Research Progress on the Antioxidant Activity of Natural Diarylheptanoids: Mechanisms and Structure-activity Relationships.

Antioxidant research has recently become a popular topic. Medicinal plants are important sources of novel active compounds. Diarylheptanoids, a typical family of secondary plant metabolites, are of great interest owing to their extensive spectrum of biological activities. They possess a unique 1,7-diphenylmethane structural skeleton. Thus, this review summarizes the natural linear or macrocyclic diarylheptanoids with antioxidant activity in the last two decades. In addition, the relationships between the structural characteristics of natural diarylheptanoids and their antioxidant capacity were also discussed. All the available data highlight the potential of natural diarylheptanoids as novel antioxidants.

Limosilactobacillus fermentum-fermented ginseng improved antibiotic-induced diarrhoea and the gut microbiota profiles of rats.

AIMS: This study investigated the efficacy of Limosilactobacillus fermentum-fermented ginseng for improving colitis and the gut microbiota profiles in rats and explored the benefits of the L. fermentum fermentation process to ginseng. METHODS AND RESULTS: Ginseng polysaccharide and ginsenoside from fermented ginseng were analysed by UV and HPLC. Antibiotic-fed rats were treated with fermented ginseng and a L. fermentum-ginseng mixture. Histopathology- and immune-related factors (TNF-α, IL-1ß, IL-6 and IL-10) of the colon were assayed by using pathological sections and ELISA. After treatment, fermented ginseng relieved the symptoms of antibiotic-induced diarrhoea and colon inflammation, and the expression of colon immune factors returned to normal. The gut microbial communities were identified by 16S rRNA gene sequencing. The results showed that the alterations in the gut microbiota returned to normal. In addition, the gut microbiota changes were correlated with immune factor expression after treatment. The fermented ginseng had better biological functions than a L. fermentum-ginseng mixture. CONCLUSIONS: Fermented ginseng can relieve diarrhoea and colon inflammation and restore the gut microbiota to its original state. The process of L. fermentum fermentation can expand the therapeutic use of ginseng. SIGNIFICANCE AND IMPACT OF THE STUDY: This research suggested the potential function of fermented ginseng to relieve diarrhoea and recover the gut microbiota to a normal level and explored the benefits of the Limosilactobacillus fermentum fermentation process to ginseng.

Paecilomyces cicadae-fermented Radix astragali ameliorate diabetic nephropathy in mice by modulating the gut microbiota.

The occurrence and development of diabetic nephropathy (DN) are closely related to gut microbiota. Paecilomyces cicadae is a medicinal and edible fungus. Radix astragali is a therapeutic material for unifying Chinese Qi. They can delay the occurrence and development of kidney disease. In recent years, solid-state fermentation of edible fungi and traditional Chinese medicine has become a hot issue.Hypothesis/Gap Statement. We assumed that solid-state fermentation products of R. astragali and Paecilomyces cicadidae (RPF) could ameliorate diabetic nephropathy and modulate gut microbiota composition. We aimed to study the function and mechanism of the RPF for ameliorating DN in mice. We investigated the effect of the potential roles of RPF in DN mice and interaction between DN and gut microbiota using animal experiments and gut microbiota measurements. We found that RPF dramatically reduced urine protein, serum creatinine and blood urea nitrogen in DN mice. Furthermore, RPF ameliorated the physiological condition of DN mice by regulating the abundance of intestinal microbiota such as Ruminococcaceae_UCG-014, Allobaculum, Unclassified_f__Lachnospiraceae Alloprevotella and Bacteroides. RPF can ameliorate diabetic nephropathy and modulate gut microbiota composition.

Gene silencing, knockout and over-expression of a transcription factor ABORTED MICROSPORES (SlAMS) strongly affects pollen viability in tomato (Solanum lycopersicum).

BACKGROUND: The tomato (Solanum lycopersicum L.) is an economically valuable crop grown worldwide. Because the use of sterile males reduces the cost of F1 seed production, the innovation of male sterility is of great significance for tomato breeding. The ABORTED MICROSPORES gene (AMS), which encodes for a basic helix-loop-helix (bHLH) transcription factor, has been previously indicated as an essential gene for tapetum development in Arabidopsis and rice. To determine the function of the SlAMS gene (AMS gene from S. lycopersicum) and verify whether it is a potential candidate gene for generating the male sterility in tomato, we used virus-induced gene silencing (VIGS), CRISPR/Cas9-mediated genome editing and over-expression technology to transform tomato via Agrobacterium infection. RESULTS: Here, the full-length SlAMS gene with 1806 bp from S. lycopersicum (Accession No. MK591950.1) was cloned from pollen cDNA. The results of pollen grains staining showed that, the non-viable pollen proportions of SlAMS-silenced (75%), -knockouted (89%) and -overexpressed plants (60%) were significantly higher than the wild type plants (less than 10%; P < 0.01). In three cases, the morphology of non-viable pollen grains appeared tetragonal, circular, atrophic, shriveled, or otherwise abnormally shaped, while those of wild type appeared oval and plump. Furthermore, the qRT-PCR analysis indicated that SlAMS in anthers of SlAMS-silenced and -knockouted plants had remarkably lower expression than in that of wild type (P < 0.01), and yet it had higher expression in SlAMS-overexpressed plants (P < 0.01). CONCLUSION: In this paper, Our research suggested alternative approaches to generating male sterility in tomato, among which CRISPR/Cas9-mediated editing of SlAMS implied the best performance. We also demonstrated that the downregulation and upregulation of SlAMS both affected the pollen formation and notably led to reduction of pollen viability, suggesting SlAMS might be essential for regulating pollen development in tomato. These findings may facilitate studies on clarifying the SlAMS-associated molecular regulatory mechanism of pollen development in tomato.

Monascus ruber fermented Panax ginseng ameliorates lipid metabolism disorders and modulate gut microbiota in rats fed a high-fat diet.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng (Panax ginseng Meyer) is rich in a variety of biologically active ingredients, which shows good effect in the treatment of metabolic diseases. Monascus has lipid-lowering activity and one of its metabolites, lovastatin, is widely used in clinical practice. AIM OF THE STUDY: The main purpose of this study was to clarify the effects of fermented Panax ginseng by Monascus ruber (PM) on lipid metabolism and gut microbiota in rats fed a high-fat diet. MATERIALS AND METHODS: SPF Sprague-Dawley rats were randomly divided into 5 groups, the therapeutic effect of PM on HFD-induced obesity, hyperlipidemia, hepatic steatosis, and disordered gut microbiota were determined in rats. RESULTS: PM could attenuate features of obesity in rats, decrease serum TC, LDL-C and IgA levels, increase excretion of bile acids in feces. Hepatic histopathologic analysis revealed that PM decrease lipid accumulation in hepatocytes. Consistently, mRNA expression levels of cholesterol metabolism-related genes were regulated in the livers of HFD-fed rats administered with PM. In addition, PM could enhance the diversity and relative abundance of gut microbiota, reduce the Firmicutes/Bacteroidetes (F/B) ratio, increase significantly the relative abundance of Prevotella_9, and decrease these of Muribaculaceae. CONCLUSIONS: PM could regulate lipid metabolism and the structure of the gut microbiota in the HFD rats. Our findings provide valuable experience for the development of ginseng. PM could be a potentially effective strategy to prevent and treat metabolic diseases and alleviate the gut microbiota disturbance caused by it.

Process optimization in ginseng fermentation by Monascus ruber and study on bile acid-binding ability of fermentation products in vitro.

Ginseng (Panax ginseng C. A. Meyer) is a famous Traditional Chinese Medicine, which is widely used to treat cardiovascular disease. Monascus ruber (M. ruber) is a fungus used in food and medicine fermentation, and lovastatin, its metabolite, is used extensively in the treatment of dyslipidemia. In this study, ginseng has been fermented by M. ruber, and the response surface methodology (RSM) was applied to optimize fermentation parameters to obtain optimal fermentation system, with further exploring to lipid-lowering activity of P. ginseng C. A. Meyer-M. ruber fermentation products (PM). The concentration of ginseng, temperature, and rotating speed were set as variables and the lovastatin yield was optimized by a Box-Behnken design (BBD) analyzed by RSM. The binding capacity of PM for sodium taurocholate and sodium cholate was assayed by UV spectrophotometry. The highest content of lovastatin production (85.53 µg g-1) was obtained at a ginseng concentration of 1.96%, temperature of 30.11 °C, and a rotating speed of 160.47 rpm. PM exhibited bile acid binding capacity, which was stronger than unfermented ginseng. The RSM can be used to optimize the fermentation system to obtain the best fermentation process. In addition, the fermentation of ginseng by M. ruber can enhance the lipid-lowering effect.

Effects of fermented ginseng on the gut microbiota and immunity of rats with antibiotic-associated diarrhea.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng (Panax ginseng Meyer) is a well-known herb in traditional Chinese medicine and has been used to treat many diseases for thousands of years. Recent studies have shown that ginseng is a promising agent for improving the gut microbiota and treating ulcerative colitis. Fermentation is a common process in traditional Chinese medicine making that can be used to enhance efficacy and reduce toxicity. AIM OF THE STUDY: The purpose of the present study was to research the efficacy of ginseng fermented with probiotics (Lactobacillus fermentum) on the gut microbiota and immunity of rats with antibiotic-associated diarrhea (AAD). MATERIALS AND METHODS: SPF Sprague-Dawley rats were randomly divided into eight groups: control group, antibiotic group, natural recovery group, and five groups treated with different doses of fermented ginseng (FG1 to FG5). A model of AAD was established by treating the rats with triple antibiotics, and obvious symptoms of AAD were observed. A histopathological analysis of the colon was performed. The total bacteria in the intestinal microbiota and five types of gut microbes in the feces were detected by quantitative PCR. The expression levels of related immune factors TLR4 and NF-κB in the colon were assayed. RESULTS: An appropriate dose of fermented ginseng (0.5 g/kg/d) relieved some of the symptoms of AAD and colon inflammation and reduced the expression of the immune factors TLR4 and NF-κB in the colon. The alteration of the gut microbiota observed in the rats treated with antibiotics also returned to normal after treatment with fermented ginseng. Moreover, different doses of fermented ginseng exerted different influences on the gut microbiota, and excessively high or low doses of fermented ginseng were disadvantageous for resolving the symptoms of AAD and promoting recovery. CONCLUSIONS: These results demonstrate that fermented ginseng can treat AAD symptoms and colon inflammation and restore the gut microbiota to its original state.

Paecilomyces cicadae-fermented Radix astragali activates podocyte autophagy by attenuating PI3K/AKT/mTOR pathways to protect against diabetic nephropathy in mice.

Radix astragali, a medicinal material for tonifying Chinese Qi, has widely been used for the treatment of Kidney disease in China and East Asia, especially in reducing the apoptosis of glomerular podocytes. Paecilomyces Cicadidae is a medicinal and edible fungus. In recent years, the application of traditional Chinese medicine (TCM) in solid-state fermentation of edible and medicinal fungi has become a hot issue. Fermentation is a special method to change the properties of TCM. Therefore, the potential roles and molecular mechanisms on podocytes of solid-state fermentation products of Radix astragali and Paecilomyces cicadidae (RPF) in diabetic nephropathy (DN) were studied. In vivo, the effect of RPF and Radix astragali on DN in mice was evaluated by detecting the biochemical indexes of blood and urine, renal function and podocyte integrity. In vitro, the expression of podocyte marker protein, autophagy marker protein and PI3K/AKT/mTOR signaling pathway protein were detected by Western blotting using a high glucose-induced podocyte injury model. The results showed that RPF had a significant alleviative effect on DN mice. RPF can significantly reduce urine protein, serum creatinine, and blood nitrogen urea in DN mice. Morphological analysis showed that RPF could improve kidney structure of DN and reduce the apoptosis of podocytes, and the effect was better than Radix astragali. In vitro results indicated that RPF could enhance autophagy and protect podocytes by inhibiting the PI3K/AKT/mTOR signaling pathway. In summary, RPF has better effect on delaying the development of DN than Radix astragali. RPF enhances autophagy in podocytes and delays DN probably by inhibiting the PI3K/AKT/mTOR signaling pathway.