Liensinine
Liensinine
CAS: 2586-96-1
Molecular Formula: C37H42N2O6
Liensinine - Names and Identifiers
Liensinine - Physico-chemical Properties
| Molecular Formula | C37H42N2O6 |
| Molar Mass | 610.74 |
| Density | 1.218±0.06 g/cm3(Predicted) |
| Melting Point | 95-99 °C |
| Boling Point | 722.0±60.0 °C(Predicted) |
| Specific Rotation(α) | (c, 0.883 in Me2CO)+15.85 |
| Flash Point | 390.4°C |
| Solubility | Soluble in chloroform, methanol and ethanol, insoluble in ether and water. |
| Vapor Presure | 1.53E-21mmHg at 25°C |
| Appearance | White amorphous powder |
| Color | White to Off-White |
| pKa | 9.28±0.45(Predicted) |
| Storage Condition | -20°C Freezer, Under inert atmosphere |
| Refractive Index | 1.618 |
| MDL | MFCD03427702 |
| Physical and Chemical Properties | Soluble in chloroform, methanol and ethanol, insoluble in ether and water. The germ is derived from the mature seed of the nellaceae lotus (Nelumbo nucifera Gaevth.). |
Liensinine - Reference
| Reference Show more | 1. Zhou Jiang Wu Tingting Li Meiyun Lei Xiaoxiao Tang Ting Guihui. Optimization of Preparation and Characterization of Liensinine Hydroxypropyl-β-Cyclodextrin Inclusion Compound by Box-Behnken Design-Effect Surface Methodology [J]. Chinese Journal of Traditional Chinese Medicine Information 2016 23(03):80-84. 2. Li Meiyun, Lei Xiaoxiao, Zhou Jiang, Tang Ting, Gui Hui. Optimization of formulation of osmotic pump controlled release tablets by star point design-effect surface methodology [J]. Chinese herbal medicine, 2016,47(18):3204-3210. 3. Tang Ting, Wu Tingting, Zhou Jiang, et al. Study on stability of liensinine-PVP-K30 solid dispersion [J]. Shi Zhen Guo Yi Guo Yao, 2014, 025(012):2907-2908. 4. Xu Bin, Zhang Tianyu, Tan Ning, etc. liensinine promotes apoptosis of bladder cancer 5637 cells and enhances Caspase-7 expression and activation [J]. Tianjin medicine, 2015(07):724-727. 5. Tang ting, Peng maijiao, Zhou Jiang, et al. preparation technology of liensinine solid dispersion [J]. journal of Hunan university of traditional Chinese medicine, 2014(04):13-16. 6. Tang ting, Yan hang, Zhou Jiang, et al. Characterization of liensinine solid dispersion and determination of dissolution in vitro [J]. Chinese patent medicine, 2015, 37(008):1853-1855. 7. Tang Ting, Zhou Jiang, Liao Qiong, et al. in vitro dissolution of liensinine solid dispersion and inclusion compound and pharmacokinetic study in rats [J]. Chinese pharmacy, 2015, 026(016):2260-2262. 8. Zhao Wenfang, Li Hui, Pan Siyi, et al. Effect of Membrane Combination on Separation of Active Components in Lotus Seed Heart Water Extraction [J]. Chinese Journal of Food Science, 2017, 17(008):165-169. 9. Sui Yue, He Xiaoshuang, wang Sicen. Determination and Extraction Optimization of Three Major Alkaloids in Lotus Seed Heart [J]. Chinese Pharmaceutical Journal, 2018, 53(22):22-28. 10. Liu Shijun, Yang Rui, Zhang Yu, Song Zhongxing, Cui Chunli, Xu Hongbo, Liu Hongbo, Zhang Junwu, Wang Shaocheng. Study on Changes of Main Active Components before and after Fastening of Jujube [J]. Shaanxi Agricultural Sciences, 2020, v.66;No.481(08):37-39. 11. Sun Chenglong, Liu Wei, Guo Lanping, Wang Xiao. Analysis of Tissue Distribution of Metabolites in Lotus Seeds Based on MALDI Mass Spectrometry [J]. Journal of Analytical Testing, 2021,40(01):86-91. 12. Liu Shijun, Yang Rui, Zhang Yu, Song Zhongxing, Cui Chunli, Xu Hongbo, Liu Hongbo, Zhang Junwu, Wang Shaocheng. Changes of Main Active Components before and after Fastening of Jujube [J]. Shaanxi Agricultural Sciences, 2020,66(08):34-36. 13. Liu Shijun, Lu Jing, Zhang Yu, Song Zhongxing, Cui Chunli, Xu Hongbo, Liu Hongbo, Zhang Junwu, Wang Shaocheng. Effect of Sand Hot on Main Active Components of Jujube [J]. Journal of traditional Chinese medicine, 2021,36(02):394-398. 14. [IF = 5.279] Xianbao Deng et al."Analysis of Isoquinoline Alkaloid Composition and Wound-Induced Variation in Nelumbo Using HPLC-MS/MS." J Agr Food Chem. 2016;64(5):1130-1136 15. [IF = 0] Pang Liang et al."Protective effect of liensinine on periodontitis through its antioxidant effect in mice." J Korean Soc Appl Bi. 2015 Dec;58(6):927-936 16. [IF = 4.171] Siyu Xie et al."Liensinine Inhibits Beige Adipocytes Recovering to white Adipocytes through Blocking Mitophagy Flux In Vitro and In Vivo." Nutrients. 2019 Jul;11(7):1640 17. [IF = 1.842] Tu Yiyuan et al."Impact of harvesting time on the chemical composition and quality of fresh lotus seeds." Hortic Environ Biote. 2020 Aug;61(4):735-744 18. [IF = 5.165] Juanning Ren et al."Qualitative and quantitative analysis of multi-components in Xing-Su-Ning Capsules for quality improvement." Arab J Chem. 2022 Jun;15:103825 |
Liensinine - Reference Information
| Background and Overview | Lotus Nelumbo nucifera Gaeertn is an important Chinese herbal medicine. Its leaves can clear summer heat and dampness, stop bleeding, and its stems can widen the middle and regulate qi. The efficacy of lotus seed heart is mainly for antihypertensive effect. The "Compendium of Materia Medica" records that its nature and taste are bitter and cold, and it has the effect of clearing the heart and removing heat. Therefore, it is basically positioned as a drug that acts on the cardiovascular system, especially anti-arrhythmia. It is reported that lotus seed heart mainly contains alkaloids such as liensine (liensinine), neferine (neferine), isoliensine (isoliensinine) and flavonoids such as luteolin and rutin. In the lotus seed heart, the high-content phenolic alkaloid-liensinine is a diazepine isoquinoline mono-ether bond alkaloid, which is a kind of limited distribution in the plant kingdom, diverse structure types, and physiological activities. The benzyl carbon in this type of alkaloid molecule is at the β position of the nitrogen atom and is easily oxidized by oxidants (such as potassium permanganate) or photooxidation occurs in the presence of O2 and ultraviolet lamp irradiation; when H2O2 is used as an oxidant, the nitrogen atom will be protonated, and the product is generally a mixture of N-oxides; this product can be reduced to the original alkaloid under the action of 6% H2SO3 or zinc powder; when metal sodium/liquid ammonia As a reducing agent, the ether bond can be broken and reduced and cracked; under the condition of aprotic solvent, sodium phenothiol can convert the hydrohalate of the alkaloid into the original alkaloid. Because this kind of alkaloid molecule contains phenolic hydroxyl group, it can also undergo O-acylation reaction with acylating agents such as acid anhydride, acid chloride, and carboxylic acid. Modern studies have shown that liensinine has a variety of cardiovascular activities such as lowering blood pressure, slowing heart rate, inhibiting myocardial contractility, anti-arrhythmia, etc.; it can also reduce lipid peroxidation damage and protect myocardial injury in rats with ischemia-reperfusion. Liensinine can reduce the production of lipid peroxide MDA, enhance serum SOD and GSH-Px activities, thereby reducing a series of cell damage reactions caused by free radicals; it can also effectively increase the local ATP content in the cerebral ischemia area, reduce the lactic acid content, and significantly improve the energy metabolism of cerebral ischemia tissue, thereby improving the neurological dysfunction of cerebral ischemia-reperfusion rats and reducing the scope of cerebral infarction. |
| pharmacological action | antiarrhythmic liensinine 5 mg/kg, iv, can significantly resist arrhythmia induced by aconitine in rats and ouabain in guinea pigs; It can also prevent the occurrence of ventricular fibrillation in guinea pigs caused by epinephrine, and can also resist arrhythmia caused by myocardial ischemia and reperfusion in rats. Liensinine 85mg/kg,iv, it can slow down the heart rate and prolong the P-R interval in rabbits. Liensinine 30 μmol/L can prolong the functional refractory period of isolated guinea pig left atrium. Liensinine slows down the heart rate and prolongs the ventricular diastole, which is conducive to blood perfusion from the epicardial area to the intimal area, improving ischemia and hypoxia; inhibiting myocardial contraction, reducing afterload, thereby reducing myocardial oxygen consumption, Conducive to the anti-arrhythmia effect. Liensinine has an effect on myocardial slow response action potential and slow inward current. 10~100 μmol/L can reduce the slow response action potential amplitude (APA) and zero-phase maximum rise rate (Vmax) of isolated rabbit sinus node (SAN) pacemaker cells in a concentration-dependent manner, prolong sinus circumference (SCL), and its effect is stronger than quinidine at the same concentration. It can also significantly antagonize Bay k8644, increase the APA and Vmax effects of SAN pacemaker cells and high K +-induced slow response action potentials in guinea pig papillary muscles, and liensinine 1~100 μmol/L can inhibit the slow inward flow of canine Purkinje fibers in a concentration-dependent manner. It can also resist the effect of acetylcholine on shortening the action potential duration, which all suggest that liensinine has an inhibitory effect on the transmembrane transport of Na +, K + and Ca2 +. Using the patch clamp full recording method, it was found that liensinine has the effect of concentration-dependent blocking L-type calcium channel current in guinea pig ventricular myocytes, which may be one of the important mechanisms of liensinine against various experimental arrhythmias. Antihypertensive Liensinine has a short-term antihypertensive effect. After intravenous injection of liensinine 10 mg/kg to the cat, the blood pressure immediately dropped to the original level 40%, while the electrocardiogram showed tachycardia, but it recovered within 10~20min. About 20min after administration of 100 mg/kg into the 12-finger intestine, the blood pressure began to drop. After observation for 2 hours, the blood pressure dropped to the 30% of the original level and the heart rate slowed down. The antihypertensive effect and effective action time of liensinine are dose-dependent, which is basically the same as the antihypertensive effect of the same dose of neferine (another alkaloid extracted from the lotus seed heart), but the effective action time is shorter than that of neferine. Experiments show that the effect of liensinine on diastolic blood pressure is greater than systolic blood pressure, suggesting that the main action site of the drug is in the peripheral blood vessels, not the central effect. Inhibition of smooth muscle contraction liensinine has different degrees of inhibition on the contraction of rabbit aortic rings caused by phenylephrine (P E), 5-hydroxytryptamine (5-HT) and histamine (His), and its inhibition effect on PE-induced contraction is more obvious. Liensinine can also inhibit the contraction of rabbit urethral smooth muscle caused by PE. On the isolated rabbit aortic ring and rat anal-caudal muscle, it can make the α1 receptor agonist methoxyamine and PE dose-effect parallel to the right. The maximum response remains unchanged. The measured PA2 values are 6.8 and 6.6, respectively, indicating that liensinine has high selectivity to α1 receptors and is competitive antagonistic; it also significantly inhibits the release of internal calcium caused by norepinephrine (NE), but has little effect on the internal calcium flow caused by NE, and has the effect of inhibiting the release of intracellular calcium. |
| extraction and separation | the extraction methods of liensinine include ion exchange resin method, membrane separation method, water extraction method, methyl (B) alcohol solvent cold leaching method and methanol solvent reflux method. the main common method is methanol solvent cold leaching method. 1. methanol solvent cold leaching method: the dried lotus seed core is ground into coarse powder, soaked with appropriate amount of methanol, methanol is recovered, the residual liquid is adjusted to pH 2~3 with 3% hydrochloric acid, filtered, the filtrate is degreased with diethyl ether, the concentrated ammonia water is adjusted to pH 9 or more, diethyl ether is extracted, and water-insoluble total alkali is obtained from the ether layer; Dissolve in appropriate amount of chloroform, filter, extract phenolic components with 3% sodium hydroxide from the filtrate, and separate the alkaline water layer, adjust the pH above 9 with ammonium chloride saturated solution, and then extract with ether to recover the ether to obtain the phenolic total alkali; take an appropriate amount of the phenolic total alkali on a silica gel column with thin layer chromatography (using the standard as a control) Check, combine the same components, after concentration under reduced pressure, extract with 5% hydrochloric acid, separate the water layer, adjust the pH to 9 with concentrated ammonia water to a large amount of flocculent precipitation, extract with ether, wash the ether to neutral, and recover the ether under reduced pressure, the white loose amorphous powder obtained by vacuum drying is liensinine. 2. water extraction method: including water extraction reflux method, water extraction alcohol precipitation method and semi-bionic extraction method, semi-bionic extraction alcohol precipitation method, acid percolation extraction method. 1) Water extraction and reflux method: The dry extract heavy water extraction method that uses atmospheric pressure heating reflux method combined with ether extraction to obtain Lianxin total alkali is a low-cost and easy-to-operate extraction method, but Lianxin The solubility of alkali in water is low, and pure water is directly used to extract Lianxin alkali. The water consumption is large, the extraction efficiency is low, and the extract yield is not ideal. The process is as follows: 2) water extraction and alcohol precipitation method: this method is based on the water extraction and reflux method, adding the calculated amount of ethanol to make the ethanol concentration in the water extraction solution reach 60%. Let stand for 24 hours, filter with filter paper, the filtrate is recovered to the end of ethanol, the volume is fixed, and the extract is obtained. 3) semi-bionic extraction method: the operation is also similar to the water extraction and reflux method. only water with pH values of 5.0, 6.0 and 8.0 is used for the first, second and third times of extraction, and semi-bionic extraction solution is prepared according to law to obtain extract. It is better than water extraction, water extraction and alcohol precipitation and semi-bionic alcohol precipitation. 4) semi-bionic extraction alcohol precipitation method: on the basis of semi-bionic extraction method, the calculated amount of ethanol is added to make the ethanol concentration reach 60%. Let stand for 24 hours, filter with filter paper, the filtrate is recovered to the end of ethanol, the volume is fixed, and finally the extract is obtained. 5) acid percolation extraction method: percolation method is a leaching method in which the medicinal material powder is immersed and expanded for 24~48 h, and then new solvent is continuously added to make it permeate through the medicinal material from top to bottom and flow out from the lower part of the percolator and collect the leaching solution. 3. ion exchange resin method strong acid cation exchange resin was used to exchange and adsorb the total base of lotus. Before going to the column, use 2‰ HCl solution to percolate and acidify the lotus seed powder to make the alkaloid molecule positively charged; then the column is used to exchange the cation of the alkaloid salt with the hydrogen ion on the resin and separate from other components and impurities; Finally, use 10% ammonia to alkalize to obtain free alkaloids. After the resin is dried, it is eluted by ether reflux. The final yield is 1.1%, and the effect is ideal. 4. membrane separation method membrane separation process includes microfiltration, ultrafiltration, nanofiltration, reverse osmosis, etc. Because the relative molecular mass of liensinine and chlorophyll is close, the separation effect of the two directly using membrane is poor. The salt generated by the reaction of liensinine and acid is dissolved in water, and chlorophyll is a kind of fat. According to its insoluble in water, the separation and pretreatment of chlorophyll in the alcohol extract is first carried out, and then three different materials are compared. The microfiltration membrane and an ultrafiltration membrane, through the stable permeation flux of the filtrate, the recovery rate of liensinine and the rate of chlorophyll rejection, and finally the improved polyethersulfone microfiltration membrane is selected to separate liensinine. On this basis, the cross-flow microfiltration method was used to improve the membrane technology of Liensinine separation by polyethersulfone membrane, and provided the basis for reducing membrane pollution and measures to improve the membrane filtration rate. |
| determination of content | 1. TLCS method 1) chromatographic conditions: silica gel G-CMCNa plate; Chloroform-diethylamine (9:1) is the developing agent; Inspection under 365nm ultraviolet light. 2) preparation of reference substance solution: precisely weigh liensinine and add methanol to make 1.23 mg/ml solution as reference substance solution. 3) preparation of sample solution: take 5g of lotus seed coarse powder, weigh it accurately, cold soak it in 100ml of methanol for 24, 12 and 12h, filter it into a 100ml volumetric flask and add methanol to dilute it to scale, and serve as sample solution. 4) determination: accurately measure 6 μl of sample solution, 2 μl and 6 μl of reference substance solution, cross spot samples on the same thin layer plate respectively, expand, take out, dry and locate. Scanning by thin layer scanning method, λ S = 223nm,λ R = 300nm; Sawtooth scanning by reflection method; SX = 3; Sensitivity × 5. 5) determination results: the content of liensinine in lotus seed core was 0.939% (cold soaking method) and 0.853% (reflux method). 2. HPLC method 1) chromatographic conditions: the column Ultrasphere Si 4.6mm × 250mm; Mobile phase: dichloromethane-isopropanol-diethylamine (70:30:0.2); Flow rate: 1 ml/min; Detection wavelength: 282nm. 2) preparation of reference substance solution: accurately weigh the dried to constant weight of liensinine, isoliensinine and neferine, and add methanol respectively to prepare solutions containing 0.1mg, 0.01mg and 0.04mg respectively per milliliter as reference substance solution. 3) preparation of sample solution precisely weigh 1.0g of the ground lotus seed core, place it in a 100ml volumetric flask, add methanol for cold dip for 12h, then extract it by ultrasonic wave for 45min, take 5ml of supernatant after placement, dilute it to 10ml with mobile phase, shake well, and take it as sample solution. 4) determine 20 μl of sample solution and 20 μl of reference solution for accurate absorption, sample injection and content calculation. 5) chromatogram a. standard; B. sample; I. liensinine; II. Isoliensinine; III. Neferine 6) Determination results |
| pharmacokinetics | the main pharmacokinetic parameters are T1/2α = 8.303min, indicating that the drug is distributed rapidly from the central chamber to the peripheral chamber. T1/2β = 129.961min indicates faster drug excretion or metabolism. The apparent distribution volume Vc of the central chamber is 2.768L/ kg, accounting for 37.16% of the total apparent distribution volume Vss, this shows that the drug is widely distributed, which may be related to its strong fat solubility and easy entry into tissue cells. Cl = 0.0452 ml/min,AUC = 132.671 μg/(min • ml). |
| stability | the stability of liensinine injection was studied by classical constant temperature acceleration experiment method. the results showed that its decomposition reaction was in line with the first-order reaction, and its activation energy was 75030J /mol,T25 ℃ 0.9 was only 3mo,T10 ℃ 0.9 was 15mo, which indicated that the product had poor stability and should be stored in the dark. |
| main reference materials | [1] Xu lei et al. research overview of liensinine. Chinese herbal medicine. 2000,31(22):956-957. [2] Yu Wangui et al. Antioxidant effect of liensinine on focal cerebral ischemia/reperfusion injury in rats. Pharmacology and clinic of traditional Chinese medicine. 2013;29 (2):32-35. [3] Huang xianju et al.. extraction and separation of liensinine by acid percolation. journal of Hubei medical college of health workers. 2002 ,15(3):51-52. [4] Chen changguo et al.. research progress in extraction and separation of liensinine. chemical industry and engineering technology. 2008, 29 (2):21-25. [5] Sun Wenji, edited by Xie Shichang; edited by Zhao Ye, Zhang Xingqun, Chen Qianliang, etc. Quantitative analysis of natural pharmaceutical ingredients. [6] Luo Shunde et al. Research overview and progress of liensinine. Chinese pharmacy. 2001,12(10):624-625. |
| use | used for content determination/identification/pharmacological experiments, etc. Pharmacological effects: lowering blood pressure. It has the effects of lowering blood pressure and anti-arrhythmia, and also has the effects of blocking adrenal alpha receptors and inhibiting intracellular calcium release. |
Last Update：2024-04-09 20:48:19
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