INFLAMMOPHARMACOLOGY
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2025
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IF 5.3
Xiang Meixian,Wu Songtao,Liu Minxin,Zhang Bin,Xia Xiankun,Tan Wenjing,Xiang Shijian
Iota-carrageenan oligosaccharides (iCOs), derived from marine red algae, are traditionally used as antithrombotic and anti-inflammatory agents in folk medicinal practice. Despite the prevailing emphasis on these aspects in their applications, the potential of iCOs as a prebiotic agent for gut health and its subsequent impact on intestinal disorders such as colitis remains largely unexplored. A DSS-induced colitis model was employed in C57BL/6 male mice to analyze the gut microbiota via 16S rRNA sequencing. Fecal microbiota transplantation (FMT) was used to assess the therapeutic effects of iCOs on colitis. RNA sequencing (RNA-Seq) identified pathways and genes affected by iCOs. ELISA measured inflammatory cytokines, while western blot and RT-qPCR evaluated protein and gene expressions, respectively. The iCOs increased beneficial bacteria, such as Lactobacillus , Bifidobacterium , and Akkermansia . They enhanced short-chain fatty acid production and upregulated GPR41, GPR43, and GPR109A mRNA, influencing cytokine secretion. The iCOs reduced mRNA of SPHK1 , BDKRB1 , LCN2 , and so on, potentially through PI3K-Akt pathway inhibition, and promoted tight junction protein expression. Our findings highlight the novel therapeutic potential of iCOs in colitis, indicating a multifaceted approach to treatment that includes gut microbiota modulation, intestinal barrier restoration, and the suppression of inflammatory responses. Graphical abstract
研究领域:
医学
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微生物学
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分子生物学
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DOI
PubMed
高影响因子
RSC Advances
·
2018
·Vol. 8
·期 52
·29637-29644
·
IF 2.936
Minyu Zhu,Jinwei Ying,Chaowei Lin,Yu Wang,Kelun Huang,Yang Zhou,Honglin Teng
β-Escin exhibits anticancer effects on a panel of established cancer cells. However, the effects of β-escin on human osteosarcoma (OS) are still unknown. The aim of the present study was to investigate whether β-escin was effective against OS both in vivo and in vitro. Our results showed that β-escin induced dose- and time-dependent effects against MG-63, OS732, U-2OS, HOS and SAOS-2 cell proliferation. β-Escin also exhibited excellent anti-proliferative and pro-apoptotic effects in an established OS xenograft model. β-Escin and cytotoxic drugs, including cisplatin, methotrexate (MTX), doxorubicin (Dox) and ifosfamide (Ifos), synergistically inhibited proliferation of MG-63 and OS732 cells in vitro. Moreover, β-escin induced apoptotic death, activated caspase-3, caspase-8 and caspase-9, and regulated expression of Bax and Bcl-2 in MG-63 cells. In addition, our results showed that β-escin treatment reduced expression of p-PI3K, p-Akt and p-mTOR both in MG-63 cells and in an MG-63 xenograft OS model. Interestingly, SC79, which is an Akt activator, inhibited the anti-proliferative effects of β-escin on MG-63 cells. Taken together, our data support the conclusion that β-escin effectively inhibits OS proliferation both in vivo and in vitro. The inhibitory effect of β-escin, at least in part, is due to the inactivation of the PI3K/Akt signalling pathway.
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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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
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2025
·Vol. 39
·期 9
·e70455
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IF 2.8
Lihan Xie,Weinan Li,Shiqi Fan,Jinsong Jin
Diabetic kidney disease (DKD) is a common complication of diabetes, often characterized by podocyte injury, proteinuria, and eventual renal failure. Sinomenine hydrochloride (SH), an active component derived from traditional Chinese medicine, is clinically effective in treating kidney diseases. This study investigates the protective effects of SH on podocytes under high-glucose conditions and its mechanism of action. Mouse podocytes (MPC-5) were treated with SH at concentrations of 50, 200, and 600 μg/mL under high-glucose conditions (30 mmol/L) for 24 h to establish a DKD model. Cell viability was assessed using CCK-8 assays, and apoptosis rates were measured using flow cytometry. Autophagy levels were evaluated by detecting LC3-II, Beclin-1, and P62 proteins via Western blot analysis, while the involvement of the PI3K/AKT/mTOR pathway was analyzed by examining phosphorylated AKT and mTOR. Transmission electron microscopy was employed to observe autophagosomes. SH improved podocyte viability, reduced apoptosis, and enhanced autophagic activity by increasing LC3-II and Beclin-1 expression while decreasing P62 levels. SH also downregulated p-AKT and p-mTOR, indicating inhibition of the PI3K/AKT/mTOR pathway. Electron microscopy confirmed increased autophagosomes in SH-treated groups. SH protects podocytes in a high-glucose environment by enhancing autophagy through inhibition of the PI3K/AKT/mTOR pathway. These findings provide insights into SH as a potential therapeutic agent for DKD management.
研究领域:
药理学
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细胞生物学
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肾病学
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分子生物学
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中医学
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DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2020
·
IF 9.038
Lanqiao Wang,Lanxi Wang,Xu Shi,Shiwen Xu
Excessive chlorpyrifos (CPF) in the environment causes toxicity to nontarget organisms by triggering oxidative stress. Phosphatase and tensin homolog deleted on chromosome ten (PTEN) plays an important role in controlling apoptosis and necrosis by negatively regulating the phosphatidylinositol 3-kinase/threonine kinase (PI3K/AKT) pathway. However, the effects of different concentrations of CPF on grass fish liver cell injury and the role of the ROS/PTEN/PI3K/AKT axis remain poorly understood. In this study, L8824 cells treated with different concentrations of CPF (0, 40, 60, or 80 μM) were used as the research object. The results showed that the median inhibitory concentration (IC50) was 112.226 μM. As the CPF concentrations increased, the ROS and MDA levels increased, and the T-AOC levels and SOD/GPx/GST activities decreased. As PTEN expression increased, PI3K/AKT, BCL-2, and Caspase-8 expression dramatically decreased. Conversely, RIPK1/RIPK3/MLKL and Bax/Cyt-c/Caspase-3 expression increased. Additionally, necroptosis increased in a dose-dependent manner, while apoptosis first increased and then decreased. In conclusion, our study showed that CPF could trigger oxidative stress and induce apoptosis and necroptosis in fish liver cells by regulating the ROS/PTEN/PI3K/AKT axis, and the type of damage induced was dose-dependent. These results are meaningful for toxicological studies of CPF and efforts to protect the ecosystem.
研究领域:
毒理学
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细胞生物学
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环境科学
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DOI
PubMed
高影响因子
Food & Function
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2025
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IF 5.4
Xiaoran Kong,Li Zhao,He Huang,Qiaozhen Kang,Jike Lu,Jia-Qing Zhu
Hyperuricemia is chronic metabolic disease with a high incidence, and it has become the “fourth highest” health risk in modern times. Isorhamnetin is a natural flavonoid found in a variety of plants, especially fruits such as buckthorn. In vivo hyperuricemia ameliorating effect of isorhamnetin and the specific molecular mechanism were profoundly investigated through a hyperuricemia mice model in the present study. The results demonstrated that isorhamnetin showed a significant uric acid-lowering effect in mice. Isorhamnetin was able to reduce uric acid production by inhibiting XOD activity. On the other hand, it reduced the expression of GLUT9 to inhibit uric acid reabsorption and enhanced the expression of ABCG2, OAT1, and OAT3 to promote uric acid excretion. Metabolomics analysis revealed that isorhamnetin gavage restored the purine metabolism and riboflavin metabolism disorders, and thus significantly alleviated the hyperuricemia in mice. Further, the alleviating effect of isorhamnetin on hyperuricemia-induced renal inflammation and its specific mechanism were explored through network pharmacology and molecular validation experiments. Network pharmacology predicted that seven targets were enriched in the PI3K/AKT pathway (CDK6, SYK, KDR, RELA, PIK3CG, IGF1R, MCL1) and four targets were enriched in the NF-κB pathway (SYK, PARP1, PTGS2, RELA). Western blot validated that isorhamnetin inhibited the phosphorylation of PI3K and AKT and down-regulated the expression of NF-κB p65. It indicated that isorhamnetin could inhibit the PI3K/AKT/NF-κB signaling pathway to reduce the levels of renal inflammatory factors (TNF-α, IL-β and IL-6) and ultimately ameliorate the hyperuricemia-induced renal inflammation in mice. This study will provide comprehensive and penetrating theoretical basis for the application of isorhamnetin in the field of functional foods or dietary supplements to improve hyperuricemia.
研究领域:
药理学
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代谢生物学
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分子生物学
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DOI
PubMed
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2023
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IF 4.7
Qian Wu,Wenrui Yang,Yanju Bi,Yujie Yao,Chengzhi Li,Xiaojing Li
Chlorpyrifos (CPF), a widely used organophosphate pesticide that has caused large-scale contamination globally, has become a major concern. Baicalein (BAI), as a flavonoid extract, shows anti-inflammatory as well as antioxidant activities . The kidneys of fish serve to excrete toxins and are major target organs for environmental contaminants. However, it is not obvious whether BAI can counteract the damage caused by CPF exposure to fish kidneys . Therefore, we conducted a 30-day simulation of CPF poisoning and/or BAI treatment by adding 23.2 μg/L CPF to water and/or 0.15 g/kg BAI to feed. In the transmission electron microscopy results, we observed obvious phenomenon of autophagy and apoptosis in the CPF group, and the TUNEL staining and immunofluorescence of LC3B and p62 double-staining results confirmed that CPF induced autophagy and apoptosis in the kidney of common carp . Furthermore, CPF induced the increase of ROS level and inhibition of PI3K and Nrf2 pathways, which in turn triggered oxidative stress , autophagy and apoptosis in carp kidney according to western blot , RT-qPCR and kit assays. However, addition of BAI significantly alleviated oxidative stress , autophagy and apoptosis due to binding to PI3K protein. Additionally, through phylogenetic tree and structural domain analyses, we also found that the binding sites of BAI and PI3K are conserved in a variety of representative species. These results suggest that BAI antagonizes CPF-caused renal impairments in carp involving the PI3K/AKT pathway and the Nrf2 pathway. Our findings provide new insights into the nephrotoxicity effects of CPF and the potential use of BAI as a detoxification agent for CPF intoxication.
研究领域:
环境毒理学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
TISSUE & CELL
·
2023
·
IF 2.6
Ying Wang,Yongjun Li,Dongxia Liu
Background This study aimed to investigate role of erythropoietin in atherosclerosis and explore whether underlying mechanism is associated with PI3K/AKT/mTOR pathway. Methods High-fat-diet-induced atherosclerosis model was established in apolipoprotein E knockout mice (C57BL/6 genetic background). Mice were randomly divided into the control group and the EPO group. Hematoxylin-eosin was performed for the determination of atherosclerotic lesions. The expression levels of related proteins were detected by western blot analysis . Results Erythropoietin significantly enhanced the incidence of hemorrhage in atherosclerotic plaques compared with the control group. The proteins’ expression signaling pathways (including PI3K , AKT, and mTOR) and angiogenesis-related proteins (VEGF, COX-2, and HIF-1α) were proved to be up-regulated by erythropoietin. Additionally, erythropoietin significantly enhanced the incidence of hemorrhage in the atherosclerotic plaques compared with the control group. The vitro experiments were conducted in macrophages at 21% O 2 or 1% O 2 . The data showed that expression of p -PI3K, p -AKT, p -mTOR, VEGF, COX-2, and HIF-1α related proteins increased in 1% O 2 group than 21% O 2 group. Moreover, compared with control group, protein expression including p -PI3K, p -AKT, p -mTOR, VEGF, COX-2, and HIF-1α was markedly increased in EPO group, decreased in inhibitors group, and similar results were observed in EPO+ inhibitors group. Conclusion The present study demonstrated that erythropoietin might promote angiogenesis in atherosclerotic vulnerable by activating PI3K/AKT/mTOR signaling pathway in atherosclerotic, providing a novel therapeutic target for atherosclerotic targeted therapy.
研究领域:
心血管疾病
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分子生物学
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病理学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Tong Liu,Siqing Fan,Pengfei Meng,Mingxia Ma,Yanxin Wang,Jiaojiao Han,Yufei Wu,Xiao Li,Xiurong Su,Chenyang Lu
Gut microbiota provides an important insight into clarifying the mechanism of active substances with low bioavailability, but its specific action mechanism varied case by case and remained unclear. Dihydroquercetin (DHQ) is a bioactive flavonoid with low bioavailability, which showed beneficial effects on colitis alleviation and gut microbiota modulation. Herein, we aimed to explore the microbiota-dependent anticolitis mechanism of DHQ in sight of gut microbiota metabolites and their interactions with microRNAs (miRNAs). Dietary supplementation of DHQ alleviated dextran sulfate sodium-induced colitis phenotypes and improved gut microbiota dysbiosis. Fecal microbiota transplantation further revealed that the anticolitis activity of DHQ was mediated by gut microbiota. To clarify how the modulated gut microbiota alleviated colitis in mice, the tandem analyses of the microbiome and targeted metabolome were performed, and altered profiles of metabolite short-chain fatty acids (SCFAs) and bile acids and their producers were observed in DHQ-treated mice. In addition, SCFA treatment showed anticolitis activity compared to that of bile acids, along with the specific inhibition on the phosphoinositide-3-kinase (PI3K)-protein kinase B (Akt) pathway. Subsequently, the colonic miRNA profile of mice receiving SCFA treatment was sequenced, and a differentially expressed miR-10a-5p was identified. Both prediction analysis and dual-luciferase reporter assay indicated that miR-10a-5p directly bind to the 3′-untranslated regions of gene pik3ca, inhibit the PI3K-Akt pathway activation, and lead to colitis alleviation. Together, we proposed that gut microbiota mediated the anticolitis activity of DHQ through the SCFAs/miR-10a-5p/PI3K-Akt axis, and it provided a novel insight into clarifying the microbiota-dependent mechanism via the interaction between metabolites and miRNAs.
研究领域:
微生物学
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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
FOOD AND CHEMICAL TOXICOLOGY
·
2023
·
IF 4.3
Eun-Ji Han,Eun-Young Choi,Su-Ji Jeon,Sang-Woo Lee,Jun-Mo Moon,Soo-Hyun Jung,Bumseok Kim,Sung-Dae Cho,Jeong-Seok Nam,Changsun Choi,Jeong-Hwan Che,Ji-Youn Jung
Natural products are continuously being researched to develop safe and effective treatment options for cervical cancer , the fourth most common cancer in women. Piperlongumine (PL), an amide alkaloid mainly present in long pepper , exhibits neuroprotective and anti-cancer properties. However, the specific effect of PL in cervical cancer and the relationship between the anti-cancer pathway and autophagy remain unclear. Therefore, we aimed to investigate PL-induced apoptosis in KB human cervical cancer cells and the relationship between apoptosis and autophagy therein. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and wound-healing assays showed that PL treatment suppressed KB cell viability and proliferation. Apoptosis was identified through 4′,6-diamidino-2-phenylindole and annexin V-propidium iodide staining, increased cleaved-poly (ADP-ribose) polymerase and Bcl-2 associated X levels, and decreased B cell lymphoma 2 levels. Acridine orange staining and increased microtubule-associated protein 1A/1B-light chain 3-II and Beclin-1 levels confirmed autophagy. We determined that KB cell-related autophagy exerted cytoprotective effects using the autophagy inhibitors 3-methyladenine and hydroxychloroquine . PL treatment promoted apoptosis by inhibiting the phosphatidylinositol-3-kinase (PI3K)/protein kinase B/mammalian target of rapamycin pathway in KB cells; inhibiting the pathway using PI3K inhibitors increased autophagy. We suggest that PL is a potential natural anticancer agent for cervical cancer treatment.
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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天然产物化学
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DOI
PubMed
高影响因子
Advanced Therapeutics
·
2019
·Vol. 2
·期 5
·1800136
·
IF 0
Yalu Zou,Yuanyuan Wang,Shengsheng Zhang,Yuntang Wu,Xiaofei Liu
Islet β cell failure is a critical metabolic disorder in the development of type 2 diabetes (T2DM), and the decreased viability and dysfunction of β cells accelerate diabetic pathogenesis in association with higher mortality. In this study, the therapeutic effects of chitooligosaccharide biguanide (COSG), which is similar in structure to metformin and has negligible side effects, on islet β-cell dysfunction and the possible mechanism are explored. Streptozocin-induced diabetic rats are administered COSG via daily intragastric gavage for 8 weeks. COSG significantly controlled body weight loss, attenuated glucose levels in blood and urine, and increased serum insulin. Histological examination of the pancreas reveals that COSG also alleviated pancreatic atrophy in T2DM rats. Furthermore, COSG stimulated insulin receptor substrate-2 (IRS-2) signaling in rat islet β cells, thereby mediating the activation of the phosphatidylinositol 3 kinase/protein kinase (PI3K/Akt) signaling pathway. In addition, COSG promoted downstream forkhead transcription factor O1 (FoxO1) nuclear output to potentially activate pancreas duodenum homeobox-1 (PDX-1)/glucose transporter type-2 (GLUT-2)/glucose kinase (GCK) pathway-regulated insulin secretion. COSG also inhibited the glycogen synthase kinase-3β (GSK-3β)/caspase-3 pathway to prevent cell apoptosis. The intrinsic protective effects of COSG on the impaired insulin signaling system to delay β-cell apoptosis, increase β-cell growth and proliferation, improve β-cell function and promote insulin secretion highlight the possibilities of COSG as a novel strategy for the prevention of T2DM.
研究领域:
医学
·
内分泌学
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产品关联
DOI
ANTI-CANCER DRUGS
·
2021
·Vol. 32
·期 7
·727
·
IF 2.248
Zhang Zuo-yan,Dong Shu-min,Liu Ye-han,Zhang Man-man,Zhang Jian-kang,Zhu Hua-jian,Shao Jia-an,Liu Hua-qing,Li Yang-ling,Zhang Chong,Zeng Ling-hui
Vinpocetine is widely used to treat cerebrovascular diseases. However, the effect of vinpocetine to treat hepatocellular carcinoma (HCC) has not been investigated. In this study, we revealed that vinpocetine was associated with antiproliferative activity in HCC cells, but induced cytoprotective autophagy, which restricted its antitumor activity. Autophagy inhibitors improved the antiproliferative activity of vinpocetine in HCC cells. Sorafenib is effective to treat advanced HCC, but the effect of autophagy induced by sorafenib is indistinct. We demonstrated vinpocetine plus sorafenib suppressed the cytoprotective autophagy activated by vinpocetine in HCC cells and significantly induced apoptosis and suppressed cell proliferation in HCC cells. In addition, vinpocetine plus sorafenib activates glycogen synthase kinase 3β (GSK-3β) and subsequently inhibits cytoprotective autophagy induced by vinpocetine in HCC cells. Meanwhile, overexpression of GSK-3β was efficient to increase the apoptosis induced by vinpocetine plus sorafenib in HCC cells. Our study revealed that vinpocetine plus sorafenib could suppress the cytoprotective autophagy induced by vinpocetine and subsequently show synergistically anti-HCC activity via activating GSK-3β and the combination of vinpocetine and sorafenib might reverse sorafenib resistance via the PI3K/protein kinase B/GSK-3β signaling axis. Thus, vinpocetine may be a potential candidate for sorafenib sensitization and HCC treatment, and our results may help to elucidate more effective therapeutic options for HCC patients with sorafenib resistance.
研究领域:
肿瘤学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Molecular Biosciences
·
2025
·
IF 4
Li Ji,Anqi Deng,Huiying Chen,Shuangyan Guo,Pingyu Wang,Ruiyi Zhang,Wenyang Chen,Taotao Fan,Lijuan Jiang,Bing Shen
Introduction BaoTaiyin (BTY) is a traditional Chinese medicine decoction. It has been used to treat recurrent miscarriage (RM). However, there are no comprehensive systematic studies to identify the chemical compositions of BTY and molecular mechanisms on RM. Finding the chemical components of BTY and clarifying the underlying processes in the treatment of RM were the goals of the study. Methods We used ultra-high-performance liquid chromatography coupled with triple quadruple time-of-flight tandem mass spectrometry to analyze the chemical components of BTY, network analysis to predict the pharmacological effects of the identified active ingredients, and cell experiments to identify potential molecular mechanisms. Results We found 12 active ingredients among 61 components identified in BTY. These identified activities were linked to regulatory effects on 127 key signaling pathways, targeting 107 proteins. Through network analysis, we determined that insulin-like growth factor 1 receptor, matrix metalloproteinases, PI3K, and STAT3 may be the core targets of BTY’s therapeutic effects on RM. We further explored this mechanism to find that aqueous extracts of BTY significantly enhanced IGFBP2 and CaMKK2 expression and trophoblast proliferation, whereas inhibitors of IGF1R/PI3K/AKT pathway or CaMKK2 blocked the effect of BTY on trophoblast proliferation. In addition, IGFBP2 siRNA suppressed BTY-induced CaMKK2 expression. Caffeic acid, as one of components of BTY, increased intracellular Ca 2+ concentration and proliferation in trophoblast. Conclusion Our research showed that BTY may have therapeutic benefits on RM through multiple targets and pathways, such as the IGF1R/PI3K/AKT and Ca 2+ /calmodulin signaling pathways.
研究领域:
中药学
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分子生物学
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生殖医学
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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）