Risk signals are characteristic of many common inflammatory diseases and can function to activate nucleotide-binding oligomerization (NLR) family pyrin domain-containing 3 (NLRP3), the innate immune signal receptor in cytoplasm. The NLRP3 inflammasome plays an important role in the development of liver fibrosis. Activated NLRP3 nucleates the assembly of inflammasomes, leading to the secretion of interleukin (IL)-1β and IL-18, the activation of caspase-1, and the initiation of the inflammatory process. Therefore, it is essential to inhibit the activation of the NLRP3 inflammasome, which plays a vital role in the immune response and in initiating inflammation. RAW 264.7 and LX-2 cells were primed with lipopolysaccharide (LPS) for 4 h and subsequently stimulated for 30 min with 5 mM of adenosine 5′-triphosphate (ATP) to activate the NLRP3 inflammasome. Thymosin beta 4 (Tβ4) was supplemented to RAW264.7 and LX-2 cells 30 min before ATP was added. As a result, we investigated the effects of Tβ4 on the NLRP3 inflammasome. Tβ4 prevented LPS-induced NLRP3 priming by inhibiting NF-kB and JNK/p38 MAPK expression and the LPS and ATP-induced production of reactive oxygen species. Moreover, Tβ4 induced autophagy by controlling autophagy markers (LC3A/B and p62) through the inhibition of the PI3K/AKT/mTOR pathway. LPS combined with ATP significantly increased thee protein expression of inflammatory mediators and NLRP3 inflammasome markers. These events were remarkably suppressed by Tβ4. In conclusion, Tβ4 attenuated NLRP3 inflammasomes by inhibiting NLRP3 inflammasome-related proteins (NLRP3, ASC, IL-1β, and caspase-1). Our results indicate that Tβ4 attenuated the NLRP3 inflammasome through multiple signaling pathway regulations in macrophage and hepatic stellate cells. Therefore, based on the above findings, it is hypothesized that Tβ4 could be a potential inflammatory therapeutic agent targeting the NLRP3 inflammasome in hepatic fibrosis regulation.

Advanced glycation end-products (AGEs) and their receptor cause diabetic liver disease by increasing oxidative stress and inflammation. We investigate the potential therapeutic benefits of Cirsium japonicum (CJ) in preventing the progression of diabetes, focusing on complications for both liver and kidney health associated with AGEs. Streptozotocin (STZ, 30 mg/kg) was injected into SD rats and CJ (50, 100 mg/kg) was orally administered for 4 weeks. CJ treatment led to a marked reduction in key diabetic markers (glucose, reaction oxygen species, and lactate dehydrogenase), compared with the rats treated only with STZ. Moreover, the hepatic tissues of STZ-treated rats exhibited heightened biomarkers associated with AGE induction and formation, and these were notably attenuated in the CJ-treated rats. This effectively alleviated oxidative stress, inflammation, and AGE accumulation in the liver. Similarly, in the context of diabetic nephropathy, CJ treatment resulted in significant improvements in the rats with STZ-induced diabetes. Biomarkers associated with AGE induction and formation were significantly reduced in CJ-treated rats, demonstrating the ability of CJ to combat renal oxidative stress, inflammation, and AGE-related complications in diabetic nephropathy. CJ thus shows potential as a promising natural remedy that might mitigate the detrimental effects of diabetes on both the liver and kidneys through its anti-oxidation, anti-inflammation, and anti-AGE activities. These findings suggest that CJ is a beneficial agent for preventing and treating diabetic complications.

This study aimed to assess the effect of fermented fig (Ficus carica L., FF) on obesity and diabetes in a mouse model. FF was cultured with the lactic acid bacterium Lactobacillus plantarum BT-LP-01 and isolated from fig peels. The antioxidant results demonstrated that FF exhibited DPPH and ABTS radical scavenging activities. In addition, FF showed high levels of total polyphenol and total flavonoids. Body and organ weight and dietary intake were significantly decreased in the FF groups compared to the HFD group. The FF group showed improved recovery in lipid metabolism and liver function compared to the HFD group. In addition, the FF group showed a significant decrease in serum C-P and insulin concentrations compared to the HFD group. FF-administered mice showed a dose-dependent recovery of fasting blood glucose and IPGTT and AUC levels compared to the HFD group. Furthermore, FF groups showed a decreased expression in FAS, C/EBPα, and FABP4, as well as significantly increased expression in ACC in the liver. This study demonstrates that FF is effective in reducing and inhibiting adipogenesis as well as lowering body weight, the blood glucose level, and lipid-related factors. These research findings demonstrate that FF is effective in treating obesity and diabetes.

Background: This study investigated the anti-diabetic effects of Astragalus membranaceus (Fisch.) Bunge fermented by Aspergillus awarmori in db/db mice.BRMethods and Results: Astragalus membranaceus roots were fermented with A. awarmori for 4 days and extracted with hot water. The male mice were divided into five groups: db/m (non-diabetic db/+mice), db/db (C57BLKs/J db/db mice), MT (db/db + 1% metformin), AM (db/db + 1% A. membranaceus extract), and FAM (db/db + 1% fermented A. membranaceus extract). After 10 weeks of treatment, we measured the body weight, food intake, and blood glucose, hemoglobin A1C (HbA1c), plasma insulin, adiponectin, and transaminase levels. Oral glucose tolerance test was performed and serum lipid profile was determined. As expected, the AM and FAM groups had significantly reduced body weight, fasting glucose, lipid content, and HbA1c, transaminase, and serum insulin levels, and increased serum adiponectin levels.BRConclusions: Therefore, based on these research results, A. membranaceus extract and fermented A. membranaceus extract can be used to prevent and treat type 2 diabetes by reducing blood glucose levels and lipid content.

This study sought to investigate the antioxidant and immune-stimulatory effects of different Curcuma longa (C. longa) extracts based on their color (random, light, medium, dark orange), the soil of cultivation (clay, granite), drying temperature (50∼80℃), and extraction methods (water, ethanol). The antioxidant factors of C. longa were determined by the total phenolic content and DPPH and ABTS radical scavenging activities. The nitric oxide (NO) production of the macrophage cell line (RAW264.7) and the proliferation of splenocytes were investigated to assess the immune-enhancing effects of C. longa. The antioxidant activity was higher in the dark color and the ethanol extracts. All the types of extracts were nontoxic and enhanced the production of NO in RAW264.7 at less than 250 ㎍/mL of C. longa. When mouse splenocytes were exposed to various concentrations of hot water or ethanol extracts of C. longa with media, concanavalin A (Con A), lipopolysaccharide (LPS), and cyclophosphamide (CPA), their proliferation increased. Specifically, the 70% ethanol extract of C. longa showed the highest levels of splenocyte proliferation among all samples. These results suggest that the antioxidant and immune-stimulating activities of C. longa were most affected by the extracting solvent rather than color, soil in which it was cultured, and drying temperature. Appropriate extraction methods for C. longa should be researched further to develop good healthy foods with high antioxidant and immune-enhancing activities.

Constipation is a functional disorder of the gastrointestinal system characterized by difficult bowel movements, infrequent defecation, reduced water content, and hard stools. This study aims to evaluate the preventive effects of fermented gold kiwis (FGK) on loperamide-induced constipation in rats and investigate its efficacy in improving constipation symptoms in human patients through a randomized clinical trial. In the animal study, FGK was administered orally at doses of 50, 125, and 250 mg/kg to constipated rats for two weeks, resulting in significant improvements in constipation parameters. FGK increased serum serotonin and acetylcholine levels and suppressed increases in serum dopamine concentration. FGK also upregulated mRNA expression of the serotonin-synthesizing receptors 5-HT3R and 5-HT4R and suppressed the expression of the dopamine 2-receptor (D2R) in the duodenum. Furthermore, FGK inhibited inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. In the clinical trials, the improvement in constipation symptoms was evaluated using the gastrointestinal symptom rating scale (GSRS). Clinical trial participants reported significant improvements in constipation symptoms after receiving FGK. These findings suggest that FGK effectively relieves constipation in both animals and humans, indicating its potential as an effective dietary supplement.