The American journal of Chinese medicine
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Diabetic kidney disease (DKD) is a prominent etiological factor underlying the onset of end-stage kidney disease, which is characterized by the presence of microalbuminuria. Recent studies have found that high glucose can induce mitochondrial dysfunction and ferroptosis in podocytes, leading to renal impairment and proteinuria. Triptolide was extracted from traditional Chinese medicine Tripterygium wilfordii Hook F., which has anti-inflammatory, anti-oxidant, and podocyte protective activities. ⋯ Additionally, triptolide up-regulated the expression of NFE2-related factor 2 (Nrf2) and change the expression of its downstream targets related to ferroptosis. Furthermore, the podocyte actin cytoskeleton was stabilized by triptolide, and the transition from slit diaphragm (SD) to tight junction (TJ), which is a pivotal character of filtration barrier damage, was attenuated by triptolide. In conclusion, our results suggest that triptolide could stabilize the glomerular podocyte cytoskeleton and attenuate renal SD-TJ transition in DKD by upregulating Nrf2 and thereby inhibiting ferroptosis.
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Fucoxanthin, sourced from marine brown algae, diatoms, and microalgae, is known to possess strong anti-inflammatory activity. To explore its intrinsic mechanism, we investigated its effects on acute lung injury (ALI) with an experiment using lipopolysaccharide (LPS)-induced RAW264.7 inflammatory cells and an ALI animal model. Fucoxanthin was observed to suppress the inflammatory response in vitro by reducing the levels of inflammatory markers such as PTGS2, iNOS, and TNF-α. ⋯ Further research revealed that fucoxanthin could raise the levels of [Formula: see text]-Glu-Cys and carbamyl glycine, which are intermediate metabolites of glutathione synthesis, in RAW264.7 cells. This implies that fucoxanthin can inhibit ferroptosis by regulating the [Formula: see text]-glutamyl cycle. Our research demonstrated that fucoxanthin is capable of activating phosphorylated STAT3 and raising the expression of Nrf2 and HO-1, implying that fucoxanthin may be able to prevent LPS-induced ferroptosis in ALI through the Nrf2/STAT3 pathway.
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This study is to explore the effects of paeoniflorin (PF) on oxidative stress (OS) and inflammation in Parkinson's disease (PD) via the HSF1-NRF1 axis. SH-SY5Y cells were pretreated with PF and induced with α-synuclein preformed fibrils (PFF), followed by gain- and loss-of-function assays. Afterward, detection was conducted on cell viability, mitochondrial membrane potential ([Formula: see text]m), and reactive oxygen species (ROS), cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) levels. ⋯ PF dose-dependently reduced RGMa expression, ROS, MDA, TNF-α, IL-2, and IL-6 levels; mitigated apoptosis; and lowered cleaved-Caspase 3, cleaved-Caspase 8, COX-2, and iNOS expression while improving cell viability; increasing [Formula: see text]m, GAP-43, and BDNF expression; and raising SOD, GSH-Px, CAT, and IL-10 levels in PFF-induced SH-SY5Y cells. These effects were neutralized by HSF1 knockdown. In conclusion, PF dose-dependently activated the HSF1-NRF1 axis and alleviated OS and inflammation in PFF-treated mice, thereby impeding PD progression in mice.
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Cellular senescence is an adverse factor in the development of pulmonary fibrosis (PF). Ginsenoside Rb1 has been found to inhibit both cellular senescence and PF. This study aimed to elucidate the molecular mechanisms by which ginsenoside Rb1 regulates cellular senescence and PF. ⋯ As expected, ginsenoside Rb1 alleviated ARD-induced senescence and fibrosis in MRC-5 cells by activating the NRF2/QKI/SMAD7 axis. Therefore, it was found that ginsenoside Rb1 mitigates cellular senescence and fibrosis during PF progression by activating the NRF2/QKI/SMAD7 axis. This study provides a potential therapeutic strategy for the treatment of PF and elucidates its mechanism of action.
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Hemorrhagic shock (HS) is a critical condition with high mortality caused by acute blood loss. Cardiac injury and dysfunction induced by HS is a major factor associated with the poor prognosis of affected patients. Schisandrin A (Sch A), a dibenzocyclooctadiene lignan extracted from Fructus schisandrae, exhibits multiple biological activities, including anti-inflammatory, and antioxidant effects. ⋯ The transformation of cytochrome c (Cyto c) induced by HS was also restored by Sch A. Importantly, the activation of the Nrf2 signaling pathway mediated the protective effects of Sch A against cardiac injury induced by HS. In conclusion, it was found that Sch A ameliorated HS-induced cardiac injury and dysfunction through suppressing apoptosis and oxidative stress, as well as alleviating mitochondrial dysfunction via the Nrf2 signaling pathway.