TOXICOLOGY
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2024
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IF 4.8
Xueping Liu,Rongxia Li,Zi Xiu,Siling Tang,Yancang Duan
Acrolein (ACR), an unsaturated, highly reactive aldehyde, is a widespread environmental toxin. ACR exerts permanent and irreversible side effects on ovarian functions. Granulosa cells play a crucial role in supporting ovarian function. Thus, in this study, we investigated the toxicity effects of granulosa cells induced by ACR. Following treatment with varying ACR concentrations (0, 12.5, 25, 50, and 100 μM), we observed that ACR exposure induced reactive oxygen species accumulation, mitochondrial energy metabolism disorder, and apoptosis in KGN cells (a human ovarian granulosa cell line) in a dose-dependent manner. In addition, mitochondrial biogenesis in KGN cells displayed biphasic changes after ACR exposure, with activation at a low ACR dose (12.5 μM), but inhibition at higher ACR doses (≥50 μM). SIRT1/PGC-1α-mediated mitochondrial biogenesis is crucial for maintaining intracellular mitochondrial homeostasis and cellular function. The inhibition/activation of the SIRT1/PGC-1α pathway in KGN cells validated its role in ACR-induced damage. The results indicated that the inhibition of the SIRT1/PGC-1α pathway aggravated ACR-induced cell damage, whereas its activation partially counteracted ACR-induced cell damage. This study attempted to uncover a novel mechanism of ACR-induced ovarian toxicity so as to provide an effective treatment option for safeguarding female reproductive health from the adverse effects of ACR.
研究领域:
毒理学
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生殖生物学
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细胞生物学
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环境健康
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2024
·
IF 5.7
Bailin Li,Shengtao Bo,Zhili Sheng,Hong Zhu,Yueming Jiang,Bao Yang
Dietary prenylated stilbenoids, found in various food sources, offer multiple health benefits, including liver protection. However, the underlying mechanisms of hepatoprotection remain unclear. In this study, we synthesized 13 natural prenylated stilbenoids and examined their hepatoprotective activities, with silent mating type information regulation 2 homologue-1 (SIRT1) as the primary target for screening. Among all of the prenylated stilbenoids tested, 4-C-geranyl oxyresveratrol demonstrated superior performance. It activated SIRT1 activity more effectively than resveratrol, a well-known SIRT1 activator. To further investigate the mechanism of liver protection, two in vitro models were used: the palmitic acid-induced lipid accumulation model and the H2O2-induced apoptosis model. Our findings suggested that 4-C-geranyl oxyresveratrol mitigated lipid accumulation through the SIRT1-PGC1α pathway, reduced apoptosis via the SIRT1-p53-p21 pathway, and exerted antioxidant effects through the SIRT1-Nrf2 pathway. These findings provide new insights into the chemical basis of the health benefits of prenylated stilbenoids and their potential use as functional food additives.
研究领域:
药理学
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分子生物学
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营养学
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Food Frontiers
·
2025
·Vol. 7
·期 1
·e70204
·
IF 6.9
Suwen Liu,Wenhong Jiang,Hanchen Li,Xuli Wang,Jiancheng Ma,Lina Dong
Lonicera caerulea berry polyphenols (LCBP) exhibit multiple physiological effects. In this study, we investigated the role of LCBP in reducing cholesterol accumulation in rats with type 2 diabetes mellitus (T2DM) and its underlying mechanism. LCBP reduced the content of neutral lipids in the aorta and decreased the plaque area by 47.3% ( p < 0.01) compared with that in the model group. LCBP also reduced the expression of CD11b and F4/80 in peritoneal macrophages. The cholesterol efflux rate in the LCBP group increased significantly by 61.2% ( p < 0.01). Western blotting and immunohistochemical experiments revealed that LCBP promoted cholesterol efflux via a dual mechanism of activating silent information regulator 1 (SIRT1) in macrophages in a high-glucose environment and the miR-33/SREBP2-ABCA1 pathway. SIRT1 activation enhanced the effects of LCBP on cholesterol regulation. Molecular dynamics simulation experiments revealed that the three main monomer components of LCBP—cyanidin-3-glucoside, catechin, and chlorogenic acid—could stably bind to the active site of SIRT1 and serve as key components in the regulation of cholesterol by this protein. This study provides new insights into the use of LCBP as a functional food additive for T2DM-related atherosclerosis.
研究领域:
营养生物化学
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分子生物学
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内分泌学
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心血管研究
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功能食品
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Antioxidants
·
2026
·Vol. 15
·期 3
·
IF 8.2
Jianhong Wang,Ting Jiang,Siqi Chen,Yajing Li,Qing Li,Lan Xiang,Jianhua Qi
Traditional Chinese medicine plays an important role in human health, but due to the complexity of its active fraction, its therapeutic mechanism still needs further clarification.Polygalae Radixis one of the traditional Chinese medicines, which was recorded inShennong Classic of Materia Medicawith the effect of prolonging life. In the present study, we isolated a small molecule compound with anti-aging effects, 3,6′-disinapoyl sucrose (DISS), fromPolygalae Radixunder the guidance of the replicative lifespan assay of K6001 yeast strain. It extended the lifespan of yeast and alleviated etoposide-induced aging in 3T3 cells. Furthermore, this compound increased the telomerase activity and the length of telomeres, and targeted the SIRT1 signaling pathway, respectively. In addition, it improved the survival ability of yeast under oxidative stress conditions, decreased ROS and MDA levels, and increased the activity of SOD, CAT and GPx enzymes. Moreover, DISS enhanced autophagic flux, as demonstrated by assay of the YOM38-GFP-ATG8 yeast strain. In conclusion, DISS fromPolygalae Radixexerts anti-aging effects by protecting telomeres, regulating the SIRT1/p53/p21 signaling pathway, mitigating oxidative stress and modulating autophagy. Thus, this study provides scientific evidence for the use ofPolygalae Radixas an anti-aging herb.
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PHYTOMEDICINE
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2026
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IF 11.3
Yeqiu Xu,Junrui Jonathan Hai,Duan Sun,Yihan Yang,Chen Wang,Xinan Zhang,Huanli Xu,Yajin Liao,Xianjun Qu,Bo Han,Weishi Liang,Yong Hai
Background Distractive spinal cord injury (DSCI) is a severe complication of spinal deformity correction surgery, causing early disruption of the blood–spinal cord barrier (BSCB). However, the molecular mechanisms that translate mechanical stress into vascular endothelial dysfunction remain unclear, and effective pharmacological strategies targeting this process are lacking. Purpose This study aimed to investigate the therapeutic effects of sodium rutin (NaR), a water-soluble derivative of rutin, on BSCB disruption following DSCI, and to elucidate the underlying molecular mechanisms. Methods In vivo rat DSCI models and in vitro mechanical distraction models of spinal cord microvascular endothelial cells were employed. The therapeutic effects of oral NaR administration on locomotor function and BSCB permeability in rats following DSCI were systematically evaluated. Mechanistic investigations targeting the SIRT1/β-catenin axis and oxidative stress were conducted utilizing RNA sequencing, interventions with small interfering RNA and SIRT1 inhibitors, alongside standard molecular biology techniques. Results NaR treatment dose-dependently improved locomotor recovery in DSCI rats and significantly reduced BSCB permeability by restoring the expression of tight junction proteins. Mechanical distraction caused a significant downregulation of SIRT1 in endothelial cells. NaR treatment upregulated SIRT1 expression and promoted its nuclear-to-cytoplasmic translocation. This upregulation of SIRT1 was associated with significant inhibition of mitochondrial oxidative stress. Furthermore, oxidative stress was found to promote β-catenin phosphorylation and subsequent degradation via the ubiquitin-proteasome pathway. NaR stabilized β-catenin through SIRT1-mediated antioxidant effects, promoting its nuclear translocation and the downstream expression of tight junction genes. Consequently, by repairing the BSCB, NaR restricted the infiltration of immune cells (CD68 + macrophages/microglia and MPO + neutrophils) into the spinal parenchyma, thereby attenuating secondary neuroinflammation. Conclusion The SIRT1/β-catenin axis may serve as a critical mechanotransduction pathway regulating BSCB integrity. NaR protects the BSCB after DSCI by restoring SIRT1 activity, suppressing oxidative stress, and stabilizing β-catenin signaling. NaR may be a promising pharmacological strategy for the treatment of DSCI. In brief: Hai et al. identify a mechanism by which mechanical distraction disrupts the blood-spinal cord barrier through suppression of SIRT1 and oxidative destabilization of β-catenin. Oral sodium rutin restores barrier integrity, limits inflammation, and thus improves locomotor recovery, highlighting a vascular-targeted therapeutic strategy for distraction-induced spinal cord injury Download: Download high-res image (296KB) Download: Download full-size image
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MOLECULAR NEUROBIOLOGY
·
2025
·Vol. 63
·期 1
·1-14
·
IF 4.3
Cai Minghui,Guo Qi,Li Jiaxin,Dai Xiaoqi,Su Huiyu,Zhang Wenwen,Qiang Na,Li Geng,Jin Zihan,Zhu Hui
The factors influencing hippocampal aging are complex, and it remains challenging to identify effective anti-aging drugs and reveal pharmacological mechanisms. This study investigates the effects of autophagy mediated by the SIRT1/FoxO1 signaling pathway on resveratrol resistance to H 2 O 2 -induced aging and apoptosis in mouse hippocampal neurons. HT22 cells were treated with resveratrol and H 2 O 2 to evaluate the effects of resveratrol on H 2 O 2 -induced aging and apoptosis. The levels of P21, P53, BAX, Cleaved Caspase-3, and Bcl-2 were measured to estimate aging and apoptosis. Western blot, immunofluorescence assays, and transmission electron microscopy observation were used to detect the regulation of resveratrol on autophagy. 3-Methyladenine was used to block autophagy, and EX-527 was used to inhibit SIRT1. The changes of autophagy factors and the levels of SIRT1/FoxO1 signaling pathway were assayed. H 2 O 2 treatment induced aging in HT22 cells, manifesting increased levels of P21 and P53 and decreased cell viability. H 2 O 2 treatment aggravated apoptosis, showing increased levels of BAX and Cleaved Caspase-3, decreased levels of Bcl-2, and increased apoptotic cells. Resveratrol alleviated aging and apoptosis in H 2 O 2 -induced HT22 cells. Mechanically, resveratrol activated autophagy by up-regulating the levels of LC3B Ⅱ/Ⅰ and Beclin1 and down-regulating P62 against aging and apoptosis, which was abolished by 3-Methyladenine. Western blot results showed resveratrol activated SIRT1/FoxO1 signaling pathway which was related to regulation of autophagy. EX-527 treatment suggested resveratrol could not activate autophagy when the SIRT1/FoxO1 signaling pathway was blocked. These findings indicated that resveratrol activated autophagy via SIRT1/FoxO1 signaling pathway to protect against H 2 O 2 -induced aging and apoptosis in HT22 cells.
研究领域:
神经科学
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分子生物学
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细胞生物学
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药理学
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Evidence-based Complementary and Alternative Medicine
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2023
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IF 2.65
Zhiqiang Gong,Sha Han,Chenlin Li,Tianxiu Meng,Yu Huo,Xianfu Liu,Yanhong Huang,Lifang Yang
Rhinacanthin C (RC) is a naphthoquinone ester with an anti-inflammatory activity extracted from Rhinacanthus nasutus (L.) Kurz (Rn). It has been proven to improve hyperglycemia and hyperlipidemia, but the prevention and mechanism of RC in nonalcoholic fatty liver disease (NAFLD) are not clear. In the current study, we first extracted RC from Rn using ethyl acetate and identified it by HPLC, MS, and NMR. At the same time, molecular docking analysis of RC with AMPK and SREBP-1c was performed using AutoDock software. In addition, the mouse model of NAFLD was induced by a high-fat diet in vivo, and low, medium, and high concentrations of RC were used for intervention. The results showed that RC significantly reduced the body mass and liver body coefficient of NAFLD mice, inhibited liver inflammation and fat accumulation, and improved insulin resistance. Further studies showed that RC significantly reduced the levels of serum leptin and resistin, upregulated the expression levels of adiponectin and adiponectin receptor in the liver, and inhibited the expression levels of MCP-1, TNF-α, and IL-6. In terms of mechanism, RC upregulates the expression of p-AMPK and SIRT1 and downregulates the expression of p-p65, SREBP-1c, Fas, Acc-α, PPAR-γ, and SCD1. These studies suggest that RC improves insulin resistance and lipid accumulation in NAFLD by activating the AMPK/SIRT1 and SREBP-1c/Fas/ACC pathways, respectively.
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Nutrients
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2020
·Vol. 12
·期 6
·1889
·
IF 4.546
Nancy Saji,Nidhish Francis,Lachlan J. Schwarz,Christopher L. Blanchard,Abishek B. Santhakumar
Oxidative stress is known to modulate insulin secretion and initiate gene alterations resulting in impairment of β-cell function and type 2 diabetes mellitus (T2DM). Rice bran (RB) phenolic extracts contain bioactive properties that may target metabolic pathways associated with the pathogenesis of T2DM. This study aimed to examine the effect of stabilized RB phenolic extracts on the expression of genes associated with β-cell function such as glucose transporter 2 (Glut2), pancreatic and duodenal homeobox 1 (Pdx1), sirtuin 1 (Sirt1), mitochondrial transcription factor A (Tfam), and insulin 1 (Ins1) in addition to evaluating its impact on glucose-stimulated insulin secretion. It was observed that treatment with different concentrations of RB phenolic extracts (25-250 µg/mL) significantly increased the expression ofGlut2,Pdx1,Sirt1, Tfam,andIns1genes and glucose-stimulated insulin secretion under both normal and high glucose conditions. RB phenolic extracts favourably modulated the expression of genes involved in β-cell dysfunction and insulin secretion via several mechanisms such as synergistic action of polyphenols targeting signalling molecules, decreasing free radical damage by its antioxidant activity, and stimulation of effectors or survival factors of insulin secretion.Keywords:rice bran;phenolic extracts;β-cell function;gene expression;insulin secretion
研究领域:
营养学
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分子生物学
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内分泌学
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药理学
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Food Bioscience
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2026
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IF 6.2
Qing Liu,Zengying Sui,Shiyi Li,Miaomiao Wan,Meilan Xue,Xia Qiu,Hui Liang,Lirui Sun
Fucoidan is a sulfated polysaccharide derived from brown algae ( Saccharina japonica ), and exhibits immunomodulatory properties. Emerging evidence suggests a strong correlation between the development of food allergy and intestinal dysfunction. The present study aimed to investigate the potential anti-food allergy activity of fucoidan and to elucidate its mechanism at the intestinal barrier function. The ovalbumin (OVA)-induced allergy mouse model was established, exhibiting increased OVA-specific IgE, histamine, Th2 inflammatory response, and intestinal damage. Oral administration of fucoidan markedly alleviated allergic symptoms by inhibiting mast cell activation and modulating intestinal immune responses. Furthermore, fucoidan significantly ameliorated intestinal immunological dysregulation, maintained barrier integrity, modulated gut microbiota composition, and enhanced short-chain fatty acid (SCFA) production. Mechanistically, the protective effects of fucoidan were closely associated with activation of the AMPK/SIRT1/FOXO1 pathway, which correlated with improved intestinal barrier function. Collectively, these results demonstrate that fucoidan may protect against food allergy by enhancing intestinal barrier function, highlighting the potential of natural biological substances in addressing food allergy.
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Scientific Reports
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2026
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IF 4.9
Yi Tingting,Xu Mei,Wang Lihua,Wang Pengwei
Recently, mesenchymal stem cells (MSCs), valued for their multipotent properties, have attracted significant attention in disease therapy. Transforming growth factor-β1(TGF-β1), a cytokine involved in regulating cellular stress responses, is closely associated with neurological function and the differentiation of MSCs. The primary purpose of this research was to assess the neuroprotective capacity of exosomes from TGF-β1-pretreated human umbilical cord mesenchymal stem cells (hUCMSCs) on neuronal injury in epilepsy. In this study, we established epileptic models using male C57BL/6 mice and hippocampal Neurons. Exosomes from TGF-β1- pretreated hUCMSCs were characterized via transmission electron microscopy (TEM) combined with nanoparticle tracking analysis (NTA) and were then applied as a therapeutic intervention. Our research demonstrated that TGF-β1 upregulated the level of the long non-coding RNA urothelial carcinoma-associated 1 (lncRNA UCA1) in hUCMSC-derived exosomes. Exosomes from TGF-β1-pretreated hUCMSCs enhanced neuronal viability, inhibited apoptosis, and reduced inflammation and oxidative stress levels, whereas UCA1 knockdown reversed these beneficial effects. Furthermore, lncRNA UCA1 directly binds to miR-132. Knockdown of UCA1 upregulated miR-132 levels and downregulated SIRT1 expression; this downregulation could be rescued by inhibiting miR-132. In vivo, we further observed that exosomes from TGF-β1-pretreated hUCMSCs alleviated neuronal damage in the hippocampal CA3 region, inhibited glial activation, and suppressed the increase of related inflammatory factors. In contrast, UCA1 knockdown produced the opposite effects. The in vivo findings paralleled the results of the in vitro cell experiments. In conclusion, these results demonstrated that exosomes from TGF-β1-pretreated hUCMSCs exert anti-epileptic effects by modulating the lncRNA UCA1 / miR-132 / SIRT1 axis.
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MOLECULES
·
2023
·Vol. 28
·期 21
·7307
·
IF 4.6
Yecheng Lei,Xiao Lei,Anqi Zhu,Shijie Xie,Tiantian Zhang,Chuo Wang,Anning Song,Xiaoming Wang,Guangwen Shu,Xukun Deng
Acetaminophen (APAP)-induced liver injury is a common hepatic disease resulting from drug abuse. Few targeted treatments are available clinically nowadays. The flower bud ofRosa rugosahas a wide range of biological activities. However, it is unclear whether it alleviates liver injury caused by APAP. Here, we prepared an ethanol extract ofRosa rugosa(ERS) and analyzed its chemical profile. Furthermore, we revealed that ERS significantly ameliorated APAP-induced apoptosis and ferroptosis in AML-12 hepatocytes and dampened APAP-mediated cytotoxicity. In AML-12 cells, ERS elevated Sirt1 expression, boosted the LKB1/AMPK/Nrf2 axis, and thereby crippled APAP-induced intracellular oxidative stress. Both EX527 and NAM, which are chemically unrelated inhibitors of Sirt1, blocked ERS-induced activation of LKB1/AMPK/Nrf2 signaling. The protection of ERS against APAP-triggered toxicity in AML-12 cells was subsequently abolished. As expression of LKB1 was knocked down, ERS still upregulated Sirt1 but failed to activate AMPK/Nrf2 cascade or suppress cytotoxicity provoked by APAP. Results of in vivo experiments showed that ERS attenuated APAP-caused hepatocyte apoptosis and ferroptosis and improved liver injury and inflammation. Consistently, ERS boosted Sirt1 expression, increased phosphorylations of LKB1 and AMPK, and promoted Nrf2 nuclear translocation in the livers of APAP-intoxicated mice. Hepatic transcriptions of HO-1 and GCLC, which are downstream antioxidant genes of Nrf2, were also significantly increased in response to ERS. Our results collectively indicated that ERS effectively attenuates APAP-induced liver injury by activating LKB1/AMPK/Nrf2 cascade. Upregulated expression of Sirt1 plays a crucial role in ERS-mediated activation of LKB1.Keywords:extract ofRosa rugosa;acetaminophen;liver injury;Sirt1;Nrf2
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Frontiers in Microbiology
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2022
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IF 6.064
Jiang Hui,Mao Tangyou,Sun Zhongmei,Shi Lei,Han Xiao,Zhang Yang,Zhang Xiaosi,Wang Jiali,Hu Juncong,Zhang Liming,Li Junxiang,Han Haixiao
Yinchen Linggui Zhugan decoction (YLZD) is an effective and classical traditional herbal prescription for treating the nonalcoholic fatty liver disease (NAFLD) and has been proven to be effective in the regulation of lipid metabolism disorder and attenuate inflammation for a NAFLD rat model. However, the exact underlying mechanism has not been elucidated. In the current study, a NAFLD rat model was established using a high-fat diet (HFD) for 10 weeks, followed by YLZD treatment with 1.92 g/kg/day for 4 weeks to explore the mechanisms of YLZD. Our results showed that YLZD decreased the hepatic lipid deposition, restored the liver tissue pathological lesions, inhibited the expression of oxidative stress, and decreased the inflammatory cytokines levels. Meanwhile, the genes and proteins expressions of SIRT1/Nrf2 signaling pathway together with downstream factors including HO-1 and NQO1 were elevated in the YLZD treated NAFLD rats. For further elaborating the upstream mechanism, short-chain fatty acids (SCFAs) in serum and feces were measured by liquid chromatograph mass spectrometer and gas chromatograph mass spectrometer, and the differences in gut microbiota of rats in each group were analyzed through high-throughput sequencing of 16S rRNA. The results demonstrated that the contents of butyric acid (BA) and total SCFAs in YLZD-treated NAFLD rats were significantly increased in serum and feces. 16S rRNA sequencing analysis illustrated that YLZD intervention led to a modification of the gut microbiota composition, with a decrease of Oribacterium, Lactobacillus and the ratio of Firmicutes/Bacteroides, as well as the increase in SCFAs-producing bacteria such as Christensenellaceae, Clostridia, Muribaculaceae, and Prevotellaceae. Spearman rank correlation analysis indicated that BA and total SCFAs were negatively co-related with oxidative stress-related factors and inflammatory cytokines, while they were positively co-related with SIRT1/Nrf2 pathway related genes and proteins. Furthermore, in vitro study confirmed that BA effectively reduced oxidative stress by activating SIRT1/Nrf2 signaling pathway in L02 cells. Together, the present data revealed YLZD could ameliorate HFD-induced NAFLD in rats by the modulation of SIRT1/Nrf2 signaling pathway and gut microbiota.
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