Product name: Neferine
Synonym name: 4''-O-Methylliensinine; Methylliensinine
Catalogue No.: BP0987
Cas No.: 2292-16-2
Formula: C₃₈H₄₄N₂O₆
Mol Weight: 624.778
Botanical Source: Nelumbo nucifera Gaertn.
Physical Description:
Type of Compound: Alkaloids

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle


The product could be supplied from milligrams to grams
Inquire for bulk scale.

Description:

Neferine, a autophagy inducer, which has anti-amnesic, sedative, anti-anxiety, antidepressant, cardioprotective, anti- pulmonary fibrosis,anti-cancer, antioxidant and anti-inflammatory capacities. It inhibited ChEs, BACE1, NF-kappaB, PI3K/Akt/mTOR pathway, Neferine has effects similar to rosiglitazone in decreasing fasting blood glucose, insulin, TG, TNF-alpha and enhancing insulin sensitivity in insulin resistant rats.

References:

Eur J Pharmacol. 2012 Feb 29;677(1-3):47-54.    

Neferine, an alkaloid ingredient in lotus seed embryo, inhibits proliferation of human osteosarcoma cells by promoting p38 MAPK-mediated p21 stabilization.    

Identification of natural products that have antitumor activity is invaluable to the chemoprevention and therapy of cancer. The embryos of lotus (Nelumbo nucifera) seeds are consumed in beverage in some parts of the world for their presumed health-benefiting effects. 

METHODS AND RESULTS:

In this report we studied the effects of Neferine, a major alkaloid component in lotus embryos, on human osteosarcoma cells and the underlying mechanisms. We found that Neferine possessed a potent growth-inhibitory effect on human osteosarcoma cells, but not on non-neoplastic human osteoblast cells. The inhibitory effect of Neferine on human osteosarcoma cells was largely attributed to cell cycle arrest at G1. The induction of G1 arrest was p21(WAF1/CIP1)-dependent, but was independent of p53 or RB (retinoblastoma-associated protein). The up-regulation of p21 by Neferinewas due to an increase in the half-life of p21 protein. We examined four kinases that are known to affect the stabilization of p21, and found that p38 MAPK and JNK were activated by Neferine. However, only SB203580 (an inhibitor of p38), but not SP600125 (the inhibitor of JNK), can attenuate the up-regulation of p21 in response to Neferine. Furthermore, the p21-stabilizing effect of Neferine was abolished when p38 was silenced by RNA interference. Finally, we showed that Neferine treatment led to an increased phosphorylation of p21 at Ser130 that was dependent on p38. 

CONCLUSIONS:

Our results for the first time showed a direct antitumor effect of Neferine, suggesting that consumption of Neferine may have cancer-preventive and cancer-therapeutic benefit.    

J Ethnopharmacol. 2009 Jul 6;124(1):98-102.    

Neferine enhances insulin sensitivity in insulin resistant rats.   

Neferine was isolated from green seed embryo of Nelumbo nucifera Gaertn which has been used as an anti-obesity agent in traditional Chinese herbal medicine. This study was conducted to investigate the effects of Neferine on enhancing insulin sensitivity in insulin resistant rats compared with rosiglitazone and to potentially reveal its role in mediating the anti-obesity properties of Nelumbo nucifera Gaertn. 

METHODS AND RESULTS:

Fasting blood glucose (FBG), fasting blood insulin (FINS), triglycerides (TG) and tumor necrosis factor-alpha (TNF-alpha) were measured, and the oral glucose tolerance test for 2-h plasma glucose level (2-h PG) was carried out. The glucose infusion rate (GIR) was used to measure the insulin sensitivity by hyperinsulinemic euglycemic clamp technique. The levels of FBG, FINS, TG, TNF-alpha and 2-h PG all decreased significantly in the rosiglitazone and Neferine groups compared with the insulin resistance (IR) model group. Neferine diminished the 2-h PG more than did rosiglitazone treatment. Compared to the IR model group, the treatments of Neferine and rosiglitazone remarkably increased GIRs but no difference between these two treatments themselves was evident. 

CONCLUSIONS:

These data demonstrate that Neferine has effects similar to rosiglitazone in decreasing fasting blood glucose, insulin, TG, TNF-alpha and enhancing insulin sensitivity in insulin resistant rats.    

Phytomedicine. 2008 Dec;15(12):1117-24.    

Effects of extracts and neferine from the embryo of Nelumbo nucifera seeds on the central nervous system.    

The effects of embryos of the seeds of Nelumbo nucifera on the central nervous system were studied in mice. 

METHODS AND RESULTS:

MeOH extracts of embryos of Nelumbo nucifera seeds significantly inhibited locomotor activity in mice. The MeOH extract was successively partitioned between H(2)O and n-hexane, between H(2)O and CHCl(3), and between H(2)O and n-BuOH. CHCl(3) extracts strongly inhibited locomotor activity in mice, although other extracts had no effect on locomotor activity. The main alkaloid of CHCl(3) extracts, Neferine, dose-dependently inhibited locomotor activity in mice. Neferine induced hypothermia in mice and apparently potentiated thiopental-induced sleeping time. An anxiolytic, diazepam, decreased locomotor activity, rectal temperature and enhanced sleep elicited by thiopental, similar to Neferine. In addition, Neferine and diazepam showed anti-anxiety effects in the elevated plus maze test. Neferine did not affect muscle coordination by the rota-rod test. Neferine did not affect strychnine- nor picrotoxin-induced seizure. In contrast, diazepam had apparent muscle relaxant and anti-convulsant effects. 

CONCLUSIONS:

These results suggest that Neferine has several central effects and that Neferine may participate in the efficacy of the sedative effects of embryos of the seeds of Nelumbo nucifera. The mechanisms of the sedative effects of Neferine are not similar to those of diazepam.    

Cardiovasc Toxicol. 2013 Jun;13(2):168-79.    

Protective effect of neferine against isoproterenol-induced cardiac toxicity.    

The present study was designed to investigate the cardioprotective effect of Neferine against isoproterenol-induced myocardial infarction. 

METHODS AND RESULTS:

Neferine was given orally for 30 days, and isoproterenol was injected subcutaneously for 2 days. Histopathological examination of heart tissue of isoproterenol-treated rats showed myocardial necrosis. Biochemical analysis of isoproterenol-treated rats showed significant increase in the serum marker enzymes--creatine kinase, lactate dehydrogenase, and aspartate transaminase and increased serum glycoprotein components with a concomitant decrease in the heart tissue homogenate when compared to control. Increased lipid peroxidation and decreased antioxidants reduced glutathione, superoxide dismutase, catalase, glutathione-S-transferase, glutathione peroxidase and altered lipid profile in serum and tissue was also recorded in the isoproterenol-treated rats, whereas the rats which received Neferine pre-treatment followed by isoproterenol injection showed minimal histological changes, absence of inflammation, and a significant decrease in the serum marker enzymes and serum glycoprotein components with a concomitant increase in the heart tissue homogenate when compared to isoproterenol group. Neferine pre-treatment restored the altered biochemical parameters and lipid profile to near normal. 

CONCLUSIONS:

The results of the present study showed that Neferine exerts strong antioxidant property against isoproterenol-induced oxidative stress and can be used as a potent cardioprotective agent against isoproterenol-induced myocardial infarction.    

HPLC of Neferine

HNMR of Neferine

Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃

Introduction/Overview

Neferine, also known as methyl lotus heart alkaloid, is a typical bibenzyl isoquinoline alkaloid, mainly isolated from the seeds of the genus Nelumbo (Nelumbo nucifera Gaertn.). As one of the main active ingredients in traditional Chinese medicine lotus seeds, lotus flower alkaloid has attracted widespread attention in the field of natural product pharmacology in recent years due to its diverse biological activities and potential medicinal value. Especially in the prevention and treatment of cardiovascular diseases, lotus alkaloid demonstrates significant protective effects, with its mechanism closely related to various cellular signaling pathways and molecular targets.

The pharmacological activities of lotus root cover multiple aspects, including anti-inflammatory, antioxidant, anti-fibrotic, antitumor, and neuroprotective effects, with particularly strong inhibitory effects on the nuclear factor κB (NF-κB) signaling pathway. NF-κB is a key regulator of inflammatory responses and cell survival, and its abnormal activation is closely related to the occurrence and development of various cardiovascular diseases. Lotus alkaloids demonstrate good cardiovascular protective potential by regulating NF-κB and its downstream targets.

This paper systematically reviews the chemical structure and physicochemical properties of lotus alkalin, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation and pharmacokinetic characteristics, and conducts an in-depth discussion in conjunction with its clinical application prospects, aiming to provide scientific basis and theoretical support for the drug development and clinical application of this natural product.

Chemical structure and physicochemical properties

Neferine has the chemical formula C38H44N2O6 and a molecular weight of 624.7780, belonging to the bibenzyl isoquinoline alkaloids. Its structural feature is that two isoquinoline units are connected by methyl bridges, forming a dimeric structure with high molecular complexity and stereochemical characteristics. This structure endows lotus alkalin with unique biological activity and the ability to bind to multiple targets.

In terms of physicochemical properties, the LogP value of alkaloid is 6.4982, indicating high hydrophobicity and extremely low water solubility (0.0146 mg/mL), which significantly affects its absorption and distribution in the body. Its polar surface area (TPSA) is 72.86 Ų, suggesting that the molecule has certain polar groups that facilitate interaction with biomacromolecules. The blood-brain barrier penetration ability is relatively low, indicating limited distribution in the central nervous system.

Additionally, lotus root exhibits hERG channel inhibitory activity, suggesting a possible cardiotoxicity risk and requiring special attention during drug development. The Ames test result was 0.0, indicating no significant genotoxicity and relatively high safety.

Plant Origins and Extraction Methods

Lotus root is mainly found in the seeds (lotus seeds) and lotus heart of the lotus plant Nelumbo nucifera. Lotus seeds, as a traditional Chinese medicinal material, have a long history and are widely used in the field of traditional Chinese medicine. The content of alkaloid varies depending on plant species, growing environment, and harvest period.

The extraction method typically combines organic solvent extraction with column chromatography technology. Common extraction solvents include methanol, ethanol, and their aqueous solutions. The general steps are as follows:

1. Crush the dried lotus seeds or cores.
2. 70%-95% ethanol is used for reflux extraction, with extraction time generally lasting 2-4 hours.
3. After concentration and cooling for crystallization, the extract is further purified by silica gel column chromatography or high-performance liquid chromatography (HPLC).
4. Pure products are confirmed for structure through mass spectrometry (MS), nuclear magnetic resonance (NMR), and other methods.

In recent years, the application of new technologies such as ultrasound-assisted extraction and microwave-assisted extraction has improved the extraction efficiency and purity of alkalin, laying the foundation for its industrial production.

Pharmacological activity research

Cardiovascular protective effects

Lotus alkaloid exhibits multiple protective effects in the cardiovascular system. Numerous in vivo and in vitro experiments have shown that lotus root can significantly improve myocardial ischemia-reperfusion injury, reduce myocardial cell apoptosis, suppress inflammatory responses, alleviate myocardial fibrosis, and regulate vasomotor function.

Specifically, it is reflected in:

• Inhibits platelet aggregation and reduces the risk of thrombosis.
• Promotes endothelial nitric oxide synthase (eNOS/NOS3) activity, enhancing vasodilation.
• Regulates potassium channel function (such as KCNH2), stabilizes myocardial electrical activity, and prevents arrhythmias.
• Inhibits the expression of vascular endothelial cell adhesion molecules (ICAM1, VCAM1), reducing infiltration of inflammatory cells.
• Regulates calcium homeostasis (SLC8A1) in myocardial cells and protects myocardial function.

Anti-inflammatory and antioxidant activities

Lotus alkaloids reduce the expression of pro-inflammatory cytokines (such as TNF-α and IL-6) by inhibiting the NF-κB signaling pathway, thereby alleviating inflammatory responses. Additionally, its antioxidant effects include scavenging free radicals, inhibiting lipid peroxidation, and protecting cells from oxidative damage.

Other pharmacological effects

In addition to cardiovascular protection, lotus root also exhibits multiple biological activities such as anti-tumor, neuroprotective, and anti-fibrotic properties, making it possible for multi-target drug development.

Mechanism of action and molecular targets

The pharmacological effects of lotusine mainly occur through regulation of multiple signaling pathways and key molecular targets. Its core mechanism of action focuses on inhibiting NF-κB activation, thereby regulating downstream inflammation and the expression of genes related to cell survival.

NF-κB signaling pathway inhibition

NF-κB serves as a hub for inflammatory responses and is involved in various cardiovascular pathological processes. Lotus alkaloids block the phosphorylation and degradation of IκBα, inhibit NF-κB nuclear translocation and DNA binding activity, reduce the transcription of pro-inflammatory genes, and achieve anti-inflammatory protection.

Key molecular targets

• SELP (Selectin P): Lotus alkaloids reduce SELP expression, decrease the interaction between platelets and endothelial cells, and inhibit thrombosis.
• PPARG (Peroxisome Proliferator-Activated Receptor γ): Activates PPARG to promote lipid metabolism and anti-inflammatory responses; lotus alkaloids may improve metabolic cardiovascular diseases by modulating PPARG activity.
• ACE (angiotensin-converting enzyme): Lotus alkali inhibits ACE activity, reduces angiotensin II production, and lessens vasoconstriction and cardiac burden.
• AKT1 (protein kinase B): By activating the AKT1 signal, lotus alkaloid promotes cell survival and anti-apoptosis, protecting heart muscle cells.
• ADRB2 (β2 adrenergic receptor): Regulates myocardial contraction and vasodilation; lotus alkaloids may regulate cardiovascular function through ADRB2.
• KCNH2 (hERG potassium channel): The inhibitory effect of alkaloid on hERG channels suggests its potential impact on heart rhythm regulation.
• NOS3 (endothelial nitric oxide synthase): enhances NOS3 activity, promotes NO production, and improves vascular function.
• ICAM1 and VCAM1 (cell adhesion molecules): Inhibit their expression to reduce adhesion and infiltration of inflammatory cells.
• SLC8A1 (sodium-calcium exchanger): regulates intracellular calcium homeostasis and protects cardiomyocyte function.

In summary, lotus root achieves complex pharmacological effects through multi-target and multi-pathway synergistic effects, demonstrating the advantages of multi-target regulation in natural products.

Druggability evaluation and pharmacokinetics

The drug-making properties of lotus root are influenced by its physicochemical properties and biological activity. High hydrophobicity (LogP 6.4982) and extremely low water solubility limit its oral bioavailability, requiring drug formulation technologies such as nanocarriers and liposomes to improve absorption in vivo.

The low permeability of the blood-brain barrier suggests it mainly acts on peripheral tissues, reducing the risk of central nervous system side effects. HERG channel inhibition suggests potential cardiotoxicity and requires special attention in preclinical safety evaluations.

A negative Ames test indicates a low genotoxicity risk and good safety. Current pharmacokinetic studies show that lotus root is absorbed slowly and widely distributed after oral administration, but its metabolic pathways and excretion mechanisms still require further study.

Prospects and outlooks for clinical applications

Given the multi-target effects of lotus root in cardiovascular protection and its excellent anti-inflammatory and antioxidant properties, its development prospects as an adjunct therapy for cardiovascular diseases are promising. Future research should focus on:

• Further clarification of the pharmacokinetic characteristics and metabolic mechanisms of lotusine.
• Optimize formulation technology to improve bioavailability and targeting.
• Systematically assess their safety, especially the risks associated with cardiotoxicity.
• Combining modern molecular pharmacological methods, this paper deeply analyzes its multi-target mechanism of action.
• Conduct clinical trials to verify its efficacy and safety in coronary heart disease, hypertension, myocardial ischemia, and other diseases.

Moreover, the multiple biological activities of lotus root provide potential applications in fields such as oncology and neurodegenerative diseases, which are worth further exploration.

Conclusion

Lotus alkaloids, derived from traditional Chinese medicine lotus seeds, are bibenzyl isoquinoline alkaloids, and demonstrate promising potential for drug development due to their significant NF-κB inhibitory effects and multi-target cardiovascular protective activity. Although there are certain challenges in its physicochemical properties and safety, modern drug design and formulation technologies are expected to overcome these limitations and achieve clinical translation.

In the future, combined with systematic pharmacological mechanism research and clinical validation, lotus root is expected to become an important candidate in the development of natural product drugs, providing new strategies and options for cardiovascular disease prevention and treatment.