High Concentrations Of Capsaicin Research Articles

Identification of ascorbic acid and phytochemical profiles of Scotch Bonnet pepper (Capsicum chinense) using High-Performance Liquid Chromatography-Ultraviolet Detector (HPLC-UV)

Researchers have discovered that red and green scotch peppers are extremely rich in phytochemicals and that these secondary metabolites are connected to several biological processes in the human body. This study aimed to determine the numerous phytochemicals present in scotch pepper seeds, flesh, and red and green varieties. The samples were pulverized after being air-dried. The phytochemicals and ascorbic acid contents were examined using a High-performance Liquid Chromatography-Ultraviolet detector (HPLC-UV). Twelve phytochemicals and ascorbic acid were identified in the flesh and seed of red scotch pepper, with lycopene having the highest content (83.10 mg/kg), the ascorbic acid content of 8.80 mg/kg; moreover, the seed of red scotch pepper revealed twelve phytochemicals and lycopene being the highest content (75.60 mg/kg) and ascorbic acid content of 6.80 mg/kg, furthermore, fourteen phytochemicals were identified in the flesh of red scotch bonnet pepper with lycopene the highest quantity (86.00 mg/kg) and ascorbic content of 10.60 mg/kg. Twelve phytochemicals were identified in the flesh and seed of green scotch bonnet pepper, lycopene (68.70 mg/kg) being the highest content, ascorbic acid content (6.50 mg/kg), twelve phytochemicals were revealed in the flesh of green pepper and lycopene had highest quantity (76.30 mg/kg), in the seed of green pepper, the lycopene content was 68.70 mg/kg. However, it has been shown that capsaicin, dihydrocapsaicin, and lutein concentrations varied, with red scotch pepper flesh having the highest concentration of capsaicin (7.50 mg/kg). The lycopene and ascorbic acid contents of flesh were the highest (86.00 mg/kg) and (10.60 mg/kg). The study's findings showed that red pepper flesh was better than other components that were looked at.

The contribution of subliminal perceptions, dietary habits, and psychological traits to the perception of oral tingling and burning sensations

The tingling evoked by Sichuan pepper and the burning elicited by chili pepper constitutes the typical flavor of Sichuan cuisine and is a component of leisure food. Although factors affecting the burning sensation have extensively been studied, few studies have examined the factors of individual sensitivity, personality traits, and dietary habits that contribute to the perception of oral tingling sensation, which hinders the formulation of tingling products and the development of new products. In contrast, many studies have examined the factors influencing the burning sensation. In this web-based survey, 68 participants disclosed their dietary habits, liking for tingling and hot foods, and psychological traits. Individual sensitivity to the tingling and burning sensation produced by a range of Sichuan pepper oleoresin and capsaicin solutions was determined using rated differences from control, generalized labeled magnitude scale method and ranking test. The consistency score indicated the accuracy of individual ranking results while also providing an indirect response to the sensitivity of the participant to supra-threshold for burning or tingling. Individual ratings for medium Sichuan pepper oleoresin concentrations significantly correlated with the just noticeable difference (p < 0.01), and ratings for medium and high capsaicin concentrations correlated significantly with 6-n-propylthiouracil ratings (p < 0.01). Notably, the power exponent of burning was significantly correlated with the burning recognition threshold (p < 0.01), and the power exponent of tingling and burning were significantly correlated (r = 0.340, p < 0.05). There was a negative correlation between supra-threshold tingling and burning sensation perceptions and life satisfaction ratings. Further, intensity ratings for oral tingling and burning sensation did not always correspond with individual sensitivity indicators (e.g., recognition threshold, 6-n-propylthiouracil, just noticeable difference, and consistency score). Thus, this study provides new insight into establishing a sensory selection method for chemesthetic sensation panelists and theoretical guidelines for formulation design and in-depth analysis of popular tingling dishes and foods.

Stability of High Concentration Capsaicin in Transfersome Carriers in Gel Dosage Form

Topical capsaicin with high concentrations (8%) is effective in the treatment of pain in Post-Herpetic Neuralgia (PHN) and HIV-Associated Distal Sensory Polyneuropathy (HIV-DSP) patients. High concentrations of capsaicin encapsulated in transfersome nanovesicles aim to reduce the irritating ability of capsaicin when using as drugs. Gel preparations were chosen in the formulation because they are non-sticky, easy to wash, easy to apply, and more practical. The components contained in the gel affect the stability of the gel. Physical and chemical stability tests need to be carried out to ensure the quality, safety and efficacy of the gel so that it meets the expected specifications during its shelf life. This study aims to determine the stability of selected gel formulas containing high concentrations of transfersome capsaicin. The selected gel formula is a gel containing a mixture of phosphatidylcholine (Phospholiphon 90G®) and Tween 80 (80:20). Stability was carried out at high temperature (40±2oC), room temperature (30±2oC), low temperature (5±3oC), and cycling test. The stability parameters tested included organoleptic, pH, viscosity, and assay. The results of the transfersom capsaicin gel stability test showed no change in pH, viscosity, and assay in all storage conditions, but the gel showed a change in color, smell, and taste when stored at high temperatures (40 ± 2oC). It can be concluded that the resulting capsaicin transfersome gel formula with a phospholipid:tween ratio of 80 (80:20) was less stable during 12 weeks of storage at 40 oC

Mitigation of the Toxicity of Capsaicin on Anaerobic Codigestion of Food Waste and Waste Activated Sludge Using Calcium Peroxide: A Comprehensive Analysis Using Computational and Biological Approaches

Increasing amounts of food waste with high concentrations of capsaicin are generated globally. Capsaicin concentration has been proven to inhibit methane production in the anaerobic codigestion process; thus, strategies to alleviate this toxicity are urgently needed. This study focuses on the use of calcium peroxide for alleviating the inhibitory effect of capsaicin and methane production promotion in anaerobic codigestion for the first time. Results show that calcium peroxide increases the rate of capsaicin degradation significantly. Based on active site prediction, degradation product identification, and density functional theory calculations, the main pathways of capsaicin degradation are verified to be O-demethylation and hydrogen abstraction. According to the quantitative structure–activity relationship, the main degradation products are less toxic than capsaicin. With an increase of calcium peroxide addition from 0 to 0.10 g/g VS (volatile solid), the methane yield and production rate are promoted from 174.92 ± 7.12 mg/g VS and 10.54 ± 0.32 mL/(g VS·d) to 307.56 ± 10.43 mg/g VS and 23.15 ± 0.72 mL/(g VS·d), respectively. This study provides insights into calcium peroxide-enhanced capsaicin degradation and demonstrates an effective niche to mitigate the capsaicin toxicity toward anaerobic codigestion.

Capsaicin suppresses ciliary function, while inducing permeability in bronchial epithelial cell cultures of COPD patients.

Take Home Message: Capsaicin modified inflammatory response and caused toxicity in bronchial epithelial cultures from patients with COPD. More importantly, capsaicin decreased ciliary beat frequency and induced epithelial permeability and these effects were partially prevented by formoterol and roflumilast.Tear gas is widely used to halt mass demonstrations. Studies have reported its adverse effects on multiple organ systems; however, its effect on individuals with chronic respiratory diseases and the underlying mechanisms of these effects are unclear. For the first time in the literature, we investigated the effects of capsaicin, the active ingredient of tear gas, on bronchial epithelial cell (BEC) cultures obtained from well-characterized groups of nonsmokers, smokers, and patients with chronic obstructive pulmonary disease (COPD). BEC cultures were incubated with 50-500 μM capsaicin in the absence and presence of formoterol (1μM) and roflumilast (0.1 μM) for 24 h. Ciliary beat frequency (CBF) and transepithelial electrical resistance (TEER) were assessed at T1/4, T1/2, T1, T2, T4, T6, and T24 h, whereas the release of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-8, and lactate dehydrogenase (LDH) was measured at T24 h. Capsaicin (250 µM) significantly decreased CBF of all BEC cultures from T1/4 h to T24 h (p<0.05). Formoterol significantly prevented decreases in CBF induced by capsaicin. Higher concentrations of capsaicin (250-500 μM) significantly reduced TEER of BECs from nonsmokers (T2-T24 h), smokers (T24 h) and COPD patients (T2 and T24 h), which was partially prevented by roflumilast. Capsaicin (500 μM) decreased release of IL-8 (p<0.0001) and GM-CSF (p<0.05) while inducing release of LDH in BECs (p<0.05), and this was more prominent in BEC from patients with COPD. In conclusion, our findings demonstrate that capsaicin can suppress ciliary activity and cytokine release from BECs, induce BEC culture permeability and cellular toxicity and that these effects can be partially prevented by formoterol and roflumilast.

NGF Enhances CGRP Release Evoked by Capsaicin from Rat Trigeminal Neurons: Differential Inhibition by SNAP-25-Cleaving Proteases.

Nerve growth factor (NGF) is known to intensify pain in various ways, so perturbing pertinent effects without negating its essential influences on neuronal functions could help the search for much-needed analgesics. Towards this goal, cultured neurons from neonatal rat trigeminal ganglia—a locus for craniofacial sensory nerves—were used to examine how NGF affects the Ca2+-dependent release of a pain mediator, calcitonin gene-related peptide (CGRP), that is triggered by activating a key signal transducer, transient receptor potential vanilloid 1 (TRPV1) with capsaicin (CAP). Measurements utilised neurons fed with or deprived of NGF for 2 days. Acute re-introduction of NGF induced Ca2+-dependent CGRP exocytosis that was inhibited by botulinum neurotoxin type A (BoNT/A) or a chimera of/E and/A (/EA), which truncated SNAP-25 (synaptosomal-associated protein with Mr = 25 k) at distinct sites. NGF additionally caused a Ca2+-independent enhancement of the neuropeptide release evoked by low concentrations (<100 nM) of CAP, but only marginally increased the peak response to ≥100 nM. Notably, BoNT/A inhibited CGRP exocytosis evoked by low but not high CAP concentrations, whereas/EA effectively reduced responses up to 1 µM CAP and inhibited to a greater extent its enhancement by NGF. In addition to establishing that sensitisation of sensory neurons to CAP by NGF is dependent on SNARE-mediated membrane fusion, insights were gleaned into the differential ability of two regions in the C-terminus of SNAP-25 (181–197 and 198–206) to support CAP-evoked Ca2+-dependent exocytosis at different intensities of stimulation.

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.

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.

Post-synthesis nanostructuration of BSA-Capsaicin nanoparticles generated by sucrose excipient

In the pharmaceutical industry nano-hydrocolloid systems frequently coalesce or present nanoparticle aggregation after a long storage periods. Besides, the lyophilization process used to dry nanoparticles (NPs) produces loss of their original properties after dispersion. In this work we evaluated the effect on morphology and physicochemical properties of different protective excipients during drying of bovine serum albumin (BSA) NPs loaded with different concentrations of capsaicin. Capsaicin concentrations of 0, 812, 1625, 2437, and 3250 µg mL−1 were used; subsequently, NPs were dried with deionized water (DW), NaCl (DN), sucrose (DS), and not dried (ND). We found that ND, DW, and DN treatments showed a negative effect on the NPs properties; while, DS reduced the aggregation and produced the formation of isolated nanoparticles at higher concentrations of capsaicin (3250 µg mL−1), improving their circular shape, morphometrical parameters, and ζ-potential. The stability of the BSA-capsaicin NPs was associated to complex capsaicin/amino acid/water, in which GLY/GLN, ALA/HIS, ARG, THR, TYR, and Iso/CYS amino acids are involved in the restructuration of capsaicin molecules into the surface of nanoparticles during the drying process. The secondary nanostructuration in the post-synthesis stage can improve the molecular stability of the particles and the capacity of entrapping hydrophobic drugs, like capsaicin.

Dual regulation of TRPV1 channels by phosphatidylinositol via functionally distinct binding sites

Regulation of the heat- and capsaicin-activated transient receptor potential vanilloid 1 (TRPV1) channel by phosphoinositides is complex and controversial. In the most recent TRPV1 cryo-EM structure, endogenous phosphatidylinositol (PtdIns) was detected in the vanilloid binding site, and phosphoinositides were proposed to act as competitive vanilloid antagonists. This model is difficult to reconcile with phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] being a well-established positive regulator of TRPV1. Here we show that in the presence of PtdIns(4,5)P2 in excised patches, PtdIns, but not PtdIns(4)P, partially inhibited TRPV1 activity at low, but not at high capsaicin concentrations. This is consistent with PtdIns acting as a competitive vanilloid antagonist. However, in the absence of PtdIns(4,5)P2, PtdIns partially stimulated TRPV1 activity. We computationally identified residues, which are in contact with PtdIns, but not with capsaicin in the vanilloid binding site. The I703A mutant of TRPV1 showed increased sensitivity to capsaicin, as expected when removing the effect of an endogenous competitive antagonist. I703A was not inhibited by PtdIns in the presence of PtdIns(4,5)P2, but it was still activated by PtdIns in the absence of PtdIns(4,5)P2 indicating that inhibition, but not activation by PtdIns proceeds via the vanilloid binding site. In molecular dynamics simulations, PtdIns was more stable than PtdIns(4,5)P2 in this inhibitory site, whereas PtdIns(4,5)P2 was more stable than PtdIns in a previously identified, nonoverlapping, putative activating binding site. Our data indicate that phosphoinositides regulate channel activity via functionally distinct binding sites, which may explain some of the complexities of the effects of these lipids on TRPV1.

Anti‐proliferative activities, phytochemical levels and fruit quality of pepper (Capsicum spp.) following prolonged storage

SummaryPeppers are rich in health‐promoting phytochemicals, which are involved in the defence mechanisms against cancer. To select a lead variety of pepper with anti‐proliferative activity against colon cancer cells and liver cancer cells, high antioxidant activity, and high concentrations of capsaicin, flavonoids and phenolics, we compared these attributes in nine different pepper accessions belonging to Capsicum annuum and C. chinense. Quality parameters such as weight loss and total soluble solids content were tested as well. The different parameters were determined immediately after harvest and after prolonged storage and marketing simulation. A significant variation of these traits was detected among the accessions. C. chinense line 1745 had the highest antioxidant activity, the highest levels of capsaicin and flavonoids, a high and specific anti‐cancer activity, and the lowest weight loss level during postharvest storage. It is proposed that line 1745 has potential for use as a source for health‐promoting traits and should be further evaluated for use as a nutraceutical for the prevention and treatment of colon and liver cancers.

Enhanced Transdermal Delivery of Concentrated Capsaicin from Chili Extract-Loaded Lipid Nanoparticles with Reduced Skin Irritation.

The aim of this study was to develop lipid-based nanoparticles that entrapped a high concentration of capsaicin (0.25%) from a capsicum oleoresin extract. The solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) were strategically fabricated to entrap capsaicin without a hazardous solvent. Optimized nanosize lipid particles with high capsaicin entrapment and loading capacity were achieved from pair-wise comparison of the solid lipid mixtures consisting of fatty esters and fatty alcohols, representing small and large crystal-structure molecules combined with a compatible liquid lipid and surfactants (crystallinity index = 3%). This report was focused on selectively captured capsaicin from oleoresin in amorphous chili extract-loaded NLCs with 85.27% ± 0.12% entrapment efficiency (EE) and 8.53% ± 0.01% loading capacity (LC). The particle size, polydispersity index, and zeta potential of chili extract-loaded NLCs were 148.50 ± 2.94 nm, 0.12 ± 0.03, and −29.58 ± 1.37 mV, respectively. The favorable zero-order kinetics that prolonged capsaicin release and the significantly faster transdermal penetration of the NLC attributed to the reduction in skin irritation of the concentrated capsaicin NLCs, as illustrated by the in vitro EpiDermTM three-dimensional human skin irritation test and hen’s egg test chorioallantoic membrane assay (HET-CAM).

Influence of irrigation on yield and primary and secondary metabolites in two chilies species, Capsicum annuum L. and Capsicum chinense Jacq

The effects of water stress on plant growth, yield, primary metabolites (sugars, organic acids, ascorbic acid) and secondary metabolites (total phenolic content, capsaicin and dihydrocapsaicin) accumulation, were evaluated for greenhouse production. A pot experiment was conducted on two species of chilies Capsicum annuum L. var 'Chili-AS Rot' and Capsicum chinense Jacq. var 'Naga Morich'. Plants were irrigated at two different treatments, optimal irrigation or field capacity and deficit irrigation or 50 % field capacity, which can be treated as drought stress. The effects of drought stress on quantity and quality of the yield, (primary and secondary metabolites) were studied. Deficit irrigation affected yield quantity, as both chili species had lower yield at deficit irrigation. Species C. chinense 'Naga Morich' under deficit irrigation abscised the flowers, thus no fruits were harvested at the third picking. Concentrations of sugars were lower at both plant species under deficit irrigation. Concentrations of organic acids in fruits of C. annuum 'Chili-AS Rot', such as citric acid, oxalic acid, fumaric acid, quinic acid were higher at optimal irrigation. Malic acid concentrations were similar at both irrigation treatments. In the fruits of C. chinense Jacq. 'Naga Morich' the concertation of citric acid and ascorbic acid was higher with optimal irrigation. Concentrations of other organic acids were higher at deficit irrigation. C. annuum 'Chili-AS Rot' had higher concentration of ascorbic acid and total phenolic content at optimal irrigation and higher capsaicin and dihydrocapsaicin concentrations in stressed plants. C. chinense 'Naga Morich' had higher concentrations of capsaicin, dihydrocapsaicin and total phenolic content at optimal irrigation regime.

Generation of BSA-capsaicin Nanoparticles and Their Hormesis Effect on the Rhodotorula mucilaginosa Yeast.

Capsaicin is a chemical compound found in pungent chili peppers (Capsicum spp.). In biotechnology, capsaicin has been proposed as a pathogen control; however, its low solubility in water and high instability limits its uses. The aim of this work was to study the effect of high concentrations of capsaicin on the synthesis of nanoparticles and to evaluate their inhibitory effect on the growth of Rhodotorula mucilaginosa yeast. Bovine serum albumin (BSA)-capsaicin nanoparticles were formulated at 0, 16.2, 32.5, 48.7 and 65.0 µg of capsaicin per mg of BSA. Nanoparticle properties were evaluated and they were added to cultures of R. mucilaginosa to quantify their effect on cell viability. We found that increased capsaicin levels caused several changes to the physicochemical parameters, probably due to changes in the hydrophobicity sites of the albumin during the nanostructuration. The administration of nanoparticles to cultures of R. mucilaginosa produced a maximal viability with nanoparticles at 16.2 µg/mg; on the contrary, nanoparticles at 65.0 µg/mg caused maximal cell death. R. mucilaginosa cells displayed a hormesis effect in response to the nanoparticle dose concentration. The nanoparticles showed different responses during the uptake process, probably as a consequence of the nanostructural properties of capsaicin in the BSA molecules.

Dry eye sensitizes cool cells to capsaicin-induced changes in activity via TRPV1.

Corneal cool cells are sensitive to the ocular fluid status of the corneal surface and may be responsible for the regulation of basal tear production. Previously, we have shown that dry eye, induced by lacrimal gland excision (LGE) in rats, sensitized corneal cool cells to the transient receptor potential melastatin 8 (TRPM8) agonist menthol and to cool stimulation. In the present study, we examined the effect of dry eye on the sensitivity of cool cells to the transient receptor potential vanilloid 1 (TRPV1) agonist capsaicin. Single-unit recordings in the trigeminal ganglion were performed 7-10 days after LGE. At a concentration of 0.3 μM, capsaicin did not affect ongoing or cool-evoked activity in control animals yet facilitated ongoing activity and suppressed cool-evoked activity in LGE animals. At higher concentrations (3 μM), capsaicin continued to facilitate ongoing activity in LGE animals but suppressed ongoing activity in control animals. Higher concentrations of capsaicin also suppressed cool-evoked activity in both groups of animals, with an overall greater effect in LGE animals. In addition to altering cool-evoked activity, capsaicin enhanced the sensitivity of cool cells to heat in LGE animals. Capsaicin-induced changes were prevented by the application of the TRPV1 antagonist capsazepine. With the use of fluorescent in situ hybridization, TRPV1 and TRPM8 expression was examined in retrograde tracer-identified corneal neurons. The coexpression of TRPV1 and TRPM8 in corneal neurons was significantly greater in LGE-treated animals when compared with sham controls. These results indicate that LGE-induced dry eye increases TRPV1-mediated responses in corneal cool cells at least in part through the increased expression of TRPV1. NEW & NOTEWORTHY Corneal cool cells are known to detect drying of the ocular surface. Our study is the first to report that dry eye induced alterations in cool cell response properties, including the increased responsiveness to noxious heat and activation by capsaicin. Along with the changes in cell response properties, it is possible these neurons also function differently in dry eye, relaying information related to the perception of ocular irritation in addition to regulating tearing and blinking.

English

In this study, the capsaicin content of chile pepper extracts from 29 unexplored varieties of Capsicum (twenty five varieties of Capsicum chinense and five of Capsicum annuum) was quantified and correlated with the antimicrobial potential against bacterial and fungal pathogens. The capsaicin content and bactericidal activity against numerous human pathogens (Salmonella, Escherichia coli O157:H7, Listeria monocytogenes, Staphylococcus aureus, Candida albicans) was compared to identify the most effective chile pepper varieties in the treatment of bacterial and fungal pathogens. The capsaicin content of the tested varieties varied from 29 to 42,633 ppm (139 - 682,135 SHU). On average, the fruits of C. chinense cultivars contained much higher concentrations of capsaicin than C. annuum cultivars. The undiluted chile peppers extracts with capsaicin concentrations greater than 25,000 SHU demonstrated bactericidal and antifungal effects. Overall, it was determined that L. monocytogenes and S. aureus were more susceptible to the antimicrobial effects of capsaicin than Salmonella and E. coli O157:H7, while C. albicans was markedly more susceptible than all bacterial species examined. The extract of the sixth most pungent cultivar, C. chinense Bhut Jolokia Red, showed the greatest antimicrobial potency of all screened peppers. The antimicrobial activity of pepper extracts was not directly correlated with increasing capsaicin concentrations, indicating that various Capsicum cultivars may possess distinct capsaicin derivatives. This is the first study which showed the relationship between capsaicin contents in different Capsicum varieties and their antimicrobial potential, and opens avenues in the study of capsaicin derivatives and their role in health and medicines. Key words: Capsicum, pathogen, capsaicin, peppers, antimicrobial, bactericidal.

TRPV1 mediates capsaicin-stimulated metabolic activity but not cell death or inhibition of interleukin-1β release in human THP-1 monocytes

Human monocytes and dendritic cells express transient receptor potential vanilloid 1 (TRPV1) which may play a role in mediating the inflammatory, immune and cancer surveillance responses of these cells. The aim of the present study was to investigate TRPV1 expression and function in THP-1 monocytic cells. RT-PCR and Western blot were used to detect TRPV1. The metabolic activity and viability of THP-1 cells following exposure to vanilloids was assessed using resorufin production from rezazurin. Cytokine release was measured using ELISA. TRPV1 was expressed in cultured THP-1 monocytic cells and naïve monocytes. Lower concentrations (<250 μM) of capsaicin, but not other putative TRPV1 agonists, were shown to stimulate cell metabolic activity, whereas at concentrations >250 μM, all agonists decreased metabolic activity. Capsaicin-stimulated THP-1 metabolic activity was blocked by the TRPV1 antagonist, 5-iodo-resiniferatoxin (5′-IRTX), whereas the decline in resorufin production by THP-1 cells at higher capsaicin concentrations (due to cell death), was not affected by 5′-IRTX. Finally, capsaicin (≤125 μM) significantly increased lipopolysaccharide-stimulated IL-6 and TNF-α release from THP-1 cells, whereas phytohaemagglutinin-stimulated IL-1β, TNF-α, MCP-1 and IL-6 release were concentration-dependently inhibited by capsaicin. Modulation of IL-1β release was not TRPV1 mediated. Overall, these results show that functional TRPV1 channels are present in naïve monocytes and THP-1 cells, and when activated, increase cell metabolic activity. In addition, capsaicin modifies cytokine release from THP-1 cells and induces cell death, most likely by a mechanism that is independent of TRPV1 activation.

Capsaicin 8% Dermal Patch: A Review in Peripheral Neuropathic Pain.

The adhesive capsaicin dermal patch (Qutenza®) delivers a high concentration (8% w/w) of synthetic capsaicin, a highly selective agonist of transient receptor potential vanilloid-1 (TRPV-1), directly to the site of pain. The capsaicin 8% dermal patch is indicated in the EU for the treatment of peripheral neuropathic pain (PNP) in adults, either alone or in combination with other medicinal products for pain. In patients with painful diabetic peripheral neuropathy, a single 30-min application of the capsaicin 8% dermal patch provided 12weeks of pain relief and improved sleep quality compared with placebo. Repeat treatment with the capsaicin 8% dermal patch plus standard of care over 52weeks provided sustained pain relief, with no negative neurological effects compared with standard of care alone. The capsaicin 8% dermal patch was non-inferior to oral pregabalin in relieving pain in patients with non-diabetic PNP, with a faster onset of action and greater treatment satisfaction. A single 60-min application of the capsaicin 8% dermal patch provided rapid and sustained pain relief in patients with postherpetic neuralgia. Results in patients with HIV-associated neuropathy were equivocal, with a significant improvement in pain intensity observed in one trial, but not in the other. The capsaicin 8% dermal patch was generally well tolerated; transient application-site reactions were the most common adverse events. In conclusion, the capsaicin 8% dermal patch is a useful addition to the treatment options currently available for patients with PNP.

Capsaicin inhibits proliferation and induces apoptosis in osteosarcoma cell lines via the mitogen‑activated protein kinase pathway.

Capsaicin, a pungent molecular compound present in many hot peppers, exerts anticancer activities against various human cancer cell lines by inducing apoptosis. However, the effects of capsaicin on human osteosarcoma (OS) as well as the related mechanisms remain to be fully elucidated. In the present study, the anticancer effects of capsaicin on 3 human OS cell lines (MG63, 143B and HOS) were investigated. Various concentrations of capsaicin (50–300 µM) effectively decreased cell viability in all 3 OS cell lines in a dose-dependent manner. Notably, capsaicin-induced apoptosis was observed when OS cells were treated with relatively high concentrations of capsaicin (starting at 250 µM). In addition, the mitochondrial apoptotic pathway was involved in the capsaicin-induced apoptosis in the OS cells. Meanwhile, our results also indicated that at relatively low concentrations (e.g., 100 µM), capsaicin could inhibit the proliferation, decrease the colony forming ability and induce G0/G1 phase cell cycle arrest of OS cells in a dose-dependent manner. Moreover, our results revealed that the anticancer effects induced by capsaicin on OS cell lines involved multiple MAPK signaling pathways as indicated by inactivation of the ERK1/2 and p38 pathways and activation of the JNK pathway. Furthermore, the results of animal experiments showed that capsaicin inhibited tumor growth in a xenograft model of human OS. In conclusion, these results indicate that capsaicin may exert therapeutic benefits as an adjunct to current cancer therapies but not as an independent anticancer agent.

Capsaicin and Its Role in Chronic Diseases.

A significant number of experimental and clinical studies published in peer-reviewed journals have demonstrated promising pharmacological properties of capsaicin in relieving signs and symptoms of non-communicable diseases (chronic diseases). This chapter provides an overview made from basic and clinical research studies of the potential therapeutic effects of capsaicin, loaded in different application forms, such as solution and cream, on chronic diseases (e.g. arthritis, chronic pain, functional gastrointestinal disorders and cancer). In addition to the anti-inflammatory and analgesic properties of capsaicin largely recognized via, mainly, interaction with the TRPV1, the effects of capsaicin on different cell signalling pathways will be further discussed here. The analgesic, anti-inflammatory or apoptotic effects of capsaicin show promising results in arthritis, neuropathic pain, gastrointestinal disorders or cancer, since evidence demonstrates that the oral or local application of capsaicin reduce inflammation and pain in rheumatoid arthritis, promotes gastric protection against ulcer and induces apoptosis of the tumour cells. Sadly, these results have been paralleled by conflicting studies, which indicate that high concentrations of capsaicin are likely to evoke deleterious effects, thus suggesting that capsaicin activates different pathways at different concentrations in both human and rodent tissues. Thus, to establish effective capsaicin doses for chronic conditions, which can be benefited from capsaicin therapeutic effects, is a real challenge that must be pursued.

Capsaicin 8 % Patch: A Review in Peripheral Neuropathic Pain.

The capsaicin 8 % patch (QUTENZA®) is an adhesive patch containing a high concentration (8 % w/w) of synthetic capsaicin, a selective agonist of transient receptor potential vanilloid 1 channel. It is approved for treatment of peripheral neuropathic pain in adults either alone or in combination with other medicinal products for pain in the EU; it is only approved to treat postherpetic neuralgia (PHN) in the USA. In patients with painful diabetic peripheral neuropathy (PDPN), a single 30-min application of the capsaicin 8 % patch significantly improved pain relief and sleep quality compared with placebo in a 12-week double-blind trial. In a 52-week, randomized trial, up to seven consecutive 30-min treatments with the capsaicin 8 % patch (≤7 treatments each at least 8 weeks apart) plus standard of care therapy was associated with sustained pain relief and no negative neurological safety consequences compared with standard of care. In two randomized trials, a single 60-min application of the capsaicin 8 % patch reduced pain scores significantly more than a low-concentration (0.04 %) capsaicin control patch in patients with PHN. Capsaicin 8 % patch treatment was noninferior to pregabalin (optimized dosage) in a randomized trial in patients with nondiabetic peripheral neuropathic pain. Results in two trials in patients with HIV-AN were equivocal, with a significant improvement in pain intensity observed in one trial, but not in the other. The capsaicin 8 % patch was associated with expected, transient, capsaicin-related application-site adverse events such as erythema and pain.