The American journal of Chinese medicine
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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.
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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.
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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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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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Subarachnoid hemorrhage (SAH), a specific subtype of cerebrovascular accident, is characterized by the extravasation of blood into the interstice between the brain and its enveloping delicate tissues. This pathophysiological phenomenon can precipitate an early brain injury (EBI), which is characterized by inflammation and neuronal death. Rutaecarpine (Rut), a flavonoid compound discovered in various plants, has been shown to have protective effects against SAH-induced cerebral insult in rodent models. ⋯ These findings highlight the importance of SIRT6 in the regulation of inflammation and suggest a potential mechanism for the protective effect of Rut on EBI. In summary, Rut may have the potential to prevent and treat SAH-induced brain injury by interacting with SIRT6. Our findings may provide a new therapeutic strategy for the treatment of SAH-induced EBI.