RSC Advances
·
2018
·Vol. 8
·期 43
·24470-24476
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IF 2.936
Xiaofang Chen,Jianyang Tan,Lu Zhang,Yonggang Liu,Yahong Cheng,Qianying Zhang,Hong Ding
The abuse of fructose in daily diet may cause cardiovascular diseases that seriously threaten human health, and both safe and efficient solutions need to be developed. We investigated whether apigenin can prevent the harmful impact of excessive fructose on cardiovascular events. Based on the reduction of percentage of body fat and systolic pressure as well as the improvements in insulin resistance, lipid metabolism, and pathological injury to the thoracic aorta, we suggested that high levels of fructose cause vascular injury and metabolic disorders, which can be improved to some extent by using apigenin. Fundamentally, apigenin down-regulates levels of phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and glucose transporter 1 (GLUT1), which increase with high concentrations of fructose. Moreover, the inflammation and asymmetric dimethylarginine (ADMA) levels increased in fructose group, but they decreased when the rats were fed with apigenin. The results suggest that PI3K/AKT/GLUT1 may have potential for alleviating cardiovascular injury, and apigenin can be an excellent candidate for supplements to ameliorate cardiovascular diseases related to high fructose consumption.
研究领域:
药理学
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心血管疾病
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代谢
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营养学
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PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2025
·
IF 4.7
Ming Luo,Yawei Du,Xuanchen Liu,Shuwen Zhang,Wenwen Zhu,Kaipeng Liu,Xiubao Ren,Ningning Zhang
Background Portal hypertension (PHT) is a severe complication of liver cirrhosis, with limited therapeutic options. Despite emerging evidence linking gut microbiota dysbiosis to PHT progression, the mechanisms by which microbial metabolites modulate liver sinusoidal endothelial cells (LSECs) dysfunction and the therapeutic efficacy of fecal microbiota transplantation (FMT) remain poorly understood. This study investigated the potential of FMT to alleviate PHT in cirrhotic rats, exploring the underlying mechanisms involving butyrate-mediated HDAC3 inhibition and PI3K/Akt/eNOS signaling regulation in LSECs. Methods Cirrhosis with PHT was induced in Sprague-Dawley rats via intraperitoneal carbon tetrachloride injection, followed by FMT or butyrate supplementation via oral gavage. Analyses included portal hemodynamic measurements, gut microbiota sequencing, serum SCFA metabolomics profiling, HDAC3 activity assays, NO level quantification, and assessments of liver fibrosis, liver function, and LSEC ultrastructure. LSECs were isolated for PI3K/Akt/eNOS signaling analysis via qRT-PCR, Western blotting, and immunofluorescence staining. Results A two-week FMT intervention in cirrhotic rats with PHT enriched butyrate-producing bacteria and increased serum butyrate levels, which were associated with reduced portal pressure and intrahepatic vascular resistance, without affecting liver fibrosis, function, or LSEC ultrastructure. FMT reduced HDAC3 activity by 2.17-fold and increased Akt and eNOS phosphorylation in primary LSECs by 1.69-fold and 1.25-fold, respectively, elevating plasma NO levels by 1.66-fold compared to untreated controls. In vitro experiments with primary LSECs confirmed these butyrate-mediated effects. Conclusion FMT alleviates cirrhotic PHT through butyrate-mediated HDAC3 inhibition and subsequent PI3K/Akt/eNOS signaling activation in LSECs, highlighting the therapeutic potential of targeting the gut-liver axis via microbial metabolites for PHT management.
研究领域:
医学
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分子生物学
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PubMed
高影响因子
JOURNAL OF DERMATOLOGICAL TREATMENT
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2020
·
IF 2.156
Yifeng Xiao
Background This study explored the function and mechanism of miR-486-5p in HSFBs.Methods Qualitative real-time-polymerase chain reaction (qRT-PCR) was performed to detect the expression of miR-486-5p in HS and hypertrophic scar fibroblasts (HSFBs). Viability, migration, invasion ability, apoptosis, and expressions of Collagen I, Collagen III, α-SMA and Cleaved caspase-3 in HSFBs after transfection with miR-486-5p mimic or inhibitor were measured by CCK-8, wound-healing, transwell, and Western blot, respectively. Interaction between miR-486-5p and IGF1 was predicted by Targetscan version 7.2 and further confirmed by dual-luciferase assay, and functional rescue experiments were conducted to verify the predicted molecular mechanism. The activation of PI3K/AKT pathway was also analyzed by Western blot.Results MiR-486-5p was low-expressed in HS and HSFBs, and that overexpression of miR-486-5p suppressed the viability, migration, invasion, and expressions of Collagen I, Collagen III, and α-SMA of HSFBs, meanwhile, it also promoted apoptosis and Cleaved caspase-3 expression in HSFBs. Moreover, IGF1 was targeted by miR-486-5p, and increased viability, migration, invasion, and collagens expressions, the activation of PI3K/Akt pathway, and decreased apoptosis and Cleaved caspase-3 induced by miR-486-5p inhibitor could be partly alleviated by siIGF1.Conclusions Overexpressed miR-486-5p inhibited the hyperproliferation and excessive production of collagen in HSFBs via IGF1/PI3K/AKT pathway.
研究领域:
分子生物学
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细胞生物学
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皮肤病学
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PubMed
高影响因子
PHYTOMEDICINE
·
2019
·
IF 4.18
Jun-Shan Liu,Chu-Ying Huo,Hui-Hui Cao,Chun-Lin Fan,Jian-Yang Hu,Li-Juan Deng,Zi-Bin Lu,Hua-Yi Yang,Lin-Zhong Yu,Zhi-Xian Mo,Zhi-Ling Yu
Background Hepatocellular carcinoma (HCC) ranks third among the most common causes of cancer-related deaths worldwide. The chemotherapy for HCC is still insufficient, so far. In searching for effective anti-HCC agents from traditional Chinese medicine , we discovered that aloperine (ALO), a quinolizidine alkaloid from Sophora alopecuroides L., exerts anti-HCC activities. However, the effects of ALO on HCC have been rarely studied, and its underlying mechanisms remain unknown. Purpose This study aims to evaluate the anti-HCC activities of ALO and explore its underlying mechanisms. Methods MTT assay and colony formation assay were used to investigate the anti-proliferative effects of ALO on human HCC Hep3B and Huh7 cells. Hoechst 33258 staining was used to observe the morphological changes of cells after ALO treatment . Flow cytometry was used to analyze apoptosis induction, the collapse of the mitochondrial membrane potential and cell cycle distribution. Western blotting was used to examine the expression levels of proteins associated with apoptosis and cell cycle arrest , and key proteins in the PI3K/Akt signaling pathway . Small interfering RNA (siRNA) transfection was used to investigate the role of Akt in ALO-induced apoptosis and cell cycle arrest. Zebrafish tumor model was used to evaluate the anti-HCC effects of ALO in vivo. Results ALO inhibited the proliferation of Hep3B and Huh7 cells. ALO induced apoptosis in HCC cells, which was accompanied by the loss of mitochondrial potential, the release of cytochrome c into cytosol, as well as the increased cleavages of caspase-9, caspase-3 and PARP . Moreover, ALO induced G2/M cell cycle arrest by downregulating the expression levels of cdc25C, cdc2 and cyclin B1 . In addition, ALO inhibited activation of the PI3K/Akt signaling pathway by decreasing the expression levels of p110α , p85, Akt and p-Akt (Ser473) . Further study showed that inhibition of Akt by siRNA augmented ALO-mediated apoptosis and G2/M cell cycle arrest in HCC cells. Critically, ALO inhibited the growth of Huh7 cells in vivo. Conclusion We first demonstrated that ALO induced apoptosis and G2/M cell cycle arrest in HCC cells through inhibition of the PI3K/Akt signaling pathway. This study provides a rationale for ALO as a potential chemotherapeutic agent for HCC.
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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细胞生物学
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PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2023
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IF 5.4
Yong-Yu Yang,Jing-Jing Qi,Si-Yi Jiang,Ling Ye
Ethnopharmacological relevance Cortex fraxini (also known as qinpi)—the bark of Fraxinus rhynchophylla Hance (Oleaceae)—is widely used as a Chinese traditional medicinal for its anti-inflammatory and anti-hyperuricemic activities. Aim of the study Obesity-induced insulin resistance (IR) is driving the rising incidence of type 2 diabetes mellitus and is related to pathological adipose tissue remodeling. Esculin, a major active component of Cortex fraxini , has anti-diabetic effects. However, whether esculin improves obesity-induced IR by regulating adipose tissue remodeling is unclear. The aims of the present study were to assess the effects of esculin on obesity-induced IR and to explore the underlying mechanisms. Materials and methods Obese IR C57BL/6J mice were treated with esculin (40 or 80 mg/kg/day) for 4 weeks. Oral glucose tolerance tests were used to assess insulin sensitivity. Histological analyses were performed to analyze the number and size distribution of adipocytes. Glucose uptake was assessed using 2-NBDG. Results Esculin had no effect on body weight gain but reduced fasting blood glucose, improved oral glucose tolerance, and increased insulin sensitivity. Esculin reduced adipocyte size and the expression levels of collagen 4A1 and tumor necrosis factor α and increased the number of adipocytes and the expression of vascular endothelial growth factor A. Esculin promoted the differentiation of 3T3-L1 cells and upregulated the mRNA expression of CCAAT/enhancer-binding protein α and peroxisome proliferator-activated receptor-γ, activated the insulin receptor substrate 1 (IRS1)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, and enhanced the translocation of glucose transporter type 4 (GLUT4) and glucose uptake in adipocytes treated with palmitic acid. Conclusions These data suggest that esculin increases insulin sensitivity by improving adipose tissue remodeling and activating the IRS1/PI3K/AKT/GLUT4 pathway.
研究领域:
药理学
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内分泌学
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代谢
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中药
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PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Shuang Chai,Yanbing Yang,Liwei Wei,Yuju Cao,Jiangtao Ma,Xuxia Zheng,Junyan Teng,Na Qin
Background Recently, osteoblast pyroptosis has been proposed as a potential pathogenic mechanism underlying osteoporosis, although this remains to be confirmed. Luteolin (Lut), a flavonoid phytochemical, plays a critical role in the anti-osteoporosis effects of many traditional Chinese medicine prescriptions. However, its protective impact on osteoblasts in postmenopausal osteoporosis (PMOP) has not been elucidated. Purpose This research aimed to determine the effect of Lut in ameliorating PMOP by alleviating osteoblast pyroptosis and sustaining osteogenesis. Study design This research was designed to investigate the novel mechanism of Lut in alleviating PMOP both in cell and animal models. Methods Ovariectomy-induced PMOP models were established in mice with/without daily gavaged of 10 or 20 mg/kg body weight Lut. The impact of Lut on bone microstructure, metabolism and oxidative stress was evaluated with 0.104 mg/kg Estradiol Valerate Tablets daily gavaged as positive control. Network pharmacological analysis and molecular docking were employed to investigate the mechanisms of Lut in PMOP treatment. Subsequently, the impacts of Lut on the PI3K/AKT axis, oxidative stress, mitochondria, and osteoblast pyroptosis were assessed. In vitro, cultured (MC3T3-E1(14) cells were exposed to H 2 O 2 with/without Lut to examine its effects on the PI3K/AKT signaling pathway, osteogenic differentiation, mitochondrial function, and osteoblast pyroptosis. Results Our findings demonstrated that 20 mg/kg Lut, similar to the positive control drug, effectively reduced systemic bone loss and oxidative stress, and enhanced bone metabolism induced by ovariectomy. Network pharmacological analysis and molecular docking indicated that the PI3K/AKT axis was a potential target, with oxidative stress response and nuclear membrane function being key mechanisms. Consequently, the effects of Lut on the PI3K/AKT axis and pyroptosis were investigated. In vivo data revealed that the PI3K/AKT axis was deactivated following ovariectomy, and Lut restored the phosphorylation of key proteins, thereby reactivating the axis. Additionally, Lut alleviated osteoblast pyroptosis and mitochondrial abnormalities induced by ovariectomy. In vitro, Lut intervention mitigated the inhibition of the PI3K/AKT axis and osteogenesis, as well as H 2 O 2 -induced pyroptosis. Furthermore, Lut attenuated ROS accumulation and mitochondrial dysfunction. The effects of Lut, including osteogenesis restoration, anti-pyroptosis, and mitochondrial maintenance, were all reversed with LY294002 (a PI3K/AKT pathway inhibitor). Conclusion In summary, Lut could improve mitochondrial dysfunction, alleviate GSDME-mediated pyroptosis and maintain osteogenesis via activating the PI3K/Akt axis, offering a new therapeutic strategy for PMOP.
研究领域:
药理学
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骨生物学
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细胞信号传导
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骨质疏松研究
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PubMed
高影响因子
International Journal of Biological Sciences
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2021
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IF 6.582
Deng-Pan Wu,Yan Zhou,Li-Xiang Hou,Xiao-Xiao Zhu,Wen Yi,Si-Man Yang,Tian-Yu Lin,Jin-Lan Huang,Bei Zhang,Xiao-Xing Yin
Tamoxifen (TAM) resistance has indicated a significant challenge during endocrine therapy for hormone-sensitive breast cancer. Thus, it is significant to elucidate the molecular events endowing TAM resistance to endocrine therapy. In this study, we found that epithelial-mesenchymal transition (EMT) was an important event to confer TAM resistance, and attenuating EMT by elevating connexin (Cx) 43 expression could reverse TAM resistance. Specifically, Cx43 overexpression improved TAM sensitivity, while Cx43 depletion facilitated TAM insensitivity by modulating EMT in T47D TAM-resistant and -sensitive cells, and transplanted xenografts. Importantly, we found a novel reciprocal regulation between Cx43 and c-Src/PI3K/Akt pathway contributing to EMT and TAM resistance in breast cancer. Moreover, we identified that Cx43 deficiency was significantly correlated with poor relapse-free survival in patients undergoing TAM treatment. Therefore, Cx43 represents a prognostic marker and an attractive target for breast cancer treatments. Therapeutic strategies designed to increase or maintain Cx43 function may be beneficial to overcome TAM resistance.
研究领域:
肿瘤学
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分子生物学
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癌症治疗
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PubMed
高影响因子
CELLULAR SIGNALLING
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2024
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IF 4.4
Xin Chen,Liming Yu,Shan Meng,Jikai Zhao,Xinyi Huang,Zhishang Wang,Zijun Zhou,Yuting Huang,Tao Hong,Jinfeng Duan,Tong Su,Zijun Cao,Yanbang Chi,Tao Huang,Huishan Wang
Inflammation and infiltration of immune cells are intricately linked to the pathogenesis of atrial fibrillation (AF). Triggering receptor expressed on myeloid cells-1 (TREM-1), an enhancer of inflammation, is implicated in various cardiovascular disorders. However, the precise role and potential mechanisms of TREM-1 in the development of AF remain ambiguous. Atrial samples from patients with AF were used to assess the expression levels of TREM-1. An angiotensin II (Ang II)-induced AF mouse model was established to assess the functionality of TREM-1. Cardiac function and AF inducibility were assessed through echocardiography, programmed transvenous cardiac pacing, and atrial electrophysiological mapping. Peripheral blood and atrial inflammatory cells were assessed using flow cytometry. Using histology, bulk RNA sequencing, biochemical analyses, and cell cultures, the mechanistic role of TREM-1 in AF was elucidated. TREM-1 expression was upregulated and co-localized with macrophages in the atria of patients with AF. Pharmacological inhibition of TREM-1 decreased Ang II-induced atrial enlargement and electrical remodeling. TREM-1 inhibition also ameliorated Ang II-induced NLRP3 inflammasome activation, inflammatory factor release, atrial fibrosis, and macrophage infiltration. Transcriptomic analysis revealed that TREM-1 modulates Ang II-induced inflammation through the PI3K/AKT/FoxO3a signaling pathway. In vitro studies further supported these findings, demonstrating that TREM-1 activation exacerbates Ang II-induced inflammation, while overexpression of FoxO3a counteracts this effect. This study discovered the critical role of TREM-1 in the pathogenesis of AF and its underlying molecular mechanisms. Inhibition of TREM-1 provides a new therapeutic strategy for the treatment of AF.
研究领域:
心脏病学
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免疫学
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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
FOOD RESEARCH INTERNATIONAL
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2025
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IF 8
Mingxiu Long,Hui Wang,Fang Zhang,Yaoqi Ran,Yongfu Li,Jingwen Luo,Zhaojun Chen,Zhuxi Tian,Shuming Tan,Xiong Liu
Rosa roxburghii Tratt fruit polyphenols (RP) possess antioxidant, anti-inflammatory, and immunomodulatory properties, showing potential for ulcerative colitis (UC) treatment. However, their efficacy is limited by bioavailability and targeting efficiency. To address this, RP were encapsulated into acylated chitosan-crosslinked carboxymethyl konjac glucomannan (ACs-CKGM) nanogel (RPNG). Experimental results demonstrated that RPNG significantly enhanced intestinal barrier function by upregulating tight junction proteins (ZO-1, Occludin and Claudin-3) and mucus secretion (MUC2). It effectively mitigated oxidative stress by restoring antioxidant enzymes (SOD, GSH-Px and CAT) while reducing MPO, COX-2 and iNOS activation. Through integrated ELISA, western blot, and transcriptomic analyses, we emonstrated that RPNG specifically inhibited PI3K/Akt/mTOR and NF-κB signaling pathways, decreasing inflammatory cytokines (e.g., TNF-α, IL-6) while increasing anti-inflammatory mediators (e.g., IL-10). Gut microbiome analysis showed RPNG reversed DSS-induced dysbiosis by enriching beneficial bacteria (e.g., Muribaculum sp.) and suppressing pathogens (e.g., Escherichia coli ). These findings highlight RPNG as a novel targeted strategy for UC management, supported by multi-omics mechanistic insights.
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高影响因子
PHYTOTHERAPY RESEARCH
·
2021
·Vol. 35
·期 10
·5767-5780
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IF 5.882
Lin Zhu,Zhenchao Liu,Yuqian Ren,Xiaolin Wu,Yingjuan Liu,Tingting Wang,Yizhao Li,Yusheng Cong,Yunliang Guo
Studies have found that salidroside, isolated from Rhodiola rosea L , has various pharmacological activities, but there have been no studies on the effects of salidroside on brain hippocampal senescence. The purpose of this study was to investigate the mechanistic role of salidroside in hippocampal neuron senescence and injury. In this study, long-term cultured primary rat hippocampal neurons and naturally aged C57 mice were treated with salidroside. The results showed that salidroside increased the viability and MAP2 expression, reduced β-galactosidase (β-gal) levels of rat primary hippocampal neurons. Salidroside also improved cognition dysfunction in ageing mice and alleviated neuronal degeneration in the ageing mice CA1 region. Moreover, salidroside decreased the levels of oxidative stress and p21, p16 protein expressions of hippocampal neurons and ageing mice. Salidroside promoted telomerase reverse transcriptase (TERT) protein expression via the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway. In conclusion, our findings suggest that salidroside has the potential to be used as a therapeutic strategy for anti-ageing and ageing-related disease treatment.
研究领域:
神经科学
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药理学
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衰老研究
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分子生物学
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PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
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2025
·Vol. 29
·期 15
·e70744
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IF 4.2
Xuan Li,Shiyu Meng,Jiayi Liu,Meixian Sun,Mao Zhou,Fengtao Ji,Yu Hong
In this study, we investigated the therapeutic potential of Berberine (BBR), an anti‐inflammatory agent capable of penetrating the blood–brain barrier, for mitigating postoperative cognitive dysfunction (POCD) in aged mice. BBR was administered at a dose of 10 mg/kg daily for 2 weeks and significantly improved cognitive impairments induced by surgical and anaesthesia‐related factors. Specifically, BBR markedly suppressed glial cell activation and reduced levels of pro‐inflammatory cytokines such as tumour necrosis factor alpha (TNF‐α) and interleukin‐1 beta (IL‐1β). Additionally, it alleviated oxidative stress markers and lipid accumulation. Using network pharmacology analysis, we demonstrated that BBR modulates neuroinflammation, oxidative processes and lipid metabolism by inhibiting the phosphorylation of the phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (Akt) pathway. Furthermore, extended research revealed that BBR upregulated the expression of PPAR‐ γ mRNA, suggesting a neuroprotective mechanism via regulation of the PI3K‐Akt pathway. These findings support the potential application of BBR as a therapeutic agent for managing POCD in elderly populations.
研究领域:
药理学
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神经科学
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老年医学
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分子生物学
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免疫学
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PubMed
高影响因子
Journal of Functional Foods
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2020
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IF 3.701
Fenfen Li,Danfei Huang,Weiyu Yang,Xiaozhen Liu,Shaoping Nie,Mingyong Xie
The preventive role of polysaccharide from the seeds of Plantago asiatica L. (PLCP) against reproductive system injury induced by nonylphenol (NP) was investigated. Male Sprague-Dawley rats were exposed orally to NP 1 h after PLCP intragastric administration continuously for 45 days. The results showed that NP induced significant decrease in relative weight of testes and epididymis, changed testicular histomorphology, and disrupted hormone secretions. Moreover, oxidative stress occurred after NP exposure by overproduction of Malondialdehyde, lipid peroxidation, inducible nitric oxide synthase, and low activities of superoxide dismutase and catalase. Furthermore, the induction of apoptosis and disturbance of PI3K/Akt/mTOR pathway by NP were also proved. Interestingly, PLCP alleviated NP toxicity by improving antioxidant enzymes, recovering hormone secretions, inhibiting apoptosis and autophagy, which involves PI3K/Akt/mTOR pathway. These findings provide a good direction that PLCP may be a good candidate to help body defend against toxic substance, particularly endocrine disrupting chemicals induced reproductive toxicity.
研究领域:
药理学
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毒理学
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生殖生物学
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高影响因子
危险品化学品经营许可证（带存储）