Comparison of in vitro metabolism and cytotoxicity of capsaicin and dihydrocapsaicin

Halme, Mia; Pesonen, Maija; Salo, Heta; Söderström, Martin; Pasanen, Markku; Vähäkangas, Kirsi; Vanninen, Paula

doi:10.1016/j.jchromb.2015.11.042

Cited by 24 publications

(18 citation statements)

References 21 publications

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“…Although the anti-inflammatory and anti-oxidant effects of capsaicin are mentioned [ 6 , 71 , 72 ], the high dose of capsaicin induces neurogenic inflammation and cytotoxicity [ 73 , 74 ]. Here, the dose-related enterocyte toxicity of capsaicin was indicated as the low dose capsaicin (0.02 mM) induced only enterocyte inflammation (IL-8 production) without an effect on cell viability, transepithelial electrical resistance (TEER), and cell energy.…”

Section: Discussionmentioning

confidence: 99%

Lactobacillus rhamnosus attenuates Thai chili extracts induced gut inflammation and dysbiosis despite capsaicin bactericidal effect against the probiotics, a possible toxicity of high dose capsaicin

et al. 2021

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Because of a possible impact of capsaicin in the high concentrations on enterocyte injury (cytotoxicity) and bactericidal activity on probiotics, Lactobacillus rhamnosus L34 (L34) and Lactobacillus rhamnosus GG (LGG), the probiotics derived from Thai and Caucasian population, respectively, were tested in the chili-extract administered C57BL/6 mice and in vitro experiments. In comparison with placebo, 2 weeks administration of the extract from Thai chili in mice caused loose feces and induced intestinal permeability defect as indicated by FITC-dextran assay and the reduction in tight junction molecules (occludin and zona occludens-1) using fluorescent staining and gene expression by quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, the chili extracts also induced the translocation of gut pathogen molecules; lipopolysaccharide (LPS) and (1→3)-β-d-glucan (BG) and fecal dysbiosis (microbiome analysis), including reduced Firmicutes, increased Bacteroides, and enhanced total Gram-negative bacteria in feces. Both L34 and LGG attenuated gut barrier defect (FITC-dextran, the fluorescent staining and gene expression of tight junction molecules) but not improved fecal consistency. Additionally, high concentrations of capsaicin (0.02–2 mM) damage enterocytes (Caco-2 and HT-29) as indicated by cell viability test, supernatant cytokine (IL-8), transepithelial electrical resistance (TEER) and transepithelial FITC-dextran (4.4 kDa) but were attenuated by Lactobacillus condition media (LCM) from both probiotic-strains. The 24 h incubation with 2 mM capsaicin (but not the lower concentrations) reduced the abundance of LGG (but not L34) implying a higher capsaicin tolerance of L34. However, Lactobacillus rhamnosus fecal abundance, using qRT-PCR, of L34 or LGG after 3, 7, and 20 days of the administration in the Thai healthy volunteers demonstrated the similarity between both strains. In conclusion, high dose chili extracts impaired gut permeability and induced gut dysbiosis but were attenuated by probiotics. Despite a better capsaicin tolerance of L34 compared with LGG in vitro, L34 abundance in feces was not different to LGG in the healthy volunteers. More studies on probiotics with a higher intake of chili in human are interesting.

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Section: Discussionmentioning

confidence: 99%

Lactobacillus rhamnosus attenuates Thai chili extracts induced gut inflammation and dysbiosis despite capsaicin bactericidal effect against the probiotics, a possible toxicity of high dose capsaicin

et al. 2021

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“…The growth-inhibitory effects of DHC (Fig. 3B) were mediated via cell cycle arrest, apoptosis, and autophagy inhibition of cellular metabolism (Oh et al, 2008;Halme et al, 2016). The antitumor activity of DHC was observed in athymic mouse models of human gliomas as well (Xie et al, 2016).…”

Section: Antineoplastic Activity Of Natural Capsaicin Analogsmentioning

confidence: 93%

Anticancer Activity of Natural and Synthetic Capsaicin Analogs

Friedman

Nolan

Brown

et al. 2017

J Pharmacol Exp Ther

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The nutritional compound capsaicin is the major spicy ingredient of chili peppers. Although traditionally associated with analgesic activity, recent studies have shown that capsaicin has profound antineoplastic effects in several types of human cancers. However, the applications of capsaicin as a clinically viable drug are limited by its unpleasant side effects, such as gastric irritation, stomach cramps, and burning sensation. This has led to extensive research focused on the identification and rational design of second-generation capsaicin analogs, which possess greater bioactivity than capsaicin. A majority of these natural capsaicinoids and synthetic capsaicin analogs have been studied for their pain-relieving activity. Only a few of these capsaicin analogs have been investigated for their anticancer activity in cell culture and animal models. The present review summarizes the current knowledge of the growth-inhibitory activity of natural capsaicinoids and synthetic capsaicin analogs. Future studies that examine the anticancer activity of a greater number of capsaicin analogs represent novel strategies in the treatment of human cancers.

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“…Previous studies suggest that both oxidative and non-oxidative pathways are involved in the metabolism of capsaicin and that several cytochrome P450 (CYP) isozymes participate in the metabolism of capsaicin. ,− CYPs are oxidative enzymes, which are involved in activation as well as detoxification of various xenobiotics. It was reported that biotransformation of capsaicin could give rise to various reactive metabolites (RMs) such as phenoxyl radical, quinone, quinone methide, and epoxide intermediates. ,,− Such RMs usually possess an electrophilic carbon center, making them highly amendable for nucleophilic attack through various endogenous molecules such as glutathione (GSH), proteins, and DNA. While covalent modifications of protein or DNA may in turn lead to toxicity including necrosis, mutagenesis, and carcinogenesis, conjugation with GSH is widely recognized as the major detoxification pathway in mammalian systems. − …”

Section: Introductionmentioning

confidence: 99%

“…Fifteen new conjugates were reported. In 2016, Halme et al reported one new metabolite and two new GSH conjugates . Recently, Qin et al further extended the number of known metabolites and conjugates .…”

Section: Introductionmentioning

confidence: 99%

Electrochemical Simulation of the Oxidative Capsaicin Metabolism

Kreidl

Rainer

Bonn

et al. 2021

Chem. Res. Toxicol.

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Capsaicin, primarily known as the pungent ingredient in hot peppers, is rapidly metabolized in the human body by enzymatic processes altering the pharmacological as well as toxicological properties. Herein, the oxidative transformation of capsaicin was investigated in vitro with electrochemistry as well as human liver microsomal incubations. The reaction mixtures were analyzed with liquid chromatography−mass spectrometry. Structure elucidation involved accurate mass measurements and multistage tandem mass spectrometry experiments. In total, 126 transformation products were detected. Electrochemistry provided evidence for 101 transformation products and the microsomal incubations for 46 species. 21 compounds were observed with both approaches. Identified oxidative pathways likely occurring during the phase I metabolism included dehydrogenation, O-demethylation, and hydroxylation reactions as well as combinations thereof. Furthermore, trapping of reactive intermediates either with glutathione or with electrochemically activated ribonucleosides provided evidence for the possible production of phase II metabolites and covalent adducts with a genetic material. Evidence for the occurrence of some capsaicin metabolites in humans was obtained by urine screening.

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Comparison of in vitro metabolism and cytotoxicity of capsaicin and dihydrocapsaicin

Cited by 24 publications

References 21 publications

Lactobacillus rhamnosus attenuates Thai chili extracts induced gut inflammation and dysbiosis despite capsaicin bactericidal effect against the probiotics, a possible toxicity of high dose capsaicin

Lactobacillus rhamnosus attenuates Thai chili extracts induced gut inflammation and dysbiosis despite capsaicin bactericidal effect against the probiotics, a possible toxicity of high dose capsaicin

Anticancer Activity of Natural and Synthetic Capsaicin Analogs

Electrochemical Simulation of the Oxidative Capsaicin Metabolism

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