Chemical properties & pharmacological effects of Neferine

Abstract

Neferine is a natural bisbenzylisoquinoline alkaloid, mainly extracted from plants of the Nelumbo family (such as lotus seed embryo). In recent years, its wide range of biological activities (such as cardiovascular protection, anti-tumor, antioxidant, etc.) has attracted the attention of researchers. This paper reviews its chemical structure, pharmacological mechanism and potential applications, and looks forward to future research directions.

1. Introduction

Neferine has a long history in traditional medicine. Lotus seed heart (embryo) is recorded in the Compendium of Materia Medica as a medicinal material for clearing heat, calming the nerves and lowering blood pressure. As one of the main active ingredients of lotus seed heart, neferine exhibits diverse biological activities due to its unique bisbenzylisoquinoline structure. With the rise of natural product research, the pharmacological potential of neferine has gradually been revealed.

2. Chemical properties

Methyl neferine (C₃₈H₄₄N₂O₆, CAS number: 2292-16-2) belongs to the bis-benzylisoquinoline alkaloids, which are composed of two benzylisoquinoline units connected by ether bonds (Figure 1). It has a large molecular weight (624.77 g/mol) and high lipid solubility. It can be separated and purified from lotus seed germ by high performance liquid chromatography (HPLC) or mass spectrometry.

3. Pharmacological effects and mechanisms

3.1 Cardiovascular system protection

1. Anti-arrhythmic: By inhibiting the L-type calcium channel (LTCC) and delayed rectifier potassium channel (IK) of myocardial cells, it regulates the action potential duration and reduces the risk of arrhythmia.

2. Anti-hypertension and vasodilation: It activates the nitric oxide (NO) signaling pathway, promotes the release of NO by endothelial cells, and leads to relaxation of vascular smooth muscle.

3. Anti-thrombosis: Inhibits platelet aggregation induced by platelet activating factor (PAF) and reduces the risk of thrombosis.

3.2 Antioxidant and anti-inflammatory

- Scavenges free radicals: Neutralizes reactive oxygen species (ROS) through phenolic hydroxyl structure and reduces oxidative stress damage.

- Inhibits inflammatory factors: Downregulates NF-κB pathway, reduces the release of pro-inflammatory factors such as TNF-α and IL-6, and shows protective effects in acute lung injury models.

3.3 Anti-tumor activity

- Induce apoptosis: Activates mitochondrial apoptosis pathway (such as Bax/Bcl-2 imbalance, caspase-3 activation), inhibits breast cancer MCF-7 cell proliferation.

- Inhibits metastasis: Inhibits lung cancer A549 cell invasion and migration by blocking PI3K/Akt/mTOR pathway.

3.4 Neuroprotective effect

- Anti-Alzheimer's disease (AD): Reduce β-amyloid protein (Aβ) deposition, inhibit tau protein hyperphosphorylation, and improve cognitive dysfunction in mice.

4. Applications and challenges

4.1 Traditional and modern applications

- Traditional Chinese medicine uses: Lotus seeds are used to make tea to reduce internal heat and calm the nerves.

- Modern drug development: As a lead compound, explore the application of its derivatives in anti-tumor or cardiovascular diseases.

4.2 Safety and limitations

- Toxicity: Animal experiments show low acute toxicity (LD₅₀ > 2 g/kg), but long-term use may affect liver and kidney function.

- Bioavailability: High lipid solubility but poor water solubility, and the absorption rate needs to be improved through nanoformulation or structural modification.

5. Future research directions

1. Clinical transformation: Promote clinical trials to verify its efficacy on human diseases (such as hypertension and cancer).

2. Structural optimization: Enhance targeting and reduce side effects through chemical modification.

3. Multi-omics research: Combine metabolomics and proteomics to analyze its multi-target mechanism of action.

6. Conclusion

As a natural active molecule, neferine has multi-target and multi-pathway pharmacological properties and has significant potential in the treatment of cardiovascular diseases, tumors and neurodegenerative diseases. In the future, it is necessary to strengthen the connection between basic and clinical research and promote its application from laboratory to clinical application.

References ：

1. Deng Y, et al. *Neferine inhibits colorectal cancer cell growth through ROS-mediated PI3K/Akt pathway*. Cancer Lett. 2019.

Liu CM, et al. *Neferine induces apoptosis by modulating Bcl-2 family proteins in human breast cancer cells*. Phytomedicine. 2020.

3. Chinese Pharmacopoeia Commission. *Pharmacopoeia of the People’s Republic of China*. 2020 Edition.