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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Evidence-based Complementary and Alternative Medicine
·
2023
·
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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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.
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INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2015
·Vol. 36
·期 3
·873-880
·
IF 2.088
Yu Lou,Zhen Wang,Yi Xu,Ping Zhou,Junxian Cao,Yuanshi Li,Yeping Chen,Junfeng Sun,Lu Fu
Treatment with doxorubicin (DOX) is one of the major causes of chemotherapy-induced cardiotoxicity and is therefore, the principal limiting factor in the effectiveness of chemotherapy for cancer patients. DOX‑induced heart failure is thought to result from endoplasmic reticulum (ER) stress and cardiomyocyte apoptosis. Resveratrol (RV), a polyphenol antioxidant found in red wine, has been shown to play a cardioprotective role. The aim of the present study was to examine the effects of RV on DOX‑induced cardiotoxicity in H9c2 cells. We hypothesized that RV would protect H9c2 cells against DOX‑induced ER stress and subsequent cell death through the activation of the Sirt1 pathway. Our results demonstrated that the decrease observed in the viability of the H9c2 cells following exposure to DOX was accompanied by a significant increase in the expression of the ER stress‑related proteins, glucose‑regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP). However, we found that RV downregulated the expression of ER stress marker protein in the presence of DOX and restored the viability of the H9c2 cells. Exposure to RV or DOX alone only slightly increased the protein expression of Sirt1, whereas a significant increase in Sirt1 protein levels was observed in the cells treated with both RV and DOX. The Sirt1 inhibitor, nicotinamide (NIC), partially neutralized the effects of RV on the expression of Sirt1 in the DOX‑treated cells and completely abolished the effects of RV on the expression of GRP78 and CHOP. The findings of our study suggest that RV protects H9c2 cells against DOX‑induced ER stress through ER stabilization, and more specifically through the activation of the Sirt1 pathway, thereby leading to cardiac cell survival.
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ENVIRONMENTAL POLLUTION
·
2021
·
IF 8.071
Wen Chen,Qiang Chu,Xiang Ye,Yuhao Sun,Yangyang Liu,Ruoyi Jia,Yonglu Li,Pengcheng Tu,Qiong Tang,Ting Yu,Chuan Chen,Xiaodong Zheng
Increasing attention has been brought to microplastics pollution recently, while emerging evidences indicate that nano-plastics degraded from microplastics are more of research significance owing to stronger toxicity. However, there is little study focused on the prevention of nano-plastics induced toxicity until now. Canidin-3-glucoside (C3G), a natural anthocyanin proved to possess multiple functions like antioxidant and intestinal tissue protection. Thus, we proposed whether C3G could act as a molecular weapon against nano-plastics induced toxicity. In Caco2 cell and Caenorhabditis elegans ( C. elegans ) models, we found that polystyrene (PS) nano-plastics exposure resulted in physiological toxicity and oxidative damage, which could be restored by C3G. More significantly in Caco2 cells, we observed that autophagy was activated via Sirt1-Foxo1 signaling pathway to attenuate PS induced toxicity after C3G intervention and further verified by adding autophagy inhibitor 3-Methyladenine (3-MA). Meanwhile, PS co-localization with lysosomes was observed, indicating the encapsulation and degradation of PS. In C. elegans , by detecting LGG-1/LC3 expression in GFP-targeted LGG-1 report gene (LGG-1:GFP) labeled transgenic DA2123 strain, the co-localization of LGG-1:GFP with PS was found as well, means that autophagy is involved in C3G’s beneficial effects. Furthermore, we were surprised to find that C3G could promote the discharge of PS from N2 nematodes, which reduces PS toxicity more directly.
研究领域:
环境科学
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毒理学
·
细胞生物学
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分子生物学
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Food Bioscience
·
2026
·
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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Frontiers in Microbiology
·
2022
·
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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Scientific Reports
·
2026
·
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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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.
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TOXICOLOGY
·
2025
·
IF 4.6
Mei-Ling Le,Jia-Yu Xue,Li-Hai Wu,Xin-Yuan Zhao,Jing Ding,Yang-Yang Yuan,Yi-Qi Wan,Da-Lei Zhang
Hexafluoropropylene oxide (HFPO) homologues (HFPOs), specifically HFPO-dimeric acid (DA), HFPO-trimeric acid (TA) and HFPO-tetrameric acid (TeA), have emerged as industrial replacements for phased-out perfluorooctanoic acid (PFOA), garnering considerable attention due to their environmental ubiquity and bioaccumulation potential. Nevertheless, the reproductive toxicity of HFPOs remains incompletely characterized, particularly regarding their endocrine-disrupting effect and the underlying mechanisms involving Leydig cell dysfunction. In this study, we investigated the cytotoxic influences of HFPOs on TM3 Leydig cells, focusing on mitochondrial function and dynamics, oxidative stress, and apoptosis. Our findings demonstrated that exposure to HFPOs significantly compromised mitochondrial function and fusion-fission dynamics by disrupting the SIRT1/PGC1α signaling pathway. The mitochondrial dysfunction further triggered excessive ROS production and apoptosis, ultimately impairing TM3 Leydig cell viability and testosterone secretion. However, supplementation with the SIRT1 agonist SRT1720 relieved the inhibitory effect of HFPOs on SIRT1/PGC1α signaling pathway and reversed the expression of apoptosis-associated proteins (BAX/BCL2), oxidative stress-associated proteins (SOD1/SOD2), as well as proteins associated with mitochondrial fusion (MFN2/OPA1) and fission (DRP1/FIS1). These results elucidated the involvement of the SIRT1/PGC1α pathway in mediating the cytotoxicity of HFPOs. Notably, the activation of SIRT1 mitigated HFPO-induced toxicity in the TM3 cells, uncovering its potential in safeguarding testicular cells from the damage caused by HFPOs exposure.
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JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2025
·Vol. 29
·期 8
·e70566
·
IF 4.2
Ying‐jie Ren,Tian‐qi Sun,Yu Lu,Dan‐Li Liu,Rui Gao,Ting Li,Min Guo,Qing‐hua Liu,Hai‐long Wang,Min Pang
Chronic obstructive pulmonary disease (COPD) is a widespread lung disease marked by alveolar wall damage, leading to inflammation and fibrosis. Key risk factors include age, smoking, sex, and education, with smoking being the most crucial. These factors are globally consistent and linked with aging. Club cell secretory protein 16 (CC16), primarily secreted by non‐ciliated bronchial epithelial cells, is crucial for pulmonary health, offering anti‐inflammatory and antioxidant benefits. CC16 levels are notably reduced in COPD, suggesting its enhancement as a potential treatment. In this study, cellular senescence of BEAS‐2B cells was stimulated using cigarette smoke extract (CSE) and the function of recombinant human CC16 protein (rhCC16) in cellular senescence was assessed by detecting the levels of β‐galactosidase, p16, p21, ROS and the underlined mechanism was revealed by measuring mitochondrial biogenesis and metabolism. Additionally, COPD mice were prepared, and rhCC16's role on the cellular senescence of lung tissues was examined. Our findings showed that rhCC16 ameliorated cellular senescence in BEAS‐2B cells and lung tissues of COPD mice accompanied by lower levels of β‐galactosidase, p16, p21 and ROS. Mechanically, rhCC16 mitigated senescence via triggering PGC‐1α expression through the AMPK/SIRT1 pathway and fostering mitochondrial biogenesis and metabolism to reduce the levels of ROS. Furthermore, the results also indicated that rhCC16 exerted its effect via both integrin α4β1 and clathrin‐mediated endocytosis. Collectively, rhCC16 suppresses cellular senescence and ameliorates COPD‐like symptoms by activating the AMPK/Sirt1‐PGC‐1‐α‐TFAM pathway to foster mitochondrial function.
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