The intestinal epithelial barrier is the primary and most significant defense barrier against ingested toxins and pathogenic bacteria. When the intestinal epithelium barrier is breached, inflammatory response is triggered. GWAS data showed that endoplasmic reticulum (ER) stress markers are elevated in Inflammatory Bowel Disease (IBD) patients, which suggests ER stress regulation might alleviate IBD symptoms. Ferulic acid (FA) is a polyphenol that is abundant in plants and has antioxidant and anti-inflammatory properties, although it is unclear whether FA has these effects on the intestine. Therefore, we investigated the effect of FA in vitro and in vivo. It was found that FA suppressed ER stress, nitric oxide (NO) generation, and inflammation in polarized Caco-2 and T84 cells, indicating that the ER stress pathway was implicated in its anti-inflammatory activities. The permeability of polarized Caco-2 cells in the presence and absence of proinflammatory cytokines were decreased by FA, and MUC2 mRNA was overexpressed in the intestines of mice fed a high-fat diet (HFD) supplemented with FA. These results suggest that FA has a protective effect on intestinal tight junctions. In addition, mouse intestine organoids proliferated significantly more in the presence of FA. Our findings shed light on the molecular mechanism responsible for the antioxidant effects of FA and its protective benefits on the health of the digestive system.

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.

Sword bean (SB) contains various phytochemicals, such as flavonoids, tannins, saponins, and terpenoids. Although the evaluation of its potential functions, including antioxidant, anti-obesity, anti-inflammatory, liver protection, and antiangiogenic activities, has been widely reported, research on their use in osteoporosis prevention is insufficient. Furthermore, while various studies are conducted on SB, research on sword bean pods (SBP) is not yet active, and little is known about it. Therefore, this study investigated the effects of promoting osteoblast differentiation of MC3T3-E1 cells using SB and SBP extracts and their mechanisms. We show that SBP extracts increase osteoblast proliferation, mineralization-activated alkaline phosphatase (ALP), and collagen synthesis activities. Additionally, treatment with SBP extract increased the expression of markers related to osteoblast differentiation, such as ALP, SPARC, RUNX2, COL-I, BMP2, OCN, and OPN. It was confirmed that SBP induces differentiation by activating the BMP2/SMAD/RUNX2 pathway. We also show that SBP is more effective than SB, and SBP may be useful in assimilating bone minerals and preventing osteoporosis.

Alcohol and drug overdoses cause liver diseases such as cirrhosis, hepatitis, and liver cancer globally. In particular, an overdose of acetaminophen (APAP), which is generally used as an analgesic and antipyretic agent, is a major cause of acute hepatitis, and cases of APAP-induced liver damage are steadily increasing. Potential antioxidants may inhibit the generation of free radicals and prevent drug-induced liver damage. Among plant-derived natural materials, radishes (RJ) and turnips (RG) have anti-inflammatory, anticancer, and antioxidant properties due to the presence of functional ingredients, such as glucosinolate and isothiocyanate. Although various functions have been reported, in vivo studies on the antioxidant activity of radishes are insufficient. Therefore, we aim to evaluate the hepatoprotective effects of RG and RJ in APAP-induced liver-damaged mice. RG and RJ extracts markedly improved the histological status, such as inflammation and infiltration, of mice liver tissue, significantly decreased the levels of alanine transaminase, aspartate aminotransferase, and malondialdehyde, and significantly increased the levels of glutathione, superoxide dismutase and catalase in the APAP-induced liver-damaged mice. In addition, RG and RJ extracts significantly increased the expression of Nrf-2 and HO-1, which are antioxidative-related factors, and regulated the BAX and BCL-2, thereby showing anti-apoptosis activity. These results indicated that RG and RJ extracts protected mice against acute liver injury, attributed to a reduction in both oxidative stress and apoptosis. These findings have clinical implications for the use of RG and RJ extracts as potential natural candidates for developing hepatoprotective agents.

Background: Allergic rhinitis is an IgE-mediated condition of nasal congestion, runny nose, and sneezing which significantly impairs the quality of life. Current treatments, including antihistamines, often have long-term side effects, leading patients to seek safer alternatives. Objectives: Therefore, in this study, we aimed to evaluate the symptom relief efficacy of immature sword bean pod (SBP) extract, a natural material, in patients with allergic rhinitis, explore the mechanisms by which SBP regulates allergic immune responses, and evaluate its efficacy and safety as a functional ingredient in the management of allergic rhinitis. Methods: In a double-blind, placebo-controlled, randomized trial involving 64 participants with perennial allergic rhinitis, the subjects were assigned to receive either SBP or placebo orally for six weeks. Results: The SBP group exhibited significant improvements in nasal congestion (interaction p = 0.031), RQLQ (interaction p = 0.001), sleep (interaction p = 0.004), systemic reaction (interaction p = 0.002), daily life (interaction p = 0.047), and nasal symptoms (interaction p = 0.002). SBP treatment in EoL-1 and HMC-1 cells also led to a notable reduction in eosinophil cationic protein levels (p < 0.05), a key biomarker of allergic inflammation, by inhibiting PI3K/Akt/mTOR activation, resulting in decreased eosinophil activity. Conclusions: These findings suggest that the SBP extract is a promising natural treatment for allergic rhinitis, offering both efficacy and safety by improving key symptoms and reducing inflammatory responses.

Mustard leaf (Brassica juncea var. crispifolia L. H. Bailey) has been reported to have psychological properties such as anti-depressant activities. However, studies on chronic stress and depression caused by restraint have not been conducted. Therefore, this study aimed to evaluate the effects of a mustard leaf (ML) extract on chronic restraint stress (CRS) in mice. Male mice were subjected to a CRS protocol for a period of four weeks to induce stress. The results showed that the ML extract (100 and 500 mg/kg/perorally administered for four weeks) significantly decreased corticosterone levels and increased neurotransmitters levels in stressed mice. Apoptosis by CRS exposure was induced by Bcl-2 and Bax expression regulation and was suppressed by reducing caspase-3 and poly (ADP-ribose) polymerase expression after treatment with the ML extract. Our results confirmed that apoptosis was regulated by increased expression of brain-derived neurotrophic factor (BDNF). Additionally, cytokine levels were regulated by the ML extract. In conclusion, our results showed that the ML extract relieved stress effects by regulating hormones and neurotransmitters in CRS mice, BDNF expression, and apoptosis in the brain. Thus, it can be suggested that the studied ML extract is an agonist that can help relieve stress and depression.