Antioxidants
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2026
·Vol. 15
·期 7
·888
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IF 8.2
Yin Liu,Yan Wang,Xinyu Shi,Ruomei Che,Xiaoli He
Background:Danshen–Gegen is a classic herb pair in traditional Chinese medicine, which has been used to treat cardiovascular and cerebrovascular diseases. Ischemic stroke (IS) is a prevalent cerebrovascular condition; ferroptosis is one of the contributing factors driving the progression of IS. This study aims to determine the underlying mechanism and examine if Danshen–Gegen (DG) extract may prevent cerebral ischemia–reperfusion injury by preventing ferroptosis.Methods:The comprehensive compositional characterization of DG was analyzed by ultra-high-performance liquid chromatography coupled with hybrid quadrupole-orbitrap high-resolution mass spectrometry (UPLC-Q-orbitrap MS). The experiments were conducted in middle cerebral artery occlusion/reperfusion (MCAO/R) rats and oxygen-glucose deprivation/re-oxygenation (OGD/R) cells. The neuroprotective effects of DG on IS were assessed by examining rat survival rates, infarct volume, behavioral scores, and cerebral water content. Then, we tested the accumulation of Fe2+and lipid peroxidation products such as reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA), myeloperoxidase (MPO), and 4-hydroxynonenal (4-HNE) in rats and cells. The expression of nuclear factor erythroid-derived 2-like 2 (Nrf2), Solute Carrier Family 7 Member 11 (-xCT), Glutathione peroxidase 4 (GPX4), Cyclooxygenase-2 (COX-2), Transferrin Receptor 1 (TFR1), and Long-chain-fatty-acid–CoA ligase 4 (ACSL4) was also assessed in vivo and in vitro.Results:UPLC-Q-orbitrap MS analysis was performed to characterize the chemical profile of DG, and a total of 33 chemical constituents were successfully identified. DG significantly alleviated the ischemic damage to brain tissue, reduced infarct volume, and improved neurological dysfunction. The content of Fe2+and lipid peroxidation products was markedly decreased. Furthermore, DG could restore the expression of Nrf2, -xCT, and GPX4 with the inhibition of COX-2, TFR1, and ACSL4, thus achieving a suppressive effect on ferroptosis.Conclusions:The regulatory influence of DG via the Nrf2/System xc-/GPX4 axis may play a crucial role in alleviating ferroptosis and enhancing recovery from cerebral ischemia injury.
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PHYTOTHERAPY RESEARCH
·
2025
·
IF 6.3
Shushu Jiang,Cheng Wang,Yin Dong,Long Chen,Menghao Shi,Fengxiao Zhang,Zhaohui Wang,Minglu Liang
Numerous studies have documented erucin's anticancer and vasodilatory properties, yet its impact on pathological cardiac hypertrophy remains to be fully understood. This study aimed to explore the therapeutic potential of erucin in cardiac hypertrophy induced by pressure overload. Cardiac hypertrophy was induced in mice by transverse aortic constriction (TAC) surgery, and in neonatal rat cardiomyocytes via phenylephrine (PE) treatment. Cardiac function and remodeling were evaluated using echocardiography, histological assessment, and molecular analyses. Mitochondrial function was assessed by measuring mitochondrial respiration, ATP concentration, the NAD+/NADH ratio, and reactive oxygen species (ROS) levels. Molecular docking was performed to identify erucin's downstream effector. Nrf2 and Sirt3 were silenced using siRNAs, and their activities were inhibited with ML385 and 3-TYP, respectively. Here, we found that erucin improved cardiac function and remodeling in TAC-induced hypertrophic mice, mitigated PE-induced cell hypertrophy, and restored mitochondrial function. Molecular docking analysis identified Nrf2 as a target protein of erucin. Erucin increased Nrf2 protein levels and activated the Nrf2 signaling pathway, which in turn promoted Sirt3 transcription. This effect was blocked by silencing Nrf2 or using ML385. Additionally, silencing Nrf2 and Sirt3 or using ML385 and 3-TYP abolished erucin's protective effects. This study is the first to demonstrate that erucin protects against cardiac hypertrophy by improving mitochondrial function through the activation of the Nrf2-Sirt3 pathway. Erucin may emerge as a promising therapeutic candidate for treating cardiac hypertrophy.
研究领域:
心血管生物学
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药理学
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Cong Zhang,Yangkun Xiong,Mingyang Gong,Haixia Zhao,Shan Li,Xin Chen,Xiaochuan Ye,Zhenpeng Qiu
Hyperuricemic nephropathy, a common subtype of chronic kidney disease (CKD), has become an important global public health issue and is closely related to the dramatic increase in fructose consumption. Pachymic acid, the primary active ingredient of the edible fungal herb Poria cocos, has demonstrated the protective capacity against renal injury, but its beneficial effect on hyperuricemic nephropathy remains unclear. In this study, a fructose-diet-induced hyperuricemia nephropathy mouse model was established to reveal the efficacy of pachymic acid in inhibiting hyperuricemic nephropathy the progression. Our results showed that pachymic acid restored abnormal renal function indexes and pathological manifestations such as tubular dilatation and glomerular fibrosis in fructose-fed mice. Transcriptome sequencing results showed marked alterations in glutathione metabolism and ferroptosis signaling pathways in the kidneys of fructose-fed mice after pachymic acid treatment. Mechanistically, pachymic acid activated the Nrf2/GPX-4 signaling pathway by directly binding to Nrf2 and promoting its nuclear translocation, thereby inhibiting ferroptosis, oxidative stress, and inflammatory responses in the kidneys of fructose-fed mice. Consistent results were observed in uric acid-treated HK-2 cells. Notably, both Nrf2 inhibitor ML385 and GPX-4 inhibitor RSL3 treatments reversed the protective effects of pachymic acid against renal injury by suppressing ferroptosis in vitro and in vivo. Summary, our study provides compelling evidence that pachymic acid ameliorates renal injury in fructose-fed mice by inhibiting ferroptosis through targeted activating an Nrf2/GPX-4 pathway, suggesting that dietary supplementation with Poria cocos or pachymic acid might be an effective strategy for CKD prevention, particularly in the subtype of fructose-diet-driven hyperuricemic nephropathy.
研究领域:
药理学
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肾脏病学
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生物化学
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分子生物学
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营养学
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药物化学
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PHYTOMEDICINE
·
2025
·
IF 8.3
Yang Tang,Zheng Wang,Feng Zhou,Ling Li,Chen Sun,Linhui Li,Fei Tang,Dongqin Huang,Zewei Li,Yang Tan,Gang Pei
Background Ulcerative colitis (UC) is a clinically refractory diseases of the digestive system. Benzoylpaeoniflorin (BP) is a compound from Baishao, a Chinese herbal medicine documented with effects of anti-enteritis. However, the potential of BP in treating UC, along with its underlying mechanisms, requires further elucidation. Purpose This research was conducted to assess the effects of BP on dextran sulfate sodium (DSS)-induced UC and to elucidate its underlying mechanisms. Methods The C57BL/6 mouse model of UC was developed by administering the mice to freely drink DSS solution for 7 days. The mice were also subjected to intragastric administration of BP. Histopathology, nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways, and ferroptosis indicators were determined in vivo . Besides, NCM460 cells were used to further evaluate the anti-ferroptosis effect of BP and its potential mechanisms. Ferroptosis agonists iron-dextrin (ID) and Erastin were employed to investigate whether BP exerts anti-UC effect by inhibiting ferroptosis. Similarly, Nrf2 inhibitor ML385 was conducted to ascertain the role of the Nrf2 signaling pathway in the downregulating ferroptosis effect of BP. Moreover, an ultra-performance liquid chromatography coupled with mass spectrometry was utilized to evaluate the changes in glucose metabolism within colon tissues of UC mice following BP treatment. Cellular thermal shift assay (CETSA), surface-plasmon resonance (SPR) and molecular docking were carried out to reveal the binding ability of BP and phosphogluconate dehydrogenase (PGD) protein. The PGD inhibitor, 6PGD-IN-S3 was used to evaluated whether BP inhibits anti-ferroptosis effect by upregulating the expression of PGD. Results BP exhibited significant anti-UC activity, leading to a reduction in both the disease activity index and histological damage in mice afflicted with UC. BP effectively mitigated DSS-induced ferroptosis both in vivo and in vitro . Additionally, ID and Erastin treatment diminished the therapeutic efficacy of BP against UC. A similar trend was observed in mice treated with ML385. Metabolomics analysis indicated that BP had a notable effect in restoring the pentose phosphate pathway (PPP) of colon tissues following DSS administration. The treatment of BP upregulated the activity of PGD. The inhibition of PGD weakened the anti-ferroptosis effect of BP. Subsequent analysis revealed that BP has the potential to effectively bind to PGD, thereby inhibiting PGD entries lysosomes. Conclusion The above findings provide robust evidence for the anti-UC mechanism of BP in inhibiting ferroptosis through upregulation of the Nrf2 signal. PGD, a key enzyme in the PPP, is proved as the target protein of BP to inhibit ferroptosis first time. BP has been further proved to inhibit the lysosomal degradation pathway of PGD.
研究领域:
药理学
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胃肠病学
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分子生物学
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生物化学
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中医学
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细胞生物学
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JOURNAL OF ETHNOPHARMACOLOGY
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2025
·
IF 5.4
Song-Xue Yang,Wei-Lie Xiao,Xing-Jie Zhang
Ethnopharmacological relevance The root of Saposhnikovia divaricata has been traditionally used in Chinese medicine to treat inflammation and immune related skin diseases, such as skin allergy and itchy rash. However, scientific research supporting its efficacy, particularly in curing inflammation from acne, is still scarce. Aim of the study To evaluate the therapeutic effects of essential oil of Saposhnikovia divaricata (EOSD) on Cutibacterium acnes ( C. acnes )-induced acne and investigate its mechanisms. Materials and Methods An acute acne model was established by injecting C. acnes into mouse ears, followed by topical EOSD treatment (0.25 %, 0.5 % and 1 %). Ear tissues were analyzed 24 hours post-treatment. In vitro, C. acnes -stimulated J774A.1 macrophages were treated with EOSD (3, 10 and 30 μg/ml) to assess mitochondrial damage, oxidative stress, and inflammatory responses. Key markers were analyzed using electron microscopy, real-time PCR, immunoblotting, ELISA, and immunofluorescence. Nrf2 knockdown was achieved via siRNA transfection. Results C. acnes suppressed Nrf2 activation, increased ROS levels, and triggered NLRP3 inflammasome activation, leading to inflammation. EOSD restored Nrf2 activity, reduced ROS levels, and inhibited NLRP3 activation. In vitro, EOSD disrupted Nrf2/Keap1 interaction, enhanced Nrf2 nuclear translocation, reduced mitochondrial damage, and suppressed pyroptosis by downregulating IL-1β, Caspase-1, GSDMD, and NF-κB signaling. These effects were reversed by Nrf2 knockdown. Conclusion EOSD alleviates oxidative stress and modulates NLRP3 inflammasome activation through upregulating Nrf2 pathway and inhibiting NF-κB pathway, as well as improving mitochondrial homeostasis and inflammatory responses in acne. These findings suggest that EOSD may be a promising therapeutic agent for the treatment of acne vulgaris.
研究领域:
药理学
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皮肤科学
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分子生物学
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天然药物化学
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免疫学
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氧化应激研究
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信号转导
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Food Bioscience
·
2023
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IF 5.2
Hengju Ge,Jiaxin Li,Yang Xu,Jiahong Xie,Naymul Karim,Fujie Yan,Jianling Mo,Wei Chen
Fructus Gardeniae (FG) is the dried ripe fruit of Gardenia jasminoides Ellis, having beneficial effects for human health. In this study, we discovered that the most relevant pathway influenced by Fructus Gardeniae extract (FGE) is lipid metabolism according to the analysis of network pharmacology. Furthermore, the protective effect of FGE against palmitic acid-induced lipotoxicity was investigated. In L02 cells, FGE significantly promoted cellular proliferation after being treated with palmitic acid , and reduced the accumulation of lipid droplets and triglyceride level . Palmitic acid led to an increase of ROS content, which was reduced by FGE. Additionally, FGE could facilitate Nrf2 localized to nuclear and followed by activating its downstream targets. ML385 (a Nrf2 inhibitor) treatment further proved that FGE attenuated lipotoxicity through regulating Nrf2/ARE pathway. Consequently, we demonstrated for the first time FGE could be regarded as potential functional food materials for hepatic protection.
研究领域:
药理学
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肝脏病学
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INTERNATIONAL IMMUNOPHARMACOLOGY
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2022
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IF 5.714
Yun Zhang,Maihuan Wang,Kebin Zhang,Junze Zhang,Xinpu Yuan,Guijun Zou,Zhen Cao,Chaojun Zhang
As a common disease of the digestive system, chronic gastritis is inflammation of the gastric mucosa caused by various factors. Helicobacter pylori (H. pylori) is one of the main causes of chronic gastritis, which can lead to gastric mucosal damage and gland atrophy, thereby promoting gastrocarcinogenesis. Oxidative stress and the inflammatory response are important mechanisms of H. pylori -induced gastritis. 6′-O-Galloylpaeoniflorin (GPF) is a substance isolated from peony root with antioxidant and anti-inflammatory activities. However, its role and mechanism in the pathogenesis of H. pylori -induced chronic gastritis remain unclear. This study explored the effects of GPF on H. pylori -induced gastric mucosal oxidative stress and inflammation using flow cytometry, western blotting, real-time quantitative PCR, and immunohistochemistry. We found that H. pylori infection increased oxidative stress and expression of inflammatory cytokines in vitro and in vivo and that these outcomes were inhibited by GPF. Furthermore, GPF activated nuclear factor erythroid-related factor-2 (Nrf2) and its downstream target genes in H. pylori -infected GES-1 cells and mice. The anti-inflammatory and antioxidant effects of GPF on H. pylori -infected cells were attenuated by an Nrf2 inhibitor. Taken together, these data suggest that GPF reduces H. pylori -induced gastric mucosa injury by activating Nrf2 signaling and that GPF is a potential candidate for the treatment of H. pylori -associated gastritis.
研究领域:
药理学
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胃肠病学
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分子生物学
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Bing-hao Lin,Run-xun Ma,Jing-tao Wu,Shi-qi Du,Yi-yun Lv,Hao-nan Yu,Wei Zhang,Shu-ming Mao,Guang-yao Liu,Yi-tian Bu,Zi-hao Chen,Chen Jin,Zong-yi Wu,Lei Yang
Osteoporosis (OP) is typically brought on by disruption of bone homeostasis. Excessive oxidative stress and mitochondrial dysfunction are believed to be the primary mechanisms underlying this disorder. Therefore, in order to restore bone homeostasis effectively, targeted treatment of oxidative stress and mitochondrial dysfunction is necessary. Cinnamaldehyde (CIN), a small molecule that acts as an agonist for the nuclear factor erythroid 2-related factor (Nrf2), has been found to possess antiapoptotic, anti-inflammatory, and antioxidant properties. We found that CIN, while rescuing apoptosis, can also reduce the accumulation of reactive oxygen species (ROS) to improve mitochondrial dysfunction and thus restore the osteogenic differentiation potential of BMSCs disrupted by hydrogen peroxide (H2O2) exposure. The role of CIN was preliminarily considered to be a consequence of Nrf2/HO-1 axis activation. The ovariectomized mice model further demonstrated that CIN treatment ameliorated oxidative stress in vivo, partially reversing OVX-induced bone loss. This improvement was seen in the trabecular microarchitecture and bone biochemical indices. However, when ML385 was concurrently injected with CIN, the positive effects of CIN were largely blocked. In conclusion, this study sheds light on the intrinsic mechanisms by which CIN regulates BMSCs and highlights the potential therapeutic applications of these findings in the treatment of osteoporosis.
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CHINESE JOURNAL OF PHYSIOLOGY
·
2023
·Vol. 66
·期 6
·437
·
IF 1.8
Fan Wenbo,Zhou Jianwu
Parkinson's disease (PD) is recognized as a degenerative and debilitating neurodegenerative disorder. The novel protective role of icariside II (ICS II) as a plant-derived flavonoid compound in neurodegenerative diseases has aroused much attention. Herein, the definite impacts of ICS II on the process of PD and the relevant action mechanism were studied. Human neuroblastoma SK-N-SH cells were challenged with 1-methyl-4-phenylpyridinium ion (MPP + ) to construct the PD cell model. MTT assay and flow cytometry analysis, respectively, appraised cell viability and apoptosis. Caspase 3 Activity Assay examined caspase 3 activity. Corresponding kits examined oxidative stress levels. BODIPY 581/591 C11 assay evaluated lipid reactive oxygen species. Iron Assay Kit assessed iron content. Western blot tested the expression of apoptosis-, ferroptosis- and Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) signaling-associated proteins. Molecular docking verified the binding of ICS II with Keap1. The existing experimental results unveiled that ICS II elevated the viability whereas reduced the apoptosis, oxidative stress, and ferroptosis in MPP + -treated SK-N-SH cells in a concentration-dependent manner. Furthermore, ICS II declined Keap1 expression while raised Nrf2, heme oxygenase 1, and GPX4 expression. In addition, ICS II had a strong binding with Keap1 and Nrf2 inhibitor ML385 partially abolished the suppressive role of ICS II in MPP + -triggered apoptosis, oxidative stress, and ferroptosis in SK-N-SH cells. To summarize, ICS II might inhibit apoptosis, oxidative stress, and ferroptosis in the MPP + -stimulated PD cell model, which might be due to the activation of Keap1/Nrf2/GPX4 signaling.
研究领域:
神经科学
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药理学
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细胞生物学
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分子生物学
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