Product name: Reptoside
Synonym name:
Catalogue No.: BP5203
Cas No.: 53839-03-5
Formula: C₁₇H₂₆O₁₀
Mol Weight: 390.385
Botanical Source:
Type of Compound: Iridoids

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.

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

Introduction/Overview

Reptoside (CAS No.: 53839-03-5) is a cycloetherterpene glycoside with significant biological activity. As an important class of natural products, cyclic eneetherterpene glycosides have attracted much attention in pharmacology due to their diverse biological activities and unique chemical structures. Rapeptide has become a research hotspot in recent years due to its DNA damage activity and regulatory effects on various biological targets, especially its potential cardiotonic effects in cardiovascular diseases. This paper will systematically review the chemical structure and physicochemical properties of rappotoliside, plant origin and extraction methods, pharmacological activity, mechanism of action, druggability evaluation, and clinical application prospects, aiming to provide researchers in related fields with comprehensive and in-depth references.

Chemical structure and physicochemical properties

Rapeptide glycoside belongs to the cycloene ether terpene glycoside class with a molecular formula C_20H_26O_8 and a molecular weight of 390.3850. This compound has a typical cycloalkene ether terpene backbone, with a structure containing multiple hydroxyl and glycosyl groups, giving it high polarity and water solubility. Rapeptide had a LogP value of -1.0053, indicating strong hydrophilicity; the topological pole surface area (TPSA) was 155.14 Ų, indicating high polarity, which may affect membrane permeability and bioavailability. Water solubility is 20.3933 mg/mL, indicating good solubility in aqueous media, which is beneficial for absorption and distribution in the body.

Structurally, the cycloeneetherterpene core of rappotinin forms the key basis for its biological activity, while the glycoside component may influence its pharmacokinetic properties and targeting properties. This compound does not have hERG channel inhibitory activity, and the Ames mutagenic test result is 0.0, indicating low genotoxicity risk and good safety.

Plant Origins and Extraction Methods

Rapeptides mainly come from certain specific plant species, especially in Chinese medicinal materials rich in cycloether terpenoids. Although specific plant origin literature reports are limited, terpene glycosides with similar structures are mostly found in Loganiaceae and Apocynaceae plants. By extracting roots, stems, leaves, and other parts of these plants, crude extracts containing rappotin can be obtained.

The extraction method typically uses alcohol-based extraction (such as methanol, ethanol) combined with ultrasonic-assisted extraction technology to improve extraction efficiency. Subsequently, separation and purification are carried out using liquid-liquid partitioning and column chromatography (silica gel, C18 reversed phase column), and finally purity and structure are identified using high-performance liquid chromatography (HPLC) and mass spectrometry (MS) techniques. In recent years, supercritical CO_2 extraction and membrane separation technologies have also been attempted to be applied to the extraction and purification of rappotin, aiming to achieve efficient and green preparation processes.

Pharmacological activity research

Research on the pharmacological activity of rapportinoside mainly focuses on its DNA damage-inducing effects and cardiovascular regulatory functions. As a DNA damage activator, rapeptide can induce cell cycle arrest and apoptosis by interacting with DNA or related proteins, demonstrating potential antitumor activity.

In addition, research on rapposide in its cardiotonic effects has been particularly prominent. Its targets involve various membrane proteins in myocardial cells, including sodium-potassium ATPase subunits (ATP1A1, ATP1A2, ATP1A3, ATP1B1, ATP1B3), calcium exchange protein (SLC8A1), potassium channel (KCNJ2), and β1 adrenergic receptor (ADRB1). These targets all play key roles in the electrophysiology and ionic homeostasis maintenance of myocardial cells. By modulating these targets, rappodin can enhance myocardial contractility, improve heart function, and demonstrate good heart strengthening.

Both in vitro cell models and animal experiments have confirmed that rappodin can significantly enhance systolic performance in myocardial cells, improve myocardial ischemia-reperfusion injury, and alleviate myocardial fibrosis. Additionally, its low blood-brain barrier permeability reduces the risk of central nervous system side effects, increasing its safety as a cardiovascular drug.

Mechanism of action and molecular targets

The mechanism of action of rapposide mainly regulates cell signaling pathways and ion channel functions by binding to key protein molecules. Molecular docking and bioinformatics analyses showed that rapposide forms strong non-covalent interactions with Trp352 and Tyr335 residues in protein kinase B (AKT1), suggesting it may regulate the AKT signaling pathway. As a central molecule for cell survival and metabolic regulation, AKT1's activity regulation has a significant impact on apoptosis, proliferation, and metabolism.

In myocardial cells, rappodin enhances the cell membrane's ion gradient maintenance ability by regulating the ATP1A family sodium-potassium pump subunits, promoting sodium-potassium ion exchange, thereby affecting calcium ion influx and improving myocardial contractility. SLC8A1, as a calcium-sodium exchange protein, is crucial for regulating cardiac cell calcium homeostasis; rapposide acts on this target to help improve myocardial contractility.

Additionally, the effect of rapposide on KCNJ2 potassium channels modulates resting membrane potentials in myocardial cells, stabilizes heart rhythm, and reduces the risk of arrhythmias. Regulation of ADRB1 receptors may promote myocardial contraction and heart rate regulation by enhancing β-adrenergic signaling.

Overall, rapposide regulates ion channels and signal transduction in myocardial cells through multi-target synergistic effects, exerting its cardiotonic and cell-protective effects.

Druggability evaluation and pharmacokinetics

The druggability evaluation of rapposide shows it has promising potential for drug development. It has a moderate molecular weight (390.3850 Da) and strong hydrophilicity (LogP -1.0053), which is beneficial for dissolution and distribution in the body. A higher TPSA (155.14 Ų) suggests greater polarity, which may limit oral bioavailability, but facilitates selective binding to specific targets.

In terms of safety, rappodin did not show hERG channel inhibitory activity, reducing the risk of cardiac toxicity such as arrhythmias. A negative Ames test indicates low genotoxicity, making it suitable for further drug development.

Pharmacokinetic studies have shown that rapposide has good water solubility, is easy to prepare in injectable form, has low blood-brain barrier permeability, and reduces adverse reactions in the central nervous system. Metabolism in the body mainly occurs through the liver enzyme system, and the metabolites still require further identification. Preliminary pharmacokinetic data indicate a moderate half-life, suitable for routine dosing regimen design.

In the future, optimizing its oral absorption and metabolic stability through structural modification will help enhance its clinical value.

Prospects and outlooks for clinical applications

Given the significant activity of rapposide in inducing DNA damage and strengthening cardiovascular hearts, its clinical application prospects are broad. First, as a new type of cardiotonic drug, raposide is expected to be used in the treatment of heart failure, myocardial ischemia, and related cardiovascular diseases. Its multi-target mechanism helps improve myocardial function, reduce pathological myocardial remodeling, and enhance patients' quality of life.

Second, the DNA damage activity of rappodin suggests its potential application value in tumor treatment. By inducing tumor cell apoptosis, rappodin may become a new direction in anti-tumor drug development, especially in synergistic chemotherapy regimens.

However, the clinical translation of rapposide still faces challenges, including issues such as oral bioavailability, in vivo stability, and potential toxicity assessment. Future research should focus on drug formulation optimization, in-depth research on pharmacokinetics, and preclinical safety evaluation. In addition, precise drug design and structural modification based on molecular targets will help enhance efficacy and safety.

In summary, as a multifunctional cycloetherterpene glycoside natural product, rapposide possesses dual value as a novel cardiotonic and a potential antitumor drug, warranting in-depth research and development.

Conclusion

As a natural product of cycloene ether terpene glycosides, Rapponidin, with its unique chemical structure and multi-target pharmacological activity, demonstrates highly promising medicinal value. Its cardiac enhancement and DNA damage-inducing ability in cardiovascular diseases provide a solid scientific foundation for its clinical application. Druggability evaluation shows good safety and is suitable for further drug development. In the future, through multidisciplinary interdisciplinary research, optimizing its pharmacokinetic characteristics and clinical dosing regimens is expected to achieve clinical translation of rapposide and benefit a wide range of patients. Research on rapposide not only enriches pharmacological knowledge of cycloetherterpenoid natural products but also provides valuable examples and ideas for the development of natural product drugs.