Chinese Medicine
·
2024
·Vol. 19
·期 1
·1-19
·
IF 5.3
Geng Xiaoyu,Wang Ying,Li Huan,Song Liang,Luo Chen,Gu Xiaojie,Zhong Haixin,Chen Huilin,Chen Xinzhu,Wang Jianwei,Pan Zheng
Background Lamiophlomis rotata (Benth.) Kudo ( L. rotata ), the oral Traditional Tibetan herbal medicine, is adopted for treating knife and gun wounds for a long time. As previously demonstrated, total iridoid glycoside extract of L. rotata (IGLR) induced polarization of M2 macrophage to speed up wound healing. In diabetic wounds, high levels inflammatory and chemotactic factors are usually related to high reactive oxygen species (ROS) levels. As a ROS target gene, nuclear factor erythroid 2-related factor 2 (NRF2), influences the differentiation of monocytes to M1/M2 macrophages. Fortunately, iridoid glycosides are naturally occurring active compounds that can be used as the oxygen radical scavenger. Nevertheless, the influence of IGLR in diabetic wound healing and its associated mechanism is largely unclear. Materials and methods With macrophages and dermal fibroblasts in vitro, as well as a thickness excision model of db/db mouse in vivo, the role of IGLR in diabetic wound
healing and the probable mechanism of the action were investigated. Results Our results showed that IGLR suppressed oxidative distress and inflammation partly through the NRF2/cyclooxygenase2 (COX2) signaling pathway in vitro . The intercellular communication between macrophages and dermal fibroblasts was investigated by the conditioned medium (CM) of IGLR treatment cells. The CM increased the transcription and translation of collagen I (COL1A1) and alpha smooth muscle actin (α-SMA) within fibroblasts. With diabetic wound mice, the data demonstrated IGLR activated the NRF2/KEAP1 signaling and the downstream targets of the pathway, inhibited COX2/PEG2 signaling and decreased the interaction inflammatory targets of the axis, like interleukin-1beta (IL-1β), interleukin 6 (IL-6), apoptosis-associated speck-like protein (ASC), cysteinyl aspartate specific proteinase1 (caspase1) and NOD-like receptor-containing protein 3 (NLRP3).In addition, the deposition of COL1A1, and the level of α-SMA, and Transforming growth factor-β1 (TGF-β1) obviously elevated, whereas that of pro-inflammatory factors reduced in the diabetic wound tissue with IGLR treatment. Conclusion IGLR suppressed oxidative distress and inflammation mainly through NRF2/COX2 axis, thus promoting paracrine and accelerating wound healing in diabetes mice. Graphical Abstract
研究领域:
药理学
·
分子生物学
·
传统医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2023
·
IF 7.9
Qi-Rui Hu,Qing-Xin Huang,Huan Hong,Yao Pan,Ting Luo,Jing Li,Ze-Yuan Deng,Fang Chen
s Background Liver cancer is a topical global health issue. The treatment of liver cancer meets significant challenges in the high recurrence rate and invasive incidence. Therefore, the treatment strategies that target epithelial-mesenchymal transition (EMT) induced by cyclooxygenase 2 (COX2)/ prostaglandin E2 (PGE2) pathway have become epidemic. Ginsenoside Rh2 has been proved to inhibit the EMT. However, the underlying mechanisms remain unclear. Moreover, the octyl ester derivative of Rh2 (Rh2-O) exhibited superior anti-proliferative and immunomodulatory effects than Rh2 in our previous researches, which indicated that Rh2-O might also exert inhibitory effects on invasion and metastasis . Purpose The aim of current study is to explore the inhibitory effects of Rh2 and Rh2-O on invasion and metastasis of hepatocellular carcinoma , and to investigate whether these effects are dependent on the c-Jun/COX2/PGE2 pathway. Study Design The Huh-7 liver cancer cells and the H22 tumor-bearing mice were treated with Rh2 and Rh2-O. Method In this paper, the inhibitory effects of Rh2 and Rh2-O on invasion and metastasis were tested by wound healing, trans-well assay and tumor-bearing mice, and the involvement of c-Jun/COX2/PGE2 pathway were verified by exogenous PGE2, activation of COX2 and overexpression of c-Jun. Results The results showed that Rh2 and Rh2-O could efficiently inhibit the invasion and metastasis in a dose-dependent manner ( p < 0.05). And the Rh2-O showed stronger effects than Rh2. Moreover, the exogenous PGE2, activation of COX2 by exogenous LPS and the overexpression of c-Jun by transfection all reversed the inhibitory effects of Rh2 and Rh2-O on metastasis or EMT ( p < 0.05). Conclusion Rh2 and Rh2-O could inhibit the invasion and metastasis of hepatocellular carcinoma via restraining the EMT, which was mediated by c-Jun/COX2/PGE2 pathway.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
·
2022
·Vol. 37
·期 1
·e23229
·
IF 3.568
He-Yu Yang,Ji Wu,Hong Lu,Meng-Lin Cheng,Bang-Hua Wang,Hai-Li Zhu,Ling Liu,Min Xie
Oxaliplatin (OXA) is a common chemotherapy drug for colorectal, gastric, and pancreatic cancers. The anticancer effect of OXA is often accompanied by neurotoxicity and acute and chronic neuropathy. The symptoms present as paresthesia and pain which adversely affect patients' quality of life. Herein, five consecutive intraperitoneal injections of OXA at a dose of 4 mg/kg were used to mimic chemotherapy. OXA administration induced mechanical allodynia, activated spinal astrocytes, and increased inflammatory response. To develop an effective therapeutic measure for OXA-induced neuropathic pain, emodin was intrathecally injected into OXA rats. Emodin developed an analgesic effect, as demonstrated by a significant increase in the paw withdrawal threshold of OXA rats. Moreover, emodin treatment reduced the pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-1β) which upregulated in OXA rats. Furthermore, autodock data showed four hydrogen bonds were formed between emodin and cyclooxygenase-2 (COX2), and emodin treatment decreased COX2 expression in OXA rats. Cell research further proved that emodin suppressed nuclear factor κB (NF-κB)-mediated inflammatory signal and reactive oxygen species level. Taken together, emodin reduced spinal COX2/NF-κB mediated inflammatory signal and oxidative stress in the spinal cord of OXA rats which consequently relieved OXA-induced neuropathic pain.
研究领域:
药理学
·
神经科学
·
炎症
·
疼痛管理
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Death Discovery
·
2026
·
IF 10.4
Hao Wenli,Gao Song,Guo Suhan,Luo Jingjing,Li Siyu,Lu Junze,Jiang Lulu,Lu Jie,Wang Nan,Ran Aijia,Qian Xiaoyun,Gao Xia,Yu Chenjie,Cheng Cheng
Lipid metabolism is an important biological process that maintains the dynamic balance of several key functions, such as intracellular energy metabolism, signal transduction, and membrane remodeling. However, the role of lipid metabolism in auditory function and the underlying mechanisms remain unclear. Our results reveal that the neomycin exposure disrupts lipid metabolism in auditory system. We find that neomycin-induced hair cells (HC) damage leads to abnormal lipid droplets (LD) accumulation. Further research reveals that decreased YAP expression is a key factor that contributes to abnormal LD accumulation. In both in vivo and in vitro studies, Yap overexpression reduces abnormal LD accumulation and mitigated HC damage. To further investigate its downstream mechanisms, we perform a cross-analysis of Yap -related and lipid metabolism–related genes, identifying that Cox2 is a key downstream target of Yap that contributes to LD accumulation and HC damage. Our work provides clear evidence for the role of lipid metabolism in neomycin-induced hearing loss and elucidates underlying mechanism of Yap/Cox2 pathway. These findings provide new perspectives and avenues for the clinical treatment of sensorineural hearing loss.
✓ 已验证
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2020
·
IF 4.872
Biao Chen,Qing Chai,Shengmin Xu,Qian Li,Tao Wu,Shaopeng Chen,Lijun Wu
Silver nanoparticles (AgNPs) are widely used as antimicrobial agents and resulted in their accumulation in environment. The purpose of this study was to investigate the detailed molecular mechanisms underlying AgNP-induced lung cellular senescence which has been proposed as a pathogenic driver of chronic lung disease. Herein, we demonstrate that exposure to AgNPs elevates multiple senescence biomarkers in lung cells, with cell cycle arrest in the G2/M phase, and potently activates genes of the senescence-associated secretory phenotype (SASP) in human fetal lung fibroblast cell line MRC5. Fluorescence-based assay also reveals that apoptosis induced by AgNPs is associated with senescence. Furthermore, we show that AgNPs cause premature senescence through an increase in transcription factor nuclear factor kappa B (NF- κ B), cyclooxygenase-2 (COX2) expression and over-production of prostaglandin E2 (PGE2) in lung cells. Inhibition of COX2 reduces AgNPs-induced senescence to a normal level. Moreover, AgNPs also induce upregulation of COX2 and accelerate lung cellular senescence in vivo and cause mild fibrosis in the lung tissue of mice. Taken together, our studies support a critical role of AgNPs in the induction of lung cellular senescence via the upregulation of the COX2/PGE2 intracrine pathway, and suggest the adverse effects to the human respiratory system.
研究领域:
毒理学
·
呼吸医学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Zhiliang Sun,Zhongshi Zhou,Kezheng Liao,Yanju Liu,Yanyun Liu,Chaoyang Wang,Zhihua Zhang,Li Wen
Background: Non-alcoholic fatty liver disease (NAFLD), a chronic liver disease posing a severe threat to human health, currently lacks specific therapeutic drugs. Our previous studies have demonstrated that Polygala tenuifolia Willd. Extract (EPT) can significantly suppress the PGE2 inflammatory pathway, thereby exerting anti-inflammatory and antioxidant effects, as well as improving lipid metabolism. These findings suggest that EPT might hold potential value for the prevention and treatment of NAFLD.Purpose: This study aims to investigate the role of EPT in NAFLD and its multi - target synergistic mechanisms, and to preliminarily explore its impact on the early progression of NAFLD.Methods: The detection of EPT components in rat blood was performed by UPLC-MS/MS. A rat NAFLD model was established using a high-fat emulsion gavage method, and pathological changes in liver tissue were assessed via H&E, Oil Red O, and Sirius Red staining. RNA-seq, immunohistochemistry, RT-qPCR, and Western blotting were used to evaluate the expression of cyclooxygenase 1 (COX1), cyclooxygenase 2 (COX2), inflammatory factors (IL-1, IL-6, TNF-α), oxidative stress-related proteins in the KEAP1 pathway, proteins involved in the protein kinase R-like endoplasmic reticulum kinase (PERK) pathway, and apoptosis-related proteins (Bcl-2 and Caspase-3).Results: EPT significantly attenuated the histopathological alterations in liver tissue and ameliorated lipid accumulation in the livers of NAFLD rats. RNA-seq identified differential changes in the arachidonic acid metabolism, inflammatory, and endoplasmic reticulum-related pathways. Immunohistochemistry showed that EPT reversed the elevated expression of COX2, the ER stress marker GRP78, and PERK in the liver tissue of model rats. RT-qPCR and Western blot analyses confirmed that EPT reduced the expression of COX1, COX2, IL-1β, IL-6, TNF-α, and KEAP1, while increasing Nrf2 and HO-1 levels. Furthermore, EPT downregulated GRP78, PERK, p-PERK, eIF2α, p-eIF2α, ATF4, CHOP, Bcl-2, and Caspase-3.Conclusion: These results suggest that EPT might exert anti - inflammatory and antioxidant effects by modulating the COX2 pathway in NAFLD rats, downregulate the ER stress PERK - eIF2α - ATF4 signaling pathway, alleviate ER stress, inhibit apoptosis, and delay NAFLD progression.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2021
·
IF 4.932
Jingjing Li,Suiyuan Ren,Meng Li,Jingai Bi,Guang Yang,Erguang Li
Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) that causes inflammation and ulcers in the digestive tract. The treatment commonly includes anti-inflammatory agents like 5-aminosalicylic acid or corticosteroids or biologics for people with UC who are no longer responding to corticosteroids. The radices of Paeonia lactiflora Pall. or similar plants of the Paeonia genus have been used in Chinese medicine to treat certain diseases that resemble the symptoms of UC. Paeoniflorin, a terpenoid glycoside, is a major active component for the anti-inflammatory and antitumor activity. In this study, we evaluated the therapeutic effect of paeoniflorin (PF) against dextran sulfate sodium (DSS)-induced colitis in mice and found that PF exhibited protective activity against colitis. PF treatment suppressed NF-κB pathway activation, resulting down regulation of pro-inflammatory factor expression. In addition, we detected reduction in eosinophil-related chemokine gene expression and eosinophil infiltration. The treatment also reversed Treg cell population suppression. Although PF treatment did not block COX2 induction, the compound weakly inhibited COX2 activity in an enzymatic assay. Taken together, PF exerts its therapeutic activity against UC through inhibition of inflammation and eosinophil infiltration.
研究领域:
药理学
·
免疫学
·
胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cells
·
2024
·Vol. 13
·期 3
·206
·
IF 5.1
Meng-Yuan Li,Ying Wang,Ying Wu,Xu-Yu Zhao,Zhen-Shan Yang,Bo Li,Si-Ting Chen,Yu-Ying He,Zeng-Ming Yang
(1) Background: Inflammatory responses are implicated in embryo implantation, decidualization, pregnancy maintenance and labor. Both embryo implantation and decidualization are essential to successful pregnancy in rodents and primates. S100A6 is involved in inflammation, tumor development, apoptosis and calcium homeostasis. S100A6 is strongly expressed in mouse decidua, but the underlying mechanisms of how S100A6 regulates implantation and decidualization are poorly defined. (2) Methods: Mouse endometrial stromal and epithelial cells are isolated from day 4 pseudopregnant mouse uteri. Both immunofluorescence and Western blotting are used to analyze the expression and localization of proteins. The molecular mechanism is verified in vitro by Western blotting and the quantitative polymerase chain reaction. (3) Results: From days 4 to 8 of pregnancy, S100A6 is specifically expressed in mouse subluminal stromal cells. Blastocyst-derived lactic acid induces AA secretion by activating the luminal epithelial p-cPLA2. The epithelial AA induces stromal S100A6 expression through the COX2/PGI2/PPAR δ pathway. Progesterone regulates S100A6 expression through the progesterone receptor (PR). S100A6/RAGE signaling can regulate decidualization via EGFR/ERK1/2 in vitro. (4) Conclusions: S100A6, as an inflammatory mediator, is important for mouse implantation and decidualization.Keywords:decidualization;implantation;S100A6;RAGE;inflammation
研究领域:
生殖生物学
·
分子生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2018
·
IF 3.47
Yaser Gamallat,Xiaomeng Ren,Williams Walana,Abdo Meyiah,Ren Xinxiu,Yanyan Zhu,Meiqi Li,Siyuan Song,Luhan Xie,Yazeed Jamalat,Mohammad Zubair Saleem,Yufang Ma,Yi Xin,Dong Shang
Lactobacillus rhamnosus (LGG) is well documented strain with wide clinical applications. We investigated herein the possible protection role of LGG in against early preneoplastic colon carcinogenesis Aberrant crypt foci (ACF) in rat model. Sprague Dawley rats were pre-treated with or without LGG via oral gavage, followed by ACF induction with Dimethylhydrazine (DMH). LGG treated groups showed significant decrease in total number of ACF’s, and increased Bax, P53, and Caspase-3 proteins expression with significant attenuation of NFkB, Cox2 and β catenin expression compared to DMH group. Serum cytokines array revealed significant elevation of IL-2, IL-6, and IFN-γ, and attenuated level of IL-10 in LGG+DMH treated animals. Finally, the 16S rRNA fecal microbiome genomic analysis showed that LGG alters the gut microbiome structure, composition and functions at phylum, family and genus level. Collectively, LGG reduces colon ACFs incidence and multiplicity via inhibition of pro-carcinogenesis biomarkers and modulate the gut microbiome.
研究领域:
胃肠病学
·
微生物学
·
肿瘤学
·
分子生物学
✓ 已验证
DOI
高影响因子
CHEMOSPHERE
·
2020
·
IF 5.778
Jiafeng Zhou,Ruonan Shu,Chunan Yu,Ze Xiong,Qingfeng Xiao,Zezhi Li,Xiaoxian Xie,Zhengwei Fu
Trifluoromethanesulfonic acid (TFMS) is the shortest chain perfluorinated compound . Recently, it has been identified as a persistent and mobile organic chemical with a maximum concentration of 1 μg/L in the environment. However, its toxicological mechanism remains unclear. In this study, to evaluate the liver and intestinal toxicity of TFMS in mammals, male mice were orally exposed to 0, 1, 10 and 100 μg/kg for 12 weeks. Our results showed that TFMS exposure reduced the epididymal fat weight in mice, caused the decrease of serum and liver triglyceride (TG) level and the increase of serum low density lipoprotein (LDL) level. Also, we observed the inflammatory cell infiltration in the liver of mice exposed to 10 μg/kg and 100 μg/kg TFMS, which was coupled with the increased mRNA expression levels of inflammatory factors such as COX2 , TNF-α , IL-1β in the liver. In addition, the mRNA expression levels of lipid metabolism-related genes ( PPAR-α , ACOX , SCD1 , PPAR-γ , etc.) were significantly decreased in the liver of mice after exposure to both doses of TFMS. We also found TFMS exposure caused the imbalance of cecal gut microbiota and change of cecal microbiota diversity. KEGG pathway predictions showed that the exposure of 100 μg/kg TFMS changed the synthesis and degradation of ketone bodies, benzoate degradation and several other metabolic pathways. Our findings indicated that TFMS exposure disturbed the liver lipid metabolism possibly via altering the gut microbiota.
研究领域:
毒理学
·
分子生物学
·
微生物学
·
环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2023
·
IF 3.4
Yao Wang,Lili Liu,Cheng Cheng,Shuxuan Wang,Qirui Zhai,Yunyang Song,Ronghua Dai
Zishen Pill (ZSP) is a traditional Chinese medicine that is frequently used to treat Benign Prostatic Hyperplasia (BPH), however its specific mechanism of action and active ingredients are yet unknown. We used a combination of serum pharmacochemistry and network pharmacology and a series of biochemical assays to explore the action mechanism of ZSP in the treatment of BPH. The BPH rat model was created using testosterone propionate , and following oral ZSP administration, the components of ZSP in rat serum were detected by UPLC-Q-Exactive Orbitrap/MS method. A "component-target-disease" network and PPI networks were constructed on this foundation. The primary mechanism of ZSP decreasing BPH in rats was studied by KEGG pathway and GO analysis. Finally, the potential pathways and key targets were further verified in vivo by molecular biology and immunological methods . 46 substances were charactered from rat serum, and 164 anti-BPH targets were screened from the database. According to network pharmacology, the primary targets were CASP3, STAT3, JUN, and PTGS2/COX2. Three related pathways (PI3K/Akt signaling pathway, AGE-RAGE signaling pathway and EGFR tyrosine kinase inhibitor resistance) were closely related to the therapeutic effects of ZSP. The findings of molecular biology demonstrated that ZSP may bring Bcl-2, BAX, CASP3, COX2, and 5LOX protein and gene expression in BPH rats appreciably closer to that of normal rats. Additionally, ZSP can lessen the expression of inflammatory cytokines in BPH rats, including VEGF, TNF-α, CCL5, and interleukin. Conclusion The above results suggest that ZSP may reduce BPH through inflammation/immunity and apoptosis/proliferation-related pathways. This study offers a fresh approach to investigate the basic pharmacological effects and mechanism of ZSP in the treatment of BPH.
研究领域:
药理学
·
中医药
·
分子生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
American Journal of Cancer Research
·
2022
·
IF 5.942
Shan-Mei Chen,Jun-Nan Feng,Chuan-Ke Zhao,Li-Cheng Yao,Li-Xin Wang,Lin Meng,Shao-Qing Cai,Cai-Yun Liu,Li-Ke Qu,Yan-Xing Jia,Cheng-Chao Shou
Cancer is one of the main causes of death in humans worldwide, the development of more effective anticancer drugs that can inhibit the malignant progression of cancer cells is of great significance. Aiphanol is a natural product identified from the seeds of Arecaceae and the rhizome of Smilax glabra Roxb . Our preliminary studies revealed that it had potential antiangiogenic and antilymphangiogenic activity by directly targeting VEGFR2/3 and COX2 in endothelial cells. However, the influence of aiphanol on cancer cells per se remains largely undefined. In this study, the effects and related mechanisms of aiphanol on cancer growth and metastasis were evaluated in vitro and in vivo . Acute toxicity assay and pharmacokinetic analysis were utilized to investigate the safety profile and metabolism characteristics of aiphanol. We revealed that aiphanol inhibited the proliferation of various types of cancer cells and the growth of xenograft tumors in mice and zebrafish models. The possible mechanism was associated with the inactivation of multiple kinases, including FAK, AKT and ERK, and the upregulation of BAX and cleaved caspase-3 to promote cancer cell apoptosis. Aiphanol significantly inhibited cancer cell migration and invasion, which was related to the inhibition of epithelial-mesenchymal transition (EMT) and F-actin aggregation. Aiphanol effectively attenuated the metastasis of several types of cancer cells in vivo . In addition, aiphanol exerted no significant toxicity and had fast metabolism. Collectively, we demonstrated the anticancer effects of aiphanol and suggested that aiphanol has potential as a safe and effective therapeutic agent to treat cancer.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）