Dihydrocapsaicin

J Agric Food Chem. 2006 Aug 23;54(17):6436-9.

Effects of capsaicin, dihydrocapsaicin, and curcumin on copper-induced oxidation of human serum lipids.[Pubmed: 16910741 ]

The oxidation of low-density lipoprotein (LDL) is believed to be the initiating factor for the development and progression of atherosclerosis. The active ingredients of spices such as chili and turmeric (capsaicin and curcumin, respectively) have been shown to reduce the susceptibility of LDL to oxidation.
METHODS AND RESULTS:
One of the techniques used to study the oxidation of LDL is to isolate LDL and subject it to metal-induced (copper or iron) oxidation. However, whole serum may represent a closer situation to in vivo conditions than using isolated LDL. We investigated the effects of different concentrations (0.1-3 microM) of capsaicin, Dihydrocapsaicin, and curcumin on copper-induced oxidation of serum lipoproteins. The lag time (before initiation of oxidation) and rate of oxidation (slope of propagation phase) were calculated. The lag time increased, and the rate of oxidation decreased with increasing concentrations of the tested antioxidants (p < 0.05). A 50% increase in lag time (from control) was observed at concentrations between 0.5 and 0.7 microM for capsaicin, Dihydrocapsaicin, and curcumin.
CONCLUSIONS:
This study shows that oxidation of serum lipids is reduced by capsaicinoids and curcumin in a concentration-dependent manner.

Regul Pept. 2000 Jul 28;91(1-3):97-106.

Dihydrocapsaicin treatment depletes peptidergic nerve fibers of substance P and alters mast cell density in the respiratory tract of neonatal sheep.[Pubmed: 10967206]

METHODS AND RESULTS:
In the present study we administered Dihydrocapsaicin (DHC) to neonatal lambs to deplete C-fibers of neuropeptides. We measured the density of substance P (SP)-fibers in nasal septum to assess the effectiveness of the treatment at 3, 9, and 21 days. The numbers of mast cells in the upper and lower respiratory tract were determined at the same time points and histamine content was determined from lung tissue. DHC treatment depleted SP-fibers for up to the 21 day time point. This depletion was estimated as 85% in comparison with controls. In vehicle-treated lambs, the density of SP-fibers decreased progressively with age, but not to the degree of DHC-treated lambs whose SP-fibers were depleted from the initial 3-day measurement. In both, vehicle- and DHC-treated lambs, numbers of mast cells increased progressively with time; however, the density of mast cells was augmented in the entire respiratory tract of DHC-treated animals. Apparently, DHC treatment exerts a single and initial effect in increasing mast cells whereas time maintains a continuous influence; both factors exert their influence independently. Despite large numbers of mast cells in DHC-treated animals, histamine content in the lung had similar levels as controls.
CONCLUSIONS:
Our study provides fundamental data for a better understanding of conditions that may influence defense mechanisms dependent on the mast cell-nerve axis in the respiratory tract.

Autophagy. 2008 Nov;4(8):1009-19.

Dihydrocapsaicin (DHC), a saturated structural analog of capsaicin, induces autophagy in human cancer cells in a catalase-regulated manner.[Pubmed: 18818525]

Although capsaicin, a pungent component of red pepper, is known to induce apoptosis in several types of cancer cells, the mechanisms underlying capsaicin-induced cytotoxicity are unclear.
METHODS AND RESULTS:
Here, we showed that Dihydrocapsaicin (DHC), an analog of capsaicin, is a potential inducer of autophagy. DHC was more cytotoxic than capsaicin in HCT116, MCF-7 and WI38 cell lines. Capsaicin and DHC did not affect the sub-G(1) apoptotic peak, but induced G(0)/G(1) arrest in HCT116 and MCF-7 cells. DHC caused the artificial autophagosome marker GFP-LC3 to redistribute and upregulated expression of autophagy-related proteins. Blocking of autophagy by 3-methyladenine (3MA) as well as siRNA Atg5 induced a high level of caspase-3 activation. Although pretreatment with zVAD completely inhibited caspase-3 activation by 3MA, it did not prevent cell death. DHC-induced autophagy was enhanced by zVAD pretreatment, as shown by increased accumulation of LC3-II protein. DHC attenuated basal ROS levels through catalase induction; this effect was enhanced by antioxidants, which increased both LC3-II expression and caspase-3 activation. The catalase inhibitor 3-amino-1,2,4-triazole (3AT) abrogated DHC-induced expression of LC3-II, overexpression of the catalase gene increased expression of LC3-II protein, and knockdown decreased it. Additionally, DHC-induced autophagy was independent of p53 status.
CONCLUSIONS:
Collectively, DHC activates autophagy in a p53-independent manner and that may contribute to cytotoxicity of DHC.

J Pharm Biomed Anal. 2014 Oct 25;103C:59-66.

A validated HPLC-FLD method for analysis of intestinal absorption and metabolism of capsaicin and dihydrocapsaicin in the rat.[Pubmed: 25462121]

METHODS AND RESULTS:
A sensitive and selective reverse-phase high performance liquid chromatographic method with fluorescence detection has been developed for determination of capsaicin (8-methyl-N-vanillyl-(trans)-6-nonenamid) and Dihydrocapsaicin (8-methyl-N-vanillylnonanamide) in samples generated in rat small intestine luminal perfusion experiments. The experiments were designed to study the biotransformation of capsaicinoids in the small intestine in the rat. The chromatographic separation was performed at room temperature on a ZORBAX Eclipse(®) XDB-C8 column using isocratic elution with a mobile phase consisting 0.05M orthophosphoric acid solution and acetonitrile (60:40, v/v; pH 3.0) with a flow rate of 1.5mL/min. Fluorescence detection was performed at excitation and emission wavelengths of 230 and 323nm, respectively. The method was evaluated for a number of validation characteristics (accuracy, repeatability and intermediate precision, limit of detection, limit of quantification and calibration range). The limit of detection (LOD) was 50ng/mL and the limit of quantification (LOQ) was 100ng/mL for both capsaicin and Dihydrocapsaicin reference standards dissolved in blank perfusate. The method was successfully applied for investigation of intestinal absorption of capsaicin and Dihydrocapsaicin while 30μg/mL standardized Capsicum extract - containing capsaicin and Dihydrocapsaicin - was luminally perfused for a 90min period.
CONCLUSIONS:
The structure of the glucuronide metabolites of capsaicin and Dihydrocapsaicin appeared in the perfusate was identified by mass spectrometry.