Amyloid-beta-induced neuronal cell death contributes to cognitive decline in Alzheimer’s disease.Citri Reticulatae Semen has diverse beneficial effects on neurodegenerative diseases,including Parkinson’s and Hunting...Amyloid-beta-induced neuronal cell death contributes to cognitive decline in Alzheimer’s disease.Citri Reticulatae Semen has diverse beneficial effects on neurodegenerative diseases,including Parkinson’s and Huntington’s diseases,however,the effect of Citri Reticulatae Semen on Alzheimer’s disease remains unelucidated.In the current study,the anti-apoptotic and autophagic roles of Citri Reticulatae Semen extract on amyloid-beta-induced apoptosis in PC12 cells were first investigated.Citri Reticulatae Semen extract protected PC12 cells from amyloid-beta-induced apoptosis by attenuating the Bax/Bcl-2 ratio via activation of autophagy.In addition,Citri Reticulatae Semen extract was confirmed to bind amyloid-beta as revealed by biolayer interferometry in vitro,and suppress amyloid-beta-induced pathology such as paralysis,in a transgenic Caenorhabditis elegans in vivo model.Moreover,genetically defective Caenorhabditis elegans further confirmed that the neuroprotective effect of Citri Reticulatae Semen extract was autophagy-dependent.Most importantly,Citri Reticulatae Semen extract was confirmed to improve cognitive impairment,neuronal injury and amyloid-beta burden in 3×Tg Alzheimer’s disease mice.As revealed by both in vitro and in vivo models,these results suggest that Citri Reticulatae Semen extract is a potential natural therapeutic agent for Alzheimer’s disease via its neuroprotective autophagic effects.展开更多
Hesperidin is a dihydroflavonoids, accounting for more than 50% of the total flavonoids in Citri Reticulatae Pericarpium(CRP) of traditional Chinese medicine. It is an effective antioxidant and free radical scavenger ...Hesperidin is a dihydroflavonoids, accounting for more than 50% of the total flavonoids in Citri Reticulatae Pericarpium(CRP) of traditional Chinese medicine. It is an effective antioxidant and free radical scavenger that has anti-inflammatory, antiviral and hypoglycemic properties.The latest studies reported that hesperidin has a potential for novel coronavirus resistance. However, little is known about the synthesis regulation and accumulation site of hesperidin in plants. In this study, hesperidin synthase gene Crc1,6RhaT was cloned, and the protein can be completely transformed flavanone-7-O-glucoside into hesperidin in vitro and in vivo. Studies on biological characteristics of ovary walls and exocarps showed that the relative expression levels of the Crc1,6RhaT gene and protein decreased gradually with the development of citrus fruits, and the relative content of hesperidin firstly increased, then sequentially decreased. In situ hybridization results further revealed that Crc1,6RhaT transcription was mainly concentrated in the secretory cavity cells, which are revealed to be the site of flavonoid synthesis.Immunocytochemistry localization results showed that the Crc1,6RhaT was mainly located in the endoplasmic reticulum, nucleus and vacuole of secretory cells. We inferred that the Crc1,6RhaT was synthesized in the endoplasmic reticulum, then was transported into the vacuoles through enlarged vesicles at the end of the endoplasmic reticulum. Our results not only revealed that Crc1,6RhaT may be involved in the synthesis of hesperidin of the main bioactive substance in the medicinal plant Citrus reticulata ‘Chachi' fruit, but also provided novel insights into the main subcellular sites of hesperidin biosynthesis in vacuoles.展开更多
[Objectives]To investigate the mechanisms and pharmacologic effects of Citri Reticulatae Pericarpium against keloids by network pharmacology systematically.[Methods]TCMSP,Uniprot and BATMAN-TCM databases were used to ...[Objectives]To investigate the mechanisms and pharmacologic effects of Citri Reticulatae Pericarpium against keloids by network pharmacology systematically.[Methods]TCMSP,Uniprot and BATMAN-TCM databases were used to obtain the active constituents and targets of Citri Reticulatae Pericarpium."Keloid"was used as key word to search for related therapeutic targets from Drug Bank,OMIM,TTD,and GEO databases.The Chinese medicine compound-target network was constructed by Cytoscape software.Besides,gene ontology(GO)and Kyoto Encyclopedia of genes and genome enrichment analysis were also performed.Afterward,Discovery Studio software was used to assess the interaction of key components and genes.[Results]Five active components of Citri Reticulatae Pericarpium,773 compound targets and 676 keloid treatment targets were obtained in the databases.After the intersection,there are 47 targets of Citri Reticulatae Pericarpium for treating keloids.Hub genes were identified such as MMP9,IL6,TNF,TP53,and VEGFA,which were enriched in tumor necrosis factor-α,nuclear factor kappa-B,and other signaling pathways.The molecular docking stimulation confirmed the interaction between the MMP9 and three components of Citri Reticulatae Pericarpium.[Conclusions]Citri Reticulatae Pericarpium may play an important role in treating keloids through modulating genes and signaling pathways.The present study sheds light on the mechanisms of active compounds of Citri Reticulatae Pericarpium for the treatment of keloids.展开更多
[Objectives] This study aimed to establish HPLC fingerprint and conduct cluster analysis and principle component analysis for Citri Reticulatae Pericarpium Viride. [Methods] Using the HPLC method, the determination wa...[Objectives] This study aimed to establish HPLC fingerprint and conduct cluster analysis and principle component analysis for Citri Reticulatae Pericarpium Viride. [Methods] Using the HPLC method, the determination was performed on XSelect~® HSS T3-C_(18) column with mobile phase of acetonitrile-0.5% acetic acid solution(gradient elution) at the flow rate of 1.0 mL/min. The detection wavelength was 360 nm. The column temperature was 25℃. The sample size was 10 μL. With peak of hesperidin as the reference, HPLC fingerprints of 10 batches of Citri Reticulatae Pericarpium Viride were determined. The similarity of the 10 batches of samples was evaluated by Similarity Evaluation System for Chromatographic Fingerprint of TCM(2012 edition) to determine the common peaks. Cluster analysis and principal component analysis were performed by using SPSS 17.0 statistical software. [Results] The HPLC fingerprints of the 10 batches of medicinal materials had total 11 common peaks, and the similarity was 0.919-1.000, indicating that the chemical composition of the 10 batches of medicinal materials was consistent. There were 11 common components in the 10 batches of medicinal materials, but their contents were different. When the Euclidean distance was 20, the 10 batches of samples were divided into two categories, S4 in the first category, and the others in the second one. When the Euclidean distance was 5, the second category could be further divided into two sub-categories, S1 and S10 in one sub-category, and S2, S3, S5, S6, S7, S8 and S9 in the other one. The principle component analysis showed that cumulative contribution rate of the two main component factors was 92.797%, and the comprehensive score of S7 was the highest with the best quality. [Conclusions] The results of HPLC fingerprinting, cluster analysis and principle component analysis can provide reference for the quality control of Citri Reticulatae Pericarpium Viride.展开更多
Background:To explore the differences of 14 batches of Citri Reticulatae Pericarpium from different regions.Methods:The main aim of this study was to develop a high-performance liquid chromatography method-photodiode ...Background:To explore the differences of 14 batches of Citri Reticulatae Pericarpium from different regions.Methods:The main aim of this study was to develop a high-performance liquid chromatography method-photodiode array detection for determining the contents of five flavonoids and the chromatographic fingerprints of Citri Reticulatae Pericarpium from different regions.Theα-glucosidase inhibitory activities and antioxidant properties of Citri Reticulatae Pericarpium,based on free-radical scavenging assays against 1,1-diphenyl-2-picrylhydrazyl,2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid),and hydroxyl radicals,were estimated and compared.Results:Among the tested compounds,the content of hesperidin(13.386-68.235 mg/g)was the highest and that of hesperitin(0.045-0.277 mg/g)was the lowest.In comparing different sources of Citri Reticulatae Pericarpium,the contents of narirutin in Citri Reticulatae Pericarpium from Guangdong(0.824-0.851 mg/g)and Sichuan(1.069-1.204 mg/g)provinces of China were lower than in other provinces.In contrast,nobiletin(8.429-12.237 mg/g)and tangeretin(3.947-4.613 mg/g)were most abundant in Guangdong sources of Citri Reticulatae Pericarpium,followed by samples from Sichuan Province(nobiletin:6.761-7.658 mg/g;tangeretin:3.422-3.933 mg/g).Correlation analysis showed that nobiletin and tangeretin were the main contributors to the antioxidant capacity,and narirutin was the main active component inhibiting theα-glucosidase activity of Citri Reticulatae Pericarpium.Conclusion:This work revealed that the intrinsic quality of Citri Reticulatae Pericarpium was affected by different growing regions,which provides a scientific basis for controlling the quality of Citri Reticulatae Pericarpium and rationally developing and utilizing Citri Reticulatae Pericarpium.展开更多
[Objectives]To observe the clinical effect of dark tea with pericarpium citri reticulateae combined with metformin for type 2 diabetes mellitus.[Methods]A total of 80 cases of patients with type 2 diabetes mellitus we...[Objectives]To observe the clinical effect of dark tea with pericarpium citri reticulateae combined with metformin for type 2 diabetes mellitus.[Methods]A total of 80 cases of patients with type 2 diabetes mellitus were randomly divided into the control group and the observation group with 40 cases in each group.The control group was given metform for treatment,and the observation group was given dark tea with pericarpium citri reticulateae combined with metformin for treatment.The two groups were continuously treated for 12 weeks.The indexes of patients were observed and recorded,such as the body mass index(BMI),abdominal circumference(AC),hemoglobin A1c(HbA1c),fasting blood glucose(FBG),postprandial 2 h blood glucose(P2hBG),uric acid(UA),total cholesterol(TC),and triglyceride(TG).The incidence of adverse reactions during the treatment period and the patient satisfaction for treatment in the two groups were counted.[Results]After treatment,the FBG,P2hBG and HbA1c in the two groups were decreased when compared with those before treatment(P<0.05)and the decrease of the above indexes in the observation group was more significant than that in the control group(P<0.05).After treatment,the BMI,AC,UA,TC and TG in the observation group were decreased more significantly when compared with those before treatment and those in the control group after treatment,differences were statistically significant(P<0.05).The above indexes in the control group did not change significantly before and after treatment(P>0.05).The incidence of adverse reactions was 2.5%in the observation group and 5.0%in the control group,the difference was not statistically significant(P>0.05).The patient satisfaction was 97.5%in the observation group and 55.0%in the control group,the difference was significant(P<0.05).[Conclusions]The curative effect of dark tea with pericarpium citri reticulateae combined with metformin for type 2 diabetes mellitus is better than that of western medicine alone and has no obvious adverse reactions,thus it is worthy of clinical promotion and application.展开更多
基金supported by FDCT grants from the Macao Science and Technology Development Fund,China,No.002/2023/ALC(to BYKL)Foshan Medicine Dengfeng Project of China 2019-2021(to BYKL)+3 种基金the Science and Technology Program of Sichuan Province,Nos.2022YFS0620(to DQ)and MZGC20230041(to XFW)the TCMs Commission of Sichuan Province,No.2021MS469(to YT)the Science and Technology Program of Luzhou,No.2022-WGR-194(to YT)the Southwest Medical University Science and Technology Program,No.2021NJXNYD04(to DQ).
文摘Amyloid-beta-induced neuronal cell death contributes to cognitive decline in Alzheimer’s disease.Citri Reticulatae Semen has diverse beneficial effects on neurodegenerative diseases,including Parkinson’s and Huntington’s diseases,however,the effect of Citri Reticulatae Semen on Alzheimer’s disease remains unelucidated.In the current study,the anti-apoptotic and autophagic roles of Citri Reticulatae Semen extract on amyloid-beta-induced apoptosis in PC12 cells were first investigated.Citri Reticulatae Semen extract protected PC12 cells from amyloid-beta-induced apoptosis by attenuating the Bax/Bcl-2 ratio via activation of autophagy.In addition,Citri Reticulatae Semen extract was confirmed to bind amyloid-beta as revealed by biolayer interferometry in vitro,and suppress amyloid-beta-induced pathology such as paralysis,in a transgenic Caenorhabditis elegans in vivo model.Moreover,genetically defective Caenorhabditis elegans further confirmed that the neuroprotective effect of Citri Reticulatae Semen extract was autophagy-dependent.Most importantly,Citri Reticulatae Semen extract was confirmed to improve cognitive impairment,neuronal injury and amyloid-beta burden in 3×Tg Alzheimer’s disease mice.As revealed by both in vitro and in vivo models,these results suggest that Citri Reticulatae Semen extract is a potential natural therapeutic agent for Alzheimer’s disease via its neuroprotective autophagic effects.
基金supported by the National Natural Science Foundation of China (Grant No.32270381)Natural Science Foundation of Guangdong (Grant No.2022A1515011086)+2 种基金Key Realm R&D Program of Guangdong Province (Grant No.2020B020221001)Provincial Special Fund for Modern Agriculture Industry Technology Innovation Teams (Grant No.2019KJ125)Research Fund of Maoming Branch,Guangdong Laboratory for Lingnan Modern Agriculture (Grant No.2022KF009)。
文摘Hesperidin is a dihydroflavonoids, accounting for more than 50% of the total flavonoids in Citri Reticulatae Pericarpium(CRP) of traditional Chinese medicine. It is an effective antioxidant and free radical scavenger that has anti-inflammatory, antiviral and hypoglycemic properties.The latest studies reported that hesperidin has a potential for novel coronavirus resistance. However, little is known about the synthesis regulation and accumulation site of hesperidin in plants. In this study, hesperidin synthase gene Crc1,6RhaT was cloned, and the protein can be completely transformed flavanone-7-O-glucoside into hesperidin in vitro and in vivo. Studies on biological characteristics of ovary walls and exocarps showed that the relative expression levels of the Crc1,6RhaT gene and protein decreased gradually with the development of citrus fruits, and the relative content of hesperidin firstly increased, then sequentially decreased. In situ hybridization results further revealed that Crc1,6RhaT transcription was mainly concentrated in the secretory cavity cells, which are revealed to be the site of flavonoid synthesis.Immunocytochemistry localization results showed that the Crc1,6RhaT was mainly located in the endoplasmic reticulum, nucleus and vacuole of secretory cells. We inferred that the Crc1,6RhaT was synthesized in the endoplasmic reticulum, then was transported into the vacuoles through enlarged vesicles at the end of the endoplasmic reticulum. Our results not only revealed that Crc1,6RhaT may be involved in the synthesis of hesperidin of the main bioactive substance in the medicinal plant Citrus reticulata ‘Chachi' fruit, but also provided novel insights into the main subcellular sites of hesperidin biosynthesis in vacuoles.
基金Supported by Central Government Funds of Guiding Local Scientific and Technological Development for Sichuan Province(2021ZYD0057).
文摘[Objectives]To investigate the mechanisms and pharmacologic effects of Citri Reticulatae Pericarpium against keloids by network pharmacology systematically.[Methods]TCMSP,Uniprot and BATMAN-TCM databases were used to obtain the active constituents and targets of Citri Reticulatae Pericarpium."Keloid"was used as key word to search for related therapeutic targets from Drug Bank,OMIM,TTD,and GEO databases.The Chinese medicine compound-target network was constructed by Cytoscape software.Besides,gene ontology(GO)and Kyoto Encyclopedia of genes and genome enrichment analysis were also performed.Afterward,Discovery Studio software was used to assess the interaction of key components and genes.[Results]Five active components of Citri Reticulatae Pericarpium,773 compound targets and 676 keloid treatment targets were obtained in the databases.After the intersection,there are 47 targets of Citri Reticulatae Pericarpium for treating keloids.Hub genes were identified such as MMP9,IL6,TNF,TP53,and VEGFA,which were enriched in tumor necrosis factor-α,nuclear factor kappa-B,and other signaling pathways.The molecular docking stimulation confirmed the interaction between the MMP9 and three components of Citri Reticulatae Pericarpium.[Conclusions]Citri Reticulatae Pericarpium may play an important role in treating keloids through modulating genes and signaling pathways.The present study sheds light on the mechanisms of active compounds of Citri Reticulatae Pericarpium for the treatment of keloids.
基金Supported by National Natural Science Foundation of China(81603251)Key Research and Development Plan of Shanxi Province(201603D3113021)Project of Collaborative Innovation Center for the Comprehensive Development and Utilization of Medicinal Herbs in Shanxi Province(2017-JYXT-05)
文摘[Objectives] This study aimed to establish HPLC fingerprint and conduct cluster analysis and principle component analysis for Citri Reticulatae Pericarpium Viride. [Methods] Using the HPLC method, the determination was performed on XSelect~® HSS T3-C_(18) column with mobile phase of acetonitrile-0.5% acetic acid solution(gradient elution) at the flow rate of 1.0 mL/min. The detection wavelength was 360 nm. The column temperature was 25℃. The sample size was 10 μL. With peak of hesperidin as the reference, HPLC fingerprints of 10 batches of Citri Reticulatae Pericarpium Viride were determined. The similarity of the 10 batches of samples was evaluated by Similarity Evaluation System for Chromatographic Fingerprint of TCM(2012 edition) to determine the common peaks. Cluster analysis and principal component analysis were performed by using SPSS 17.0 statistical software. [Results] The HPLC fingerprints of the 10 batches of medicinal materials had total 11 common peaks, and the similarity was 0.919-1.000, indicating that the chemical composition of the 10 batches of medicinal materials was consistent. There were 11 common components in the 10 batches of medicinal materials, but their contents were different. When the Euclidean distance was 20, the 10 batches of samples were divided into two categories, S4 in the first category, and the others in the second one. When the Euclidean distance was 5, the second category could be further divided into two sub-categories, S1 and S10 in one sub-category, and S2, S3, S5, S6, S7, S8 and S9 in the other one. The principle component analysis showed that cumulative contribution rate of the two main component factors was 92.797%, and the comprehensive score of S7 was the highest with the best quality. [Conclusions] The results of HPLC fingerprinting, cluster analysis and principle component analysis can provide reference for the quality control of Citri Reticulatae Pericarpium Viride.
基金supported by the National Natural Science Foundation of China(No.81872956)National Key R&D Program of China(No.2019YFC1710604)+1 种基金Key Project at Central Government Level(No.2060302)the Science and Technology Project of Tianjin(No.18ZXXYSY00080).
文摘Background:To explore the differences of 14 batches of Citri Reticulatae Pericarpium from different regions.Methods:The main aim of this study was to develop a high-performance liquid chromatography method-photodiode array detection for determining the contents of five flavonoids and the chromatographic fingerprints of Citri Reticulatae Pericarpium from different regions.Theα-glucosidase inhibitory activities and antioxidant properties of Citri Reticulatae Pericarpium,based on free-radical scavenging assays against 1,1-diphenyl-2-picrylhydrazyl,2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid),and hydroxyl radicals,were estimated and compared.Results:Among the tested compounds,the content of hesperidin(13.386-68.235 mg/g)was the highest and that of hesperitin(0.045-0.277 mg/g)was the lowest.In comparing different sources of Citri Reticulatae Pericarpium,the contents of narirutin in Citri Reticulatae Pericarpium from Guangdong(0.824-0.851 mg/g)and Sichuan(1.069-1.204 mg/g)provinces of China were lower than in other provinces.In contrast,nobiletin(8.429-12.237 mg/g)and tangeretin(3.947-4.613 mg/g)were most abundant in Guangdong sources of Citri Reticulatae Pericarpium,followed by samples from Sichuan Province(nobiletin:6.761-7.658 mg/g;tangeretin:3.422-3.933 mg/g).Correlation analysis showed that nobiletin and tangeretin were the main contributors to the antioxidant capacity,and narirutin was the main active component inhibiting theα-glucosidase activity of Citri Reticulatae Pericarpium.Conclusion:This work revealed that the intrinsic quality of Citri Reticulatae Pericarpium was affected by different growing regions,which provides a scientific basis for controlling the quality of Citri Reticulatae Pericarpium and rationally developing and utilizing Citri Reticulatae Pericarpium.
文摘[Objectives]To observe the clinical effect of dark tea with pericarpium citri reticulateae combined with metformin for type 2 diabetes mellitus.[Methods]A total of 80 cases of patients with type 2 diabetes mellitus were randomly divided into the control group and the observation group with 40 cases in each group.The control group was given metform for treatment,and the observation group was given dark tea with pericarpium citri reticulateae combined with metformin for treatment.The two groups were continuously treated for 12 weeks.The indexes of patients were observed and recorded,such as the body mass index(BMI),abdominal circumference(AC),hemoglobin A1c(HbA1c),fasting blood glucose(FBG),postprandial 2 h blood glucose(P2hBG),uric acid(UA),total cholesterol(TC),and triglyceride(TG).The incidence of adverse reactions during the treatment period and the patient satisfaction for treatment in the two groups were counted.[Results]After treatment,the FBG,P2hBG and HbA1c in the two groups were decreased when compared with those before treatment(P<0.05)and the decrease of the above indexes in the observation group was more significant than that in the control group(P<0.05).After treatment,the BMI,AC,UA,TC and TG in the observation group were decreased more significantly when compared with those before treatment and those in the control group after treatment,differences were statistically significant(P<0.05).The above indexes in the control group did not change significantly before and after treatment(P>0.05).The incidence of adverse reactions was 2.5%in the observation group and 5.0%in the control group,the difference was not statistically significant(P>0.05).The patient satisfaction was 97.5%in the observation group and 55.0%in the control group,the difference was significant(P<0.05).[Conclusions]The curative effect of dark tea with pericarpium citri reticulateae combined with metformin for type 2 diabetes mellitus is better than that of western medicine alone and has no obvious adverse reactions,thus it is worthy of clinical promotion and application.