Fermented Angelica sinensis activates Nrf2 signaling and modulates the gut microbiota composition and metabolism to attenuate D-gal induced liver aging.

Aging is an inevitable physiological process associated with an imbalance in the oxidative defense system. Angelica sinensis, a kind of traditional Chinese medicine (TCM), has anti-oxidant effects and has been considered as a potential supplement in anti-aging treatment. Nevertheless, it has the disadvantages of slow efficacy and long duration of treatment. Fermentation, as an efficient biotechnological approach, is beneficial for improving the nutritional capacity of the material. Fermented TCMs are considered to be more effective. In this study, fermented Angelica sinensis (FAS) and non-fermented Angelica sinensis (NFAS) were used to investigate changes in the chemical constituents. Furthermore, the improvement effect of FAS on D-galactose-induced aging in mice and the potential mechanisms were explored. The results revealed that FAS and NFAS had different constituents under the influence of fermentation, such as 3-phenyllactic acid, L-5-hydroxytryptophan, taxifolin and methyl gallate. These elevated constituents of FAS might help increase the ability of FAS to improve aging. The aging model was established by intraperitoneal injection of D-galactose (2.5 g kg-1 day-1) for 44 days, and FAS (3 g kg-1 day-1) was administered daily by oral gavage after 2 weeks of induction with D-galactose. FAS was observed to significantly ameliorate changes associated with liver aging, such as reduction of MDA, AGEs and 8-OHdG. The contents of pro-inflammatory cytokines containing TNF-α, IL-1ß and IL-6 were significantly suppressed in the FAS group. In addition, FAS activated Nrf2 signaling better than NFAS, improved the expression of Nrf2, HO-1, NQO1, GCLC, GCLM and GSS, and further increased the activities of SOD, CAT and other antioxidant enzymes in the liver. Simultaneously, it had a certain repair effect on the liver tissues of mice. The intestinal microbiota analysis showed that FAS could regulate the microbiota imbalance caused by aging, increase the ratio of Firmicutes/Bacteroidetes by 95% and improve the relative abundance of beneficial bacteria related to Nrf2 signaling, such as Lactobacillus. Besides, fecal metabolite analysis identified uric acid as an evidential metabolite, suggesting that FAS participates in purine metabolism to improve aging. Therefore, the regulation of intestinal microbiota and metabolism may be one of the important mechanisms of FAS in alleviating hepatic oxidative stress via the gut-liver axis. The results of this study could provide information for the future development of postbiotic products that may have beneficial effects on the prevention or treatment of aging.

Overcoming Anxiety Disorder by Probiotic Lactiplantibacillus plantarum LZU-J-TSL6 through Regulating Intestinal Homeostasis.

Lactiplantibacillus plantarum LZU-J-TSL6 with high γ-aminobutyric acid (GABA) production (3.838 g/L) was screened and isolated from the Chinese fermented food snack "Jiangshui". The improvement effect on anxiety disorder was explored using mice as animal models. In vitro results revealed that LZU-J-TSL6 had the potential to colonize the intestine (p < 0.01) and the anxiety-like behavior of the mice after seven days' gavage with LZU-J-TSL6 was significantly improved (p < 0.01) when compared to the model group. LZU-J-TSL6 was able to effectively increase the GABA content in the mice hippocampus (p < 0.0001) and restore some markers related to anxiety such as brain-derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), and 5-hydroxytryptamine (5-HT). Simultaneously, it had a certain repair effect on Nissl bodies and colon tissue in mice hippocampus. In addition, LZU-J-TSL6 increased the relative abundance of beneficial bacteria Bacteroides and Muribaculum, thereby regulating the imbalance of intestinal microbiota caused by anxiety disorder. It also affects the nerve pathway and intestinal mucosal barrier by increasing the content of glutamine and γ-aminobutyric acid and other related metabolites, thereby improving anxiety. Therefore, the GABA-producing Lactobacillus plantus LZU-J-TSL6 can be used as a probiotic to exert an indirect or direct anti-anxiety effect by maintaining the balance of the intestinal environment, producing related metabolites that affect nerve pathways and repair the intestinal mucosal barrier. It can be used as an adjuvant treatment to improve anxiety disorders.

The shikimate pathway regulates programmed cell death.

Programmed cell death (PCD) is essential for both plant development and stress responses including immunity. However, how plants control PCD is not well-understood. The shikimate pathway is one of the most important metabolic pathways in plants, but its relationship to PCD is unknown. Here, we show that the shikimate pathway promotes PCD in Arabidopsis. We identify a photoperiod-dependent lesion-mimic mutant named Lesion in short-day (lis), which forms spontaneous lesions in short-day conditions. Map-based cloning and whole-genome resequencing reveal that LIS encodes MEE32, a bifunctional enzyme in the shikimate pathway. Metabolic analysis shows that the level of shikimate is dramatically increased in lis. Through genetic screenings, three suppressors of lis (slis) are identified and the causal genes are cloned. SLISes encode proteins upstream of MEE32 in the shikimate pathway. Furthermore, exogenous shikimate treatment causes PCD. Our study uncovers a link between the shikimate pathway and PCD, and suggests that the accumulation of shikimate is an alternative explanation for the action of glyphosate, the most successful herbicide.

Release and conformational changes in allergenic proteins from wheat gluten induced by high hydrostatic pressure.

The gluten proteins of wheat are major causative agents of harmful immune responses. This study investigated the effects of high hydrostatic pressure (200, 300, 400, and 500 MPa), treatment time (5-25 min) and protein concentration (1%-5% protein weight/volume) on the structures underlying the allergenicity wheat gluten. The results showed that a combination of 400 MPa, 20 min treatment time and 3% protein reduced the wheat gluten allergenicity by 72.2%. Moreover, a Western blotting showed that the allergenicity of 26, 28, 48, 68 kDa and high molecular weight glutenin was sharply reduced. Fourier infrared spectroscopy and surface hydrophobicity indicated that gluten molecules aggregated after HHP treatment. Intermolecular forces indicated that gluten aggregated mainly through hydrophobic interactions and disulfide bonds but not by hydrogen bonds after HHP treatment. These results suggest that structural changes contributed to the reduction of wheat gluten allergenicity and that HHP may enhance safety for susceptible individuals.