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.
Physiological processes in skin are associated with exposure to UV light and are essential for skin maintenance and regeneration. Here, we investigated whether the leaf and callus extracts of Perilla frutescens (Perilla), a well-known Asian herb, affect DNA damage response and repair in skin and keratinocytes exposed to Untraviolet B (UVB) light. First, we examined the protective effects of Perilla leaf extracts in UVB damaged mouse skin in vivo. Second, we cultured calluses using plant tissue culture technology, from Perilla leaf explant and then examined the effects of the leaf and callus extracts of Perilla on UVB exposed keratinocytes. HaCaT cells treated with leaf and callus Perilla extracts exhibited antioxidant activities, smaller DNA fragment tails, and enhanced colony formation after UVB exposure. Interestingly, keratinocytes treated with the leaf and callus extracts of Perilla showed G1/S cell cycle arrest, reduced protein levels of cyclin D1, Cyclin Dependent Kinase 6 (CDK6), and γH2AX, and enhanced levels of phosphorylated checkpoint kinase 1 (pCHK1) following UVB exposure. These observations suggest that the leaf and callus extracts of Perilla are candidate nutraceuticals for the prevention of keratinocyte aging.
Glucosamine and chondroitin sulfate have been used as nutritional supplementation for joint tissues and osteoarthritis (OA). Biofermented glucosamine is of great interest in the supplement industry as an alternative source of glucosamine. The purpose of this study is to compare the pharmacokinetics of chitosan-derived glucosamine and biofermentation-derived glucosamine as nutritional supplementation. In a randomized, double-blind and cross-over study design, we recruited subjects of healthy men and women. The pharmacokinetics of glucosamine were examined after a single dose of glucosamine sulfate 2KCl (1500 mg) with two different sources of glucosamine (chitosan-derived glucosamine and biofermentation-derived glucosamine) to male and female subjects fitted with intravenous (iv) catheters for repeated blood sampling up to 8 h. According to plasma concentration–time curve of glucosamine after an oral administration of 1500 mg of glucosamine sulfate 2KCl, AUC0–8h and AUC0–∞ values of glucosamine following oral administration of chitosan-derived and biofermentation-derived glucosamine formulations were within the bioequivalence criteria (90% CI of ratios are within 0.8–1.25). The mean Cmax ratios for these two formulations (90% CI of 0.892–1.342) did not meet bioequivalence criteria due to high within-subject variability. There were no statistically significant effects of sequence, period, origin of glucosamine on pharmacokinetic parameters of glucosamine such as AUC0–8h, AUC0–∞, Cmax. Our findings suggest that biofermentation-derived glucosamine could be a sustainable source of raw materials for glucosamine supplement.
Opuntia ficus-indica (OF) phytochemicals have received considerable attention because of their health benefits. However, the structure-activity relationship between saponin and flavonoid antioxidant compounds among secondary metabolites has rarely been reported. In a molecular docking study, selected compounds from both Opuntia ficus-indica callus (OFC) and OF ethanol extract were found to be involved in Toll-like receptor 4 and mitogen-activated protein kinase (MAPK) signaling pathways. High affinity was specific for MAPK, and it was proposed to inhibit the oxidative and inflammatory responses with poricoic acid H (−8.3 Kcal/mol) and rutin (−9.0 Kcal/mol). The pro-inflammatory cytokine factors at a concentration of 200 μg/mL were LPS-stimulated TNF-α (OFC 72.33 ng/mL, OF 66.78 ng/mL) and IL-1β (OFC 49.10 pg/mL, OF 34.45 pg/mL), both of which significantly decreased OF (p < 0.01, p < 0.001). Taken together, increased NO, PGE2, and pro-inflammatory cytokines were significantly decreased in a dose-dependent manner in cells pretreated with OFC and the OF extract (p < 0.05). These findings suggest that OFC and OF have important potential as natural antioxidant, anti-inflammatory agents in health-promoting foods and medicine.
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