DNA and those with positive HBV DNA (P>0.05). For the liver failure group, the content of HBV cccDNA in liver tissue was positively correlated with the content of HBV DNA in liver tissue (r=0.426, P=0.043) and was not significantly correlated with the content of HBV DNA in serum (P>0.05). ConclusionThere is a significant reduction in the content of HBV cccDNA in liver tissue in the convalescence stage of HBV-ACLF. HBV cccDNA exists continuously and stably in liver tissue and can better reflect the persistent infection and replication of HBV than HBV DNA in serum and liver tissue.
3.Effect of Shenqi Yiliu Formula (参芪抑瘤方) Drug-Containing Serum on the Cycle of Gastric Cancer Cell AGS and Wnt/β-Catenin Pathway
Na WEI ; Chongyuan GUO ; Min BAI ; Yaorong AN ; Sichao ZHANG ; Liyang WU ; Yongqiang DUAN
Journal of Traditional Chinese Medicine 2025;66(4):399-406
ObjectiveTo investigate the potential mechanism of Shenqi Yiliu Formula (参芪抑瘤方) in treating precancerous lesions of gastric cancer (PLGC) by the Wnt/β-catenin signaling pathway. MethodsThe CCK-8 assay was used to determine the optimal intervention time for Shenqi Yiliu Formula drug-containing serum and the concentration of the Wnt/β-catenin pathway inhibitor XAV939 depends on the survival rate of AGS gastric cancer cell line. AGS cells were divided into the gastric cancer cell group (15% blank serum), inhibitor group (selected concentration of XAV939), high-dose Shenqi Yiliu Formula group (12% Shenqi Yiliu Formula drug-containing serum + 3% blank serum), medium-dose Shenqi Yiliu Formula group (6% Shenqi Yiliu Formula drug-containing serum + 9% blank serum), and low-dose Shenqi Yiliu Formula group (3% Shenqi Yiliu Formula drug-containing serum + 12% blank serum). Each group was tested in triplicate. After culturing for 24 and 48 hours, cell migration and invasion were assessed by scratch assays; after a selected intervention period (48 hours), cell cycle distribution was analyzed using flow cytometry, Ki67 protein levels were detected by immunofluorescence, the protein levels of Wnt, β-catenin, GSK-3β, and intranuclear T-cell specific factor(TCF) were measured by the protein immunoblotting assay, and the mRNA expressions of these above factors were determined by quantitative real-time PCR. ResultsThe optimal intervention time for Shenqi Yiliu Formula drug-containing serum was determined to be 48 hours, and the effective concentration of XAV939 was 20 μmol/L. Compared with the gastric cancer cell group, Shenqi Yiliu Formula at all doses reduced the cell migration rate at 24 and 48 hours (P<0.05), except for the low-dose group at 24 hours. Compared to the low-dose group at corresponding time points, high- and medium-dose Shenqi Yiliu Formula groups showed significantly reduced migration rates, particularly the high-dose group at 48 hours (P<0.05). Compared with the gastric cancer cell group, the high-dose Shenqi Yiliu Formula and inhibitor groups exhibited reduced protein and mRNA levels of Wnt, β-catenin, and TCF, along with reduced Ki67 protein levels and a decreased proportion of cells in the S and G2 phases of the cell cycle, but GSK-3β protein levels, GSK-3β mRNA expression, and the proportion of cells in the G1 phase increased (P<0.05). Compared to the inhibitor group, the high-dose Shenqi Yiliu Formula group showed a decreased proportion of G1-phase cells and an increased proportion of G2-phase cells (P<0.05), although differences in Wnt and β-catenin protein levels and mRNA expressions were not statistically significant (P>0.05). ConclusionShenqi Yiliu Formula drug-containing serum inhibits the migration and invasion of gastric cancer AGS cells and block the cell cycle at G1 phase, and its underlying mechanism may be related to the regulation of the Wnt/β-catenin signaling pathway.
4.Processing History and Modern Research of Jianghuanglian: A Review
Ying LI ; Yun WANG ; Zhe JIA ; Lin YAN ; Min JIN ; Cun ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):275-282
Jianghuanglian is one of the representative processed products of Coptidis Rhizoma for treating cold syndrome with drugs of heat nature, and ginger is used to restrict the bitter cold of Coptidis Rhizoma, which can be traced back to Bojifang, and it is suitable for stagnation of damp-heat in middle-jiao, cold-heat mutual knots and other symptoms. Jianghuanglian retains the alkaloids, phenylpropanoids and flavonoids of Coptidis Rhizoma, and also introduces gingerol components such as 6-gingerol in ginger, which has pharmacological activities such as anti-inflammatory, antibacterial, anti-tumor, and improving gastrointestinal function. The 2020 edition of Chinese Pharmacopoeia and many local processing specifications have included the traditional processing process and quality standards of Jianghuanglian, but the specific process parameters and quality standards are incomplete, which limits the production and clinical application of this processed product. By summarizing the processing history, process research, quality evaluation, pharmacodynamic and medicinal property changes and application of Jianghuanglian in the past 20 years, there are differences in the processing methods and standards in various provinces and cities, which are mainly reflected in the preparation method, dosage, processing process and quantitative standards of ginger juice. In addition, there are also certain differences in the changes of the main components of Jianghuanglian prepared from ginger or dried ginger, as well as their efficacy and medicinal properties. The research on the processing process of Jianghuanglian plays an important role in improving its quality standards, and this review can provide a reference for improving the quality evaluation system of Jianghuanglian.
5.Effect of a novel initiation model on initiating behavioral requests in children with autism spectrum disorder
Guanzhu ZHANG ; Qiaoyun LIU ; Min LIU ; Yuexin ZHANG ; Lian XU
Chinese Journal of Rehabilitation Theory and Practice 2025;31(2):136-140
ObjectiveTo explore the effect of a novel initiation model on initiating behavioral requests in children with autism spectrum disorder (ASD). MethodsFrom November to December, 2022, 44 children with ASD were selected from Jiaxing Sunlight Rehabilitation Kindergarten, and divided into prelinguistic group (n = 23) and linguistic group (n = 21) according to the language function. The initiation-requested skills, and types and frequency of initiation-requested behaviors were observed under the novel initiation model and the conventional initiation model. ResultsBoth the groups scored higher in the novel initiation model than in the conventional initiation model for initiation-requested skills (|t| > 2.794, P < 0.05) and types of initiation-requested behaviors (|t| > 3.697, P < 0.01), and it increased for the frequency of the use of two- and three-behavioral initiation of requests (χ2 > 7.986, P < 0.05). ConclusionThe novel initiation model can improve initiation request skills in children with ASD.
6.Mechanism of Ruyan Neixiao Cream in Promoting Ferroptosis in Breast Precancerous Lesion Cells by Regulating Nrf2/SLC7A11/GPX4 Signaling Pathway
Haotian ZHANG ; Yebei QIU ; Ran SU ; Xianxin YAN ; Min MA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):98-107
ObjectiveTo explore the mechanism by which Ruyan Neixiao cream (RUC) induces ferroptosis in breast precancerous lesion (BPL) cells, and to enrich the theoretical foundation for its use in the treatment of BPL. MethodsThe inhibition of cell proliferation by 1%, 2%, and 4% concentrations of Ruyanneixiao Cream transdermal solution (RUT) was assessed using cell counting kit-8 (CCK-8) and a colony formation assay. Reactive oxygen species (ROS) were measured using the DCFH-DA probe, and the levels of ferrous ions (Fe2+), glutathione (GSH), and malondialdehyde (MDA) were determined using appropriate kits. Lipid peroxidation was detected with the C11-BODIPY581/591 fluorescent probe. The expression of nuclear factor E2-related factor 2 (Nrf2), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) proteins was analyzed by Western blot. The BPL rat model was constructed using 2,2′-bis(hydroxymethyl)butyric acid (DMBA) combined with estrogen and progesterone, and the rats were treated with RUC for external application. After the 12th cycle, the rats were euthanized, and histopathological changes in breast tissue were observed by hematoxylin-eosin (HE) staining. Fe2+ and MDA levels in breast tissue were measured using corresponding kits. The expression of Nrf2, SLC7A11, and GPX4 proteins in BPL rat breast tissue was detected by immunohistochemistry (IHC) and Western blot. ResultsCompared with the matrix group, the cell viability of MCF-10AT cells in the 1%, 2%, and 4% RUT groups was significantly reduced (P<0.05) in a concentration-dependent manner, with the 24-hour half inhibitory concentration (IC50) being 2.23%. Compared with the 4% RUT group, cell viability in the RUT + Fer-1 group was significantly increased (P<0.05). Compared with the matrix group, the colony formation rates of MCF-10AT cells in the 1%, 2%, and 4% RUT groups were significantly decreased (P<0.05). Compared with the 4% RUT group, the cell colony formation rate of the RUT + Fer-1 group was significantly increased (P<0.05). Compared with the matrix group, the levels of ROS and Fe2+ in the 1%, 2%, and 4% RUT groups were significantly increased (P<0.05), while GSH levels were significantly decreased (P<0.05), and MDA and lipid peroxidation levels were significantly increased (P<0.05). Compared with the 4% RUT group, ROS and Fe2+ levels in the RUT + Fer-1 group were significantly reduced (P<0.05), while GSH levels were significantly increased (P<0.05), and MDA and lipid peroxidation levels were significantly reduced (P<0.05). Compared with the matrix group, the protein expression levels of Nrf2, SLC7A11, and GPX4 in the 1%, 2%, and 4% RUT groups were significantly decreased (P<0.05). Compared with the 4% RUT group, the protein expression levels of Nrf2, SLC7A11, and GPX4 in the RUT + Fer-1 group were significantly increased (P<0.05). In the in vivo experiment, compared with the matrix group, the breast tissue histopathological status of the BPL rats in the RUC group was effectively improved, with less dilatation of the mammary ducts and more orderly duct arrangement. No pathological morphology indicative of invasive cancer was observed. Compared with the matrix group, Fe2+ and MDA levels in the mammary tissue of the RUC group were significantly increased (P<0.05). Compared with the matrix group, the protein expression levels of Nrf2, SLC7A11, and GPX4 in the mammary tissue of the RUC group were significantly reduced (P<0.05). ConclusionRUC may induce ferroptosis in BPL cells by inhibiting the Nrf2/SLC7A11/GPX4 signaling pathway, increasing Fe2+ accumulation, and promoting lipid peroxidation.
7.Mechanism of Ruyan Neixiao Cream in Promoting Ferroptosis in Breast Precancerous Lesion Cells by Regulating Nrf2/SLC7A11/GPX4 Signaling Pathway
Haotian ZHANG ; Yebei QIU ; Ran SU ; Xianxin YAN ; Min MA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):98-107
ObjectiveTo explore the mechanism by which Ruyan Neixiao cream (RUC) induces ferroptosis in breast precancerous lesion (BPL) cells, and to enrich the theoretical foundation for its use in the treatment of BPL. MethodsThe inhibition of cell proliferation by 1%, 2%, and 4% concentrations of Ruyanneixiao Cream transdermal solution (RUT) was assessed using cell counting kit-8 (CCK-8) and a colony formation assay. Reactive oxygen species (ROS) were measured using the DCFH-DA probe, and the levels of ferrous ions (Fe2+), glutathione (GSH), and malondialdehyde (MDA) were determined using appropriate kits. Lipid peroxidation was detected with the C11-BODIPY581/591 fluorescent probe. The expression of nuclear factor E2-related factor 2 (Nrf2), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) proteins was analyzed by Western blot. The BPL rat model was constructed using 2,2′-bis(hydroxymethyl)butyric acid (DMBA) combined with estrogen and progesterone, and the rats were treated with RUC for external application. After the 12th cycle, the rats were euthanized, and histopathological changes in breast tissue were observed by hematoxylin-eosin (HE) staining. Fe2+ and MDA levels in breast tissue were measured using corresponding kits. The expression of Nrf2, SLC7A11, and GPX4 proteins in BPL rat breast tissue was detected by immunohistochemistry (IHC) and Western blot. ResultsCompared with the matrix group, the cell viability of MCF-10AT cells in the 1%, 2%, and 4% RUT groups was significantly reduced (P<0.05) in a concentration-dependent manner, with the 24-hour half inhibitory concentration (IC50) being 2.23%. Compared with the 4% RUT group, cell viability in the RUT + Fer-1 group was significantly increased (P<0.05). Compared with the matrix group, the colony formation rates of MCF-10AT cells in the 1%, 2%, and 4% RUT groups were significantly decreased (P<0.05). Compared with the 4% RUT group, the cell colony formation rate of the RUT + Fer-1 group was significantly increased (P<0.05). Compared with the matrix group, the levels of ROS and Fe2+ in the 1%, 2%, and 4% RUT groups were significantly increased (P<0.05), while GSH levels were significantly decreased (P<0.05), and MDA and lipid peroxidation levels were significantly increased (P<0.05). Compared with the 4% RUT group, ROS and Fe2+ levels in the RUT + Fer-1 group were significantly reduced (P<0.05), while GSH levels were significantly increased (P<0.05), and MDA and lipid peroxidation levels were significantly reduced (P<0.05). Compared with the matrix group, the protein expression levels of Nrf2, SLC7A11, and GPX4 in the 1%, 2%, and 4% RUT groups were significantly decreased (P<0.05). Compared with the 4% RUT group, the protein expression levels of Nrf2, SLC7A11, and GPX4 in the RUT + Fer-1 group were significantly increased (P<0.05). In the in vivo experiment, compared with the matrix group, the breast tissue histopathological status of the BPL rats in the RUC group was effectively improved, with less dilatation of the mammary ducts and more orderly duct arrangement. No pathological morphology indicative of invasive cancer was observed. Compared with the matrix group, Fe2+ and MDA levels in the mammary tissue of the RUC group were significantly increased (P<0.05). Compared with the matrix group, the protein expression levels of Nrf2, SLC7A11, and GPX4 in the mammary tissue of the RUC group were significantly reduced (P<0.05). ConclusionRUC may induce ferroptosis in BPL cells by inhibiting the Nrf2/SLC7A11/GPX4 signaling pathway, increasing Fe2+ accumulation, and promoting lipid peroxidation.
8.Effect of Tuina at "Weizhong (BL 40)" on Spinal Microglial Activation-related Proteins and the IL-10/β-EP Pathway in a Rat Model of Chronic Sciatic Nerve Compression Injury
Tianwei ZHANG ; Xiangqian LYU ; Yani XING ; Liuchen ZHU ; Qingguang ZHU ; Lingjun KONG ; Yanbin CHENG ; Zhen YAN ; Wuquan SUN ; Min FANG ; Zhiwei WU
Journal of Traditional Chinese Medicine 2025;66(7):734-740
ObjectiveTo investigate the analgesic effect of Tuina at the "Weizhong (BL 40)" on neuropathic pain in a rat model of chronic constriction injury (CCI) of the sciatic nerve and its potential central spinal mechanisms. MethodsThirty-two Sprague-Dawley rats were randomly divided into four groups (8 rats in each group), sham-operated group, model group, Tuina group, and blockade group. The CCI model was established in the model group, Tuina group, and the blockade group by ligating the sciatic nerve with catgut, while the sham-operated group underwent only sciatic nerve exposure without ligation. From postoperative day 4 to day 14, rats in the Tuina group and the blockade group received Tuina manipulation at the "Weizhong (BL 40)" using a dynamic pressure distribution measurement system (5 N pressure, 2 Hz frequency, 10 min per session, once daily). The blockade group also received intraperitoneal injections of the microglial inhibitor minocycline (10 mg/kg) once daily. The sham-operated and the model group underwent the same handling and fixation as the Tuina group without actual Tuina. Mechanical withdrawal threshold (MWT) and paw withdrawal latency (PWL) were measured before surgery and on day 3, 7, 10, and 14 post-surgery. Transmission electron microscopy was used to evaluate sciatic nerve injury and repair, measuring axon diameter and total myelinated fiber diameter to calculate the g-ratio. Western Blotting was performed to detect the protein levels of ionized calcium-binding adapter molecule 1 (Iba-1), CD206, CD68, interleukin-10 (IL-10), and β-endorphin (β-EP) precursor pro-opiomelanocortin (POMC) in the ipsilateral spinal dorsal horn. ResultsCompared with the sham-operated group, the model group showed significantly reduced MWT and PWL on day 3, 7, 10, and 14 (P<0.01). Compared with the model group, the Tuina group and the blockade group showed increased MWT and PWL on day 10 and 14 (P<0.05). Compared with the Tuina group, the blockade group exhibited higher MWT on day 7, 10, and 14, and higher PWL on day 10 (P<0.05). Sciatic nerve pathological morphology revealed intact and well-structured myelin in the sham-operated group, while the model group exhibited myelin collapse, distortion, and myelin ovoid formation. The Tuina group displayed partially irregular myelin with occasional myelin collapse, whereas the blockade group exhibited partial myelin irregularities and phospholipid shedding. Compared with the sham-operated group, the model group showed a decreased g-ratio and increased levels of Iba-1 and CD68 in the spinal dorsal horn (P<0.05 or P<0.01). Compared with the model group, the Tuina group and the blockade group exhibited an increased g-ratio and reduced Iba-1 and CD68 levels. Additionally, the Tuina group showed elevated levels of CD206, IL-10, and POMC, whereas the blockade group had decreased CD206 levels (P<0.05). ConclusionTuina at "Weizhong (BL 40)" alleviates neuropathic pain in CCI rats, potentially by regulating microglial activation in the spinal cord, inhibiting M1 polarization while promoting M2 polarization, and activating the IL-10/β-EP pathway to exert analgesic effects.
9.Clinical observation of metformin in the treatment of diabetes mellitus type 2 complicated with sarcopenia in elderly patients
Xuemei ZHONG ; Min CHEN ; Yayun LING ; Bingqian ZHANG
China Pharmacy 2025;36(6):732-736
OBJECTIVE To investigate the efficacy and safety of metformin in the treatment of diabetes mellitus type 2 (T2DM) complicated with sarcopenia in elderly patients. METHODS From January 2022 to January 2024, clinical data from eligible patients with T2DM complicated with sarcopenia treated at the First Affiliated Hospital of Chongqing Medical and Pharmaceutical College were collected. Patients were randomly assigned into control group (70 cases) and observation group (70 cases) using a random number table. Both groups received routine interventions; control group additionally received subcutaneous injections of Insulin glargine injection before bedtime and Human insulin injection 30 minutes before breakfast, lunch and dinner every day. In addition to the same treatments as the control group, the observation group was administered 0.5 g of Metformin hydrochloride sustained-release tablets orally once daily. Both groups were treated continuously for 24 weeks. Comparisons were made between the two groups in terms of glucose metabolism indexes [fasting blood glucose (FBG), 2 h postprandial blood glucose (2 hBG), and glycosylated hemoglobin (HbA1c)], homeostasis model assessment of insulin resistance (HOMA-IR), appendicular skeletal mass muscle index (ASMI), grip strength, walking speed, lipid metabolism indexes [serum total triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)], serological markers [high-sensitivity C reactive protein (hs-CRP), interleukin-6 (IL-6), and ferritin levels] and quality of life. The occurrence of ADR was recorded in both groups. RESULTS 65 patients in the control group and 63 patients in the observation group completed this study, respectively. After treatment, the levels of FBG, 2 hBG, HbA1c, HOMA-IR,TG and TC in both groups, and the levels of hs-CRP, IL-6 and ferritin in observation group were all significantly reduced compared to those before treatment (P<0.05), and the HOMA-IR in observation group was significantly lower than control group (P<0.05); additionally, the grip strength, walking speed, and scores for daily living and activity abilities of observation group were increased than those before treatment and the control group (P<0.05). The incidence of adverse drug reactions in both groups was 2.86%. CONCLUSIONS Metformin can reduce inflammatory factors and ferritin levels, promote the recovery of muscle mass and strength, improve insulin resistance, and quality of life in elderly patients with T2DM complicated with sarcopenia, and does not increase the occurrence of adverse drug reactions.
10.Efficacy and Mechanism of Action of Ermiao Situ Decoction in Modulating JAK/STAT Pathway in Rats with Damp-heat Eczema
Kangning HAN ; Junjie HU ; Juan LI ; Min ZHANG ; Xian ZHOU ; Songlin LIU ; Xin CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):37-47
ObjectiveUltra performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) coupled with network pharmacology and molecular docking was utilized to explore the efficacy and mechanism of action of Ermiao Situ decoction on rats with damp-heat eczema. MethodsA rat model of damp-heat eczema was established by artificial climate chamber intervention combined with sensitization induction by dinitrochlorobenzene (DNCB), and it was randomly divided into the normal group, the model group, the medium- and high-dose groups of Ermiao Situ decoction (3.40 g·kg-1 and 6.80 g·kg-1), and the prednisone acetate group (2.51 mg·kg-1), with eight rats in each group, totalling 46 rats, of which six rats were tested with the drug-containing serum. The chemical analysis of drug-containing serum from rats was carried out by UPLC-Q-TOF-MS/MS, combined with network pharmacology for the prediction of key components, core targets, and signaling pathways, and molecular docking experiments were performed by CB-Dock2 online website. The pharmacological effects of Ermiao Situ decoction in the treatment of damp-heat eczema were investigated by epitaxial indexes combined with the pathologic tissue staining method. The serum levels of gastrin (GAS), interleukin-4 (IL-4), and interleukin-13 (IL-13) were measured by enzyme-linked immunosorbent assay (ELISA). Interleukin-6 (IL-6), Janus kinase 1 (JAK1), phosphorylated (p)-JAK1, signal transduction and activation of transcription factor 3 (STAT3), and p-STAT3 protein expression level was determined by Western bolt. ResultsA total of 19 active ingredients were detected in drug-containing serum samples of rats, which were predicted to act on 198 targets for the treatment of damp-heat eczema, among which the key ingredients included rhodopsin, huangpai alkaloids, and quercetin, and the main core targets included STAT3, tumor necrosis factor (TNF), and IL-6, which were mainly involved in the cancer signaling pathway, phosphatidylinositol 3-kinase (PI3K)/protein kinase (Akt) signaling pathway, T helper 17 (Th17) cell differentiation signaling pathway, and JAK/STAT signaling pathway. The molecular docking results suggested that the key components had strong binding activities with the core targets IL-6, JAK1, and STAT3 in the JAK/STAT signaling pathway. The results of animal experiments showed that compared with those in the normal group, rats in the model group were depressed. They had loose hair, loose stools, epidermal oozing, vesiculation, and generation of thick scabs in the form of scales, decreased body weight, increased anus temperature and water intake, and increased indexes of the spleen, thymus gland, and stomach (P<0.05, P<0.01), and the lesion tissue could be seen to be hyperkeratotic, with the aggregation of inflammatory cells and nonsignificant separation of epidermis and dermis. The gastric mucosa was thinned, deficient, and structurally disorganized, and obvious inflammatory cell aggregation was seen. The levels of GAS, IL-4, and IL-13 in serum were significantly reduced (P<0.05, P<0.01), and the protein expression levels of IL-6, JAK1, p-JAK1, and p-STAT3 in the lesion tissue were significantly increased (P<0.05, P<0.01). Compared with those in the model group, rats in each administration group had stable mental states, formed feces, a clean perianal area, and basically normal epidermis. Only a small amount of scaly scabs existed, and the rats had body weight increased, with decreased anal temperature and water intake, as well as decreased spleen, thymus, and gastric indexes (P<0.05, P<0.01). Epidermal thickness was decreased, and epidermal and dermal separation boundaries were obvious, but hyperkeratotic and accumulation of inflammatory cells could still be seen. The thickness of gastric mucosa increased, and the structure was restored to varying degrees. The levels of GAS, IL-4, and IL-13 content in the serum of rats were increased to varying degrees, and the protein expression levels of IL-6, JAK1, p-JAK1, and p-STAT3 in the dermal lesion tissue were significantly decreased (P<0.05, P<0.01). ConclusionErmiao Situ decoction may exert therapeutic effects on rats with damp-heat eczema by modulating the JAK/STAT signaling pathway.

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