The American journal of Chinese medicine
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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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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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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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Panax notoginseng saponins (PNS), the primary medicinal ingredient of Panax notoginseng, mitigates cerebral ischemia-reperfusion injury (CIRI) by inhibiting inflammation, regulating oxidative stress, promoting angiogenesis, and improving microcirculation. Moreover, PNS activates nuclear factor erythroid 2-related factor 2 (Nrf2), which is known to inhibit ferroptosis and reduce inflammation in the rat brain. However, the molecular regulatory roles of PNS in CIRI-induced ferroptosis remain unclear. ⋯ Mechanistically, PNS treatment facilitated Nrf2 activation, thereby regulating the expression of iron overload and lipid peroxidation-related proteins and the activities of anti-oxidant enzymes. This cascade inhibited ferroptosis and mitigated CIRI. Altogether, these results suggest that the ferroptosis-mediated activation of Nrf2 by PNS reduces inflammation and is a promising therapeutic approach for CIRI.
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Recent research has indicated that formononetin demonstrates a potent anti-inflammatory effect in various diseases. However, its impact on sterile inflammation kidney injury, specifically acute kidney injury (AKI), remains unclear. In this study, we utilized an ischemia/reperfusion-induced AKI (IRI-AKI) mouse model and bone marrow-derived macrophages (BMDMs) to investigate the effects of formononetin on sterile inflammation of AKI and to explore the underlying mechanism. ⋯ The mechanism involved the KLF6 and p-STAT3 pathway, as overexpression of KLF6 restored pro-inflammatory cytokine levels and pro-inflammatory polarization. Our findings demonstrate that formononetin can significantly improve renal function and reduce inflammation in IRI-AKI, which may be attributed to the inhibition of KLF6/STAT3-mediated macrophage pro-inflammatory polarization. This discovery presents a new promising therapeutic option for the treatment of IRI-AKI.