NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
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2023
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IF 3.6
Chen Xiaohui,Lin Shengrong,Liang Yunbang,Xue Xiaomin,Yasen Miersalijiang
Shikonin is a natural product with antioxidant and anti-inflammatory activities. The biological activity of shikonin is still not fully understood, as well as its association with innate immunity and immune and inflammatory bowel disease (IBD) in humans. In this study, the toxicity of shikonin on Raw264.7 cells was assayed by MTT, and polarization of inflammatory macrophages was determined by flow cytometry. The results showed that shikonin can inhibit the polarization of macrophages towards M1 type and significantly inhibited the production of NO in the concentration range of 0.5–1 μM. In addition, after treatment with shikonin, the production of IL-1β and TNF-α was significantly decreased. After shikonin administration, the body weight loss and decrease of colon length were significantly suppressed in DSS-treated colitis C57BL/6 mice. The pro-inflammatory cytokines TNF-α and IL-1β in colonic homogenate were significantly decreased. Shikonin treatment resulted in a notable improvement in the histopathological manifestations in DSS-treated animals at 25/50 mg/kg. Meanwhile, we found that shikonin can regulate differentiation of T helper 17 cell (Th17)/regulatory T cell (Treg), thereby regulating the balance of Th17/Treg cells and exerting an anti-inflammatory effect in IBD animal models. In conclusion, we found that shikonin protects against DSS-induced acute colitis by, among other things, reducing immune cell infiltration, polarizing macrophages, and regulating Th17/Treg differentiation, as well as by downregulating the release of inflammatory cytokines. These findings showed that shikonin can improve inflammation by affecting macrophage polarization. Our experimental data provide experimental evidence and theory basis for research on anti-inflammatory effects for the shikonin as health or functional food. Graphical Abstract
研究领域:
免疫学
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药理学
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消化病学
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PubMed
高影响因子
BIOLOGICAL & PHARMACEUTICAL BULLETIN
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2025
·Vol. 48
·期 5
·555-562
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IF 1.7
Junli Han,Lianghe Wang,Li Wang,Hua Lei
Pulmonary arterial hypertension (PAH) is a progressive disorder that lacks a validated and effective therapy. Thus, further investigation of the pathogenesis of PAH will help explore novel treatments. The increase in T helper 17 (Th17) cell-mediated pro-inflammatory response and reduction of regulatory T (Treg) cell-mediated anti-inflammatory effect exacerbates PAH progression. Increasing evidence indicates that 5-hydroxytryptamine (5-HT) is closely related to Th17 and Treg polarization. Here, a decrease of 5-HT was found in hypoxia-induced CD4 + T cells. Hypoxia also resulted in a reduction in Treg cells and an increase in Th17 cells, but the addition of 5-HT rescued Th17/Treg balance, confirming that hypoxia destroyed Th17/Treg balance by inducing a 5-HT decrease. Furthermore, we found that 5-HT-restored Th17/Treg balance mitigated primary pulmonary artery smooth muscle cell (PASMC) proliferation, migration, and contraction, which are important factors in vascular remodeling in PAH. In summary, our findings demonstrate that hypoxia-induced 5-HT decline interferes with the balance of Th17/Treg, which affects the biofunction of PASMCs, thus accelerating PAH development. 5-HT-mediated Th17/Treg balance is expected to act as a novel immunotherapy for PAH treatment.
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JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Anhui Wang,Xue Yang,Jiachun Lin,Yali Wang,Jinni Yang,Yuting Zhang,Yuan Tian,Haijuan Dong,Zunjian Zhang,Rui Song
Ethnopharmacological relevance Si-Ni-San (SNS), a traditional Chinese medicinal formula derived from Treatise on Febrile Diseases , is considered effective in the treatment of inflammatory bowel diseases based upon thousands of years of clinical practice. However, the bioactive ingredients and underlying mechanisms are still unclear and need further investigation. Aim of the study This study aimed to evaluate the effect, explore the bioactive ingredients and the underlying mechanisms of SNS in ameliorating ulcerative colitis (UC) and associated liver injury in dextran sodium sulphate (DSS)-induced mouse colitis models. Materials and methods The effect of SNS (1.5, 3, 6 g/kg) on 3% DSS-induced acute murine colitis was evaluated by disease activity index (DAI), colon length, inflammatory cytokines, hematoxylin-eosin (H&E) staining, tight junction proteins expression, ALT, AST, and oxidative stress indicators. HPLC-ESI-IT/TOF MS was used to analyze the chemical components of SNS and the main xenobiotics in the colon of UC mice after oral administration of SNS. Network pharmacological study was then conducted based on the main xenobiotics. Flow cytometry and immunohistochemistry techniques were used to demonstrate the inhibitory effect of SNS on Th17 cells differentiation and the amelioration of Th17/Treg cell imbalance. LC-MS/MS, Real-time quantitative polymerase chain reaction (RT-qPCR), and western blotting techniques were performed to investigate the oxysterol-Liver X receptor (LXRs) signaling activity in colon. Targeted bile acids metabolomics was conducted to reveal the change of the two major pathways of bile acid synthesis in the liver, and the expression of key metabolic enzymes of bile acids synthesis was characterized by RT-qPCR and western blotting techniques. Results SNS (1.5, 3, 6 g/kg) decreased the DAI scores, protected intestinal mucosa barrier, suppressed the production of pro-inflammatory cytokines, improved hepatic and splenic enlargement and alleviated liver injury in a dose-dependent manner. A total of 22 components were identified in the colon of SNS (6 g/kg) treated colitis mice, and the top 10 components ranked by relative content were regarded as the potential effective chemical components of SNS, and used to conduct network pharmacology research. The efficacy of SNS was mediated by a reduction of Th17 cell differentiation, restoration of Th17/Treg cell homeostasis in the colon and spleen, and the experimental results were consistent with our hypothesis and the biological mechanism predicted by network pharmacology. Mechanistically, SNS regulated the concentration of 25-OHC and 27-OHC by up-regulated CH25H, CYP27A1 protein expression in colon, thus affected the expression and activity of LXR, ultimately impacted Th17 differentiation and Th17/Treg balance. It was also found that SNS repressed the increase of hepatic cholesterol and reversed the shift of BA synthesis to the acidic pathway in UC mice, which decreased the proportion of non-12-OH BAs in total bile acids (TBAs) and further ameliorated colitis and concomitant liver injury. Conclusions This study set the stage for considering SNS as a multi-organ benefited anti-colitis prescription based on the significant effect of ameliorating intestinal and liver damage, and revealed that derivatives of cholesterol, namely oxysterols and bile acids, were closely involved in the mechanism of SNS anti-colitis effect.
研究领域:
中药学
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药理学
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免疫学
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PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2026
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IF 5.7
Mengting Li,Danyang Chen,Yu Shao,Zimeng Wang,Yanan Peng,Qiu Zhao,Lan Liu
Sinomenine (SIN), a bioactive alkaloid with anti-inflammatory activity, has shown therapeutic potential in ulcerative colitis (UC), but its precise molecular targets remain unclear. This study investigated the key targets and mechanisms underlying SIN-mediated protection in UC. In a dextran sulfate sodium (DSS)-induced colitis mouse model, SIN dose-dependently alleviated colitis symptoms, restored colon length, improved histopathology injury, and enhanced intestinal barrier integrity by increasing ZO-1 and claudin-1 expression. Integrated bioinformatics analyses, including differential expression analysis, WGCNA, network pharmacology, and machine-learning algorithms, identified farnesoid X receptor (FXR) as a core therapeutic target of SIN. Molecular docking predicted stable SIN-FXR binding, and cellular thermal shift assay further supported engagement of SIN with FXR. FXR expression was reduced in UC tissues and DSS-induced colitis mice but was restored after SIN treatment. Functional enrichment and single-cell RNA sequencing analyses linked FXR to lipid metabolism, immune regulation, and the Th17/Treg balance. Mechanistically, SIN suppressed arachidonic acid metabolism, reduced pro-inflammatory cytokines, increased anti-inflammatory cytokines, decreased Th17 cells, and promoted Treg accumulation. Co-administration of SIN with the FXR agonist fexaramine further potentiated its protective effects, whereas the FXR antagonist glycine-β-muricholic acid markedly reversed SIN-mediated improvements in intestinal inflammation, barrier integrity, arachidonic acid metabolism, and Th17/Treg homeostasis. Collectively, these findings demonstrate that SIN ameliorates experimental colitis, at least in part, by targeting FXR to modulate lipid metabolism and restoring Th17/Treg balance. This study provides a mechanistic basis for the therapeutic application of SIN, either alone or in combination with FXR agonists, in UC treatment.
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npj Biofilms and Microbiomes
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2026
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IF 11.4
Huang Yue,Hu Yu,Zhao Yifei,Li Yuerui,Liu Yunkun,Wang Miao,Wang Qian,Hu Huan
Ulcerative colitis (UC) and periodontitis, both microbial dysbiosis-driven chronic inflammatory disorders, coexist and mutually exacerbate, but the causal mechanisms remain unclear. Using ligature-induced periodontitis plus DSS-colitis mice, we found UC doubles alveolar bone loss, heightens systemic inflammation, oxidative stress, and osteoclastogenesis. 16S rRNA and LC–MS metabolomics showed UC enriches oral pathogens, depletes gut Firmicutes, expands Bacteroides, and correlates with suppressed amino-acid/bile-acid biosynthesis. Fecal microbiota transplantation (FMT) from DSS donors into antibiotic-pretreated periodontitis-prone mice replicated aggravated bone loss, systemic inflammation, gut-barrier leakage, and Th17/Treg imbalance, while healthy-donor FMT protected. GC–MS revealed 35–60% reductions in acetate, propionate, and butyrate; keystone taxa Parabacteroides and Muribaculum inversely correlated with SCFAs and host inflammatory genes. Collectively, UC-driven gut dysbiosis is a transmissible causal factor that simultaneously remodels oral and intestinal biofilms, erodes epithelial barriers, and amplifies osteoclastic bone resorption. SCFAs-producing microbes or supplementation may be potential therapeutics for UC-associated periodontitis patients. The alternative text for this image may have been generated using AI.
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高影响因子
Evidence-based Complementary and Alternative Medicine
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2022
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IF 2.65
Xiufeng Wang,Yunqing Zhong,Rongzhen Zhang,Yueqiao Chen,Minggang Wang,Chao Lv,Dewen Mao
Objective. Acute-on-chronic liver failure (ACLF) is a group of chronic liver diseases and caused by acute internal and external liver injury. Wenyang Huazhuo Tuihuang (WYHZTH) formula had a good clinical effect on promoting the resolution of jaundice. The aim of this study is to further investigate the mechanism of the WYHZTH formula in the ACLF rat model. Methods. The ACLF rat model was constructed by combining human serum albumin with LPS and D-gal. WYHZTH was used to intervene and treat. The cytokines IL-17, IL-23, IL-10, and TGF-β were detected by ELISA and fluorescence-quantitative PCR. Flow cytometry was used to detect the percentage of Th17 and Treg cells in the peripheral blood and liver tissues of each group of rats. The pathological changes in the liver tissue were detected by hematoxylin-eosin staining, immunohistochemistry, and electron microscopy. Results. Compared with the ACLF group, the WYHZTH formula and Thy significantly decreased the levels of ALT, AST, and CHE in the ACLF group. After drug intervention, apoptosis was significantly reduced. The PCNA expression decreased in the ACLF model group but increased in the WYHZTH or Thy group. Under transmission electron microscope, hepatocytes in the ACLF group showed obvious necrosis. After drug intervention, hepatocyte necrosis was reduced with most of the structure returning to normal. Conclusion. This present study demonstrated that WYHZTH formula may protect against acute-on-chronic liver failure, which may be related to the inhibition of Th17/Treg cell imbalance.
研究领域:
肝病学
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免疫学
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药理学
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病理学
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DOI
PubMed
高影响因子
Diabetology & Metabolic Syndrome
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2025
·Vol. 17
·期 1
·427
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IF 3.9
Wang Wenyan,Yang Shurui,Liu Jing,Huang Shang,Li Yong,Liang Fengxia
Background The prevalence of obesity and its associated complications poses a significant threat to human health. The application of electroacupuncture (EA) in the treatment of obesity has been extensively studied. This study aims to investigate the immunological mechanisms underlying the beneficial effects of EA on obesity-related inflammation. Methods In the present study, obesity was induced in rats through a high-fat diet (HFD), followed by the implementation of EA treatment for a duration of 8 weeks. Additionally, the obese rats were subjected to treatment with both an agonist (Resveratrol) and inhibitor (Sirtinol) of silent information regulator 1 (SIRT1). The body weight, fasting blood glucose, and 2-hour postprandial blood glucose levels were regularly monitored throughout the treatment of obese rats. Insulin sensitivity was evaluated through intraperitoneal insulin tolerance test and intraperitoneal glucose tolerance test upon completion of the treatment. The weight of perirenal adipose of obese rats was measured, and the size of adipocytes was observed using HE staining. The quantification of helper T 17 (Th17) cells and regulatory T (Treg) cells in peripheral blood and perirenal adipose tissue was performed using flow cytometry. The expression levels of SIRT1 and acetylated NF-κB in perirenal adipose tissue of rats were observed using immunofluorescence staining and Western blotting analysis. Results Compared to rats on a normal diet, HFD-induced obese rats exhibited insulin resistance (IR), pronounced accumulation of perirenal adipose, an imbalance between Th17 and Treg cells, as well as down-regulated expression of SIRT1. The administration of Resveratrol resulted in the alleviation of the aforementioned symptoms in obese rats. The EA treatment also ameliorated body weight gain, adipose accumulation, IR, and adipose tissue inflammation in rats. Additionally, it was found to enhance SIRT1 expression and reduce acetylation of NF-κB protein. However, the effects of EA treatment on HFD-induced obese rats were partially attenuated by Sirtinol. Conclusion EA exhibits a favorable therapeutic effect on IR and adipose inflammation in obese rats. The underlying mechanism is associated with the promotion of the SIRT1-mediated anti-inflammatory pathway, which regulates the balance between Th17 and Treg cells.
研究领域:
内分泌学
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免疫学
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代谢性疾病
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补充与替代医学
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分子生物学
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高影响因子
MOLECULAR IMMUNOLOGY
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2025
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IF 3
Linmao Lyu,Yanfei Ma,Xuyan Sun,Meng Luo,Zhong Wang,Lijun Fang,Wenqiang Li,Yuguo Chen,Shize Liu,Xiaopeng Jia
Background Cord blood mononuclear cells (CB–MNCs) are a potential alternative therapy for inflammatory bowel disease (IBD). Gut metabolites, T helper 17 (Th17) and regulatory T (Treg) cells are crucial for intestinal hemeostasis and recovery. However, the role of CB–MNCs in modulating IBD, gut metabolites and the Th17/Treg balance remains unclear. Methods In this study, dextran sodium sulfate (DSS) was used to induce acute colitis in male C57BL/6 J mice, followed by treatment with CB–MNCs, umbilical cord-derived mesenchymal stem cells (UC–MSCs), or mesalazine. The severity of colitis was assessed daily using the disease activity index (DAI), and feces were collected for metabolomic analysis. Upon sacrifice, the colons, mesenteric lymph nodes (MLNs) and spleens of the mice were preserved for further study. Results Our findings demonstrated that compared with UC–MSCs and mesalazine, CB–MNCs treatment had superior efficacy in improving clinical symptoms, tissue repair, promoting intestinal regeneration and integrity. While CB-MNCs were equivalent to UC–MSCs and mesalazine in terms of preserving colon length and anti-inflammatory activity. At the molecular level, CB-MNCs exhibited unique and powerful effects. CB-MNCs were found to significantly increase the abundance of cortisol, corticosterone, and several metabolites with anti-inflammatory and antioxidant activities in the feces of colitis mice. CB–MNCs were also more effective than UC–MSCs and mesalazine at maintaining Th17/Treg balance than UC–MSC and mesalazine in colitis mice. Conclusions The intravenous injection of CB-MNCs can alleviate intestinal inflammation and barrier dysfunction by modulating gut metabolites and the Th17/Treg balance. Therefore, CB-MNCs be a promising treatment for IBD.
研究领域:
免疫学
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胃肠病学
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干细胞治疗
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代谢组学
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炎症性疾病
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PubMed
高影响因子
TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE
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2026
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IF 1.5
Ting Zhou,Shanshan Xu,Juan Tang,Xiaomei Han,Yu Jiang,Huaying Chen
Diminished ovarian reserve (DOR) is a critical challenge in reproductive health, leading to reduced fertility and hormonal imbalances. Current treatments such as assisted reproductive technologies and hormone replacement therapy often have limited success and adverse effects. Progesterone receptor membrane component 2 (PGRMC2) is a protein essential for various reproductive processes and is involved in ovarian folliculogenesis, with its increased expression associated with DOR. This study investigates the protective mechanisms of total flavonoids from Semen Cuscutae (TFSC) on ovarian reserve through PGRMC2 modulation and T helper 17 cell (Th17)/regulatory T cell (Treg) immune balance in a DOR rat model. DOR was induced in rats by administering 50 mg/kg tripterygium glycosides (TG) via intragastric administration once daily for 15 days. Various analytical techniques were used to assess the effects of TFSC, including immunohistochemistry for ovarian tissue analysis, Western blotting to measure PGRMC2 protein expression, flow cytometry for evaluating Th17/Treg ratio, and Enzyme-linked immunosorbent assay (ELISA) to quantify serum cytokine levels. Results demonstrate that TFSC enhances ovarian function, up-regulates PGRMC2 expression, and restores immune homeostasis, highlighting its potential as an alternative therapeutic strategy. By elucidating TFSC’s role in immune modulation and ovarian function, this study paves the way for developing targeted therapies to improve outcomes for women with DOR.
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2024
·Vol. 22
·期 1
·1-20
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IF 10.6
Liu Lisha,Deng Dashi,Li Chenchen,Huang Guixiao,Zhang Wenjuan,Liang Ting,Liang Rui,Liang Mingkang,Su Yilin,Lin Chongyang,Li Guangzhi,Wu Song
Rheumatoid arthritis (RA) involves chronic joint inflammation. Combining acupuncture and medication for RA treatment faces challenges like spatiotemporal variability, limited drug loading in acupuncture needles, and premature or untargeted drug release. Here, we designed a new type of tubular acupuncture needles, with an etched hollow honeycomb-like structure to enable the high loading of therapeutics, integrating the traditional acupuncture and drug repository into an all-in-one therapeutic platform. In these proof-of-concept experiments, we fabricated injectable hollow honeycomb electroacupuncture needles (HC-EA) loaded with melittin hydrogel (MLT-Gel), enabling the combination treatment of acupuncture stimulation and melittin therapy in a spatiotemporally synchronous manner. Since the RA microenvironment is mildly acidic, the acid-responsive chitosan (CS)/sodium beta-glycerophosphate (β-GP)/ hyaluronic acid (HA) composited hydrogel (CS/GP/HA) was utilized to perform acupuncture stimulation and achieve the targeted release of injected therapeutics into the specific lesion site. Testing our therapeutic platform involved a mouse model of RA and bioinformatics analysis. MLT-Gel@HC-EA treatment restored Th17/Treg-mediated immunity balance, reduced inflammatory factor release (TNF-α, IL-6, IL-1β), and alleviated inflammation at the lesion site. This novel combination of modified acupuncture needle and medication, specifically melittin hydrogel, holds promise as a therapeutic strategy for RA treatment. Graphical abstract
研究领域:
风湿病学
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生物医学工程
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药学
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免疫学
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PubMed
高影响因子
Science Bulletin
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2023
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IF 18.9
Zheng-Meng Jiang,Su-Ling Zeng,Tian-Qing Huang,Yang Lin,Fang-Fang Wang,Xing-Jiao Gao,Jing Li,Ping Li,E-Hu Liu
Gut microbiota dysbiosis is associated with the development of rheumatoid arthritis (RA). Sinomenine (SIN) is an effective immunosuppressive and anti-inflammatory drug used for treating RA, but how SIN regulates gut microbiota to alleviate RA remains underexplored. To identify the critical gut microbial species and microbial metabolites associated with the RA-protective effects of SIN, the microbiota-dependent anti-RA effects of SIN were assessed by 16S rRNA gene sequencing, antibiotic treatment, and fecal microbiota transplantation. Metabolomics analysis, transcriptional analysis, and targeted bacteria/metabolites gavage were conducted to explore how SIN regulates gut microbiota to reduce the severity of RA. SIN could restore intestinal microbial balance by mainly modulating the abundance of Lactobacillus , and significantly relieve collagen-induced arthritis (CIA) symptoms in a gut microbiota-dependent manner. SIN significantly elevated microbial tryptophan metabolites indole-3-acrylic acid (IA), indole-3-propionic acid (IPA), and indole-3-acetic acid (IAA). Tryptophan metabolites supplementation could activate aryl hydrocarbon receptor (AhR) and regulate Th17/Treg balance in CIA rats. Intriguingly, SIN relieved the arthritis symptoms involving the enrichment of two beneficial anti-CIA Lactobacillus species, L. paracasei and L. casei by mono-colonization. The promising therapeutic function of SIN was mostly attributed to the activation of AhR by explicitly targeting the Lactobacillus and microbial tryptophan metabolites. The intestinal bacterium L. paracasei and L. casei may be used to reduce the severity of CIA.
研究领域:
免疫学
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药理学
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微生物学
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代谢组学
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风湿病学
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高影响因子
ACS Applied Materials & Interfaces
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2025
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IF 8.2
Junjie Chen,Yixian Cheng,Rui Fu,Xinyu Chen,Peng Zhang,Yixiao Lu,Bingsheng Liu,Peng Chen,Jiahao Wang,Haikun Cao,Jinghua Gu,Haosong Chen,Zilong Jiang,Ting Li,Jiawei Zhang,Bo Chen,Guodong Cao
Microplastics (MPs), as emerging global environmental pollutants, exhibit intestinal toxicity mechanisms that are closely associated with the particle size. Nonphagocytosable MPs (NPMs), though incapable of being internalized by intestinal epithelial cells, still provoke colonic inflammatory damage. However, the exact mechanisms remain elusive. This study established a BALB/c mouse model subjected to long-term oral exposure to 10 μm polystyrene MPs (PS MPs) to comprehensively explore how NPMs induce colonic inflammation and injury. The results demonstrate that prolonged PS MPs exposure disrupts the colonic redox balance, leading to oxidative stress. Simultaneously, it disturbs intestinal immune homeostasis by elevating the Th17/Treg cell ratio and upregulating pro-inflammatory cytokines. Additionally, PS MPs notably compromise intestinal mechanical barrier function, diminishing mucin secretion and downregulating tight junction protein expression. Multiomics analysis further uncovered that PS MPs induce bile acid (BA) metabolic dysregulation by interfering with liver function and gut microbiota, causing a marked accumulation of total bile acids in the colon, especially conjugated BAs. Both in vitro and in vivo experiments confirmed that specific concentrations of taurochenodeoxycholic acid (TCDCA) activate the reactive oxygen species-mitochondrial pathway, triggering apoptosis in colonic epithelial cells and exacerbating PS MPs-induced colonic inflammatory injury. This study provides the first evidence of a cross-organ regulatory mechanism in which NPMs mediate intestinal toxicity via the “liver-BA-gut axis,” offering novel theoretical insights for assessing the intestinal toxicity of MPs.
研究领域:
环境毒理学
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免疫学
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胃肠病学
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微生物学
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代谢组学
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生物信息学
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高影响因子
危险品化学品经营许可证（带存储）