Evaluating the Antidiabetic, Anticancer, Anti-Alzheimer, Antiviral, and AntimicrobialActivities of Silymarin from Milk Thistle Extract: Hepatoprotective Properties, Histology andGene Regulators in HgCl2-Challenged Rats

This study investigated the effects of methyl jasmonate (MeJA) and yeast extract (YE) as elicitors on silymarin yield in cell suspension cultures of Silybum marianum L. The main objective was to evaluate the hepatoprotective and generegulatory effects of a silymarin-enriched extract (SME), known for its antidiabetic, anticancer, anti-Alzheimer, and antimicrobial properties, in rats challenged with HgCl.MeJA-treated cultures produced the highest silymarin content, reaching 0.17 mg per 100 g dry weight after 48 hours.High-resolution HPLC analysis revealed that silymarin components in MeJA cultures totaled 595 g/g, with silibinin A and B accounting for 0.134 mg/g and isosilibinin A and B for 0.025 mg/g of SME.The MeJA-silymarin-enriched extract inhibited -amylase and glucosidase activities, indicating notable antidiabetic activity.It also demonstrated considerable antimicrobial effects against a range of pathogens, including Salmonella Typhi, Escherichia coli, Bacillus cereus, Klebsiella pneumoniae, Candida albicans, Aspergillus niger, Fusarium oxysporum, Fusarium solani, Alternaria alternata, Pythium aphanidermatum, and Botrytis cinerea.Antiviral assays showed dosedependent inhibition of Human parvovirus B19 (PVB-19) and Sapporo virus (SaV) replication in vitro, with 89% and 76% inhibition at 100 g/mL and IC values of 32 g/mL and 45 g/mL, respectively.Moreover, a concentration of 18 g/mL, SME significantly reduced the viability of 50% of HepG2 liver cancer cells.Furthermore, SME exhibited potent antioxidant activity, reaching 96% DPPH inhibition, and demonstrated distinct neuroprotective effects.For in vivo evaluation, 120 Wistar rats were randomly divided into four groups (10 rats per group, in triplicate): a basal diet group, an HgCl-challenged group, a group fed a diet supplemented with SME (500 mg/kg), and an HgCl-challenged group treated with SME (500 mg/kg).The SMEtreated groups showed significant reductions in the gene expression of precancerous markers (BAX and Casp-3) and proinflammatory cytokines (IL-1 and TNF-) in HgCl-stressed rats.These groups also exhibited lower ALT, AST, and glucose levels (a 30% decrease compared to the challenged group), maintained normal liver and intestinal structure, and showed a predominance of beneficial gut microbes compared to the control.Additionally, SME inhibited 86% of acetylcholinesterase (AChE) activity compared to donepezil, supporting its neuroprotective role in HgCl-treated