Nonalcoholic steatohepatitis (NASH) and hepatic fibrosis are leading causes of cirrhosis with rising morbidity and mortality worldwide. Currently, there is no appropriate treatment for NASH and hepatic fibrosis. Many studies have shown that oxidative stress is a main factor inducing NASH. Nomilin (NML) and obacunone (OBA) are limonoid compounds naturally occurring in citrus fruits with various biological properties. However, whether OBA and NML have beneficial effects on NASH remains unclear. Here, we demonstrated that OBA and NML inhibited hepatic tissue necrosis, inflammatory infiltration and liver fibrosis progression in methionine and choline-deficient (MCD) diet, carbon tetrachloride (CCl 4 )-treated and bile duct ligation (BDL) NASH and hepatic fibrosis mouse models. Mechanistic studies showed that NML and OBA enhanced anti-oxidative effects, including reduction of malondialdehyde (MDA) level, increase of catalase (CAT) activity and the gene expression of glutathione S-transferases ( GSTs ) and Nrf2-keap1 signaling. Additional, NML and OBA inhibited the expression of inflammatory gene interleukin 6 ( Il-6 ), and regulated the bile acid metabolism genes Cyp3a11 , Cyp7a1 , multidrug resistance-associated protein 3 ( Mrp3 ). Overall, these findings indicate that NML and OBA may alleviate NASH and liver fibrosis in mice via enhancing antioxidant and anti-inflammation capacity. Our study proposed that NML and OBA may be potential strategies for NASH treatment.
Perfluorooctanoic acid (PFOA), a pervasive environmental contaminant, is implicated in ocular diseases through prenatal/embryonic exposure. This study investigated the protective effects of nomilin, a citrus-derived bioactive compound with therapeutic properties, against PFOA-induced ocular and visual impairments in zebrafish. Integrating network toxicology and molecular docking, we identified seven shared targets (including PIK3CA and mTOR) linking PFOA, nomilin, and ocular diseases. Experimental results demonstrated that PFOA exposure suppressed the PIK3CA/AKT/mTOR/pax6 axis, significantly downregulated (by approximately 0.23- to 0.65-fold) ocular development genes (rx1, vsx1, rpgra, lhx4), and induced structural defects (reduced eye size, lens diameter and retinal layer thickness) and visual dysfunction. Nomilin treatment dose-dependently reversed these effects by activating the PIK3CA/AKT/mTOR/pax6 axis, restoring the expression of ocular developmental related genes by 1.45- to 2.85-fold compared to the PFOA-exposed group, improving ocular morphology, and enhancing visual response behaviors. Furthermore, nomilin attenuated PFOA-induced apoptosis. These findings reveal that nomilin mitigates PFOA-mediated ocular toxicity via PIK3CA activation, offering novel therapeutic insights for environmental pollutant-related ocular disorders.
Shortage of soluble Fe in seawater is a limiting condition for benthic seaweeds growth. Utilizing steelmaking slag as the Fe source for seaweeds growth has been proposed. Aiming to find a cost-effective method to promote Fe release, we investigate the effect of adding municipal green wastes. By conducting leaching experiments in freshwater, a sharp improvement in Fe release was observed with the addition of tangerine peel together with steelmaking slag. The flavonoids supplied from the tangerine peel, vicenin-2, apigenin, hesperidin, vitexin, hesperetin and diosmin were observed to have a promotion effect on Fe release. Formation of stable flavonoid-Fe(II) chelates changes the thermodynamic property of Fe(II) in water and disturbs the equilibrium between Fe(II) in slag and Fe(II) in water, which promotes Fe release from slag. These results demonstrate the feasibility to develop a technology for Fe supply in seawater by utilizing the mixture of steelmaking slag and municipal green wastes.
危险品化学品经营许可证（带存储）