Heliyon
·
2024
·
IF 3.4
Jing Tian,Yun Lu,Qiao-ling Zhao,Qiu-yan Pu,Su Jiang,Yun-ping Tang
To investigate the alleviating effect and mechanism of the docosahexaenoic acid-enriched phosphatidylserine (DHA-PS) on bisphenol A (BPA)-induced liver injury in mice, the murine liver injury model was established by gavage of BPA (5 mg/kg) or co-administration of BPA and DHA-PS (50 mg/kg or 100 mg/kg) for 6 weeks. The results showed that after administration of 100 mg/kg DHA-PS, the liver index, serum levels of AST, ALT, TC, TG, NEFA, and LDL-C in mice were significantly decreased, while HDL-C was significantly increased. The LPS, IL-6, IL-1β, TNF-α, and MDA levels in liver tissues were effectively down-regulated, and IL-10, SOD, GSH-Px, and CAT levels were effectively up-regulated. The H&E and Oil Red O staining results showed that liver damage was notably repaired and lipid deposition was notably reduced after DHA-PS administration. Furthermore, metabolomics and immunohistochemical studies revealed that DHA-PS mainly regulates glycerophospholipid metabolism and the SIRT1-AMPK pathway to improve metabolic disorders of the liver caused by BPA. Therefore, DHA-PS could potentially alleviate BPA-induced murine liver injury through suppressing inflammation and oxidative stress, and modulating lipid metabolism disorders.
研究领域:
毒理学
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肝病学
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代谢组学
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药理学
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2021
·
IF 4.451
Xian Zheng,Xiao-Gai Zhang,Yao Liu,Li-Ping Zhu,Xiao-Shuang Liang,Hui Jiang,Gao-Feng Shi,Yuan-Yuan Zhao,Zhi-Wei Zhao,Yuan Teng,Ke Pan,Jian Zhang,Zhi-Qi Yin
Arjunolic acid (AA), as the most abundant triterpenoid component in Cyclocarya paliurus (Batal) Iljinskaja, previously displayed delipidating effects in free fatty acid (FFA)-induced HepG2 steatosis cells. However, whether AA still possesses the ameliorative effects on nonalcoholic fatty liver disease (NAFLD) in normal hepatocytes and in vivo remains vacant and the detailed mechanisms are not defined. In vitro , AA dose-dependently alleviated lipid accumulation in FFA-challenged primary hepatocytes without cytotoxicity. In vivo , AA showed pleiotropic benefits, including attenuating adiposity, mitigating hepatic steatosis and inflammation, improving lipid disorders and insulin resistance, and restoring the impaired gut barrier. Mechanically, we found that AA indirectly activated Sirt1/AMPK-modulated lipid metabolism through elevating NAMPT-mediated NAD + level, and triggering autophagy, together mediating the lipid-lowering effects. Collectively, our results convey that AA can substantially mitigate NAFLD via indirectly activating Sirt1/AMPK signaling, inducing autophagy and restoring gut barrier, and will be considered as a promising candidate for NAFLD therapy.
研究领域:
药理学
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肝病学
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分子生物学
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营养学
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产品关联
DOI
高影响因子
MOLECULAR BIOLOGY REPORTS
·
2024
·Vol. 51
·期 1
·1-10
·
IF 2.6
Li Zhipeng,Jiao Yang,Wu Zhisong,Liu Haoge,Li Yang,Cai Yaodong,Wei Wan,Cao Fang
Background Idiopathic pulmonary fibrosis (IPF) is a disease of unknown etiology characterized by a constant incidence rate. Unfortunately, effective pharmacological treatments for this condition are lacking and the identification of novel therapeutic approaches and underlying pathological mechanisms are required. This study investigated the potential of quercetin in alleviating pulmonary fibrosis by promoting autophagy and activation of the SIRT1/AMPK pathway. Methods Mouse models of IPF were divided into four treatment groups: control, bleomycin (BLM), quercetin (Q), and quercetin + EX-527 (Q + E) treatment. Pulmonary fibrosis was induced in the mouse models through intratracheal instillation of BLM. Various indexes were identified through histological staining, Western blotting analysis, enzyme-linked immunosorbent assay, immunohistochemistry, and transmission electron microscopy. Results Quercetin treatment ameliorated the pathology of BLM-induced pulmonary fibrosis of mice by reducing α-smooth muscle actin (α-SMA), collagen I (Col I), and collagen III (Col III) levels, and also improved the level of E-cadherin in lung tissue. Furthermore, Quercetin significantly enhanced LC3II/LC3I levels, decreased P62 expression, and increased the number of autophagosomes in lung tissue. These effects were accompanied by the activation of the SIRT1/AMPK pathway. Treatment with EX-527, an inhibitor for SIRT1, reversed all effects induced by quercetin. Conclusion This study showed that quercetin could alleviate pulmonary fibrosis and improve epithelial-mesenchymal transition by acting on the SIRT1/AMPK signaling pathway, which may be achieved by regulating the level of autophagy.
研究领域:
药理学
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病理学
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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
LIFE SCIENCES
·
2020
·
IF 3.647
Yaoxiang Zhu,Ruijue Liu,Zhenglin Shen,Guoqiang Cai
Aim Luteolin and lycopene are common natural products, widely existing in nature, and both of which were reported to have various biological functions including anti-inflammatory, anti-obesity and anti-NAFLD. In the present study, we aimed to evaluate the therapeutic efficacy of luteolin and lycopene in combination and its latent molecular mechanisms in vitro and in vivo models of NAFLD. Main methods Sodium palmitate (PA)-induced steatotic HepG2 cells and primary hepatocytes, and high-fat diet-induced C57BL/6J obese mice were treated with luteolin, lycopene and their combination. Metabolic parameters were measured. Key findings We found that luteolin (20 μM) + lycopene (10 μM) was the best therapeutic combination in PA-induced HepG2 cells, and significantly improve cell viability and lipid accumulation in PA-induced HepG2 cells and primary hepatocytes. In addition, luteolin (20 mg/kg) + lycopene (20 mg/kg) could ameliorate increased body weight and hepatocyte steatosis; regulate serum triglycerides, serum total cholesterol, hepatic triglycerides and hepatic total cholesterol; decrease serum alanine transaminase and aspartate transaminase. Furthermore, in vivo and in vitro, luteolin, lycopene and their combination had no effect on Sirt1 expression, but all of them could upregulate the expression of NAMPT, which could increase the level of NAD+, the co-substrate of Sirt1, indirectly activating Sirt1/AMPK pathway, and then inhibited lipogenesis and increased β-oxidation, defensing the “first hit”; they also inactivated nuclear factor-κB (NF-κB) and decreased the levels of IL-6, IL-1β and TNF-α, defensing the “second hit”. Significance Thus, luteolin and lycopene in combination can effectively ameliorate “two-hit” in NAFLD through activation of the Sirt1/AMPK 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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代谢
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营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Ginseng Research
·
2026
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IF 5.6
Hongbo Zhu,Hang Li,Yinong Shi,Jinhui Liu,Hua Zhi,Xuelu Zhao,Zhiwen Wang,Fumin Ping
Background Pressure injuries (PIs) remain a therapeutic challenge due to persistent inflammation and ferroptosis-driven tissue damage. Ginsenoside Rb1, a key bioactive component of Panax ginseng, demonstrates anti-inflammatory and anti-ferroptotic properties, but its clinical application is limited by poor bioavailability and rapid degradation in wound environments. Purpose This study aimed to develop a chitosan/alginate nanocomposite hydrogel loaded with ginsenoside Rb1 (Rb1@CS@ALG) to enhance Rb1 delivery and investigate its therapeutic mechanisms in PI repair, focusing on SIRT1-AMPK-mediated ferroptosis inhibition and angiogenesis promotion. Methods The pH-responsive Rb1@CS@ALG hydrogel was synthesized and characterized (TEM/DLS/HPLC). In vitro studies evaluated ferroptosis markers (GPX4, SLC7A11), ROS levels, and cell migration in HaCaT cells under ischemia-reperfusion. A rat PI model (n=6/group) assessed wound closure rates, histopathology (H&E/Masson's), and protein expression (CD31/Col I). RNA-seq analyzed differential gene expression. Results The hydrogel showed sustained Rb1 release (82.3% at 24 h) and pH-dependent drug delivery. Treatment upregulated GPX4/SLC7A11 (2.3-fold) while reducing ROS (58%) and ACSL4 (45%) via SIRT1-AMPK activation (p-AMPK↑2.9-fold). In vivo, it accelerated wound closure by 75% (vs. controls, p<0.001), increased angiogenesis (CD31↑3.1-fold), and improved collagen organization (Col I/III ratio↑2.7-fold). RNA-seq confirmed enrichment in ferroptosis and extracellular matrix pathways. Conclusion This study establishes ginsenoside Rb1 as a potent therapeutic agent for PIs when delivered via nanocomposite hydrogel, with dual mechanisms of ferroptosis inhibition and angiogenesis activation. The findings provide a scientific foundation for applying ginseng-derived compounds in chronic wound management.
✓ 已验证
产品关联
DOI
高影响因子
EXPERIMENTAL ANIMALS
·
2026
·
IF 2
Yang LI,Xinchang FENG,Lingpeng ZHENG
Insulin resistance (IR) and hepatic steatosis are key pathological features of type 2 diabetes mellitus (T2DM). Fraxin, a natural flavonoid with potential metabolic regulatory properties, has been proposed to modulate metabolic disorders. This study aimed to investigate whether fraxin protects against IR and steatosis via Sirt1/AMPK/mTOR-mediated autophagy activation. A T2DM rat model was established using high-fat diet (HFD) feeding combined with streptozotocin (STZ) injection. Rats were treated with fraxin (25 or 50 mg/kg) for 4 weeks, followed by assessment of fasting blood glucose (FBG), insulin (FINS), HOMA-IR index, serum lipid profiles and liver function. Histopathological examination (H&E and Oil Red O staining) evaluated hepatic steatosis. BRL 3A cells exposed to palmitic acid (PA) were treated with fraxin (40 or 80 μM), and glucose uptake, lipid accumulation, and protein expression (IRS-1 phosphorylation, GLUT-2 translocation, autophagy markers and Sirt1/AMPK/mTOR pathway components) were analyzed. The specific autophagy inhibitor chloroquine (CQ) was used to verify whether the regulatory effects of fraxin were dependent on autophagy activation. Fraxin significantly reduced FBG, FINS, HOMA-IR, and dyslipidemia in diabetic rats. In PA-treated BRL 3A cells, fraxin enhanced glucose uptake, reduced lipid droplets, and restored IRS-1 phosphorylation and GLUT-2 membrane localization. Mechanistically, fraxin activated autophagy and modulated the Sirt1/AMPK/mTOR pathway, which were abolished by the Sirt1 inhibitor EX527. In conclusion, fraxin alleviates IR and hepatic steatosis in HFD/STZ-induced diabetic rats by activating autophagy through Sirt1/AMPK/mTOR pathway, suggesting its potential as a therapeutic agent for diabetes-associated metabolic disorders.
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2026
·
IF 3.9
Yifan Zheng,Kunying Ding,Haojie Jin,Zhaorong Wang,Liujie Zheng,Zhengwei Fu,Yinhua Ni
Cellular senescence is a core hallmark of aging and a major risk factor for most chronic diseases. Natural products targeting senescent cells have garnered increasing attention for anti-senescence potential in aging-related disease intervention. Previous studies revealed that hydrolyzed chicken extract (HCE) exerts neuroprotective effects, but its role in senescent cell clearance and underlying mechanisms remains unclear. Here, we investigated the anti-senescent effects and mechanisms of HCE in D-galactose-induced senescent HT-22 hippocampal neurons, compared with the traditional essence of chicken (EC). HCE significantly enhanced cellular antioxidant capacity, reduced SA-β-gal positivity, restored cell cycle progression, inhibited senescence-associated secretory phenotype (SASP) secretion, and promoted autophagic flux, with a slightly stronger efficacy than EC. We further identified cyclo (Val-Pro), cyclo (His-Pro), and cyclo(Gly-Pro) as bioactive components, with cyclo(His-Pro) showing the strongest potency. Mechanistically, HCE and these cyclopeptides exerted effects via SIRT1/AMPK/mTOR-mediated autophagy, which was fully abolished by SIRT1 knockdown or targeted pathway inhibition.
✓ 已验证
DOI
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2021
·
IF 6.475
Suwen Liu,Jincheng Yu,Mengfan Fu,Xinfang Wang,Xuedong Chang
Hawthorn polyphenol extract (HPE) is beneficial for patients with type 2 diabetes (T2D). However, the mechanism underlying its beneficial effects remains unclear. We investigated the inhibitory effects and mechanisms of HPE on insulin resistance, inflammation, and aortic injury in T2D rats, using metformin (MF) as a positive control. High-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) was used to determine the primary polyphenols in HPE. Hematoxylin & Eosin (H&E) staining was used to evaluate pathological conditions of the skeletal muscle, liver, and aorta vessels in each group. The levels of serum and intestinal tissue oxidative stress, tumor necrosis factor α (TNF-α), and inflammatory interleukin-6 (IL-6) were also assessed. Western blotting was used to evaluate protein expression levels in the associated molecular pathway. Volatile organic compounds (VOCs) from colon contents were determined using headspace-gas chromatography-ion mobility chromatography. Our results showed that supplementation with 300 mg HPE/kg body weight over four weeks significantly improved total cholesterol (TC), total triglyceride (TG), insulin, and lipopolysaccharide (LPS) levels in diabetic rats ( p < 0.01). The lesions of skeletal muscle, liver, and aorta in diabetic rats were significantly improved. HPE supplementation also significantly downregulated the inflammatory factors (IL-6, TNF-α, and MCP-1) in the liver of diabetic rats via the SIRT1/AMPK/NF-κB signaling pathway. Furthermore, HPE significantly reduced insulin resistance in T2D rats by upregulating the phosphorylation of glucose absorption protein (GLUT4) and insulin resistance-associated proteins, p-IRS1, p-AKT, and p-PI3K, in the rat liver ( p < 0.01). The findings show that HPE could also alleviate aortic injury by activating SIRT1 and regulating the NF-κB and Wnt2/β-catenin signaling pathways. Overall, the results of this study suggest that both HPE and MF have similar inhibitory effects on T2D in rats and that HPE could be used as a functional food component in the adjuvant treatment of T2D.
研究领域:
药理学
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内分泌学
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分子生物学
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营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2022
·Vol. 10
·期 25
·4840-4855
·
IF 7.571
Yujie Tan,Jing Feng,Yu Xiao,Chongyun Bao
Host-modulation therapy is generally accepted as a novel promising method for diabetic periodontitis (DP) treatment and screening an appropriate drug model is the key to success. Resveratrol (RSV), because of its viable antioxidative and anti-inflammatory properties and its ability to control glucose metabolism, is considered a potential candidate. However, poor water solubility, rapid decomposition and short serum half-life period significantly limit its application. Therefore, in this study, we designed a RSV-grafted mesoporous silica nanoparticle (MSN-RSV) drug carrier system to enhance RSV's stability effectively and prolong its duration. Further analyses have verified the indispensable role of MSNs in improving the bioavailability of RSV, which could result in a more favorable therapeutic efficacy in DP related to regulating the polarization of the macrophage. The reason for this could be explained by activating the SIRT1/AMPK signaling pathway and inhibiting the NF-κB signaling pathway. This study also focused on the auxiliary effect of MSN-RSV on alleviating insulin resistance (IR) and controlling glucose metabolism. In brief, the study has provided a potential alternative strategy for DP therapy. It is also helpful for future intensive research topics like the immunoregulatory mechanisms in the bidirectional relationship between diabetes and periodontitis.
研究领域:
纳米技术
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药学
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牙科学
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分子生物学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2023
·
IF 4.3
Qiuyan Pu,Fei Yang,Rui Zhao,Su Jiang,Yunping Tang,Tao Han
In order to investigate the amelioration of docosahexaenoic acid-enriched phosphatidylserine (DHA-PS) on bisphenol A (BPA)-induced nephrotoxicity , the murine nephrotoxicity model was established by intragastric administration of BPA (5 mg/kg/B.W.) for 6 weeks. The biochemical indices, hematoxylin-eosin (H&E) staining, kidney metabolomics, and related protein expression levels of SIRT1-AMPK pathway were then determined. Our results indicated that DHA-PS (100 mg/kg/B.W.) ameliorated the BPA-induced nephrotoxicity after 6 weeks of intragastric administration, primarily by decreasing the serum creatinine (CRE) and blood urea nitrogen (BUN), renal inflammatory cytokines and lipid levels, and increasing the antioxidant enzyme activities . In addition, the untargeted metabolomics of the kidney indicated that BPA perturbed the tryptophan metabolism, pyridine metabolism, and valine , leucine , and isoleucine biosynthesis, while DHA-PS administration significantly affected the glycerophospholipid metabolism, valine, leucine, and isoleucine biosynthesis to ameliorate the BPA-induced metabolic disorder . Moreover, DHA-PS administration could ameliorate the BPA-induced lipid disturbance by upregulating the expressions of AMPKα1, SIRT1, and PPARα while downregulating the expression of SREBP-1c through the SIRT1-AMPK pathway. This is the first time that the amelioration effects of DHA-PS on BPA-induced nephrotoxicity have been investigated from multiple perspectives, suggesting that DHA-PS might be a potential dietary supplement for reducing BPA-induced nephrotoxicity.
研究领域:
药理学
·
毒理学
·
代谢组学
·
分子生物学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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