PMID: 

Andrologia. 2020 May ;52(4):e13554. Epub 2020 Mar 6. PMID: 32141651

Abstract Title: 

Lycium barbarum polysaccharide protects against ethanol-induced spermiotoxicity and testicular degeneration in Immp2lmice.

Abstract: 

Studies have indicated that high levels of ethanol exposure impaired spermatogenesis in mice. However, the effects of chronic and low-dose alcohol consumption on susceptible populations remain unclear. The previous studies have confirmed that Immp2l mutant mice (Immp2lor Immp2l) suffered from increased levels of oxidative stress(OS) and male infertility, heterozygous lmmp2l mice (Immp2l) showed no altered ROS levels under physiological condition. Lycium barbarum polysaccharide (LBP) significantly scavenge oxygen free radicals and enhance antioxidant enzyme activity. The objectives of present study were to research the effects of chronic and low-dose alcohol-induced damage on Immp2l, explore the protective function of LBP and possible mechanism. The results indicated that chronic ethanol exposure leads to spermatogenic impairment and triggered a toxic effect on germ cell, 10 mg/kg LBP administration improved the quality of spermatozoon, decreased the ratio of apoptotic germ cells and the expression of Col1a1 and Col1a2, while increased the level of TNP2 and RPL31. In conclusion, the study may provide basic knowledge about LBP's important role against ethanol-induced spermiotoxicity and testicular degeneration in Immp2lmice, and the mechanism may be that LBP influenced the state of the spermatogenic epithelium by decreasing the expression of Collagen level leading to alterations in protein biosynthesis during the process of spermatogenesis.

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PMID: 

J Pharm Biomed Anal. 2020 Feb 29 ;185:113219. Epub 2020 Feb 29. PMID: 32145536

Abstract Title: 

Effects of extraction methods on immunology activity and chemical profiles of Lycium barbarum polysaccharides.

Abstract: 

It has been proven that polysaccharides have bioactivities and are beneficial to cure many diseases. Lycium barbarum fruit is widely used as a functional food all over the world, which main active component is L. barbarum polysaccharides (LBPs). In this study, classical hot water extraction (HWE), microwave assisted extraction (MAE), ultrasonic assisted extraction (UAE) and pressurized liquid extraction (PLE) were used to extracted LBP. The chemical properties of LBPs were evaluated in terms of total polysaccharide contents, uronic acid contents and protein contents. High performance size exclusion chromatography coupled with multi angle laser light scattering and refractive index detector was applied to measure the characters such as molecular weight, radius of gyration and polydispersity index. Then the immunomodulatory activity of LBPs was evaluated through RAW 264.7 cells. The results showed that HWE was the best method to get the highest total sugar and acidic polysaccharides, MAE was preferable to extract polysaccharide-protein complex, but PLE, UAE and HWE could get better immunomodulatory activity polysaccharides than MAE. Besides, the peak 3 in chromatogram of MAE extracted LBPs was obviously higher than those of LBPs produced by other 3 extraction methods, which suggested that peak 1 and peak 2 might be biologically active polysaccharides fractions in LBPs. Therefore, effect of different extraction methods on structure and composition of LBPs attributed to their variance of immunological activities.

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PMID: 

Molecules. 2020 Mar 16 ;25(6). Epub 2020 Mar 16. PMID: 32188121

Abstract Title: 

Immunomodulatory Effects ofPolysaccharide Extract and Its Uptake Behaviors at the Cellular Level.

Abstract: 

L. is a widely used functional food and medicinal herb in Asian countries.polysaccharides (LBP) are considered as one of the major medicinal components offruit and exhibits a wide range of biological activities. Here, we investigated the immunomodulatory effects of LBP and its uptake behaviors at the cellular level. LBP was prepared by water extraction and ethanol precipitation, and divided into two fractions based on the molecular weight distribution by ultrafiltration (LBP>10 kDa and LBP10 kDa fraction greatly enhanced the viability of macrophages RAW264.7 cells and induced cell polarization, but had weak effects to other tested tumor cell lines and normal cell line. This fraction could regulate the production of NO, TNF-α, IL-6 and ROS in RAW264.7 cells, suggesting both pro-inflammatory and anti-inflammatory effects. The dye-labeled LBP could be internalized into all tested cell lines and accumulated in lysosomes. The internalization of LBP in RAW264.7 cells is mainly through the clathrin-mediated endocytosis pathway. The Caco-2 intestinal transport experiment demonstrated that the dye labeled LBP could be transported through the Caco-2 cell monolayer (mimic intestinal epithelium) through clathrin-mediated endocytosis. These results demonstrate the immunomodulatory effects of LBP and its effective uptake bymacrophages and intestine.

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PMID: 

J Food Biochem. 2020 Mar 26:e13215. Epub 2020 Mar 26. PMID: 32215941

Abstract Title: 

Immunostimulating activity of Lycium chinense Miller root extract through enhancing cytokine and chemokine production and phagocytic capacity of macrophages.

Abstract: 

Whereas the fruits and a small portion of root bark of Lycium trees are commonly marketed in Korea as traditional medicine or functional foods, majority of their whole roots have been largely discarded. To develop the whole root of these plants as more value-added materials, this study aimed to evaluate the potential immunostimulating activity of a water extract (GTR-101) from L. chinense Miller roots using macrophages. The GTR-101 (0-500 μg/ml) significantly, dose-dependently increased the secretion of pro-inflammatory cytokines (TNF-α and IL-6), chemokines (RANTES and MIP-1α), nitric oxide, and the expression of inducible nitric oxide synthase, and activated the Akt, NF-κB, and MAPKs (ERK and p38) signaling proteins. GTR-101also significantly enhanced the phagocytic activity of RAW 264.7 cells and bone marrow-derived macrophages. These results suggest that GTR-101 stimulates the early innate immunity via inducing the pro-inflammatory cytokine and chemokine secretion and enhancing the phagocytic activity of macrophages.PRACTICAL APPLICATIONS: The GTR-101 prepared from L. chinense Miller roots may be useful for enhancing body's defense systems especially in the elderly and cancer patients with an impaired or reduced immune response and may thus be effectively used as a natural immunostimulating ingredient in health foods or complementary medicine.

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PMID: 

Food Funct. 2020 Apr 30 ;11(4):3741-3748. PMID: 32314770

Abstract Title: 

Lycium barbarum polysaccharides ameliorate intestinal barrier dysfunction and inflammation through the MLCK-MLC signaling pathway in Caco-2 cells.

Abstract: 

Impairment of the intestinal barrier often occurs in inflammatory bowel diseases, and pro-inflammatory factors play a vital role in the pathogenesis of intestinal diseases. In our study, the potential protective effects of Lycium barbarum polysaccharides (LBP) against intestinal barrier dysfunction evoked by pro-inflammatory factors and its anti-inflammatory effects were investigated. Caco-2 cells were stimulated with or without tumor necrosis factor (TNF)-α in the presence or absence of LBP. Our findings showed that LBP assuaged the increase of paracellular permeability and the decrease of transepithelial electrical resistance (TER) in Caco-2 cells. In addition, LBP also prevented the secretion of pro-inflammatory markers (IL-8, IL-6, ICAM-1 and MCP-1) in TNF-α-challenged Caco-2 cells. Moreover, LBP inhibited the overexpression of tight junction (TJ) proteins (claudin-1, ZO-3, and occludin) and the increase of MLCK, pMLC, p-IκBα and NFκBp65 protein expression evoked by TNF-α was suppressed by LBP pre-incubation. This finding indicated that LBP improve TNF-α-evoked intestinal barrier dysfunction via suppressing the MLCK-MLC signaling pathway mediated by NFκB.

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PMID: 

Front Endocrinol (Lausanne). 2020 ;11:164. Epub 2020 Apr 17. PMID: 32362869

Abstract Title: 

Polysaccharides Improve Testicular Spermatogenic Function in Streptozotocin-Induced Diabetic Rats.

Abstract: 

The objective of this study was to investigate the protective effects ofpolysaccharides (LBP) on testicular spermatogenic function in streptozotocin (STZ)-induced diabetic rats. Compared to the control group, blood glucose levels were significantly increased and the insulin resistance was markedly aggravated in STZ-induced diabetic rats. Further, the weight of testis and epididymis and the sperm number and motility were decreased in diabetic rats. Pathological changes were also observed in the spermatogenic tubules, along with a decreased number of spermatogenic cells, downregulated proliferating cell nuclear antigen (PCNA) expression, and increased cell apoptosis in the testes. Compared to the saline-treated diabetic rat group, metformin and LBP treatment significantly decreased the level of blood glucose and improved insulin resistance and testicular function. After treatment with metformin and LBP, the pathological changes in the spermatogenic tubules improved significantly, with an increase in the number of spermatogenic cells, upregulation of PCNA, and suppression of apoptosis in the testes. The expressions of sirtuin 1 (SIRT1) and hypoxia-inducible factor 1-alpha (HIF-1α) in diabetic testes were also upregulated by metformin or LBP treatment. In summary, LBP exerted protective effects by increasing cell proliferation, inhibiting cell apoptosis, and regulating SIRT1/HIF-1α expression in the testes of diabetic rats.

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PMID: 

Sci Rep. 2019 02 19 ;9(1):2301. Epub 2019 Feb 19. PMID: 30783194

Abstract Title: 

Green tea catechins alleviate autoimmune symptoms and visual impairment in a murine model for human chronic intraocular inflammation by inhibiting Th17-associated pro-inflammatory gene expression.

Abstract: 

Autoimmune uveitis is a sight-threatening disease mainly caused by dysregulation of immunity. We investigated the therapeutic effects of green tea extract (GTE) and its major component, epigallocatechin-3-gallate (EGCG), on a murine model of experimental autoimmune uveoretinitis (EAU). Oral administration of GTE, EGCG, dexamethasone, or water, which started 5 days before the induction, was fed every two days to each group. On day 21 post induction, the eyes were examined by confocal scanning laser ophthalmoscopy, optical coherence tomography (OCT), fundus fluorescein angiography (FFA) and electroretinography (ERG) prior to sacrificing the animals for histological assessments and gene expression studies. Retinal-choroidal thicknesses (RCT) and major retinal vessel diameter were measured on OCT sections and FFA images, respectively. Comparing to water-treated EAU animals, GTE attenuated uveitis clinical manifestations, RCT increase (1.100 ± 0.013 times vs 1.005 ± 0.012 times, P 

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PMID: 

J Inflamm Res. 2019 ;12:231-239. Epub 2019 Aug 29. PMID: 31695470

Abstract Title: 

Epigallocatechin-3-gallate suppresses neutrophil migration speed in a transgenic zebrafish model accompanied by reduced inflammatory mediators.

Abstract: 

Background: Polyphenol catechins from green tea, particularly (-)-epigallocatechin-3-gallate (EGCG), exhibits numerous beneficial health effects, although the mechanisms remain unclear.Methods: In this study, the mechanism of EGCG-mediated healing in an experimentally injured zebrafish model was examined at the cellular and molecular level using confocal microscopy and gene expression analysis.Results: The mechanisms of action of EGCG were shown to involve: (1) reducing neutrophil response (accumulation, travel speed, and distance) and (2) downregulating the expression of IL-1β, TNFα, and related signaling pathways. As determined by dynamic time-lapse tracking studies, the local accumulation of neutrophils with high migration speeds after wounding (n=33 cells, v=0.020 μm/s, d=37.8 μm), underwent significant reduction following treatment with EGCG doses of 300 μM (n=22 cells, v=0.013 μm/s, d=39.5 μm) and 600 μM (n=18 cells, v=0.008 μm/s, d=9.53 μm). Reverse transcription polymerase chain reaction studies revealed that several signature genes in the IL-1β, TNFα, and related signaling pathways were downregulated after EGCG treatment.Conclusion: The convenience, transparency, and simplicity of the zebrafish model facilitate tracking of fluorescent neutrophils in real time, in order to monitor inflammation, and assess the impact of therapeutic agents.

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PMID: 

Nutrients. 2020 Apr 10 ;12(4). Epub 2020 Apr 10. PMID: 32290071

Abstract Title: 

Green Tea Polyphenol EGCG Attenuates MDSCs-mediated Immunosuppression through Canonical and Non-Canonical Pathways in a 4T1 Murine Breast Cancer Model.

Abstract: 

Several studies in the past decades have reported anti-tumor activity of the bioactive compounds extracted from tea leaves, with a focus on the compound epigallocatechin-3-gallate (EGCG). However, further investigations are required to unravel the underlying mechanisms behind the anti-tumor activity of EGCG. In this study, we demonstrate that EGCG significantly inhibits the growth of 4T1 breast cancer cellsand. EGCG ameliorated immunosuppression by significantly decreasing the accumulation of myeloid-derived suppressor cells (MDSCs) and increasing the proportions of CD4and CD8T cells in spleen and tumor sites in 4T1 breast tumor-bearing mice. Surprisingly, a low dose of EGCG (0.5-5μg/mL) effectively reduced the cell viability and increased the apoptosis rate of MDSCs. EGCG down-regulated the canonical pathways in MDSCs, mainly through the Arg-1/iNOS/Nox2/NF-κB/STAT3 signaling pathway. Moreover, transcriptomic analysis suggested that EGCG also affected the non-canonical pathways in MDSCs, such as ECM-receptor interaction and focal adhesion. qRT-PCR further validated that EGCG restored nine key genes in MDSCs, including,,,,,,,and. Our results provide new insight into the mechanism of EGCG-associated key pathways/genes in MDSCs in the murine breast tumor model.

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PMID: 

Am J Respir Cell Mol Biol. 2020 May 6. Epub 2020 May 6. PMID: 32374624

Abstract Title: 

Novel Therapy of Bicarbonate, Glutathione and Ascorbic Acid Improves Cystic Fibrosis Mucus Transport.

Abstract: 

Defective airway mucus clearance is a defining characteristic of CF lung disease, and improvements to current mucolytic strategies are needed. Novel approaches targeting a range of contributing mechanisms are in various stages of preclinical and clinical development. ARINA-1 is a new, nebulized product comprised of ascorbic acid, glutathione, and bicarbonate. Using micro-optical coherence tomography, we tested the effect of ARINA-1 on central features of mucociliary clearance in F508del/F508del primary human bronchial epithelial cells to assess its potential as a mucoactive therapy in CF. We found that ARINA-1 significantly augmented mucociliary transport (MCT) rates, both alone and with CFTR modulator therapy, whereas airway hydration and ciliary beating were largely unchanged compared to PBS vehicle control. Analysis of mucus reflectivity and particle tracking microrheology indicated that ARINA-1 restores mucus clearance by principally reducing mucus layer viscosity. The combination of bicarbonate and glutathione elicited increases to MCT rate comparable to those seen with ARINA-1, indicating the importance of this interaction to the impact of ARINA-1 on mucus transport; this effect was not recapitulated with bicarbonate alone or bicarbonate combined with ascorbic acid. Assessment of CFTR chloride transport revealed an increase in CFTR-mediated chloride secretion in response to ARINA-1 in CFBE41o- cells expressing wild-type CFTR, driven by CFTR activity stimulation by ascorbate. This response was absent in CFBE41o- F508del cells treated with VX-809 and primary HBE cells, implicating CFTR-independent mechanisms for the effect of ARINA-1 on CF mucus. Together, these studies indicate that ARINA-1 is a novel potential therapy for the treatment of impaired mucus clearance in CF.

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