Jingchao Li,Yinghua Zeng,Fengjiao Liu,Xu Liao,Chongbin Zhong,Shujuan Dong,Yanbin Cai,Pingzhen Yang
Doxorubicin (DOX) chemotherapy is a cornerstone of cancer treatment, but its clinical application and effectiveness are severely restricted due to its life-threatening cardiotoxicity. Xanthohumol (XH), a compound from traditional Chinese medicine, is noted for its antioxidant properties and the potential to mitigate DOX-induced cardiotoxicity (DIC). However, its poor water solubility results in low biocompatibility, making it susceptible to immune system clearance, which severely restricts its application in vivo. In this study, we first identified and demonstrated that XH can effectively mitigate DIC by inhibiting ferroptosis. We designed a biomimetic nanodelivery system encapsulating XH within porous poly(lactic-co-glycolic acid) (PLGA) nanoparticles, further coated with an erythrocyte membrane (XH-NPs@RBCm). This system offers several advantages, including evasion of macrophage phagocytosis and prolonged circulation time, thereby enhancing the stability and bioavailability of XH in vivo. Treatment with XH-NPs@RBCm significantly reduced reactive oxygen species-dependent ferroptosis, improving the DOX-induced myocardial atrophy and cardiac dysfunction. Our study underscores the therapeutic promise of XH-NPs@RBCm in treating DIC through ferroptosis inhibition, offering key insights into biomimetic nanodelivery system development for DIC management.
Wei Liu,Xiao Chen,Chen Yang,Zequn Lin,Xinfeng Huang,Zhen Zhang,Jianjun Liu
Alzheimer's disease (AD) is a complex disease with unknown etiology and pathogenesis. We described a combined analysis of murine proteomics and microbiomics to find potential therapeutic targets of different doses of xanthohumol (Xn), with the goal of providing a biological basis for the treatment of early AD. Xn improved the spatial learning and memory ability of APP/PS1 mice; this was associated with an increased number of newborn neurons in the subgranular zone (SGZ) and dentate gyrus (DG) and a decreased inflammatory response. 108 proteins were significantly changed after 0.5 mg/kg Xn treatment while only 72 proteins changed by 5 mg/kg Xn. Eight significant microbiota were modulated by different doses of Xn at line discriminant analysis (LDA) score 3.0, but only three of which were regulated by 0.5 mg/kg Xn at LDA score 4.0. In addition, Xn treatment could significantly regulate the pathways of neurodegeneration- multiple diseases in the hippocampus and the penicillin and cephalosporin biosynthesis and atrazine degradation pathways in the gut. Interestingly, Nefl protein validated by correlation analysis was found in the common signaling pathway. 0.5 mg/kg Xn was able to reverse the correlation between hippocampal proteins and gut microbiota. Xn treatment significantly improved cognitive function in AD transgenic mice. Different doses of Xn caused significant differences in protein expression and flora composition and abundance, suggesting that the doses of Xn should be selected with caution, and low dose may be better in the prevention of AD.
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