CARBOHYDRATE POLYMERS
·
2023
·
IF 11.2
Guanghui Jiang,Bulei Wang,Yuwen Wang,Haoyue Kong,Yufei Wang,Peng Gao,Minghao Guo,Wenna Li,Jian Zhang,Zhezhi Wang,Junfeng Niu
Liver fibrosis has proven to be the main predisposing factor for liver cirrhosis and liver cancer; however, an effective treatment remains elusive. Polysaccharides , with low toxicity and a wide range of bioactivities, are strong potential candidates for anti-hepatic fibrosis applications. For this study, a new low molecular weight neutral polysaccharide ( B. striata glucomannan (BSP)) was extracted and purified from Bletilla striata . The structure of BSP was characterized and its activities for alleviating liver fibrosis in vivo were further evaluated. The results revealed that the structural unit of BSP was likely →4)-β-D-Glc p -(1 → 4)-β-D-Man p -(1 → 4)-β-D-2ace-Man p -(1 → 4)-β-D-Man p -(1 → 4)-β-D-Glc p -(1 → 4)-β-D-Man p -(1 → 4)-β-D-Man p -(1 → 4)-β-D-3ace-Man p -(1→, with a molecular weight of only 58.5 kDa. Additionally, BSP was observed to attenuate the passive impacts of liver fibrosis in a manner closely related to TLR2/TLR4-MyD88-NF-κB signaling pathway conduction. In summary, the results of this study provide theoretical foundations for the potential applications of BSP as an anti-liver fibrosis platform.
研究领域:
药理学
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生物化学
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分子生物学
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肝病学
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DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2026
·
IF 8.1
Anhao Guo,Ke Wang,Jinghao Liang,Chuanpeng Xia,Kongmei Luo,Salah Alqadhi,Hanwen Zhang,Shanying Xiao,Tao Lin,Zhe Zhang,Long Wu,Hede Yan
Peripheral nerve injury (PNI) often leads to functional impairment, and current therapeutic options are limited. Punicalagin (PUN), a polyphenolic compound derived from Punica granatum , exhibits antioxidant and anti-inflammatory properties. This study investigated the therapeutic potential of PUN for PNI and its underlying mechanisms, focusing on mitochondrial autophagy (mitophagy), TLR4/MAPK signaling, and angiogenesis. In vitro, Schwann cells were treated with PUN under oxidative stress induced by tert-butyl hydroperoxide to evaluate cell viability, mitochondrial function, mitophagy, reactive oxygen species (ROS) levels, and apoptosis. PUN at non-toxic concentrations (≤ 20 μM) promoted mitophagy, attenuated ROS accumulation, and inhibited apoptosis. These effects were partially reversed by the mitophagy inhibitor Bafilomycin A1. Network pharmacology and molecular docking identified TLR4 as a primary target, and Western blot analyses demonstrated that PUN modulated downstream MAPK signaling. In vivo, intraperitoneal PUN administration in rats after sciatic nerve crush injury improved gastrocnemius muscle preservation, promoted axonal regeneration and remyelination, enhanced neovascularization, and significantly improved functional recovery, as measured by the sciatic functional index. Collectively, these findings indicate that PUN facilitates peripheral nerve repair through coordinated regulation of mitophagy, TLR4/MAPK signaling, and angiogenesis, highlighting its potential as a non-surgical therapeutic agent to promote nerve regeneration and functional recovery after PNI.
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COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
·
2026
·
IF 4.4
Xiaofei Yang,Mingyue Qiao,Yan Deng,Songsong Chen,Cheng Li,Yuanke Shu,Li Jiang
Heavy metal pollution, particularly copper (Cu) and cadmium (Cd), poses a serious threat to aquatic ecosystems due to its toxicity and bioaccumulation potential. This study investigated the effects of individual and combined exposure to Cu and Cd on largemouth bass, focusing on the gut–liver axis and the TLR4/NF-κB pathway in hepatotoxicity. A total of 480 size-matched fish were randomly assigned to four groups (Control, Cu, Cd, and Cu + Cd) and exposed to sublethal concentrations of CuSO₄ (9.275 mg/L) and CdCl₂·2.5H₂O (1.15285 mg/L) for 14 days, followed by physiological, molecular, and omics analyses. Results showed that both single and combined exposures disrupted intestinal structure and barrier function, accompanied by downregulation of tight junction genes. Oxidative stress responses were tissue-specific, with increased reactive oxygen species (ROS) and MDA levels in the intestine but decreased levels in the liver, along with suppressed antioxidant enzyme activities. Inflammatory responses were activated, as indicated by elevated cytokine levels and upregulation of TLR4/MyD88/NF-κB signaling in the liver. Microbiota analysis revealed that Cd exposure increased gut microbial diversity, whereas Cu + Cd co-exposure reduced α-diversity and altered microbial composition, with increased Proteobacteria and decreased beneficial taxa such as Bacteroidota and Firmicutes. Untargeted metabolomics showed that hepatic metabolic profiles were altered, mainly affecting lipid, energy, and immune-related pathways. Overall, combined Cu + Cd exposure exerted stronger toxic effects than single exposures, inducing more severe intestinal damage, microbial dysbiosis, and metabolic disturbances. These findings highlight the critical role of the gut–liver axis in mediating heavy metal toxicity.
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高影响因子
CARBOHYDRATE POLYMERS
·
2026
·
IF 13.2
Jia-Mei Geng,Pei-Feng Zhu,Lu-Shuang Xu,Ji-Lai Liu,Zheng-Qing Yang,Zhu-Ya Yang,Qiong Jin,Lu Liu
The medicinal moss Rhodobryum giganteum is rich in polysaccharides, whose structural and biofunctional properties remain largely unexplored. In this study, a novel glucose-rich polysaccharide fraction (named RGP, 29.8 kDa) was isolated and characterized from R. giganteum . Structural analysis revealed a unique α -1,6-linked glucan backbone with C-2 acetylation, along with side chains composed of →4)- α - d -glucopyranosyl-(1 → and terminal α - d -glucopyranose units. RGP significantly promoted proliferation, phagocytosis, and cytokine (TNF- α , IL-6) secretion via the TLR4/PI3K-Akt/IκB α pathway in RAW264.7 cells. In immunosuppressed mice, RGP restored immune function, as shown by improved organ indices, elevated serum immunoglobulins (IgA, IgG, IgM), and alleviated splenic damage. Molecular docking revealed that RGP binds the hydrophobic pocket of the TLR4/PI3K-Akt/IκB α complex via its glucose chain, and dynamics simulations confirmed the stability of this interaction. These findings reveal the bioactivity of bryophyte polysaccharides and suggest RGP as a potential immunomodulatory agent.
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高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2020
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IF 4.872
Rili Hao,Junlin Ge,Yongfeng Ren,Xinyu Song,Yang Jiang,Dongxiao Sun-Waterhouse,Feng Li,Dapeng Li
Cadmium (Cd), an environmental pollutant, is evidenced to cause hepatotoxicity. In this study, the potential protective effect of caffeic acid phenethyl ester (CAPE) on cadmium-induced liver damage was investigated. Forty male mice were treated daily with either CdCl 2 (1.5 mg/kg body weight (b.w.), gavage) or CAPE (10 μmol/kg b.w., gavage) or both for 4 weeks. CAPE administration significantly reduced Cd level and liver and body weight, and increased AST, ALT and ALP level. Moreover, CAPE prevented CdCl 2 -induced oxidative stress via PI3K/Akt/mTOR pathway and inhibited apoptosis by regulating apoptosis markers. CAPE also suppressed the CdCl 2 -induced inflammation by reducing the inflammatory mediators, including TNF-α, IL-6 and IL-1β. Furthermore, CAPE alleviated CdCl 2 -induced reduction of TLR4. It should be noted that this effect was achieved by targeting miR-182-5p, and CAPE improved miR-182-5p level. The improvement of the liver tissue histopathology by CAPE confirmed the biochemical data. These results show for the first time that miR-182-5p/TLR4 axis involved in CAPE's protection against CdCl 2 -induced hepatotoxicity, and may provide novel insights into the treatment of cadmium-related diseases.
研究领域:
毒理学
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分子生物学
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肝脏研究
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PubMed
高影响因子
INFLAMMATION
·
2026
·Vol. 49
·期 1
·79
·
IF 5.4
Hu Rui-Jie,Ying Xiao-Long,Zhang Cheng,Wang Xu,Zhan Chang-Sheng
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) constitutes a clinically complex urological condition defined by the persistence of pelvic pain and chronic inflammation. Emerging evidence underscores the critical involvement of macrophage-mediated immune dysregulation, particularly the dominance of pro-inflammatory M1 macrophages, in driving CP/CPPS pathogenesis. Leonurine, a bioactive alkaloid derived from leonuri, exhibits various pharmacological properties and has been shown to regulate macrophage polarization in rheumatoid arthritis. This study aimed to evaluate leonurine’s therapeutic efficacy in a murine experimental autoimmune prostatitis (EAP) model, established by subcutaneous injection of complete Freund’s adjuvant-emulsified prostate antigens. Leonurine administration in EAP mice markedly reduced prostatic inflammatory responses, mitigated chronic pain, and inhibited the expression of pro-inflammatory cytokines. Likewise, leonurine decreased inducible nitric oxide synthase (iNOS) expression levels, an established marker for M1 macrophage polarization. Leonurine has been found to suppress M1 polarization and decrease the secretion of M1-related cytokines (IL-1β and TNF-α) in immortalized bone marrow-derived macrophages (iBMDMs) under in vitro conditions. Mechanistic investigations demonstrated that leonurine mediates its therapeutic effects by modulating the TLR4/NF-κB signaling pathway in both macrophages and EAP models. Molecular docking and dynamics simulations demonstrated stable binding interactions between leonurine and key proteins involved in the TLR4/NF-κB signaling cascade. As a whole, these findings verify that leonurine relieves experimental autoimmune prostatitis (EAP) by regulating M1 macrophage polarization through the TLR4/NF-κB signaling cascade.
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高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2023
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IF 5.1
Asmaa S.A. Hammad,Mohamed M. Sayed-Ahmed,Sara Mohamed Naguib Abdel Hafez,Ahmed R.N. Ibrahim,Mohamed M.A. Khalifa,Mahmoud El-Daly
Chemotherapy-induced peripheral neuropathy is a common adverse effect associated with a number of chemotherapeutic agents including paclitaxel (PTX) which is used in a wide range of solid tumors . Development of PTX-induced peripheral neuropathy (PIPN) during cancer treatment requires dose reduction which limits its clinical benefits. This study is conducted to investigate the role of toll like receptor-4 (TLR4) /p38 signaling and Klotho protein expression in PIPN and the role of trimetazidine (TMZ) in this pathway. Sixty-four male Swiss albino mice were divided into 4 groups (n = 16); Group (1) injected intraperitoneally (IP) with ethanol/tween 80/saline for 8 successive days. Group (2) received TMZ (5 mg/kg, IP, day) for 8 successive days. Group (3) treated with 4 doses of PTX (4.5 mg/kg, IP) every other day over a period of 7 days. Group (4) received a combination of TMZ as group 2 and PTX as group 3. The Effect of TMZ on the antitumor activity of PTX was studied in another set of solid Ehrlich carcinoma (SEC)-bearing mice that was similarly divided as the above-mentioned set. TMZ mitigated tactile allodynia , thermal hypoalgesia , numbness and fine motor discoordination associated with PTX in Swiss mice. The results of the current study show that the neuroprotective effect of TMZ can be attributed to inhibition of TLR4/p38 signaling which also includes a reduction in matrix metalloproteinase-9 (MMP9) protein levels as well as the proinflammatory interleukin-1β (IL-1β) and preserving the levels of the anti-inflammatory IL-10. Moreover, the current study is the first to demonstrate that PTX reduces the neuronal levels of klotho protein and showed its modulation via cotreatment with TMZ. In addition, this study showed that TMZ neither alter the growth of SEC nor the antitumor activity of PTX. In conclusion, we suggest that (1) Inhibition of Klotho protein and upregulation of TLR4/p38 signals in nerve tissues may contribute to PIPN. (2) TMZ attenuates PIPN by modulating TLR4/p38 and Klotho protein expression without interfering with its antitumor activity.
研究领域:
肿瘤学
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药理学
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神经科学
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免疫学
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DOI
PubMed
高影响因子
Scientific Reports
·
2025
·Vol. 15
·期 1
·1-14
·
IF 3.9
Yu Ling,Luo Qianwen,Rao Xiaohui,Xiao Xiao,Wang Pinghan
Kawasaki disease (KD) is a severe pediatric vasculitis leading to coronary artery complications. Hydrogen sulfide (H 2 S), a recognized endogenous gasotransmitter with anti-inflammatory properties, offers potential as a novel treatment for KD through its cardiovascular benefits. However, the specific effects and underlying mechanisms remain unclear. The objective of present study is to investigate the anti-inflammatory and therapeutic effects of exogenous H 2 S in KD using network pharmacology and experimental validation. By online database searches, a total of 405 pharmacological targets for H 2 S, 826 KD-related targets, and 107 potential therapeutic targets of H 2 S for KD were identified. Through PPI analysis and Cytoscape screening, 9 hub genes were filtered, namely TNF, IL6, JUN, AKT1, IL1B, TP53, NFKB1, MAPK1, and RELA. KEGG pathway enrichment indicated that the TLR4/MyD88/NF-κB signaling pathway may play a crucial role in the therapeutic effects of H 2 S on KD. Additionally, in vivo experiments confirmed that the treatment of sodium hydrosulfide (NaHS), an H 2 S donor, markedly improved body weight, reduced inflammatory pathology in the coronary arteries, and downregulated levels of inflammatory cytokines TNF-α, IL-1β, and IL-6. Furthermore, WB analysis confirmed that NaHS inhibited the expression of TLR4, MyD88, NF-κB, and p-NF-κB. In brief, it is the first to reveal that exogenous H 2 S attenuates the inflammatory response in KD via the TLR4/MyD88/NF-κB pathway, highlighting its potential as a novel therapeutic approach for KD. These findings lay a foundation for further development of H 2 S-based therapies for KD management.
研究领域:
儿科
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药理学
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免疫学
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心血管科学
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高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2016
·
IF 2.551
Ping Huang,Xiaoyan Lu,Baohong Yuan,Tao Liu,Liangcheng Dai,Yunjun Liu,Hui Yin
Astragaloside IV (AS-IV), an active saponin purified from Astragali Radix , has been identified with broad biological and pharmacological activities . In the present study, we continue to explore the potential effect of AS-IV on antibacterial response using an acute E. coli peritoneal infection model. Our findings implied that administration of AS-IV decreases mortality in mice challenged by lethal E. coli infection. The protection of AS-IV was related to promotion of neutrophil extravasation into the peritoneum and bacterial clearance . Toll-like receptor (TLR) activation in neutrophils has been reported to reduce CXCR2 expression and subsequent neutrophil migration. Our data indicated that AS-IV prevented the reduction of CXCR2 expression and neutrophil migration induced by LPS, the activator for TLR4 . Moreover, we found that AS-IV blocks LPS-induced suppression of CXCR2 on neutrophils by inhibiting the expression of G protein-coupled receptor kinase-2 (GRK2), an agonist that regulates desensitization and internalization of chemokine receptors . Taken together, these data propose that AS-IV, through modulating GRK2-CXCR2 signal in neutrophils, offers an essential efficacy on host antibacterial immunity.
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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DOI
PubMed
高影响因子
KAOHSIUNG JOURNAL OF MEDICAL SCIENCES
·
2025
·
IF 3.1
Meng-Si Li,Kai Liu
IgA nephropathy (IgAN), the most common form of glomerulonephritis, is a major and growing public health issue. It results from intestinal barrier dysfunction that leads to mesangial deposition of pathogenic galactose-deficient IgA1 (Gd-IgA1) and renal inflammation. This study aimed to investigate the therapeutic effects and associated mechanisms of forsythiaside A on intestinal barrier injury in IgAN in animal models. Rats were treated with bovine serum albumin (BSA), carbon tetrachloride (CCl 4 ), and lipopolysaccharide (LPS) to induce IgAN, followed by intragastric administration of forsythiaside A once daily from weeks 15 to 20 after model establishment. Biochemical markers, including 24-h urinary protein, blood urea nitrogen (BUN), serum creatinine (SCr), renal and intestinal tissue pathology, and levels of pro-inflammatory cytokines in the serum, kidney, and intestine, intestinal tight junction proteins, and TLR4/NF-κB pathway components were examined. The results showed that forsythiaside A decreased 24-h urinary protein, BUN, and SCr levels, alleviated renal damage, and attenuated glomerular and tubular lesions, collagen deposition, and glomerular IgA deposition in IgAN rats. Forsythiaside A treatment inhibited CD68-positive macrophage infiltration in renal tissues and downregulated serum and renal levels of IL-1β, IL-6, and TNF-α, while also alleviating intestinal barrier injury and intestinal inflammation, as shown by reduced levels of IL-1β, IL-6, and TNF-α and increased expression of the intestinal tight junction proteins occludin and ZO-1. Lastly, forsythiaside A treatment lowered serum LPS concentrations, as well as renal and intestinal levels of TLR4, p-NF-κB p65, and p-IκBα, and raised both renal and intestinal levels of IκBα. Collectively, forsythiaside A was found to ameliorate the progression of IgAN in rats by alleviating inflammation and intestinal barrier injury by suppression of TLR4/NF-κB signaling.
研究领域:
肾病学
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免疫学
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药理学
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分子生物学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2021
·
IF 8.071
Jiaqi Xu,Qiuhui Qian,Min Xia,Xuedong Wang,Huili Wang
Trichlorocarban (TCC) is ubiquitously detected in environmental matrices, while there is a paucity of information regarding its systemic toxicity. In the present study, we observed that TCC exposure led to high embryo mortality, delayed hatching and yolk absorption, as well as increased malformations, such as closure of swim sac and yolk sac edema. Meanwhile, TCC affected the formation and branch of subintestinal veins (SIVs), intersegmental vessels and posterior cardinal veins. Especially, the SIVs were shrunk, and their branches were reduced or even broken along with reduced coverage area. TCC-induced oxidative stress and excessive apoptosis resulted from abnormal expression of the anti/pro-apoptotic genes. Significant reduction in the number and aggregation function of immune cells proved that TCC had prominent immunotoxicity to zebrafish. TCC-targeted TLR4 signaling pathway was demonstrated by abnormal expression of the marker genes ( tlr4 , MyD88 and nf-κb ) and release of the downstream inflammatory factors (TNF-α, IL-6, etc.). Inhibition of TLR4/MyD88/NF-κB pathway by an inhibitor (CA-4948) rescued the decreasing trend of the immune cells induced by TCC. Molecular docking results demonstrated that TCC could stably bind to TLR4 receptor to form hydrogen bonds and hydrophobic interactions with amino acids. Overall, these findings reveal the underlying molecular mechanisms on TCC-induced developmental and immune toxicity to zebrafish.
研究领域:
毒理学
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环境科学
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分子生物学
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免疫学
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发育生物学
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DOI
PubMed
高影响因子
INFLAMMATION
·
2026
·Vol. 49
·期 1
·41
·
IF 5
Zheng-qing Hu,Ruijie Ma,Hang Zhang,Jiahao Miao,Jia-qing Sun,Jinlong Yuan,Jiaqiang Liu,Zihuan Zhang,Dayong Xia
This study aims to elucidate the mechanism by which Heat Shock Protein 60 (HSP60) mediates microglial pyroptosis in the context of early brain injury (EBI) following subarachnoid hemorrhage (SAH), and to investigate the effects of HSP60 inhibition on EBI after SAH. A mouse subarachnoid hemorrhage (SAH) model was established using prechiasmatic cistern blood injection. In vitro, microglia were stimulated with 25 µmol/L oxyhemoglobin (OxyHB) to simulate the SAH pathological environment. In vivo, mice received 100 mg/kg Mizoribine, while in vitro, 80 µmol/L Mizoribine was used to suppress SAH-induced HSP60 upregulation. Techniques including Western blotting, immunofluorescence, immunohistochemistry, transmission electron microscopy, ELISA, modified Garcia neurological scoring, beam walking, brain water content measurement, Morris water maze, TUNEL staining, and Nissl staining were employed to systematically investigate the role of HSP60 inhibition in neuroinflammation and microglial pyroptosis after SAH. Compared to the sham group, both in vivo and in vitro studies with blinded, random sampling of six groups demonstrated a significant increase in HSP60 expression post-SAH. In vivo, 100 mg/kg Mizoribine alleviated blood-brain barrier disruption, cerebral edema, neuronal apoptosis/necrosis, and improved neurological deficits and cognitive impairment. In vitro, 80 µmol/L Mizoribine markedly attenuated microglial activation and pyroptosis, downregulated pro-inflammatory cytokines, and mitigated neuroinflammation. The upregulation of HSP60 after SAH promotes NLRP3 inflammasome assembly by activating the TLR4/MyD88/NF-κB signaling pathway, thereby inducing microglial pyroptosis and exacerbating the progression of early brain injury. Inhibition of HSP60 represents a potential therapeutic strategy for ameliorating EBI after SAH.
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