INTERNATIONAL IMMUNOPHARMACOLOGY
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2025
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IF 4.7
Wenyang Zhou,Zhenhao Liu,Xichuan Qiu,Minghao Tian,Baoqiang He,Chao Tang,Qiang Tang,Rupei Ye,Dejun Zhong,Yehui Liao
Following spinal cord injury (SCI), pyroptosis plays a significant role in regulating neuroinflammation during the secondary phase of injury. Although 1,8-cineole possesses anti-inflammatory effects, its role in SCI and underlying molecular mechanisms remains unclear. This study revealed that 1,8-cineole promoted motor function recovery in spinal cord-injured rats, reduced NLRP3 inflammasome-mediated microglial pyroptosis and activation, enhanced neuronal regeneration, and suppressed neuronal apoptosis and glial scar formation. Network pharmacology analysis showed that 1,8-cineole targets the PI3K/AKT and P38 MAPK pathways to inhibit microglial activation and pyroptosis. Finally, using a conditional co-culture system, we demonstrated that 1,8-cineole-treated microglia facilitated neuronal regeneration while inhibiting apoptosis. These findings indicate that 1,8-cineole promotes functional recovery post-SCI by protecting neurons by suppressing microglial pyroptosis and activation through the PI3K/AKT and P38 MAPK axes.
研究领域:
神经科学
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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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神经病学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2019
·
IF 3.571
Yue Gao,Mingwei Zhang,Ruifen Zhang,Lijun You,Tong Li,Rui Hai Liu
The therapeutic benefits of whole grains on diabetes mellitus have been continuously confirmed by in-depth research. To date, limited studies have investigated the effect of extruded products of whole grains on the insulin signaling pathway in vivo. This study investigated the effects of oral consumption of whole grain extrudate, including 97% brown rice and 3% defatted rice bran (w/w, BRD), on glucose metabolism and the hepatic insulin signaling pathway in C57BL/KsJ-db/db mice. BRD treatment induced a remarkable reduction in blood glucose. Moreover, glucose intolerance and insulin resistance were ameliorated in the BRD-treated group compared with those in the db/db control group. BRD also increased the hepatic glycogen content by reducing the expression and increasing the phosphorylation of glycogen synthase kinase 3β (GSK3β). The activities of glucose-6-phosphatase and phosphoenolpyruvate carboxylase and their respective mRNA expression levels in the liver were simultaneously decreased in the BRD-treated group. BRD also significantly upregulated the expression of phosphatidylinositol 3-kinase (PI3K) and increased the phosphorylation of insulin receptor substrate 1 (IRS1) and protein kinase B (AKT). These results indicate that BRD exhibits antidiabetic potential by activating the IRS1/PI3K/AKT signaling pathway, further regulating the expression of the FOXO1 gene and p-GSK3β protein, thus inhibiting hepatic gluconeogenesis, increasing hepatic glycogen storage, and improving insulin resistance. Therefore, BRD could be used as a functional ingredient to alleviate the symptoms of hyperglycemia.
研究领域:
营养学
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内分泌学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
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IF 8.5
Mengxiang Chen,Yi Peng,Rongtao Zhu,Xiaoting Luo,Xuemin Yang,Jiazhi Chen,Haiyan Chen,Wei Zhou,Zhiyun Du
Psoriasis is a chronic inflammatory skin disease with significant impacts on quality of life. Current treatments face challenges like high costs and side effects. This study explores the therapeutic potential of Rosa rugosa polysaccharide (RRPS) and its nanofiber membrane in psoriasis treatment. RRPS was extracted using a yeast fermentation enzyme-assisted method and characterized. In vitro studies on RAW264.7 macrophages showed that RRPS significantly reduced nitric oxide (NO) production, indicating anti-inflammatory effects. The nanofiber membrane, fabricated via electrospinning, has high porosity and sustained-release properties, enhancing drug delivery and skin barrier repair. In vivo studies using an imiquimod-induced psoriasis mouse model demonstrated that both RRPS and its nanofiber membrane improved psoriasis symptoms, reduced transepidermal water loss (TEWL), and inhibited pro-inflammatory cytokines (e.g., TNF-α, IL-6, IL-17A). Mechanistically, they suppressed the PI3K-AKT/mTOR pathway. The nanofiber membrane showed superior efficacy compared to RRPS alone, highlighting the benefits of electrospinning. This study suggests that Rosa rugosa polysaccharide and its nanofiber membrane could be a novel, effective, and safe alternative for psoriasis treatment by targeting the PI3K-AKT/mTOR pathway.
研究领域:
皮肤病学
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药理学
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纳米技术
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免疫学
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生物技术
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生物化学
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DOI
PubMed
高影响因子
Chemical Biology & Drug Design
·
2024
·Vol. 104
·期 4
·e70003
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IF 3.2
Xiang Yu,Di Zhang,Chengming Hu,Zejun Yu,Yang Li,Cheng Fang,Yinsheng Qiu,Zhinan Mei,Lingyun Xu
Hepatocellular carcinoma (HCC) is the sixth most prevalent malignant tumor. Hepatocellular carcinogenesis is closely linked to apoptosis, autophagy, and inflammation. Diosmetin and chrysin, are two flavonoid compounds, exhibit anti-inflammatory and anticancer properties. In this study, the TCGA database was utilized to identify differentially expressed genes between normal subjects and HCC patients. Molecular docking and molecular dynamics analyses were employed to assess the binding affinity of chrysin and diosmetin to key proteins in the PI3K/AKT/mTOR/NF-κB signaling pathway. Western blotting and RT-qPCR were used to measure the protein and gene expression within this pathway. The results indicated that HCC patients had elevated levels of PI3K, AKT, mTOR, and P65 proteins compared to normal subjects, which adversely affected patient survival. Molecular docking and dynamics studies demonstrated that diosmetin and chrysin are effectively bound to these four proteins. In vitro experiments revealed that the combination of diosmetin and chrysin could induce apoptosis, enhance autophagy, reduce inflammatory mediator production, and improve the tumor cell microenvironment by inhibiting the PI3K/AKT/mTOR/NF-κB signaling pathway. Notably, the synergy score for the combination of diosmetin (25 μM) and chrysin (10 μM) was 16. Thus, the diosmetin–chrysin combination shows promise as an effective therapeutic approach for hepatocellular carcinoma due to its strong synergistic effect.
研究领域:
肿瘤学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR ENDOCRINOLOGY
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2025
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IF 3.6
Lei Wei,Zonggang Feng,Qian Dou,Genhong Mao,Hu Zhao,Xinghua Zhao,Bin Hao
Male reproductive disorders are responsible for approximately 50% of infertility cases. Bis (2-ethylhexyl) phthalate (DEHP) is a common environmental pollutant known for its reproductive toxicity. Oxidative stress is a key mechanism in response to DEHP exposure. Glutathione S-transferase A2 (GSTA2), a member of the glutathione S-transferase family, has the capacity to detoxify environmental toxins. However, its role in regulating DEHP-induced male reproductive disorders remains unexplored. Next, male mice aged 3 weeks were orally administered with DEHP (500 mg/kg/day) for 14 days to induce male reproductive disorders. We observed a decrease in the GSTA2 expression in the testicular tissues of DEHP-treated mice. To investigate the role of GSTA2 in DEHP exposure, lentiviral vectors carrying GSTA2 sequences (1 × 10 7 TU/mL, 20 μL) were given to mice on the first day of DEHP treatment. GSTA2 overexpression was found to alleviate testicular damage induced by DEHP, as well as to inhibit oxidative stress and subsequent cell apoptosis. In addition, the PI3K/AKT signaling pathway, which is associated with oxidative stress and DEHP exposure, was activated in DEHP-exposed mice following GSTA2 overexpression. Subsequently, mouse spermatocyte GC-2spd cells with DEHP treatment were used to mimic male reproductive disorders in vitro . Consistently, the GSTA2 expression was decreased in GC-2spd cells with DEHP treatment. GSTA2 overexpression inhibited oxidative stress and cell apoptosis in DEHP-treated GC-2spd cells by activating the PI3K/AKT signaling pathway. Moreover, we discovered that GSTA2 overexpression significantly altered the metabolic profiles of DEHP-treated GC-2spd cells. Collectively, our results suggest that GSTA2 overexpression alleviates DEHP-induced male reproductive disorders by suppressing oxidative stress-mediated cell apoptosis via the PI3K/AKT signaling pathway, providing a novel insight into mitigating reproductive toxicity caused by DEHP exposure.
研究领域:
生殖毒理学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
APOPTOSIS
·
2017
·Vol. 22
·期 5
·672-680
·
IF 3.833
Liu Shumin,Sun Zhengwu,Chu Peng,Li Hailong,Ahsan Anil,Zhou Ziru,Zhang Zonghui,Sun Bin,Wu Jingjun,Xi Yalin,Han Guozhu,Lin Yuan,Peng Jinyong,Tang Zeyao
Homocysteine (Hcy) induced vascular endothelial injury leads to the progression of endothelial dysfunction in atherosclerosis. Epigallocatechin gallate (EGCG), a natural dietary antioxidant, has been applied to protect against atherosclerosis. However, the underlying protective mechanism of EGCG has not been clarified. The present study investigated the mechanism of EGCG protected against Hcy-induced human umbilical vein endothelial cells (HUVECs) apoptosis. Methyl thiazolyl tetrazolium assay (MTT), transmission electron microscope, fluorescent staining, flow cytometry, western blot were used in this study. The study has demonstrated that EGCG suppressed Hcy-induced endothelial cell morphological changes and reactive oxygen species (ROS) generation. Moreover, EGCG dose-dependently prevented Hcy-induced HUVECs cytotoxicity and apoptotic biochemical changes such as reducing mitochondrial membrane potential (MMP), decreasing Bcl-2/Bax protein ratio and activating caspase-9 and 3. In addition, EGCG enhanced the protein ratio of p-Akt/Akt, endothelial nitric oxide synthase (eNOS) activation and nitric oxide (NO) formation in injured cells. In conclusion, the present study shows that EGCG prevents Hcy-induced HUVECs apoptosis via modulating mitochondrial apoptotic and PI3K/Akt/eNOS signaling pathways. Furthermore, the results indicate that EGCG is likely to represent a potential therapeutic strategy for atherosclerosis associated with Hyperhomocysteinemia (HHcy).
研究领域:
心血管疾病
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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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DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2017
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IF 4.581
Jinhua Hu,Zhao Mao,Shuangcheng He,Yuanran Zhan,Rui Ning,Wei Liu,Bingfang Yan,Jian Yang
Osteoporosis is a serious public health concern worldwide. Herba epimedii has been used for centuries and even thousands of years to treat osteoporotic conditions. Icariin , a flavonol glycoside , is one of the major active ingredients. In this study, we have shown that icariin protected against glucocorticoid-induced osteoporotic changes in SaoS-2 cells and mice. We have also shown that dexamethasone (a glucocorticoid) suppressed and icariin induced DEC1, a structurally distinct helix-loop-helix protein. DEC1 overexpression promoted whereas DEC1 knockdown decreased osteogenic activity. Likewise, DEC1 overexpression and knockdown inversely regulated the expression of β-catenin and PIK3CA, an essential player in the Wnt/β-catenin and PI3K/Akt signaling pathways, respectively. Interestingly, DKK1, an inhibitor of Wnt/β-catenin signaling inhibitor, and LY294002 , an inhibitor of PI3K/Akt signaling, abolished the induction of DEC1 by icariin. It is established that these two pathways are interconnected by the phosphorylation status of GSK3β. Dexamethasone decreased but icariin increased GSK3β phosphorylation. Finally, DEC1 deficient mice developed osteoporotic phenotypes. Taken together, it is concluded that DEC1 likely supports the action of icariin against glucocorticoid induced osteoporosis with an involvement of the PI3K/Akt/GSK3β/β-catenin integrated signaling pathway.
研究领域:
药理学
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分子生物学
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细胞生物学
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内分泌学
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骨生物学
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DOI
PubMed
高影响因子
Biology-Basel
·
2025
·Vol. 14
·期 9
·1114
·
IF 3.5
Jin Li,Jiawen Wang,Yaodong Li,Jingyi Guo,Ziliang Jin,Shourong Qiao,Yunxia Zhang,Guoyin Li,Huazhen Liu,Changjing Wu
Simple SummaryAlzheimer’s disease is a severe, gradually worsening brain disorder leading to memory loss and dementia, with no effective treatments currently available. In this study, we investigated a natural compound called mulberroside A, derived from the mulberry plant, to determine its potential protective effects against Alzheimer’s disease. Utilizing a mouse model and human brain cells, we discovered that mulberroside A enhanced memory and decreased brain cell damage. Additionally, it increased the levels of crucial brain chemicals, facilitating better communication between nerve cells. Moreover, it alleviated harmful stress in the brain and reduced the formation of two hallmark pathologies: toxic tau protein tangles and amyloid plaques. The compound significantly decreased phosphorylated tau—a key driver of neuronal degeneration—while simultaneously inhibiting amyloid plaque formation. Mulberroside A operated by activating specific neuroprotective pathways that promote brain health, including those that encourage nerve growth. These findings indicate it could serve as a promising new treatment to slow or prevent Alzheimer’s disease by targeting multiple disease mechanisms.Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia, with current therapies offering only limited symptomatic relief and lacking disease-modifying efficacy. Addressing this critical therapeutic gap, natural multi-target compounds like mulberroside A (MsA)—a bioactive glycoside fromMorus albaL.—present promising alternatives. This study investigated MsA’s neuroprotective potential using scopolamine-induced AD-like mice and N2a/APP695swe cells. In vivo, MsA significantly ameliorated cognitive deficits and neuronal loss, concurrently enhancing cholinergic neurotransmission through increased acetylcholine levels and inhibited acetylcholinesterase (AChE)/butyrylcholinesterase (BChE) activities. MsA also upregulated neurotrophic factors (BDNF, CREB) in critical brain regions. In vitro, MsA restored cholinergic function, mitigated oxidative stress, and crucially reduced amyloid-β (Aβ) production by dual regulation of APP processing: promoting the non-amyloidogenic pathway via ADAM10 upregulation and inhibiting the amyloidogenic pathway via suppression of BACE1 and γ-secretase components. Mechanistically, these multi-target benefits were mediated by MsA’s activation of the PI3K/AKT pathway, which triggered downstream inhibitory phosphorylation of GSK3β—directly reduced tau hyperphosphorylation—and activation of CREB/BDNF signaling. Collectively, our findings demonstrate that MsA confers comprehensive neuroprotection against AD pathology by simultaneously targeting cholinergic dysfunction, oxidative stress, Aβ accumulation, tau phosphorylation, and impaired neurotrophic signaling, highlighting its strong therapeutic candidacy.
研究领域:
神经科学
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药理学
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生物化学
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分子生物学
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药物化学
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神经退行性疾病
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产品关联
DOI
PubMed
高影响因子
American Journal of Translational Research
·
2022
·
IF 3.94
Zheng Xu,Luwei Xu,Yuzheng Ge,Hongbin Sun,Jiageng Zhu,Quanliang Dou,Ruipeng Jia
Background: Cabazitaxel has been applied to the treatment of castration-resistant prostate cancer (CRPC), but the molecular mechanism remained to be fully understood. Methods: After treatment with Cabazitaxel alone or in combination with ionizing radiation (IR), CRPC cell viability, proliferation and apoptosis were determined by Cell Counting Kit-8 (CCK-8) assay, colony formation, and flow cytometry, respectively. Tumor volume was measured after the establishment of animal xenograft model. Relative expressions of proteins related to apoptosis (B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and cleaved caspase 3) and phosphoinositide 3-kinase (PI3K)/AKT pathway were measured by Western blot, and the phosphorylated-PI3K/PI3K and p-AKT/AKT ratios were determined as well. Results: Cell viability and proliferation were suppressed, and apoptosis was promoted in CRPC cells after Cabazitaxel treatment alone, accompanied with upregulated expressions of Bax and cleaved caspase 3 and downregulated Bcl-2 expression. Also, a single treatment with Cabazitaxel resulted in suppression of PI3K/AKT pathway activation, along with downregulated expressions of p-PI3K and p-AKT and a reduced ratio of p-PI3K/PI3K to p-AKT/AKT. Meanwhile, Cabazitaxel enhanced the effects of IR on suppressing survival and promoting apoptosis in CRPC cells through downregulating Bcl-2 and upregulating Bax and cleaved caspase 3. However, Cabazitaxel suppressed IR-induced PI3K/AKT pathway activation via downregulating p-PI3K and p-AKT, leading to a reduced ratio of p-PI3K/PI3K to p-AKT/AKT. Furthermore, Cabazitaxel further promoted the effects of IR on suppressing tumor growth in vivo . Conclusion: Cabazitaxel inhibited the proliferation and promoted the apoptosis and radiosensitivity of CRPC cells, which is related to the suppression of PI3K/AKT pathway, providing a therapeutic method for CRPC in clinical practice.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
ACS Omega
·
2024
·
IF 3.7
Hong Duan,Han Li,Tianyi Liu,Yuan Chen,Mengmeng Luo,Ying Shi,Jing Zhou,Marwan M. A. Rashed,Kefeng Zhai,Lili Li,Zhaojun Wei
Atherosclerosis (AS) is a common cardiovascular disease that poses a major threat to health. Schisandra chinensis is a medicinal and edible plant that is commonly used to treat cardiovascular diseases. In this paper, HPLC was used to detect and analyze 5 different components in Schisandra chinensis. Network pharmacological predictions highlight the PI3K/AKT/mTOR pathway as an important pharmacological pathway. The effective ingredient Schisandrin C was screened by the molecular docking technique. ox-LDL-induced HUVECs were used to construct the atherosclerosis model for further experimental verification. The results showed that Schisandrin C interfered with the PI3K/AKT/mTOR autophagy pathway. This study lays a foundation for the further application of Schisandrin C in the prevention and treatment of atherosclerosis in the future.
研究领域:
心血管疾病
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药理学
·
分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2020
·
IF 3.263
Hui Zhang,Junfeng Hui,Jing Yang,Jianjun Deng,Daidi Fan
Eurocristatine (ECT) is an alkaloid isolated from Eurotium cristatum , and it has been used in multiple applications. However, its use as a treatment for type 2 diabetes mellitus (T2DM) has not yet been reported. In this study, we investigated the anti-T2DM effect of ECT and explored its potential molecular mechanism. In vivo , after treatment with ECT (20, 40 mg/kg) for 6 weeks, fasting blood glucose (FBG) was remarkably reduced in db/db mice. Moreover, glucose tolerance, insulin sensitivity and hyperinsulinemia were ameliorated treatment with ECT. The values of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) also showed that ECT could alleviate liver toxicity caused by diabetes in db/db mice. In vitro , ECT (15 and 30 μM) alleviated insulin resistance by increasing glucose consumption, glucose uptake and glycogen content in high glucose-induced HepG2 cells. The Western blotting (WB) results showed that ECT could upregulate the expression of phosphatidylinositol 3-kinase (PI3K), increase the phosphorylation of insulin receptor substrate 1 (IRS1) and protein kinase B (AKT) in vivo and in vitro . Besides, ECT improved the glycogen content by inhibiting the expression of glycogen synthase kinase3β (GSK3β) and promoting that of glycogen synthase (GS). Furthermore, administration of the PI3K/AKT signaling pathway inhibitor LY294002 abolished the beneficial effects of ECT. These findings are the first to verify that ECT has the potential to improve glucose metabolism and alleviate insulin resistance by activating the PI3K/AKT signaling pathway in db/db mice.
研究领域:
药理学
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糖尿病研究
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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 Pharmacology
·
2024
·
IF 4.4
Huang Yuechang,Zhang Xingmin,Li Qian,Zheng Wende,Wu Panpan,Wu Rihui,Chen Wen-Hua,Li Chen
Type 2 diabetes mellitus is regarded as a chronic metabolic disease characterized by hyperglycemia. Long-term hyperglycemia may result in oxidative stress, damage pancreatic β-cell function and induce insulin resistance. Herein we explored the anti-hypoglycemic effects and mechanisms of action of N-p-coumaroyloctopamine (N-p-CO) in vitro and in vivo. N-p-CO exhibited high antioxidant activity, as indicated by the increased activity of SOD, GSH and GSH-Px in HL-7702 cells induced by both high glucose (HG) and palmitic acid (PA). N-p-CO treatment significantly augmented glucose uptake and glycogen synthesis in HG/PA-treated HL-7702 cells. Moreover, administration of N-p-CO in diabetic mice induced by both high-fat diet (HFD) and streptozotocin (STZ) not only significantly increased the antioxidant levels of GSH-PX, SOD and GSH, but also dramatically alleviated hyperglycemia and hepatic glucose metabolism in a dose-dependent manner. More importantly, N-p-CO upregulated the expressions of PI3K, AKT and GSK3β proteins in both HG/PA-induced HL-7702 cells and HFD/STZ-induced mice. These findings clearly suggest that N-p-CO exerts anti-hypoglycemic and anti-oxidant effects, most probably via the regulation of a PI3K/AKT/GSK3β signaling pathway. Thus, N-p-CO may have high potentials as a new candidate for the prevention and treatment of diabetes.
研究领域:
药理学
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内分泌学
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代谢性疾病
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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）