The excessive release of reactive oxygen species (ROS) can result in the development of chronic inflammation. The mechanisms involved in inflammation are various, with endoplasmic reticulum (ER) stress known to be among them. We have previously shown that black ginseng (BG) reduced lipid accumulation in and enhanced the antioxidant function of the liver in vitro and in vivo mostly due to ginsenoside Rb1, Rg3 and Rk1 components. Therefore, this study investigated the antioxidant effect of BG on the intestines and its possible mechanistic pathway through ER stress. The results showed that BG extract decreased ROS and nitric oxide (NO) production and reduced inducible nitric oxide synthase (iNOS) expression levels in vitro, and these results were confirmed by zebrafish embryos in vivo. However, this phenotype was abolished in the absence of inositol-requiring enzyme 1 (IRE1α) but not in the absence of protein kinase RNA (PKR)-like ER-resistant kinase (PERK) or X-box-binding protein 1 (XBP1) in the mouse embryo fibroblast (MEF) knockout (KO) cells, suggesting that BG elicits an antioxidant effect in an IRE1α-dependent manner. Antioxidant and anti-inflammatory effects were assessed in the liver and intestines of the mouse model affected by nonalcoholic fatty liver disease (NAFLD), which was induced by a high-fat/high-fructose diet. In the liver, BG treatment rescued NAFLD-induced glutathione (GSH), catalase (CAT), tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 expression. In the intestines, BG also rescued NAFLD-induced shortened villi, inflammatory immune cell infiltration, upregulated IL-6, cytosine-cytosine-adenosine-adenosine-thymidine (CCAAT)/enhancer-binding homologous protein (CHOP) and binding immunoglobulin protein (BiP) expression. In conclusion, our results show that BG reduces ROS and NO production followed by inflammation in an IRE1α-dependent and XBP1-independent manner. The results suggest that BG provides antioxidant and anti-inflammatory effects through an ER stress mechanism.

Although the prevalence and incidence of inflammatory bowel disease (IBD), a defective immune response of the gastrointestinal tract, has been increasing in North America and Western Europe, recent studies have shown that this disease is also increasing rapidly in Asia. Several studies have been searching for functional foods that can prevent or reduce IBD symptoms because the drug treatments for IBD are expensive with complications. Genome-Wide Association Study (GWAS), an observational study of a genome-wide set of genetic variants in different individuals, showed that endoplasmic reticulum (ER) stress is one of the causes of IBD. Previously, we reported the effects of Lyciumbarbarum fruit and this study investigated the effects of Lycium barbarum leaf (LL) on inflammation and ER stress of the intestine. The paracellular permeability, antioxidant, and anti-inflammatory response were measured on polarized Caco-2 cells. The ER stress pathway and pro-inflammatory cytokines were evaluated on MEF-knockout cell lines, and on the intestines of the mice fed a high-fat diet with lipopolysaccharide-induced inflammation. Our data showed that the LL pretreatment strengthened the tight junction integrity and reduced NO production both in the presence and in the absence of inflammation. Furthermore, LL inhibited ER stress and inflammation via IRE1α and XBP1 in vitro as well as in the inflamed intestines of mice, highlighting the antioxidant and anti-inflammatory function of LL in an IRE1α-XBP1-dependent manner.

Ha NY, et al. J Korean Med Sci. 2024 Nov;40:e28. https://doi.org/10.3346/jkms.2025.40.e28

Perilla frutescens var. frutescens leaf extract (PFE) has previously demonstrated clinical efficacy in relieving knee joint discomfort. To establish its safety profile, good laboratory practice (GLP)-compliant nonclinical evaluations were conducted in accordance with the Organization for Economic Cooperation and Development (OECD) test guidelines. In the acute oral toxicity test, the acute oral LD₅₀ cutoff was estimated to be above 2000 mg/kg. In 28-day and 90-day repeated-dose oral toxicity studies of up to 5000 mg/kg/day, no mortalities, toxic signs, or adverse changes in body weight were observed. Minor hematological/biochemical shifts and organ weight increases at 5000 mg/kg/day lacked histopathological correlates and were largely reversible following a 28-day recovery period, establishing the no observed adverse effect level (NOAEL) at 5000 mg/kg/day. Furthermore, PFE showed no mutagenic, clastogenic, or aneugenic potential across the bacterial reverse mutation, in vitro chromosomal aberration, or in vivo bone marrow micronucleus assays. These results demonstrate a broad safety margin, supporting the safe application of PFE as a functional food ingredient and nutraceutical agent.