Molecular Formula | C38H44N2O6 |
Molar Mass | 624.77 |
Density | 1.185±0.06 g/cm3(Predicted) |
Melting Point | 59-61 °C |
Boling Point | 710.9±60.0 °C(Predicted) |
Specific Rotation(α) | -44.1°(c=0.301,chloroform) |
Flash Point | 383.8°C |
Solubility | DMSO: >15mg/mL |
Vapor Presure | 6.97E-21mmHg at 25°C |
Appearance | Amorphized loose yellowish powder (ether) |
Color | white to beige |
pKa | 9.28±0.45(Predicted) |
Storage Condition | 2-8°C |
Refractive Index | 1.601 |
MDL | MFCD01707128 |
Physical and Chemical Properties | Extraction from the green germ of the mature plant of the Lotus family |
WGK Germany | 3 |
RTECS | SM9495000 |
Reference Show more | 1. Wei Ping, Xue Chunmiao, Pan Lin, Lei Zhenzhen, Cao Junling. Effect of neferine on hypoglycemic effect of insulin resistant HepG2 cells [J]. Journal of Clinical and Experimental Medicine, 2020,19(12):1283-1286. 2. Zhao Wenfang, Li Hui, Pan Siyi, et al. Effect of Membrane Combination on Separation of Active Components in Lotus Seed Heart Aquatic Extract [J]. Chinese Journal of Food Science, 2017, 17(008):165-169. 3. 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. 4. Tu, Yixuan, Shoulei Yan, and Jie Li. "Impact of harvesting time on the chemical composition and quality of fresh lotus seeds." Horticulture, Environment, and Biotechnology 61.4 (2020): 735-744. 5. [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 6. [IF = 4.225] Zhao Ping et al."Neferine Promotes GLUT4 Expression and Fusion With the Plasma Membrane to Induce Glucose Uptake in L6 Cells." Front Pharmacol. 2019 Sep;0:999 7. [IF = 3.391] Yi Zhong et al."Neferine suppresses vascular endothelial inflammation by inhibiting the NF-κB signaling pathway." Arch Biochem Biophys. 2020 Dec;696:108595 8. [IF = 3.373] Na Zhang et al."TLC-MS identification of alkaloids in Leonuri Herba and Leonuri Fructus aided by a new developed universal derivatisation reagent optimised by the response surface method." Phytochem Analysis. 2021 May;32(3):242-251 9. [IF = 3] Qu Lala et al."Phenotypic assessment and screening of ETA/ETB receptors with label-free dynamic mass redistribution say." N-S Arch Pharmacol. 2020 Jun;393(6):937-950 10. [IF = 2.753] Nabila Jahan et al."Neferine improves oxidative stress and apoptosis in benign prostate hyperplasia via Nrf2-ARE pathway .." Redox Rep. 2021;26(1):1-9 11. [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 12. [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 |
Overview | neferine , Nef) is from the green germ of the mature seeds of the Nymphaeaceae plant (Nelumbo nuci fera Gaertn) A bisbenzyl isoquinoline alkaloid extracted from the seed is a new type of calcium channel blocker. Studies have found that methyllinine can enhance adriamycin's inhibition of human breast cancer cell proliferation, it is a chemotherapy sensitizer; it has anti-fibrosis effect and can significantly improve pulmonary fibrosis, kidney fibrosis, etc.; neferine also has vasodilation, blood pressure reduction, anti-arrhythmia, anti-platelet aggregation, Anti-thrombosis, anti-oxidation, anti-organophosphorus pesticide poisoning, anti-scar formation and other pharmacological activities. |
Source | Neferine (neferine , Nef) is derived from the green germ (lotus heart) of the mature seeds of the Nymphaeaceae plant (Nelumbo nuci fera Gaertn) Extracted. Lotus heart is also known as horns, bitter horns, and horns. The horns are slightly thin rod-shaped, 1.0~1.4cm long and 0.2cm in diameter. The young leaves are green, one long and one short, rolled into an arrow shape, the apex is folded downward, and small embryos can be seen between the two young leaves. The radicle is cylindrical, about 3mm long, yellow-white. The quality is brittle, easy to break, and there are several small holes in the section. The gas is slight and the taste is bitter. It mainly produces Hunan, Hubei, Fujian, Jiangsu, Zhejiang and other places. Fig. 1 is lotus heart |
physical properties | loose light yellow amorphous powder (ether), melting point 59-61 ℃,[α]D24-44.1 (c = 0.301, chloroform).: 283.4.: 3400(-OH),2915,1610,1510,1250,1210,1115. 1HNMR(CDCl3)δ:2.47,2.44 (3H,2 × N-CH3 each),3.78,3.70,3.68,3.51 (3H,4 × O-CH3 each),6.90~5.97(11H, aromatic-H),5.14 (1H, broad peak,-OH). MSm/z:625 (M 1). |
extraction and separation | people have used acid-base method, semi-bionic extraction alcohol precipitation method, acid percolation extraction method, ion exchange resin method, membrane separation method and other methods to extract and separate neferine from lotus seed. Take 500g of dried and purified lotus seed heart, grind it into coarse powder, pass through No.4 sieve, add 6 times the amount of methanol to soak at room temperature for 2 days, recover methanol, add the residue to 3% citric acid, add appropriate amount of activated carbon to filter, discard insoluble substances, add appropriate amount of ether to extract the filtrate, separate the ether layer, and adjust the water layer (pH is about 2.5) to turbid (pH is about 8.5) with ammonia water, then use ether to extract, separate the ether layer, extract until there is no alkaloid reaction, and evaporate the ether to obtain a light yellow solid, which is the total alkaloid in the lotus heart. Take an appropriate amount of lotus seed total alkali, dissolve it in an appropriate amount of chloroform, and extract it with a 2.5% concentration of sodium hydroxide solution at a volume ratio of 1:1, and take the chloroform layer to volatilize chloroform to obtain a yellow solid substance. It is methyl lienine. |
pharmacological effects | 1. vasodilation and antihypertensive effects of neferine can effectively reduce the blood pressure of various animals and with the increase of dose, its effect is strengthened and the action time is prolonged, indicating that it is an effective antihypertensive drug. The effect of neferine on reducing diastolic blood pressure is significantly greater than that of systolic blood pressure, and in the cat hindlimb constant-speed perfusion experiment, a small dose (0.6 mg · kg-1) of neferine without peripheral antihypertensive effect was used. It can significantly reduce the vascular resistance of the hind limbs, so it is believed that neferine has a direct dilation effect on vascular smooth muscle. In addition, in the isolated vascular ring experiment, it was found that neferine can antagonize the vasoconstriction caused by high potassium, which further confirmed that neferine has vasodilator effect. 2. Antiarrhythmic effect and effect on myocardial electrophysiological characteristics. Neferine can antagonize arrhythmia induced by ouabain and epinephrine, and can obviously prevent or reduce arrhythmia caused by coronary artery ligation and reperfusion in rats, indicating that neferine has antiarrhythmic effect. Using canine cardiac program-controlled stimulation electropharmacology model, it was found that neferine can also resist ischemic rapid ventricular arrhythmia. The antagonistic effect of neferine on these arrhythmias may be related to its inhibition of Na and Ca2 + transport in myocardial cells. 3. Anti-platelet aggregation and antithrombotic effects Neferine can dose-dependently inhibit ADP, collagen, and adrenaline (Adr)-induced platelet aggregation in humans, rats, and rabbits; in addition, Neferine can dose-dependently inhibit ADP and collagen-induced platelet aggregation in normal rats, renal hypertensive rats, and high-fat-fed rats, and can significantly prolong the time of carotid occlusive thrombosis in rats. In addition, neferine can significantly inhibit platelet aggregation in adult patients with hyperlipidemia induced by different inducers ADP, collagen and epinephrine (Adr) and has a good dose-effect relationship. The above shows that Nef has better anti-platelet aggregation and anti-thrombosis effects. 4. Antioxidation and Effects on Lipoprotein Oxidation Neferine is an effective plant-derived antioxidant. Although its O-2 scavenging effect is small SOD, the scavenging effect of OH is stronger than that of mannitol, a typical hydroxyl radical scavenger, and its scavenging effect is more obvious, indicating that it is mainly scavenging effect, but has little influence on the process of oxygen free radicals. Its mechanism of action may be related to the phenolic hydroxyl group contained in the molecular structure of neferine, and the hydrogen on the phenolic hydroxyl group is easily combined with oxygen free radicals to have antioxidant effects. Studies have shown that neferine has a protective effect on the isolated rat heart injured by electrolytic oxygen free radicals, and can significantly reduce the incidence of ventricular arrhythmia caused by electrolytic oxygen free radicals injured in the isolated rat heart, and reduce the release of lactate dehydrogenase and the production of MDA in myocardial cells. Neferine can reduce coronary flow caused by anti-oxygen free radicals, reduce left ventricular pressure (LVP) and ± dp/d tmax, and also have protective effects on vascular endothelial cell injury caused by oxygen free radicals, which may be related to its role in scavenging oxygen free radicals. 5. Chemotherapy sensitization of neferine Chemotherapy sensitization, also known as biochemical regulation, refers to the effect of drugs with no anti-tumor effect or little anti-tumor effect at the concentration used, which is known to have anti-tumor effects. The intracellular effect of the drug, thereby enhancing its killing on tumor cells or reducing its toxicity to normal cells. Studies have found that neferine, which has no obvious cytotoxic effect, can enhance the cytotoxic effect of adriamycin (ADM), fluorouracil (5-FU) and cisplatin (CDDP) on human breast cancer cells, and can enhance the inhibitory effect of ADM on human osteosarcoma, indicating that it has certain chemotherapy sensitizing effect. The sensitizing concentration of neferine does not significantly induce apoptosis of tumor cells, but it can significantly enhance the effect of adriamycin-induced apoptosis. Enhancing the apoptosis induced by anticancer drugs may be one of the sensitizing mechanisms of neferine. 6. The anti-organophosphorus poisoning effect of neferine. Organophosphate poisoning is the most common clinical poisoning. Anticholinergic drugs and cholinesterase (ChE) reenergies are organophosphorus pesticide poisoning and even organophosphorus nerve agent poisoning Effective therapeutic drugs. For lethal doses of dichlorvos and trichlorfon poisoned mice, the effect of neferine alone is similar to that of atropine alone, and it has a definite protective effect, and the protective effect of neferine is significantly better than that of chlorophos. This indicates that neferine has a definite anti-organophosphorus poisoning effect. The authors also observed that neferine showed a strong reactivation effect on the highly inhibited ChE activity of the poisoned mice, and the required dose of chlorophor at a level of comparable reactivation intensity was 1.25 times that of neferine. This suggests that before the phosphorylase is completely "aged", neferine may have a stronger effect than chlorphosphazine to detach the phosphoryl group from the toxic enzyme and restore it. 7. The anti-scarring effect of neferine Scar formation is the inevitable outcome of wound healing, but excessive scar proliferation will affect the appearance and physiological function. The prevention and treatment of excessive scar proliferation has always been a major problem in medical research. Scar hyperplasia is closely related to the growth and metabolism of fibroblasts. Neferine can inhibit the proliferation of scar fibroblasts cultured in vitro in a concentration-dependent manner, indicating that neferine may have potential anti-hypertrophic scar effect. The intracellular calcium ion concentration can stimulate the division of fibroblasts, change the balance of collagen synthesis and catabolism and the synthesis of extracellular matrix. Neferine may play a negative regulatory role in the growth of scar fibroblasts by reducing the intracellular calcium ion concentration. |
pharmacokinetic study | rats were given 20mg kg-1 of neferine by gavage. the metabolites and their pathways in rat liver were studied by liquid chromatography-tandem mass spectrometry and high performance liquid chromatography-ultraviolet detection. In the positive ion detection mode, in addition to neferine, a total of 4 metabolites M1, M2 (the main metabolites), M3 and M4. Among them, M2 and M4 were confirmed to be liensinine and isiliensinine by chromatography and mass spectrometry comparison with the reference substance, while M1 and M3 may be desmethylliensinine and desmethylisiliensinine. Ketoconazole, a specific inhibitor of CYP3AI, and quinidine, a specific inhibitor of CYP2DI, can inhibit the metabolism of neferine in the body temperature incubation fluid of liver particles, and the inhibition rates of the main metabolite liensine are 25.7% and 80.5%, respectively. It shows that both CYP2D1 and CYP3A1 are involved in the conversion of neferine into neferine. The metabolism of neferine is mainly O-demethylation, and CYP3A1 catalyzed by CYP2D1 is also partially involved in the reaction. |
use | for content determination/identification/pharmacological experiments and other pharmacological effects: calcium antagonism, antiarrhythmic effect, antihypertensive effect, inhibition of myocardial slow ion flow, anti-tumor promotion effect, anti-platelet aggregation. |