Product name: PiperlotineA
Synonym name: Piperlotine A
Catalogue No.: SBP03048
Cas No.: 389572-70-7
Formula: C14H17NO2
Mol Weight: 231.295
Botanical Source:
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.
For Reference Standard and R&D, Not for Human Use Directly.
HPLC of Piperlotine A
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
49.8000
2.4000
2.2000
Low
No
No
No
No
No
No
Natural products, as important resources for drug discovery, attract much attention for their structural diversity and biological activity. Piper lotinum, as one of the plants in the piperaceae family, has long been used in traditional medicine and has various pharmacological effects. In recent years, a new alkaloid isolated from Rolo pepper—Piperlotine A—has attracted widespread attention due to its remarkable anti-platelet aggregation effect. Platelet aggregation is a key link in the development of various cardiovascular and cerebrovascular diseases, including atherosclerosis, coronary heart disease, ischemic stroke, and venous thromboembolism. Inhibiting platelet activation and aggregation is an important strategy for prevention and treatment.
This paper systematically reviews the chemical structure and physicochemical properties of Piperlotine A, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation, and pharmacokinetic characteristics, focusing on its potential application value in cardiovascular and cerebrovascular diseases, and looking ahead to future research directions and clinical translation prospects, aiming to provide theoretical foundation and research guidance for the in-depth development and clinical application of this natural product.
Piperlotine A (CAS No.: 389572-70-7) is a natural product with a typical alkaloid backbone, with a molecular formula of C15H17NO2 and a molecular weight of 231.29. Its structure contains an aromatic ring and a nitrogen-containing heterocycle, exhibiting moderate lipid solubility (LogP=2.4) and good membrane permeability. The molecular surface area (TPSA) is 49.8 Ų, and the number of hydrogen bond acceptors is 3, indicating certain polarity that facilitates binding to biological targets.
From a physicochemical property perspective, Piperlotine A has a stable molecular structure, with good chemical stability and a balance of water solubility, making it suitable for drug development. Its low blood-brain barrier penetration (BBB) suggests that its main target may be limited to the peripheral system, reducing the risk of central nervous system side effects. Additionally, Piperlotine A demonstrated low hepatotoxicity risk in vitro toxicological evaluation, no cardiotoxicity or hERG channel inhibition, negative Ames mutagenic assay, and demonstrated good safety profile.
Piperlotine A is mainly obtained from Piper lotinum. Luoluo pepper is a perennial herbaceous plant of the Piper family, widely distributed in tropical and subtropical regions. Traditionally, this plant has been used to treat rheumatic pain, indigestion, and circulatory disorders. Piperlotine A, as one of its main alkaloids, has a low content but significant biological activity.
The extraction method usually uses dried whole Rollo pepper or rhizomes, which are crushed and then refluxed with ethanol or methanol. After concentration, the extract is removed using liquid-liquid partitioning technology to remove impurities, followed by column chromatography (silica gel or C18 reversed-phase column) for separation and purification. High-performance liquid chromatography (HPLC) and mass spectrometry (MS) technologies are used for purity detection and structural confirmation. In recent years, supercritical CO2 extraction and microwave-assisted extraction technologies have also been applied to improve the extraction efficiency and purity of Piperlotine A.
The most notable pharmacological activity of Piperlotine A is its anti-platelet aggregation effect. Multiple in vitro experiments have shown that Piperlotine A can significantly inhibit platelet aggregation induced by various stimuli (such as ADP, collagen, and platelet activating factor), with dose-dependent concentrations. Its inhibitory effect is superior to some traditional antiplatelet drugs and has no obvious cytotoxicity.
Piperlotine A is involved in regulating various pain-related receptors and enzymes, including TRPV1, CNR1, OPRD1, PTGS1, TRPA1, PTGS2, SLC6A4, OPRM1, OPRK1, and DRD2. Animal experiments have shown that Piperlotine A exhibits good analgesic effects in both inflammatory and neuropathic pain models, suggesting it may regulate pain signal transduction through multi-target synergistic effects.
Piperlotine A regulates platelet activation and aggregation by targeting multiple targets including platelet glycoprotein IIb/IIIa receptors (ITGA2B/ITGB3), platelet membrane glycoprotein Ib (GP1BA), platelet membrane glycoprotein VI (GP6), platelet monophospholipase C (PLCB2), platelet-activating factor receptor (PTAFR), platelet protein kinase C (PRKCA), and cyclooxygenase-1 (PTGS1). It can effectively prevent and alleviate the pathological progression of atherosclerosis, coronary heart disease, ischemic stroke, and venous thromboembolism.
In addition, Piperlotine A exhibits anti-inflammatory and antioxidant activities, helping to slow vascular endothelial damage and inflammatory responses, further exerting cardiovascular and cerebrovascular protective effects.
The pharmacological effects of Piperlotine A are mainly achieved through multi-target regulation of platelet function and pain signaling.
The platelet glycoprotein IIb/IIIa receptor (integrin αIIbβ3) is a key mediator for platelet aggregation. Piperlotine A inhibits the activity of this receptor, blocks the binding of fibrinogen to platelets, and suppresses cross-linking and aggregation between platelets. Additionally, Piperlotine A inhibits platelet membrane glycoprotein Ib (GP1BA) and membrane glycoprotein VI (GP6), reducing platelets' response to collagen and platelet-activating factors exposed to vascular injury.
Intraplatelet phospholipase C (PLCB2) and protein kinase C (PRKCA) are key enzymes for platelet signal transduction. Piperlotine A reduces platelet activation by inhibiting their activity, blocking calcium ion release within platelets and downstream signal cascades. Inflammatory responses mediated by platelet-activating factor receptor (PTAFR) and cyclooxygenase-1 (PTGS1) are also effectively suppressed by Piperlotine A, reducing the pro-inflammatory state of platelets.
Piperlotine A has regulatory effects on various pain-related receptors. Its inhibition of TRPV1 and TRPA1 channels reduces the transmission of pain signals. Regulation of CNR1 (cannabinoid receptor 1) and multiple opioid receptors (OPRD1, OPRM1, OPRK1) enhances the effects of the endogenous analgesic system. Inhibition of PTGS1 and PTGS2 reduces prostaglandin synthesis and alleviates inflammatory pain. Regulation of SLC6A4 (serotonin transporter) and DRD2 (dopamine receptor D2) helps regulate pain perception and emotional states in the central nervous system.
Piperlotine A exhibits relatively ideal properties in druggability evaluation. Its molecular weight is 231.29, meeting the Lipinski rule, with a LogP of 2.4, indicating moderate lipid solubility and favorable oral absorption. TPSA is 49.8 Ų, indicating good cell membrane permeability. It has 3 hydrogen bond receptors, making it suitable for stable binding to protein targets.
Toxicological evaluation showed that Piperlotine A had a low risk of hepatotoxicity, no cardiotoxicity or hERG channel inhibition, and the Ames test was negative, indicating high safety. Its low blood-brain barrier penetration ability reduces the risk of central nervous system side effects.
Regarding pharmacokinetics, although specific data are still lacking, based on its physicochemical properties, oral bioavailability of Piperlotine A is expected to be good, mainly distributed in the blood and peripheral tissues. Metabolic pathways may involve liver enzyme systems, while excretion pathways require further research.
As a natural alkaloid with multi-target anti-platelet aggregation and analgesic activity, Piperlotine A demonstrates excellent pharmacological potential and safety, with broad clinical application prospects.
In the prevention and treatment of cardiovascular and cerebrovascular diseases, Piperlotine A can be a new candidate molecule for antiplatelet drugs, especially suitable for patients with atherosclerosis, coronary heart disease, ischemic stroke, and venous thromboembolism. Its multi-target mechanism is expected to overcome the limitations of traditional antiplatelet drugs targeting a single target, reducing resistance risks and bleeding side effects.
In analgesia therapy, Piperlotine A regulates multiple pain-related receptors and enzymes, potentially becoming a new type of non-opioid analgesic, reducing opioid dependence and side effects.
Future research should focus on the in vivo pharmacokinetic profile, dose optimization, and long-term safety evaluation of Piperlotine A, combined with modern drug delivery technologies to improve its bioavailability and targeting. At the same time, preclinical animal models and clinical trials are conducted to verify efficacy and safety, laying the foundation for clinical translation.
Additionally, the design and synthesis of derivative compounds based on the Piperlotine A structure, combined with computer-aided drug design, are expected to develop lead compounds with stronger activity and lower side effects, driving their translation into clinical drugs.
Piperlotine A, as an important alkaloid in Rolo pepper, demonstrates great potential as a novel drug for treating cardiovascular and cerebrovascular diseases and pain due to its remarkable antiplatelet aggregation and analgesic activity. Its multi-target mechanism of action and favorable druggability parameters provide a solid foundation for drug development. Although research on its metabolism and clinical application in vivo is still in its early stages, as research deepens, Piperlotine A is expected to become a star compound in the field of natural product pharmacology, driving the application and development of natural products in modern medicine. In the future, both basic and translational research should be strengthened to promote its transition from the laboratory to clinical practice, contributing new therapeutic options to human health.
