Yanggan Jiangmei Formula alleviates hepatic inflammation and lipid accumulation in non-alcoholic steatohepatitis by inhibiting the NF-κB/NLRP3 signaling pathway.

The role of NF-κB and the NLRP3 inflammasome in the chronic inflammatory microenvironment of non-alcoholic steatohepatitis (NASH) has been posited as crucial. The Yanggan Jiangmei Formula (YGJMF) has shown promise in ameliorating hepatic steatosis in NASH patients, yet its pharmacological mechanisms remain largely unexplored. This study was conducted to investigate the efficacy of YGJMF in NASH and to elucidate its pharmacological underpinnings. To simulate NASH both in vivo and in vitro, high-fat-diet (HFD) rats and HepG2 cells stimulated with free fatty acids (FFAs) were utilized. The severity of liver injury and lipid deposition was assessed using serum indicators, histopathological staining, micro-magnetic resonance imaging (MRI), and the liver-to-muscle signal intensity ratio (SIRL/M). Furthermore, a combination of enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), immunofluorescence, real-time quantitative polymerase chain reaction (RT-qPCR), and Western blotting analyses was employed to investigate the NF-κB/NLRP3 signaling pathway and associated cytokine levels. The results from liver pathology, MRI assessments, and biochemical tests in rat models demonstrated YGJMF's significant effectiveness in reducing liver damage and lipid accumulation. Additionally, YGJMF markedly reduced hepatocyte inflammation by downregulating inflammatory cytokines in both liver tissue and serum. Furthermore, YGJMF was found to disrupt NF-κB activation, consequently inhibiting the assembly of the NLRP3 inflammasome in both the in vitro and in vivo models. The preliminary findings of this study suggest that YGJMF may alleviate hepatic steatosis and inhibit the NF-κB/NLRP3 signaling pathway, thereby exerting anti-inflammatory effects in NASH.

Effect of Sodium Gluconate on Properties and Microstructure of Ultra-High-Performance Concrete (UHPC).

The properties of concrete can be significantly affected by sodium gluconate (SG) at very small dosages. In this paper, the effects of SG on the fluidity, setting time, heat of hydration, and strength of ultra-high-performance concrete (UHPC) were studied. The results show that (1) in the plastic stage, SG inhibited the formation of early ettringite (AFt) and delayed the hydration of tricalcium silicate (C3S) and dicalcium silicate (C2S). SG increased the initial fluidity of UHPC without decreasing within 1 h. When the SG dosage was ≥0.06%, the slumps at 30 min and 60 min increased slightly. (2) In the setting hardening stage, the addition of SG inhibited the formation of calcium hydroxide (CH), which significantly extended the setting time of UHPC. When the dosage of SG was 0.15%, the initial and final setting times were 5.0 times and 4.5 times that of the blank group, respectively. SG had no obvious effect on the hydration rate of cement in the accelerated period, but the peak hydration temperature of UHPC was increased when the SG dosage was 0.03~0.12%. (3) In the strength development stage, the 1 d and 3 d strength of UHPC decreased significantly with the increase in the SG dosage. However, SG could promote the formation of AFt at the pores and aggregate interface in the later stage, reduce the porosity of cementite, and improve the compressive strength of UHPC in 28 d, 60 d, and 90 d. When the SG dosage was 0.12%, the 90d strength increased by 13%.

Yang-Gan-Jiang-Mei formula alleviates non-alcoholic steatohepatitis by inhibiting NLRP3 inflammasome through mitophagy.

As an effective formula of traditional Chinese medicine, Yang-Gan-Jiang-Mei (YGJM) formula exhibited a unique advantage in ameliorating liver injury and hepatic steatosis of non-alcoholic steatohepatitis (NASH). Nevertheless, the related pharmacological mechanism needs to be elucidated. This study aimed to explore the molecular mechanism of YGJM formula on mitophagy mediated by PINK1/parkin signaling pathway and NOD-like receptor protein 3 (NLRP3) inflammasome in NASH. High-fat-diet rats and HepG2 cells induced by free fatty acid were used as NASH models in vivo and in vitro. Liver pathology and serum indicator embodying liver function (aspartate transferase, alanine transferase, triglyceride, and total cholesterol) were applied to evaluate the extent of hepatic damage and lipid accumulation. Besides, transmission electron microscopy, JC-1 and 2',7'-dichlorofluorescein diacetate were utilized to observe hepatic mitochondrial morphology, as well as cellular mitochondrial membrane potential and reactive oxygen species level. Additionally, expression of PINK1/parkin-mediated mitophagy and NLRP3 inflammasome was detected to elucidate the underlying mechanism of YGJM formula by immunohistochemistry, immunofluorescence, RT-PCR (reverse transcription-polymerase chain reaction) and Western blot. The manifestations of pathology and biochemical detection confirmed the efficacy of YGJM formula in relieving hepatic damage and lipid deposition. Simultaneously, YGJM formula could obviously improve mitochondrial function. In addition, YGJM formula exhibited the promotion of PINK1/parkin-mediated mitophagy, which could perturb NLRP3 inflammasome activation, and as a result, the hepatocyte inflammation was also suppressed both in vitro and in vivo. Our preliminary results indicate that YGJM formula can ameliorate NASH mechanistically by interfering with PINK1/parkin-mediated mitophagy and NLRP3 inflammasome to exert anti-inflammation ability and promote mitochondrial function restoration.