Bovine colostrum derived-exosomes prevent dextran sulfate sodium-induced intestinal colitis via suppression of inflammation and oxidative stress.

Despite the rise in the global burden of inflammatory bowel disease, there is a lack of safe and effective therapies that can meet the needs of clinical patients. In this study, we investigated the beneficial effects of bovine milk, especially colostrum-derived exosomes (Col-exo) in a murine model of ulcerative colitis induced by dextran sodium sulfate (DSS). Col-exo activated the proliferation of colonic epithelial cells and macrophages, and created an environment to relieve inflammation by effectively removing reactive oxygen species and regulating the expression of immune cytokines. Besides, Col-exo could pass through the gastrointestinal tract intact and efficiently deliver bioactive cargoes to the stomach, small intestine, and colon. Our results showed that oral gavage of Col-exo can alleviate colitis symptoms including weight loss, gastrointestinal bleeding, and chronic diarrhea by modulating intestinal inflammatory immune responses. Overall, bovine colostrum-derived exosomes with excellent structural and functional stability may offer great potential as natural therapeutics for the recovery of colitis.

Harnessing the Natural Healing Power of Colostrum: Bovine Milk-Derived Extracellular Vesicles from Colostrum Facilitating the Transition from Inflammation to Tissue Regeneration for Accelerating Cutaneous Wound Healing.

As wound healing is an extremely complicated process, consisting of a cascade of interlocking biological events, successful wound healing requires a multifaceted approach to support appropriate and rapid transitions from the inflammatory to proliferative and remodeling phases. In this regard, here the potential use of bovine milk extracellular vesicles (EVs) to enhance wound healing is investigated. The results show that milk EVs promote fibroblast proliferation, migration, and endothelial tube formation. In particular, milk EVs derived from colostrum (Colos EVs) contain various anti-inflammatory factors facilitating the transition from inflammation to proliferation phase, as well as factors for tissue remodeling and angiogenesis. In an excisional wound mouse model, Colos EVs promote re-epithelialization, activate angiogenesis, and enhance extracellular matrix maturation. Interestingly, Colos EVs are further found to be quite resistant to freeze-drying procedures, maintaining their original characteristics and efficacy for wound repair after lyophilization. These findings on the superior stability and excellent activity of milk Colos EVs indicate that they hold great promise to be developed as anti-inflammatory therapeutics, especially for the treatment of cutaneous wounds.

Curcubinoyl flavonoids from wild ginseng adventitious root cultures.

Wild ginseng (Panax ginseng) adventitious root cultures were prepared by elicitation using methyl jasmonate and investigated further to find new secondary metabolites. Chromatographic fractionation of wild ginseng adventitious root cultures led to the isolation of eleven compounds. The chemical structures of isolated compounds were identified as four known flavanone derivatives (1-4), one new curcubinoyl derivative, jasmogin A (5) and six new curcubinoyl-flavanone conjugates, jasmoflagins A-F (6-11) by extensive spectroscopic analysis. Newly isolated curcubinoyl derivatives showed inhibitory activity against lipopolysaccharide-stimulated nitric oxide production in RAW 264.7 macrophages. Therefore, our present study suggested that elicitor stimulated plant cell cultures might contribute to the production of new metabolites.

Effect of desalted Salicornia europaea L. ethanol extract (PM-EE) on the subjects complaining memory dysfunction without dementia: a 12 week, randomized, double-blind, placebo-controlled clinical trial.

Desalted Salicornia europaea L. (SE) inhibits acetylcholine esterase, attenuates oxidative stress and inflammatory cytokines, and activates neurotrophic pathway. We performed 12-week, randomized, double-blind, placebo-controlled study to evaluate the efficacy of PhytoMeal(a desalted SE)-ethanol extract (PM-EE), in improving the cognitive performance in patients with subjective memory impairment. 63 participants complaining memory dysfunction without dementia (Korean Mini-Mental State Examination [K-MMSE] score ≥ 23) were assigned to PM-EE 600 mg/day or placebo. The cognitive domain of the Alzheimer's disease assessment scale-Korean version (ADAS-K) was set as the primary outcome. After 12 weeks, there was no differences in the changes in the primary outcome or the frequency of adverse events between the groups. In the subgroup analysis for the 30 subjects with mild cognitive impairment (MCI, baseline K-MMSE scores ≤ 28), PM-EE significantly improved the color-reading score of the Korean color-word stroop test (8.2 ± 25.0 vs. - 4.7 ± 13.2, P = 0.018). Our findings suggest that PM-EE is safe but might not be effective in this setting of this study. However, PM-EE may improve the frontal executive function in the patients with MCI. Further large-sized studies with longer follow-up period is warranted (trial registration number KCT0003418).

SGL 121 Attenuates Nonalcoholic Fatty Liver Disease through Adjusting Lipid Metabolism Through AMPK Signaling Pathway.

A ginsenoside F2-enhanced mixture (SGL 121) increases the content of ginsenoside F2 by biotransformation. In the present study, we investigated the effect of SGL 121 on nonalcoholic fatty liver disease (NAFLD) in vitro and in vivo. High-fat, high-carbohydrate-diet (HFHC)-fed mice were administered SGL 121 for 12 weeks to assess its effect on improving NAFLD. In HepG2 cells, SGL 121 acted as an antioxidant, a hepatoprotectant, and had an anti-lipogenic effect. In NAFLD mice, SGL 121 significantly improved body fat mass; levels of hepatic triglyceride (TG), hepatic malondialdehyde (MDA), serum total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL); and activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In HepG2 cells, induced by oxidative stress, SGL 121 increased cytoprotection, inhibited reactive oxygen species (ROS) production, and increased antioxidant enzyme activity. SGL 121 activated the Nrf2/HO-1 signaling pathway and improved lipid accumulation induced by free fatty acids (FFA). Sterol regulatory element-binding protein-1 (SREBP-1) and fatty acid synthase (FAS) expression was significantly reduced in NAFLD-induced liver and HepG2 cells treated with SGL 121. Moreover, SGL 121 activated adenosine monophosphate-activated protein kinase (AMPK), which plays an important role in the regulation of lipid metabolism. The effect of SGL 121 on the improvement of NAFLD seems to be related to its antioxidant effects and activation of AMPK. In conclusion, SGL 121 can be potentially used for the treatment of NAFLD.

Effect of echinalkamide identified from Echinacea purpurea (L.) Moench on the inhibition of osteoclastogenesis and bone resorption.

Plant cell cultures have been exploited to provide stable production and new secondary metabolites for better pharmacological activity. Fractionation of adventitious root cultures of Echinacea purpurea resulted in the isolation of eleven constituents, including three new compounds. The structures of the three new compounds were determined to be an alkylamide (1), a polyacetylene (2) and a lignan (3) on the basis of combined spectroscopic analysis. To discover new types of antiresorptive agents, we screened for new compounds that regulate osteoclast differentiation, and survival. Among three new compounds, echinalkamide (compound 1) had considerably inhibitory effects on RANKL-induced osteoclast differentiation, and on proliferation of osteoclasts and efficiently attenuated osteoclastic bone resorption without toxicity. In addition, echinalamide treatment inhibited the osteoclast-specific gene expression level. Echinalkamide achieved this inhibitory effect by disturbing phosphorylation of MAPK and activation of osteoclast transcription factors c-Fos and NFATc1. Conclusionally, our study investigated that echinalkamide remarkably inhibited osteoclast differentiation and osteoclast specific gene expression through repression of the MAPK-c-Fos-NFATC1 cascade.

Lactobacillus plantarum NK3 and Bifidobacterium longum NK49 Alleviate Bacterial Vaginosis and Osteoporosis in Mice by Suppressing NF-κB-Linked TNF-α Expression.

Excessive expression of TNF-α worsens bacterial vaginosis (BV) and osteoporosis. Therefore, to understand whether probiotics could alleviate vaginosis and osteoporosis, we isolated anti-inflammatory Lactobacillus plantarum NK3 and Bifidobacterium longum NK49 from kimchi and human fecal lactic acid bacteria collection and examined their effects on Gardnerella vaginalis (GV)-induced vaginosis and ovariectomy-induced osteoporosis in female mice. Oral gavage of NK3 and/or NK49 significantly alleviated GV-induced vaginosis; these inhibited NF-κB activation and TNF-α expression in the vagina and uterus, and decreased the GV population in the vagina. Furthermore, treatment with NK3 and/or NK49 alleviated ovariectomy-induced osteoporosis and obesity; these increased blood calcium, phosphorus, and osteocalcin levels and suppressed body weight. GV-induced vaginosis and ovariectomy increased colonic myeloperoxidase activity, TNF-α expression, and fecal Proteobacteria population. NK3 and/or NK49 treatments reduced TNF-α expression and NF-κB activation in the colon. NK3 and NK49 treatment also restored GV- or ovariectomy-disrupted gut microbiota composition. In conclusion, NK3 and NK49 may simultaneously alleviate BV and osteoporosis by suppressing NF-κB-linked TNF-α expression through the regulation of gut microbiota population.