Dihydroartemisinin attenuates ischemia/reperfusion-induced renal tubular senescence by activating autophagy.

Acute kidney injury (AKI) is an important factor for the occurrence and development of CKD. The protective effect of dihydroartemisinin on AKI and and reported mechanism have not been reported. In this study, we used two animal models including ischemia-reperfusion and UUO, as well as a high-glucose-stimulated HK-2 cell model, to evaluate the protective effect of dihydroartemisinin on premature senescence of renal tubular epithelial cells in vitro and in vivo. We demonstrated that dihydroartemisinin improved renal aging and renal injury by activating autophagy. In addition, we found that co-treatment with chloroquine, an autophagy inhibitor, abolished the anti-renal aging effect of dihydroartemisinin in vitro. These findings suggested that activation of autophagy/elimination of senescent cell might be a useful strategy to prevent AKI/UUO induced renal tubular senescence and fibrosis.

ß-Hydroxybutyric acid upregulated by Suhuang antitussive capsule ameliorates cough variant asthma through GSK3ß/AMPK-Nrf2 signal axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Cough variant asthma (CVA) is a chronic inflammatory disease characterized by cough as the main symptom. Suhuang antitussive capsule (Suhuang), one of traditional Chinese patent medicines, mainly treats CVA clinically. Previous studies have shown that Suhuang significantly improved CVA, post-infectious cough (PIC), sputum obstruction and airway remodeling. However, the effect of Suhuang on ovalbumin-induced (OVA-induced) metabolic abnormalities in CVA is unknown. AIM OF THE STUDY: This study aimed to identify potential metabolites associated with efficacy of Suhuang in the treatment of CVA, and determined how Suhuang regulates metabolites, and differential metabolites reduce inflammation and oxidative stress. MATERIALS AND METHODS: Rats were given 1 mg OVA/100 mg aluminum hydroxide in the 1st and 7th days by intraperitoneal injection and challenged by atomizing inhalation of 1% OVA saline solution after two weeks to establish the CVA model. Rats were intragastrically (i.g.) administrated with Suhuang at 1.4 g/kg and ß-hydroxybutyric acid (ß-HB) were given with different concentrations (87.5 and 175 mg/kg/day) by intraperitoneal injection for 2 weeks. After 26 days, GC-MS-based metabolomic approach was applied to observe metabolic changes and search differential metabolites. The number of coughs, coughs latencies, enzyme-linked immunosorbent assay (ELISA), histological analysis and quantitative-polymerase chain reaction (Q-PCR) were used to investigate the effects of Suhuang. Then ß-HB on CVA rats, NLRP3 inflammasome and GSK3ß/AMPK/Nrf2 signalling pathway were detected by western blotting. RESULTS: The results showed that Suhuang treatment significantly enhanced the serum level of ß-HB. Interestingly, exposure to exogenous ß-HB was also protective against OVA-induced CVA. ß-HB significantly reduced the number of coughs and lengthened coughs latencies, improved lung injury, reduced the secretion of various cytokines, and directly inhibited the NLRP3 inflammasome. In addition, ß-HB increased the nuclear accumulation of Nrf2 by activating the GSK3ß/AMPK signaling axis, and then inactivating the NF-κB signaling pathway, effectively protecting OVA-induced CVA from oxidative stress and inflammation. CONCLUSIONS: The results of this study shows that ß-HB can reduce inflammation and oxidative stress, the increased production of ß-HB in serum might be the crucial factor for Suhuang to exert its effect in the treatment of CVA.