Product name: Carpaine
Synonym name: Carpaine chloride
Catalogue No.: BP4124
Cas No.: 3463-92-1
Formula: C₂₈H₅₀N₂O₄
Mol Weight: 478.718
Botanical Source: Papaya Leaf
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

Storage: Store in a well closed container, protected from air and light. Put into refrigerate or freeze for long term storage.
Whenever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20℃. Generally, these will be useable for up to two weeks.

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

For Reference Standard and R&D, Not for Human Use Directly.

HPLC of Carpaine

NMR of Carpaine

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

Introduction/Overview

Carpaine is a natural alkaloid derived from the leaves of carica papaya and belongs to the major dilactone compounds. As the main active ingredient in papaya leaves, papain has attracted widespread attention in recent years due to its significant cardiovascular regulatory effects and potential anti-inflammatory properties. Natural products play an irreplaceable role in modern drug development, especially in the treatment of cardiovascular and inflammatory diseases. Papain, with its unique chemical structure and multi-target mechanism of action, demonstrates good pharmacological activity and high safety, making it an important candidate molecule for the research and development of novel herbal medicines.

This paper aims to systematically review the chemical structure and physicochemical properties of papain, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation, and pharmacokinetic characteristics, and to look ahead to its clinical application prospects, providing theoretical basis and research directions for subsequent basic research and clinical translation.

Chemical structure and physicochemical properties

Papain has a molecular formula of C_27H_43NO_6, a molecular weight of 478.7180, and a CAS number of 3463-92-1. Its chemical structure features the combination of the large dilactone ring system with the alkaloid backbone, exhibiting a typical cyclic lactone structure and nitrogen-containing heterocycle structure. This structure endows papain with unique physicochemical properties and biological activity.

In terms of physicochemical properties, papain has a LogP value of 4.5390, indicating strong lipophilic properties, which facilitate cell membrane penetration and distribution in vivo. The topological pole surface area (TPSA) is 76.6600, indicating moderate polarity that facilitates binding to biological macromolecule targets. Its low water solubility (0.3516 mg/mL) suggests limited solubility in the aqueous phase, which may affect its bioavailability. High permeability of the blood-brain barrier suggests it may have central nervous system activity or side effects. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. Ames mutagenicity test result was 0.0, indicating no significant genotoxicity and good safety.

In summary, the chemical structure and physicochemical properties of papain provide a foundation for its multi-target pharmacological effects, while also offering important references for drug design and formulation development.

Plant Origins and Extraction Methods

Papaya mainly occurs in the leaves of carica papaya L. Papaya is a widely cultivated economic crop in tropical and subtropical regions, with leaves rich in alkaloids, phenols, and other secondary metabolites. Papain, as the main alkaloid component, endows papaya leaves with significant pharmacological activity.

Traditional methods for extracting papain mainly include solvent extraction and acid-base extraction, and column chromatography separation. Generally, ethanol or methanol is used as extraction solvents, and extraction efficiency is improved through ultrasound-assisted extraction or reflux extraction. After concentration and acid-base adjustment, the extract is separated using organic solvents and purified using silica gel column chromatography or high-performance liquid chromatography (HPLC) technology, ultimately obtaining high-purity papayaline.

In recent years, with the development of green chemistry and efficient separation technologies, supercritical CO_2 extraction, microwave-assisted extraction, and membrane separation technologies have also been applied to the extraction and purification of papain, significantly improving extraction efficiency and purity, reducing the use of organic solvents, and meeting the environmental requirements of modern pharmaceutical production.

Pharmacological activity research

Cardiovascular protective effects

Papain, as a natural alkaloid, was first discovered to have significant cardiovascular regulatory effects. In vitro and in vivo experiments show that papain can dilate blood vessels, lower heart rate and blood pressure, improve myocardial ischemic damage, and exert heart-protective effects. Its mechanism involves multiple pathways, including calcium channel blockade, regulation of β-adrenergic receptors, and antioxidant stress.

In animal experiments, papain significantly reduced systolic and diastolic blood pressure in rats, improved myocardial ischemia-reperfusion injury, and decreased myocardial cell apoptosis. Additionally, papain can regulate calcium ion homeostasis within myocardial cells, inhibit myocardial hypertrophy and fibrosis, and demonstrate good heart-protective potential.

Anti-inflammatory activity

Inflammation is the core pathological process in many chronic diseases. Papain demonstrates good anti-inflammatory activity by modulating various inflammation-related targets. Both in vitro cell and animal inflammation models confirmed that papain significantly inhibits the expression of pro-inflammatory factors such as IL-6 and TNF-α, suppresses activation of inflammatory signaling pathways, and alleviates tissue inflammatory responses.

Specific targets include IL-6, STAT3, CASP1, TRPV1, PTGS1, PTGS2, TNF, TRPA1, NOS2, and NFKB1. Papain acts synergistically through multiple targets to inhibit the release of inflammatory mediators and activate inflammatory cells, reducing inflammatory damage and showing potential value in treating inflammatory diseases.

Other pharmacological activities

In addition to cardiovascular and anti-inflammatory effects, papain also exhibits certain antioxidant, antibacterial, and immunomodulatory activities. Research shows that papain can eliminate free radicals, strengthen the body's antioxidant defense system, and slow the progression of oxidative stress-related diseases. Additionally, it has inhibitory effects on certain pathogens, suggesting its potential application in infectious diseases.

Mechanism of action and molecular targets

The pharmacological effects of papain depend on its regulation of multiple molecular targets, reflecting the multi-target and multi-pathway nature of natural products.

Anti-inflammatory mechanism

• IL-6/STAT3 signaling pathway: IL-6, as a key pro-inflammatory cytokine, promotes inflammatory responses by activating the STAT3 transcription factor. Papain can inhibit IL-6 expression and STAT3 phosphorylation, blocking inflammatory signaling and reducing inflammatory responses.
• NFKB pathway: NFKB is a core regulator of inflammatory responses. Papain exerts anti-inflammatory effects by inhibiting NFKB1 activation and reducing the expression of pro-inflammatory genes.
• CASP1 and inflammasomes: CASP1 is involved in the activation of inflammasomes and regulates the maturation of the pro-inflammatory cytokine IL-1β. Papain inhibits CASP1 activity and blocks inflammatory responses mediated by inflammasomes.
• TRPV1 and TRPA1 ion channels: These two transient receptor potential ion channels are involved in transducting inflammation and pain signals. Papain alleviates inflammation-related pain and neuroinflammation by regulating TRPV1 and TRPA1 activities.
• PTGS1/PTGS2 (COX-1/COX-2): As prostaglandin synthase, PTGS1 and PTGS2 play key roles in the synthesis of inflammatory mediators. Papain inhibits its activity, reduces prostaglandin production, and alleviates inflammation.
• NOS2 (iNOS): Induced nitric oxide synthase participates in the production of large amounts of NO during inflammation; papain inhibits NOS2 expression and reduces NO-mediated inflammatory damage.

Cardiovascular protection mechanisms

Papain works by regulating multiple targets in the cardiovascular system:

• Calcium channel regulation: By blocking L-type calcium channels, it reduces the inflow of calcium ions into myocardial cells, lowers myocardial contractility and heart rate, and protects heart function.
• Antioxidant stress: By scavenging reactive oxygen species (ROS), it reduces oxidative stress damage to myocardial cells, preventing myocardial necrosis and fibrosis.
• Anti-fibrotic effect: Inhibits the proliferation of myocardial fibroblasts and collagen deposition, reducing myocardial remodeling.
• β - Adrenaline receptor regulation: modulates the sensitivity of heart β receptors and improves myocardial function.

Druggability evaluation and pharmacokinetics

Druggability analysis of papain shows its promising potential for drug development. The molecular weight of 478.7180 falls within the suitable range for drug molecules, and the LogP value of 4.5390 indicates good lipid solubility, which is beneficial for cell membrane penetration. The TPSA was 76.66, meeting the polarity requirements for oral medications. Low water solubility suggests the need to improve bioavailability through formulation technology.

The high permeability of the blood-brain barrier may confer activity on the central nervous system, but potential central side effects should also be considered. hERG channel inhibition negative, reducing the risk of cardiotoxicity. The Ames test is non-mutagenic and relatively safe.

In terms of pharmacokinetics, current research is relatively limited. Preliminary in vivo experiments show that papain is absorbed orally quickly, widely distributed, mainly metabolized by the liver, and excreted primarily through bile and urine. Its half-life is moderate, and it has a certain degree of internal stability. Future studies are needed to systematically study its metabolic enzyme activity, drug interactions, and in vivo kinetic characteristics.

Prospects and outlooks for clinical applications

Papain, as a multi-target natural alkaloid, has demonstrated good cardiovascular protection and anti-inflammatory activity, with broad clinical application potential.

In the field of cardiovascular diseases, papain can be used as an adjunct therapy for the prevention and treatment of hypertension, myocardial ischemia, and cardiomyopathy. Its multi-target effect helps comprehensively regulate cardiovascular function and reduce the risk of cardiovascular events.

In inflammatory diseases, papain inhibits key inflammatory signaling pathways and is expected to be used in the treatment of rheumatoid arthritis, inflammatory bowel disease, neuroinflammation, and other conditions. Its good safety profile ensures long-term medication.

Future research should focus on preclinical pharmacokinetic optimization, formulation development, and clinical trial validation of papain, exploring its potential for combined application with existing drugs. Additionally, based on its multi-target characteristics, modern molecular docking and systems biology methods are used to deeply analyze its network of action, providing theoretical support for new drug design.

Conclusion

Papayaline, as the main alkaloid in papaya leaves, demonstrates significant cardiovascular protection and anti-inflammatory activity due to its unique chemical structure and multi-target pharmacological effects. Its excellent druggability parameters and safety have laid a solid foundation for its drug development. In the future, through in-depth pharmacological mechanism research, pharmacokinetic optimization, and clinical validation, papain is expected to become a new natural drug for treating cardiovascular and inflammatory diseases, bringing new breakthroughs and development opportunities to the field of natural product pharmacology.