Ultrafine garlic powder alleviates non-alcoholic steatohepatitis by inhibiting hepatocyte ferroptosis and modulating ERK-dependent oxidative stress

Junhui Yu¹Ningning Shao¹Jianming Yang¹Long Yang¹Kaiwen Hong¹Yuzhu Chen¹Xiaoming Zhao²Hongzhi Yu¹涛 张³Jinrui Dong^1*

• ¹Tianjin University, Tianjin, China
• ²Lafayette College, Easton, United States
• ³School of Materials Science and Engineering, Beihang University,, Beijing, China

Nonalcoholic steatohepatitis (NASH) is a chronic liver disease associated with 33 oxidative stress and ferroptosis, leading to liver injury and fibrosis. Garlic, 34 renowned for its antioxidant and hepatoprotective properties, is commonly 35 used in traditional medicine. Ultrafine powder technology enhances the 36 physicochemical properties of natural products, improving their bioavailability 37 and efficacy. This study explores the protective effects of ultrafine garlic 38 powder (UGP) on NASH and its underlying mechanisms.In this study, UGP 39 was prepared by high-speed particle collision technology and compared with 40 traditional garlic powder (TGP). UGP exhibited a particle size (d(0.5) of 41 approximately 4 µm) that is 30 times smaller than TGP, showing significantly 42 smaller particle size and lower contact angle (UGP=59.775°vs TGP=83.545°). 43 UGP also demonstrated improved solubility and dispersibility, along with an 44 enrichment of key organosulfur compounds such as allicinAllicin, Alliin, SAC, 45 and GSAC. In vitro, UGP significantly reduced palmitic acid-induced ROS 46 production (n=4, p< 0.0001), prevented mitochondrial dysfunction (n=4, 47 p=0.0035), and thereby reduced hepatic stellate cell activation. UGP lowered 48 intracellular Fe2+ levels in hepatocytes from 68.72% to 34.48% (n=4) and 49 significantly protected hepatocytes from erastin-induced ferroptosis (cell 50 viability: UGP treatment 23.46% vs erastin stimulation 53.91%, n = 4, p 51 <0.0001).In the acute liver fibrosis model induced by methionine-and 52 choline-deficient diet supplemented with 60 kcal% fat (CDHF), UGP