ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2025
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IF 6.1
Siqi Yu,Fudong Wang,Yuan Zhang,Xiaofeng Wang,Hongyu Zhao,Qiang Zheng
Autophagy inhibition induced by paraquat (PQ) poisoning is an important factor causing multi-organ damage, including renal tissue. Dihydrocapsaicin (DHC), the main active ingredient in chili peppers, was reported to induce autophagy, but its effect on PQ-induced AKI remains unclear. Rats were intraperitoneally injected with 25 mg/kg PQ to establish AKI rat model followed immediately by DHC administration (2.5, 5, or 10 mg/kg, i.p.). Rat renal tubular epithelial cells were exposed to PQ (300 μM) in combination with DHC (25, 50, or 100 μM) for 24 h. The results showed that DHC treatment attenuated PQ-induced renal injury and dysfunction while suppressing apoptosis and oxidative stress in vivo and in vitro . Furthermore, DHC administration induced autophagy—a protective mechanism against oxidative stress and apoptosis—as demonstrated by: 1) increased autophagosome/autophagolysosome formation, 2) upregulated LC3-II and autophagy-related gene 7 expressions and reduced p62 protein level. Blocking of autophagy by 3-methyladenine (3-MA) reversed the effects of DHC. Interestingly, transcription factor sex determining region Y-box 9 (Sox9) and autophagy inducer Sestrin2 RNA levels were increased by DHC treatment. Sox9 activated Sestrin2 transcription through direct binding to its promoter region. Sox9 or Sestrin2 silencing reversed the effects of DHC. Collectively, our findings demonstrate that DHC attenuates PQ-induced AKI via Sox9/Sestrin2 axis-mediated autophagy, indicating therapeutic utility of DHC against AKI.
研究领域:
药理学
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毒理学
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分子生物学
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肾脏病学
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DOI
PubMed
高影响因子
iScience
·
2025
·
IF 4.1
Zizheng Liu,Huiming Jiang,Zhaofeng Zhang,Ruiyang Jiang,Rongliang Wang,Jiawei Li,Weitong Li,Guihua Tan,Yuxiang Fei,Zhongyang Lv,Hu Guo,Ziyin Sun,Rui Wu,Hongfei Shi,Dongquan Shi
Chondrocytes experience adverse lipid metabolism disorders during the degeneration of cartilage in osteoarthritis (OA), while the underlying mechanisms remain poorly understood. SESN2, a highly conserved stress-inducible protein, plays a crucial role in regulating lipid metabolism. This study aims to investigate the role of SESN2 in the regulation of fatty acid metabolism in chondrocytes and elucidate the underlying molecular mechanisms in OA. The expression of SESN2 was significantly decreased in OA-affected human cartilage, and this decrease correlated with the upregulation of lipogenic enzymes. Sesn2 inhibited lipogenic enzyme expression in chondrocytes and improved cartilage homeostasis. Mechanistically, SESN2 inhibited the expression of SREBP1 and interacted with SCAP to deactivate SREBP1-mediated transcription for lipogenesis. Finally, overexpression of Sesn2 in mice undergoing DMM surgery ameliorated OA pathological manifestations and improved behavioral experiments performance through inhibiting fatty acid synthesis. Our findings revealed that SESN2 suppresses SREBP1-mediated transcription for lipogenic enzyme in chondrocytes and ameliorates OA progression. These results highlighted that targeting SESN2 may serve as a promising therapeutic strategy for OA.
研究领域:
分子生物学
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生物化学
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细胞生物学
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骨科
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医学研究
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2026
·
IF 6.7
Wang Haijing,Gao Jie,Bai Xuefei,Liu Xiaofeng,Qu Shurong,Gao Yugang,Zhao Yan,Teng Hongbo
Age-related hearing loss (ARHL) is a pervasive sensorineural
deficit
lacking effective pharmacological interventions. Although Eleutherococcus senticosus fruit extracts exhibit
otoprotective potential, their precise bioactive constituents and
underlying molecular mechanisms remain elusive. Using network pharmacology
and transcriptomic analysis as hypothesis-generating tools, followed
by experimental validation, this study identifies chiisanoside (CSS)
as a key bioactive compound mitigating d -galactose-induced
cellular senescence and auditory impairment, with an optimal effective
dose of 25 μM in vitro (HEI-OC1 cells) and 50 mg/kg/day in vivo
(oral gavage in C57BL/6 mice). Mechanistically, the in vitro and in
vivo models demonstrate that CSS suppresses age-related auditory decline
primarily by targeting the SESN2/AMPK signaling axis. Specifically,
CSS upregulates SESN2 to activate AMPK, which not only enhances autophagy
via the mTOR/ULK1 pathway but also concurrently inhibits the HIF-1α/TFRC/FTH1
cascade. These findings provide mechanistic insights supporting the
potential of CSS as a therapeutic candidate in ARHL.
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2026
·
IF 6.2
Yanan Zhao,Rui Wang,Ziyang Huang,Siting Ju,Binghua Dong,Hui Teng,Lei Chen
The gut is often referred to as the “second brain” and is highly vulnerable to alcohol exposure. Galangin, a flavonoid extracted from traditional medicinal herbs, Alpinia officinarum Hance, has manifested auspicious clinical application potential. This study aims to explore the regulatory effect of galangin on ferroptosis in an alcohol-related intestinal injury model and its underlying mechanism. In vivo, we confirmed that galangin administration could alleviate alcohol-induced iron metabolism dysfunction and ferroptosis and activate the SESN2/KEAP1/NRF2 signaling pathway in mice colon. In vitro, alcohol-caused disruption of iron homeostasis and ferroptosis could also be significantly reduced by galangin. Using specific small interfering RNA targeting SESN2 (Si-SESN2) or the NRF2 inhibitor ML385 significantly abrogated the protective effect of galangin. Molecular docking and Co-IP results further revealed that galangin activates NRF2 nuclear translocation by promoting KEAP1/SESN2 formation as well as KEAP1/NRF2 dissociation. Collectively, galangin suppressed ferroptosis by activating the SESN2/KEAP1/NRF2 pathway in mice and Caco-2 cells.
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DOI
PubMed
高影响因子
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