JOURNAL OF ETHNOPHARMACOLOGY
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2026
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IF 5.4
Aoyu Zhang,Shuying Li,Jie Qiao,Chuanqi Zhong,Zhiwen Zhang,Xiguang Ye,Jun Jin,Shiyan Shang,Song Wu,Qing Zhang,Gongxu Yang
Ethnopharmacological relevance The therapeutic effect of Psoralea corylifolia L. on knee joint pain was recorded as early as the Ming Dynasty in the Compendium of Materia Medica, which notes its actions of tonifying the kidney, strengthening tendons, and bones. Isopsoralen (ISO), derived from the Psoralea corylifolia L., has shown efficacy in improving osteoarthritis (OA) in both traditional use and our previous screening, demonstrating effects in alleviating joint inflammation and protecting cartilage. Aim of the study OA is a common disabling disease. Its progression connects local joint pathology to systemic metabolic and inflammatory states, extending to gut microbiota and metabolites. This study examines the therapeutic mechanism of isopsoralen against OA using a DMM-induced model. Materials and methods ISO's targets were predicted by network pharmacology approaches. Therapeutic effects were evaluated through behavioral tests, micro-CT, histology, Western blot, and PCR, while safety was assessed via liver/kidney staining. 16S rDNA sequencing and targeted metabolomics were employed to analyze gut microbiota structure and short-chain fatty acids (SCFAs). Pseudo germ-free mice and fecal microbiota transplantation (FMT) were used to validate the role of gut microbiota. Results Network pharmacology indicated ISO's multi-target action against OA. ISO downregulated the MAPK/NF-κB pathway, attenuated subchondral bone abnormalities, and alleviated joint degeneration in DMM mice. It also modulated gut microbiota composition and SCFA levels. FMT confirmed the essential role of gut microbiota in ISO's efficacy. Furthermore, no hepatorenal toxicity was observed. Conclusion ISO alleviates OA by modulating gut microbiota/SCFAs and inhibiting the MAPK/NF-κB pathway, thereby reducing inflammation and improving bone abnormalities, without hepatorenal toxicity.
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POULTRY SCIENCE
·
2026
·
IF 4.5
Jie Qi,Haotian Yang,Yang Yang,Xinyi Dou,Xin Chen,Qiuyue An,Tingyang Wu,Xiuzhi Liu,Yu Boyuan,Hao Wang,Siqi Wang,Yinkang Song,Chenjia Shi,Chao Ma,Jia Chen,Yuan Zhao,Honggang Fan
This study evaluated the effects of esculetin on heat stress-induced splenic immunosuppression in broilers. Esculetin significantly reduced rectal temperature and respiratory rate in heat-stressed broilers ( P < 0.05), improved growth performance, serum biochemical parameters, and the spleen index, and attenuated heat stress-induced splenic histopathological damage and HSP70 expression. Concurrently, esculetin elevated serum levels of immunoglobulins (IgA, IgM, and IgG) and upregulated the gene expression of anti-inflammatory cytokines, while downregulating pro-inflammatory cytokine genes (IL-1β, IL-6, and TNF-α). Network pharmacology analysis, molecular docking, and in vivo validation demonstrated that the immunomodulatory effects of esculetin were primarily mediated through targeting NF-κB, TNF-α, and IL-6, thereby modulating the NF-κB/MAPK signaling pathway. These findings provide a scientific basis for the application of esculetin as a functional feed additive to alleviate heat stress-induced immune dysfunction in poultry.
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CYTOTECHNOLOGY
·
2021
·Vol. 73
·期 5
·697-713
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IF 2.058
Lu Zhihong,Zhu Xiujuan,Ye Yuhong,Fu Haidong,Mao Jianhua
Protein phosphatase 2A (PP2A) is one of the major protein serine/threonine phosphatases (PPPs) with regulatory effects on several cellular processes, but its role and function in Adriamycin (ADR)-treated podocytes injury needs to be further explored. Mice podocytes were treated with ADR and PP2A inhibitor (okadaic acid, OA). After transfection, cell apoptosis was detected by flow cytometry. Expressions of podocytes injury-, apoptosis- and epithelial-to-mesenchymal transition (EMT)- and JNK-interacting protein 4/p38-Mitogen-Activated Protein Kinase (JIP4/p38-MAPK) pathway-related factors were measured using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot as needed. Interaction between PP2A and JIP4/MAPK pathway was confirmed using co-immunoprecipitation (Co-Ip) assay. In podocytes, ADR inhibited PP2A, Nephrin and Wilms’ tumor (WT) 1 expressions yet upregulated apoptosis and Desmin expression, and suppressing PP2A expressionenhanced the effects. PP2A overexpression reversed the effects of ADR on PP2A and podocyte injury-related factors expressions and apoptosis of podocytes. JIP4 was the candidate gene interacting with both PP2A and p38-MAPK pathway, and PP2A overexpression alleviated the effects of ADR on p38-MAPK pathway-related factors expressions. Additionally, in ADR-treated podocytes, PP2A suppression enhanced the effects of ADR, yet silencing of JIP4 reversed the effects of PP2A suppression on regulating p38-MAPK pathway-, apoptosis- and EMT-related factors expressions and apoptosis, with upregulations of B-cell lymphoma-2 (Bcl-2) and E-cadherin and down-regulations of Bcl-2 associated protein X (Bax), cleaved (C)-casapse-3, N-cadherin, Vimentin and Snail. PP2A protects ADR-treated podocytes against injury and EMT by suppressing JIP4/p38-MAPK pathway, showing their interaction in podocytes.
研究领域:
肾病学
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细胞生物学
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分子生物学
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Oncology Letters
·
2021
·Vol. 23
·期 2
·1-10
·
IF 2.967
Zheng Han,Liu Meng,Xiaodong Huang,Jie Tan,Weijie Liu,Wei Chen,Yanli Zou,Yishan Cai,Shasha Huang,Aifang Chen,Ting Zhan,Min Huang,Xiaoli Chen,Xia Tian,Qingxi Zhu
A major cause of treatment failure in advanced colon cancer is resistance to chemotherapy. p38 mitogen‑activated protein kinase (MAPK) has been associated with cellular apoptosis and plays an important role in multidrug resistance (MDR) in cancer cells. In the present study the effect of p38 MAPK on the sensitivity of 5‑fluorouracil (5‑FU)‑resistant SW480 (SW480/5‑FU) human colon cancer cells to noscapine was investigated. Following p38 MAPK interference, the inhibitory effect of noscapine on cell viability and proliferation was increased in the SW480/5‑FU cells and there was also a decrease in the expression level of minichromosome maintenance proteins, recombinant Ki‑67 and proliferating cell nuclear antigen. Inhibition of p38 MAPK also enhanced noscapine‑induced G1‑phase cell cycle arrest in the SW480/5‑FU cells and there was also a decrease in the protein and mRNA expression level of cyclin D, cyclin E and cyclin‑dependent kinase 2, and an increase in the expression level of P57. Furthermore, p38 MAPK interference increased noscapine‑induced apoptosis of the SW480/5‑FU cells and there was an increase in the protein and mRNA expression level of caspases‑3 and 8 and Bax, and decreased Bcl‑2 expression level. The sensitivity of the SW480/5‑FU cells to noscapine was also increased following p38 MAPK interference, as demonstrated by MDR inhibition via decreased Akt activity and reduced protein expression level of the MDR proteins P‑glycoprotein, multidrug resistance protein 1 and ATP‑binding cassette G2. These observations indicated that inhibition of p38 MAPK increased the sensitivity of the SW480/5‑FU cells to noscapine by suppressing proliferation, induction of cell cycle arrest and apoptosis, and reversal of MDR in the SW480/5‑FU cells.
研究领域:
肿瘤学
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药理学
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细胞生物学
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分子生物学
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Chemical Biology & Drug Design
·
2023
·Vol. 103
·期 1
·e14408
·
IF 3
Xiao-Wen Nie,Ali Adnan Nasim,Xiao-Jun Yao,Xing-Xing Fan
The emergency of tyrosine kinase inhibitors has remarkably enhanced the clinical outcomes of cancer therapy, especially the use of EGFR inhibitors for non-small cell lung cancer (NSCLC). However, acquired resistance is inevitable after 8–12 months treatment. New agents or treatments are urgently required to resolve this problem. In this study, we identified that compound ZYZ384 can selectively inhibit the growth of gefitinib-resistant (G-R) lung cancer cells, without affecting that of normal lung epithelial cells. ZYZ384 induced G2 arrest in G-R NSCLC cells, decreasing the expression of Cyclin B1 and increasing the expression of P21. Meanwhile, ZYZ384 also induced apoptosis in NSCLC cells and correspondingly increased the expression of cleaved Caspase 3, 8, and 9 proteins. The expression of p-JNK, p-P38, and p-ERK were also increased in H1975 NSCLC cells treated with ZYZ384. Finally, we observed that the JNK inhibitor effectively reversed the pro-apoptotic effect of ZYZ384. In conclusion, ZYZ384 is a potential therapeutic agent to inhibit the growth of NSCLCs with EGFR mutations through activating JNK, which will help the development of related anticancer drugs.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Shaojie Zhang,Qian Zhang,Chong Li,Na Xing,Pengfei Zhou,Yukun Jiao
Anemarrhena asphodeloides polysaccharide (AAP70–1) was reported to have immunomodulatory effects in our previous report. To further improve the immunomodulatory effects of AAP70–1, an A. asphodeloides polysaccharide-zinc complex (AAP-Zn) was synthesized using a ZnCl 2 modification method, and the potential mechanisms by which AAP-Zn activates macrophages were investigated. The results showed that the structural features of AAP-Zn were similar to those of AAP70–1 with a Zn content of 0.2 %, confirming that Zn mainly interacted with AAP70–1 by forming Zn O coordination bonds and Zn…OH bonds. In addition, the administration of AAP70–1 and AAP-Zn effectively improved the immunomodulatory effects by enhancing phagocytosis and upregulating the mRNA expression of cytokines (TNF- α , IL-6, IL-1 β , and IL-18), as well as increasing the production levels of nitric oxide (NO) and reactive oxygen species (ROS) in zebrafish embryos. The intracellular mechanism by which AAP-Zn activates macrophages was found to involve activation of the NF- κ B and MAPK signaling pathways. Our findings suggest that AAP-Zn may be a potential immunopotentiator in the field of biomedicine or functional foods.
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INTERNATIONAL IMMUNOPHARMACOLOGY
·
2018
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IF 3.118
Jing Xing,Zhenlong Yu,Xiangyu Zhang,Wenyang Li,Dongna Gao,Jian Wang,Xiaochi Ma,Xinshi Nie,Wei Wang
The p38 MAPK signaling pathway plays a key role in lung inflammation and the development of acute lung injury (ALI). We previously reported that the phenolic compound procyanidin B1 inhibits inflammation by suppressing the p38 MAPK signaling pathway. Here, we asked whether the monomer of procyanidin B1, epicatechin (EC), can alleviate LPS-induced ALI in mice, and if so, whether EC acts by inhibiting p38 MAPK. C57BL/6 mice were randomly divided into four groups ( n = 8) and received EC alone, vehicle (sham group), LPS alone, or LPS and EC. LPS was administered via intraperitoneal injection and EC via nasogastric feeding. Lung histopathology , alveolocapillary membrane permeability , inflammation, and p38 MAPK pathway activation were assessed by immunohistochemistry , tissue wet/dry weight analysis, quantitative PCR, protein assays, ELISA , and western blot analysis using lung tissue and/or bronchoalveolar fluid. We also performed molecular modeling and in vitro enzymatic assays to examine the potential interaction between EC and p38 MAPK at the molecular level. We found that LPS caused an increase in ALI-associated lung pathology accompanied by activation of p-p38 pathway components and the transcription factor AP1. All of these effects were substantially reduced by treatment with EC. Furthermore, molecular modeling suggested that EC suppressed p38 MAPK signaling by hydrogen bonding with Glu71, Ala 111, Asp112, and Leu171 in the active site of p38α. In vitro kinase assays confirmed the ability of EC to directly inhibit purified p38 MAPK. Collectively, our data suggest that the naturally occurring compound EC could be a new therapeutic option for ALI.
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Experimental and Therapeutic Medicine
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2022
·Vol. 24
·期 6
·1-8
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IF 2.751
Na Ren,Shanshan Shi,Na Zhao,Lingyan Zhang
Dual specificity phosphatase 22 (DUSP22) regulates fibrosis and inflammation, which may be implicated in the development of diabetic nephropathy (DN). Hence, the current study aimed to assess the effect of DUSP22 on cell proliferation, apoptosis, fibrosis and inflammation in mouse mesangial cell line (SV40‑MES13) under both high glucose (HG) and low glucose (LG) conditions. SV40‑MES13 cells were treated with HG and LG, then HG‑group cells were transfected with DUSP22 overexpression and control plasmids, meanwhile LG‑group cells were transfected with DUSP22 and control siRNAs. Then, cell proliferation using Cell Counting Kit‑8, cell apoptosis by TUNEL assay, protein expression using western blotting, inflammatory cytokines using ELISA and RNA using reverse transcription‑quantitative PCR were determined. DUSP22 mRNA and protein were decreased in SV40‑MES13 cells under the HG condition compared with those under the LG condition. Under the HG condition, DUSP22 overexpression suppressed SV40‑MES13 cell proliferation at 48 and 72 h as well as Bcl2, but it facilitated TUNEL‑reflected apoptotic rate and cleaved‑caspase‑3; besides, DUSP22 overexpression restrained proteins of fibronectin 1, collagen I, transforming growth factor beta 1, and their corresponding mRNAs. As to the inflammation, DUSP22 overexpression downregulated TNF‑α, IL‑1β, IL‑6 and IL‑12 under the HG condition. By contrast, DUSP22 siRNA promoted SV40‑MES13 cell proliferation, fibrosis and inflammation, but attenuated apoptosis in SV40‑MES13 cells under the LG condition. Additionally, DUSP22 overexpression inactivated phosphorylated (p)‑ERK, p‑JNK, and p‑P38 in HG‑treated SV40‑MES13 cells; differently, DUSP22 small interfering RNA facilitated them under the LG condition. In conclusion, DUSP22 suppresses HG‑induced mesangial cell hyperproliferation, fibrosis, inflammation and the MAPK pathway, implying its potency in DN treatment.
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Food & Function
·
2021
·Vol. 12
·期 23
·11956-11965
·
IF 5.396
Fangfang Yan,Wanbing Chen,Li Zhao,Qun Lu,Chengming Wang,Rui Liu
Procyanidins can alleviate small-intestine damage induced by acrylamide (ACR). However, little is known about whether procyanidins, after gastrointestinal digestion, can prevent ACR-induced intestinal barrier damage and the possible mechanism. Here, Caco-2 cells were differentiated into an intestinal epithelial cell monolayer membrane, which was stimulated with or without ACR in the presence or absence of procyanidin A1 (A1) and its digestive products (D–A1). Our findings show that both A1 and D–A1 significantly increased the transepithelial electrical resistance (TEER) value; decreased FITC-dextran 4 kDa (FITC-4 kDa) permeability, apoptosis and lactic dehydrogenase (LDH) release; and enhanced the expression of claudin-1, occludin and zonula occludens-1 (ZO-1) in ACR-induced Caco-2 cell monolayer membrane. In addition, A1 and D–A1 suppressed ACR-induced phosphorylation of mitogen-activated protein kinase (MAPK). Finally, A1 and D–A1 inhibited the myosin light chain kinase (MLCK) signaling pathway, thereby maintaining normal intestinal barrier functions, similar to the MLCK inhibitor in ACR-induced Caco-2 cell monolayer membrane. These findings indicate that A1 can alleviate ACR-induced intestinal barrier dysfunction via inhibiting the MAPK/MLCK signaling pathway, and it still has excellent inhibitory effects after digestion.
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JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY
·
2024
·
IF 11.2
Ce Zhu,Miaomiao He,Juehan Wang,Yong Huang,Wei Deng,Limin Liu,Ganjun Feng,Li Zhang,Yueming Song
Photothermal therapy (PTT) is a desirable way to attain on-demand hyperthermia owing to the heat generated by photothermal materials absorbing near-infrared) light. The mild heat (42 ± 0.5 °C) can not only accelerate bone tissue regeneration but also promote the release of bioactive ions from biomaterials. Based on this one-stone-two-birds strategy, a 3D printed PEEK-graphene composite scaffold (PG) with hydroxyapatite (HA) coating (PGH) for photothermally remote control of bone regeneration was well designed in this study. The results showed that the HA coating on PGH could release Ca 2+ and PO 4 3– ions easily under NIR irradiation, which was ascribed to the mild heat generated from graphene in the composite scaffold. The mild heat and the boosted Ca 2+ /PO 4 3– release could synergistically enhance the bone regeneration ability both in vitro and in vivo . The underlying mechanism was further explored and confirmed to be closely related to the upregulation of HSP 70, by which the MAPK/ERK signaling pathway was activated selectively. The favorable results demonstrate that the 3D-printed PEEK/graphene composite scaffold is promising in the applications of bone defect repair.
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EUROPEAN JOURNAL OF PHARMACOLOGY
·
2017
·
IF 2.896
Han-bin Chen,Chao-dan Luo,Jia-li Liang,Zhen-biao Zhang,Guo-sheng Lin,Jia-zhen Wu,Cai-lan Li,Li-hua Tan,Xiao-bo Yang,Zi-ren Su,Jian-hui Xie,Hui-fang Zeng
Coptisine is one of the main constituents of Coptis chinensis which has been widely used for the remedy of inflammatory disorders. Although the biological activities of coptisine have been well known, the pharmacological properties of its free base have seldomly been elucidated thus far. The aim of this study was to investigate the potential anti-inflammatory properties of coptisine free base (CFB, 8-hydroxy-7,8-dihydrocoptisine) on three animal models, namely xylene-induced ear edema, acetic acid-induced vascular permeability and carrageenan-induced paw edema . The results exhibited that CFB exerted a dose-dependent suppression on ear edema induced by xylene, significantly mitigated the aggravation of vascular permeability caused by acetic acid and paw edema induced by carrageenan . Additionally, CFB significantly suppressed the productions of interleukin-1β (IL-1β), interleukin-6 (IL-6), prostaglandinE2 (PGE 2 ) and tumor necrosis factor (TNF-α) in the drug-treated groups as compared with the vehicle group after treatment with carrageenan. Signaling events of nuclear factor-κB (NF-κB) translocation, such as p-IKKα, p-IKKβ, p-IκBα and p65 (nucleus) were significantly inactivated, while inhibitor of nuclear factor κBα (IκBα) and p65 (cytosolic) were markedly up-regulated by CFB. Furthermore, CFB also significantly suppressed the mitogen-activated protein kinase (MAPK) pathway by blocking the phosphorylation of p-p38 (phospho-p38 mitogen-activated protein kinases) and p-JNK (phospho-c-jun N-terminal kinase) but not p-ERK (phospho-extracellular signal-regulated kinase). Hence, CFB efficiently prevented inflammation, at least partially, via inhibition of NF-κB and MAPK pathways. These findings provided a pioneering pharmacological basis for the anti-inflammatory effect of CFB and suggested CFB might be a potential candidate for the therapy of inflammatory disorders.
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Frontiers in Pharmacology
·
2025
·
IF 4.8
Tianyao Li,Jiaxin Chen,Zhouyuan Xie,Jiansong Fang,Qiqing Wu,Xinyue Cao,Ziying Chen,Yiyun Wang,Qiqi Fan,Qi Wang,Jinman Liu
Introduction Ginseng, known as the “king of herbs,” has long been used in traditional Chinese medicine due to its beneficial properties, including anti-aging, anti-inflammatory, and anti-apoptotic effects. Ginsenosides, the active compounds in ginseng, have shown promise in treating neurodegenerative diseases such as Alzheimer’s disease (AD). This study investigates the therapeutic potential of Ginsenoside Ro and its underlying mechanisms in AD treatment. Methods In this study, male APP/PS1 transgenic mice were divided into five groups and treated with Ginsenoside Ro or ginseng for one month. Cognitive function and anxiety were assessed through behavioral tests, including the open field test (OFT) and Morris water maze (MWM). To evaluate Aβ deposition, neuronal apoptosis, neuroinflammation, and the MAPK pathway, various techniques were employed: Thioflavin-T staining, Nissl staining, immunofluorescence, Western blot, and qRT-PCR analyses. Results Ginsenoside Ro significantly improved cognitive function and reduced anxiety in APP/PS1 mice. It also decreased Aβ deposition and ameliorated neuronal apoptosis in the cerebral cortex. The treatment regulated the expression of pro-apoptotic proteins (Bax and Caspase3) and increased the anti-apoptotic protein Bcl-2. Additionally, Ginsenoside Ro reduced neuroinflammation by decreasing IBA1-positive microglia and GFAP-positive astrocytes and lowering pro-inflammatory cytokines while enhancing anti-inflammatory cytokine IL-10. Furthermore, the phosphorylation levels of p38 and JNK in the MAPK pathway were significantly reduced, suggesting a key mechanism for its therapeutic effects. Discussion These findings provide strong evidence supporting Ginsenoside Ro as a potential therapeutic agent for Alzheimer’s disease. Its effects appear to be mediated through the modulation of the IBA1/GFAP-MAPK pathway, which may offer new insights into AD treatment strategies.
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