Alkaloidal compounds and bioactivities of three medicinal plants of Menispermaceaefamily in Qinling Montain

Aim To find the original active compounds from three medicinal plants of Menispermaceae family in Qinling Montain,Shaanxi,China.Method Several kinds of isolation techniques such as liquid-liquid partition,column chromatography,thin layer chromatography and sephadex LH-20 gel chromatography are used to separate the compounds and all kinds of identification techniques such as mass,high resolution mass,1H-NMR,13C-NMR,all kinds of 2D-NMR,CD spectra and X-ray diffraction analysis are used to determine the structure of the isolated compounds;several enzymes linked immunosorbent assay are used to test the biological activities of some isolated compounds.Results 30 alkaloids were isolated and identified from Sinomenium acutum of which 8 are new compounds;nine alkaloids were isolated and identified from Menispermum dauricum of which 6 are new compounds;six alkaloids were isolated and identified from Stephania epigaea.Among all the identified alkaloids,six compounds show protective effects against hydrogen peroxide induced cell injury;eight compounds show weak or strong cytotoxicity activity;one compound shows neuroprotective effect against hydrogen peroxide and.β-amyloid25-35-induced oxidative injury.Conclusion These three plants of Menispermaceae family may be considered as the potential drugs for Alzheimer's disease therapy and anticancer agents.

Acute and Sub-Acute Toxicological Evaluations of Bioactive Alkaloidal Extract from Melodinus henryi and Their Main Chemical Constituents

Melodinus henryi is a good source of terpenoid indole alkaloids,and traditionally used as a folk medicine in the treatment of meningitis and fracture.In order to further exploit their potential uses,its anti-inflammatory and immunosuppressive activi-ties,safety evaluations and chemical profiles have been illustrated.Compared to the crude methanol extract from M.henryi and its non-alkaloidal fraction,the total alkaloidal fraction(MHTA)had the strongest anti-inflammatory and immunosup-pressive activities.In the acute oral toxicity assay,the half lethal dose(LD50)of MHTA was more than 2000 mg/kg.The sub-acute toxicity assay for consecutive 28 days exhibited MHTA at a lower concentrations of less than 500 mg/kg might be regarded as safe,and might damage spleen,liver,kidney,and heart when the dose is higher than 1000 mg/kg.In addition,a phytochemical investigation on MHTA led to the isolation of 15 monoterpenoid indole alkaloids.Thus,in regard with the potent side effects of MHTA,it should be used with caution in the development of phytomedicine.

DNA G-Quadruplexes as Targets for Natural Product Drug Discovery

DNA guanine(G)-quadruplexes(G4s)are unique secondary structures formed by two or more stacked Gtetrads in G-rich DNA sequences.These structures have been found to play a crucial role in highly transcribed genes,especially in cancer-related oncogenes,making them attractive targets for cancer therapeutics.Significantly,targeting oncogene promoter G4 structures has emerged as a promising strategy to address the challenge of undruggable and drug-resistant proteins,such as MYC,BCL2,KRAS,and EGFR.Natural products have long been an important source of drug discovery,particularly in the fields of cancer and infectious diseases.Noteworthy progress has recently been made in the discovery of naturally occurring DNA G4-targeting drugs.Numerous DNA G4s,such as MYC-G4,BCL2-G4,KRAS-G4,PDGFR-b-G4,VEGF-G4,and telomeric-G4,have been identified as potential targets of natural products,including berberine,telomestatin,quindoline,sanguinarine,isaindigotone,and many others.Herein,we summarize and evaluate recent advancements in natural and nature-derived DNA G4 binders,focusing on understanding the structural recognition of DNA G4s by small molecules derived from nature.We also discuss the challenges and opportunities associated with developing drugs that target DNA G4s.

The Clausena lansium genome provides new insights into alkaloid diversity and the evolution of the methyltransferase family

Wampee(Clausena lansium)is an important evergreen fruit tree native to southern China that has a long history of use for medicinal purposes.Here,a chromosome-level genome of C.lansium was constructed with a genome size of 282.9 Mb and scaffold N50 of 30.75 Mb.The assembled genome contains 48.70%repetitive elements and 24,381 protein-coding genes.Comparative genomic analysis showed that C.lansium diverged from Aurantioideae 15.91-24.95 million years ago.Additionally,some expansive and specific gene families related to methyltransferase activity and S-adenosylmethionine-dependent methyltransferase activity were also identified.Further analysis indicated that N-methyltransferase(NMT)is mainly involved in alkaloid biosynthesis and O-methyltransferase(OMT)participates in the regulation of coumarin accumulation in wampee.This suggested that wampee's richness in alkaloids and coumarins might be due to the gene expansions of NMT and OMT.The tandem repeat event was one of the major reasons for the NMT expansion.Hence,the reference genome of C.lansium will facilitate the identification of some useful medicinal compounds from wampee resources and reveal their biosynthetic pathways.

Identification and Molecular Characterization of the Alkaloid Biosynthesis Gene Family in Dendrobium catenatum

As one of the main active components of Dendrobium catenatum, alkaloids have high medicinal value. The physicochemicalproperties, conserved domains and motifs, phylogenetic analysis, and cis-acting elements of the genefamily members in the alkaloid biosynthesis pathway of D. catenatum were analyzed by bioinformatics, and theexpression of the genes in different years and tissues was analyzed by qRT-PCR. There are 16 gene families,including 25 genes, in the D. catenatum alkaloid biosynthesis pathway. The analysis of conserved domains andmotifs showed that the types, quantities, and orders of domains and motifs were similar among members ofthe same family, but there were significant differences among families. Phylogenetic analysis indicated that thegene family members showed some evolutionary conservation. Cis-acting element analysis revealed that therewere a large number of light-responsive elements and MYB (v-myb avian myeloblastosis viral oncogene homolog)-related elements in these genes. qRT-PCR showed that expressions of gene family members involved in alkaloidsynthesis were different in different years and tissues of D. catenatum. This study provides a theoretical basisfor further exploration of the regulatory mechanisms of these genes in the alkaloid biosynthesis of D. catenatum.

Study of the Effectiveness of Papaver Sp. Alkaloids as Future Therapeutic Alternatives against Enterococcus Sp. Causing Hospital-Acquired Septicemic Infections

Background and Objective: In recent years, control of Enterococcus sp. It has been proven in the local medical environment to be a cause of acquired septicemia in various age groups, and medical instruments are considered an effective means of transmitting enterococcal septicemia, and catheters are at the forefront in terms of danger. Based on this risk, this study aimed to monitor the spread of Enterococcus sp., which causes blood poisoning acquired from catheters, and to compare its response to antibiotics with that of those isolated from clinical samples in children, as a first study locally. The effectiveness of alkaloids of different types of Papaver sp. In Syrian plants, they were tested against infection with this bacteria. Materials and Methods: The study dealt with two parts: The first part included collecting clinical samples from the University Children’s Hospital in Damascus/bacterial diagnostic laboratories/then isolating and diagnosing the bacteria by following a set of tests to identify the most prevalent genera and species and comparing their prevalence rate with Enterococcus. The second part;It included collecting plant samples, confirming the species taxonomically, then extracting alkaloids from plant parts (fruit, stem, Flowers), then comparing the extent of resistance of bacterial strains to antibiotics compared to the Enterococcus sp., and then confirming the antibacterial activity of the Papaver sp. alkaloids against Enterococcus sp. Result:In its first part, the study confirmed the significant contribution of the Enterococcus sp. to infections acquired from various sources, largely in catheter tip infections (9.09%) and to a lesser extent in other sources (3.7%), The second part was to confirm the effective-ness of the alkaloid extract of the Papaver sp., especially the two species Papaver syriacum, and Papaver dubium, against Enterococcus sp. with areole diameters that ranged between (15 - 26 mm) for the fruit extract and at a minimum inhibitory concentration (3.12 - 6.25 mml) and then the stem (5 - 20 mm). And the effectiveness of the Flowers extract is very weak to almost non-existent. Conclusions: The catheter and medical sources surrounding the patient constitute a dangerous source of multi-resistant Enterococcus sp., which poses a real threat to the lives of children, with new mechanisms represented by colonization of the skin and the ability to form biofilms Surfaces of medical instruments, with are resistant to a wide range of antibiotics. As an alternative and effective modern source to limit its spread in the future, the alkaloid extract of the fruits and stems of the wild Papaver sp. has proven a strong antibiotic effect, especially the two types: Papaver syriacum and Papaver dubium.

Pharmacokinetics of Gelsemium elegans in female rats

Background:Gelsemium elegans Benth(G.elegans)is a poisonous perennial evergreen vine plant that has been applied in livestock production and veterinary clinical practice.Early studies found that the toxicity of G.elegans showed significant gender differences in rats,but the underlying reasons for this difference are still not well understood.Methods:In order to explore whether the gender differences in the toxicity of G.elegans are related to pharmacokinetic differences,based on the previous pharmacokinetic study of multiple components of G.elegans in male rats,this study used HPLC-MS/MS method established in the laboratory to conduct a pharmacokinetic study of multiple alkaloids in the plasma of female rats after a single gavage administration of G.elegans(dose of 0.1 g/kg).Results:Through detection,17 alkaloid components in the plasma of female rats were identified,and the pharmacokinetic parameters of 11 of these alkaloids were calculated.We find that in female rats.The T_(max)values were generally less than 0.5 h,and the T_(1/2)values exceeded 3 h,with the longest reaching up to 32.80 h half elimination time.Additionally,the C_(max)and AUC results indicated that female rats had generally higher absorption and exposure levels for most alkaloids.Conclusion:These results suggest that the reason for the differences in the toxicology of G.elegans may be related to the absorption and exposure of gelsemidine-type alkaloids in animals.

Synergistic effect of pinellia total alkaloids and uncaria total alkaloids on anticonvulsant action in mice and rats

Aim To investigate the synergistic effect of the combination of pinellia total alkaloid （PTA） and uncaria total alkaloid （UTA）, and explore the mechanism of anticonvulsant action. Methods Anticonvulsant and toxic effect profiles of combinations of PTA with UTA, alone and at three fixed ratios of 1：4, 1 ：1, 4：1, were evaluated in maximal electroshock （MES）-induced seizures and acute toxicity test in mice. Respective ED50 and LD50 were calculated with Bliss＇s method. Their synergistic effect were evaluated by isobolographic analysis and allowed the determination of benefit indices （BI） for respective combinations. The model of convulsive rats kindled by penicillin topically injected into cortex was used to investigated the content of Glu, Asp, Gly and GABA in hippocampus using high performance liquid chromatography （HPLC）. Results Combinations of PTA and UTA at the ratio of 4：1 were synergistic in MES test and antagonistic in acute toxicity test, showing the best profile for combinations of PTA with UTA. In contrast, the ratios of 1 ：4 and 1 ： 1, despite synergistic in MES test, were additive in acute toxicity test. The 4：1 combination and two drugs alone significantly decreased Glu level and increased GABA level in the hippocampus, but the GABA level in the 4：1 combination group was higher than that in the two drugs alone groups. They did not have significant influence on the levels of ASp and Gly. Conclusion Combinations of PTA and UTA at 4：1 ratio demonstrated synergistic effect in anticonvulsant action and antagonistic effect in toxicity. The anticonvulsant mechanism might be related to decreasing the excitability of Glutamatergic neurons and increasing the inhibition of GABAergic neurons.

Two Novel Hydroperoxylated Lycopodium Alkaloids from Huperzia serrata

Two novel hydroperoxylated Lycopodium alkaloids, 11alpha-hydroperoxyphlegmariurine B (1) and 7-hydroperoxyphlegmariurine B (2), along with a known compound, phlegmanurine B (3), were isolated from the total alkaloid fraction of the Chinese medicinal herb Huperzia serrata (Thunb.) Trev. Their structures and relative configurations were elucidated on the basis of spectroscopic analyses.

Effect of Potato Extract on its Phenolic Metabolism,SAGs Accumulation and Allelopathic Autotoxicity

[Objective] The paper was to study the effect of potato extract on its phenolic metabolism,SAGs accumulation and allelopathic autotoxicity.[Method] With water treatment as control,the effects of aqueous extracts of potato bud,leaf-stem and tuber on its morphological characteristics,phenolic metabolism,glycoside alkaloids accumulation and allelopathic autotoxicity were studied.[Result] After the treatment of aqueous extract,the germination rate of potato reduced,germination was delayed,the plants became smaller,and the growth of root slowed down;the content of phenolic substances in roots,stems and leaves of potato increased,glycoside alkaloids accumulated,the activity of PPO and PAL increased.The effects of aqueous extract treatment on germination,growth,phenolic metabolism,glycoside alkaloid content and allelopathic autotoxicity successively were bud extractleaf-stem extracttuber extractcontrol.Treatment of aqueous extract did not affect the distribution of phenolic substances and glycosidic alkaloid in potato.[Conclusion] Phenolic substances and glycosidic alkaloid involved in the allelopathic autotoxicity of aqueous extract of potato,which had inhibition effect on germination and growth of potato.

Isolation and Identification of Eleven Tertiary Alkaloidsin Corydalis decumbens

Eleven tertiarv alkaloids were isolated from Corvdalis decumbens rhizome Their structures were identified as protopine(Ⅶ),allocryptopine(Ⅷ),cryptopine (Ⅸ),muramine(ⅩⅦ);(+)-tetrahydropalmatine(Ⅲ),(+)-kikemanine (Ⅳ),(一)-scoulerine (ⅩⅧ),(十)-bulbo- capnine (ⅩⅨ),and(一)一capnoidine(Ⅰ),(一)一bicuculline(Ⅴ),(+) coriumidine(ⅩⅣ), respecti vely。 Among these,cryptopine,muramine,(+)-kikemanine,(-)-scoulerine,(一)capnoidine,(一)一bicuculline were isolated for the first time from this plant

Total Synthesis of Anisodine

Aim To design a practical synthetic route of anisodine. Methods Starting from3α-hydroxy-6β-acetyltropine, anisodine was synthesized in 11 steps. Result Anisodine wasobtainded with an overall yield of 2.6 % . Conclusion Total synthetic route of anisodine wasachieved which may afford a possible route for commercial preparation of anisodine.

Expression of Recombinant Tryptophan Decarboxylase in Different Subcellular Compartments in Tobacco Plant

The gene encoded for tryptophan decarboxylase (TDC), which is the key enzyme in terpenoil indole alkaloids pathway, was targeted to different subcellular compartments and stably expressed in transgenic tobacco (Nicotiana tabacum L.) plants at the levels detected by Western blot and tryptamine accumulation analysis. It was shown that the TDC was located in subcellular compartments, the chloroplasts and cytosol. The recombinant TDC targeted to chloroplasts and cytosol in tobacco plants was effectively expressed as soluble protein by Western blot analysis and enzymatic assay. The level of tryptamine accumulation in chloroplast was higher than that in cytosol and very low in vacuole and endoplasmic reticulum (ER) to be hardly detected by Western blot analysis. It was indicated that the highest amount of tryptamine was in chloroplasts, lower in endoplasmic reticula and the lowest in vacuoles as compared to those in wild type plants. The TDC targeted to different subcellular compartments of tobacco plants and its expression level were studied by different nucleotide sequences coding signal peptides at 5'-end of tdc gene in order to know the effects of the TDC in compartmentation on its functionality.

微波加工对附子中酯型生物碱的影响

[目的]探讨微波加工对附子中双、单酯型生物碱含量的影响,为附子新型炮制品及药食两用加工品的开发提供参考。[方法]通过正交设计、直观分析和方差分析,探讨烫漂时间(A)、干燥温度(B)和微波时间(C)对附子中双、单酯型生物碱含量的影响。[结果]微波时间对双酯型生物碱含量具有极显著影响(P<0.01),对单酯型生物碱含量具有显著影响(P<0.05);烫漂时间和干燥温度仅对双酯型生物碱含量具有显著影响(P<0.05)。最佳的因素水平组合为A3B3C3,即烫漂时间为3 min,干燥温度为60℃,微波时间为5 min;在此条件下,双酯型生物碱含量为590.33μg/g,单酯型生物碱含量为802.14μg/g。[结论]微波加工能够降低附子中双酯型生物碱含量,增加单酯型生物碱含量。

Kiridine, A C18-Diterpene Alkaloid from Aconitum kirinense

Kiridine, a new C18-diterpenoid alkaloid, was isolated from the roots of Aconitum kirinense. Its structure was elucidated by MS, 1D- and 2D- NMR, and mono-crystal X-ray analysis. It is the first norditerpene alkaloid containing a 9,14-methylenedioxy group and the substituent at C-14 is (-configuration.

The Alkaloids from Leaves of Croton hemiargyerius var. gymnodiscus

Aim Investigation of alkaloids from the leaves of Brazilian medicinal plantCroton hemiargyerius var. gymnodiscus. Methods Silica gel column chromatography was used repeatedlyfor the isolation and purification, and their structures were identified by extensive spectroscopyand comparison of the chemical and physical data with those of authentic samples reported inliterature. Results Twelve alkaloids were isolated and their structures were identified. ConclusionFour new alkaloids named hemiargines A (1), B (5), C (6) and D (7), together with eight knownalkaloids namely isoc-orydine (2), corydine (3), norcorydine (4), salutaridine (8), glaucine (9),tetrahydropalmatrubine (10), xylopinoine (11), and norlaudanosine (12) were isolated.

Insecticidal Activities of Alkaloids Extracted from Poisonous Plants

[Objective] Insecticidal activities of alkaloids extracted from 12 poisonous plants in Changbai Mountain were studied in the paper,to provide the basis for development and utilization of poisonous plants in Changbai Mountain.[Method] Leaf disc method was used to study the effects of alkaloids extracted from 12 poisonous plants on the growth and development of 3-5 instars of cabbage worm （Pieris rapae） and their antifeedant activities.[Result] The effects of alkaloids extracted from different poisonous plants on the growth and development of cabbage worm were also different.Five treatments of alkaloids extracted from Sophora flavescens,Datura stramonium L.,Arisaema amurense Maxim.,Veratum dahuricum Loes.and Tripterygium regelii Spragne et Takeda made the weight of test insects gradually decrease and finally die;the alkaloid treatments of Pueraria lobata （Willd.） Ohwi,Aconitum kusnezoffii Reichb.,Cimicifuga dahurica （Turcz.） Maxim.and Corydalis ambigua Schleeht.could make cabbage worm pupate ahead of time,but the pupa state was deformed;the antifeedant rates of cabbage worm after the treatments of P.lobata,A.kusnezoffii,C.dahurica,A.amurense,V.dahuricum and C.ambigua for 48 h were all over 90%,and the antifeedant rates of C.dahurica and C.ambigua were the highest as 100%.[Conclusion]The reports on the insecticidal activities of five poisonous plants including P.lobata,A.kusnezoffii,C.dahurica,C.ambigua and A.amurense are rare,and they have important values on the development of botanical pesticides.

Norditerpenoid Alkaloids from Delphinium orthocentrum (Ranunculaceae)

Two new norditerpenoid alkaloids, orthocentrine (1) and deacetylswinanine A (2), together with a known alkaloid, swinanine A (3), were isolated from the whole plants of Delphinium orthocentrum Franch. The structures of the new alkaloids (1 and 2) were elucidated as 7,10_dihydroxy_8,14,16_trimethoxy_19,20_didehydro_aconitane (7β,8β,14α,16β) (1) and 20_ethyl_2,3_didehydro_6,10_dihydroxy_7,8_methylenedioxy_1,14,16_trimethoxy_aconitane (1α,6β,14α,16β) (2) by spectroscopic evidence and chemical transformation.

苦地丁总生物碱对小鼠Ⅱ型胶原关节炎的影响

目的探讨苦地丁对小鼠Ⅱ型胶原关节炎的影响。方法小鼠尾根部皮内注射Ⅱ型胶原乳剂建立小鼠关节炎模型(CIA),苦地丁总生物碱(50,100,200mg·kg-1组灌胃给药,每日1次;模型组和空白组灌胃给予等量蒸馏水;实验结束时考察各组临床积分、发病时间、血清中抗-CⅡ抗体含量、胶原所致耳廓DTH;ELISA法检测PGE2、TNF-α、IL-1的水平。结果苦地丁剂量依赖性延迟CIA小鼠的发病时间,减少关节的肿胀和红斑,缓解CIA小鼠体质量减轻,降低小鼠血清中抗-CⅡ抗体水平,抑制CⅡ诱导的小鼠耳廓迟发型超敏反应;明显抑制巨噬细胞释放肿瘤坏死因子(TNF-α)、白介素1(IL-1),但对前列腺素(PGE2)的产生无明显影响。结论苦地丁对小鼠CIA有明显的抑制作用。

Abnormal Secondary Growth and Histochemical Localization of Alkaloids in Root System of Aconitum flavum Hand.-Mazz.

[Objective] The purpose of this study was to clarify the structure,growth pattern and histochemical localization of alkaloids in root system of Aconitum flavum Hand.-Mazz.[Method] Paraffin sectioning and histochemistry were employed for performing the analysis in this study.[Result] The root system of Aconitum flavum Hand.-Mazz.consists of taproot,lateral root and adventitious root.The primary structure of root system is normal,but secondary structure shows abnormal.The cambium and the extra cambium of taproot form a ＂U＂-shaped secondary vascular bundle and tertiary bundle in abnormal secondary structure.The sieve tube group is made of little sieve tube group which is differentiated from primary phloem and cambium.Meanwhile,the secondary xylem in tuberous root also appears to be a ＂U＂ shape.Parenchyma cells of secondary phloem occupy most of the tuberous root.The sieve tube group of tuberous root is mainly differentiated from parenchyma cell of secondary phloem.[Conclusion] The difference in abnormal secondary structure of taproot and tuberous root are attributed to their varied cambium compose and activity pattern.Alkaloids are mainly accumulated in parenchyma cell of the inside cortex and between bundle in taproot,while parenchyma of secondary phloem and pith in tuberous root.