Oxidative Medicine and Cellular Longevity
·
2018
·
IF 4.936
Hong-Xin Cui,Ya-Nan Hu,Jing-Wan Li,Ke Yuan
Both alterations to the intestinal microflora and chronic systemic inflammation predispose towards type 2 diabetes (T2D). Changes in the composition of the intestinal microflora are associated with glucose metabolism changes in rats with T2D. Here, we demonstrate that a berberine fumarate (BF) has a hypoglycemic effect by regulating the intestinal microflora and metabolism of diabetic rats. The T2D rats had disorders of glucose and lipid metabolism, an abnormal intestinal microflora, fewer butyrate-producing and probiotic-type bacteria, larger numbers of potentially pathogenic and sulfate-reducing bacteria, and tissue inflammation. Administration of berberine fumarate significantly ameliorated the metabolic disorder; increased the populations of Bacteroidetes, Clostridia, Lactobacillales, Prevotellaceae, and Alloprevotella; and reduced those of Bacteroidales, Lachnospiraceae, Rikenellaceae, and Desulfovibrio. In addition, it reduced inflammation, inhibiting the overexpression of TLR4 and p-JNK and increasing the expression of PI3K, GLUT2, and other proteins, which are closely related to oxidative stress, thereby promoting the metabolism of glucose.
研究领域:
药理学
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微生物学
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内分泌学
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代谢学
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PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
·
IF 5.4
Zhengwen Zhang,Zhaojun Wang,Yushun Cui,Min Yao,Jiajian Lu,Mingzhen He,Yulin Feng,JunMao Li
Ethnopharmacological relevance Ainsliaea fragrans Champ. (AFC) , a traditional Chinese medicinal herb with a well-documented history in the management of gynecological disorders, serves as the principal component of several Chinese patent medicines that have demonstrated significant clinical efficacy against cervicitis, endometritis, and pelvic inflammatory disease. However, its specific mechanism of action against cervicitis has not been fully elucidated. Purpose This study aims to determine the therapeutic efficacy and underlying mechanisms of AFC in treating cervicitis, and identifying its key active components. Materials and methods First, an in vivo model of cervicitis was established using a phenolic mucilage solution, while an in vitro LPS induced RAW264.7 cell inflammation model was employed. The therapeutic effects of AFC were evaluated through HE staining, uterine index measurements, RT-qPCR and ELISA. The chemical constituents of AFC were identified using ultra-performance liquid chromatography coupled with UPLC-Q-TOF/MS. Subsequently, cellular metabolomics and network pharmacology were utilized to predict the potential targets, mechanisms, and active components of AFC in treating cervicitis. Finally, the underlying mechanisms and active ingredients were validated using methods such as RT-qPCR, Western blot, and molecular docking. Results Both in vivo and in vitro experiments demonstrated that AFC ameliorated phenol mucilage-induced cervicitis in rats and significantly suppressed the expression of inflammatory factors including IL-6, TNF-α, and IL-1β. UPLC-Q-TOF-MS/MS analysis identified 93 chemical constituents in AFC. Cellular metabolomics revealed 79 differential metabolites, including PGE2 and COX-2, among others. Integrated network pharmacology analysis identified potential targets including IDO1 and COX-2, and enriched signaling pathways such as TLR4 and PI3K/AKT-mTOR. Among the nine candidate compounds screened, luteolin, apigenin, and isorhamnetin ranked as the top three by degree value were hypothesized to be the primary active constituents of AFC against cervicitis. Subsequent experimental validation through RT-qPCR, Western blot, and molecular docking demonstrated that AFC treats cervicitis by modulating the PGE2/COX-2/IDO1-FLG in coordination with the TLR4 and PI3K/AKT-mTOR pathways, with luteolin, apigenin, and isorhamnetin confirmed as the key active compounds. Conclusion AFC exerts its therapeutic effects against cervicitis through coordinated regulation of the PGE2/COX-2/IDO1-FLG in conjunction with the TLR4 and PI3K/AKT-mTOR signaling pathways.
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高影响因子
FASEB JOURNAL
·
2025
·Vol. 39
·期 5
·e70439
·
IF 4.2
Yun Li,Site Yu,Jizhang Zeng,Situo Zhou,Xu Cui,Jie Zhou,Pihong Zhang
Excessive inflammation is a prominent issue in diabetic wounds, leading to delayed healing or amputation. Corilagin (Cori) is a natural polyphenolic compound with diverse pharmacological activities, particularly its anti-inflammatory properties. The aim of this study was to evaluate the anti-inflammatory effect of Cori on diabetic wounds and to explore the potential underlying mechanisms. The impact of Cori on wound healing was assessed in streptozotocin (STZ)-induced diabetic mice through morphological observation, histological staining, and gene expression analysis. Flow cytometry, qRT-PCR, western blot analysis, and RNA sequencing were conducted to elucidate the underlying mechanisms in RAW264.7 cells. The results demonstrated that Cori accelerated wound healing, inhibited excessive inflammation, and regulated macrophage polarization in diabetic mice. In Vitro, Cori decreased M1 polarization and inhibited the expression of pro-inflammatory mediators in RAW264.7 cells. Sequencing analysis revealed that Cori exerts anti-inflammatory effects on RAW 264.7 cells through multiple targeted mechanisms. Moreover, in LPS-induced macrophages, Cori dramatically decreased the activation of TLR4, MyD88, and NF-κB. Additionally, Cori enhanced M2 polarization by promoting fatty acid oxidation. In conclusion, the findings suggest that Cori modulates macrophage polarization through various targeted mechanisms, effectively suppressing inflammation and accelerating diabetic wound healing. Graphical Diabetic ulcers are common chronic wounds marked by excessive and persistent inflammation, imposing significant healthcare and economic burdens. Corilagin (Cori) was shown to accelerate wound healing in STZ-induced diabetic mice by modulating macrophage polarization and suppressing inflammation. In vitro, Cori inhibited M1 polarization and reduced the expression of pro-inflammatory mediators via the TLR4/MyD88/NF-κB pathway, while promoting M2 polarization by enhancing fatty acid oxidation. This study highlights Cori's potential as a therapeutic agent for diabetic wound management through its multi-targeted anti-inflammatory mechanisms.
研究领域:
药理学
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免疫学
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分子生物学
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糖尿病研究
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PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Junjun Liu,Naibo Feng,Xinyu Jiang,Xirui Xin,Yubo Hou,Zhende Jiang,Laijin Lu,Weixian Yu,Bai Yang
Periodontitis is a common chronic inflammatory disease and the local accumulation of excessive reactive oxygen species (ROS) could cause oxidative damage to periodontal tissues. Thus, antioxidative therapy is considered to be the promising strategy for treating periodontitis. However, highly efficient antioxidant activity of biomaterials with low cost, ease of synthesis, and good biocompatibility are still highly desired. Here amylopectin from maize (AFM)-derived carbonized polymer dots (AFM-CPDs-240) with excellent antioxidant activity, good water solubility and biosafty is parepared. Detailed characterizations identify that the antioxidant properties and formation mechanism of AFM-CPDs, and antioxidant activity of AFM-CPDs-240 is much higher than Trolox (a hydrophilic derivative of vitamin E) due to the large contents of conjugated C=C and C=O. Besides, in vitro and in vivo experiments suggest AFM-CPDs-240 could effectively alleviate inflammatory response, inhibit alveolar bone resorption and promote bone formation, showing excellent therapeutic effects on periodontitis. Moreover, the label-free proteomics and western blot results demonstrate AFM-CPDs-240 could accelerate the recovery of periodontitis by blocking TLR4/NF-κB (Toll-like receptor 4/ nuclear factor-kappa B) signaling pathway. This study will develop a simple approach to design highly efficient antioxidant carbon dots with good biocompatibility, and also provide a new promising nanoplatform for treating diseases associated with ROS.
研究领域:
牙医学
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材料科学
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生物化学
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药理学
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高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2020
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IF 3.69
Pengfei Li,Jingkang Wang,Chunguo Wang,Long Cheng,Quantao Ma,Yaqi Li,Yongcheng An,Hongyu Dai,Yuhui Duan,Tieshan Wang,Xuan Ma,Minghui Zhang,Ting Wang,Baosheng Zhao
Ethnopharmacological relevance Hanchuan Zupa Granule (HCZP), a traditional Chinese ethnodrug, has the functions of supressing a cough, resolving phlegm, warming the lungs, and relieving asthma. In clinical practice employing traditional Chinese medicine (TCM), HCZP is commonly used to treat acute colds, cough and abnormal mucous asthma caused by a cold, or “Nai-Zi-Lai” in the Uygur language. Studies have confirmed the use of HCZP to treat cough variant asthma (CVA) and other respiratory diseases . However, the pharmacological mechanisms of HCZP remain unrevealed. Aim of the study To investigate the anti-tussive and anti-asthmatic effects and the possible pharmacological mechanisms of HCZP in the treatment of CVA. Materials and methods A guinea pig CVA animal model was established by intraperitoneal injection of ovalbumin (OVA) combined with intraperitoneal injection of aluminium hydroxide adjuvant and atomized OVA. Meanwhile, guinea pigs with CVA received oral HCZP (at dosages of 0.571, 0.285 and 0.143 g/kg bodyweight). The number of coughs induced by aerosol capsaicin was recorded, and the airway hyperresponsiveness (AHR) of CVA guinea pigs was detected with the FinePointe series RC system. H&E staining of lung tissues was performed to observe pathological changes. ELISA was used to detect inflammatory cytokines. qRT-PCR and western blotting analyses were used to detect the expression of Th1-specific transcription factor (T-bet), Th2-specific transcription factor (GATA3), and Toll-like receptor 4 (TLR4) signal transduction elements. These methods were performed to assess the protective effects and the potential mechanisms of HCZP on CVA. Results Great changes were found in the CVA guinea pig model after HCZP treatment. The number of coughs induced by capsaicin in guinea pigs decreased, the body weights of guinea pigs increased, and inflammation of the eosinophilic airway and AHR were reduced simultaneously. These results indicate that HCZP has a significant protective effect on CVA. A pharmacological study of HCZP showed that the levels of interleukin-4 (IL-4) and IL-5 and tumour necrosis factor-α (TNF-α) in serum decreased. The amount of interferon-γ (IFN-γ) increased, mRNA and protein expression of TLR4 and GATA3 weakened, and mRNA and protein expression of T-bet increased. Conclusions HCZP ameliorated the symptoms of guinea pigs with CVA induced by OVA by regulating the Th1/Th2 imbalance and TLR4 receptors.
研究领域:
药理学
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传统中药
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呼吸系统疾病
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免疫学
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DOI
PubMed
高影响因子
LIFE SCIENCES
·
2018
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IF 3.234
Rongzong Qiu,Weifeng Yao,Haocong Ji,Dongdong Yuan,Xiaofeng Gao,Weiping Sha,Fei Wang,Pinjie Huang,Ziqing Hei
Background Acute kidney injury occurred after sepsis, resulting in high mortality. This research aims to elucidate the mechanistic effect of DEX on the renal inflammation resolution during sepsis in rats. Methods The rats were randomly divided into a sham group and the other three cecal ligation and puncture (CLP) model groups, based on different treatments: placebo, DEX and 2-adrenergic receptor (AR) inhibitor atipamezole (AT) treatment (DEX + AT) groups. The survival of septic rats within 24 h was recorded. Tissue pathology, plasma IL-1β, IL-6, TNF-α, lipoxygenase-5 and lipoxin A4 were evaluated. Western blotting and immunostaining was used to determine expression of TLR4 , IκB , IKK , NF-κB p65 and pp65 in kidney tissue. Then qPCR was used to analyze the mRNA expression of renal α 2A -AR, α 2B -AR and α 2C -AR. Results Rat mortality and kidney inflammation were significantly increased in septic rats. Specifically, IL-1β, IL-6 and TNF-α plasma levels, NF-κB activity, and TLR4 expression in rat kidney tissues were increased after CLP. In the DEX treatment group, mortality was reduced, histology changes were minor, and lipoxygenase-5, and lipoxin A4 expression were increased. The expression of IL-1β, IL-6 and TNF-α, NF-κB activity and TLR4 expression in rat kidney tissues were also decreased. These results indicated that DEX treatment alleviates acute kidney injury induced by CLP. However, the effects of DEX were apparently suppressed by atipamezole in the DEX + AT group. Conclusion The current study demonstrated the protective effect of DEX on CLP-induced kidney injury, which may be effective by attenuating NF-κB pathway activation with lipoxin A4.
研究领域:
药理学
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肾病学
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免疫学
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重症医学
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DOI
PubMed
高影响因子
MOLECULAR THERAPY
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2022
·
IF 12.91
Yibin Zhang,Hui Zhang,Xing Sun,Tianhuan Peng,Tiantian Xie,Yijun Yuan,Junxiao Guo,Yinglei Chen,Lingli Zhou,Neng Ling,Hui Li,Ling Li,Lin Zhang,Xiaodong Li,Long Liang,Jing Liu,Mao Ye,Weihong Tan
Esophageal cancer is one of the most frequent malignant tumors of the digestive tract, among which esophageal squamous cell carcinoma (ESCC) is the main pathological type worldwide. Previous studies have shown microbial infections in the upper digestive tract to be a potential risk factor in ESCC etiology. In this study, we identified that Mycoplasma hyorhinis infection promoted the malignancy of ESCC. In response, we generated a single-stranded DNA aptamer, ZY3A, against M. hyorhinis using the cell-SELEX strategy. The underlying recognition mechanism of ZY3A on M. hyorhinis involves its binding to M. hyorhinis -specific p37 protein. This tool allowed us to provide the first proof-of-concept evidence using a nucleic acid aptamer to control mycoplasma infection. More specifically, we found that ZY3A could neutralize M. hyorhinis infection on ESCC cells by blocking the interaction between p37 protein and its receptor TLR4 on the ESCC cell membrane. As a result, ZY3A inhibited the migration and invasion of M. hyorhinis -infected ESCC cells in vitro and metastasis in vivo . Taken together, these findings indicate that aptamer ZY3A is a potential candidate for development into a novel molecular tool for treatment of M. hyorhinis infection and a safe first-in-class M. hyorhinis -targeting antitumor agent.
研究领域:
肿瘤学
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微生物学
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分子生物学
·
癌症治疗
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2021
·
IF 5.279
Linlin Qu,Xiaoxuan Ma,Daidi Fan
Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. Our previous reports showed that ginsenoside Rk3 provided excellent efficacy in alleviating the intestinal inflammatory response and protecting the liver, but its mechanism for HCC prevention remains to be explored. Here, the results suggested that Rk3 displayed potent antitumor effects against a dimethyl nitrosamine- and CCl4-induced HCC mouse model. Results revealed that Rk3 application inhibited liver injury, fibrosis, and cirrhosis. In parallel, Rk3 lowered the inflammatory response by decreasing the expression of inflammatory cytokines, inducing apoptosis, and blocking the cell cycle. Meanwhile, Rk3 effectively ameliorated the gut microbiota dysbiosis. Furthermore, correlation analysis revealed that the LPS-TLR4 signaling pathway, which was inhibited by Rk3, plays a key role in preventing HCC. To conclude, our research provides valuable insights into how Rk3 application targets the gut-liver axis and suppresses HCC development, suggesting that Rk3 might be a promising candidate for clinical treatment of HCC.
研究领域:
肿瘤学
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药理学
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胃肠病学
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免疫学
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产品关联
DOI
PubMed
高影响因子
CARDIOVASCULAR DRUGS AND THERAPY
·
2021
·Vol. 36
·期 6
·1075-1089
·
IF 3.727
Wang Li,Peng Yunfan,Song Lijun,Xia Dasheng,Li Chao,Li Zhuqing,Li Qi,Yu Ao,Lu Chengzhi,Wang Yongjian
Purpose Anti-inflammatory therapy is important for reducing myocardial injury after acute myocardial infarction (MI). New anti-inflammatory drugs and their mechanism are necessary to be explored to improve clinical efficacy. We aimed to improve the efficacy of colchicine on attenuating MI injury by nano-drug delivery systems and to investigate the mechanism of anti-inflammatory. Methods A colchicine-containing delivery system based on calcium carbonate nanoparticles (ColCaNPs) was synthesized. The protection against MI by ColCaNPs was evaluated using an in vivo rat model established by ligating the left anterior descending coronary artery. Macrophage polarization and the levels of inflammatory cytokines were determined using immunohistochemistry, Western blot, and ELISA analysis. Results ColCaNP treatment showed about a 45% reduction in myocardial infarct size and attenuating myocardial fibrosis compared with groups without drug intervention after MI. Furthermore, ColCaNPs significantly decreased the levels of CRP, TNF-α, and IL-1β in serum and the expression of proinflammatory cytokine in myocardial tissues after MI ( p < 0.05). We also found that ColCaNPs notably restrained pyroptosis and inhibited inflammatory response by modulating on M1/M2 macrophage polarization and suppressing TLR4/NFκB/NLRP3 signal pathway. Conclusion Colchicine-containing nanoparticles can protect against MI injury in a clinically relevant rat model by reducing inflammation. In addition, calcium carbonate nanoparticles can increase the cardioprotective effects of colchicine.
研究领域:
心脏病学
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药学
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纳米技术
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炎症研究
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DOI
PubMed
高影响因子
Current Research in Food Science
·
2026
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IF 7.7
Kai Na,Cheng Chao,Tianfei Yu,Liqun Wang,Xiaotong Liu,Li Zhang,Kejue Feng,Junhua Lei,Yu Xiong,Xiaohua Guo
2′-Fucosyllactose (2′-FL), the most abundant human milk oligosaccharide (HMO), exhibits potent anti-inflammatory properties, yet the underlying mechanisms remain incompletely understood. This study employed an integrated approach combining in vitro fermentation systems, Caco-2 cell assays, in vivo murine colitis models, and molecular docking simulations to elucidate the dual mechanisms of 2′-FL action. In vitro fermentation revealed that 2′-FL selectively enhanced propionate and butyrate production while enriching Bacteroides acidifaciens and Allobaculum stercoricanis , key short-chain fatty acids (SCFAs)-producing taxa. In enterotoxigenic Escherichia coli (ETEC)-infected Caco-2 cells, 2′-FL suppressed TLR4/p38 MAPK signaling and inflammation, an effect mirrored by propionate and butyrate. Similarly, in the dextran sulfate sodium (DSS)-induced mouse colitis model, 2′-FL inhibited this signaling pathway, alleviated inflammation, and, in parallel, specifically elevated levels of propionate and butyrate. Molecular docking analyses also indicated that 2′-FL and its metabolites, propionate and butyrate, exhibit binding to the TLR4–MD2 complex with specific affinity. These results support a coordinated mechanism whereby 2′-FL alleviates intestinal inflammation through putative TLR4 antagonism and the microbiota-derived SCFAs, both of which converge to modulate the TLR4/p38 MAPK-dependent signaling axis. Our work provides a mechanistic foundation for 2′-FL as a precision prebiotic targeting gut inflammation via host-microbe crosstalk.
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高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2020
·
IF 3.943
Jia-Hui Cheng,Xiang Xu,Ying-Biao Li,Xu-Dong Zhao,Fumie Aosai,Su-Yun Shi,Cheng-Hua Jin,Jing-Shu Piao,Juan Ma,Hu-Nan Piao,Xue-Jun Jin,Lian-Xun Piao
Toxoplasma gondii ( T. gondii ) is a known neurotropic protozoan that remains in the central nervous system and induces neuropsychiatric diseases in intermediate hosts. Arctigenin (AG) is one of the major bioactive lignans of the fruit Arctium lappa L. and has a broad spectrum of pharmacological activities such as neuroprotective, anti-inflammatory and anti- T. gondii effects. However, the effect of AG against depressive behaviors observed in T. gondii -infected hosts has not yet been clarified. In the present study, we analyzed the effects of AG against T. gondii -induced depressive behaviors in intermediate hosts using a microglia cell line (BV2 cells) and brain tissues of BALB/c mice during the acute phase of infection with the RH strain of T. gondii . AG attenuated microglial activation and neuroinflammation via the Toll-like receptor/nuclear factor-kappa B (NF-κB) and tumor necrosis factor receptor 1/NF-κB signaling pathways, followed by up-regulating the dopamine and 5-hydroxytryptamine levels and inhibiting the depression-like behaviors of hosts. AG also significantly decreased the T. gondii burden in mouse brain tissues. In conclusion, we elucidated the effects and underlying molecular mechanisms of AG against depressive behaviors induced by T. gondii infection.
研究领域:
神经科学
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药理学
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传染病学
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免疫学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2022
·
IF 5.195
Zhenhua Bian,Yuwen Qin,Lin Li,Lianlin Su,Chenghao Fei,Yu Li,Minmin Hu,Xiaowei Chen,Wei Zhang,Chunqin Mao,Xiaohang Yuan,Tulin Lu,De Ji
Ethnopharmacological relevance the fruit of Schisandra chinensis (Turcz.) Baill. (SC) is an important traditional Chinese herbal medicine, which has been widely used in traditional Chinese medicine (TCM) for treating intestinal diseases . It is also traditionally used as health product and medicine in Russia and other countries. However, the effect of SC ethanol extract on anti-ulcerative colitis (UC) has not been systematically studied yet. Aim of the study We investigated the protective effects and underlying action mechanisms of SC extract (SCE) for UC treatment. Materials and methods An animal model of UC induced by dextran sulfate sodium (DSS) was established. After oral administration of SCE, the Disease Activity Index (DAI) was calculated, the length of colon measured, levels of proinflammatory factors determined, and histopathology carried out to assess the therapeutic efficacy of SCE on UC. The effects of SCE on the toll-like receptor 4/nuclear factor-kappa B/nucleotide-binding and oligomerization domain-like receptor family pyrin domain containing 3 inflammasome (TLR4/NF-κB/NLRP3 inflammasome) signaling pathway were evaluated by western blotting . High-throughput sequencing was done to reveal the effect of SCE on the change of the gut microbiota (GM) in mice with DSS-induced colitis. Results SCE significantly reduced the DAI score, restored colon-length shortening, and ameliorated colonic histopathologic injury in mice with DSS-induced colitis. SCE inhibited the inflammatory response by regulating the TLR4/NF-κB/NLRP3 inflammasome pathway in mice with UC. SCE also maintained gut barrier function by increasing the levels of zonula occludens (ZO)-1 and occludin . 16S rRNA sequencing showed that SCE could reverse the GM imbalance caused by UC. Conclusions SCE can ameliorate DSS-induced colitis, and that its effects might be associated with suppression of the TLR4/NF-κB/NLRP3 inflammasome pathway and GM regulation, which may provide significant supports for the development of potential candidates for UC treatment.
研究领域:
药理学
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免疫学
·
微生物学
·
传统中医
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DOI
PubMed
高影响因子
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