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Synonym name:
Catalogue No.: BP1006
Cas No.: 28789-35-7
Formula: C17H27NO3
Mol Weight: 293.407
Botanical Source: the pungent principle of red pepper (Capsicum annuum)
Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Can be supplied from milligrams to grams.
For Reference Standard and R&D, Not for Human Use Directly.
Inquire for bulk scale.
HPLC of Nordihydrocapsaicin
HNMR of Nordihydrocapsaicin
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
58.5600
3.6940
3.6926
.0592
2.6326
7.0286
High
90.1581
1.8517
Yes
No
Yes
No
No
No
0.0
No
No
No
No
Nordihydrocapsaicin (CAS No.: 28789-35-7), an important analog of capsaicin, has attracted widespread attention in the field of natural product pharmacology in recent years due to its unique chemical structure and significant biological activity. Dihydrocapsaicine is mainly found in fresh and processed chili peppers, has oral activity, can cause a typical burning sensation, and also demonstrates good analgesic and anticancer potential. Capsaicin compounds have shown significant pharmacological value in pain regulation, inflammatory response, and tumor treatment due to their interactions with various ion channels and receptors. This paper aims to systematically review the chemical structure, physicochemical properties, plant origin, extraction methods, pharmacological activity, mechanism of action, druggability evaluation, and clinical application prospects of dihydrocapsaicinine, aiming to provide a theoretical foundation and reference for further research and development of this compound.
Dihydrocapsaicine has a molecular formula of C18H27NO3 and a molecular weight of 293.4070, structurally belonging to the reduced derivative of capsaicin compounds. Its core structure includes an aromatic ring and a long-chain fatty alcohololamine side chain. Unlike capsaicin, the double bond on the side chain is reduced, hence the name "reduced dihydrogen." This structural feature gives it high lipid solubility (LogP=3.6940), which facilitates penetration of cell membranes and the blood-brain barrier (BBB has high penetration). Its polar surface area (TPSA) is 58.56 Ų, indicating moderate polarity that helps form stable interactions with protein targets. Low water solubility (0.0592 mg/mL) suggests that strategies to enhance solubility should be considered in formulation development. In terms of safety, dihydrocapsaicine did not show hERG channel inhibitory activity, and the Ames mutagenic test was negative, indicating a solid safety foundation.
Dihydrocapsaicin, mainly found in the fruits of Capsicum spp., especially abundant in fresh and processed chili peppers. The content of capsaicin compounds is greatly influenced by variety, maturity, cultivation environment, and processing technology. Traditional extraction methods mostly use organic solvent extraction such as ethanol, methanol, or ethyl acetate, combined with ultrasonic-assisted extraction or Soxhlet extraction to improve extraction efficiency. Subsequently, purification and separation were performed through liquid-liquid distribution, silica gel column chromatography, and high-performance liquid chromatography (HPLC), ultimately obtaining high-purity dihydrocapsaicin. In recent years, supercritical CO2 extraction technology has been gradually applied to the extraction of capsaicin compounds due to its environmental friendliness and high efficiency, showing promising application prospects.
Dihydrocapsaicin, as a capsaicin analog, exhibits significant analgesic activity. Its analgesic effect is mainly reflected in relieving acute pain and chronic neuropathic pain. In vivo and in vitro studies have shown that dihydrocapsaicine participates in the transmission and regulation of pain signals by activating and modulating various pain-related receptors and ion channels. Similar to capsaicin, dihydrocapsaicine activates TRPV1 receptors, induces calcium ion influx, and causes desensitization of sensory nerve endings, thereby achieving analgesic effects. Additionally, it regulates various neurotransmitter receptors such as CNR1 (cannabinoid receptor 1), OPRD1 (δ-opioid receptor), OPRM1 (μ-opioid receptor), and OPRK1 (κ-opioid receptor), jointly participating in pain relief.
Besides analgesics, dihydrocapsaicine shows potential in the field of anti-tumor treatment. In vitro cell experiments show that dihydrocapsaicine can induce apoptosis in various cancer cell lines, inhibiting cell proliferation and migration. Its anticancer mechanism involves regulating the cell cycle, inducing mitochondrial-dependent apoptosis pathways, and inhibiting the expression of the inflammation-related enzyme PTGS2 (COX-2), thereby weakening pro-inflammatory signals in the tumor microenvironment. Additionally, dihydrocapsaicinine may affect tumor cell metabolism and signal transduction by regulating the TRPA1 channel and the dopamine receptor DRD2, thereby exerting antitumor effects.
Dihydrocapsaicine also exhibits certain anti-inflammatory, antioxidant, and neuroprotective activities. By inhibiting the enzyme activity of PTGS1 (COX-1) and PTGS2 (COX-2), it reduces prostaglandin synthesis and alleviates inflammatory responses. The regulatory effect of SLC6A4 (the 5-hydroxytryptamine transporter) suggests that it may affect the neurotransmitter balance of the central nervous system, with potential antidepressant and anxiety effects.
The pharmacological action of dihydrocapsaicine depends on its interactions with various molecular targets, especially key receptors and ion channels in pain signaling pathways.
TRPV1 (Transient Receptor Potential Vanillic Acid Receptor 1) is a classic target of capsaicin compounds, mainly distributed at the terminals of sensory neurons. Dihydrocapsaicine activates TRPV1, inducing calcium ion influx, leading to depolarization of nerve endings and neurotransmitter release, initially causing a burning sensation. However, continuous activation of TRPV1 can lead to nerve ending desensitization and suppression of pain signaling, exerting its analgesic effect.
Dihydrocapsaicine modulates the opioid receptors of μ (OPRM1), δ (OPRD1), and κ (OPRK1), synergistically alleviating pain by enhancing endogenous analgesia signals in the opioid system. In addition, activation of opioid receptors also helps regulate neuroinflammation and emotional states.
CNR1 receptors are widely expressed in the central nervous system and are involved in pain regulation, inflammatory responses, and neuroprotection. Dihydrocapsaicin's effect on CNR1 may enhance its analgesic and anti-inflammatory effects.
Dihydrocapsaicine inhibits cyclooxygenases 1 and 2 (COX-1 and COX-2), reduces prostaglandin synthesis, alleviates inflammatory responses, indirectly relieves pain, and inhibits tumor-related inflammation.
TRPA1 channels are involved in the transmission of inflammatory and neuropathological pain, and the regulatory effect of dihydrocapsaicine helps alleviate complex pain states. Regulation of SLC6A4 suggests it may affect the reuptake of the neurotransmitter 5-hydroxytryptamine, thereby modulating mood and pain perception. Regulation of DRD2 dopamine receptors may affect neuronal excitability and tumor cell metabolism.
Dihydrocapsaicinine has excellent druggability parameters. Its molecular weight is moderate (293.4 Da), in accordance with the Lipinski rule, and the LogP value (3.694) indicates suitable lipophilic properties, which are beneficial for oral absorption and blood-brain barrier penetration. A TPSA value of 58.56 Ų indicates moderate polarity, which is beneficial for target binding and membrane permeability. Low water solubility, suggesting the need to optimize formulations to improve bioavailability.
In terms of safety, dihydrocapsaicine did not show hERG channel inhibitory activity, reducing the risk of cardiotoxicity. The Ames test was negative, indicating no significant mutagenicity and relatively high safety. It has good oral activity and a high blood-brain barrier penetration ability, making it suitable for developing central nervous system-related indications.
Currently, pharmacokinetic (PK) research on dihydrocapsaicine is limited, but based on its structure similar to capsaicin, it is expected that its metabolism in vivo will mainly be carried out through redox reactions and binding metabolism through hepatic enzyme systems. In the future, further studies on in vivo absorption, distribution, metabolism, and excretion (ADME) are needed to clarify its pharmacokinetic characteristics and dose adjustment protocols.
As a naturally derived compound, dihydrocapsaicine demonstrates broad clinical application potential due to its remarkable analgesic and anticancer properties.
Currently, there are still significant challenges in the treatment of chronic and neuropathic pain in clinical practice, as traditional opioid dependence and side effects limit its application. Dihydrocapsaicinine offers a potential new non-opioid analgesic strategy through a multi-target mechanism, especially the co-regulation of TRPV1 and opioid receptors. Its oral activity and good blood-brain barrier penetration make it suitable for development as a central analgesic agent. In addition, local application of dihydrocapsaicine can also be used to relieve local pain and inflammation.
The ability of dihydrocapsaicine to induce cancer cell apoptosis and inhibit tumor growth provides a theoretical basis for its use as an adjunct anticancer drug. In the future, it may be combined with chemotherapy drugs to explore their role in tumor microenvironment regulation and chemotherapy sensitization. Based on its anti-inflammatory and immunomodulatory properties, the potential of dihydrocapsaicine in tumor immunotherapy is also worth further exploration.
The regulatory effects of dihydrocapsaicine on neuroprotection, antidepressant, and anxiety prevention suggest its potential for development in the field of neuropsychiatric diseases. Moreover, its anti-inflammatory and antioxidant activities make its application prospects in chronic inflammatory diseases noteworthy.
Although dihydrocapsaicine demonstrates good pharmacological activity and druggability, its low water solubility and oral bioavailability remain challenges in formulation development. In the future, technologies such as nanocarriers and solid dispersions need to improve their pharmacokinetic performance. Systematic toxicological evaluation and preclinical research are also key to advancing its clinical translation. The multi-target and multi-mechanism characteristics of action make precision medicine and personalized treatment possible.
As an important member of capsaicin natural products, dihydrocapsaicin, with its unique chemical structure and multi-target pharmacological activity, shows broad application prospects in pain relief, anti-cancer, and neurological diseases. Its excellent druggability parameters and safety foundation lay a solid foundation for subsequent drug development. In the future, through in-depth mechanistic research, pharmacokinetic optimization, and clinical evaluation, dihydrocapsaicine is expected to become a star compound in the field of natural product pharmacology, providing new strategies and options for the treatment of related diseases.
Shenshuai
Wenjing
Hedandan
