Kuida Chen, Shipeng Lu, Ke Shi, Mustafa Hussein Ali, Jian Liu, Fangzhou Yin, Wu Yin
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引用次数: 0
Abstract
Sepsis-induced acute lung injury (ALI) is a life-threatening condition associated with high morbidity and mortality rates in intensive care units (ICUs). Emerging evidence from clinical studies suggests that compounds derived from traditional Chinese medicine (TCM) have shown promising therapeutic effects in treating sepsis-induced ALI. Hyperoside is a bioactive compound extracted from TCM. Prior studies reported that hyperoside exhibits potent anti-inflammatory, antioxidant, and organ-protective properties, however, the underlying mechanisms of its effects on ALI remain unclear. Hyperoside pretreatment significantly reduced inflammation, iron accumulation, and lipid peroxidation in the pulmonary tissues of ALI mice induced by CLP and in LPS-stimulated MLE-12 cells. In particular, hyperoside preferentially binds with Keap1 at Arg380 and Arg415, thereby inhibiting the ubiquitin-mediated degradation of nuclear Nrf2, promoting its translocation to the nucleus, and leading to upregulation of anti-ferroptosis gene expression. Moreover, the protective effects of hyperoside were significantly abrogated after Nrf2 expression was silenced or its activity was inhibited by chemical inhibitors, highlighting that Nrf2 is critically involved in the impact of hyperoside. This study confirms that hyperoside exhibits a therapeutically protective effect against sepsis-induced ALI by inhibiting ferroptosis through Nrf2-mediated signaling pathway. Hyperoside acts as an Nrf2 activator by preferentially binding to Arg380 and Arg415 of Keap1 and disrupting the Keap1/Nrf2 interaction.
期刊介绍:
International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome.
The subject material appropriate for submission includes:
• Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders.
• Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state.
• Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses.
• Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action.
• Agents that activate genes or modify transcription and translation within the immune response.
• Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active.
• Production, function and regulation of cytokines and their receptors.
• Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.