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Product name: Dihydromethysticin
Synonym name: ψ-Methysticin; Pseudomethysticin
Catalogue No.: BP0497
Cas No.: 19902-91-1
Formula: C15H16O5
Mol Weight: 276.288
Botanical Source: Piper methysticum Forst
Physical Description:
Type of Compound: Phenols
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.
Chengdu Biopurify Phytochemicals Ltd. is a leading company in the research, development, manufacture and marketing of High Quality Phytochemicals and Extracts(especially Active Ingredients from Traditional Chinese Medicine，TCM), Natural Active Pharmaceutical Ingredients worldwide.
The main services:
A. Supply active ingredients and reference standards of TCM, from mgs to kgs scale
B. Custom extraction and purification, target Herb Active Ingredients
C. Custom synthesis and semi-synthesis for Natural Active Ingredients
D. CR(contract research), CM(contract manufacture) and PD(process development) services from lab scale, pilot scale to commercial scale(GMP is also available)
E. TCM compounds library for drug screen,more than 3000 compounds available, many of them are rare and unique.
HPLC of Dihydromethysticin
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
53.9900
2.1425
2.1425
.1446
4.3384
9.0494
High
83.9802
3.0739
No
No
Yes
No
No
No
0.0
No
Yes
No
Yes
Dihydromethysticin (CAS No. 19902-91-1) is a natural active ingredient derived from the traditional medicinal plant Piper methysticum (commonly known as Kava) in the South Pacific. As one of the various active ingredients in numbing pepper, dihydro anesthetic pepper bitter extract has attracted widespread attention in the field of natural product pharmacology in recent years due to its unique bioactivity and good oral bioavailability. Research shows that dihydroanesthetic pepper bitter extract not only has traditional pharmacological effects such as analgesic and anti-inflammatory but also demonstrates significant antitumor activity against colorectal cancer and lung adenoma. Its mechanism of action involves multi-target regulation, including enzyme inhibition, signaling pathway regulation, and apoptosis induction, demonstrating its potential as a multifunctional drug candidate.
This review aims to systematically summarize the chemical structure and physicochemical properties of dihydroanesthetic pepper bitter, plant origin, and extraction methods, with a focus on evaluating its pharmacological activity and mechanism of action, deeply exploring its druggability and pharmacokinetic characteristics, and looking ahead to its clinical application prospects, aiming to provide theoretical basis and practical guidance for related research.
The molecular formula of dihydroanesthetic pepper-bitter is C17H20O4, with a molecular weight of 276.2880. Its chemical structure belongs to the anesthetic pepper lactone compounds, containing typical methylene dioxybenzene rings and side-chain saturated cyclole ether structures, demonstrating high chemical stability and biological activity. The LogP value was 2.1425, indicating moderate lipid solubility, which facilitates cell membrane penetration and oral absorption. The polar surface area (TPSA) is 53.99 Ų, indicating moderate polarity and conducive binding to biological targets. Its low water solubility (0.1446 mg/mL) suggests limited solubility in aqueous systems, but its lipophilic characteristics help it cross biofilms.
Dihydroanesthetic pepper quasin has excellent blood-brain barrier penetration ability, which is crucial for the role of the central nervous system. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. The Ames mutagenic test result was 0.0, indicating that the genotoxicity risk is extremely low and meets safety requirements.
Dihydroanesthetic piskostic is mainly found in the rhizome of Piper methysticum, a traditional medicinal and ritual plant in the South Pacific region, widely used for its sedating, anxiolytic, and analgesic effects. The rhizome of the numbing pepper contains various polylide compounds, with dihydroanesthetic pepper bitter being one of the important active components.
The extraction method typically uses organic solvent extraction combined with chromatography separation technology. Common extraction solvents include ethanol, methanol, and their aqueous solutions, leveraging their excellent dissolution ability for lipid-soluble components. The extraction process generally includes the following steps:
In recent years, ultrasound-assisted extraction and supercritical CO2 extraction technologies have also been applied to improve extraction efficiency and purity, while reducing the use of organic solvents, aligning with the concept of green chemistry.
Dihydroanesthetic pepper-bitter acid exhibits significant analgesic activity, and related studies have shown that it achieves analgesic effects through multi-target regulation. Its targets include TRPV1 (transient receptor potential vanillate receptor 1), CNR1 (cannabinoid receptor 1), OPRD1 (δ-opioid receptor), OPRM1 (μ-opioid receptor), OPRK1 (κ-opioid receptor), PTGS1/2 (cyclooxygenase 1 and 2), TRPA1 (transient receptor potential vanillin receptor-related 1), and SLC6A4 (serotonin transporter). These targets involve pain conduction, inflammatory responses, and neurotransmitter regulation. Dihydroanesthetic pepper bitter extract co-modulates these targets to reduce neuroinflammation and pain sensitivity, exerting analgesic effects.
Dihydroanesthetic pepper bitter showed significant inhibitory effects on colorectal cancer and lung adenoma cells. In vitro cell experiments have shown that dihydroanesthetic pepper bittern can induce apoptosis in tumor cells and inhibit cell proliferation and migration. Its anticancer mechanism is partly attributed to upregulating the NLR family protein 3 (NLRC3), which contains the CARD structure, which plays an important role in regulating immune responses and apoptosis. By activating the NLRC3 signaling pathway, dihydroanesthetic pepper-bitter promotes tumor cell apoptosis and inhibits tumor growth.
Additionally, dihydroanesthetic pepper-bitter inhibits the hepatic metabolic enzymes carboxylesterase 1 (CES1) and cytochrome P450 2A5 (CYP2A5) (Ki=68.2 μM), suggesting that it may influence tumor cell drug metabolism and drug resistance by regulating drug-metabolizing enzyme activity.
Some studies have also found that dihydroanesthet-pikossin has anti-inflammatory, antioxidant, and neuroprotective effects, which may be related to its regulation of inflammatory factor expression and oxidative stress levels. These actions provide a theoretical basis for its potential applications in neurological diseases and chronic inflammatory diseases.
The pharmacological effects of dihydroanesthetic pepper bitter are based on its multi-target and multi-pathway regulatory characteristics. In terms of pain relief, dihydroanesthetic pissokosin regulates TRPV1 and TRPA1 channels, inhibits calcium ion influx into pain nerve endings, and reduces pain conduction signals; By activating CNR1 and opioid receptors (OPRD1, OPRM1, OPRK1), the effects of endogenous analgesia systems are enhanced; At the same time, it inhibits PTGS1/2, reduces prostaglandin synthesis, and relieves inflammatory pain.
In terms of anticancer mechanisms, dihydroanesthetic pepper-bitter upregulate NLRC3, promoting intracellular regulation of inflammasome and inducing tumor cell apoptosis. Additionally, by inhibiting CES1 and CYP2A5, it affects intracellular drug metabolism and redox status, further inhibiting tumor cell growth and spread.
Molecular docking and cell signaling pathway analyses indicate that dihydroanesthetic-capsokurin has strong binding affinity with the above targets, regulating key pathways such as NF-κB, MAPK, and PI3K/Akt, and controlling cell proliferation, apoptosis, and inflammatory responses.
From the perspective of drug-making, dihydroanesthetic pepper bitter has good medicinal properties. Its moderate molecular weight and LogP value give it good oral absorption potential. Although the lower polar surface area and water solubility limit its water solubility, lipid solubility helps cross cell membranes and the blood-brain barrier, supporting central nervous system activity.
The high penetration of the blood-brain barrier supports its potential application in central nervous system diseases. hERG inhibitory tests were negative, and Ames tests showed no mutagenicity, indicating high safety and reduced risks of cardiotoxicity and genotoxicity.
Pharmacokinetic studies show that dihydroanesthetic pepper bitter extract is well absorbed orally and widely distributed in the body, especially at high concentrations in brain tissue. Its metabolism mainly occurs through the hepatic enzyme system, and some metabolites may be active. The main excretory routes are bile and urine. Moderate half-life, suitable for daily administration.
However, its low water solubility may limit its bioavailability, so formulation optimization (such as nanocarriers, solid dispersions, etc.) is needed to improve solubility and stability.
Dihydroanesthetic pepper bitter extract, as a multi-target natural active ingredient, has broad clinical application potential. Its analgesic effect provides a new candidate drug for the treatment of chronic pain, neuropathic pain, and inflammatory pain, especially suitable for patients who require central analgesia and have fewer side effects.
Its anticancer activity gives it potential value in adjuvant therapy for colorectal cancer and lung adenoma, especially in combination chemotherapy or targeted therapy, where it may enhance efficacy and reduce drug resistance by modulating the tumor microenvironment and drug metabolism.
Future research should focus on the following directions:
Dihydroanesthetic pepper bitter, as an important active ingredient in Piper methysticum, demonstrates good analgesic and anticancer potential due to its multi-target and multi-mechanism pharmacological properties. Its excellent druggability parameters and safety indicators lay the foundation for clinical development. In the future, through in-depth mechanistic research and optimized drug development, dihydroanesthetic pepper-bitter compound is expected to become a star molecule in the field of natural product pharmacology, providing new therapeutic strategies for pain management and tumor treatment. The research community and the pharmaceutical industry should strengthen cooperation to advance their clinical application and achieve the successful transformation of natural products into modern medicines.
Shenshuai
Wenjing
Hedandan
