The American journal of Chinese medicine
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This study explores the anti-inflammatory properties of lupeol, a notable phytosterol found in various medicinal plants, highlighting its potential as a candidate for new drug development. We examined the effects of lupeol on heme oxygenase (HO)-1, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs), as well as its impact on inflammatory markers in the lung tissues of LPS-challenged mice. ⋯ In vivo, lupeol significantly lowered iNOS expression and tumor necrosis factor (TNF)-α levels in bronchoalveolar lavage fluid from LPS-treated mice. These findings suggest that lupeol exerts its anti-inflammatory effects by modulating key signaling pathways, positioning it as a promising candidate for the development of novel therapeutics targeting pathological inflammation.
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Diabetic kidney disease (DKD) has become the primary cause of end-stage renal disease (ESRD), causing an urgent need for preventive strategies for DKD. Astragaloside I (ASI), a bioactive saponin extracted from Astragalus membranaceus (Fisch.) Bunge has been demonstrated to possess a variety of biological activities. This study investigates the therapeutic potential of ASI in DKD and the underlying molecular mechanism using db/db mice in vivo and high glucose (HG)-induced SV40-MES-13 cells in vitro. ⋯ Furthermore, ASI downregulated HDAC3 expression, upregulated Klotho expression, and enhanced Klotho release. ASI is directly bound to HDAC3, and the beneficial effects of ASI on Klotho/TGF-β1/Smad2/3-mediciated renal fibrosis in DKD were reversed by the HDAC3 agonist ITSA-1. In conclusion, ASI attenuates renal fibrosis in DKD, and may act through concurrently inhibiting HDAC3 and TGF-β1, thereby regulating HDAC3-mediciated Klotho/TGF-β1/Smad2/3 pathway.
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Astragaloside IV (AS-IV), a natural triterpenoid isolated from Astragalus membranaceus, has been used traditionally in Chinese medicine. Previous studies have highlighted its benefits against carcinoma, but its interaction with the gut microbiota and effects on adenomatous polyps are not well understood. This present study investigates the effects of AS-IV on colonic adenomatous polyp (CAP) development in high-fat-diet (HFD) fed [Formula: see text] mice. [Formula: see text] mice were fed an HFD with or without AS-IV or Naringin for 8 weeks. ⋯ Finally, the anti-adenoma efficacy of AS-IV alone was significantly suppressed post pseudoaseptic intervention in HFD-fed [Formula: see text] mice but could be reinstated following a combined with Bifidobacterium pseudolongum transplant. AS-IV attenuates CAP development in HFD-fed [Formula: see text] mice by regulating gut microbiota and metabolomics, impacting the Wnt3a/β-catenin signaling pathway. This suggests a potential new strategy for the prevention of colorectal cancer, emphasizing the role of gut microbiota in AS-IV's antitumor effects.
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Acute kidney injury (AKI) is a major public health problem worldwide that still lacks effective treatments. Recent studies have suggested that ferroptosis is a key mediator of AKI due to its activation of lipid peroxidation. Therefore, we hypothesized that antiferroptosis agents might be a novel potential therapeutic strategy for AKI. ⋯ Moreover, knockdown of VKORC1 diminished the renal protective and antiferroptosis roles of LG. Collectively, our findings demonstrated that LG protected against AKI by inhibiting VKORC1-mediated ferroptosis. This suggests that inhibiting ferroptosis might be a novel therapeutic approach in the future.
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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.