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Efficacy of Lycium barbarum polysaccharide in adolescents with subthreshold depression: interim analysis of a randomized controlled study

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Neural Regeneration Research 2022年第7期17卷 1582-1587页

作者： Xiaoyue Li Xuan Mo Tao Liu Robin Shao Kayla Teopiz Roger S.McIntyre Kwok-Fai So Kangguang Lin Department of Affective Disorders The Affiliated Brain Hospital of Guangzhou Medical University(Guangzhou Huiai Hospital)GuangzhouGuangdong ProvinceChina Laboratory of Emotion and Cognition The Affiliated Hospital of Guangzhou Medical University(Guangzhou Huiai Hospital)GuangzhouGuangdong ProvinceChina Department of Psychiatry The Fifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Canadian Rapid Treatment Center of Excellence MississaugaONCanada Mood Disorders Psychopharmacology Unit Poul Hansen Family Centre for DepressionUniversityHealth NetworkTorontoONCanada Department of Psychiatry University of TorontoTorontoONCanada Brain and Cognition Discovery Foundation TorontoONCanada Ministry of Education Joint International Research Laboratory of CNS Regeneration Jinan UniversityGuangzhouGuangdong ProvinceChina Neuroscience and Neurorehabilitation Institute University of Health and Rehabilitation SciencesQingdaoShandong ProvinceChina

Subthreshold depression is a highly prevalent condition in adolescents who are at high risk for developing major depressive disorder.In preclinical models of neurological and psychiatric diseases,Lycium barbarum polysaccharide(LBP)extracted from Goji berries had antidepressant effects including but not limited to anti-oxidative and anti-inflammatory properties.However,the effect of LBP on subthreshold depression is unclear.To investigate the clinical efficacy and safety of LBP for treating subthreshold depression in adolescents,we conducted a randomized,double-blind,placebo-controlled trial(RCT)with 29 adolescents with subthreshold depression recruited at The Fifth Affiliated Hospital of Guangzhou Medical University.The participants were randomly assigned to groups where they received either 300 mg LBP(LBP group,n=15,3 boys and 12 girls aged 15.13±2.17 years)or a placebo(placebo group,n=14,2 boys and 12 girls aged 15±1.71 years)for 6 successive weeks.Interim analyses revealed that the LBP group exhibited a greater change in Hamilton Depression Scale(HAMD-24)scores relative to the baseline and a higher remission rate(HAMD-24 total score≤7)at 6 weeks compared with the placebo group.Scores on the Beck Depression Inventory-II(BDI-II),Pittsburgh Sleep Quality Index(PSQI),Kessler Psychological Distress Scale(Kessler),and Screen for Child Anxiety-Related Emotional Disorders(SCARED)were similar between the LBP and placebo groups.No side effects related to the intervention were reported in either group.These results indicate that LBP administration reduced depressive symptoms in adolescents with subthreshold depression.Furthermore,LBP was well tolerated with no treatment-limiting adverse events.Clinical trials involving a larger sample size are needed to further confirm the anti-depressive effects of LBP in adolescents with subthreshold depression.This study was approved by the Medical Ethics Committee of the Fifth Affiliated Hospital of Guangzhou Medical University(Guangzhou,China;approval No.L2019-08)on April 4,2019 and

关键词： adolescents efficacy Goji berry Lycium barbarum polysaccharide randomized clinical trial safety subthreshold depression tolerance

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A novel anticancer property of Lycium barbarum polysaccharide in triggering ferroptosis of breast cancer cells

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2022年第4期23卷 286-299页

作者： Xing DU Jingjing ZHANG Ling LIU Bo XU Hang HAN Wenjie DAI Xiuying PEI Xufeng FU Shaozhang HOU Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education School of Basic Medical SciencesNingxia Medical UniversityYinchuan 750004China Department of Clinical Pathology School of Basic Medical SciencesNingxia Medical UniversityYinchuan 750004China

Breast cancer is one of the most malignant tumors and is associated with high mortality rates among women.Lycium barbarum polysaccharide(LBP)is an extract from the fruits of the traditional Chinese herb,L.barbarum.LBP is a promising anticancer drug,due to its high activity and low toxicity.Although it has anticancer properties,its mechanisms of action have not been fully established.Ferroptosis,which is a novel anticancer strategy,is a cell death mechanism that relies on iron-dependent lipid reactive oxygen species(ROS)accumulation.In this study,human breast cancer cells(Michigan Cancer Foundation-7(MCF-7)and MD Anderson-Metastatic Breast-231(MDA-MB-231))were treated with LBP.LBP inhibited their viability and proliferation in association with high levels of ferroptosis.Therefore,we aimed to ascertain whether LBP reduced cell viability through ferroptosis.We found that the structure and function of mitochondria,lipid peroxidation,and expression of solute carrier family 7 member 11(SLC7 A11,also known as x CT,the light-chain subunit of cystine/glutamate antiporter system X_(c)^(-))and glutathione peroxidase 4(GPX4)were altered by LBP.Moreover,the ferroptosis inhibitor,Ferrostatin-1(Fer-1),rescued LBP-induced ferroptosis-associated events including reduced cell viability and glutathione(GSH)production,accumulation of intracellular free divalent iron ions and malondialdehyde(MDA),and down-regulation of the expression of x CT and GPX4.Erastin(x CT inhibitor)and RSL3(GPX4 inhibitor)inhibited the expression of x CT and GPX4,respectively,which was lower after the co-treatment of LBP with Erastin and RSL3.These results suggest that LBP effectively prevents breast cancer cell proliferation and promotes ferroptosis via the x CT/GPX4 pathway.Therefore,LBP exhibits novel anticancer properties by triggering ferroptosis,and may be a potential therapeutic option for breast cancer.

关键词： Lycium barbarum polysaccharide Ferroptosis Breast cancer cells xCT Glutathione peroxidase 4(GPX4)

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Lycium barbarum polysaccharide-glycoprotein preventative treatment ameliorates aversive stimuli-induced depression

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Neural Regeneration Research 2021年第3期16卷 543-549页

作者： Yun-Wei Fu Yan-Fang Peng Xiao-Dan Huang Yan Yang Lu Huang Yue Xi Zheng-Fang Hu Song Lin Kwok-Fai So Chao-Ran Ren Guangdong-Hongkong-Macao Institute of CNS Regeneration Ministry of Education CNS Regeneration Collaborative Joint LaboratoryJinan UniversityGuangzhouGuangdong ProvinceChina Aier Eye Institute ChangshaHunan ProvinceChina Department of Physiology School of MedicineJinan UniversityGuangzhouGuangdong ProvinceChina Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory) GuangzhouGuangdong ProvinceChina Center for Brain Science and Brain-Inspired Intelligence Guangdong-Hong Kong-Macao Greater Bay AreaGuangzhouGuangdong ProvinceChina Co-innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina Department of Ophthalmology and State Key Laboratory of Brain and Cognitive Sciences The University of Hong KongHong Kong Special Administrative RegionChina

Previous studies have shown that Lycium barbarum polysaccharide,the main active component of lycium barbarum,exhibits antiinflammatory and antioxidant effects in treating neurological diseases.However,the therapeutic action of Lycium barbarum polysaccharide on depression has not been studied.In this investigation,we established mouse models of depression using aversive stimuli including exposure to fox urine,air puff and foot shock and physical restraint.Concurrently,we administered 5 mg/kg per day Lycium barbarum polysaccharide-glycoprotein to each mouse intragastrically for the 28 days.Our results showed that long-term exposure to aversive stimuli significantly enhanced depressive-like behavior evaluated by the sucrose preference test and the forced swimming test and increased anxietylike behaviors evaluated using the open field test.In addition,aversive stimuli-induced depressed mice exhibited aberrant neuronal activity in the lateral habenula.Importantly,concurrent Lycium barbarum polysaccharide-glycoprotein treatment significantly reduced these changes.These findings suggest that Lycium barbarum polysaccharide-glycoprotein is a potential preventative intervention for depression and may act by preventing aberrant neuronal activity and microglial activation in the lateral habenula.The study was approved by the Jinan University Institutional Animal Care and Use Committee(approval No.20170301003)on March 1,2017.

关键词： aversive stimuli behaviors depression immune response inflammation lateral habenula Lycium barbarum polysaccharide mice microglia neuron

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Lycium barbarum polysaccharide ameliorates radiation-induced brain injury by regulating gut microbiota

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Journal of Traditional Chinese Medical Sciences 2023年第1期10卷 42-51页

作者： Jinglu Hu Chunqing Wang Qi Li Wencheng Jiao Xiaojuan Chen Baiping Ma Lina Du Pharmaceutical College of Henan University Henan UniversityKaifeng 475004China Department of Pharmaceutical Sciences Beijing Institute of Radiation MedicineBeijing 100850China School of Pharmacy Shandong University of Traditional Chinese MedicineJinan 250355China Institute of Life Sciences and Green Development Hebei UniversityBaoding 071002China

Objective: To determine the extent to which Lycium barbarum polysaccharide(LBP) improves60Co γ-ray radiation-induced brain injury(RIBI) by regulating the gut microbiota.Methods: The RIBI model of mice was established with the appropriate dose of60Co γ-ray to identify the changes in the body weight, behaviors, gut microbiota, and inflammatory reactions of mice. Mice were randomly divided into healthy, RIBI model, and LBP groups. The related inflammatory cytokines were determined using an enzyme linked immunosorbent assay kit. Then, 16S rRNA sequencings of feces were carried out to evaluate the differences in intestinal flora.Results: Compared with the spontaneous activity and exploratory spirit of the healthy group, those traits in the RIBI model mice in the open field significantly decreased, the freezing time in the elevated plus maze(EPM) significantly increased, and the number of times the mice discriminated the novel object was significantly lower. Hematoxylin-eosin slides showed that the main histopathological changes of RIBI occurred in the hippocampus. In addition, the diversity and relative abundances ratio of the gut bacterial phylum, order, family, and genus in the model group varied widely. Changes in Bacteroidetes,Firmicutes, and Proteobacteria were the most obvious after head radiation exposure. In comparison, LBP could accelerate the recovery of weight loss in RIBI mice. The frequency that mice entered the center of the open field, facing the open arm in the EPM, and the number of times they discriminated the novel object were significantly increased with LBP administration. LBP could also reduce the levels of inflammatory factor caused by RIBI. LBP increased the diversity and abundance of gut microbiota in RIBI model mice. In addition, LBP increased the relative abundance of Bacteroidetes but decreased the levels of Firmicutes and Proteobacteria for irradiated mice.Conclusion: LBP can improve depression and tension by regulating the composition of gut microbiota,including lowering the relative abun

关键词： Lycium barbarum polysaccharide Gut microbiota Diversity Radiation Brain injury Behavior Cognition Inflammatory

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Effects of Lycium barbarum polysaccharide on cytokines in adolescents with subthreshold depression:a randomized controlled study

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Neural Regeneration Research 2024年第9期19卷 2036-2040页

作者： Xiaoyue Li Tao Liu Xuan Mo Runhua Wang Xueyan Kong Robin Shao Roger S.Mclntyre Kwok-Fai So Kangguang Lin Department of Affective Disorders The Affiliated Brain Hospital of Guangzhou Medical University(Guangzhou Huiai Hospital)GuangzhouGuangdong ProvinceChina Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Department of Psychiatry The Fifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Mood Disorders Psychopharmacology Unit Poul Hansen Family Centre for DepressionUniversity Health NetworkTorontoONCanada Department of Psychiatry University of TorontoTorontoONCanada Brain and Cognition Discovery Foundation TorontoCanada Ministry of Education Joint International Research Laboratory of CNS Regeneration Jinan UniversityGuangzhouGuangdong ProvinceChina Neuroscience and Neurorehabilitation Institute University of Health and Rehabilitation SciencesQingdaoShandong ProvinceChina

Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory responses.Moreover,anti-inflammatory treatment has shown partial effectiveness in alleviating depression symptoms.Lycium barbarum polysaccharide(LBP),derived from Goji berries,exhibits notable antioxidative and anti-inflammatory properties.In our recent double-blinded randomized placebo-controlled trial,we found that LBP significantly reduced depressive symptoms in adolescents with subthreshold depression.It is presumed that the antidepressant effect of LBP may be associated with its influence on inflammatory cytokines.In the double-blinded randomized controlled trial,we enrolled 29 adolescents with subthreshold depression and randomly divided them into an LBP group and a placebo group.In the LBP group,adolescents were given 300 mg/d LBP.A 6-week follow up was completed by 24 adolescents,comprising 14 adolescents from the LBP group(15.36±2.06 years,3 men and 11 women)and 10 adolescents from the placebo group(14.9±1.6 years,2 men and 8 women).Our results showed that after 6 weeks of treatment,the interleukin-17A level in the LBP group was lower than that in the placebo group.Network analysis showed that LBP reduced the correlations and connectivity between inflammatory factors,which were associated with the improvement in depressive symptoms.These findings suggest that 6-week administration of LBP suppresses the immune response by reducing interleukin-17A level,thereby exerting an antidepressant effect.

关键词： adolescents cytokines efficacy Goji berry inflammatory responses interleukin-17A Lycium barbarum polysaccharide randomized controlled study subthreshold depression

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Effect of nano-selenium loaded with Lycium barbarum polysaccharide on the proliferation of lens epithelial cells after UVB damage in vitro

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International Journal of Ophthalmology(English edition) 2022年第1期15卷 9-14页

作者： Jing-Xiang Zhong Shan-Shan Jin Kang-Sheng Wu Guo-Cheng Yu Lei-Lei Tu Lian Liu Department of Ophthalmology the First Affiliated Hospital of Jinan UniversityGuangzhou 510630Guangdong ProvinceChina

AIM:To investigate the effect of nano-selenium loaded with different concentrations of Lycium barbarum polysaccharide(LBP-Se NPs)on the proliferation of human lens epithelial cells(HLECs)from UV irradiation.METHODS:LBP-Se NPs were prepared and their particle size was detected.HLECs(SRA01/04)were irradiated with UVB for different time(0,10,20,30,40,50,60 min)to construct a damaged model,the survival rate of cells was determined by methylthiazol tetrazolium(MTT)assay.The 4’,6-Diamidine-2’-phenylindole dihydrochloride(DAPI)staining was used to observe the status of cell nucleus and drug entering cytoplasm through cell membrane in SRA01/04 cells after adding LBP-SENPS loaded with coumarin fluorescence agent 24 h under fluorescence microscope.SRA01/04 normal and UVB-damaged cells were treated with different amounts of LBP-Se NPs at different concentrations,cells proliferation were observed.RESULTS:The particle size of LBP-Se NPs was stable in the range of 150-200 nm.The survival rate changes with time after UVB irradiation were statistically significant.The 10 min of UVB exposure as the time was chosen to construct the cell damage model.With DAPI staining,LBPSe NPs were observed to enter the cytoplasm through the cell membrane under fluorescence inverted microscope.Cytotoxicity of SRA01/04 at different concentrations of LBPSe NPs were measured.Cell survival rate was statistically different compared with the control group.The higher the loading concentration of LBP in nano-Se drugs was,the higher the cell proliferation rate was(P<0.05).The lower the concentration of LBP-Se NPs,the higher the cell proliferation rate,showing a negative growth trend(P<0.05).The group with the highest average cell proliferation rate was 0.5μmol/L 2.0 mg/m L LBP-Se NPs(128.80%).When the 2.0 mg/m L LBP-Se NPs group was selected for cell photography,the cell density was higher at 0.5μmol/L.With the increase of concentration,SRA01/04 cells appeared more cytoplasm dehydration,cell shrinkage and apoptotic bodies,and cell density decreased.CONCLU

关键词： Lycium barbarum polysaccharide nano-selenium human lens epithelial cells ultraviolet irradiation

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Effects of Lycium barbarum polysaccharide on the photoinduced autophagy of retinal pigment epithelium cells

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International Journal of Ophthalmology(English edition) 2022年第1期15卷 23-30页

作者： Yuan-Yuan Gao Juan Li Jie Huang Wu-Jun Li Yang Yu Ningxia Medical University Yinchuan 750004Ningxia Hui Autonomous RegionChina Yulin Hospital of Traditional Chinese Medicine Yulin 719000Shaanxi ProvinceChina

AIM:To investigate the relationship between autophagy and apoptosis in photoinduced injuries in retinal pigment epithelium(RPE)cells and how Lycium barbarum polysaccharide(LBP)contributes to the increased of RPE cells to photoinduced autophagy.METHODS:In vitro cultures of human RPE strains(ARPE-19)were prepared and randomly divided into the blank control,model,low-dose LBP,middle-dose LBP,high-dose LBP,and 3-methyladenine(3MA)groups.The viability of the RPE cells and apoptosis levels in each group were tested through cell counting kit-8(CCK8)method with a flow cytometer(Annexin V/PI double staining technique).The expression levels of LC3II,LC3I,and P62 proteins were detected with the immunofluorescence method.The expression levels of beclin1,LC3,P62,PI3K,P-mTOR,mTOR,P-Akt,and Akt proteins were tested through Western blot.RESULTS:LBP considerably strengthens cell viability and inhibits the apoptosis of RPE cells after photoinduction.The PI3K/Akt/mTOR signal pathway is activated because of the upregulation of the phosphorylation levels of Akt and mTOR proteins,and thus autophagy is inhibited.CONCLUSION:LBP can inhibit the excessive autophagy in RPE cells by activating the PI3K/Akt/mTOR signaling pathways and thereby protect RPE cells from photoinduced injuries.

关键词： autophagy Lycium barbarum polysaccharide retinal pigment epithelial cell photoinduced apoptosis

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Impact of Lycium barbarum polysaccharide and Danshensu on vascular endothelial growth factor in the process of retinal neovascularization of rabbit

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International Journal of Ophthalmology(English edition) 2013年第1期6卷 59-61页

作者： Xue-Min Tian Rui Wang Bai-Ke Zhang Chun-Lei Wang Hao Guo Shi-Jin Zhang Department of Ophthalmology Department of Traditional Chinese Medicine People's Hospital of Zhengzhou

AIM:To discuss the impact of Lycium barbarum polysaccharide (LBP) and Danshensu purified from Traditional Chinese Medicine (TCM) on vascular endothelial growth factor (VEGF) of rabbits with retinal neovascularization. METHODS:Forty rabbits were divided into normal control group, model control group, LBP group and Danshensu group. Animals in the normal control group were fed in the normal oxygen environment. Animals in the other three groups were put into the environment with 70% oxygen for 5 days in order to build the model of oxygen-induced vascular proliferation retinopathy. And then different TCM extract was injected into the abdominal cavities of these annimals. After 7 days, the VEGF content of in the serum of rabbit was measured by double antibody sandwich method. RESULTS:Data analysis indicated that VEGF content was as follows:Danshensu group was lower than model control group (12.92 ±3.84ng/L vs 19.32 ±4.15ng/L, P < 0.05); LBP group and normal control group were lower than model control group (12.92±3.84ng/L, 9.26±1.61ng/L vs 19.32±4.15ng/L, P<0.01); total blood viscosity, plasma viscosity, cholesterol content, fibrinogen content and triacylglycerol content after peritoneal injection of LBP and Danshensu were obviously lower than before injection. CONCLUSION:TCM extract-LBP and Danshensu can prominently reduce the content of VEGF in the process of vascular proliferative retinopathy of rabbit; can prevent the occurrence of retinal microvascular disease by improving partial oxygen -deficient environment or affecting all kinds of new growth factor.

关键词： Lycium barbarum polysaccharide Danshensu vascular endothelial growth factor retinal neovascularization rabbit

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Protective effect of Lycium barbarum polysaccharide on retinal ganglion cells in vitro

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International Journal of Ophthalmology(English edition) 2011年第4期4卷 377-379页

作者： Min Yang, Xue-Jing Lu Pharmacy Faculty Chengdu University of TCM Chengdu 610075 Sichuan Province China The Teaching Hospital of Chengdu University of TCM Chengdu 610075 Sichuan Province China Key Laboratory for Visual Function and Eye Diseases Chengdu University of TCM Chengdu 610075 Sichuan Province China

AIM: To observe the effect of Lycium barbarum polysaccharide (LBP) on rat retinal ganglion cells (RGCs) In vitro METHODS: Retinal cells of neonatal Sprague-Dawley rats were collected 1 to 3 days after birth, and co-cultured with different concentrations of LBP for 24 hours. Absorbance values (OD) were recorded using MTT assay for calculating survival rates. RESULTS: All the test groups had protective effects on RGCs. The group with 10mg/mL concentration of LOP had the most significantly difference of OD value compared with that in control group ( P<0.01). CONCLUSION: LBP can increase the survival rate and promote the growth of mixed cultured rat RGCs.

关键词： Lycium barbarum polysaccharide in vitro retinal ganglion cells

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Hypoglycemic mechanism of Lycium barbarum polysaccharide based on the “incretin effect” of GLP1

Hypoglycemic mechanism of Lycium barbarum polysaccharide bas...

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中国营养学会第十五届全国营养科学大会

作者： He Zhao Kang Chen Chun-chen Zhang Yang Xue Xiao-hui Yang Shu-ying Deng Hui-zhen Cai School of Public Health and Management Ningxia Medical University Disease Prevention and Control Center in Xiang Yang

polysaccharides have the potential to activate GLP1 promoting insulin secretion. This study was based on GLP1 "incretin action" to explore the hypoglycemic mechanism of LBP. Methods We assessed the function of Lycium barbarum polysaccharide(LBP) on incretin effect of GLP1 from the transcription of GCG gene(GLP1 coding gene), GLP1 secretion and its activity maintenance. Results The results indicated that LBP stimulated the binding of TCF7 L2 to β-catenin, regulating gene expression of GCG by activating β-catenin and cAMP/Epac proteins. SGLT1 transporters in STC cells were inhibited by LBP which further led to a decrease in intracellular calcium ion. At the same time, the GLP1 level in cells and in supernatant increased. LBP also stimulated the secretion of GCG and inhibited the activity of alpha-glucosidase in diabetic mice, but it didn’t inhibit the activity of DPP4. Conclusion The findings from the studies suggest that LBP can regulate GCG gene expression by regulating Wnt/β-catenin and cAMP/Epac pathways and inhibit alphaglucosidase activity to stimulate and to increase secretion of GLP1. But it cannot inhibit DPP4 activity and prevent degradation of GLP1.

关键词： Lycium barbarum polysaccharide incretin effect GLP1

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