Tea polyphenols (TPP) as a promising wound healing agent: TPP exerts multiple and distinct mechanisms at different phases of wound healing in a mouse model.

Polyphenols have been widely used to treat various chronic skin diseases because they are beneficial in wound healing and show anti-inflammatory effects, however, the mechanism of action remains ambiguous. Previously, we reported the wound healing capability of tea polyphenols (TPP), the major functional component of tea, in vivo. The current study aimed to address the mechanisms of TPP in wound healing during different phases (inflammation, proliferation and remodeling). During the inflammation phase, TPP reduced the production of proinflammatory cytokines (IL-1ß, IL-6 and TNF-α) and inhibited infiltration of neutrophils; during the proliferation phase, TPP promoted the expression of growth factor VEGF-A, which can promote vascular endothelial cell division and induce angiogenesis; TPP improved the morphology of the wound and restored the ratio of type III/I collagens during the remodeling phase, as determined by Masson-trichrome staining and Sirius red staining assays. By tracking the changes in the wound area, TPP and recombinant human epidermal growth factor (rhEGF), rather than povidone-iodine (PVP-I), were able to promote wound healing. These results suggest that TPP plays a pivotal role in all the key stages of wound healing and displays distinct mechanisms from rhEGF, suggesting clinical significance for the future application of TPP as a natural wound healing agent.

L-Theanine and Immunity: A Review.

L-theanine (N-ethyl-γ-glutamine) is the main amino acid in tea leaves. It not only contributes to tea flavor but also possesses several health benefits. Compared with its sedative and calming activities, the immunomodulatory effects of L-theanine have received less attention. Clinical and epidemiological studies have shown that L-theanine reduces immunosuppression caused by strenuous exercise and prevents colds and influenza by improving immunity. Numerous cell and animal studies have proven that theanine plays an immunoregulatory role in inflammation, nerve damage, the intestinal tract, and tumors by regulating γδT lymphocyte function, glutathione (GSH) synthesis, and the secretion of cytokines and neurotransmitters. In addition, theanine can be used as an immunomodulator in animal production. This article reviews the research progress of L-theanine on immunoregulation and related mechanisms, as well as its application in poultry and animal husbandry. It is hoped that this work will be beneficial to future related research.

Correlation between serum zinc and testosterone: A systematic review.

Zinc is a vital trace element for normal function of the living system. In male, zinc is involved in various biological processes, an important function of which is as a balancer of hormones such as testosterone. For this purpose, studies related to the influence of zinc on serum testosterone were selected and summarized, including the effect of dietary zinc deficiency and zinc supplementation on testosterone concentrations. After preliminary searching of papers on databases, 38 papers including 8 clinical and 30 animal studies were included in this review. We concluded that zinc deficiency reduces testosterone levels and zinc supplementation improves testosterone levels. Furthermore, the effect degree of zinc on serum testosterone may vary depending on basal zinc and testosterone levels, zinc dosage form, elementary zinc dose, and duration. In conclusion, serum zinc was positively correlated with total testosterone, and moderate supplementation plays an important role in improving androgen.

Saponins from Camellia sinensis Seeds Stimulate GIP Secretion in Mice and STC-1 Cells via SGLT1 and TGR5.

Glucose-dependent insulinotropic polypeptide (GIP) is one of the important incretins and possesses lots of physiological activities such as stimulating insulin secretion and maintaining glucose homeostasis. The pentacyclic triterpenoid saponins are the major active ingredients in tea (Camellia sinensis) seeds. This study aimed to investigate the effect of tea seed saponins on the GIP secretion and related mechanisms. Our data showed that the total tea seed saponins (TSS, 65 mg/kg BW) and theasaponin E1 (TSE1, 2-4 µM) could increase the GIP mRNA and protein levels in mice and STC-1 cells. Phlorizin, the inhibitor of Sodium/glucose cotransporter 1 (SGLT1), reversed the TSE1-induced increase in Ca2+ and GIP mRNA level. In addition, TSE1 upregulated the protein expression of Takeda G protein-coupled receptor 5 (TGR5), and TGR5 siRNA significantly decreased GIP expression in TSE1-treated STC-1 cells. Network pharmacology analysis revealed that six proteins and five signaling pathways were associated with SGLT1, TGR5 and GIP regulated by TSE1. Taken together, tea seed saponins could stimulate GIP expression via SGLT1 and TGR5, and were promising natural active ingredients for improving metabolism and related diseases.

Poria cocos polysaccharides attenuate chronic nonbacterial prostatitis by targeting the gut microbiota: Comparative study of Poria cocos polysaccharides and finasteride in treating chronic prostatitis.

Finasteride is an antiandrogenic drug used for the clinical treatment of chronic nonbacterial prostatitis (CNP). Recently, we reported the anti-CNP activity of Poria cocos polysaccharides (PPs) in a rat model. In this study, we compared the differences between PPs and finasteride in treating CNP, especially their effects on the gut microbiota. Results showed that both PPs and finasteride significantly reduced the prostate weight and prostate index of CNP rats, and improved the histological damages in the inflamed prostate. Moreover, PPs and finasteride inhibited the production of pro-inflammatory cytokines (TNF-α, IL-2 and IL-8) and androgens (dihydrotestosterone and testosterone). By 16S rDNA sequencing, PPs and finasteride were found to reprogram the gut microbiota into distinct profiles. Further analysis presented that PPs but not finasteride recovered CNP-induced changes in the gut microbiota, including Ruminococcaceae NK4A214 group, uncultured bacterium f Ruminococcaceae, Ruminiclostridium 9, Phascolarctobacterium, Coriobacteriaceae UCG-002 and Oribacterium. LDA effect size (LEfSe) analysis revealed that PPs recovered the gut microbiota by targeting Ruminococcaceae NK4A214 group. Our results suggested that PPs alleviated CNP via different mechanisms from finasteride, especially by regulating the gut microbiota, which offers therapeutic target for the treatment of CNP.

Reprogrammed intestinal functions in Astragalus polysaccharide-alleviated osteoporosis: combined analysis of transcriptomics and DNA methylomics demonstrates the significance of the gut-bone axis in treating osteoporosis.

Researchers have noted that organ-organ communication between bone and intestine has significant effects on bone health and its related diseases. In this study, we collected colonic epithelial tissue from dexamethasone-induced osteoporotic rats and Astragalus polysaccharide (APS)-alleviated osteoporotic rats and employed transcriptome sequencing to investigate the functional changes that occurred in the intestine. Principal component analysis showed that both dexamethasone (inducer of osteoporosis) and APS reprogrammed the gene expression profile of the intestine. Further analysis identified 496 and 291 differentially expressed genes (DEGs) in osteoporotic and APS-treated osteoporotic rats, respectively. KEGG enrichment analysis of these DEGs demonstrated osteoporosis-induced intestinal dysfunctions that were further modified by APS treatment. Further analysis demonstrated that APS could restore intestinal functions by reversing the expression of 53 DEGs in osteoporotic rats. Recovery of osteoclast differentiation and the calcium signalling pathway might contribute to the improvement of osteoporosis. Moreover, utilizing methylC-capture sequencing (MCC-Seq), we studied the changes in DNA methylation and performed epigenetic analysis of dexamethasone- and APS-induced gene expression changes. In this study, osteoporosis was observed to cause intestinal dysfunction, which is a complication of this disease. More importantly, APS was determined to reprogram intestinal functions to alleviate osteoporosis via the gut-bone axis. Our results support the existence of a gut-bone axis and suggest new therapeutic opportunities for the treatment of osteoporosis via the gut-bone axis.

Reprogrammed Epigenetic Landscape-Prophesied Functions of Bioactive Polysaccharides in Alleviating Diseases: A Pilot Study of DNA Methylome Remodeling in Astragalus Polysaccharide (APS)-Improved Osteoporosis in a Rat Model.

DNA methylation is an epigenetic event that plays critical roles in the pathogenesis, progression, and treatment of human diseases. In this study, we investigated the epigenetic mechanisms for Astragalus polysaccharide (APS)-improved osteoporosis in a rat model. The results showed that APS significantly changed the DNA methylome in colonic epithelia with great efficiency. Gene set enrichment analysis (GSEA) based on differentially methylated sites (DMSs) revealed that APS caused promoter DNA methylation changes of genes associated with calcium homeostasis, osteoclast/osteoblast balance, Wnt signaling, and hormone-related processes. Further analysis showed high consistency of APS-induced gene methylomic changes in colonic epithelia and its effects on diabetes, virus infection, and wound healing, which had been reported already. Moreover, we suggested new functions and the involved mechanisms of APS in heart disease, neurological disorder, reproductive problem, and olfactory dysfunction. In this study, we offered epigenetic mechanisms for APS-improved osteoporosis. More importantly, we proposed and proved a reliable method to explore the beneficial effects of bioactive polysaccharides by studying DNA methylation changes at nonfocal sites. We firmly believed the promising prospects of this method for its great efficiency, rapidness, and economy in exploring possible beneficial or therapeutic effects of functional macromolecules with one single experiment.

Recovery of Ggt7 and Ace Expressions in the Colon Alleviates Collagen-Induced Arthritis in Rats by Specific Bioactive Polysaccharide Intervention.

Rheumatoid arthritis (RA) causes swollen joints and irreversible joint damage and may even elevate cancer risks. Several bioactive nonstarch polysaccharides (NSPs) were reported to alleviate RA, but the key colonic genes accountable for this alleviation were elusive. Using collagen-induced arthritis as an RA model, colonic candidate genes related to RA were selected by transcriptome and methylome. The key genes were determined by comparing the transcriptome, methylome, and quantitative reverse transcription polymerase chain reaction profiles in RA rats with and without Lycium barbarum polysaccharides' treatment and further validated using Angelica sinensis polysaccharides and Astragalus propinquus polysaccharides for comparison. Both colonic genes γ-glutamyltransferase 7 (Ggt7) and angiotensin-I-converting enzyme (Ace) were downregulated by RA, and they were upregulated after L. barbarum polysaccharides' and A. sinensis polysaccharides' intervention that reduced the RA-caused hypermethylation status in nucleotide sites in the exon/promoter region of the two genes. However, the A. propinquus polysaccharides' intervention barely reduced the hypermethylation in the corresponding sites, failing to recover the expressions of these two genes and improve RA. Therefore, the colonic Ggt7 and Ace can be considered as key genes accountable for RA alleviation by bioactive NSP intervention. This study provides a more comprehensive insight into diet intervention to improve RA.

Poria cocos Polysaccharides Alleviates Chronic Nonbacterial Prostatitis by Preventing Oxidative Stress, Regulating Hormone Production, Modifying Gut Microbiota, and Remodeling the DNA Methylome.

Chronic nonbacterial prostatitis (CNP) is a common male disease with high incidence and low cure rate. This study aims to investigate the anti-CNP potential of Poria cocos polysaccharides (PPs) in a λ-carrageenan-induced CNP rat model. Results showed that PPs exerted anti-CNP functions by reducing the prostate weight and prostate index as well as the level of C-reactive protein (CRP) and pro-inflammatory cytokines (TNF-α and IL-1ß). Further analysis on sex hormones revealed that PPs could favor CNP alleviation by regulating the production of testosterone (T), dihydrotestosterone (DTH), and estradiol (E2). PPs could also alleviate CNP by regulating the level of inducible nitric oxide synthase (iNOS), malonaldehyde (MDA), and superoxide diamutase (SOD) in inflamed prostate, thereby enhancing the anti-oxidative stress activity. As most non-digestive polysaccharides are fermented by gut microbiota rather than being digested directly by the host, we further analyzed PP-induced changes in gut microbiota. Microbiomic analysis revealed that PPs significantly change the profile of gut microbiota. Moreover, the relative abundance of five genera was recovered by PPs with a dose-effect relationship, thereby being suggested to play critical roles in the alleviation of CNP. Epigenomic (methylomic) analysis showed that PPs remodeled the DNA methylome of intestinal epithelia, by which PPs might modify hormone production. In the present study, we reported the anti-CNP activity of PPs as well as the involved mechanisms.

Dietary Supplementation of n-3 LCPUFAs Prevents Salmonellosis in a Murine Model.

Salmonellosis is a world-wide epidemic, and n-3 long chain polyunsaturated fatty acids (LCPUFAs) possess various health benefits. This study is aimed to investigate the preventive effects of n-3 LCPUFAs against Salmonella infection. By pretreatment with n-3 LCPUFAs, but not n-6 LCPUFAs, the survival rate of the infected mice was increased. Further studies showed that n-3 LCPUFAs significantly increased the fecal contents of short-chain fatty acids (SCFAs). The cytokine expression in the liver and production in serum were both modulated by n-3 LCPUFAs into an anti-inflammatory profile against infection. Moreover, the changes in gut microbiota by n-3 LCPUFAs favored the host against pathogens, closely related to the modified SCFA production and immune responses. In conclusion, n-3 LCPUFAs prevented Salmonella infection through multiple mechanisms, especially by the interaction with gut microbiota and host immunology. Our results suggested great perspectives for n-3 LCPUFAs and their related products to control the prevalence of Salmonella, a most predominant food-borne pathogen.

Strain-specific properties of Lactobacillus plantarum for prevention of Salmonella infection.

Salmonella is a common food-borne pathogen; since lactobacilli show great potential for protecting against Salmonella infections, they are used as dietary supplements in functional foods. The aim of this study is to investigate the strain-specific properties and the involved mechanisms of action of Lactobacillus plantarum towards prevention of Salmonella infection. Mice were pretreated with mixed strains or single strain of Lactobacillus plantarum for 10 d prior to infection with Salmonella typhimurium SL1344, and the survival rates showed that lactobacilli exhibited strain-specific properties for preventing Salmonella infection. Then, in vitro and in vivo studies were carried out to investigate the involved mechanism of the strain-specific properties. The results showed that different Lactobacillus plantarum strains had different effects on inhibiting Salmonella growth, thus preventing adhesion to and invasion of epithelial cells by pathogens and enhancing immune responses. The present study demonstrated strain-specific properties of probiotics to prevent Salmonella infection and elucidated their underlying mechanisms.