FOOD AND CHEMICAL TOXICOLOGY
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2020
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IF 4.679
Rili Hao,Xinyu Song,Feng Li,Xintong Tan,Dongxiao Sun-Waterhouse,Dapeng Li
Exposure to nonbiodegradable cadmium (Cd) causes many health problems including the damage to the nervous system. This study aimed to increase knowledge about its neurotoxic effects and the neuroprotective potential of caffeic acid phenethyl ester (CAPE, a polyphenol abundant in honeybee propolis). In mice, CAPE (10 μmol/kg/day body weight) attenuated significantly learning and memory deficits induced by CdCl 2 (1.5 mg/kg/day body weight). For the CdCl 2 -treated mice, CAPE increased crossing number in open field test, decreased the alternation in Y-maze test, and increased the latency time and error number in step down test. CAPE also inhibited CdCl 2 -initiated Aβ accumulation and activation of pro-inflammatory factors and microglia in the brains. Therefore, CAPE could be a food-derived neuroprotective agent against Cd-induced neurotoxicity and neurodegenerative disorders, through attenuating neuronal apoptosis and neuroinflammation via the AMPK/SIRT1 pathway and amyloid-tau-neuroinflammation axis.
研究领域:
神经科学
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毒理学
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药理学
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PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2023
·
IF 7.2
Man Hu,Wen Jiang,Chen Ye,Ting Hu,Qingqing Yu,Moran Meng,Lijuan Sun,Jichao Liang,Yong Chen
Schwann cells injury induced by high glucose (HG) contributes to the development of diabetic peripheral neuropathy (DPN). Honokiol has been reported to regulate glucose metabolism, however, its effect on DPN and the precise molecular mechanisms remain unclear. This study aimed to investigate the role of AMPK/SIRT1/PGC-1α axis in the protective effects of honokiol on DPN. The biochemical assay and JC-1 staining results demonstrated that honokiol reduced HG-induced oxidative stress and ferroptosis as well as mitochondrial dysfunction in Schwann cells. RT-qPCR and western blotting were utilized to investigate the mechanism of action of honokiol, and the results showed that HG-induced inhibition of AMPK/SIRT1/PGC-1α axis and changes of downstream gene expression profile were restored by honokiol. Moreover, silencing of Sirt1 by siRNA delivery markedly diminished the changes of gene expression profile induced by honokiol in HG-induced Schwann cells. More importantly, we found that administration of honokiol remarkably attenuated DPN via improving sciatic nerve conduction velocity and increasing thermal and mechanical sensitivity in streptozotocin-induced diabetic rats. Collectively, these results demonstrate that honokiol can attenuate HG-induced Schwann cells injury and peripheral nerve dysfunction, suggesting a novel potential strategy for treatment of DPN.
研究领域:
神经科学
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药理学
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糖尿病
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细胞生物学
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分子生物学
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PubMed
高影响因子
BRAIN RESEARCH BULLETIN
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2024
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IF 3.5
Zhijuan Cheng,Jianglong Tu,Kai Wang,Fang Li,Yuan He,Wei Wu
Cerebral ischemia-reperfusion (IR) is the main pathophysiological process after stroke and can seriously impair neurological function. Wogonin, a natural flavonoid extracted from the roots of Scutellaria baicalensis, has potent anti-inflammatory properties. In this study, we investigated the protective mechanism of wogonin against middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R) model-induced cerebral IR injury through adenosine 5‘-monophosphate-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome axis. Our results showed that wogonin (20 mg/kg, intraperitoneal injection) effectively reduced infarct size, attenuated brain edema, improved neurological deficits, and alleviated histopathological damage. In addition, wogonin reduced microglial cell activation and inflammatory factors, including tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), IL-6, and IL-10, in brain tissue and serum after cerebral IR injury. Wogonin also effectively activated the AMPK/SIRT1 signaling pathway and inhibited NLPR3 inflammasome-related molecules upregulation in cerebral IR injury as well as in OGD/R-stimulated HT-22 cells. Furthermore, inhibition of the AMPK/SIRT1 signaling pathway by Compound C, an AMPK inhibitor, significantly reversed the protective effect of wogonin on OGD/R-induced NLRP3 inflammasome. Meanwhile, the protective effect of wogonin against brain IR injury was also reversed in the presence of compound C. These results suggest that wogonin ameliorates cerebral IR injruy-induced inflammation by inhibiting NLRP3 inflammasome through the AMPK/SIRT1 signaling pathway.
研究领域:
神经科学
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药理学
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炎症研究
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF ANIMAL SCIENCE
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2026
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IF 3.7
Zheng Jikang,Zhao Junyin,Li Minhao,Cheng Yuqin,Fang Xingqiang,Zhao Le,Zhao Yongju
Goat semen cryopreservation generates excessive reactive oxygen species (ROS), which impair post-thaw quality and physiological function. This study investigated the effects of resveratrol (RES) on cryopreserved goat sperm and the underlying signaling pathway. The results showed that supplementation with 150 μM RES significantly improved post-thaw sperm motility, plasma membrane integrity, and acrosome integrity (P < 0.05), enhanced SOD, CAT, and T-AOC activities, and reduced MDA content and sperm deformity rates (P < 0.05), while higher concentration (200 μM) showed no significant improvement compared to control, suggesting a detrimental effect of excessive RES. Furthermore, RES effectively alleviated cryo-induced ultrastructural damage to sperm. Mechanistically, RES activated AMPK signaling, increased AMPK phosphorylation, and upregulated the expression of SIRT1 and FoxO1 proteins. In contrast, the AMPK inhibitor Compound C partially blocked these beneficial effects. These findings indicate that RES improves the quality and antioxidant capacity of cryopreserved goat sperm by activating the AMPK/SIRT1/FoxO1 pathway, suggesting that RES can serve as a promising antioxidant additive for goat semen cryopreservation.
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高影响因子
CELLULAR AND MOLECULAR LIFE SCIENCES
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2024
·Vol. 81
·期 1
·1-24
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IF 6.2
Hong Ling,Xiao Shan,Diao Lianghui,Lian Ruochun,Chen Cong,Zeng Yong,Liu Su
Polycystic ovary syndrome (PCOS) is a complex common endocrine disorder affecting women of reproductive age. Ovulatory dysfunction is recognized as a primary infertile factor, however, even when ovulation is medically induced and restored, PCOS patients continue to experience reduced cumulative pregnancy rates and a higher spontaneous miscarriage rate. Hyperandrogenism, a hallmark feature of PCOS, affects ovarian folliculogenesis, endometrial receptivity, and the establishment and maintenance of pregnancy. Decidualization denotes the transformation that the stromal compart of the endometrium must undergo to accommodate pregnancy, driven by the rising progesterone levels and local cAMP production. However, studies on the impact of hyperandrogenism on decidualization are limited. In this study, we observed that primary endometrial stromal cells from women with PCOS exhibit abnormal responses to progesterone during in vitro decidualization. A high concentration of testosterone inhibits human endometrial stromal cells (HESCs) decidualization. RNA-Seq analysis demonstrated that pyruvate dehydrogenase kinase 4 (PDK4) expression was significantly lower in the endometrium of PCOS patients with hyperandrogenism compared to those without hyperandrogenism. We also characterized that the expression of PDK4 is elevated in the endometrium stroma at the mid-secretory phase. Artificial decidualization could enhance PDK4 expression, while downregulation of PDK4 leads to abnormal decidualization both in vivo and in vitro. Mechanistically, testosterone excess inhibits IGFBP1 and PRL expression, followed by phosphorylating of AMPK that stimulates PDK4 expression. Based on co-immunoprecipitation analysis, we observed an interaction between SIRT1 and PDK4, promoting glycolysis to facilitate decidualization. Restrain of AR activation resumes the AMPK/SIRT1/PDK4 pathway suppressed by testosterone excess, indicating that testosterone primarily acts on decidualization through AR stimulation. Androgen excess in the endometrium inhibits decidualization by disrupting the AMPK/SIRT1/PDK4 signaling pathway. These data demonstrate the critical roles of endometrial PDK4 in regulating decidualization and provide valuable information for understanding the underlying mechanism during decidualization.
研究领域:
生殖内分泌学
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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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PubMed
高影响因子
Antioxidants
·
2026
·Vol. 15
·期 5
·652
·
IF 8.2
Haoyang Dai,Qinqin Zhang,Pei Chen,Suiqing Chen
The pathogenesis of acute liver injury (ALI) involves the loss of hepatic detoxification function, massive death of liver parenchymal cells within a short period, and excessive inflammatory responses. Studies have shown that Esculetin (Esc) possesses potent anti-inflammatory, antioxidant, and anti-tumor properties. In this study, we investigate whether Esc has a protective effect against ALI in mice and its potential mechanism. Esculetin markedly decreased ROS, MitoSOX, and apoptosis levels in AML12 cells and restored MMP. H&E staining demonstrated that Esc alleviated hepatic histopathological injury, and its intervention reduced serum ALT and AST levels. Moreover, Esc diminished ROS and apoptosis levels in the liver. Hepatic proteomic profiling identified the AMPK signaling pathway. Esc reduced the protein levels of p-AMPK/AMPK, PGC-1α, p-SIRT1/SIRT1, and BAX and upregulated the levels of Bcl-2 in liver tissue. Concomitantly, we added inhibitor Compound C (CC) to the AML12 cells to assess whether Esc acted through the AMPK pathway. The results showed that CC exacerbated the degree of liver injury, whereas Esc was able to reverse these phenomena, thus exerting an anti-liver injury effect. These findings provide mechanistic insights into the protective effects of Esc against ALI and support its potential as a therapeutic candidate for ALI.
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高影响因子
Journal of Ginseng Research
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2026
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IF 7.5
Chongyang Zhang,Yuning chen,Wei Liu,Rong-chang Chen
Background Ginsenoside RK3 was first isolated from heat-processed ginseng. Our study aimed to explore the underlying mechanism of RK3 in combating isoproterenol (ISO)-induced heart failure (HF) in mice. Methods HF was induced in mice by subcutaneous injection of ISO (80mg/kg/d) 1 hour after intraperitoneal administration of RK3 (10 and 20 mg/kg/d) for 28 days. Cardiac function and heart injury were assessed and comprehensive metabolic alterations in the serum were profiled. Western blot analysis was conducted. In vitro experiments, H9c2 cells were pretreated with RK3 before hypoxia exposure. Cell viability and LDH release were determined. Results In vivo experiments demonstrated that RK3 treatment prevented ISO-induced myocardial damage. Additionally, RK3 reduced serum inflammatory factors and levels of myocardial fibrosis. Metabolomics data indicated that RK3 mitigated the ISO-induced increase in glycolytic intermediates, including 3-phenyllactic acid, D-glucose-6-phosphate, D-glucose-1-phosphate, and D-fructose-6-phosphate and the decrease in intermediates of the TCA cycle, such as citric acid. Treatment with RK3 also inhibited the expression of MCT4 while enhancing the expression of MPC2, PGC-1α, Sirt1, and p-AMPK in heart tissues. In vitro investigations revealed that the protective effect of RK3 on H9c2 cells was abolished by AMPK inhibition. Conclusions Our study, for the first time, confirmed that RK3 protects against ISO-induced HF, which may be related to the restoration of balance in the pyruvate-lactate axis through the activation of the AMPK/Sirt1/PGC1 pathway.
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DOI
高影响因子
MEDIATORS OF INFLAMMATION
·
2022
·
IF 4.529
Jieru Han,Wenhao Li,Guangyu Shi,Yunlei Huang,Xutao Sun,Na Sun,Deyou Jiang
Ulcerative colitis (UC) is a complex inflammatory bowel disease (IBD) associated with mitochondrial function. Atractylenolide III (AT III) is a natural product with anti-inflammatory effects. The aim of this work is to investigate the protective effect of AT III on UC and its underlying mechanisms. Herein, dextran sulfate sodium- (DSS-) induced mice and lipopolysaccharide- (LPS-) stimulated intestinal epithelial cells (IEC-6) were employed to mimic UC pathologies in vivo and in vitro. The results showed that in DSS-induced mice, AT III significantly reversed the body weight loss, colon length reduction, disease activity index (DAI) increase, and histological damage. The production of proinflammatory factors and reduction of antioxidants in colitis were suppressed by AT III. In addition, we demonstrated that AT III attenuated the intestinal epithelial barrier destruction and mitochondrial dysfunction induced by DSS, which was similar to the in vitro results in LPS-treated IEC-6 cells. The protein levels of p-AMPK, SIRT1, and PGC-1α along with acetylated PGC-1α were also upregulated by AT III in vivo and in vitro. In conclusion, these findings support that AT III may protect against mitochondrial dysfunction by the activation of the AMPK/SIRT1/PGC-1α signaling pathway during UC development.
研究领域:
药理学
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免疫学
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胃肠病学
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分子生物学
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细胞生物学
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高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Jing Liu,Wenyue Zhang,Xiaojing Li,Shiwen Xu
Chlorpyrifos (CPF) is widely used in agriculture, plants, and buildings to kill pests and worms. Excessive environmental residues of CPF will result in soil and ecological contamination and toxicity to animals and humans. Baicalein (Bai), derived from the root of natural Scutellaria baicalensis, is a potent anti-inflammatory, antioxidant, and antitumor agent. The objective of this paper is to investigate the molecular mechanism by which Bai prevents CPF-induced hepatotoxic injury. Carp were kept in water containing CPF (23.2 μg/L) and/or fed diets containing Bai (0.15 g/kg). We found that Bai attenuated liver tissue damage and vacuolization caused by CPF. We confirmed that CPF causes M1/M2 polarization imbalance in macrophages and hepatocyte pyroptosis, which ultimately leads to liver injury. Further exploration of the internal mechanism shows that CPF participates in liver toxicity damage by destroying the AMPK/SIRT1/pGC-1α pathway and causing mitochondrial biogenesis and mitochondrial dynamics imbalance. Notably, Bai significantly attenuated CPF-induced inhibition of the AMPK/SIRT1/pGC-1α pathway. In summary, our results suggest that Bai alleviates CPF exposure-induced inhibition of the AMPK/SIRT1/pGC-1α pathway, thereby attenuating macrophage M1 hyperpolarization and pyroptosis by inhibiting the NF-κB pathway. These results may provide new insights into the detoxification mechanism of Bai on the same type of organophosphorus pesticides.
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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水生毒理学
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产品关联
DOI
PubMed
高影响因子
BRAIN RESEARCH BULLETIN
·
2022
·
IF 3.715
Bihui Song,Wenhao Zhou
Amarogentin (AMA), a secoiridoid glycoside that is mainly derived from SwertiaandGentiana roots, has been confirmed to exhibit antioxidative, tumor-suppressive and anti-diabetic properties. This research intends to investigate the protective effect of AMA against sepsis-induced brain injury and its mechanism. NSC-34 and HT22 cells were treated with lipopolysaccharide (LPS) to induce an in-vitro sepsis model and then treated with varying concentrations (1, 5, 10 µM) of AMA. Cell proliferation and apoptosis were evaluated. The intensity of inflammation and oxidative stress were assessed by different methods. The AMPK/SIRT1/NF-κB pathway expression was determined by WB . An in-vitro sepsis model was set up with cecal ligation and puncture (CLP) in adult C57/BL6J mice, and different concentrations (25, 50, 100 mg/kg) of AMA were applied for treatment. Neurological function was evaluated using the modified neurological severity scores (mNSS), and the brain tissue damage was measured using hematoxylin-eosin (H&E) staining and Nissl staining. Tissue apoptosis was tested using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Then, the AMPK inhibitor Compound C (CC) was administered to confirm AMA-mediated mechanism. Our finding illustrated that AMA mitigated LPS-induced neuronal damage, inflammation and oxidative stress, activated the AMPK/SIRT1 pathway and choked NF-κB phosphorylation. Furthermore, AMA improved neurological functions of sepsis mice by reliving neuroinflammation and oxidative stress. Inhibition of AMPK attenuated the protective effect of AMA on neurons or the mice’s brain tissues. In conclusion, AMA protected against sepsis-induced brain injury by modulating the AMPK/SIRT1/NF-κB pathway.
研究领域:
药理学
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神经科学
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炎症研究
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2026
·
IF 6.8
Linxin Zhang,Mengyang Wang,Wei Liu,Xiaoli Cui,Chang Liu,Hui Yu,Jiangning Hu,Di Yang,Haiming Sun
Ethnopharmacological relevance Shenfu Decoction (SFD) is a traditional famous prescription for replenishing qi and restoring yang . Pharmacological research has confirmed that SFD can warm and tonify yang qi and exerts good therapeutic effects on cardiovascular-related diseases. However, there are no reports on kidney diseases caused by hypertension, and its molecular mechanism needs further exploration. Aim of the study This study aimed to investigate whether SFD ameliorates hypertensive renal disease (HRD) and to clarify whether such protection is achieved through alleviate mitochondrial dysfunction and subsequent inhibition of apoptosis via the AMPK/SIRT1/PGC 1α signaling pathway. Methods and materials Combining network pharmacology, an Ang II-induced hypertensive kidney injury model in C57BL/6 mice, and the NRK-52E cell model, renal function, mitochondrial function, oxidative stress, inflammatory factors, and apoptosis were assessed. Co-immunoprecipitation was used to verify the interaction between SIRT1 and PGC-1α. Results SFD treatment improved AngII-induced renal dysfunction without altering blood pressure. Network pharmacology combined with experiments identified stigmasterol (STI) as the active component, which alleviates mitochondrial dysfunction, reduces oxidative stress/inflammation, and decreases apoptosis by activating the AMPK/SIRT1/PGC-1α pathway. Mechanistically, the N-terminus of SIRT1 can directly interact with the PGC-1α D2 domain. Conclusions This study provides evidence that SFD and its active STI alleviate HRD by activating the AMPK/SIRT1/PGC-1α pathway to alleviate mitochondrial dysfunction and oxidative stress in renal epithelial cells.
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高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2020
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IF 3.943
Dan Li,Jiangping Xu,Yunyun Qin,Ningbo Cai,Yufang Cheng,Haitao Wang
Roflupram (ROF) is a novel phosphodiesterase 4 inhibitor. We previously found that ROF suppressed the production of pro-inflammatory factors in microglial cells; however, the underlying mechanisms are largely unknown. The present study aimed to elucidate the underlying molecular mechanisms of the anti-neuroinflammatory effects of ROF in lipopolysaccharide (LPS)-activated microglial cells and LPS-challenged mice. Treatment with ROF suppressed LPS-induced expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-α in BV-2 microglia cell line. Immunofluorescence and Western blotting analysis showed that ROF significantly inhibited the activation of microglia, as evidenced by decreased expression of ionized calcium binding adaptor molecule-1 (Iba1). Similar results were obtained in primary cultured microglial cells. ROF induced the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of Sirtuin 1 (Sirt1). Interestingly, the AMPK inhibitor, compound C, blocked the role of ROF in both the phosphorylation of AMPK and the expression of Sirt1 in BV-2 cells stimulated with LPS. More importantly, the Sirt1 inhibitor, EX527, abolished the inhibitory role of ROF on the production of pro-inflammatory factors, and reactivated BV-2 cells. In mice challenged with LPS, ROF improved cognition and decreased the levels of IL-6 and TNF-α in both the cortex and hippocampus. In contrast, EX527 weakened the effects of ROF on cognitive enhancement and reduction of pro-inflammatory factors in the cortex and hippocampus. Furthermore, EX527 blocked the inhibitory role of ROF in the activation of microglial cells in both the hippocampus and cortex. Taken together, our results indicated that ROF attenuated LPS-induced neuroinflammatory responses in microglia, and the AMPK/Sirt1 pathway is essential for the anti-inflammatory effects of ROF.
研究领域:
神经科学
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药理学
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免疫学
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PubMed
高影响因子
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