Antioxidants
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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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Journal of Ginseng Research
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2026
·
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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Frontiers in Genetics
·
2022
·
IF 4.772
Tang Han,Du Han,Kuang Xielan,Huang Hao,Zeng Jingshu,Long Chongde,Zhu Binbin,Fu Licheng,Wang Hua,Zhang Qingjiong,Lin Shuibin,Yan Jianhua,Shen Huangxuan
Age-related macular degeneration (AMD), which is the leading cause of blindness among the elderly in western societies, is majorly accompanied by retinal pigment epithelium (RPE) degeneration. Because of the irreversible RPE cell loss among oxidative stress, it is crucial to search for available drugs for atrophic (dry) AMD. RNA-Seq analysis revealed that genes related to aging and mitochondrial health were differentially expressed under Arbutin treatment, whereas compared to oxidative injury, our study demonstrated that Arbutin substantially abrogated oxidative stress-induced cell senescence and apoptosis linked to intracellular antioxidant enzyme system homeostasis maintenance, restored mitochondrial membrane potential (MMP), and reduced the SA-β-GAL accumulation in RPE. Furthermore, Arbutin alleviated oxidative stress-mediated cell apoptosis and senescence via activation of SIRT1, as evidenced by the increase of the downstream FoxO3a and PGC-1α/β that are related to mitochondrial biogenesis, and the suppression of NF-κB p65 inflammasome, whereas rehabilitation of oxidative stress by SIRT1 inhibitor attenuated the protective effect of Arbutin. In conclusion, we validated the results in an in vivo model constructed by NAIO3-injured mice. OCT and HE staining showed that Arbutin sustained retinal integrity in the case of oxidative damage in vivo, and the disorder of RPE cytochrome was alleviated through fundus observation. In summary, our findings identified that oxidative stress-induced mitochondrial malfunction and the subsequent senescence acceleration in RPE cells, whereas Arbutin inhibited TBHP-induced RPE degeneration via regulating the SIRT1/Foxo3a/PGC-1α/β signaling pathway. These findings suggested that Arbutin is a new agent with potential applications in the development of AMD diseases.
研究领域:
眼科学
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分子生物学
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药理学
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衰老研究
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JOURNAL OF ETHNOPHARMACOLOGY
·
2026
·
IF 6.8
Hongxuan Yang,Yun Liang,Yue’e Chen,Lin Liu,Yingfang Wang,Qiting Dou,Jinmei Gong,Zijing Liao,Junqiu Dong,Xuguang Hu
Ethnopharmacological relevance Lonicera japonica Thunb (honeysuckle), a traditional Chinese medicine, has been historically used to clear heat, detoxify, and dispel wind-heat. Modern research has identified various bioactive constituents from honeysuckle, supporting its potential in managing inflammatory and metabolic disorders. However, the anti-hyperuricemic activity and mechanism of its peptide components remain unexplored. Aim of the study: This study aimed to investigate the anti-hyperuricemic effect of honeysuckle-derived peptides and the underlying mechanisms, with a focus on uric acid production, excretion, and gut microbiota modulation. Materials and methods Nine novel peptides were identified from honeysuckle by HPLC-MS/MS and screened through molecular docking against xanthine oxidase (XOD). In vitro XOD inhibition and antioxidant assays were performed. A hyperuricemic mouse model was induced by potassium oxonate and hypoxanthine. Mice were treated with honeysuckle peptides at low, medium, and high doses. Serum biomarkers, renal and ileal histopathology, protein and mRNA expression of PGC-1α/PPARγ/ABCG2 pathway components, and gut microbiota composition (16S rRNA sequencing) were analyzed. Results Molecular docking confirmed strong binding between the peptides and XOD. In vitro , honeysuckle peptides significantly inhibited XOD activity and exhibited potent antioxidant capacity. In vivo , peptide treatment effectively reduced serum uric acid, XOD, creatinine, and blood urea nitrogen levels, alleviated renal and intestinal tissue damage, and suppressed inflammatory cytokines. The treatment also significantly upregulated the renal PGC-1α/PPARγ/ABCG2 pathway at both protein and mRNA levels. Furthermore, the peptides restored gut microbial diversity and corrected the Firmicutes/Bacteroidota ratio. Conclusion Honeysuckle peptides ameliorate hyperuricemia through a dual mechanism: inhibiting uric acid production by suppressing XOD activity and promoting its renal excretion by activating the PGC-1α/PPARγ/ABCG2 pathway, coupled with restoring gut microbiota homeostasis. This study provides a pharmacological basis for the traditional use of honeysuckle and highlights its peptides as promising candidates for managing hyperuricemia.
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JOURNAL OF MOLECULAR HISTOLOGY
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2025
·Vol. 56
·期 6
·1-14
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IF 2.2
Wang Pu,Sun Congcong,Shi Chao,Gao Yong,Luan Chunyu,Yan Chao
Osteoarthritis (OA) is a degenerative joint disease characterized by pathological changes such as articular cartilage degeneration and bone hyperplasia. Mitochondrial dysfunction in chondrocytes has been identified as a critical factor contributing to the progression of OA. Although Evodiamine (Evo) has been demonstrated effeicacy in inhibiting inflammatory responses and matrix degradation in OA chondrocytes, its effects and underlying mechanisms regarding mitochondrial dysfunction in these cells remain to be elucidated. IL-1β was utilized to stimulate chondrocytes in order to establish an in vitro OA model. Subsequently, the proliferation, lactate dehydrogenase (LDH) release, and apoptosis of chondrocytes were systematically evaluated. Mitochondrial function in chondrocytes was evaluated by quantifying of ATP content, ROS level, mitochondrial DNA (mtDNA) copy number, activities of mitochondrial respiratory chain Complexes I and III, as well as mitochondrial membrane potential change. Furthermore, the protein expression levels of the SIRT1/PGC-1α signaling pathway were examined, and an intervention involving the SIRT1 inhibitor EX527 was conducted to elucidate the potential mechanisms underlying the effects of Evo on chondrocytes. Evo treatment significantly elevated the proliferation activity of IL-1β-stimulated chondrocytes, inhibited LDH release and apoptosis, increased mtDNA copy number and ATP content, enhanced the enzymatic activities of Complexes I and III, and suppressed ROS production as well as mitochondrial membrane potential loss. Furthermore, Evo treatment activated the SIRT1/PGC-1α signaling pathway. However, the addition of the SIRT1 inhibitor EX-527 partially attenuated the protective effects of Evo against IL-1β-induced chondrocyte injury by exacerbating mitochondrial dysfunction. Evo promotes mitochondrial biosynthesis, reduces ROS production and improves mitochondrial function by activating SIRT1/PGC-1α pathway, thereby inhibiting IL-1β-induced chondrocyte injury.
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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风湿病学
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线粒体医学
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CELLULAR SIGNALLING
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2026
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IF 4.7
Yuan Wang,Li Zhu,Xinyi Huang,Zijun Zhou,Yinli Xu,Boxuan Sun,Jiahui Li,Liming Yu,Huishan Wang
Muscle-specific histone methyltransferase 1 (Smyd1) is required for skeletal and cardiac muscle development, yet its roles and mechanisms in diabetes-associated atrial fibrillation (AF) remain poorly defined. This study aims to elucidate the role of the Smyd1-PGC-1α pathway in the pathogenesis of AF and to investigate the underlying mechanisms. In this study, employing bioinformatic data and in vivo/in vitro experiment, we demonstrated that Smyd1 is significantly down-regulated in the atrium of diabetic mice and in HL-1 cardiomyocytes treated with high-glucose/palmitic acid (HG/PA). This detrimental effect was coincided with diminished PGC-1α transcription and impaired mitochondrial biogenesis, contributing to pathological atrial enlargement, structural and electrical remodeling, fibrosis, lipid droplet accumulation, and increased AF susceptibility. Crucially, Smyd1 overexpression reversed the aforementioned damage. Mechanistically, cardiac-specific overexpression of Smyd1 enhanced mitochondrial biogenesis and respiration by activating PGC-1α transcription and ameliorated HG/PA-induced dysfunction in mitochondrial dynamics and membrane potential. This pathway attenuates high-fat-diet/streptozotocin (HFD/STZ) -induced myocardial injury and reduces susceptibility to diabetes-associated AF. These findings indicate that the Smyd1-PGC-1α axis represents a promising preclinical target that warrants further investigation in human tissues and clinical settings.
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JOURNAL OF ETHNOPHARMACOLOGY
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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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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2023
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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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Frontiers in Nutrition
·
2026
·
IF 5.5
Binhong Hu,Ling Yao,Xin Deng,Wei Zhao,Kuo Chen,Jiacheng Zhang,Zhiqiang Li,Jin-ping Li,Wei Jiang,Huabao Liu
AimsThis study aims to explore the potential therapeutic effect of Dendrobium officinale polysaccharide (DOP) on non-alcoholic fatty liver disease (NAFLD) induced by high-fat diet (HFD), and to elucidate the underlying mechanism involving the SIRT6/PGC-1α signaling axis and the regulation of the gut microbiota.MethodsWe extracted and characterized DOP. We established a rat model of NAFLD induced by HFD and evaluated the efficacy of DOP by integrating multi-omics techniques (transcriptomics, metabolomics) and 16S rRNA sequencing. To verify the specific role of SIRT6, we introduced the SIRT6 inhibitor OSS_128167 in the primary hepatocyte model induced by oleic acid/palmitic acid (OA/PA).ResultsDOP significantly alleviated liver steatosis, oxidative stress, and lipid metabolism disorders induced by HFD. Multi-omics analysis indicated that DOP regulated liver glycerophospholipid metabolism and restored intestinal microbiota homeostasis, significantly increasing the abundance of beneficial bacteria such as Lactobacillus. Mechanistically, DOP activated the liver SIRT6/PGC-1α signaling axis, thereby enhancing antioxidant defense and inhibiting lipogenesis. Crucially, in vitro experiments confirmed that the SIRT6 inhibitor OSS_128167 eliminated the protective effect of DOP on lipid accumulation, confirming that the effect of DOP depends on SIRT6.ConclusionDOP improves NAFLD through dual mechanisms of regulating the gut-liver axis homeostasis and directly activating the liver SIRT6/PGC-1α signaling pathway. The results of this study provide a theoretical basis for developing DOP as a drug for the treatment of NAFLD.
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Food & Function
·
2020
·Vol. 11
·期 7
·5815-5826
·
IF 4.171
Yi Zhao,Mu-Zi Li,Milton Talukder,Yu Luo,Yue Shen,Hao-Ran Wang,Jin-Long Li
Di(2-ethylhexyl) phthalate (DEHP) is a widespread environmental contaminant, which is mainly used as a plasticizer to improve the flexibility of products; however, its extensive use causes male reproductive damage. Lycopene (LYC) has a protective effect on male reproductive toxicity. Nevertheless, the underlying role of LYC in DEHP-induced spermatogenic cell damage remains unclear. Our study aimed to investigate the role of LYC in DEHP-induced spermatogenic cell damage and its underlying mechanism. Male ICR mice were treated with LYC (5 mg kg−1) and/or DEHP (500 mg kg−1 or 1000 mg kg−1) for 28 days. The results showed that LYC alleviated the DEHP-induced decrease in mitochondria volume density and mitochondrial membrane potential (ΔΨm). Subsequently, LYC prevented the DEHP-induced PGC-1α-mediated reduction in mitochondrial biogenesis in spermatogenic cells. LYC exhibited a potential preventive effect against DEHP-induced mitophagy caused by mitochondrial dynamics disorder in the spermatogenic cells. Meanwhile, LYC relieved DEHP-induced mitochondrial stress in the spermatogenic cells by activating UPRmt. These results proved that mitochondrial quality control may be related to the beneficial role of LYC in preventing DEHP-induced mitophagy in spermatogenic cells. This study provides new evidence of mitochondrial quality control as a target for LYC treatment, which can prevent DEHP-induced toxicity.
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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TROPICAL JOURNAL OF PHARMACEUTICAL RESEARCH
·
2022
·Vol. 21
·期 10
·2139-2146
·
IF 0.523
Limei Du,Xinglan Huo,Ying Liu
Purpose: To study the influence of resveratrol on chronic obstruction in Aspergillus fumigatus infection-induced chronic lung disease (COPD) in rats, and the process involved.
Methods: Seventy-five Sprague Dawley SD) rats were assigned to blank control, COPD model, Aspergillus fumigatus-infected COPD model, low (100 mg/kg) and high-dose (200 mg/kg) resveratrol groups, with 15 rats in each group. Enzyme-linked immunosorbent assay (ELISA) was used to assay IL-6, IL-8 and TNF-α in bronchoalveolar lavage fluid (BALF), while lung protein concentrations of AMPK and PGC-1α were assayed by immunoblotting.
Results: In low- and high-dose resveratrol groups, inflammatory factor levels were significantly lower than the corresponding levels in COPD model and Aspergillus fumigatus-infected COPD model (p < 0.05), while lung tissue proteins of AMPK, PGC-1α, and AQP5 of the rats given high-dose resveratrol were significantly raised, relative to corresponding levels in rats given low-dose resveratrol (p < 0.05).
Conclusion: Resveratrol modulates expression levels of secretory factors and surface markers in alveolar macrophages in COPD model rats infected with Aspergillus fumigatus. Resveratrol exerts this effect through the regulation of AMPK/PGC-1α signaling pathway.
研究领域:
药理学
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免疫学
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呼吸医学
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Biology-Basel
·
2026
·Vol. 15
·期 13
·999
·
IF 4.3
Xiang Li,Bo Tian,Yuxin Chen,Huili Tong,Xiaoming Chen,Zhifeng Cheng
Simple SummaryType 2 diabetes (T2DM) often leads to skeletal muscle loss and weakness, a condition called sarcopenia, which worsens human health. This study explored whether carnosine, a natural dipeptide found in meat and present in human muscle, can help protect against muscle wasting. Using a T2DM sarcopenia mouse model and a high-glucose-treated C2C12 myotube in vitro model, the researchers found that carnosine levels were reduced in T2DM sarcopenia muscles. Oral carnosine supplementation in the mice helped alleviate skeletal muscle atrophy. Carnosine works by activating a cellular signaling pathway that boosts the number of mitochondria (the energy powerhouses of cells) and shifts muscle fibers toward a more oxidative type, leading to stronger and healthier muscles in T2DM sarcopenia mice. These findings suggest that carnosine supplementation could be a simple and promising nutritional strategy to help manage skeletal muscle loss in people with type 2 diabetes, though further studies in humans are needed to confirm its effectiveness.Type 2 diabetes mellitus (T2DM) accounts for over 90% of diabetes cases, and T2DM-related sarcopenia is a growing concern. Carnosine, abundant in human skeletal muscle, helps maintain muscle quality and function. This study investigated whether carnosine deficiency contributes to T2DM-related sarcopenia and whether exogenous carnosine supplementation alleviates muscle atrophy. A mouse model of T2DM sarcopenia was established using streptozotocin combined with a high-fat diet. LC-MS metabolomics revealed a significant reduction in carnosine content in the gastrocnemius muscle of model mice. A C2C12 myotube atrophy model was induced by high-glucose (HG), and qRT-PCR showed altered expression of carnosine metabolism-related enzymes, suggesting disrupted carnosine homeostasis under T2DM conditions. Mechanistic investigations using immunofluorescence, Western blotting, transcriptome sequencing, mitochondrial staining, and molecular docking indicated that carnosine may alleviate high-glucose-induced myotube atrophy through the PI3K/AMPK/PGC-1α signaling pathway. In vivo, carnosine supplementation increased the number of mitochondria and the proportion of slow muscle fibers in gastrocnemius muscle, ameliorating the atrophic phenotype. These findings suggest that carnosine has potential as a candidate for intervention in T2DM-related sarcopenia, though further validation of its direct molecular targets is required.
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