PHYTOMEDICINE
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2024
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IF 6.7
Tingwen Zhang,Yue Zhong,Yan Shi,Chengcheng Feng,Lu Xu,Zheng Chen,Xin Sun,Yan Zhao,Xialin Sun
Background The pathogenesis of acute liver injury (ALI) has been a pressing issue in the medical scientific community. We previously found that 5-O-methylvisammioside (MeV) from Saposhnikovia divaricata (Turcz.) Schischk has excellent anti-inflammatory properties. However, the mechanism by which MeV protects against ALI still needs to be deeply investigated. Purpose In the present study, we established an acetaminophen (APAP) -induced ALI mouse model and pre-protected the mice with MeV. Methods & Results Our findings indicate that MeV (5 and 10 mg/kg) lowered the blood levels of alanine aminotransferase and aspartate aminotransferase and reduced the infiltration of inflammatory cells in the liver. MeV initially showed an inhibitory effect on ALI. We then analyzed the molecular mechanisms underlying the effects of MeV by transcriptomic and metabolomic analyzes. Through transcriptomic analysis, we identified 4675 differentially expressed genes between the APAP+MeV group and the APAP-induced ALI group, which were mainly enriched in the MAPK pathway, the TNF pathway, and the NF-κB pathway. Through metabolomic analysis, we found that 249 metabolites in the liver were differentially regulated between the APAP+MeV group and the APAP- induced ALI group, which were mainly enriched in the arachidonic acid pathway. The mRNA expression levels of key genes (encoding TNF-α, p38, AP-1, RelB, IL-1β, and Ptges), as determined by RT-PCR analysis, were consistent with the RNA-seq data. The ELISA results indicate that MeV markedly decreased the serum levels of TNF-α and IL-1β in mice. Finally, the key proteins in the NF-κB and MAPK pathways were examined using immunoblotting. The results showed that MeV decreased IκB-α phosphorylation and inhibited the nuclear translocation of NF-κB. In addition, MeV reduced the hepatic inflammatory burst mainly by inhibiting the phosphorylation of p38 and JNK in the MAPK pathway. Conclusion The present study demonstrated (i) that MeV could ameliorate APAP-induced ALI by inhibiting arachidonic acid metabolism and the TNF, MAPK, and NF-κB pathways, and (ii) that MeV is a promising drug candidate for the prevention of ALI.
研究领域:
药理学
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分子生物学
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肝病学
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炎症研究
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DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2023
·
IF 4.7
Hao Cai,Ke Li,Yilin Yin,Xiaotong Ni,Shiwen Xu
Bis(2-ethylhexyl) phthalate (DEHP) is not only a widely used plasticizer but also a common endocrine disruptor that frequently lingers in water, posing a threat to the health of aquatic organisms . Quercetin (Que) is a common flavonol found in the plant kingdom known for its antioxidant, anti-inflammatory, and immunomodulatory effects. However, it is still unclear whether DEHP can cause pyroptosis and affect the expression of cytokines of grass carp L8824 cells and whether Que has antagonistic effect in this process. In our study, grass carp L8824 cells were treated into four groups after 24 h, namely NC group, DEHP group (1000 μM DEHP), Que group (5 μM Que), and DEHP + Que group (1000 μM DEHP + 5 μM Que). Our results indicate a significant increase in the level of ROS in L8824 cells after exposure to DEHP. DEHP upregulated oxidative stress markers (H 2 O 2 and MDA) and downregulated antioxidant markers (CAT, GSH, SOD , and T-AOC). DEHP also upregulated MAPK and NF-κB signal pathway-related proteins and mRNA expressions (p-p38, p-JNK, p-EPK, and p65). As for cell pyroptosis and its related pathways, DEHP upregulated pyroptosis-related protein and mRNA expressions (GSDMD, IL-1β, NLRP3, Caspase-1, LDH , pro-IL-18, IL-18, and ASC). Finally, DEHP can up-regulated cytokines (IL-6 and TNF-α) expression, down-regulated cytokines (IL-2 and IFN-γ) expression, and antimicrobial peptides (β-defensin, LEAP2, and HEPC). The co-treatment of L8824 cells with DEHP and Que inhibited the activation of the ROS/MAPK/NF-κB axis, alleviated pyroptosis, and restored expression of immune-related indicators. Finally, NAC was applied to reverse intervention of oxidative stress. In summary, Que inhibited DEHP-induced pyroptosis and the influence on cytokine and antimicrobial peptide expression in L8824 cells by regulating the ROS/MAPK/NF-κB pathway. Our results demonstrate the threat to fish health from DEHP exposure and confirmed the harm of DEHP to the aquatic ecological environment and the detoxification effect of Que to DEHP, which provides a theoretical basis for environmental toxicology.
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高影响因子
CHEMICAL RESEARCH IN TOXICOLOGY
·
2022
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IF 3.973
Xiaoying He,Jiali Wang,Qian Wang,Jing Liu,Xi Yang,Lingjuan He,Haihong Hu,Su Zeng,Lushan Yu,Yunqing Qiu,Yan Lou
Hand-foot syndrome (HFS) is a major adverse reaction to capecitabine (CAP). The exact pathogenesis of this disease remains unclear. In this study, metabolomics combined with cell RNA sequencing was used to study the mechanisms of CAP-induced HFS. The murine model of HFS was constructed by intragastric administration of CAP or its metabolites. Quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assays were used to verify the mechanisms. Metabolomics showed the phosphatidylinositol signaling pathway and amino acid and fatty acid metabolism to be the major metabolic alterations related to the occurrence of HFS. Transcriptomics profiles further revealed that the cytokine–cytokine receptor interaction, IL17 signaling pathway, Toll-like receptor signaling pathway, arachidonic acid metabolism, MAPK signaling pathway, and JAK-STAT3 signaling pathway were the vital steps in skin toxicity induced by CAP or its metabolites. We also verified that the inflammation mechanisms were primarily mediated by the abnormal expression of interleukin (IL) 6 or IL8 and not exclusively by COX-2 overexpression. Finally, the P38 MAPK, NF-κB, and JAK-STAT3 signaling pathways, which mediate high levels of expression of IL6 or IL8, were identified as potential pathways underlying CAP-induced HFS.
研究领域:
药理学
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毒理学
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分子生物学
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免疫学
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生物化学
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PubMed
高影响因子
Environment & Health
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2026
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IF 6.3
Shiyin Zhong,Qiongli Zhou,Jirui Yang,Zhimin Zhang,Xueting Chai,Jinghao Luo,Xin Zhang,Jingjing Liu,Yangzong Yixi,Lei Shi,Xuhong Chang,Hui Wang
Manganese (Mn) is an essential trace element, but increasing industrial and agricultural use has led to elevated levels of environmental Mn levels. Chronic overexposure to Mn can cause a Parkinson’s-like neurodegenerative disorder; however, the underlying mechanisms remain incompletely understood. This study combined in vitro and in vivo models to investigate the role of the cGAS–STING/NLRP3 axis in regulating the p38 MAPK/NF–κB pathway in the process of Mn-induced Tau aggregation leading to neurotoxicity. Our results demonstrated that MnCl2 exposure significantly activated both the cGAS–STING/NLRP3 signaling axis and the p38 MAPK/NF–κB pathway, accompanied by increased Tau expression. Genetic ablation of cGAS, STING, or NLRP3 attenuated Mn-induced Tau upregulation, indicating that the cGAS–STING/NLRP3 signaling axis mediates Tau expression. RNA-seq analysis further revealed that the decreased Tau expression in knockout cells is associated with the MAPK/NF–κB signaling pathway. Pharmacological inhibition of p38 MAPK or NF–κB markedly downregulated cGAS–STING signaling, inflammatory cytokine release, and phosphorylated Tau (p-Tau) levels. Moreover, we observed colocalization and interaction among p-p38, p-p65, and p-Tau. Overall, these findings reveal that Mn activates the cGAS–STING/NLRP3 signaling axis regulated by the p38 MAPK/NF–κB pathway, driving pathological Tau aggregation.
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高影响因子
MOLECULES
·
2026
·Vol. 31
·期 12
·1990
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IF 5.1
Jinghan Zhang,Yue Sun,Jinhao Zheng,Can Yang,Mingshuo Yang,Liming Pan
Dendrobium officinalehas attracted increasing attention as a functional food because of its diverse biological activities; however, the photoprotective potential of its protein-derived peptides remains poorly understood. In this study,D. officinaleprotein hydrolysates were fractionated by ultrafiltration according to molecular weight, and their protective effects against ultraviolet B (UVB)-induced photoaging were systematically evaluated in HaCaT keratinocytes. Among the tested fractions, low-molecular-weight peptide fractions exhibited relatively stronger antioxidant activity and effectively reduced intracellular reactive oxygen species (ROS) accumulation in UVB-irradiated cells. In addition, the peptide fractions alleviated UVB-induced inflammatory responses and decreased matrix metalloproteinase (MMP) expression, which was associated with modulation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways. Higher-molecular-weight fractions showed relatively stronger effects on maintaining skin barrier-related functions and were associated with regulation of transforming growth factor-β/Smad (TGF-β/Smad) signaling and collagen-related protein expression. Overall, these findings demonstrate functional differences amongDendrobium officinalepeptide fractions and suggest their potential application as natural photoprotective ingredients in functional foods and cosmeceutical products.
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高影响因子
CARBOHYDRATE POLYMERS
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2021
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IF 9.381
Fei He,Shihai Zhang,Yanan Li,Xia Chen,Zhenyun Du,Chenghao Shao,Kan Ding
The fruit of Lycium ruthenicum Murr is used as traditional medicine and functional food . Previously we reported that one RG-I pectin from this fruit might inhibit pancreatic cancer cells growth. We further hypothesized that there might be other type of polysaccharides in this fruit also have anti-tumor effect. Here, we showed novel structure of a homogeneous polysaccharide named LRP1-S2 from this fruit and its anti-pancreatic cancer effect. Structure analyses suggested that LRP1-S2 was a novel arabinogalactan with the molecular weight ( Mw ) of 17.0 kDa. Bioactivity test showed that LRP1-S2 might attenuate the proliferation of pancreatic cancer cells in vitro and in vivo without significant cytotoxicity to normal pancreatic HPDE6-C7 cells and LO2 liver cells. Mechanism study indicated that it might induce apoptosis of BxPC-3 by inactivating P38 MAPK/NF-κB and GSK-3β/β-Catenin signaling pathways . These results suggested that LRP1-S2 could be a potential anti-tumor leading compound for functional food and new drug development. Chemical compounds arabinogalactan, pectin, galactan , arabinan , RN-1, HH1-1, LRP1-S2, LRP3-S1.
研究领域:
药理学
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癌症研究
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分子生物学
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植物学
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PubMed
高影响因子
TOXICOLOGY LETTERS
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2022
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IF 4.271
Jianjun Lin,Ke Lin,Lijiang Huang,Yongsheng Jiang,Xiaoxiao Ding,Wu Luo,Aleksandr V. Samorodov,Valentin N. Pavlov,Guang Liang,Jianchang Qian,Yi Wang
Heme, as an essential component of hemoproteins , is a prosthetic co-factor found in many cells, which is essential for physiologically vital oxygen transport. However, extracellular or circulatory heme is cytotoxic and triggers inflammation. Although the proinflammatory role of heme has been reported to be associated with Toll-like receptor 4 (TLR4) signaling, the exact mechanism remains unknown. Here, we show that heme promotes TLR4 signaling and inflammation via directly physically interacting with TLR4 and its adaptor protein myeloid differentiation protein 2 (MD2). Genetic loss of MD2 ameliorates heme-induced inflammation and inflammatory cytokine production in the spleen of MD2 knockout (MD2 -/- ) mice. Using mouse macrophage RAW 264.7 cell line, we show that heme induces TLR4 dimerization and MD2/TLR4/MyD88 activation by physically interacting with TLR4 and MD2 in vitro . Genetic loss of MD2 inhibits heme-induced inflammation and MAPK/NF-κB pathway in mouse primary macrophages extracted from MD2 -/- mice. Furthermore, pharmacological inhibition of MD2 by L6H9 ameliorates heme-induced inflammation in macrophages. These findings demonstrate that heme causes inflammation by directly binding to MD2/TLR4 complex, leading to activation of TLR4/MAPK/NF-κB signaling pathway and production of downstream effectors of inflammation.
研究领域:
免疫学
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细胞生物学
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分子生物学
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Shiyi Xiong,Jinjiao Dong,Wenjun Wang,Guodong Zheng,Nansheng Wu,Jingjing Xie,Ruiling Wang,Xiaojin He,Jingen Li
This study aimed to elucidate the structure of a polysaccharide from Choerospondias axillaris fruit (CAP) and to evaluate the immunomodulatory effect against cyclophosphamide (CTX)-induced immunosuppression mice. The solution of CAP exhibited non-Newtonian pseudoplastic fluid behavior. The backbone of CAP was defined as →2)- α -L-Rha p -(1 → 4)- α -D-Gal p A-(1 → 4)- α -D-Gal p A-(1 → [4)- α -D-Gal p A-(1] 5 →, with side chains attached at the O -4 and O -3 positions, demonstrating that CAP is a pectic polysaccharide with partial methyl esterification. Administration of CAP improved immune organ indices, reduced levels of inflammation cytokines, and diminished oxidative stress of the immunosuppression mice. Furthermore, CAP significantly promoted the expression of intestinal barrier proteins (Claudin-1, Occludin and ZO-1). Additionally, CAP markedly up-regulated the phosphorylation levels of ERK1/2, p38, IκBα and p65 in the colon tissue, suggesting that CAP might alleviate intestinal inflammation by modulating MAPK/NF-κB signaling pathway. Moreover, CAP could restore the abundance of probiotic species ( Lactobacillus and Bacteroides ), while decreasing pathogenic species ( Oscillospira and Helicobacter ). These findings underscore the substantial immunomodulatory potential of CAP.
研究领域:
食品科学
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免疫学
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分子生物学
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PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2024
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IF 10.7
Quanfu Zeng,Hongkai Chen,Zhuxian Wang,Yinglin Guo,Yufan Wu,Yi Hu,Peiyi Liang,Zeying Zheng,Tao Liang,Dan Zhai,Yaling Guo,Li Liu,Chunyan Shen,Cuiping Jiang,Qun Shen,Yankui Yi,Qiang Liu
Acne vulgaris ranks as the second most prevalent dermatological condition worldwide, and there are still insufficient safe and reliable drugs to treat it. Cryptotanshinone (CTS), a bioactive compound derived from traditional Chinese medicine Salvia miltiorrhiza , has shown promise for treating acne vulgaris due to its broad-spectrum antimicrobial and significant anti-inflammatory properties. Nevertheless, its local application is hindered by its low solubility and poor skin permeability. To overcome these challenges, a carrier-free pure drug self-assembled nanosystem is employed, which can specifically modify drug molecules based on the disease type and microenvironment, offering a potential for more effective treatment. We designed and synthesized three distinct structures of cationic CTS-peptide conjugates, creating self-assembled nanoparticles. This study has explored their self-assembly behavior, skin permeation, cellular uptake, and both in vitro and in vivo anti-acne effects. Molecular dynamics simulations revealed these nanoparticles form through intermolecular hydrogen bonding and π-π stacking interactions. Notably, self-assembled nanoparticles demonstrated enhanced bioavailability with higher skin permeation and cellular uptake rates. Furthermore, the nanoparticles exhibited superior anti-acne effects compared to the parent drug, attributed to heightened antimicrobial activity and significant downregulation of the MAPK/NF-κB pathway, leading to reduced expression of pro-inflammatory factors including TNF-), IL-1β and IL-8. In summary, the carrier-free self-assembled nanoparticles based on CTS-peptide conjugate effectively address the issue of poor skin bioavailability, offering a promising new approach for acne treatment.
研究领域:
药学
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纳米技术
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皮肤病学
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生物医学工程
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
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2022
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IF 6.117
Xiaohua Pan,Liya Ye,Zhengnan Ren,Jiahong Li,Binbin Li,Li-Long Pan,Jia Sun
Acute pancreatitis (AP) is an acute inflammatory abdominal disease frequently associated with intestinal barrier dysfunction. Biochanin A (BCA), a dietary isoflavone , has gained increasing interest with its pronounced biological activities. However, its potential beneficial effects on AP have not been demonstrated. Herein, we explored the protective effect of BCA on caerulein-induced AP in BALB/c mice and underlying mechanisms. BCA alleviated AP as evidenced by reduced serum amylase and lipase levels, pancreatic edema, pancreatic myeloperoxidase activity, and improved pancreatic morphology. Amelioration of pancreatic damage by BCA was associated with reduced levels of tumor necrosis factor -α , interleukin (IL)-1β , IL-6 , and monocyte chemotactic protein -1 in both pancreas and colon. Moreover, BCA attenuated AP-associated barrier damage by upregulating the expression of tight junction proteins zonulin occluding (ZO)-1, ZO-2, occludin , and claudin-1. Concomitantly, the translocation of pathogenic bacteria Escherichia coli ( E. coli ) to pancreas was reduced by BCA. More importantly, reduction of E. coli dissemination by BCA inhibited the TLR4-MAPK/NF-κB signaling and NLRP3 inflammasome activation, thereby protecting against AP and related intestinal injury . Consistently, TLR4 inhibition by TAK-242 pre-treatment counteracted the anti-inflammatory effects of BCA in acinar cells . Taken together, our study extends beneficial effects of BCA to AP prevention, and dietary BCA supplement may be a potential strategy to safeguard AP.
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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分子生物学
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DOI
PubMed
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 15
·5035
·
IF 4.927
Fengmao An,Xinran Xuan,Zheng Liu,Ming Bian,Qingkun Shen,Zheshan Quan,Guowei Zhang,Chengxi Wei
Alzheimer’s disease (AD) is a major neurodegenerative disease, but so far, it can only be treated symptomatically rather than changing the process of the disease. Recently, triazoles and their derivatives have been shown to have potential for the treatment of AD. In this study, the neuroprotective effects of 4-(4-(heptyloxy)phenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one (W112) against β-amyloid (Aβ)-induced AD pathology and its possible mechanism were explored both in vitro and in vivo. The results showed that W112 exhibits a neuroprotective role against Aβ-induced cytotoxicity in PC12 cells and improves the learning and memory abilities of Aβ-induced AD-like rats. In addition, the assays of the protein expression revealed that W112 reversed tau hyperphosphorylation and reduced the production of proinflammatory cytokines, tumor necrosis factor-α and interleukin-6, both in vitro and in vivo studies. Further study indicated that the regulation of mitogen-activated protein kinase/nuclear factor-κB pathways played a key role in mediating the neuroprotective effects of W112 against AD-like pathology. W112 may become a potential drug for AD intervention.Keywords:triazoles;Alzheimer’s disease;amyloid beta-peptides;neuroinflammation;mitogen-activated protein kinase/NF-kappa B signaling pathways
研究领域:
神经科学
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药理学
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神经退行性疾病
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2021
·
IF 5.811
Feng Yunhui,Mei Liyan,Wang Maojie,Huang Qingchun,Huang Runyue
18β-Glycyrrhetinic acid (18β-GA), an active component from Glycyrrhiza glabra L. root (licorice), has been demonstrated to be able to protect against inflammatory response and reduce methotrexate (MTX)-derived toxicity. This study was therefore designed to test the therapeutic possibility of 18β-GA on rheumatoid arthritis (RA) and to explore the underlying mechanism. LPS or TNF-α-induced inflammatory cell models and collagen-induced arthritis (CIA) animal models were applied in this study. Real-time quantitative PCR (RT-qPCR) was used to measure the mRNA levels of various cytokines and FOXO family members. The protein levels of molecules in the MAPK/NF-κB signaling pathway were analyzed using western blot. The cell proliferation assay and colony-forming assay were used to test the influence of 18β-GA on cell viability. The cell apoptosis assay and cell cycle assay were performed to detect the effect of 18β-GA on cell proliferative capacity by using flow cytometry. Hematoxylin and eosin (H&E) staining was performed to evaluate pathological changes after drug administration. The enzyme-linked immunosorbent assay (ELISA) was carried out for the detection of cytokines in serum. In vitro, we found that 18β-GA decreased the mRNA levels of IL-1β, IL-6, and COX-2 by inhibiting the MAPK/NF-κB signaling pathway in MH7A and RAW264.7 cell lines. Moreover, 18β-GA was able to suppress cell viability, trigger cell apoptosis, and G1 phase cell cycle arrest in our in vitro studies. 18β-GA dramatically enhanced the mRNA level of FOXO3 in both TNF-α- and LPS-induced inflammation models in vitro. Interestingly, after analyzing GEO datasets, we found that the FOXO3 gene was significantly decreased in the RA synovial tissue as compared to healthy donors in multiple microarray studies. In vivo, 18β-GA exhibited a promising therapeutic effect in a collagen-induced arthritis mouse model by alleviating joint pathological changes and declining serum levels of TNF-α, IL-1β, and IL-6. Finally, we observed that 18β-GA administration could mitigate liver damage caused by collagen or MTX. Collectively, the current study demonstrates for the first time that 18β-GA can inhibit inflammation and proliferation of synovial cells, and the underlying mechanism may be associated with its inhibition of MAPK/NF-κB signaling and promotion of FOXO3 signaling. Therefore, 18β-GA is expected to be a new drug candidate for RA therapy.
研究领域:
药理学
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免疫学
·
风湿病学
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DOI
PubMed
高影响因子
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