In this study,Ganoderma lucidumpolysaccharide decreased blood uric acid in potassium oxonate induced hyperuricemic mice and exerted renal protective effect.

Hyperuricemia (HUA) can lead to hyperuricemic nephropathy (HN) as a result of prolonged uric acid (UA) supersaturation, primarily characterized by excessive inflammation and oxidative stress. In clinical practice, the absence of specific drugs for HN treatment necessitates the use of urate-lowering drugs, despite their lack of reno-protective properties. Linarin, the principal pharmacological constituent of Chrysanthemum indicum L. (C. indicum L.), exhibits diverse bioactivities, including anti-inflammatory, antioxidant, and nephroprotective effects. However, there have been no reports on linarin's ability to mitigate HN, and the underlying mechanisms remain unexplored. This study aimed to investigate the mechanisms of linarin on ameliorating HN, with a particular emphasis on oxidative stress and inflammatory pathways. A HUA mouse model was developed using male ICR mice treated with hypoxanthine and potassium oxonate. Additionally, an adenosine-induced hyperuricemic cell model was established in NRK-52E cells. Following linarin treatment, serum UA levels and renal function parameters were assessed. The expression of proteins associated with UA production and excretion, oxidative stress, inflammation, and apoptosis was evaluated using western blot, immunohistochemical, and immunofluorescence analyses. Furthermore, Nrf2 knockout mice and Nrf2 inhibitor ML385 were utilized to investigate the mechanism of linarin on improving HN. Linarin significantly decreased the serum UA levels, inhibited XO activity and regulated UA transporter in the HUA mice. Moreover, linarin reversed the renal index, serum BUN and Cr levels, along with the expression levels of KIM-1, apoptosis-related molecules. Additionally, linarin obviously reduced the levels of TNF-α, IL-1β and IL-6, and alleviated renal inflammatory via suppressing the TLR4, p-NF-κB and p-IκBα levels. Furthermore, linarin was able to reverse the levels of SOD and MDA, and the expression of Nrf2, Keap1, NQO1, and HO-1 to mitigate oxidative stress both in vitro and in vivo. Inhibition of Nrf2 further confirmed that the renoprotective effect of linarin was linked to the activation of Nrf2. This study is the first to propose linarin as a potential natural compound for alleviating HN by modulating the Nrf2/Keap1 and TLR4/NF-κB signaling pathways, providing a promising strategy for HN.

Non‐alcoholic steatohepatitis (NASH) is a severe inflammatory phase of the non‐alcoholic fatty liver disease (NAFLD) spectrum and can progress to advanced stages of NAFLD if left untreated. This study uses multi‐omics data to elucidate the underlying mechanism of naringenin's reported benefit in alleviating (NASH). Male mice were fed a NASH‐inducing (methionine‐choline‐deficient) MCD diet with or without naringenin supplementation for 6 weeks. Naringenin prevented NASH‐induced histopathological liver damage and reversed the abnormal levels of hepatic triglyceride (TG)/total cholesterol (TC), serum TG/TC, serum alanine aminotransferase/aspartate transaminase, and hepatic malondialdehyde and glutathione. Importantly, naringenin intervention significantly modulated the relative abundance of gut microbiota and the host metabolomic profile. We detected more than 700 metabolites in the serum and found that the gut genus levels of Anaeroplasma and the [Eubacterium] nodatum group were closely associated with xanthine, 2‐picoline, and securinine, respectively. Tuzzerella alterations showed the highest number of associations with host endogenous metabolites such as FAHFA (8:0/10:0), FFA (20:2), carnitine C8:1, tridecanedioic acid, securinine, acetylvaline, DL‐O‐tyrosine, and Phe‐Asn. This study indicates that the interplay between host serum metabolites and gut microbiota may contribute to the therapeutic effect of naringenin against NASH.

Luteolin is a natural flavonoid, which exists in many plants, including onions, broccoli, carrots, peppers, celery, olive oil, and mint. Luteolin is a dietary flavonoid with potent uric acid‐lowering and antioxidant bioactivities. To date, the mechanism by which luteolin alleviates hyperuricemia nephropathy (HN) still needs to be better defined. This study aims to evaluate the therapeutic efficacy of luteolin in a preclinical mouse model and in vitro. Luteolin was administered in the HN mice induced by the combination of potassium oxonate and hypoxanthine to evaluate the potential renoprotective effects in vivo. The NRK‐52E cells were stimulated with adenosine for in vitro evaluation. Hematoxylin and eosin staining, biochemical analysis, immunoblotting, immunofluorescence, and immunohistochemistry were performed for the histopathologic and mechanistic investigations. The results suggest that luteolin attenuated tubular dilation and epithelial atrophy in the renal tissue of HN mice. Further, luteolin improved biochemical indicators concerning renal functions and oxidative stress in vivo. Mechanistically, luteolin reduced the renal expressions of KIM‐1 and caspase‐3. Luteolin activated renal SIRT1/6 cascade and its downstream Nrf2‐mediated antioxidant pathway. Furthermore, luteolin elevated the renal expressions of ATP‐binding cassette subfamily G isoform 2 protein (ABCG2) and organic anion/cation transporters. In addition, livers of luteolin‐treated HN mice exhibited robust inhibition of xanthine oxidase. Together, our study shows that luteolin alleviates renal injury in the HN mice by activating urate excretion and Nrf2/HO‐1/NQO1 antioxidant pathways and inhibiting liver xanthine oxidase activity. Thus, luteolin may be a potential agent for the treatment of HN.