石蒜碱抗炎作用研究进展

石蒜碱是从传统药用植物石蒜鳞茎中分离出的生物碱成分.已有研究表明石蒜碱具有良好的抗炎作月除对多种炎症模型都有明确的防治作用外,石蒜碱还可抑制LPS诱导的炎症相关诱导酶类的合成以及多种炎症质的释放.在石蒜碱抗炎的分子机制方面,石蒜碱可显著抑制脂多糖（LPS）诱导的P38和STATs通路的激活,而ERK1/2,JNK1/2和NF-κB通路无影响.     

石蒜鳞茎的新用途

石蒜科植物石蒜、水仙等的鳞茎,含有多种生物碱,既有毒又具有一定的药用价值。如水仙鳞茎捣烂可敷治痈肿,提取物有抗癌和抗病毒作用;石蒜鳞茎有祛痰、利尿、解毒、催吐作用,亦可作农药。     

红花石蒜生物碱成分研究

我们实验室的前期研究发现红花石蒜中的石蒜西啶类生物碱具有较强的抗烟草花叶病毒(TMV)活性,为进一步研究其作用机制,开展了对红花石蒜化学成分的研究。从红花石蒜中共分离的到11个化合物,通过波谱数据结合理化性质鉴定(~1H NMR、~(13)C NMR、2D NMR、HR-ESI-MS)分别鉴定为pancratinine D(1)、小星蒜碱(2)、8-O-去甲基高石蒜碱(3)、6α-O-甲基石蒜伦碱(4)、力克拉敏(5)、水仙花碱(6)、石蒜碱(7)、力克拉敏N-氧化物(8)、去甲基加兰他敏(9)、二氢石蒜碱(10)、文殊兰碱(11)。采用半叶枯斑法,对其中的三个化合物1、3、10进行了抗TMV活性筛选,发现均有一定的抗TMV活性。其中化合物3的抑制率超过阳性对照宁南霉素。     

石蒜科药用植物生物碱的药理学研究

石蒜科药用植物主要含生物碱成分,具有广泛的药理活性.参阅近十多年来国内外石蒜科生物碱化学成分及药理学的研究文献,对石蒜科植物生物碱的几种主要药理活性进行归纳.石蒜科植物生物碱药理作用主要包括对心血管系统作用、中枢神经系统作用、对多种癌细胞的细胞毒活性或抗肿瘤作用、抗炎抗菌、抗病毒、免疫功能等方面.石蒜科药用植物生物碱有着潜在而广泛的药用价值.     

南京地区两种石蒜不同生长时期中石蒜碱、加兰他敏和力可拉敏含量的比较

本试验采用薄层层析分离和分光光度法测定南京地区黄花石蒜和红花石蒜不同生长时期中三种生物碱的含量,黄花石蒜鳞茎中石蒜碱的含量:叶子出土期>开花初期>生长旺盛期>叶子变黄期。加兰他敏和力可拉敏的含量:开花初期>叶子出土期,生长旺盛期>叶子变黄期。开花初期的红花石蒜鳞茎中石蒜碱的含量多于黄花石蒜,而加兰他敏和力可拉敏则相反。黄花石蒜叶子变黄期的叶子中加兰他敏和力可拉敏的含量多于生长旺盛期,而在这两个时期的叶子中加兰他敏均多于力可拉敏。试验结果表明,南京地区两种石蒜在12月叶子出土期和8月开花初期的石蒜碱、加兰他敏和力可拉敏含量较高。此段期间采集药材似较适宜。黄花石蒜(Lycoris aurea Herb)和红花石蒜(Lycoris radiata Herb)均属于石蒜科(Amaryllidaceae)石蒜属,为多年生草本植物。上尾等曾系统地从红花石蒜中先后分出石蒜碱(Lycorine)、多花水仙碱(Tazettine)、伪石蒜碱(Pseudolycorien)、加兰他敏(Galanthamine)和力可拉敏(Lycoramine)等十多种生物碱。Boit等从黄花石蒜中分出石蒜碱和加兰他敏。中国科学院上海药物研究所洪山海等从紫花石蒜(Lycoris squamigera Maxim)鳞茎中分得19种结晶性生物碱。从石蒜属分出的多种生物碱,其中已知可供药用的有石蒜碱、加兰他敏和力可拉敏等。在一系列的药理研究中,已经证实,石蒜碱具有抗炎,解热和催吐等作用。加兰他敏和力可拉敏对胆碱酯酶具有抑制作用,力可拉敏季铵化后对外周胆碱能效应器的作用增强。石蒜碱、加兰他敏和力可拉敏在国内已进行生产,据有关单位称,得率不稳。本文的目的是分析南京地区两种石蒜不同生长时期中不同部位的石蒜碱、加兰他敏和力可拉敏的含量,这将为药材采集提供有益的资料。     

中国水仙中伪石蒜碱、石蒜碱的动态变化及其薄层定量

研究了中国水仙在三月初、六月初、八月中、十月中及十二月中鳞茎中伪石蒜碱、石蒜碱的含量变化,以及十一月下旬至五月中旬水仙地上部及鳞茎中该两种生物碱的月变化。鳞茎及地上部中两种碱的含量在十二月下旬水仙开花前均升高,之后下降;鳞茎中伪石蒜碱含量在三月下旬又迅速上升,石蒜碱却显著下降,四、五月份伪石蒜碱下降,而石蒜碱却上升。地上部中这两个碱,自二月份开始一直下降。伪石蒜碱和石蒜碱的含量变化和水仙生长发育关系密切。在开花后伪石蒜碱和石蒜碱之间消长似有相关性。 建议在十二月或三月全株采收以提取伪石蒜碱,可合理地利用水仙资源。     

伪石蒜碱、前多花水仙碱盐酸盐对细胞延长及分裂的抑制作用

目前已知石蒜科植物含有约一百五十种生物碱。其中有些生物碱具植物生长调节作用。Yamagu-chi (1953)曾以石蒜碱(Lycorinc)或石蒜裂碱(Lycorenine)处理蚕豆种子,降低其细胞分裂。Ceriotti(1967)从水仙鳞茎分离出一种生物碱Narciclasine,强烈抑制小麦侧根的生长,显示似秋水仙素的作用。Toshihiko(1968)从石蒜鳞茎分离得两个植物生长抑制剂Lycoricidinol和Lycoricidine,抑制燕麦胚     

夏枯草的化学成分及药理作用研究进展

夏枯草主要含有三萜及其苷类、甾醇及其苷类、黄酮类、香豆素、苯丙素、有机酸、挥发油及糖类等成分,具有降压、降糖、抗茵、抗炎、抗过敏及抗病毒等作用,近年来由于其明确的抗病毒及抗癌作用受到研究者的重视。     

石蒜属植物生物碱成分研究进展

石蒜属为东亚特有属。该属植物富含生物碱,且此类次生代谢产物具有细胞毒、抗疟疾、抗病毒以及对乙酰胆碱酯酶的抑制作用等活性。本文概述了该属中生物碱类成分的化学结构、药理活性及其生源途径。     

忽地笑中石蒜碱酶法提取及分离工艺研究

对复合酶法提取忽地笑石蒜碱的工艺进行优化,并用阳离子交换树脂分离石蒜碱。以纤维素酶与果胶酶的水溶液为提取溶剂,采用L9(34)正交试验考察了酶解p H、酶加入量、酶解时间和酶解温度等影响因素,以石蒜碱得率为指标,得最优提取工艺为:料液比1∶10,p H 4.5,酶添加量4%,酶解温度50℃,提取时间2.0 h,石蒜碱得率为0.1750%。D-001树脂纯化条件为:上样液p H为2,以3 BV/h流速上样,以含1.5 mol/L氨水的70%乙醇洗脱,流速为3 BV/h,初步分离后石蒜碱含量为15.28%。研究结果可为石蒜碱工业化生产提供参考。     

Lycorine,a non-nucleoside RNA dependent RNA polymerase inhibitor,as potential treatment for emerging coronavirus infections

Background: Highly effective novel treatments need to be developed to suppress emerging coronavirus (CoV) infections such as COVID-19. The RNA dependent RNA polymerase (RdRp) among the viral proteins is known as an effective antiviral target. Lycorine is a phenanthridine Amaryllidaceae alkaloid isolated from the bulbs of Lycoris radiata (L'Hér.) Herb. and has various pharmacological bioactivities including antiviral function.Purpose: We investigated the direct-inhibiting action of lycorine on CoV's RdRp, as potential treatment for emerging CoV infections.Methods: We examined the inhibitory effect of lycorine on MERS-CoV, SARS-CoV, and SARS-CoV-2 infections, and then quantitatively measured the inhibitory effect of lycorine on MERS-CoV RdRp activity using a cell-based reporter assay. Finally, we performed the docking simulation with lycorine and SARS-CoV-2 RdRp.Results: Lycorine efficiently inhibited these CoVs with IC₅₀ values of 2.123 ± 0.053, 1.021 ± 0.025, and 0.878 ± 0.022 μM, respectively, comparable with anti-CoV effects of remdesivir. Lycorine directly inhibited MERS-CoV RdRp activity with an IC₅₀ of 1.406 ± 0.260 μM, compared with remdesivir's IC₅₀ value of 6.335 ± 0.731 μM. In addition, docking simulation showed that lycorine interacts with SARS-CoV-2 RdRp at the Asp623, Asn691, and Ser759 residues through hydrogen bonding, at which the binding affinities of lycorine (−6.2 kcal/mol) were higher than those of remdesivir (−4.7 kcal/mol).Conclusions: Lycorine is a potent non-nucleoside direct-acting antiviral against emerging coronavirus infections and acts by inhibiting viral RdRp activity; therefore, lycorine may be a candidate against the current COVID-19 pandemic.     

Up-regulation of p21 and TNF-α is mediated in lycorine-induced death of HL-60 cells

Background  

Leukemia is one of the most life-threatening cancers today, and acute promyelogenous leukemia (APL) is a common type of leukemia. Many natural compounds have already been found to exhibit significant anti-tumor effects. Lycorine, a natural alkaloid extracted from Amaryllidaceae, exhibited anti-leukemia effects in vitro and in vivo. The survival rate of HL-60 cells exposed to lycorine was decreased, cell growth was slowed down, and cell regeneration potential was inhibited. HL-60 cells exhibited typical apoptotic characteristic. Lycorine can suppress leukemia growth and reduce cell survival and inducing apoptosis of tumor cells. The purpose of this work is to elucidate the mechanism by which lycorine induces APL cells.     

Further researches upon the inhibiting action of lycorine on ascorbic acid biosynthesis

Lycorine, an alkaloid extracted from Amarillidaceae, strongly inhibits the "in vivo" conversion of galactono-gamma-lactone to ascorbic acid. Lycorine seems to act as a non-competitive inhibitor on galactono-gamma-lactone oxidase, because the alkaloid rapidly forms a stable bound with the enzyme. In fact, a short incubation period with 50 microM lycorine gets a high inhibitory effect that persists when the alkaloid is removed from the incubation medium. Considering that lycorine induces scurvy-like symptoms in ascorbic acid-synthesising animals, it is reasonable to suppose that in both plants and animals lycorine inhibits the last step in the biosynthetic pathway leading from sugar to ascorbate.     

Lycorine induces cell death in the amitochondriate parasite, Trichomonas vaginalis, via an alternative non-apoptotic death pathway

In this study, the mechanism of action of the pro-apoptotic alkaloid lycorine on an amitochondriate cell, the parasite Trichomonas vaginalis, was investigated. The cytotoxicity of lycorine against T. vaginalis was studied from 2.5 to 1000 μM and several important ultrastructural alterations were observed by electron microscopy. Lycorine arrested the T. vaginalis cell cycle, although no hallmarks of apoptosis, such as apoptotic bodies, were observed. Consequently, the underlying mechanism of action fails to completely fulfill the criteria for apoptosis. However, some similarities to paraptotic cell death were observed.     

Lycorine inhibits breast cancer growth and metastasis via inducing apoptosis and blocking Src/FAK-involved pathway

Breast cancer is the most commonly diagnosed cancer type worldwide among women and more than 90% of patients die from tumor metastasis. Lycorine, a natural alkaloid, has been widely reported possessing potential efficacy against cancer proliferation and metastasis. In our study, the anti-tumor potency on breast cancer was evaluated in vitro and in vivo for the first time. Our results indicated that lycorine inhibited breast cancer cells growth, migration and invasion as well as induced their apoptosis.In in vivo study, lycorine not only suppressed breast tumor growth in xenograft models and inhibited breast tumor metastasis in MDA-MB-231 tail vein model. More importantly, we found lycorine had less toxicity than first-line chemotherapy drug paclitaxel at the same effective dose in vivo. Furthermore, on mechanism, lycorine inhibited tumor cell migration and invasion via blocking the Src/FAK(focal adhesion kinase)-involved pathway. In conclusion, our study implied lycorine was a potential candidate for the treatment of breast cancer by inhibition of tumor growth and metastasis.     

Lycorine,a natural alkaloid,promotes the degradation of alpha-synuclein via PKA-mediated UPS activation in transgenic Parkinson's disease models

BackgroundParkinson's disease (PD) is one of the most common neurodegenerative motor disorders, and is characterized by the presence of Lewy bodies containing misfolded α-synuclein (α-syn) and by selective degeneration of midbrain dopamine neurons. Studies have shown that upregulation of ubiquitin-proteasome system (UPS) activity promotes the clearance of aggregation-prone proteins such as α-syn and Tau, so as to alleviate the neuropathology of neurodegenerative diseases.PurposeTo identify and investigate lycorine as a UPS enhancer able to decrease α-syn in transgenic PD models.MethodsDot blot was used to screen α-syn-lowering compounds in an inducible α-syn overexpression cell model. Inducible wild-type (WT) and mutant α-syn-overexpressing PC12 cells, WT α-syn-overexpressing N2a cells and primary cultured neurons from A53T transgenic mice were used to evaluate the effects of lycorine on α-syn degradation in vitro. Heterozygous A53T transgenic mice were used to evaluate the effects of lycorine on α-syn degradation in vivo. mCherry-GFP-LC3 reporter was used to detect autophagy-dependent degradation. Ub-R-GFP and Ub-G76V-GFP reporters were used to detect UPS-dependent degradation. Proteasome activity was detected by fluorogenic substrate Suc-Leu-Leu-Val-Tyr-AMC (Suc-LLVY-AMC).ResultsLycorine significantly promoted clearance of over-expressed WT and mutant α-syn in neuronal cell lines and primary cultured neurons. More importantly, 15 days’ intraperitoneal administration of lycorine effectively promoted the degradation of α-syn in the brains of A53T transgenic mice. Mechanistically, lycorine accelerated α-syn degradation by activating cAMP-dependent protein kinase (PKA) to promote proteasome activity.ConclusionLycorine is a novel α-syn-lowering compound that works through PKA-mediated UPS activation. This ability to lower α-syn implies that lycorine has the potential to be developed as a pharmaceutical for the treatment of neurodegenerative diseases, such as PD, associated with UPS impairment and protein aggregations.     

Various sensitivities of yeasts to lycorine

Lycorine, an Amaryllidaceae alkaloid, is a powerful inhibitor of growth in higher plants and algae. Thirty-one strains of yeasts, belonging to different genera and species, were screened to study the effect of lycorine on their growth. The strains were incubated at 25 degrees C in a 2% glucose medium with different concentrations of lycorine (10, 50 and 100 microM), and their growth after 72 hours was evaluated. Most of the strains showed no sensitivity to lycorine. However, in Schizosaccharomyces pombe (IMAT-V Pbx) and Aureobasidium pullulans (DBV A77) lycorine significantly inhibited growth (59-73%), while, on the contrary, in Saccharomycopsis fibuligera (DBV 3812) and Cryptococcus terreus (CBS 1895) it was clearly stimulated (76-140%). The fact that lycorine inhibits growth in some yeasts while it stimulates it in others means that neither of the two previously formulated interpretations on the molecular mechanism of action of alkaloid can explain all cases. In other words, it does not seem that lycorine just inhibits protein synthesis, as claimed by Kukhanova et al. (1983), nor, on the other hand, do the data presented here prove that lycorine specifically inhibits ascorbic acid biosynthesis (Arrigoni et al., 1975). We must now check the ability of yeasts to split lycorine and study whether yeasts do actually have an ascorbic acid system.