[Objectives]To study the effects of different alkaloids in Coptis chinensis on inhibiting the proliferation of Transmissible gastroenteritis virus(TGEV).[Methods]The components and content of the main alkaloids in the...[Objectives]To study the effects of different alkaloids in Coptis chinensis on inhibiting the proliferation of Transmissible gastroenteritis virus(TGEV).[Methods]The components and content of the main alkaloids in the extract of C.chinensis were analyzed.The main alkaloids were selected as drugs to inhibit the proliferation of TGEV.The maximum non-toxic concentration of Columbamine,Jatrorrhizine,Epiberberine,Coptisine,Palmatine,and Berberine was screened.The protective rate of each drug on TGEV-infected ST cells was determined,and the transcriptional inhibitory effect of the drug on TGEV N gene was detected by fluorescent quantitative PCR.[Results]The extract of C.chinensis mainly contains 6 alkaloids:Columbamine,Jatrorrhizine,Epiberberine,Coptisine,Palmatine,and Berberine,accounting for 2.03%,8.88%,9.21%,15.07%,14.63%,and 50.18%,respectively.In the range of the safe concentration,Jatrorrhizine,Palmatine,and Coptisine had better protective effects on ST cells infected with TGEV;compared with the Columbamine group,the cell protection rate was significantly different(P<0.05);compared with the Berberine group,the difference was extremely significant(P<0.01).The Coptisine and Palmatine groups had significant inhibitory effects on the transcription of TGEV N gene,and the difference was extremely significant compared with the virus group(P<0.05).[Conclusions]Jatrorrhizine and Palmatine in C.chinensis are the main components to inhibit the proliferation of TGEV.展开更多
New alkaloid,(E)-2-(hydroxyimino)-4-methylpentanamide(1)and a new cyclopentano[b]pyridine,4-hydroxy-7-methyl-6,7-dihydro-5H-cyclopenta[c]pyridin-5-one(2),together with ten known compounds(3–12)were isolated from the ...New alkaloid,(E)-2-(hydroxyimino)-4-methylpentanamide(1)and a new cyclopentano[b]pyridine,4-hydroxy-7-methyl-6,7-dihydro-5H-cyclopenta[c]pyridin-5-one(2),together with ten known compounds(3–12)were isolated from the mangrove soil-derived fungus Arthrinium sp.SCSIO 41305.Extensive spectroscopic analysis and X-Ray crystallographic analysis were used to elucidate the structure of(E)-2-(hydroxyimino)-4-methylpentanamide(1),including its absolute configuration.All the isolated compounds(1–12)were evaluated for their antimicrobial and enzyme inhibitory activities against acetylcholinesterase(ACh E),neuraminidase(NAs),and phosphatidylinositol 3-kinase(PI3K).Among them,compounds 1 and 3 exhibited strong neuraminidase inhibitory activity with IC_(50)values of 12.04,1.92μmol L^(-1)(IC_(50)20μmol L^(-1)for oseltamivir acid),while compounds 5,6,8,and 10showed moderate neuraminidase inhibitory activity,and compounds 6–10 displayed weak enzyme inhibitory activities against PI3K.展开更多
Hepatic sinusoidal obstruction syndrome (HSOS) can be caused by the intake of pyrrolizidine alkaloids (PAs). To date, PAs-induced HSOS has not been extensively studied. In view of the difference in etiology of HSOS be...Hepatic sinusoidal obstruction syndrome (HSOS) can be caused by the intake of pyrrolizidine alkaloids (PAs). To date, PAs-induced HSOS has not been extensively studied. In view of the difference in etiology of HSOS between the West and China, clinical profiles, imaging findings, treatment, and outcomes of HSOS associated with hematopoietic stem cell transplantation or oxaliplatin might be hardly extrapolated to PAs-induced HSOS. Reactive metabolites derived from PAs form pyrrole-protein adducts that result in toxic destruction of hepatic sinusoidal endothelial cells. PAs-induced HSOS typically manifests as painful hepatomegaly, ascites, and jaundice. Laboratory tests revealed abnormal liver function tests were observed in most of the patients with PAs-induced HSOS. In addition, contrast computed tomography and magnetic resonance imaging scan show that patients with PAs-induced HSOS have distinct imaging features, which reveal that radiological imaging provides an effective noninvasive method for the diagnosis of PAs-induced HSOS. Liver biopsy and histological examination showed that PAs-induced HSOS displayed distinct features in acute and chronic stages. Therapeutic strategies for PAs-induced HSOS include rigorous fluid management, anticoagulant therapy, glucocorticoids, transjugular intrahepatic portosystemic shunt, liver transplantation, etc. The aim of this review is to describe the pathogenesis, clinical profiles, diagnostic criteria, treatment, and outcomes of PAs-induced HSOS.展开更多
Two new indole alkaloids. wuchuyuamide Ⅰ and Ⅱ were isolated from the fruits of Evodia rutaecarpa (Juss.) Benth and their structures were elucidated on the basis of spectral data.
According to the Chinese Pharmacopoeia 2015, only processed Aconitum tubers can be clinically applied, and the effect of processing is unclear. This research aimed to explore the effect of processing on cardiac effica...According to the Chinese Pharmacopoeia 2015, only processed Aconitum tubers can be clinically applied, and the effect of processing is unclear. This research aimed to explore the effect of processing on cardiac efficacy of alkaloids in Aconitum tubers. First, the chemical ingredients in unprocessed and processed Aconitum tubers were identified and compared by using high performance liquid chromatography time-of-flight mass spectrometry(HPLC-TOF/MS) and multivariate pattern recognition methods. Then the representative alkaloids in Aconitum tubers, aconitine, benzoylaconine, and aconine, which belong to diester-diterpenoid alkaloids,monoester-diterpenoid alkaloids, and amine-diterpenoid alkaloids, respectively, were selected for further validation of attenuated mechanism. Subsequent pharmacological experiments with aconitine, benzoylaconine,and aconine in SD rats were used to validate the effect of processing on cardiac functions. After processing the Aconitum tubers, it was found that the contents of diester-diterpenoid alkaloids were reduced, and those of monoester-diterpenoid alkaloids and amine-diterpenoid alkaloids were increased, suggesting that diesterditerpenoid alkaloids were transformed into monoester-diterpenoid alkaloids and amine-diterpenoid alkaloids.Through further decocting the aconitine in boiling water, it was confirmed that the three alkaloids could be progressively transformed. Pharmacological experiments with aconitine, benzoylaconine, and aconine in SD rats showed that aconitine at a dose of 0.01 mg/kg and aconine at a dose of 10 mg/kg enhanced the cardiac function, while benzoylaconine at a dose of 2 mg/kg weakened the cardiac function. The effect of processing is attributed to the transformation of the most toxic diester-diterpenoid alkaloids into less toxic monoesterditerpenoid alkaloids and amine-diterpenoid alkaloids.展开更多
Mahonia leschenaultia(ML) and Mahonia napaulensis(MN) are less known and unexplored medicinal plants of the family Berberidaceae. They are used by the Todas of Nilgiris in their religious and medical practices but che...Mahonia leschenaultia(ML) and Mahonia napaulensis(MN) are less known and unexplored medicinal plants of the family Berberidaceae. They are used by the Todas of Nilgiris in their religious and medical practices but chemically less identified. Hence, we decided to do extensive phytochemical analysis to explore the potential of these plant extracts. An ultrahigh performance electrospray tandem mass spectrometry(UHPLC–ESI–MS/MS)method was successfully developed for qualitative analysis of the bioactive components in Mahonia species using Orbitrap Velos Pro mass spectrometer. Sixteen compounds were identified by comparison of their retention times and mass spectra(MS) with authentic standards and reported literature. Multi-stage mass spectra(MS^(2–8)) for the identification of protoberberine and aporphine alkaloids showed the sequential expulsion of all the substituents attached with their basic skeleton followed by CO loss. Eight of the identified compounds(berberine, jatrorrhizine, palmatine, magnoflorine, isocorydine, glaucine, tetrahydropalmatine and tetrahydroberberine) were simultaneously determined by another UHPLC–ESI–MS/MS method under the multiple reactions monitoring(MRM) mode quantitatively using triple quadrupole linear ion trap mass spectrometer. The analytical method was validated for 8 bioactive compounds with overall recovery in the range98.5%–103.6%(RSD≤2.2%), precise(RSD≤2.07%) and linear(r≥0.9995) over the concentration range of 0.5–1000 ng/mL and successfully applied in ML and MN roots, which suggests the suitability of the proposed approach for the routine analysis of Mahonia species and their quality control.展开更多
Rauwolfia species(Apocynaceae) are medicinal plants well known worldwide due to its potent bioactive monoterpene indole alkaloids(MIAs) such as reserpine,ajmalicine,ajmaline,serpentine and yohimbine.Reserpine,ajmalici...Rauwolfia species(Apocynaceae) are medicinal plants well known worldwide due to its potent bioactive monoterpene indole alkaloids(MIAs) such as reserpine,ajmalicine,ajmaline,serpentine and yohimbine.Reserpine,ajmalicine and ajmaline are powerful antihypertensive,tranquilizing agents used in hypertension.Yohimbine is an aphrodisiac used in dietary supplements.As there is no report on the comparative and comprehensive phytochemical investigation of the roots of Rauwolfia species,we have developed an efficient and reliable liquid chromatography-tandem mass spectrometry(LC–MS/MS) method for ethanolic root extract of Rauwolfia species to elucidate the fragmentation pathways for dereplication of bioactive MIAs using highperformance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry(HPLC–ESI–QTOF–MS/MS) in positive ion mode.We identified and established diagnostic fragment ions and fragmentation pathways using reserpine,ajmalicine,ajmaline,serpentine and yohimbine.The MS/MS spectra of reserpine,ajmalicine,and ajmaline showed C-ring-cleavage whereas E-ring cleavage was observed in serpentine via Retro Diels Alder(RDA).A total of 47 bioactive MIAs were identified and characterized on the basis of their molecular formula,exact mass measurements and MS/MS analysis.Reserpine,ajmalicine,ajmaline,serpentine and yohimbine were unambiguously identified by comparison with their authentic standards and other 42 MIAs were tentatively identified and characterized from the roots of Rauwolfia hookeri,Rauwolfia micrantha,Rauwolfia serpentina,Rauwolfia verticillata,Rauwolfia tetraphylla and Rauwolfia vomitoria.Application of LC–MS followed by principal component analysis(PCA) has been successfully used to discriminate among six Rauwolfia species.展开更多
Catharanthus roseus contains important anti-tumor terpenoid indole alkaloids (TIAs) such as vinblastine and vincristine. Cytochrome P450 enzyme geraniol 10-hydroxylase (G10H) is a putative rate-limiting enzyme involve...Catharanthus roseus contains important anti-tumor terpenoid indole alkaloids (TIAs) such as vinblastine and vincristine. Cytochrome P450 enzyme geraniol 10-hydroxylase (G10H) is a putative rate-limiting enzyme involved in the TIAs biosynthetic pathway in C. roseus. In this study the g10h gene driven by the cauliflower mosaic virus 35S (CaMV 35S) promoter was introduced into C. roseus through Agrobacterium-mediated transformation. The integration and overexpression of the target gene (g10h) in hairy root lines were confirmed by polymerase chain reaction and RT-QPCR analysis respectively. Overexpression of g10h in transgenic hairy root lines significantly enhanced the accumulations of monomeric alkaloid ajmalicine and dimeric alkaloids, vincristine and vinblastine. Total TIAs production in hairy roots reached (9.51) mg/g DW, over 3-fold higher than that in the untransformed root lines. This is the first report that engineering of g10h into TIAs-producing plant species results in significant enhancement of TIAs accumulation in cultured hairy roots. This study demonstrates that the putative rate-limiting step catalyzed by G10H is indeed the real rate-limiting step involved in the TIAs biosynthetic pathway in C. roseus, which is one of the key targets for promoting TIAs production by genetic engineering.展开更多
A new diterpenoid 12 -epiacetyldehydrolucidusculline (1) and a new norditerpenoid alkaloid 2-hydroxydeoxyaconitine (2) were isolated from the roots of Aconitum pendulum, together with eight known alkaloids aconitine (...A new diterpenoid 12 -epiacetyldehydrolucidusculline (1) and a new norditerpenoid alkaloid 2-hydroxydeoxyaconitine (2) were isolated from the roots of Aconitum pendulum, together with eight known alkaloids aconitine (3), deoxyaconitine (4), 3-acetylaconitine (5), 12-epiacetyldehydronapelline (6), dehydrolucidusculline (7), dehydronapelline (8), 12 -epidehydrnapelline (9), and noeline (10). The structures of the new alkaloids (1-2) were determined on the basis of spectral method.展开更多
Panax notoginseng(Araliaceae)is a famous traditional Chinese medicine mainly cultivated in Yunnan and Guangxi provinces of China.Two new alkaloids,rigidiusculamide E(1)and[-(a-oxyisohexanoyl-N-methyl-leucyl)2-](2),tog...Panax notoginseng(Araliaceae)is a famous traditional Chinese medicine mainly cultivated in Yunnan and Guangxi provinces of China.Two new alkaloids,rigidiusculamide E(1)and[-(a-oxyisohexanoyl-N-methyl-leucyl)2-](2),together with two known ones,(-)-oxysporidinone(3)and(-)-4,60-anhydrooxysporidinone(4)were isolated from the mycelia culture of Fusarium tricinctum SYPF 7082,an endophytic fungus obtained from the healthy root of P.notoginseng.Their structures were determined on the basis of extensive spectroscopic analyses.Compounds 1-4 were tested for their inhibitory effects against NO production on Murine macrophage cell line,and the new compound 2 showed significant inhibitory activity on NO production with the IC_(50)value of 18.10±0.16μM.展开更多
Diterpenoid alkaloids have neroprotective activity.Herein,three napelline-type diterpenoid alkaloids 1-3,two aconitine-type diterpenoid alkaloids 4-5,and one isoquinline-type alkaloid 6,as well as one lignan glycoside...Diterpenoid alkaloids have neroprotective activity.Herein,three napelline-type diterpenoid alkaloids 1-3,two aconitine-type diterpenoid alkaloids 4-5,and one isoquinline-type alkaloid 6,as well as one lignan glycoside 7,have been isolated from the roots of Aconitum pendulum Busch.Compounds 1 and 7 were new compounds,and their chemical structures were determined on the basis of nuclear magnetic resonance(NMR)spectra and mass spectrometry analysis.A ThT assay revealed that compound 2 showed significant disaggregation potency on the Aβ_(1−42)aggregates.展开更多
Four new alkaloids,sinensines B-E(1-4),together with one known alkaloid,sinensine(5),were isolated from the fruiting bodies of Ganoderma sinense.Their structures were elucidated on the basis of 1D and 2D NMR spectra a...Four new alkaloids,sinensines B-E(1-4),together with one known alkaloid,sinensine(5),were isolated from the fruiting bodies of Ganoderma sinense.Their structures were elucidated on the basis of 1D and 2D NMR spectra analysis.The structure of sinensine E was confirmed by X-ray crystallographic analysis of its acetyl product(4a).展开更多
In this work,a fast and efficient microwave-assisted extraction(MAE) method was developed to extract main bioactive alkaloids from lotus plumue.To optimize MAE conditions,three main factors were selected using univari...In this work,a fast and efficient microwave-assisted extraction(MAE) method was developed to extract main bioactive alkaloids from lotus plumue.To optimize MAE conditions,three main factors were selected using univariate approach experiments,and then central composite design(CCD).The optimal extraction conditions were as follows:methanol concentration of 65%,microwave power of 200 W,and extraction time of 260 s.A high performance liquid chromatography–diode array detector(HPLC–DAD) method was established to quantitatively analyze these phytochemicals in different lotus plumule samples and in different part of lotus.Chromatographic separation was carried out on an Agilent Zorbax Extend-C_(18) column(4.6 mm×150 mm,3.5 μm).Gradient elution was applied with the mobile phase constituted with 0.1% triethylamine in water(A)and acetonitrile(B):40%-70% B at 0-8 min,70%-100% B at 8–9 min,100% B for 2 min,and then equilibrated with 40% B for 2 min.展开更多
Uncaria rhynchophylla is commonly recognized as a traditional treatment for dizziness,cerebrovascular diseases,and nervous disorders in China.Previously,the neuro-protective activities of the alkaloids from U.rhyncho...Uncaria rhynchophylla is commonly recognized as a traditional treatment for dizziness,cerebrovascular diseases,and nervous disorders in China.Previously,the neuro-protective activities of the alkaloids from U.rhynchophylla were intensively reported.In current work,three new indole alkaloids(1–3),identified as geissoschizic acid(1),geissoschizic acid N4-oxide(2),and 3b-sitsirikine N4-oxide(3),as well as 26 known analogues were isolated from U.rhynchophylla.However,in the neural stem cells(NSCs)proliferation assay for all isolated compounds,geissoschizic acid(1),geissoschizic acid N4-oxide(2),isocorynoxeine(6),isorhynchophylline(7),(4S)-akuammigine N-oxide(8),and(4S)-rhynchophylline N-oxide(10)showed unexpected inhibitory activities at 10 μM.Unlike previous neuro-protective reports,as a warning or caution,our finding showcased a clue for possible NSCs toxicity and the neural lesions risk of U.rhynchophylla,while the structure–activity relationships of the isolated compounds were discussed also.展开更多
Four new alkaloids, didehydroprotostemonine, isoprotostemonine, neostemonine and stemodiol, were isolated from the roots of a Chinese medicinal plant, Stemona japonica, collected form Zhejiang Province, southern China...Four new alkaloids, didehydroprotostemonine, isoprotostemonine, neostemonine and stemodiol, were isolated from the roots of a Chinese medicinal plant, Stemona japonica, collected form Zhejiang Province, southern China. Their structures were elucidated by extensive spectral analyses.展开更多
Six new indole alkaloids,named alstoniascholarines L–Q(1–6),together with nineteen known analogues were isolated from the inadequately dried leaves of Alstonia scholaris.Their structures were elucidated on the basis...Six new indole alkaloids,named alstoniascholarines L–Q(1–6),together with nineteen known analogues were isolated from the inadequately dried leaves of Alstonia scholaris.Their structures were elucidated on the basis of extensive analysis of spectroscopic data and by comparison of their physical and spectroscopic data with the literature values.In addition,the new alkaloids were tested for their cytotoxic and neurite outgrowth-promoting activities.展开更多
Fifteen known amaryllidaceae alkaloids were isolated from the bulbs of Lycoris radiata.Some of the compounds and lycoricidine derivatives had been screened for the activities against tobacco mosaic virus(TMV)by the co...Fifteen known amaryllidaceae alkaloids were isolated from the bulbs of Lycoris radiata.Some of the compounds and lycoricidine derivatives had been screened for the activities against tobacco mosaic virus(TMV)by the conventional halfleaf method.Lycoricidine derivatives were also carried out the assay of effect on systemic infection of TMV by western-blot and RT-PCR analysis.The tested compounds showed moderate inactivation effect,whereas the lycoricidine derivatives showed good protective effect.The protective inhibitory activity of compounds L1(N-methyl-2,3,4-trimethoxyly-coricidine)(60.8%)and L3(N-methyl-2-methoxy-3,4-acetonidelycoricidine)(62.0%)was almost similar to the positive control,Ningnanmycin(66.4%).RT-PCR and Western-blot analysis displayed that compounds L1,L3,L5(N-allyl-2,3,4-triallyloxylycoricidine)exhibited antiviral activity,which was evidenced by reducing TMV-CP gene replication and TMV-CP protein expression.Additionally,defensive enzyme activities confirmed that compound L1 could increase the activity of PAL,POD,SOD to improve disease resistance of tobacco.展开更多
Three new lycopodine-type alkaloids,4a-hydroxyanhydrolycodoline(1),4a,6a-dihydroxyanhydrolycodoline(2),and 6-epi-8b-acetoxylycoclavine(3),and an artifact,lycoposerramine G nitrate(4),along with seventeen related known...Three new lycopodine-type alkaloids,4a-hydroxyanhydrolycodoline(1),4a,6a-dihydroxyanhydrolycodoline(2),and 6-epi-8b-acetoxylycoclavine(3),and an artifact,lycoposerramine G nitrate(4),along with seventeen related known compounds,were isolated from the club moss Lycopodium japonicum Thunb.ex Murray(Lycopodiaceae).Their structures were elucidated by extensive spectroscopic methods as well as X-ray analysis.Compounds 1–4 were evaluated for their acetylcholine esterase inhibitory activity.展开更多
t Three new lycodine-type Lycopodium alkaloids,namely 1-methyllycodine(1),8a-hydroxy-15,16-dehydro-desN-methyl-a-obscurine(2),N-methyl-16-hydroxyhuperzine B(3),and one new natural lycodine-type Lycopodium alkaloid,N-...t Three new lycodine-type Lycopodium alkaloids,namely 1-methyllycodine(1),8a-hydroxy-15,16-dehydro-desN-methyl-a-obscurine(2),N-methyl-16-hydroxyhuperzine B(3),and one new natural lycodine-type Lycopodium alkaloid,N-methylhuperzine A(4),along with 11 known analogues(5–15),were isolated from the whole plants of club moss Huperzia serrata.The structures of 1–4 were elucidated on the basis of NMR spectroscopic and mass spectrometry data.Among them,compound 1 was the first lycodine-type alkaloid possessing a methyl group at C-1.In addition,the structure of 5 was confirmed by the single-crystal X-ray crystallography data and its^(13)C NMR was reported for the first time in current study.Compounds 1–5 were tested their BACE1 inhibitory activity.展开更多
Isaindigotone 1 and 3-(2’-hydroxyphenyl)-4(3H)-quinazolinone 2 were isolated from the roots of Isatis indigotica. Compound 1 was elucidated as a new alkaloid.Compound 2 was discovered for the first time from a natural
基金Supported by General Project of Chongqing Natural Science Foundation(cstc2020jcyj-msxmX0757)Pilot Project of National Center of Technology Innovation for Pigs(NCTIP-XD/B12)Regional Innovation Cooperation in Sichuan Province(2022YFQ0024)。
文摘[Objectives]To study the effects of different alkaloids in Coptis chinensis on inhibiting the proliferation of Transmissible gastroenteritis virus(TGEV).[Methods]The components and content of the main alkaloids in the extract of C.chinensis were analyzed.The main alkaloids were selected as drugs to inhibit the proliferation of TGEV.The maximum non-toxic concentration of Columbamine,Jatrorrhizine,Epiberberine,Coptisine,Palmatine,and Berberine was screened.The protective rate of each drug on TGEV-infected ST cells was determined,and the transcriptional inhibitory effect of the drug on TGEV N gene was detected by fluorescent quantitative PCR.[Results]The extract of C.chinensis mainly contains 6 alkaloids:Columbamine,Jatrorrhizine,Epiberberine,Coptisine,Palmatine,and Berberine,accounting for 2.03%,8.88%,9.21%,15.07%,14.63%,and 50.18%,respectively.In the range of the safe concentration,Jatrorrhizine,Palmatine,and Coptisine had better protective effects on ST cells infected with TGEV;compared with the Columbamine group,the cell protection rate was significantly different(P<0.05);compared with the Berberine group,the difference was extremely significant(P<0.01).The Coptisine and Palmatine groups had significant inhibitory effects on the transcription of TGEV N gene,and the difference was extremely significant compared with the virus group(P<0.05).[Conclusions]Jatrorrhizine and Palmatine in C.chinensis are the main components to inhibit the proliferation of TGEV.
基金the Guangdong Basic and Applied Basic Research Foundation(Nos.2021 A1515011523,2021B1515120046)the Guangdong MEPP Funds(No.GDNRC[2021]48)+1 种基金the Finance Science and Technology Project of Hainan Province(No.ZDKJ202018)National Natural Science Foundation of China(No.41776169)。
文摘New alkaloid,(E)-2-(hydroxyimino)-4-methylpentanamide(1)and a new cyclopentano[b]pyridine,4-hydroxy-7-methyl-6,7-dihydro-5H-cyclopenta[c]pyridin-5-one(2),together with ten known compounds(3–12)were isolated from the mangrove soil-derived fungus Arthrinium sp.SCSIO 41305.Extensive spectroscopic analysis and X-Ray crystallographic analysis were used to elucidate the structure of(E)-2-(hydroxyimino)-4-methylpentanamide(1),including its absolute configuration.All the isolated compounds(1–12)were evaluated for their antimicrobial and enzyme inhibitory activities against acetylcholinesterase(ACh E),neuraminidase(NAs),and phosphatidylinositol 3-kinase(PI3K).Among them,compounds 1 and 3 exhibited strong neuraminidase inhibitory activity with IC_(50)values of 12.04,1.92μmol L^(-1)(IC_(50)20μmol L^(-1)for oseltamivir acid),while compounds 5,6,8,and 10showed moderate neuraminidase inhibitory activity,and compounds 6–10 displayed weak enzyme inhibitory activities against PI3K.
基金Supported by National Natural Science Foundation of China,No.81570555 and No.81770582
文摘Hepatic sinusoidal obstruction syndrome (HSOS) can be caused by the intake of pyrrolizidine alkaloids (PAs). To date, PAs-induced HSOS has not been extensively studied. In view of the difference in etiology of HSOS between the West and China, clinical profiles, imaging findings, treatment, and outcomes of HSOS associated with hematopoietic stem cell transplantation or oxaliplatin might be hardly extrapolated to PAs-induced HSOS. Reactive metabolites derived from PAs form pyrrole-protein adducts that result in toxic destruction of hepatic sinusoidal endothelial cells. PAs-induced HSOS typically manifests as painful hepatomegaly, ascites, and jaundice. Laboratory tests revealed abnormal liver function tests were observed in most of the patients with PAs-induced HSOS. In addition, contrast computed tomography and magnetic resonance imaging scan show that patients with PAs-induced HSOS have distinct imaging features, which reveal that radiological imaging provides an effective noninvasive method for the diagnosis of PAs-induced HSOS. Liver biopsy and histological examination showed that PAs-induced HSOS displayed distinct features in acute and chronic stages. Therapeutic strategies for PAs-induced HSOS include rigorous fluid management, anticoagulant therapy, glucocorticoids, transjugular intrahepatic portosystemic shunt, liver transplantation, etc. The aim of this review is to describe the pathogenesis, clinical profiles, diagnostic criteria, treatment, and outcomes of PAs-induced HSOS.
文摘Two new indole alkaloids. wuchuyuamide Ⅰ and Ⅱ were isolated from the fruits of Evodia rutaecarpa (Juss.) Benth and their structures were elucidated on the basis of spectral data.
基金financially supported by the National Natural Science Foundation of China (81573396)Military Innovation Funding (16CXZ012)
文摘According to the Chinese Pharmacopoeia 2015, only processed Aconitum tubers can be clinically applied, and the effect of processing is unclear. This research aimed to explore the effect of processing on cardiac efficacy of alkaloids in Aconitum tubers. First, the chemical ingredients in unprocessed and processed Aconitum tubers were identified and compared by using high performance liquid chromatography time-of-flight mass spectrometry(HPLC-TOF/MS) and multivariate pattern recognition methods. Then the representative alkaloids in Aconitum tubers, aconitine, benzoylaconine, and aconine, which belong to diester-diterpenoid alkaloids,monoester-diterpenoid alkaloids, and amine-diterpenoid alkaloids, respectively, were selected for further validation of attenuated mechanism. Subsequent pharmacological experiments with aconitine, benzoylaconine,and aconine in SD rats were used to validate the effect of processing on cardiac functions. After processing the Aconitum tubers, it was found that the contents of diester-diterpenoid alkaloids were reduced, and those of monoester-diterpenoid alkaloids and amine-diterpenoid alkaloids were increased, suggesting that diesterditerpenoid alkaloids were transformed into monoester-diterpenoid alkaloids and amine-diterpenoid alkaloids.Through further decocting the aconitine in boiling water, it was confirmed that the three alkaloids could be progressively transformed. Pharmacological experiments with aconitine, benzoylaconine, and aconine in SD rats showed that aconitine at a dose of 0.01 mg/kg and aconine at a dose of 10 mg/kg enhanced the cardiac function, while benzoylaconine at a dose of 2 mg/kg weakened the cardiac function. The effect of processing is attributed to the transformation of the most toxic diester-diterpenoid alkaloids into less toxic monoesterditerpenoid alkaloids and amine-diterpenoid alkaloids.
文摘Mahonia leschenaultia(ML) and Mahonia napaulensis(MN) are less known and unexplored medicinal plants of the family Berberidaceae. They are used by the Todas of Nilgiris in their religious and medical practices but chemically less identified. Hence, we decided to do extensive phytochemical analysis to explore the potential of these plant extracts. An ultrahigh performance electrospray tandem mass spectrometry(UHPLC–ESI–MS/MS)method was successfully developed for qualitative analysis of the bioactive components in Mahonia species using Orbitrap Velos Pro mass spectrometer. Sixteen compounds were identified by comparison of their retention times and mass spectra(MS) with authentic standards and reported literature. Multi-stage mass spectra(MS^(2–8)) for the identification of protoberberine and aporphine alkaloids showed the sequential expulsion of all the substituents attached with their basic skeleton followed by CO loss. Eight of the identified compounds(berberine, jatrorrhizine, palmatine, magnoflorine, isocorydine, glaucine, tetrahydropalmatine and tetrahydroberberine) were simultaneously determined by another UHPLC–ESI–MS/MS method under the multiple reactions monitoring(MRM) mode quantitatively using triple quadrupole linear ion trap mass spectrometer. The analytical method was validated for 8 bioactive compounds with overall recovery in the range98.5%–103.6%(RSD≤2.2%), precise(RSD≤2.07%) and linear(r≥0.9995) over the concentration range of 0.5–1000 ng/mL and successfully applied in ML and MN roots, which suggests the suitability of the proposed approach for the routine analysis of Mahonia species and their quality control.
基金Council of Scientific Industrial Research,India for providing financial support
文摘Rauwolfia species(Apocynaceae) are medicinal plants well known worldwide due to its potent bioactive monoterpene indole alkaloids(MIAs) such as reserpine,ajmalicine,ajmaline,serpentine and yohimbine.Reserpine,ajmalicine and ajmaline are powerful antihypertensive,tranquilizing agents used in hypertension.Yohimbine is an aphrodisiac used in dietary supplements.As there is no report on the comparative and comprehensive phytochemical investigation of the roots of Rauwolfia species,we have developed an efficient and reliable liquid chromatography-tandem mass spectrometry(LC–MS/MS) method for ethanolic root extract of Rauwolfia species to elucidate the fragmentation pathways for dereplication of bioactive MIAs using highperformance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry(HPLC–ESI–QTOF–MS/MS) in positive ion mode.We identified and established diagnostic fragment ions and fragmentation pathways using reserpine,ajmalicine,ajmaline,serpentine and yohimbine.The MS/MS spectra of reserpine,ajmalicine,and ajmaline showed C-ring-cleavage whereas E-ring cleavage was observed in serpentine via Retro Diels Alder(RDA).A total of 47 bioactive MIAs were identified and characterized on the basis of their molecular formula,exact mass measurements and MS/MS analysis.Reserpine,ajmalicine,ajmaline,serpentine and yohimbine were unambiguously identified by comparison with their authentic standards and other 42 MIAs were tentatively identified and characterized from the roots of Rauwolfia hookeri,Rauwolfia micrantha,Rauwolfia serpentina,Rauwolfia verticillata,Rauwolfia tetraphylla and Rauwolfia vomitoria.Application of LC–MS followed by principal component analysis(PCA) has been successfully used to discriminate among six Rauwolfia species.
基金Item supported by China national"863"high-tech program (2002AA212191)China ministry of educa-tion and science and technology commission of Shanghai(04XD14011)
文摘Catharanthus roseus contains important anti-tumor terpenoid indole alkaloids (TIAs) such as vinblastine and vincristine. Cytochrome P450 enzyme geraniol 10-hydroxylase (G10H) is a putative rate-limiting enzyme involved in the TIAs biosynthetic pathway in C. roseus. In this study the g10h gene driven by the cauliflower mosaic virus 35S (CaMV 35S) promoter was introduced into C. roseus through Agrobacterium-mediated transformation. The integration and overexpression of the target gene (g10h) in hairy root lines were confirmed by polymerase chain reaction and RT-QPCR analysis respectively. Overexpression of g10h in transgenic hairy root lines significantly enhanced the accumulations of monomeric alkaloid ajmalicine and dimeric alkaloids, vincristine and vinblastine. Total TIAs production in hairy roots reached (9.51) mg/g DW, over 3-fold higher than that in the untransformed root lines. This is the first report that engineering of g10h into TIAs-producing plant species results in significant enhancement of TIAs accumulation in cultured hairy roots. This study demonstrates that the putative rate-limiting step catalyzed by G10H is indeed the real rate-limiting step involved in the TIAs biosynthetic pathway in C. roseus, which is one of the key targets for promoting TIAs production by genetic engineering.
文摘A new diterpenoid 12 -epiacetyldehydrolucidusculline (1) and a new norditerpenoid alkaloid 2-hydroxydeoxyaconitine (2) were isolated from the roots of Aconitum pendulum, together with eight known alkaloids aconitine (3), deoxyaconitine (4), 3-acetylaconitine (5), 12-epiacetyldehydronapelline (6), dehydrolucidusculline (7), dehydronapelline (8), 12 -epidehydrnapelline (9), and noeline (10). The structures of the new alkaloids (1-2) were determined on the basis of spectral method.
基金supported by the Major Science and Technique Programs in Yunnan Province(2016ZF001-001,2017IB038)the Science and Technology Planning Project of Yunnan Province(2013FC008,2015IC017)the National Science and Technology Major Project of China(2018ZX09735001-002-002).
文摘Panax notoginseng(Araliaceae)is a famous traditional Chinese medicine mainly cultivated in Yunnan and Guangxi provinces of China.Two new alkaloids,rigidiusculamide E(1)and[-(a-oxyisohexanoyl-N-methyl-leucyl)2-](2),together with two known ones,(-)-oxysporidinone(3)and(-)-4,60-anhydrooxysporidinone(4)were isolated from the mycelia culture of Fusarium tricinctum SYPF 7082,an endophytic fungus obtained from the healthy root of P.notoginseng.Their structures were determined on the basis of extensive spectroscopic analyses.Compounds 1-4 were tested for their inhibitory effects against NO production on Murine macrophage cell line,and the new compound 2 showed significant inhibitory activity on NO production with the IC_(50)value of 18.10±0.16μM.
基金This work was financially supported by National Natural Science Foundation of China(Nos.81673325 and 81711540311)the International Partnership Program of CAS(No.153631KYSB20160004)+1 种基金Gansu Province Key International S&T Cooperation Project(No.18YF1WA127)CAS Pioneer Hundred Talents Program.
文摘Diterpenoid alkaloids have neroprotective activity.Herein,three napelline-type diterpenoid alkaloids 1-3,two aconitine-type diterpenoid alkaloids 4-5,and one isoquinline-type alkaloid 6,as well as one lignan glycoside 7,have been isolated from the roots of Aconitum pendulum Busch.Compounds 1 and 7 were new compounds,and their chemical structures were determined on the basis of nuclear magnetic resonance(NMR)spectra and mass spectrometry analysis.A ThT assay revealed that compound 2 showed significant disaggregation potency on the Aβ_(1−42)aggregates.
基金The project was financially supported by the General Program of NSFC(No.81172940)Knowledge Innovation Program of the CAS(Grant No.KSCX2-YW-G-038,KSCX2-YW-R-194,KZCX2-XB2-15-03,)as well as Foundation of State Key Laboratory of Phytochemistry and Plant Resources in West China(P2010-ZZ14).
文摘Four new alkaloids,sinensines B-E(1-4),together with one known alkaloid,sinensine(5),were isolated from the fruiting bodies of Ganoderma sinense.Their structures were elucidated on the basis of 1D and 2D NMR spectra analysis.The structure of sinensine E was confirmed by X-ray crystallographic analysis of its acetyl product(4a).
基金partially supported by grants from the Science and Technology Development Fund of Macao(FDCT059/2011/A3)the University of Macao(MYRG085 to Jing Zhao and MYRG201400041 to LSP,respectively)
文摘In this work,a fast and efficient microwave-assisted extraction(MAE) method was developed to extract main bioactive alkaloids from lotus plumue.To optimize MAE conditions,three main factors were selected using univariate approach experiments,and then central composite design(CCD).The optimal extraction conditions were as follows:methanol concentration of 65%,microwave power of 200 W,and extraction time of 260 s.A high performance liquid chromatography–diode array detector(HPLC–DAD) method was established to quantitatively analyze these phytochemicals in different lotus plumule samples and in different part of lotus.Chromatographic separation was carried out on an Agilent Zorbax Extend-C_(18) column(4.6 mm×150 mm,3.5 μm).Gradient elution was applied with the mobile phase constituted with 0.1% triethylamine in water(A)and acetonitrile(B):40%-70% B at 0-8 min,70%-100% B at 8–9 min,100% B for 2 min,and then equilibrated with 40% B for 2 min.
基金The authors are grateful to the National Natural Science Foundation of China(81225024,31500292,31770388)for financial support.
文摘Uncaria rhynchophylla is commonly recognized as a traditional treatment for dizziness,cerebrovascular diseases,and nervous disorders in China.Previously,the neuro-protective activities of the alkaloids from U.rhynchophylla were intensively reported.In current work,three new indole alkaloids(1–3),identified as geissoschizic acid(1),geissoschizic acid N4-oxide(2),and 3b-sitsirikine N4-oxide(3),as well as 26 known analogues were isolated from U.rhynchophylla.However,in the neural stem cells(NSCs)proliferation assay for all isolated compounds,geissoschizic acid(1),geissoschizic acid N4-oxide(2),isocorynoxeine(6),isorhynchophylline(7),(4S)-akuammigine N-oxide(8),and(4S)-rhynchophylline N-oxide(10)showed unexpected inhibitory activities at 10 μM.Unlike previous neuro-protective reports,as a warning or caution,our finding showcased a clue for possible NSCs toxicity and the neural lesions risk of U.rhynchophylla,while the structure–activity relationships of the isolated compounds were discussed also.
文摘Four new alkaloids, didehydroprotostemonine, isoprotostemonine, neostemonine and stemodiol, were isolated from the roots of a Chinese medicinal plant, Stemona japonica, collected form Zhejiang Province, southern China. Their structures were elucidated by extensive spectral analyses.
基金The authors are grateful to the Natural Science Foundation of China(81225024)Collaborative Innovation Center of Southwest EthnicMedicine(Guangxi Normal University),(CICSEM 2013-A)+1 种基金the Ministry of Science and Technology of the People’s Republic of China(2014ZX09301307-003)the Chinese Academy of Sciences(KSZD-EW-Z-004-03)for partial financial support。
文摘Six new indole alkaloids,named alstoniascholarines L–Q(1–6),together with nineteen known analogues were isolated from the inadequately dried leaves of Alstonia scholaris.Their structures were elucidated on the basis of extensive analysis of spectroscopic data and by comparison of their physical and spectroscopic data with the literature values.In addition,the new alkaloids were tested for their cytotoxic and neurite outgrowth-promoting activities.
基金the National Natural Science.Foundation of China(Nos.31770389,31470427,31270404).
文摘Fifteen known amaryllidaceae alkaloids were isolated from the bulbs of Lycoris radiata.Some of the compounds and lycoricidine derivatives had been screened for the activities against tobacco mosaic virus(TMV)by the conventional halfleaf method.Lycoricidine derivatives were also carried out the assay of effect on systemic infection of TMV by western-blot and RT-PCR analysis.The tested compounds showed moderate inactivation effect,whereas the lycoricidine derivatives showed good protective effect.The protective inhibitory activity of compounds L1(N-methyl-2,3,4-trimethoxyly-coricidine)(60.8%)and L3(N-methyl-2-methoxy-3,4-acetonidelycoricidine)(62.0%)was almost similar to the positive control,Ningnanmycin(66.4%).RT-PCR and Western-blot analysis displayed that compounds L1,L3,L5(N-allyl-2,3,4-triallyloxylycoricidine)exhibited antiviral activity,which was evidenced by reducing TMV-CP gene replication and TMV-CP protein expression.Additionally,defensive enzyme activities confirmed that compound L1 could increase the activity of PAL,POD,SOD to improve disease resistance of tobacco.
基金the National Natural Science Foundation of China(Nos.90813004 and U0932602)the National Basic Research Program of China(973 Program No.2011CB915503).
文摘Three new lycopodine-type alkaloids,4a-hydroxyanhydrolycodoline(1),4a,6a-dihydroxyanhydrolycodoline(2),and 6-epi-8b-acetoxylycoclavine(3),and an artifact,lycoposerramine G nitrate(4),along with seventeen related known compounds,were isolated from the club moss Lycopodium japonicum Thunb.ex Murray(Lycopodiaceae).Their structures were elucidated by extensive spectroscopic methods as well as X-ray analysis.Compounds 1–4 were evaluated for their acetylcholine esterase inhibitory activity.
基金the NSFC-Joint Foundation of Yunnan Province(No.U1502223)the National Natural Science Foundation of China(No.21402212)+1 种基金the Science and Technology Program of Yunnan province(No 2015FB173)the CAS"Light of West China"Program and Youth Innovation Promotion Association CAS(X.D.Wu).
文摘t Three new lycodine-type Lycopodium alkaloids,namely 1-methyllycodine(1),8a-hydroxy-15,16-dehydro-desN-methyl-a-obscurine(2),N-methyl-16-hydroxyhuperzine B(3),and one new natural lycodine-type Lycopodium alkaloid,N-methylhuperzine A(4),along with 11 known analogues(5–15),were isolated from the whole plants of club moss Huperzia serrata.The structures of 1–4 were elucidated on the basis of NMR spectroscopic and mass spectrometry data.Among them,compound 1 was the first lycodine-type alkaloid possessing a methyl group at C-1.In addition,the structure of 5 was confirmed by the single-crystal X-ray crystallography data and its^(13)C NMR was reported for the first time in current study.Compounds 1–5 were tested their BACE1 inhibitory activity.
文摘Isaindigotone 1 and 3-(2’-hydroxyphenyl)-4(3H)-quinazolinone 2 were isolated from the roots of Isatis indigotica. Compound 1 was elucidated as a new alkaloid.Compound 2 was discovered for the first time from a natural
