Inflammation, a biological response of body tissues to harmful stimuli, is also known to be involved in a host of diseases, such as obesity, atherosclerosis, rheumatoid arthritis, and even cancer. Isoflavones are a class of flavonoids that exhibit antioxidant, anticancer, antimicrobial, and anti-inflammatory properties. Increasing evidence has highlighted the potential for isoflavones to prevent the chronic diseases in which inflammation plays a key role, though the underlying mechanisms remain unclear. Recently, some studies have raised concerns about isoflavones induced negative effects like carcinogenesis, thymic involution, and immunosuppression. Therefore, this review aims to summarize the anti-inflammatory effects of isoflavones, unravel the underlying mechanisms, and present the potential health risks.

Ferroptosis plays a role in several diseases such as iron overload-induced liver diseases. Manipulation of ferroptosis has been explored as a potential therapeutic strategy to treat related diseases. Numerous antioxidants have been identified to control ferroptosis but the cell-autonomous mechanisms responsible for regulating ferroptosis remain elusive. In the present study, we found that iron overload promoted ferroptosis in hepatocytes by excessively inducing HO-1 expression, which contributed to the progression of liver injury and fibrosis, accompanied by the upregulation of the FGF21 protein level in vitro and in vivo. Interestingly, both recombinant FGF21 and Fgf21 overexpression significantly protected against iron overload-induced hepatocytes mitochondria damage, liver injury and fibrosis by inhibiting ferroptosis. In contrast, the loss of FGF21 aggravated iron overload-induced ferroptosis. Notably, FGF21-induced HO-1 inhibition (via the promotion of HO-1 ubiquitination and degradation) and NRF2 activation provide a mechanistic explanation for this phenomenon. Taken together, we identified FGF21 as a novel ferroptosis suppressor. Thus, FGF21 activation may provide an effective strategy for the potential treatment of iron overload-induced ferroptosis-related diseases, such as hereditary haemochromatosis (HH).

Dysbiosis and oxidative stress in the gut have contributed to the progression of intestinal inflammatory bowel disease (IBD). The current study has reported that enteric bacteria mediate redox homeostasis through the regulation of reactive oxygen species (ROS) production. Resveratrol, one of the most abundant polyphenols, with poor oral bioavailability, is considered as a scavenger of ROS and other free radicals. Recent studies have shown that resveratrol effectively enhances the growth of Lactococcus lactis and inhibits the growth of Enterococcus faecalis. (1) In terms of the two-way relationship between gut microbiota and resveratrol, resveratrol modulates gut microbiota; (2) in terms of resveratrol biotransformation by gut microbiota, we speculate that gut microbiota could be a target of resveratrol to maintain gut homeostasis. Here, we reviewed the current researches about the cellular signaling pathways in intestinal epithelial cells triggered by gut microbiota in response to oxidative stress. These results suggest that the modulation of the gut microbiota through resveratrol supplementation appears as a promising potential approach for the therapy of inflammatory bowel disease.

Background: Tannic acid (TA) is potential to reduce diarrhea in weaning pigs, but knowledge about the influence of TA on intestinal barrier integrity and function is still scarce. This experiment was conducted to investigate the effects of dietary TA supplementation on growth performance, diarrhea rate, intestinal barrier integrity and function of weaned pigs. Methods: A total of 108 crossbred (Duroc × Landrace × Yorkshire) piglets, with an initial average body weight of 6.60 ± 0.27 kg, were allotted to 3 groups (6 pigs/pen and 6 replicates/group) in a randomized complete block design according to their gender and body weight. Piglets were fed the basal diet with 0 (control, CON), 0.2% and 1.0% TA, respectively. The trial lasted for 28 d. Results: Compared with the CON group, dietary 0.2% and 1.0% TA supplementation didn’t affect ADFI, ADG and F:G (P > 0.05), but reduced diarrhea rate, diarrhea index and diarrhea score of piglets (P < 0.05), reduced diamine oxidase (DAO) activity and D-lactic acid concentration in serum (P < 0.01). The higher occludin expression and localization were observed in the duodenum, jejunum and ileum after supplementation with 0.2% or 1.0% TA (P < 0.05). Adding 0.2% TA to diet significantly decreased crypt depth, increased villus height/crypt depth ratio in the duodenum (P < 0.05), and dietary 1.0% TA tended to decrease crypt depth (P < 0.10) and significantly decreased villus height (P < 0.05) of the ileum. Moreover, lower malondialdehyde content in the ileum was detected in the pigs fed 1.0% TA (P < 0.05). In the duodenum, both 0.2% and 1.0% TA groups had higher occludin (OCLN) mRNA and 0.2% TA group had higher zonula occludens-2 (ZO-2) level (P < 0.05). Meanwhile, dietary 1.0% TA supplementation tended to up-regulate OCLN mRNA levels in the jejunum (P < 0.10) and 0.2% TA supplementation tended to up-regulate zonula occludens-1 (ZO-1) mRNA levels in the ileum (P < 0.10). Conclusion: In conclusion, dietary supplementation of 0.2% or 1.0% TA could effectively alleviate post-weaning diarrhea without altering growth performance in weaned piglets, which might be achieved by improving intestinal barrier integrity and function.

Background: Previous studies have shown that exogenous short-chain fatty acids (SCFAs) introduction attenuated the body fat deposition in conventional mice and pigs. However, limited studies have evaluated the effects of exogenously introduced SCFAs on the lipid and glucose metabolism independently of the gut microbiota. This study was to investigate the effects of exogenous introduction of SCFAs on the lipid and glucose metabolism in a germ-free (GF) pig model. Methods: Twelve hysterectomy-derived newborn pigs were reared in six sterile isolators. All pigs were hand-fed with sterile milk powder for 21 d, then the sterile feed was introduced to pigs for another 21 d. In the second 21-d period, six pigs were orally administrated with 25 mL/kg sterile saline per day and considered as the GF group, while the other six pigs were orally administrated with 25 mL/kg SCFAs mixture (acetic, propionic, and butyric acids, 45, 15, and 11 mmol/L, respectively) per day and regarded as FA group. Results: Orally administrated with SCFAs tended to increase the adiponectin concentration in serum, enhance the CPT-1 activity in longissimus dorsi, and upregulate the ANGPTL4 mRNA expression level in colon (P < 0.10). Meanwhile, the mRNA abundances of ACC, FAS, and SREBP-1C in liver and CD36 in longissimus dorsi of the FA group were decreased (P < 0.05) compared with those in the GF group. Besides, the mRNA expression of PGC-1α in liver and LPL in longissimus dorsi tended to (P < 0.10) upregulate and downregulate respectively in the FA group. Moreover, oral administration of SCFAs tended to increase the protein level of GPR43 (P < 0.10) and decrease the protein level of ACC (P < 0.10) in liver. Also, oral administration of SCFAs upregulated the p-AMPK/AMPK ratio and the mRNA expressions of GLUT-2 and GYS2 in liver (P < 0.05). In addition, the metabolic pathway associated with the biosynthesis of unsaturated fatty acids was most significantly promoted (P < 0.05) by oral administration of SCFAs. Conclusions: Exogenous introduction of SCFAs might attenuate the fat deposition and to some extent improve the glucose control in the pig model, which occurred independently of the gut microbiota.

Ferulic acid (FA) is a phenolic compound that has antioxidant, hepatoprotective, anticarcinogenic, anti-inflammatory, antiallergic, antimicrobial, antiviral, and vasodilatory effects. This study was conducted to explore the effects of dietary FA supplementation on antioxidant capacity and lipid metabolism in weaned piglets. Eighteen 21-day-old castrated male DLY (Duroc × Landrace × Yorkshire) weaned piglets were randomly divided into control, 0.05%, and 0.45% FA groups. The results showed that, in serum, CAT and T-SOD activities and content of HDL-C were increased, but the content of MDA and the activities of T-CHO and LDL-C were decreased, by FA supplementation. In liver, dietary FA supplementation increased CAT, T-SOD, and GSH-PX activities and upregulated the mRNA levels of SOD1, SOD2, CAT, GST, GPX1, GR, Nrf2, HSL, CPT1b, and PPARα but decreased the contents of MDA and TG. Furthermore, dietary FA supplementation increased the protein level of Nrf2, HO-1, and NQO-1. In longissimus dorsi muscle, dietary FA supplementation increased the activity of T-SOD and the mRNA abundance of SOD1, SOD2, CAT, GST, GPX1, GR, and Nrf2 but decreased the contents of MDA and T-CHO. Additionally, dietary FA supplementation increased the protein expressions of Nrf2, HO-1, and NQO1. Together, our data suggest that FA could improve antioxidant capacity and lipid metabolism in weaned piglets.