The most recent outbreak of 2019 novel coronavirus,named as COVID-19,caused pneumonia epidemic in Wuhan with 2121 deaths cases as of February 20th 2020.Identification of effective antiviral agents to combat the novel ...The most recent outbreak of 2019 novel coronavirus,named as COVID-19,caused pneumonia epidemic in Wuhan with 2121 deaths cases as of February 20th 2020.Identification of effective antiviral agents to combat the novel coronavirus is urgently needed.Citrus fruit peel or wild citrus are rich in flavonoids,and clinically documented for roles in relief of cough and promotion of digestive health.Therefore,citrus fruits are assumed to possess antivirus activities or enhance the host immunity.A previous study found that hesperetin could act as a high potent inhibitor of SARS-CoV 3CLpro.We determined six flavonoid compounds’content in three citrus species by using LC-MS technique.The content of naringin and naringenin was at higher levels in pummelo.Hesperetin and hesperidin were highly accumulated in mandarin and sweet orange.The subsequent in vitro and in vivo experiments indicated that naringin could inhibit the expression of the proinflammatory cytokines(COX-2,iNOS,IL-1βand IL-6)induced by LPS in Raw macrophage cell line,and may restrain cytokine through inhibiting HMGB1 expression in a mouse model.The results revealed that naringin may have a potential application for preventing cytokine storm.We simulated molecular docking to predict the binding affinity of those flavonoids to bind Angiotensin-converting enzyme 2(ACE 2),which is a receptor of the coronavirus.Consideration of the potential anti-coronavirus and anti-inflammatory activity of flavonoids,the citrus fruit or its derived phytochemicals are promising in the use of prevention and treatment of SARS-CoV-2 infection.展开更多
Objective: To investigate the potential effect of pure total flavonoids from Citrus paradisi Macfad peel(PTFC) on the proliferation and apoptosis of human myeloid leukemia cells Kasumi-1, HL-60 and K562, and the un...Objective: To investigate the potential effect of pure total flavonoids from Citrus paradisi Macfad peel(PTFC) on the proliferation and apoptosis of human myeloid leukemia cells Kasumi-1, HL-60 and K562, and the underlying mechanisms. Methods: PTFC was extracted from Citrus paradisi Macfad peel and was identified by high performance liquid chromatography. The effect of PTFC on the proliferation and apoptosis of leukemia cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, fluorescent microscopy and flow cytometry, respectively. The effect of PTFC on the expression levels of apoptosis-related regulators was determined by Western blot assay. Results: Treatment with PTFC inhibited leukemia cell proliferation in a dose-and time-dependent manner and triggered Kasumi-1 cell apoptosis. Treatment with PTFC significantly increased the levels of activated poly adenosine diphosphate-ribosepolymerase and caspase-3/-9, but reduced the levels of Mcl-1 expression in Kasumi-1 cells. However, PTFC did not obviously induce HL-60 cell apoptosis. Conclusion: PTFC inhibited leukemia cell proliferation and induced their apoptosis by modulating apoptosisrelated regulator expression in leukemia cells in vitro.展开更多
The objectives of this study were to determine the effects of dietary supplementation with citrus flavonoid extracts(CFE)on milk performance,serum biochemistry parameters,fecal volatile fatty acids,fecal microbial com...The objectives of this study were to determine the effects of dietary supplementation with citrus flavonoid extracts(CFE)on milk performance,serum biochemistry parameters,fecal volatile fatty acids,fecal microbial community,and fecal metabolites in dairy cows.Eight multiparous lactating Holstein cows were used in a replicated 4×4 Latin square design(21-day period).Cows were fed a basal diet without addition(CON)or basal diet with added CFE at 50(CFE50),100(CFE10),and 150 g/d(CFE150).Feeding CFE up to 150 g/d increased milk yield and milk lactose percentage.Supplementary CFE linearly decreased milk somatic cell count.Serum cytokines interleukin-1β(IL-1β),IL-2,IL-6,and tumor necrosis factor-α(TNF-α)concentrations decreased linearly as the levels of CFE increased.Cows in CFE150 had lower serum lipopolysaccharide and lipopolysaccharide binding protein compared with CON.These results indicate feeding CFE decreased systemic inflammation and endotoxin levels in dairy cows.Furthermore,feeding CFE linearly increased the concentrations of total volatile fatty acids,acetate,and butyrate in feces.The relative abundances of beneficial bacteria Bifidobacterium spp.,Clostridium coccoides-Eubacterium rectale group,and Faecalibacterium prausnitzii in feces increased linearly with increasing CFE supplementation.The diversity and community structure of fecal microbiota were un-affected by CFE supplementation.However,supplementing CFE reduced the relative abundances of genera Ruminococcus_torques_group,Roseburia,and Lachnospira,but increased genera Bacteroides and Phascolarctobacterium.Metabolomics analysis showed that supplementary CFE resulted in a significant modification in the fecal metabolites profile.Compared with CON,fecal naringenin,hesperetin,hippuric acid,and sphingosine concentrations were greater in CFE150 cows,while fecal GlcCer(d18:1/20:0),Cer(d18:0/24:0),Cer(d18:0/22:0),sphinganine,and deoxycholic acid concentrations were less in CFE150 cows.Predicted pathway analysis suggested that"sphingolipid metabolism"was significantly enriched.Overall,these results indicate that citrus flavonoids could exert health-promoting effects by modulating hindgut microbiome and metabolism in lactating cows.展开更多
基金supported by the National Key Research and Development Program (2018YFD1000200)Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (ZYYCXTD-D-202005)the Ability Establishment of Sustainable Use for Valuable Chinese Medicine Resources (2060302).
文摘The most recent outbreak of 2019 novel coronavirus,named as COVID-19,caused pneumonia epidemic in Wuhan with 2121 deaths cases as of February 20th 2020.Identification of effective antiviral agents to combat the novel coronavirus is urgently needed.Citrus fruit peel or wild citrus are rich in flavonoids,and clinically documented for roles in relief of cough and promotion of digestive health.Therefore,citrus fruits are assumed to possess antivirus activities or enhance the host immunity.A previous study found that hesperetin could act as a high potent inhibitor of SARS-CoV 3CLpro.We determined six flavonoid compounds’content in three citrus species by using LC-MS technique.The content of naringin and naringenin was at higher levels in pummelo.Hesperetin and hesperidin were highly accumulated in mandarin and sweet orange.The subsequent in vitro and in vivo experiments indicated that naringin could inhibit the expression of the proinflammatory cytokines(COX-2,iNOS,IL-1βand IL-6)induced by LPS in Raw macrophage cell line,and may restrain cytokine through inhibiting HMGB1 expression in a mouse model.The results revealed that naringin may have a potential application for preventing cytokine storm.We simulated molecular docking to predict the binding affinity of those flavonoids to bind Angiotensin-converting enzyme 2(ACE 2),which is a receptor of the coronavirus.Consideration of the potential anti-coronavirus and anti-inflammatory activity of flavonoids,the citrus fruit or its derived phytochemicals are promising in the use of prevention and treatment of SARS-CoV-2 infection.
基金Supported by Zhejiang Provincial Natural Science Foundation of China(No.LY14H080003)
文摘Objective: To investigate the potential effect of pure total flavonoids from Citrus paradisi Macfad peel(PTFC) on the proliferation and apoptosis of human myeloid leukemia cells Kasumi-1, HL-60 and K562, and the underlying mechanisms. Methods: PTFC was extracted from Citrus paradisi Macfad peel and was identified by high performance liquid chromatography. The effect of PTFC on the proliferation and apoptosis of leukemia cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, fluorescent microscopy and flow cytometry, respectively. The effect of PTFC on the expression levels of apoptosis-related regulators was determined by Western blot assay. Results: Treatment with PTFC inhibited leukemia cell proliferation in a dose-and time-dependent manner and triggered Kasumi-1 cell apoptosis. Treatment with PTFC significantly increased the levels of activated poly adenosine diphosphate-ribosepolymerase and caspase-3/-9, but reduced the levels of Mcl-1 expression in Kasumi-1 cells. However, PTFC did not obviously induce HL-60 cell apoptosis. Conclusion: PTFC inhibited leukemia cell proliferation and induced their apoptosis by modulating apoptosisrelated regulator expression in leukemia cells in vitro.
基金funded by the Categorized Development Project 2022(Start-up Foundation for Talent Introduction,Beijing University of Agriculture5066516004/003)the China Postdoctoral Science Foundation(2022M710181).
文摘The objectives of this study were to determine the effects of dietary supplementation with citrus flavonoid extracts(CFE)on milk performance,serum biochemistry parameters,fecal volatile fatty acids,fecal microbial community,and fecal metabolites in dairy cows.Eight multiparous lactating Holstein cows were used in a replicated 4×4 Latin square design(21-day period).Cows were fed a basal diet without addition(CON)or basal diet with added CFE at 50(CFE50),100(CFE10),and 150 g/d(CFE150).Feeding CFE up to 150 g/d increased milk yield and milk lactose percentage.Supplementary CFE linearly decreased milk somatic cell count.Serum cytokines interleukin-1β(IL-1β),IL-2,IL-6,and tumor necrosis factor-α(TNF-α)concentrations decreased linearly as the levels of CFE increased.Cows in CFE150 had lower serum lipopolysaccharide and lipopolysaccharide binding protein compared with CON.These results indicate feeding CFE decreased systemic inflammation and endotoxin levels in dairy cows.Furthermore,feeding CFE linearly increased the concentrations of total volatile fatty acids,acetate,and butyrate in feces.The relative abundances of beneficial bacteria Bifidobacterium spp.,Clostridium coccoides-Eubacterium rectale group,and Faecalibacterium prausnitzii in feces increased linearly with increasing CFE supplementation.The diversity and community structure of fecal microbiota were un-affected by CFE supplementation.However,supplementing CFE reduced the relative abundances of genera Ruminococcus_torques_group,Roseburia,and Lachnospira,but increased genera Bacteroides and Phascolarctobacterium.Metabolomics analysis showed that supplementary CFE resulted in a significant modification in the fecal metabolites profile.Compared with CON,fecal naringenin,hesperetin,hippuric acid,and sphingosine concentrations were greater in CFE150 cows,while fecal GlcCer(d18:1/20:0),Cer(d18:0/24:0),Cer(d18:0/22:0),sphinganine,and deoxycholic acid concentrations were less in CFE150 cows.Predicted pathway analysis suggested that"sphingolipid metabolism"was significantly enriched.Overall,these results indicate that citrus flavonoids could exert health-promoting effects by modulating hindgut microbiome and metabolism in lactating cows.