According to folk usage of Aconitum carmichaelii Debx., the present study was designed to determine the feasibility of the stems and leaves of Aconitum carmichaelii Debx. as a new medicinal resource. Fourteen alkaloid...According to folk usage of Aconitum carmichaelii Debx., the present study was designed to determine the feasibility of the stems and leaves of Aconitum carmichaelii Debx. as a new medicinal resource. Fourteen alkaloids in mother roots, fibrous roots, stems, and leaves of Aconitum carmichaelii Debx. were measured by HPLC-MS/MS. And multivariate analysis methods, such as clustering analysis and principal component analysis, were applied to analyze the difference among various parts. In addition, the acute toxicity, analgesia, and anti-inflammatory tests were carried out. The results suggested that the contents of alkaloids in mother roots and fibrous roots were approximate, but those of leaves and stems were different from mother roots and fibrous roots. The results of the acute toxicity testing demonstrated the toxicity of fibrous root was strongest, and mother roots were slightly less toxic than fibrous roots. The stems and leaves were far less toxic than mother and fibrous roots. In addition, the analgesia and inflammatory tests showed the effects of the various tissues had no difference each other. These results provided a basis for developing new complementary and alternative treatments for rheumatoid arthritis patients. Simultaneously, the approach may also turn wastes into treasure and promote the development of circular economy.展开更多
OBJEVTIVE: To investigate the effects of extracts from Chuanwu(Aconitum Carmichaelii) and Banxia(Rhizoma Pinelliae) on the excisional wound healing in a rat's model.METHODS: Rats were performed a surgical lesion w...OBJEVTIVE: To investigate the effects of extracts from Chuanwu(Aconitum Carmichaelii) and Banxia(Rhizoma Pinelliae) on the excisional wound healing in a rat's model.METHODS: Rats were performed a surgical lesion with a 2.0 cm resected tissue in the dorsal fascia.Following, animals were randomly divided into model group, YNB group and APE group those were respectively treated with saline, 1 mg/mL of Yunnan Baiyao and 1 mg/mL of Chuanwu(Aconitum Carmichaelii) and Banxia(Rhizoma Pinelliae) extracts. Wound contractions in days 0, 3, 7, 14 and 21 were calculated by an image analyzer. Histological analysis was analyzed using hematoxilin and eosin.Levels of tumor necrosis factor-2(IL-2), IL-4, IL-10, transformαin(TNF-g growα), interleukinth factor-1(TGF-nd basic fibroblast growth factor(bFββ1) a-GF) were determined by real-time quantitative PCR.RESULTS: Compared with that of YNB group and APE gtoup, the skin of rats showed poor re-modeling and re-epithelization characterized by a significant decrease of neovascularization, epithelialization and fibroblast in the model group. In the APE group, levels of TNF-α-and IL-2 were significantly down-regulated and IL4 and IL-10 significantly upregulated in contrasted with that of model group.In addition, levels of TGF-roup were significantly iβ1 and bFGF in the APE gnduced compared with that of model group.CONCLUSION: The results suggest that the extracts from Chuanwu(Aconitum Carmichaelii) and Banxia(Rhizoma Pinelliae) promote wound healing in the rats, which is associated with enhancing antiinflammatory ability and inducing fibroblast formation.展开更多
Two new 2-（quinonylcarboxamino）benzoates, named aconicarmiquinamides A （1） and B （2）, were isolated from an aqueous extract of the lateral roots of Aconitum carmichaelii. Their structures were determined by spec...Two new 2-（quinonylcarboxamino）benzoates, named aconicarmiquinamides A （1） and B （2）, were isolated from an aqueous extract of the lateral roots of Aconitum carmichaelii. Their structures were determined by spectroscopic data analysis, and confirmed by comparison with synthetic methyl 3.6- bis（ diethylamino ）benzoqunonylcarboxylate （3）.展开更多
Two sulfo nated seco C_(20)-diterpenoid alkaloids,aconapelsulfonines A(1) and B(2),were isolated from an aqueous extract of the raw material of "Fu Zi"(the Aconitum carmichaelii lateral roots),of which the s...Two sulfo nated seco C_(20)-diterpenoid alkaloids,aconapelsulfonines A(1) and B(2),were isolated from an aqueous extract of the raw material of "Fu Zi"(the Aconitum carmichaelii lateral roots),of which the structures were elucidated by various spectroscopic data,combined with X-ray crystallogra phic analysis.The unprecedented skeletons are biogenetically proposed to be derived via Criegee rearrangements of the napelline-type architecture.The two compounds exhibited dose-depended analgesic activities on an acetic acid-induced mice writhing test.展开更多
Two sulfonated diterpenoid alkaloids possessing different but related novel carbon skeletons,named aconidenusulfonine A(1)and 12,16-secoaconidenusulfonine A(2),respectively,were isolated as minor components from an aq...Two sulfonated diterpenoid alkaloids possessing different but related novel carbon skeletons,named aconidenusulfonine A(1)and 12,16-secoaconidenusulfonine A(2),respectively,were isolated as minor components from an aqueous extract of the lateral roots of Aconitum carmichaelii("Fu Zi").The structures of 1 and 2,representing the first two C21-diterpenoid alkaloids from nature,were determined by analysis of various spectroscopic data and chemical transformation,of which 1 was further proved by single-crystal X-ray diffraction.Especially,1 exhibited dose-depended analgesic activity consistent with the clinical function of Fu Zi.展开更多
Eight new C_(19)-diterpenoid alkaloid arabinosides, named aconicarmichosides E–L(1–8), were isolated from an aqueous extract of the lateral roots of Aconitum carmichaelii(Fu Zi). Their structures were determined by ...Eight new C_(19)-diterpenoid alkaloid arabinosides, named aconicarmichosides E–L(1–8), were isolated from an aqueous extract of the lateral roots of Aconitum carmichaelii(Fu Zi). Their structures were determined by spectroscopic and chemical methods including 2D NMR experiments and acid hydrolysis. Compounds 1–8, together with the previously reported four neoline 14-O-arabinosides from the same plant, represent the only examples of glycosidic diterpenoid alkaloids so far. At a dose of 1.0 mg/kg(i.p.), as compared with the black control, compounds 1, 2, and 4–6 exhibited analgesic effects with 465.6% inhibitions against acetic acid-induced writhing of mice. Structure–activity relationship was also discussed.展开更多
Aconitum carmichaelii is a high-value medicinal herb widely used across China,Japan,and other Asian countries.Aconitine-type diterpene alkaloids(DAs)are the characteristic compounds in Aconitum.Although six transcript...Aconitum carmichaelii is a high-value medicinal herb widely used across China,Japan,and other Asian countries.Aconitine-type diterpene alkaloids(DAs)are the characteristic compounds in Aconitum.Although six transcriptomes,based on short-read next generation sequencing technology,have been reported from the Aconitum species,the terpene synthase(TPS)corresponding to DAs biosynthesis remains unidentified.We apply a combination of Pacbio isoform sequencing and RNA sequencing to provide a comprehensive view of the A.carmichaelii transcriptome.Nineteen TPSs and five alternative splicing isoforms belonging to TPS-b,TPS-c,and TPS-e/f subfamilies were identified.In vitro enzyme reaction analysis functional identified two sesqui-TPSs and twelve di TPSs.Seven of the TPS-c subfamily genes reacted with GGPP to produce the intermediate ent-copalyl diphosphate.Five Ac KSLs separately reacted with ent-CPP to produce ent-kaurene,ent-atiserene,and ent-13-epi-sandaracopimaradie:a new diterpene found in Aconitum.Ac TPSs gene expression in conjunction DAs content analysis in different tissues validated that ent-CPP is the sole precursor to all DAs biosynthesis,with Ac KSL1,Ac KSL2 s and Ac KSL3-1 responsible for C20 atisine and napelline type DAs biosynthesis,respectively.These data clarified the molecular basis for the C20-DAs biosynthetic pathway in A.carmichaelii and pave the way for further exploration of C19-DAs biosynthesis in the Aconitum species.展开更多
Three new C20-diterpenoid alkaloids with a sulfonic acid unit,named aconicarmisulfonines B and C(1 and 2)and chuanfusulfonine A(3),respectively,were isolated from the Aconitum carmichaelii lateral roots("fu zi&qu...Three new C20-diterpenoid alkaloids with a sulfonic acid unit,named aconicarmisulfonines B and C(1 and 2)and chuanfusulfonine A(3),respectively,were isolated from the Aconitum carmichaelii lateral roots("fu zi"in Chinese).Structures of 1-3 were determined by spectroscopic data analysis.Intriguing chemical properties and reactions were observed for the C20-diterpenoid alkaloids:(a)specific selective nucleophilic addition of the carbonyl(C-12)in 1 with CD3 OD;(b)interconversion between 1 and 2 in D2 O;(c)stereo-and/or regioselective deuterations of H-11αin 1-3 and both H-11αand H-11βin aconicarmisulfonine A(4);(d)TMSP-2,2,3,3-d4 promoted cleavage of the C-12-C-13 bond of 4 in D2 O;(e)dehydrogenation of 4 in pyridine-d5,and(f)Na2 SO3-assisted dehydrogenation and N-deethylation of songorine(5,a putative precursor of 1-4).Biogenetically,1 and 2 are correlated with 4,for which the same novel carbon skeleton is proposed to be derived from semipinacol rearrangements via migrations of C-13-C-16 and C-15-C-16 bonds of the napelline-type skeleton,respectively.Meanwhile,3 is a highly possible precursor or a concurrent product in the biosynthetic pathways of 1,2,and 4.In the acetic acid-induced mice writhing assay,at 1.0 mg/kg(i.p.),compounds 1,2,5,5 a,and 5 b exhibited analgesic effects against mice writhing.展开更多
Objective:To investigate the effect and the mechanism of Astragalus membranaceus(Huangqi in Chinese,HQ)extract on the intestinal absorption of six alkaloids of Aconitum carmichaelii(Fuzi in Chinese,FZ)in rats with spl...Objective:To investigate the effect and the mechanism of Astragalus membranaceus(Huangqi in Chinese,HQ)extract on the intestinal absorption of six alkaloids of Aconitum carmichaelii(Fuzi in Chinese,FZ)in rats with spleen deficiency and provide novel insights into the application of HQ on modulating intestinal barrier.Methods:Four-week-old male Sprague-Dawley rats were fed with Xiaochengqi Decoction to induce the spleen deficiency model for 40 d.Single-pass intestinal perfusion model were used to study the effects of HQ extract on the absorption of alkaloids.Protein expression and mRNA levels of MRP2 and BCRP and tight junction proteins(TJ,including Claudin-1,Occludin and ZO-1)were measured using Western blot and real-time PCR,respectively.The location and expression of TJ protein was also investigated by the immunofluorescence method.Results:Compared with the normal group,the protein expression of MRP2,BCRP and TJ proteins in the model group were significantly down-regulated.After oral administration of HQ,the alkaloid absorption in intestinal villi was inhibited,MRP2,BCRP and TJ proteins were up-regulated,the green fluorescence staining of Claudin-1,Occludin,and ZO-1 was enhanced,and a thick layer of mucus was deposited on the surface of the epithelium of the intestinal cavity.Conclusion:HQ as an intestinal barrier modulator improves the physiological changes of the intestinal environment of spleen deficiency to reduce the absorption of toxic components,leading to a decrease in the absorption of drug-like molecules.展开更多
Background:Aconitum carmichaelii,the mother root of Aconitum,has a long-applied history for treating many diseases in China.Increased use of it has prompted significant concerns regarding its extensive cardiotoxicity ...Background:Aconitum carmichaelii,the mother root of Aconitum,has a long-applied history for treating many diseases in China.Increased use of it has prompted significant concerns regarding its extensive cardiotoxicity and neurotoxicity.The molecular mechanisms underlying A.carmichaelii-induced neurotoxicity are poorly understood.Methods:We took advantage of the zebrafish model to investigate the neurotoxic mechanism of A.carmichaelii.In addition to the behavior and neuronal activity testing,gene expression of neuronal oxidative stress,and apoptosis levels were also analyzed.Results:In contrast to the excitatory effect of low-dose A.carmichaelii decoction,hypoactivity of locomotor behavior,and neural activity,especially telencephalon,were detected in the 20 mg/mL group.High doses of A.carmichaelii induced excessive ROS bydownregulating DJ-1 and activating Nox5,and further triggered cell apoptosis through the bax/bcl2a-caspase-9 pathway in zebrafish larva.Mitochondrial protection-relatedgenes PinK1 and Parkin were upregulated to protect against mitochondrial dysfunction during cellular stress.The ROS scavenger-NAC significantly alleviated neurotoxicity in the 20mg/mL group.Conclusion:The study reveals the potential mechanism of A.carmichaelii-induced neurotoxicity and provides new insights in to a significant risk marker of A.carmichaelii poisoning.展开更多
目的系统评价“乌头-半夏”反药配伍对大鼠的毒性。方法检索中国知网、万方数据、维普网、中国生物医学文献服务系统、PubMed、Embase和Web of Science数据库,纳入国内外已发表的关于反药“乌头-半夏”对大鼠毒性的研究,检索时限均从建...目的系统评价“乌头-半夏”反药配伍对大鼠的毒性。方法检索中国知网、万方数据、维普网、中国生物医学文献服务系统、PubMed、Embase和Web of Science数据库,纳入国内外已发表的关于反药“乌头-半夏”对大鼠毒性的研究,检索时限均从建库至2024年4月3日。由2名研究者独立筛选文献、提取资料并运用SYRCLE动物实验偏倚风险评估工具进行文献质量评价,采用RevMan 5.4软件进行Meta分析。结果最终纳入13篇文献。Meta分析结果显示,与空白对照组相比,乌头-半夏(1∶1)配伍对正常大鼠的肝脏指数、谷丙转氨酶(ALT)、肌酐(Cr)和尿素氮(BUN)无显著影响,但可显著升高正常大鼠的心脏指数、肾脏指数、谷草转氨酶(AST)、碱性磷酸酶(ALP)、肌酸激酶(CK)和肌酸激酶同工酶(CK-MB)含量;与乌头单用组相比,乌头-半夏(1∶1)配伍可降低正常大鼠的AST、ALP、CK含量和肾脏指数,但不能降低心脏指数和CK-MB含量。附子-半夏(1∶1)配伍与空白对照组相比,仅CK含量显著升高,但与缺血再灌注损伤模型大鼠相比,附子-半夏可逆转模型大鼠CK水平的变化。定性分析结果显示,乌头/附子-半夏配伍对正常大鼠心、肝、肾的组织病理无影响或有轻度损伤,附子-半夏配伍可改善心脏病理模型大鼠的心脏病理损伤。结论现有动物实验表明,乌头-半夏(1∶1)配伍对正常大鼠的肝脏、心脏、肾脏指标均有一定影响,但可减轻乌头单用对正常大鼠的肝、肾损伤,对乌头引起的心脏损伤影响较小。附子-半夏(1∶1)配伍对正常大鼠肝、肾指标无明显影响,对心脏指标有一定影响,但对心脏病理模型大鼠有一定的保护作用。因此,乌头-半夏反药临床应用仍需持有谨慎态度;附子-半夏在辩证准确、方药合理的前提下,或可取得良效。展开更多
基金supported by the Sichuan Provincial Administration of Traditional Chinese Medicine Research Project(No.2018NQ008)
文摘According to folk usage of Aconitum carmichaelii Debx., the present study was designed to determine the feasibility of the stems and leaves of Aconitum carmichaelii Debx. as a new medicinal resource. Fourteen alkaloids in mother roots, fibrous roots, stems, and leaves of Aconitum carmichaelii Debx. were measured by HPLC-MS/MS. And multivariate analysis methods, such as clustering analysis and principal component analysis, were applied to analyze the difference among various parts. In addition, the acute toxicity, analgesia, and anti-inflammatory tests were carried out. The results suggested that the contents of alkaloids in mother roots and fibrous roots were approximate, but those of leaves and stems were different from mother roots and fibrous roots. The results of the acute toxicity testing demonstrated the toxicity of fibrous root was strongest, and mother roots were slightly less toxic than fibrous roots. The stems and leaves were far less toxic than mother and fibrous roots. In addition, the analgesia and inflammatory tests showed the effects of the various tissues had no difference each other. These results provided a basis for developing new complementary and alternative treatments for rheumatoid arthritis patients. Simultaneously, the approach may also turn wastes into treasure and promote the development of circular economy.
基金the Natural Science Foundation of Henan:Study of Combination Chuanwu(Aconitum Carmichaelii)and Banxia(Rhizoma Pinelliae)(No.18A330004)
文摘OBJEVTIVE: To investigate the effects of extracts from Chuanwu(Aconitum Carmichaelii) and Banxia(Rhizoma Pinelliae) on the excisional wound healing in a rat's model.METHODS: Rats were performed a surgical lesion with a 2.0 cm resected tissue in the dorsal fascia.Following, animals were randomly divided into model group, YNB group and APE group those were respectively treated with saline, 1 mg/mL of Yunnan Baiyao and 1 mg/mL of Chuanwu(Aconitum Carmichaelii) and Banxia(Rhizoma Pinelliae) extracts. Wound contractions in days 0, 3, 7, 14 and 21 were calculated by an image analyzer. Histological analysis was analyzed using hematoxilin and eosin.Levels of tumor necrosis factor-2(IL-2), IL-4, IL-10, transformαin(TNF-g growα), interleukinth factor-1(TGF-nd basic fibroblast growth factor(bFββ1) a-GF) were determined by real-time quantitative PCR.RESULTS: Compared with that of YNB group and APE gtoup, the skin of rats showed poor re-modeling and re-epithelization characterized by a significant decrease of neovascularization, epithelialization and fibroblast in the model group. In the APE group, levels of TNF-α-and IL-2 were significantly down-regulated and IL4 and IL-10 significantly upregulated in contrasted with that of model group.In addition, levels of TGF-roup were significantly iβ1 and bFGF in the APE gnduced compared with that of model group.CONCLUSION: The results suggest that the extracts from Chuanwu(Aconitum Carmichaelii) and Banxia(Rhizoma Pinelliae) promote wound healing in the rats, which is associated with enhancing antiinflammatory ability and inducing fibroblast formation.
基金Financial support from the National Natural Science Foundation of China (Nos.21132009 and 30825044)the Program for Changjiang Scholars and Innovative Research Team in University (No.IRT1007)the National Science and Technology Project of China (Nos.2012ZX09301002-002 and 2011ZX0 9307-002-01)
文摘Two new 2-（quinonylcarboxamino）benzoates, named aconicarmiquinamides A （1） and B （2）, were isolated from an aqueous extract of the lateral roots of Aconitum carmichaelii. Their structures were determined by spectroscopic data analysis, and confirmed by comparison with synthetic methyl 3.6- bis（ diethylamino ）benzoqunonylcarboxylate （3）.
基金Financial support from the National Natural Sciences Foundation of China(Nos.81630094 and 81573445)CAMS Innovation Fund for Medical Science(Nos.2017-I2M-3-010,2017-I2M-3-011,and 2016-I2M-1-010)The Drug Innovation Major Project(2018ZX09711001-003-001)is acknowledged。
文摘Two sulfo nated seco C_(20)-diterpenoid alkaloids,aconapelsulfonines A(1) and B(2),were isolated from an aqueous extract of the raw material of "Fu Zi"(the Aconitum carmichaelii lateral roots),of which the structures were elucidated by various spectroscopic data,combined with X-ray crystallogra phic analysis.The unprecedented skeletons are biogenetically proposed to be derived via Criegee rearrangements of the napelline-type architecture.The two compounds exhibited dose-depended analgesic activities on an acetic acid-induced mice writhing test.
基金support from the National Natural Sciences Foundation of China (Nos. 81630094 and 21732008)CAMS Innovation Fund for Medical Science (No. 2021-I2M-1-028)
文摘Two sulfonated diterpenoid alkaloids possessing different but related novel carbon skeletons,named aconidenusulfonine A(1)and 12,16-secoaconidenusulfonine A(2),respectively,were isolated as minor components from an aqueous extract of the lateral roots of Aconitum carmichaelii("Fu Zi").The structures of 1 and 2,representing the first two C21-diterpenoid alkaloids from nature,were determined by analysis of various spectroscopic data and chemical transformation,of which 1 was further proved by single-crystal X-ray diffraction.Especially,1 exhibited dose-depended analgesic activity consistent with the clinical function of Fu Zi.
基金Financial support from the National Natural Sciences Foundation of China(81630094,21732008,81373388,and 81573445)CAMS Innovation Fund for Medical Science(2017-I2M-3–010,2016-I2M-1–004,2016-I2M-1–010,and 2017-I2M-3–011)
文摘Eight new C_(19)-diterpenoid alkaloid arabinosides, named aconicarmichosides E–L(1–8), were isolated from an aqueous extract of the lateral roots of Aconitum carmichaelii(Fu Zi). Their structures were determined by spectroscopic and chemical methods including 2D NMR experiments and acid hydrolysis. Compounds 1–8, together with the previously reported four neoline 14-O-arabinosides from the same plant, represent the only examples of glycosidic diterpenoid alkaloids so far. At a dose of 1.0 mg/kg(i.p.), as compared with the black control, compounds 1, 2, and 4–6 exhibited analgesic effects with 465.6% inhibitions against acetic acid-induced writhing of mice. Structure–activity relationship was also discussed.
基金supported by the Major Program of National Natural Science Foundation of China(81891010,81891013)the National Natural Science Foundation of China(81822046)+1 种基金National Key R&D Program of China(2018YFA0900600,2020YFA0908000)Key project at central government level:the ability to establish sustainable use of valuable Chinese Medicine Resources(2060302,China)。
文摘Aconitum carmichaelii is a high-value medicinal herb widely used across China,Japan,and other Asian countries.Aconitine-type diterpene alkaloids(DAs)are the characteristic compounds in Aconitum.Although six transcriptomes,based on short-read next generation sequencing technology,have been reported from the Aconitum species,the terpene synthase(TPS)corresponding to DAs biosynthesis remains unidentified.We apply a combination of Pacbio isoform sequencing and RNA sequencing to provide a comprehensive view of the A.carmichaelii transcriptome.Nineteen TPSs and five alternative splicing isoforms belonging to TPS-b,TPS-c,and TPS-e/f subfamilies were identified.In vitro enzyme reaction analysis functional identified two sesqui-TPSs and twelve di TPSs.Seven of the TPS-c subfamily genes reacted with GGPP to produce the intermediate ent-copalyl diphosphate.Five Ac KSLs separately reacted with ent-CPP to produce ent-kaurene,ent-atiserene,and ent-13-epi-sandaracopimaradie:a new diterpene found in Aconitum.Ac TPSs gene expression in conjunction DAs content analysis in different tissues validated that ent-CPP is the sole precursor to all DAs biosynthesis,with Ac KSL1,Ac KSL2 s and Ac KSL3-1 responsible for C20 atisine and napelline type DAs biosynthesis,respectively.These data clarified the molecular basis for the C20-DAs biosynthetic pathway in A.carmichaelii and pave the way for further exploration of C19-DAs biosynthesis in the Aconitum species.
基金Financial support of the National Natural Sciences Foundation of China(81630094,21732008,and 81730093)CAMS Innovation Fund for Medical Science of China(2017-I2M-3-010 and 2016I2M-1-010)the Drug Innovation Major Project(2018ZX09711001-001-001,2018ZX09711001-001-003,and 2018ZX09711001-003-001,China)
文摘Three new C20-diterpenoid alkaloids with a sulfonic acid unit,named aconicarmisulfonines B and C(1 and 2)and chuanfusulfonine A(3),respectively,were isolated from the Aconitum carmichaelii lateral roots("fu zi"in Chinese).Structures of 1-3 were determined by spectroscopic data analysis.Intriguing chemical properties and reactions were observed for the C20-diterpenoid alkaloids:(a)specific selective nucleophilic addition of the carbonyl(C-12)in 1 with CD3 OD;(b)interconversion between 1 and 2 in D2 O;(c)stereo-and/or regioselective deuterations of H-11αin 1-3 and both H-11αand H-11βin aconicarmisulfonine A(4);(d)TMSP-2,2,3,3-d4 promoted cleavage of the C-12-C-13 bond of 4 in D2 O;(e)dehydrogenation of 4 in pyridine-d5,and(f)Na2 SO3-assisted dehydrogenation and N-deethylation of songorine(5,a putative precursor of 1-4).Biogenetically,1 and 2 are correlated with 4,for which the same novel carbon skeleton is proposed to be derived from semipinacol rearrangements via migrations of C-13-C-16 and C-15-C-16 bonds of the napelline-type skeleton,respectively.Meanwhile,3 is a highly possible precursor or a concurrent product in the biosynthetic pathways of 1,2,and 4.In the acetic acid-induced mice writhing assay,at 1.0 mg/kg(i.p.),compounds 1,2,5,5 a,and 5 b exhibited analgesic effects against mice writhing.
基金supported by a grant from the Key Laboratory of Modern Preparation of TCM of Ministry of Education,Jiangxi University of TCM and Affiliated Hospital,Jiujiang UniversityScience Foundation of Health and Family Planning Commission of Jiangxi Province (Grant No.20181140)+2 种基金National Natural Science Foundation of China (Grant No.81660757)Project of Jiangxi Education Department (Grant No.170732Grant No.201819)
文摘Objective:To investigate the effect and the mechanism of Astragalus membranaceus(Huangqi in Chinese,HQ)extract on the intestinal absorption of six alkaloids of Aconitum carmichaelii(Fuzi in Chinese,FZ)in rats with spleen deficiency and provide novel insights into the application of HQ on modulating intestinal barrier.Methods:Four-week-old male Sprague-Dawley rats were fed with Xiaochengqi Decoction to induce the spleen deficiency model for 40 d.Single-pass intestinal perfusion model were used to study the effects of HQ extract on the absorption of alkaloids.Protein expression and mRNA levels of MRP2 and BCRP and tight junction proteins(TJ,including Claudin-1,Occludin and ZO-1)were measured using Western blot and real-time PCR,respectively.The location and expression of TJ protein was also investigated by the immunofluorescence method.Results:Compared with the normal group,the protein expression of MRP2,BCRP and TJ proteins in the model group were significantly down-regulated.After oral administration of HQ,the alkaloid absorption in intestinal villi was inhibited,MRP2,BCRP and TJ proteins were up-regulated,the green fluorescence staining of Claudin-1,Occludin,and ZO-1 was enhanced,and a thick layer of mucus was deposited on the surface of the epithelium of the intestinal cavity.Conclusion:HQ as an intestinal barrier modulator improves the physiological changes of the intestinal environment of spleen deficiency to reduce the absorption of toxic components,leading to a decrease in the absorption of drug-like molecules.
基金National Key Research and Development Program,Grant/Award Number:2021YFF1200600China Postdoctoral Science Foundation,Grant/Award。
文摘Background:Aconitum carmichaelii,the mother root of Aconitum,has a long-applied history for treating many diseases in China.Increased use of it has prompted significant concerns regarding its extensive cardiotoxicity and neurotoxicity.The molecular mechanisms underlying A.carmichaelii-induced neurotoxicity are poorly understood.Methods:We took advantage of the zebrafish model to investigate the neurotoxic mechanism of A.carmichaelii.In addition to the behavior and neuronal activity testing,gene expression of neuronal oxidative stress,and apoptosis levels were also analyzed.Results:In contrast to the excitatory effect of low-dose A.carmichaelii decoction,hypoactivity of locomotor behavior,and neural activity,especially telencephalon,were detected in the 20 mg/mL group.High doses of A.carmichaelii induced excessive ROS bydownregulating DJ-1 and activating Nox5,and further triggered cell apoptosis through the bax/bcl2a-caspase-9 pathway in zebrafish larva.Mitochondrial protection-relatedgenes PinK1 and Parkin were upregulated to protect against mitochondrial dysfunction during cellular stress.The ROS scavenger-NAC significantly alleviated neurotoxicity in the 20mg/mL group.Conclusion:The study reveals the potential mechanism of A.carmichaelii-induced neurotoxicity and provides new insights in to a significant risk marker of A.carmichaelii poisoning.
文摘目的系统评价“乌头-半夏”反药配伍对大鼠的毒性。方法检索中国知网、万方数据、维普网、中国生物医学文献服务系统、PubMed、Embase和Web of Science数据库,纳入国内外已发表的关于反药“乌头-半夏”对大鼠毒性的研究,检索时限均从建库至2024年4月3日。由2名研究者独立筛选文献、提取资料并运用SYRCLE动物实验偏倚风险评估工具进行文献质量评价,采用RevMan 5.4软件进行Meta分析。结果最终纳入13篇文献。Meta分析结果显示,与空白对照组相比,乌头-半夏(1∶1)配伍对正常大鼠的肝脏指数、谷丙转氨酶(ALT)、肌酐(Cr)和尿素氮(BUN)无显著影响,但可显著升高正常大鼠的心脏指数、肾脏指数、谷草转氨酶(AST)、碱性磷酸酶(ALP)、肌酸激酶(CK)和肌酸激酶同工酶(CK-MB)含量;与乌头单用组相比,乌头-半夏(1∶1)配伍可降低正常大鼠的AST、ALP、CK含量和肾脏指数,但不能降低心脏指数和CK-MB含量。附子-半夏(1∶1)配伍与空白对照组相比,仅CK含量显著升高,但与缺血再灌注损伤模型大鼠相比,附子-半夏可逆转模型大鼠CK水平的变化。定性分析结果显示,乌头/附子-半夏配伍对正常大鼠心、肝、肾的组织病理无影响或有轻度损伤,附子-半夏配伍可改善心脏病理模型大鼠的心脏病理损伤。结论现有动物实验表明,乌头-半夏(1∶1)配伍对正常大鼠的肝脏、心脏、肾脏指标均有一定影响,但可减轻乌头单用对正常大鼠的肝、肾损伤,对乌头引起的心脏损伤影响较小。附子-半夏(1∶1)配伍对正常大鼠肝、肾指标无明显影响,对心脏指标有一定影响,但对心脏病理模型大鼠有一定的保护作用。因此,乌头-半夏反药临床应用仍需持有谨慎态度;附子-半夏在辩证准确、方药合理的前提下,或可取得良效。
