OBJECTIVE:This study aimed to investigate the therapeutic effect of Yueju Pill (YJP) on functional dyspepsia (FD) rats and its mechanism of promoting gastrointestinal motility. METHODS:We replicated FD rat models using classical tail pinching and irregular feeding for 14 days. After 28 days of YJP treatment, we measured the gastric emptying rate and intestinal propulsion rate of the rats. Hematoxylin-eosin (H&E) staining was used to observe the pathological damage in the gastric antrum. The serum levels of related brain-gut peptides (BGPs) were determined using the enzyme-linked immunosorbent assay (ELISA). Furthermore, we detected the expression of proteins related to the SCF/c-Kit/PI3K/AKT signaling pathway through Western blot and immunohistochemistry. Finally, we assessed the levels of apoptosis using the TUNEL assay. RESULTS:YJP improved gastric emptying and small intestine propulsion rates while reducing gastric tissue injury in FD rats. Moreover, YJP increased the levels of gastrin (GAS) and ghrelin (Ghrelin) and decreased the levels of cholecystokinin (CCK) and vasoactive intestinal peptide (VIP). YJP also elevated the levels of SCF, c-kit and Bcl-2, promoted the phosphorylation of PI3K and AKT, and inhibited the expression of Bax. CONCLUSION:YJP achieved the effect of FD treatment by regulating the SCF/c-Kit/PI3K/AKT pathway, providing a theoretical basis for the clinical treatment of FD.

Chaenomelis Fructus is the dried near-mature fruit of Chaenomeles speciosa. It is warm in nature and sour in taste with the effects of relaxing sinew, activating collaterals, harmonizing stomach, and resolving dampness. At present, the chemical constituents isolated from Chaenomelis Fructus are triterpenoids, sesquiterpenoids, flavonoids, etc. Among them, triterpenoids are the main active components. Chaenomelis Fructus has pharmacological effects such as anti-inflammatory and analgesic effects, immune enhancement, liver protection, protection against digestive tract injury, and anti-gastric cancer activity. In this review, the related studies on the chemical constituents and pharmacological effects of Chaenomelis Fructus in recent years were summarized in order to provide reference for its follow-up research, development, and utilization.

Lipid metabolism may be linked to chronic gastritis, but its causal role remains unclear. While current research emphasizes inflammation, mucosal changes, immune regulation, genetics, and the gut microbiota, the contribution of lipid metabolism is understudied. This study aims to evaluate the impact of serum lipids and the mechanistic roles of lipid-lowering drug targets in chronic gastritis. We conducted a cross-sectional study using data from real world. Multivariable logistic regression was performed to assess the association between serum lipid profiles and gastritis. Mendelian randomization (MR) analyses based on genome-wide association study (GWAS) datasets were performed to detect the causal relationship of serum lipids, plasma lipid species, and lipid-lowering drug targets. Experimental validation was conducted using high-fat diet (HFD)-fed mice and chemically induced CAG rat models. Four thousand sixty one person, including 1,023 patients with chronic atrophic gastritis (CAG), 1,742 with non-atrophic gastritis (NAG), and 1,296 as healthy population were included in the analysis. Through covariates adjustment, TC, ApoA1, and HDL-C showed to be associated with an increased risk of chronic gastritis, whereas TG exhibited a protective effect. MR analysis confirmed a significant inverse causal relationship between TG and gastritis (OR = 0.889, 95

Bisphenol A (BPA) is a globally widespread environmental pollutant in plastic products, posing a potential threat to human health. Although previous studies have shown a close association between BPA exposure and the increased risk of various tumors, its mechanism of action on the tumor immune microenvironment remains unclear. This study constructed subcutaneous xenograft models of colorectal cancer using C57bl/6 mice and BALB/c-nu mice and found that BPA significantly promoted tumor growth only in C57bl/6 mice, suggesting that its carcinogenic effect is dependent on the immune system. Single-cell transcriptome analysis reveals that BPA exposure significantly reshapes the tumor immune microenvironment (TIME), inducing an upregulation in the proportion of Cebpb-expressing MC38 cells and enhancing their interactions with cancer-associated fibroblasts (CAFs) and T cells. Metabolic profiling further suggests that activated CAFs may induce T cell exhaustion and exacerbate immunosuppression by establishing metabolic competition with T cells. Both in vivo and in vitro experiments consistently demonstrate that BPA upregulates Cebpb expression in colorectal cancer cells, while these Cebpb-expressing tumor cells further promote the activation of CAF-related markers. In summary, BPA accelerates colorectal cancer progression by remodeling the immunosuppressive tumor microenvironment. This study reveals a novel mechanism of BPA-mediated tumor immunosuppression, providing potential interventional targets for the prevention and control of BPA-related tumors.

Background Obesity prevalence is rising, increasing risks of ‌metabolic associated fatty liver disease, diabetes mellitus, and cardiovascular disease. Atractylodin (ATR), a bioactive compound from Atractylodes lancea, exhibits potential against metabolic disorders, but its mechanisms against obesity-driven hepatic steatosis remain unclear. Purpose This study aimed to investigate the therapeutic effects and underlying mechanisms of ATR in ameliorating obesity-associated hepatic steatosis via lipid droplet (LD)-mitochondria interactions. Methods Mice were fed a high-fat diet (HFD) for 12 weeks, followed by administration of ATR or Orlistat for 6 weeks beginning at week 6. Hepatic steatosis and molecular targets were assessed via serum biochemistry, histology, fluorescent staining, and Western blot. AML-12 and HepG2 cells were induced with free fatty acids (FFA) and treated with ATR, Atglistatin (ATGLi), etomoxir (ETO), subjected to CPT1A knockdown, or subjected to PLIN2 overexpression/knockdown. In addition to analyzing key proteins and lipid content by molecular and biochemical methods, LD-mitochondria contacts were visualized by transmission electron microscope and laser confocal fluorescence microscopy. Results ATR significantly ameliorated obesity-associated hepatic steatosis in mice and reduced lipid accumulation in AML-12 and HepG2 cells. Visual analysis confirmed that ATR promoted LD-mitochondria contacts. Molecular analysis showed that ATR regulated proteins for lipolysis and fatty acid oxidation (FAO) in liver. Genetic approaches validated that ATR downregulated PLIN2. Mechanistically, ATR promoted LD-mitochondria interactions, lipolysis, and FAO. The effects may be mediated through the regulation of the PLIN2-ATGL/CPT1A axis. Conclusions ATR ameliorates obesity-associated hepatic steatosis by enhancing lipolysis and FAO. Promoting LD-mitochondria interactions represents a promising therapeutic strategy, with ATR showing potential as a therapeutic agent for obesity.

Agrimonia pilosa Ledeb. (APL) is an edible and medicinal plant, which has a favorable cardioprotective effect. Myocardial fibrosis (MF) is a hallmark pathological feature of various cardiovascular diseases. This study aims to evaluate its protective effects against isoproterenol (ISO)-induced MF and investigate the underlying mechanisms. HPLC was employed to analyze the main active ingredients in APL. Network pharmacology methods, combined with experimental validation, elucidated the mechanism by which APL modulates mitophagy to alleviate MF. HPLC analysis showed that six ingredients were identified. We demonstrated that APL significantly attenuated myocardial injury, enhanced cardiac function, inhibited oxidative stress and apoptosis, and effectively ameliorated MF progression. Network pharmacological predictions and in vivo experimental validation demonstrated that APL exerts its therapeutic effects through regulation of the FOXO signaling pathway and suppression of excessive mitophagy. Furthermore, we artificially elevated FOXO1 expression in vitro, which reversed the effects of APL, as evidenced by increased expression of mitophagy and fibrosis-related proteins. Consistent results from both in vivo and in vitro experiments demonstrated that APL attenuates ISO-induced MF and suppresses mitophagy mediated by the FOXO signaling pathway.

Background Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy with a poor prognosis, characterized by early metastasis and high mortality rates. Cryptotanshinone (CTS), a diterpenoid quinone, has been extensively studied for its diverse pharmacological effects, particularly its anti-tumor properties, however, its therapeutic potential and mechanisms in the treatment of ESCC remain unclear. Objective This study aimed to examine the impact of CTS on the polarization of TAMs and its subsequent role in inhibiting the metastasis of ESCC, both as a monotherapy and in combination with cisplatin. Methods THP-1 cells were differentiated into M0, M2, and TAM-like macrophages using PMA, IL-4, and ESCC cell-conditioned medium. CTS's effects on macrophage polarization were analyzed via flow cytometry, RT-qPCR, Western blot, and ELISA. The impact of macrophage-conditioned media on ESCC cell migration and invasion was assessed through wound healing and transwell assays. Molecular mechanisms were confirmed using molecular docking, the cellular thermal shift assay (CETSA), and drug affinity responsive target stabilization assay (DARTS). An in vivo footpad xenograft model in nude mice, co-inoculated with KYSE150 cells and TAMs, tested the anti-metastatic effects of CTS with cisplatin. Results Within the tumor microenvironment of ESCC, TAMs are polarized into a pro-metastatic M2 phenotype. Our findings indicate that CTS disrupts this process by directly targeting the WNT2 protein, thereby interfering with the WNT2/STAT3/SOX4 signaling feedback loop. This disruption leads to a reduction in M2 polarization and a decrease in the secretion of pro-tumorigenic factors from TAMs. As a result, CTS attenuates the pro-tumorigenic effects of TAMs on ESCC cells and, when used in conjunction with cisplatin, synergistically inhibits ESCC metastasis. Conclusion This study demonstrates that CTS reverses the M2 polarization of TAMs by inhibiting the WNT2/STAT3/SOX4 feedback loop, thereby suppressing ESCC metastasis. These findings underscore the potential of CTS as a therapeutic agent that mitigates the pro-tumoral tumor microenvironment and enhances the efficacy of conventional chemotherapy such as cisplatin.

This study explores a green and sustainable approach based on natural ternary deep eutectic solvents (NATDES) and synergistic ultrasound-assisted extraction (UAE) of pigments from safflower florets. Choline chloride-ethylene glycol-acetamide (ChCl-EG-AM, 1:3:1) was successfully synthesized and characterized as the most effective NATDES for the one-step extraction of safflower red and yellow pigments. The optimal conditions for ChCl-EG-AM-UAE were as follows: solid-to-liquid ratio of 50.5 mg/mL, extraction temperature at 48 °C, extraction time of 21 min, and water content of 12.8 %. Moreover, this NATDES system could efficiently be recovered and reused in safflower pigments extraction. Safflower pigments also exhibit greater stability in ChCl-EG-AM under dark conditions at 4 °C. The AGREE, AGREEprep, and BAGI tools were used to evaluate this extraction process, suggestive of greenness. The Fourier transform infrared results showed that ChCl-EG-AM was mainly bonded by hydrogen bonding. Scanning electron microscope results revealed that ChCl-EG-AM disrupted the safflower florets' surface structure, facilitating the release of red and yellow pigments. Electrostatic potential, reduced density gradient, and molecular dynamic simulations were applied to reveal the extraction mechanism of ChCl-EG-AM-UAE, which demonstrated that hydrogen-bonding interactions were the key factor underlying its high performance. The isolated pigments (hydroxysafflor yellow A, anhydrosafflor yellow B, and carthamin) exhibit good antioxidant activity and cardioprotective effects in vitro. Overall, ultrasonic-assisted NATDES extraction is an eco-friendly method for the one-step recovery of safflower red and yellow pigments, which reduces resource waste and simplifies the process of extraction.

ETHNOPHARMACOLOGICAL RELEVANCE:Lianhua Qingke (LHQK) has been utilized as a complementary therapy for respiratory diseases like tracheobronchitis and acute exacerbations of COPD in China. However, its therapeutic efficacy and underlying mechanisms for COPD remain elusive. AIM OF THE STUDY:This study aimed to elucidate the mechanisms underlying the effects of LHQK on COPD, focusing on its anti-senescence properties. MATERIALS AND METHODS:The therapeutic effects of LHQK were assessed by chronic cigarette smoke exposure induced COPD mice model. Lung function, histopathology investigation, cytokines detection and bio-molecular analysis were conducted to assess the impact of LHQK on pulmonary inflammation, mucin secretion, and cellular senescence of cigarette smoke (CS)-induced COPD mice. RESULTS:A comprehensive analysis identified a total of 41 compounds as the key compounds of LHQK. Oral administration of LHQK markedly reversed the decline in pulmonary function, suppressed inflammation and mucus secretion, mitigated emphysema, and histopathology damage in lungs of COPD mice. In addition, LHQK attenuated secretory phenotype associated with cellular senescence in pulmonary and circulatory, and reduced the senescence-associated markers levels, such as SA-β-gal, miR-125a-5p, p21, p27 and p53. Network pharmacology and molecular assays indicated that LHQK enhanced Sp1 and SIRT1 expression, resulting to repression of HIF-1α, finally alleviating cellular senescence in COPD mice. CONCLUSIONS:LHQK demonstrates potential as a complementary therapy for COPD, attenuating CS-triggered emphysema and pulmonary inflammation by targeting cellular senescence processes and modulation of Sp1/SIRT1/HIF-1α pathway.

ETHNOPHARMACOLOGICAL RELEVANCE:Duodenal motility disorder is a contributing factor to dyspepsia. The traditional Chinese medicine (TCM) formula Wei-Tong-Xin (WTX), originated from the famous ancient Chinese formula "Wan Ying Yuan", has been demonstrated efficacy in alleviating dyspepsia. AIM OF THE STUDY:The current study aims to elucidate the chemical composition of WTX to establish the pharmacodynamic material basis. On the basis of component, in depth to illuminate the mechanism by which WTX treats dyspepsia via constructing the comprehensive analysis of multi-platform. MATERIALS AND METHODS:The chemical constituents of WTX were systematically analyzed by UHPLC-Q-TOF-MS/MS data processing methods. Based on this, network pharmacology was employed to predict the mechanism by which WTX improved dyspepsia. The dyspepsia mouse model was constructed, and histopathology as well as intestinal permeability were assessed using H&E staining, PAS staining and FITC-dextran assay. Protein expression was detected using Western blot, immunofluorescence, immunohistochemistry and ELISA kits. RESULTS:A total of 100 chemical components of WTX were preliminarily identified. Network pharmacological analysis indicated that the therapeutic mechanism of WTX in treating dyspepsia may be related to the regulation of inflammation and oxidative stress-related signaling pathways. In vivo studies showed that WTX mitigated duodenal inflammation and oxidative stress responses, repairing the intestinal mucosal barrier damaged by cisplatin (CIS). Additionally, WTX restored the number of glial cells diminished by inflammatory damage, and ameliorated the serotoninergic neuronal dysfunction caused by insufficient secretion of glia-derived neurotrophic factor (GDNF), and enhanced intestinal transit. CONCLUSIONS:In this study, a total of 100 components of the WTX extract were identified through literature review and mass spectrometry database search. Utilizing computer technology, in conjunction with pharmacodynamic and mechanistic studies, WTX has been found to restore serotoninergic neuronal function by reducing intestinal mucosal inflammatory and oxidative damage, ultimately promoting intestinal transport and treating dyspepsia.

Aster tataricus L.f. (A.tataricus), a perennial herb of the genus Aster in the Asteraceae (Compositae) family. It is associated with a spicy, bitter, and warm nature and belongs to the Lung Meridian. The medicinal parts of A.tataricus are flowers, leaves, roots, and rhizomes. A.tataricus was first recorded in Shuo Wen under the alias "Zi Wan" (). Traditionally, it is utilised to clear lung qi, promote fluid flow, calm adverse-rising energy, relieve cough, resolve sputum, and regulate secretions. However, it is worth noting that A.tataricus has certain hepatotoxicity. Modern pharmacology indicates that A.tataricus can be used to treat various diseases, including those of the respiratory and urinary systems. In this review, all available information on A.tataricus was collected via academic databases such as PubMed, SciFinder Scholar, CNKI, iPlant, Google Scholar, Web of Science, GBIF, and Masterpieces of Traditional Chinese Medicine. To date, more than 200 metabolites have been isolated and characterized from A.tataricus, including terpenoids, flavonoids, polypeptides, and others. These compounds demonstrate a wide range of pharmacological activities, such as anti-inflammatory effects, antitussive and bronchodilatory properties, anticancer activity, antioxidant effects, treatment of osteolytic disorders, management of urinary system diseases, alleviation of acute lung injury, and enhancement of memory. Meanwhile, the different polarity extracts of A.tataricus also exhibit some toxicological characteristics, the astin has a similar structure to that of cyclochloridine, the hepatotoxic metabolite of penicillin; its saponins also have hemolytic effects. However, there are currently few studies on the toxicology of A.tataricus. Further in-depth research is needed to explore the potential mechanisms underlying the toxicity of A.tataricus. The toxicity of A.tataricus can be reduced through compatibility and processing, but this aspect has received little discussion and further research on quality standardization is needed. To ensure the sustainable development of A.tataricus, we have also summarized its artificial cultivation techniques. Shionone and astin are the characteristic components of A.tataricus. Their pharmacological effects have been deeply studied, but the research on other metabolites is relatively scarce. Therefore, this article focuses on botany, artificial cultivation, phytochemistry, ethnopharmacology, pharmacology, toxicology, and comprehensive utilization of A.tataricus. Discuss the future research prospects and existing problems of A.tataricus, and provide references for further research on A.tataricus and the establishment of quality control standards.

OBJECTIVE:To investigate the mechanism of Dan Ze mixture (, DZM) in the treatment of lipotoxic cardiomyopathy. METHODS:Ultra-performance liquid chromatography tandem mass spectrometry was employed to characterize the serum migration constituents of DZM. A lipotoxic cardiomyopathy rat model was established through high-fat diet and intervened by different doses of DZM. The cardiac function was assessed using echocardiography, and hematoxylin and eosin, oil red O, and Masson staining were conducted to evaluate morphological changes, lipid accumulation, and fibrosis in myocardial tissue. Serum myocardial enzyme activity, lipid levels, and lipid content of myocardial tissue were measured, while fluorescent staining and colorimetry were used to assess oxidation levels in myocardial tissue. Mitochondrial membrane potential was detected by 5,5', 6,6'-Tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanineio-dide (JC-1). Transmission electron microscopy was employed to observe ultrastructure and mitochondrial structure changes in myocardial tissue. Fluorescence double staining and colocalization were utilized to observe the binding of autophagosomes and mitochondria, while immunohistochemical staining was used to detect the expression of mitophagy-related proteins. Terminal deoxynucleoitidyl transferase mediated nick end labeling staining was employed for the identification of apoptosis in myocardial tissue, while quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blot were utilized for the detection of apoptosis, B-cell lymphoma-2 adenovirus E1B 19 kDa-interacting protein 3 (BNIP3)/ mitophagy signaling pathway-related genes and proteins. In palmitic acid-induced Rat H9C2 cardiomyocytes (H9c2) cells, various cellular parameters including cell viability, lactate dehydrogenase release, apoptosis rate, oxidative stress level, mitochondrial structure and function, and mitophagy level were assessed after the treatment of DZM drug-containing serum for a duration of 24 h. The cellular expressions of BNIP3/mitophagy signaling pathway relevant genes and proteins were further evaluated using qRT-PCR and Western blot techniques. RESULTS:A total of 295 prototypes (e.g., phenolic acids, quinones, terpenoids) were identified in serum of rats after oral administration of DZM. In vivo, DZM therapy has been shown to effectively enhance cardiac function, mitigate high-fat diet-induced myocardial structural damage and lipid accumulation. Furthermore, DZM has demonstrated the ability to reduce lipid levels, attenuate cell apoptosis, combat oxidative stress, enhance mitochondrial structure and function, and activate the BNIP3/mitophagy signaling pathway. Furthermore, the silencing of BNIP3 has been shown to exacerbate palmitic acid-induced damages in H9c2 cells, while inhibiting the BNIP3/mitophagy signaling pathway can mitigate the inhibitory effects of DZM on palmitic acid-induced apoptosis, lipid deposition and oxidative stress. CONCLUSION:This study presents preliminary evidence for the therapeutic efficacy of DZM on lipotoxic cardiomyopathy through the activating BNIP3/mitophagy signaling pathway.

Background Ulcerative colitis (UC) is a chronic inflammatory bowel disease closely linked to intestinal mucosal microcirculatory dysfunction. Sweroside (SOS), a natural iridoid glycoside derived from plants such as Swertia mussotii, Swertia pseudochinensis, and Lonicera japonica, exhibits anti-inflammatory properties. Yet, its therapeutic potential and mechanisms in UC remain unexplored. This study aimed to investigate the effects of SOS on dextran sulfate sodium (DSS)-induced UC and its underlying mechanisms. Methods A DSS-induced UC mouse model was established to evaluate the efficacy of SOS. Inflammatory cytokine levels, intestinal barrier function (assessed via MUC2 immunofluorescence, FITC-dextran permeability, and tight junction protein analysis), and mucosal microcirculation (measured by Laser Speckle Contrast Imaging) were examined. Angiogenesis and endothelial cell (EC) damage were analyzed using ELISA, immunohistochemistry, and transmission electron microscopy. Transcriptomics and molecular docking were utilized to investigate SOS-mediated pathways, with subsequent validation by qRT-PCR, western blot, and immunofluorescence. Additionally, a cellular injury model was generated by treating human umbilical vein endothelial cells (HUVECs) with DSS. Cellular inflammatory and angiogenesis-related factors were quantified via ELISA, while migration and angiogenesis capabilities of HUVECs were assessed through scratch and tube-forming assays. The expression of the VEGF and Hippo pathway-related proteins was determined by western blot. Results SOS significantly ameliorated UC symptoms, reducing weight loss, diarrhea, and DAI scores while suppressing inflammatory infiltration and cytokine release. SOS enhanced intestinal barrier integrity via tight junction upregulation and improved microcirculation by attenuating EC injury and angiogenesis. Mechanistically, SOS regulated the VEGF and Hippo pathways, a key regulator of angiogenesis, as confirmed by transcriptomics and molecular docking. In vitro, SOS protected HUVECs from DSS-induced inflammation and angiogenesis, confirming the improvement of mucosal microcirculation by modulating VEGF and Hippo pathways. Conclusions SOS ameliorates DSS-induced UC by impacting the VEGF and Hippo pathways, thereby suppressing ECs' angiogenesis, restoring mucosal microcirculation, and mitigating intestinal inflammation. These findings highlight SOS as a promising therapeutic candidate for UC.

Geum japonicum Thunb. var. chinense (G. japonicum) is a cultivated medicinal plant and used as folk medicine, among which tannins are the main active ingredients. In this work, L-proline-lactic acid (Pro:La) as natural deep eutectic solvents (NADESs) was tailored for the total tannins extraction from G. japonicum with the optimal conditions as follows: water content of 29%, solid-liquid ratio of 27:1 (mg/mL), extraction time of 48 min, and extraction temperature of 48(degrees)C. In high fat diet-induced obese mice, the total tannin extract of G. japonicum can significantly reduce the body weight and serum lipid levels, improve glucose tolerance impairment and insulin resistance, reduce islet hypertrophy and protect the liver. Targeted fractionation of the total tannin extract of G. japonicum led to the isolation of sixteen tannins. Notably, the isolated tannins, except for ellagic acid and 3,3 ' di-O-methylellagic acid, possessed strong alpha-glucosidase inhibitory activities (IC50: 1.401-4.801 mu g/mL) and dosedependently inhibited glucose consumption of Caco-2 model system in vitro. These results indicate that the NADES (Pro:La) can effectively extract total tannins from G. japonicum and provide a reference for further applications in medicine and healthcare products.

Here, we presented the study of the molecular mechanisms underlying the action of Wulingsan (WLS) in rats with metabolic-associated fatty liver disease (MAFLD) induced by a high-fat diet (HFD). High-performance liquid chromatography was employed to identify the chemical components of WLS. After 2 weeks of HFD induction, MAFLD rats were treated with WLS in three different doses for 6 weeks, a positive control treatment or with a vehicle. Lipid metabolism, liver function, oxidative stress, and inflammatory factors as well as pathomorphological changes in liver parenchyma were assessed in all groups. Finally, the expressions of autophagy-related markers, adenosine monophosphate-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR)/unc-51-like kinase-1 (ULK1) signaling pathway-related genes, and proteins in liver were detected. The results revealed that WLS significantly ameliorated liver injury, the dysfunction of the lipid metabolism, the oxidative stress, and overall inflammatory status. Furthermore, WLS increased the expressions of LC3B-II, Beclin1, p-AMPK, and ULK1, along with decreased p62, p-mTOR, and sterol regulatory element-binding protein-1c levels. In conclusion, we showed that WLS is capable of alleviating HFD-induced MAFLD by improving lipid accumulation, suppressing oxidative stress and inflammation, and promoting autophagy.

Isoorientin (Iso) is a natural flavonoid present in the human diet, known for its anti-inflammatory, antioxidant, and antiviral properties. The purpose of this research was to illustrate the anti-inflammatory potential of Iso in ulcerative colitis (UC) mice and elucidate potential mechanisms. The mice model of UC was induced by cyclic intervention with Dextran Sulfate Sodium (DSS). We evaluated the efficacy of Iso in the treatment of UC, detected the expression of proteins related to the Galectin-3/NLRP3/IL-1β signaling pathway, and assessed the intestinal mucosa barrier function of colon tissue. Our findings demonstrated that Iso could improve colon length, the index of colonic weight, pathological damage to the colon, and serum cytokine secretion of UC mice. Most importantly, Iso could competitively bind Galectin-3, inhibit the interaction of Galectin-3 with NLRP3 and the expression of Galectin-3, NLRP3, ASC, caspase-1, IL-1β, and IL-18, increase the expression of MUC2, Occludin, and ZO-1. In summary, Iso had a therapeutic effect on UC mice, and its mechanism may be to inhibit the inflammatory response and improve the intestinal mucosa barrier by binding Galectin-3 and inhibiting the Galectin-3/NLRP3/IL-1β signaling pathway.

Background Gastric ulcer (GU) is a common gastrointestinal disease with high morbidity that may be caused by various pathogenic factors. Dan-Shen-Yin (DSY), a traditional prescription, improves myocardial and gastrointestinal functions; however, its effect on GU and the underlying mechanisms requires further research. Purpose We aimed to evaluate the pharmacodynamics of DSY granules in GU using three different animal models and explore their potential mechanisms. Methods DSY granules were manufactured and subjected to quality control by high-performance liquid chromatography (HPLC). Three GU models were established using ethanol, aspirin, or water immersion restraint combined with aspirin and examined using the Guth method and hematoxylin and eosin (H&E) staining. The effects of DSY granules on gastric mucosal glycoproteins and the release of defensive and aggressive factors in ethanol-induced GU were measured using periodic acid-Schiff (PAS) staining and ELISA. TUNEL staining and detection of apoptosis-related proteins were used to evaluate the role of DSY granules on apoptosis. Potential mechanisms were predicted using network pharmacology, molecular docking, and western blot to verify the related targets and pathways. Results DSY granules were prepared for the first time and quality control standard was established. Pharmacodynamic evaluation indicated that DSY granules significantly reduced the GU index and gastric mucosal injury in the three GU models, and the GU inhibition rate of DSY granules was superior to omeprazole in ethanol-induced GU model (60.32% vs 21.96%). Further studies in ethanol-induced GU model revealed that DSY granules increased the levels of the defensive factors (PGE2, NO, SOD, CAT, TAOC, and GSH) and decreased the levels of aggressive factors (MDA, TNF-α, and IL-1β), thereby inhibiting oxidative stress and inflammation, attenuating gastric mucosal injury. Moreover, the results of TUNEL staining and western blot showed that DSY granules suppressed apoptosis by reducing the ratios of Bax/Bcl-2 and cleaved-Caspase-3/Caspase-3. In addition, the results of network pharmacology and molecular docking suggested that the mechanisms of DSY granules against GU may be related to the Akt-related signaling pathway. Further study confirmed that DSY granules significantly reduced the ratio of p-Akt/Akt and promoted the expression of Nrf2 and NQO1, protecting the gastric mucosa. Conclusions Our results indicated that DSY granules had protective effects on GU caused by different mechanisms, especially ethanol-induced GU. DSY granules alleviated gastric mucosal damage by inhibiting oxidative stress, inflammation, and apoptosis, which may be associated with the regulation of Akt/Nrf2 signaling pathway. Therefore, DSY granules may be a promising drug for the treatment of GU.

Background: One of the most common microvascular complications of diabetes is diabetic kidney disease (DKD). The Huajuxiaoji formula (HJXJ) has shown clinical efficacy for DKD; however, its regulatory mechanisms against DKD remain elusive. We investigated NLRP3 inflammasome and the mechanisms of HJXJ by which HJXJ alleviates DKD. Methods: Phenyl sulfate (PS) was used to establish DKD models. HJXJ was administered to mice through intragastric or made into a pharmaceutical serum for the cell cultures. Biological indicator levels in mouse blood and urine were analyzed, and kidney tissues were used for HE, Masson, and PAS staining. ELISA and western blotting were used to detect inflammatory cytokines and protein levels, respectively. Reactive oxygen species (ROS) production and pyroptosis were evaluated using flow cytometry. Lentiviral vector-mediated overexpression of NLRP3 was performed to determine whether NLRP3 participates in the antipyroptotic effect of HJXJ. Results: HJXJ significantly reduced the severity of the injury and, in a dose-dependent manner, decreased the levels of biological markers including creatinine, blood urea nitrogen, urine protein, and endotoxin, as well as inflammatory cytokines such as interleukin (IL)-1β, IL-18, tumor necrosis factor-α, and IL-6 in DKD mice. Treatment with HJXJ reversed the downregulation of podocin, nephrin, ZO-1, and occludin and upregulated ROS, NLRP3, Caspase-1 P20, and GSDMD-N induced by PS. Moreover, the upregulation of NLRP3 expression increased the number of cells positive for pyroptosis. HJXJ suppressed pyroptosis and inflammasome activation by inhibiting NLRP3 expression. Conclusions: Generally, HJXJ has the potential to reduce DKD injury and exerts anti-DKD effects by inhibiting the NLRP3-mediated NLRP3 inflammasome activation and pyroptosis in vitro and in vivo.