Evidence-based Complementary and Alternative Medicine
·
2020
·
IF 1.813
Kai-hui Zhang,Mei-qi Wang,Lu-ling Wei,Cheng-jing Feng,Yu-si Zhang,Jian-bei Teng
Objective. Gout is a chronic disease that causes inflammatory arthritis, which is closely related to urate accumulation induced by a disorder of uric acid metabolism and the consequent deposition of monosodium urate crystals. Dendrobium loddigesii Rolfe is an herbal medicine that has been used in some traditional Chinese medicine formulae in the treatment of gout. This study aimed to explore and verify the antigout activity of Dendrobium loddigesii extract (DLE) on alleviating the hyperuricaemia of mice and the acute gouty arthritis of rats. Methods. An animal model of hyperuricaemia was established using potassium oxonate (PO). We analysed the expression of uric acid transporter mRNA in the kidney in the hyperuricaemic mice after treatment with DLE. Simultaneously, a monosodium urate crystal-induced acute gouty arthritis rat model was used to evaluate the effects of DLE, according to the level of ankle swelling, as well as the protein levels of inflammatory receptors and cytokines, as assayed by WB and ELISA. Results. DLE alleviated hyperuricaemia in mice and inhibited acute gouty arthritis in rats (). Meanwhile, DLE regulated the levels of uric acid transporters mRNA transcripts, including mouse organic anion transporter 1 (mOAT1), organic anion transporter 3 (mOAT3), urate transporter 1 (mURAT1), and glucose transporter 9 (mGLUT9) in the kidney (), suggesting that DLE promoted uric acid metabolism. Furthermore, DLE significantly suppressed the protein levels of TLRs, MyD88, and NF-κB in the ankle joint’s synovium (), and the serum levels of IL-1β, IL-6, and TNF-α were also reduced, which demonstrated the anti-inflammatory effects of DLE. Conclusion. DLE alleviates hyperuricaemia by regulating the transcription level of uric acid transporters in the kidney. It also inhibits acute gouty arthritis by inhibiting the pathway of TLRs/MyD88/NF-κB in the ankle joint’s synovium. The findings of the present study imply that DLE alleviates gout by promoting uric acid metabolism and inhibiting inflammation related to the TLRs/MyD88/NF-κB pathway.
研究领域:
药理学
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免疫学
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中医
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PubMed
高影响因子
Drug Design Development and Therapy
·
2022
·
IF 4.319
Bozhi Ye,Xudong Chen,Shanshan Dai,Jibo Han,Xiaohe Liang,Shuang Lin,Xueli Cai,Zhouqing Huang,Weijian Huang
Background Emodin has recently been reported to have a powerful antiinflammatory effect, protecting the myocardium against ischemia/reperfusion (I/R) injury. Pyroptosis is a proinflammatory programmed cell death that is related to many diseases. The present study investigated the effect of emodin on pyroptosis in cardiomyocytes.Materials and methods Sprague Dawley rats were randomly divided into sham, I/R, and I/R+Emodin groups. I/R model was subjected to 30 minutes’ ligation of left anterior descending coronary artery, followed by 2 hours of reperfusion. Cardiomyocytes were exposed to hypoxic conditions for 1 hour and normoxic conditions for 2 hours. The level of the pyroptosis was detected by Western blot, real-time PCR analysis, and ELISA.Results The level of gasdermin D-N domains was upregulated in cardiomyocytes during I/R or hypoxia/reoxygenation (H/R) treatment. Moreover, emodin increased the rate of cell survival in vitro and decreased the myocardial infarct size in vivo via suppressing the levels of I/R-induced pyroptosis. Additionally, the expression of TLR4, MyD88, phospho-IκBα, phospho-NF-κB, and the NLRP3 inflammasome was significantly upregulated in cardiomyocytes subjected to H/R treatment, while emodin suppressed the expression of these proteins.Conclusion This study confirms that emodin treatment was able to alleviate myocardial I/R injury and inhibit pyroptosis in vivo and in vitro. The inhibitory effect of emodin on pyroptosis was mediated by suppressing the TLR4/MyD88/NF-κB/NLRP3 inflammasome pathway. Therefore, emodin may provide an alternative treatment for myocardial I/R injury.
研究领域:
药理学
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心脏病学
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细胞生物学
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分子生物学
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高影响因子
PHYTOTHERAPY RESEARCH
·
2026
·
IF 8.1
Lijing Du,Shikai Yan,Xiaopeng Ren,Syed Shams ul Hassan,Yuanfang Sun,Yu Gan,Xue Xiao,Shasha Li,Huizi Jin
Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with cognitive decline and neuroinflammation. Xanthoceras sorbifolia Bunge oil (XSBO), a woody plant oil rich in bioactive fatty acids, has shown potential health benefits. This study aimed to investigate the neuroprotective effects and underlying mechanisms of XSBO in AD. A scopolamine-induced AD rat model was established to evaluate the effects of XSBO on cognitive function, pathological changes, and neuroinflammation. Gut microbiota alterations were analyzed by 16S rDNA sequencing. Fecal microbiota transplantation (FMT) and short-chain fatty acid (SCFA) supplementation experiments were performed to explore the role of gut microbiota-derived metabolites. The TLR4/MyD88/MAPK signaling pathway was further examined. XSBO treatment improved cognitive deficits, reduced neuronal damage and neuroinflammation, and enhanced intestinal barrier integrity in AD rats. XSBO restored gut microbiota dysbiosis and increased SCFA-producing bacteria. FMT and SCFA supplementation confirmed that microbiota-derived metabolites contributed to XSBO-mediated cognitive improvement and neuroprotection. Mechanistically, XSBO inhibited lipopolysaccharide-induced neuroinflammation by suppressing TLR4/MyD88/MAPK signaling activation. XSBO alleviates AD-related cognitive impairment and neuroinflammation by modulating the gut microbiota–SCFA axis and inhibiting TLR4/MyD88/MAPK-mediated inflammatory responses. These findings suggest that XSBO may serve as a promising dietary intervention for neurodegenerative disease management.
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Scientific Reports
·
2026
·
IF 4.9
Li Ruifang,Sun Yan,Feng Mingzhi,Kelsang Drolma,Cai Hanhui,Zhang Jun
Ulcerative colitis (UC) is a chronic disease characterized by intestinal inflammation, mucosal damage, and immune dysregulation. Current treatments are often inadequate, driving the search for alternatives with fewer side effects. Isoliquiritigenin (ISL), a flavonoid from licorice, has demonstrated anti-inflammatory effects, but its efficacy in UC remains uncertain. Male C57BL/6 mice were divided into six groups: Control, DSS model, low-, medium-, and high-dose ISL (25, 50, 100 mg/kg), and 5-aminosalicylic acid (5-ASA, 100 mg/kg). UC was induced by administering 3% DSS, followed by ISL or 5-ASA treatment. Disease activity index (DAI), histopathology, real-time PCR, Western blotting, immunohistochemistry, and 16 S rRNA sequencing were used to assess inflammation, intestinal barrier integrity, and gut microbiota (GM) composition. a Caco-2 cell-based model of UC was developed. After transfection to induce the overexpression of TLR4 and its adaptor protein MyD88, the cells were incubated with ISL. The effects of this intervention were evaluated by measuring the expression of inflammatory cytokines, tight junction-associated proteins, and components of the TLR4/MyD88 signaling pathway. ISL significantly alleviated DSS-induced UC symptoms, such as weight loss and colonic shortening. ISL reduced colonic mucosal damage and inflammatory cell infiltration, downregulated TLR4, MyD88, and phosphorylated NF-κB expression, and lowered TNF-α, IL-1β, and IL-6 levels. It also improved intestinal barrier function by upregulating ZO-1, Claudin-1, and Occludin expression. ISL modulated GM by increasing beneficial bacteria (Muribaculaceae) and reducing pathogenic bacteria (Escherichia-Shigella). Overexpression of TLR4 and MyD88 in the Caco-2 cell line abrogated the protective effects of ISL, as evidenced by increased expression of inflammatory cytokines and downregulated expression of tight junction proteins. Overall, these findings suggest ISL may protects against DSS-induced UC by suppressing the TLR4/MyD88/NF-κB pathway, enhancing intestinal barrier function, and modulating GM, supporting its potential as a therapeutic supplement for UC.
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PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
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2026
·
IF 2.5
Zhen Yang,Huiying Li,Wei Zhao,Yingxia Yu,Yanling Lin,Jianxuan Liu,Xinghu Fan,Moyan Wang,Xin Teng,Zhikai Qiu
Objective Evaluation of the therapeutic effect of Tongfu Zhike Formula (TFZKF) on mice with cough variant asthma (CVA) and exploration of its mechanism of action in improving CVA. Methods The main chemical components of TFZKF were detected and analyzed using UHPLC-MS/MS. Network pharmacology was employed to investigate the potential targets of TFZKF in CVA. After grouping and drug administration, the number of coughs and cough latency were observed in CVA mice. White blood cell differential counts in BALF, serum levels of IgE, IL-4, IL-5, IL-13 and IFN-γ, as well as pathological changes in lung tissue were assessed. Western blot and RT-qPCR were used to analyze the protein expression levels and mRNA changes of TLR4, MyD88, and NF-κB in the lung tissue of CVA mice. Results A total of 495 chemical components were detected in TFZKF under both positive and negative ion modes. Network pharmacology analysis identified 199 potential targets related to TFZKF and CVA, and found close associations with the TLR4 and NF-κB signaling pathways. Animal experiments showed that, compared to the Model group, TFZKF significantly reduced the number of coughs, prolonged cough latency, decreased serum levels of IgE, IL-4, IL-5, and IL-13, reduced the total number of white blood cells, neutrophils, and eosinophils in BALF, alleviated inflammatory cell infiltration and fibrosis in lung tissue, and downregulated the protein and mRNA expression of TLR4, MyD88, and NF-κB. Conclusion The interaction within the TLR4/MyD88/NF-κB signaling pathway may be a potential key target for the treatment of cough variant asthma.
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INTERNATIONAL IMMUNOPHARMACOLOGY
·
2018
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IF 3.118
Shuang Luo,Xiangliang Deng,Qi Liu,Zengfeng Pan,Zhongxiang Zhao,Lian Zhou,Xia Luo
Emodin is an anthraquinone compound derived from Rheum officinale Baill . Several reports showed that emodin had efficacy on acute pancreatitis , keratitis , myocarditis , and rheumatoid arthritis . However, the potency of emodin on ulcerative colitis(UC) remains unclear. In this study, we investigated the effect of emodin on dextran sodium sulfate (DSS)-induced ulcerative colitis in mice. Our results showed that emodin significantly alleviated the symptoms of DSS-induced UC in mice, involving prevented the loss of body weight and colon shortening, decreased the disease activity index (DAI), intestinal damages and the count of white blood cells (WBC) in peripheral blood. In addition, emodin treatment decreased the level of anti-flagellin antibody in serum and significantly down-regulated the expression of TLR5 and NF-κB p65 in colon of the UC mice. Further study in vitro showed that emodin down-regulated the expression of TLR5 and MyD88 , up-regulated the expression of IκB, inhibited the nuclear translocation of NF-κB p65 and decreased the release of IL-8 in flagellin-stimulated HT-29 cells. These results, for the first time, demonstrated that emodin had the therapeutic potential to ameliorate UC symptoms possibly via regulating the flagellin-TLR5 signaling pathway . Emodin may be a potential candidate ingredient for ulcerative colitis.
研究领域:
药理学
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免疫学
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胃肠病学
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PubMed
高影响因子
Frontiers in Microbiology
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2023
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IF 5.2
Guo Huanyu,Chen Jing,Yuan Xuemei,Zhang Jian,Wang Jiayang,Yao Jiayun,Ge Haixia
Herbal extracts have been considered as ideal alternative to antibiotics in aquaculture and application of combinatory effective extracts always can exhibit the enhanced bioactivity with high efficiency. In our study, a novel herbal extract combination GF-7, which is composed of Galla Chinensis, Mangosteen Shell extracts as well as the effective parts of Pomegranate peel and Scutellaria baicalensis Georgi extracts, was prepared and applied for the therapy of bacterial infection in aquaculture. The HPLC analysis of GF-7 was also investigated for quality control and chemical identification. In the bioassay, GF-7 had excellent antibacterial activity against various aquatic pathogenic bacteria in vitro, and the related MIC values were between 0.045 and 0.36 mg/mL. After feeding Micropterus salmoide with GF-7 (0.1, 0.3, and 0.6%, respectively) for 28 days, the activities of ACP, AKP, LZM, SOD, and CAT of the liver in each treatment group were significantly increased and the content of MDA was significantly decreased. Meanwhile, the hepatic expression of the immune regulators including IL-1β, TNF-α, and Myd88 at different times was up-regulated in varying degrees. The challenge results exhibited a good dose-dependent protective effect on M. salmoides infected with A. hydrophila, which was further confirmed by liver histopathology. Our results imply that the novel combination GF-7 is a potential natural medicine for the prevention and treatment of numerous aquatic pathogenic infectious diseases in aquaculture.
研究领域:
水产养殖
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药理学
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免疫学
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微生物学
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PubMed
高影响因子
MOLECULAR NUTRITION & FOOD RESEARCH
·
2020
·Vol. 64
·期 8
·1901251
·
IF 5.309
Lingjun Tong,Haining Hao,Xinyi Zhang,Zhe Zhang,Youyou Lv,Lanwei Zhang,Huaxi Yi
Scope Milk-derived extracellular vesicles (mEVs) as nanoparticles are being developed as novel drug vehicles due to their pivotal role in cell–cell communication. As an important bioactive component in milk, little is known about their effect on the gut microbiota and intestinal immunity. Therefore, the effects of mEVs on gut microbiota and intestinal immunity in mice are investigated. Methods and results First, a new method to obtain high-yield mEVs is developed. Afterward, the colonic contents from C57BL/6 mice fed different doses of mEVs (8 weeks) are collected and the microbial composition via 16S rRNA gene sequencing is analyzed. It is found that mEVs could alter the gut microbiota composition and modulate their metabolites—short-chain fatty acids (SCFAs). Furthermore, the effects of mEVs on intestinal immunity are evaluated. It is observed that the expression levels of Muc2, RegIIIγ, Myd88, GATA4 genes, and IgA, sIgA are increased in the intestine, which are significant for the integrity of the mucus layer. Conclusion These findings reveal that the genes with critical importance for intestinal barrier function and immune regulation are modified in mice by oral administration mEVs, which also result in the changes of the relative composition of gut microbiome and SCFAs.
研究领域:
药理学
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微生物学
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免疫学
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营养科学
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DOI
PubMed
高影响因子
BMC INFECTIOUS DISEASES
·
2025
·Vol. 25
·期 1
·1-16
·
IF 3
Lv Jiangbo,Wan Haofang,Yu Daojun,Zhou Huifen,Wang Wenba,Wan Haitong
ObjectivePenicillin-resistant Streptococcus pneumoniae (PRSP), for which novel treatment medicines are required, has expanded extensively due to the overuse of antibiotics. This study aimed to detect the optimal ratio of the combination of the main components based on Yinhuapinggan granules (YHPG) to generate novel treatment concepts for PRSP-induced lung injury.Methods Three representative main components: chlorogenic acid (C), amygdalin (A), and puerarin (P) were selected, and the optimal combination of these three components was determined by an orthogonal experiment. Investigations were conducted on the potential mechanisms underlying the protective effect of this optimized combination against PRSP-induced lung epithelial cell damage. Meanwhile, the bacteriostatic effect was further explored through the optimized combination of these natural products combined with penicillin G (PG).Results The optimized combination CAP (C: 16 µg/mL, A: 24 µg/mL, P: 24 µg/mL) screened by the orthogonal experimental design reduced cell damage in a model of human lung epithelial cells infected by PRSP, and the combination of CAP and PG had a synergistic effect. At the cellular level, CAP attenuated lung epithelial cell injury by modulating the TLRs/MyD88 inflammatory pathway. At the bacterial level, CAP modulated the virulence and drug resistance of PRSP, resulting in enhanced bacterial inhibition by the combination of CAP and PG.Conclusion Taken together, our results suggest that CAP can modulate or synergize with PG to modulate the TLRs/MyD88 pathway and attenuate PRSP-induced lung injury, and can be used as a potential drug for treating PRSP infection.
研究领域:
医学
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药理学
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感染性疾病
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中药研究
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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
BMC GASTROENTEROLOGY
·
2025
·Vol. 25
·期 1
·1-14
·
IF 2.6
Yuan Zuohui,Yang Xiaoping,Wang Xiaochun,Shi Xinlong,Chen Jia,Huang Lijun,Yang Jie,Shi Yuping,Zhang Liping,Mai Ping
Section
Background
This study aimed to investigate the effects of melatonin on diarrhea and visceral hypersensitivity in rats with diarrhea-predominant irritable bowel syndrome (IBS-D) and to explore its potential mechanisms through modulation of the TLR4/MyD88/NF-κB pathway.
Section
Methods
Adult male Sprague-Dawley (SD) rats were used to establish an IBS-D model through a combination of chronic and acute stress. The rats were randomly divided into four groups: healthy control (HC), IBS-D, IBS-D + melatonin 5 mg/kg (M-L), and IBS-D + melatonin 10 mg/kg (M-H), with six rats in each group. Visceral sensitivity was assessed using the abdominal withdrawal reflex (AWR). The expression levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in colon tissue were measured using enzyme-linked immunosorbent assay (ELISA). Western blotting and immunohistochemistry were employed to detect the expression of TLR4, MyD88, and NF-κB proteins in colon tissue. Additionally, 16 S rRNA sequencing was used to analyze the composition of the intestinal microbiota.
Section
Results
Compared to the HC group, the IBS-D group exhibited colonic inflammatory injury, increased AWR scores, elevated levels of TNF-α, IL-6, TLR4, MyD88, and NF-κB in the colon, and altered intestinal microbiota composition. Melatonin treatment reduced colonic inflammatory injury, decreased AWR scores, and lowered the levels of TNF-α, IL-6, TLR4, MyD88, and NF-κB in a dose-dependent manner. The intestinal microbiota composition in melatonin-treated groups showed a trend towards that of the HC group.
Section
Conclusion
Melatonin improved diarrhea and visceral hypersensitivity in IBS-D rats, potentially through the modulation of the TLR4/MyD88/NF-κB pathway and partial restoration of the intestinal microbiota.
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CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
·
2025
·Vol. 52
·期 4
·e70033
·
IF 2.5
Xin Zhang,Xinliu Wang,Yuanyuan Wang,Xingyou Ma,Yunyun Geng,Shuxian Zang,Ziyun Ban,Yugai Jia,Yonggang Gao
Norisoboldine (NIB) displays beneficial effects on cardiovascular diseases, although its protective role and underlying mechanisms in myocardial ischemia (MI) injury remain elusive. The aim of this study is to explore the potential cardioprotective mechanism of NIB on MI injury caused by isoproterenol (ISO). We administered NIB to SD rats at 20 and 40 mg/kg daily for 7 days in this study; this was followed by an ISO injection to induce MI injury. Parameters such as electrocardiogram readings, heart rate, serum concentrations of creatine kinase (CK) and creatine kinase-MB (CK-MB), levels of inflammatory markers, some histopathological assessments and oxidative stress markers were evaluated. We conducted Western blot analyses to evaluate protein expression related to apoptosis and the TLR4–MyD88-mediated NF-κB activation pathway. The L-type Ca 2+ current (ICa-L) and contraction of isolated ventricular cells from rats were identified using patch-clamp methods and the IonOptix detection system. The treatment with NIB resulted in improvements in heart rate and ST-segment changes, a reduction in CK and CK-MB levels, the restoration of superoxide dismutase, catalase and glutathione levels and a decrease in malondialdehyde accumulation. Furthermore, NIB reduced the expression of inflammatory markers, lowered Ca 2+ levels and reactive oxygen species production and improved myocardial tissue morphology. It also countered ISO-induced alterations in apoptosis and the TLR4–MyD88-dependent NF-κB activation pathway. Additionally, NIB considerably attenuated ICa-L and reduced the contractile function of cardiomyocytes. These results suggest that NIB effectively mitigates ISO-induced MI injury through anti-inflammatory, antioxidative, and anti-apoptotic mechanisms, potentially involving the TLR4–MyD88-dependent NF-κB activation pathway and calcium balance.
研究领域:
药理学
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心血管疾病
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分子生物学
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PubMed
高影响因子
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