Hot Chili Peppers Research Articles

Capsaicin induces CYP3A4 expression via pregnane X receptor and CCAAT/enhancer‐binding protein β activation

Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is the principal pungent ingredient in hot red and chili peppers. Many studies have focused on the anticarcinogenic or chemopreventive activities of capsaicin. However, the influence of capsaicin on CYP3A4, its involvement in drug metabolism, and the underlying mechanisms remain unclear. Here, we examined the effect of capsaicin on CYP3A4 expression and the metabolism of CYP3A1 substrate, nifedipine in male Sprague-Dawley rats. Capsaicin induced the enzymatic activity and expression of CYP3A4 in HepG2 cells. Treatment with a human pregnane X receptor (hPXR) inhibitor reduced the inductive effects of capsaicin on CYP3A4 expression. Capsaicin also induced the activation of CCAAT/enhancer-binding protein β (C/EBPβ). Moreover, capsaicin increased the activation of the transient receptor potential vanilloid type-1 receptor downstream signaling components Ca²⁺/calmodulin-dependent protein kinase and Akt. Capsaicin elevated the level of CYP3A1 in rat liver and significantly increased the biotransformation of nifedipine to dehydronifedipine. From these data, we conclude that capsaicin induces CYP3A4 expression in vitro and in vivo. This induction was achieved by the activation of hPXR and C/EBPβ. Our results suggest that capsaicin might induce CYP3A4 expression; thus, exposure to capsaicin may increase the metabolism of CYP3A4 substrate and potentially cause food-drug interactions.

Kicking Bear, John Trudell, and Anthony Kiedis (of the Red Hot Chili Peppers): “Show Indians” and Pop-Cultural Colonialism

Kicking Bear, John Trudell, and Anthony Kiedis (of the Red Hot Chili Peppers)“Show Indians” and Pop-Cultural Colonialism Cynthia L. Landrum (bio) One evening in the summer of 1989, at the inception of my twenty-second year, I walked up the steps of the Mount Royal Tavern in downtown Baltimore. Passing through the doorway, I gazed up as usual at the ceiling, a replica of the Sistine Chapel—God giving life to Adam through fingertips that never fully touch. From there my eyes moved around the room to the bartender, the painting of the three Graces, and tables of Maryland Institute of Art students, street punks, Rastafarians, and hippies. I was looking for my friends, the members of the band the Allmighty Senators (at least one of whom was of Native American descent), when I heard a familiar click in the jukebox as the next song loaded and played. It was “Higher Ground”—a new version, not the familiar Stevie Wonder version. It was faster and funkier, with a posthardcore LA edge. All of the bar’s talking, chatting, laughing, conversing, and divulging voices were overshadowed and ceased to matter. The voice of the lead singer, Anthony Kiedis, boomed out, “People, keep on learning . . .” There was a jolt in the room as glasses and bottles clinked continually in the warm July night. It was the type of evening when, regardless of your attire, sweat poured down your frame from a ninety-nine-degree day that refused to cool down. I gradually made my way through the crowd to the jukebox, midway through the bar, not quite to the pinball machine and back booth. I had to know who was singing this song. My eyes kept meeting the hand of God giving life to Adam as I drew toward the jukebox. I finally stood before the glowing Technicolor wonder, face to face with the Red Hot Chili Peppers’ album cover. A woman resembling the [End Page 182] Virgin Mary smiled and cradled the tattooed, pierced, and half-naked band. Their singer, Anthony Kiedis, was a visual fusion of musician Iggy Pop and actor Joe Dallesandro. The name of the album was Mother’s Milk, and it seemed to fit neatly into this freakish universe as the music radiated and undulated into the woodwork and brick. I stood halfway in the bar and halfway through my life on a foot inadvertently tapping to the crescendo. I knew something was different about their sound. They were a fusion of hardcore, funk, jazz, and reggae, strung together with a voice that melted into the music as if it were another instrument. It was a voice that unleashed a Pandora’s box of Generation X counterculture, that teetered on the edge but never quite fell into the nebulous abyss below. Anthony Kiedis, in a sense, was the phoenix rising over and over again out of the ashes of his own despair, reflecting this in his lyrics and voice. Spawned in 1983 from the late 1970s LA punk and hardcore scenes, the Red Hot Chili Peppers followed in the wake of seminal bands like X, Black Flag, and the Germs, slightly predating the early 1990s Seattle grunge sound, with Nirvana, Sound Garden, Pearl Jam, and Mud Honey. The Chili Peppers were not as self-consciously political as their hardcore contemporaries, yet politics was still in their sound. From its inception, Generation X was a collection of fragmented people who did not fit in with their peers, their parents’ expectations, or the conservative political climate of the 1980s. Extremely individualistic, many punk rock Gen Xers believed in and worked to build some classless utopia beyond social status or skin color using nothing but boundless youth, idealism, and anger. And music was just one of the tangible “manifestation” of this belief. Other manifestations included skateboarding, zines, film, art, and writing or simply attending shows while moving against the grain of the larger American society in a way that was much more in step with the maverick Beats of the 1950s. For over thirty years, American Indians, Alaskan Natives, and Hawaiian Natives have also actively participated in the Generation X and Y countercultures alongside non-Native participants. For...

Capsaicin, a Tasty Free Radical Scavenger: Mechanism of Action and Kinetics

The free radical scavenging activity of capsaicin (CAP), which is the pungent component of hot chili peppers, has been studied in aqueous and lipid solutions, using the density functional theory. Different mechanisms of reaction have been considered: single electron transfer (SET), hydrogen transfer (HT), and radical adduct formation (RAF). Rate constants and branching ratios of the different channels of reaction are provided, as well as an interpretation of the UV-vis spectra. CAP is predicted to react faster in aqueous solution than in nonpolar media with oxygenated free radicals, and it was found to be a more efficient scavenger than melatonin and caffeine. It was also found that while SET does not contribute to the overall reactivity of CAP toward (•)OOH, (•)OOCH(3), and (•)OCH(3) radicals, it might be important for the reactions with more electrophilic radicals such as (•)OH, (•)OCCl(3), and (•)OOCCl(3). The main process, responsible for the peroxyl scavenging activity of CAP, was found to be the HT from the OH phenolic group. For the reaction with (•)OCH(3), on the other hand, the HT from allylic sites are predicted to be the main channels of reaction. In this particular case a wider product distribution is predicted. This supports the role of the reacting free radical on the preponderant mechanism of action of free radical scavengers.

Kicking Bear, John Trudell, and Anthony Kiedis (of the Red Hot Chili Peppers): “Show Indians” and Pop-Cultural Colonialism

Kicking Bear, John Trudell, and Anthony Kiedis (of the Red Hot Chili Peppers): “Show Indians” and Pop-Cultural Colonialism

Phenolic compounds and antioxidant activities in some fruits and vegetables from Burkina Faso

Levels of total phenolic compounds (TPC), proanthocyanidins (PAs) and antioxidant activities among sixteen fruits and vegetables commonly consumed in Burkina Faso were determined. Levels of TPC ranged from 0.21 to 3.33 mg of gallic acid equivalent per gram of fresh matter. The highest contents in TPC were found in hot chili pepper, okra, lemon, spinach, onion, while the highest contents in PAs were found in spinach (3.52 mg), onion (2.35 mg), okra (1.27 mg), hot chili pepper (1.11 mg), tomato (0.54 mg) and garlic (0.46 mg). Antioxidant activities ranged from 0 to 9 µmol per gram of fresh weight, trolox equivalent antioxidant capacity (TEAC). The highest values of TEAC were found in garlic (9.6 µmol), okra (3 µmol), spinach (2.2 µmol), tamarind (2.2 µmol) and onion (2.1 µmol). These data revealed that, some local fruits and vegetables from Burkina Faso are potential sources of bioactive compounds.

Capsaicin mediates apoptosis in human nasopharyngeal carcinoma NPC-TW 039 cells through mitochondrial depolarization and endoplasmic reticulum stress

Capsaicin, a pungent compound found in hot chili peppers, has been reported to have antitumor activities in many human cancer cell lines, but the induction of precise apoptosis signaling pathway in human nasopharyngeal carcinoma (NPC) cells is unclear. Here, we investigated the molecular mechanisms of capsaicin-induced apoptosis in human NPC, NPC-TW 039, cells. Effects of capsaicin involved endoplasmic reticulum (ER) stress, caspase-3 activation and mitochondrial depolarization. Capsaicin-induced cytotoxic effects (cell death) through G0/G1 phase arrest and induction of apoptosis of NPC-TW 039 cells in a dose-dependent manner. Capsaicin treatment triggered ER stress by promoting the production of reactive oxygen species (ROS), increasing levels of inositol-requiring 1 enzyme (IRE1), growth arrest and DNA-damage-inducible 153 (GADD153) and glucose-regulated protein 78 (GRP78). Other effects included an increase in cytosolic Ca(2+), loss of the mitochondrial transmembrane potential (ΔΨ(m)), releases of cytochrome c and apoptosis-inducing factor (AIF), and activation of caspase-9 and -3. Furthermore, capsaicin induced increases in the ratio of Bax/Bcl-2 and abundance of apoptosis-related protein levels. These results suggest that ER stress- and mitochondria-mediated cell death is involved in capsaicin-induced apoptosis in NPC-TW 039 cells.

The role of capsaicin-sensitive sensory neurons in autonomic dysreflexia in the spinal cord injured-rat

Background: A subpopulation of sensory neurons express the transient receptor potential cation channel subfamily V member 1 (TRPV1). It is activated by heat (>43°C), low pH, and capsaicin (the pungent ingredient in hot chili peppers), and has emerged as a promising target for the treatment of pain. Both pain and autonomic dysreflexia that develop in the wake of SCI have been attributed to maladaptive sensory plasticity. We hypothesize that TRPV-1-positive afferents contribute to the development of autonomic dysreflexia (AD).

Dynamic mechanical allodynia: A homogeneous entity?

One intriguing symptom of neuropathic pain is dynamic echanical allodynia. It is established that dynamic mechancal allodynia in the periphery is mediated by large afferent bers [1], but despite different theories the exact underlyng mechanisms of dynamic mechanical allodynia are still nknown. Capsaicin, the active ingredient in hot chilli pepper, actiates a subpopulation of the transient receptor potential vanilloid TRPV1) receptors, which are located on smalland medium-sized ociceptors. This causes ongoing burning pain, a flare response, ypoesthesia to cold, and a secondary hyperalgesic area with eat and pinprick hyperalgesia and dynamic mechanical allodyia [2,3]. These symptoms are similar to what is seen following eat injury [4], and experimental injection or topical application f capsaicin may thus be a model of a burn injury. Due to the evelopment of allodynia and hyperalgesia, the capsaicin model as also been used to study clinical expressions of neuropathic pain 2]. In order to study the usefulness of the capsaicin model in eflecting the dynamic mechanical allodynia seen in neuropathic ain patients, Samuelsson et al. in this issue of the Scandinavian ournal of Pain compared the psychophysical characteristics of ynamic mechanical allodynia in the area of neuropathic pain and n the secondary hyperalgesic area in capsaicin-treated skin [5]. ynamic mechanical allodynia was examined in the area of neuopathic pain in nine patients with well-characterized pain due o a peripheral nerve or nerve root lesion, and subsequently in he area of the secondary hyperalgesia following intradermal capaicin injection on the contralateral side. There were no obvious

Determining the yield and several quality parameters of 'Chili Jalapeno' in comparison to 'Pical' and 'Geyik Boynuzu' pepper cultivars under Mediterranean conditions

We studied yield and quality parameters of three hot Chili pepper cultivars under Antakya conditions. The cultivars tested were 'Chili Jalapeno', 'Pical' and 'Geyik Boynuzu', which is a local cultivar. The experiment was designed as a completely randomized block design with three blocks in each treatment and conducted for two years. The variable measured in the experiment include total yield (kg/da), fruit number (number/plant), yield per plant (g/plant), fruit weight (g), fruit width (cm), fruit length (cm), skin + flesh width (mm) and soluble solids (%). The results indicated that 'Chili Jalapeno' and 'Pical' cultivars gave significantly higher total yield than 'Geyik Boynuzu' with 1951 and 1818 kg/da, respectively while 1593 kg/da yield was recovered from 'Geyik Boynuzu'. Similarly, for yield per plant, 'Chili Jalapeno' and 'Pical' cultivars gave significantly higher yield than 'Geyik Boynuzu'. The highest soluble solid was found on 'Pical' while the lowest from 'Geyik Boynuzu'. Moreover, 'Pical' was determined as the thinnest skin + flesh width. For these reasons, 'Pical' could be recommended for dry pepper production. We suggest 'Chili Jalapeno' cultivar for pickling. 'Geyik Boynuzu' is a local cultivar that is commonly grown in the region. For this cultivar, we suggest breeding studies should be initiated to further improve this cultivar. Key words: Pepper, cultivar, pepper production, Antakya, Capsicum annuum L.

Capsaicin induces apoptosis in SCC‐4 human tongue cancer cells through mitochondria‐dependent and ‐independent pathways

Although there have been advances in the fields of surgery, radiotherapy, and chemotherapy of tongue cancer, the cure rates are still not substantially satisfactory. Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is the major pungent ingredient of hot chili pepper and has been reported to have an antitumor effect on many human cancer cell types. The molecular mechanisms of the antitumor effect of capsaicin are not yet completely understood. Herein, we investigated whether capsaicin induces apoptosis in human tongue cancer cells. Capsaicin decreased the percentage of viable cells in a dose-dependent manner in human tongue cancer SCC-4 cells. In addition, capsaicin produced DNA fragmentation, decreased the DNA contents (sub-G1 phase), and induced G0/G1 phase arrest in SCC-4 cells. We demonstrated that capsaicin-induced apoptosis is associated with an increase in reactive oxygen species and Ca²⁺ generations and a disruption of the mitochondrial transmenbrane potential (ΔΨ(m)). Treatment with capsaicin induced a dramatic increase in caspase-3 and -9 activities, as assessed by flow cytometric methods. A possible mechanism of capsaicin-induced apoptosis is involved in the activation of caspase-3 (one of the apoptosis-executing enzyme). Confocal laser microscope examination also showed that capsaicin induced the releases of AIF, ATF-4, and GADD153 from mitochondria of SCC-4 cells.

Introduction of Armand Kuris, Recipient of the 2010 Clark P. Read Mentor Award

Introduction of Armand Kuris, Recipient of the 2010 Clark P. Read Mentor Award

Inhibitors of monoacylglycerol lipase, fatty-acid amide hydrolase and endocannabinoid transport differentially suppress capsaicin-induced behavioral sensitization through peripheral endocannabinoid mechanisms

Monoacylglycerol lipase (MGL) and fatty-acid amide hydrolase (FAAH) degrade the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA), respectively. Pharmacological inhibition of these enzymes in the periphery may elucidate the role of endocannabinoids in controlling nociceptive transmission. We compared effects of the MGL inhibitor JZL184, the FAAH inhibitor URB597, and the endocannabinoid uptake inhibitor VDM11, administered locally in the paw, on behavioral hypersensitivities produced by capsaicin, the pungent ingredient in hot chili peppers. Intradermal capsaicin (10 μg i.pl.) produced nocifensive behavior, thermal hyperalgesia, and mechanical allodynia in rats. JZL184 (100 μg i.pl.) suppressed capsaicin-induced nocifensive behavior and thermal hyperalgesia without altering capsaicin-evoked mechanical allodynia. Effects of JZL184 were blocked by either the CB 1 antagonist AM251 (80 μg i.pl.) or the CB 2 antagonist AM630 (25 μg i.pl.). URB597 (75 μg i.pl.) suppressed capsaicin-induced mechanical allodynia without altering capsaicin-evoked thermal hyperalgesia or nocifensive behavior. Effects of URB597 were blocked by AM251 (80 μg i.pl.), but not by AM630 (25 μg i.pl.). VDM11 (100 μg i.pl.) suppressed capsaicin-evoked hypersensitivity for all three dependent measures (nocifensive behavior, thermal hyperalgesia, and mechanical allodynia), suggesting an additive effect following putative elevation of both AEA and 2-AG. The VDM11-induced suppression of capsaicin-evoked nocifensive behavior and thermal hyperalgesia was blocked by either AM251 (80 μg i.pl.) or AM630 (25 μg i.pl.), as observed with JZL184. The VDM11-induced suppression of capsaicin-evoked mechanical allodynia was blocked by AM251 (25 μg i.pl.) only, as observed with URB597. Thus, peripheral inhibition of enzymes hydrolyzing 2-AG and AEA suppresses capsaicin-evoked behavioral sensitization with distinct patterns of pharmacological specificity and in a non-overlapping and modality-specific manner. Modulation of endocannabinoids in the periphery suppressed capsaicin-evoked nocifensive behavior and thermal hyperalgesia through either CB 1 or CB 2 receptor mechanisms but suppressed capsaicin-evoked mechanical allodynia through CB 1 mechanisms only. Inhibition of endocannabinoid transport was more effective in suppressing capsaicin-induced sensitization compared to inhibition of either FAAH or MGL alone. These studies are the first to unveil the effects of pharmacologically increasing peripheral endocannabinoid levels on capsaicin-induced behavioral hypersensitivities. Our data suggest that 2-AG, the putative product of MGL inhibition, and AEA, the putative product of FAAH inhibition, differentially suppress capsaicin-induced nociception through peripheral cannabinoid mechanisms.

Neuroprotection induced by vitamin E against oxidative stress in hippocampal neurons: Involvement of TRPV1 channels

Pretreatment of cultured hippocampal neurons with a low concentration of alpha-tocopherol (alpha-TP), the major component of vitamin E, results in a long-lasting protection against oxidative damages, via genomic effects. This neuroprotection is associated with the attenuation of a calcium influx triggered by oxidative agents such as Fe(2+) ions. This Ca(2+) influx is supported by a TRP-like channel, also partly involved in capacitive calcium entry within neurons. Here, we evidence the contribution of TRPV1 channels in this mechanism. TRPV1 channels are activated by various agents including capsaicin, the pungent component of hot chili peppers and blocked by capsazepine (CPZ) or 5'-iodo-resiniferatoxin. Both TRPV1 inhibitors strongly reduced Fe(2+) ion-mediated toxicity and Ca(2+) influx, in the same way as to alpha-TP pretreatment. Moreover, CPZ also decreased capacitive calcium entry in hippocampal neurons. Finally, both CPZ and 5'-iodo-resiniferatoxin reduced spontaneous excitatory synaptic transmission; this depression of synaptic transmission being largely occluded in alpha-TP-pretreated neurons. In conclusion, in our experimental model, TRPV1 channels are involved in the Fe(2+) ion-induced neuronal death and a negative modulation of this channel activity by alpha-TP pretreatment may account, at least in part, for the long-lasting neuroprotection against oxidative stress.

Capsaicin Induced the Upregulation of Transcriptional and Translational Expression of Glycolytic Enzymes Related to Energy Metabolism in Human Intestinal Epithelial Cells

Capsaicin is the major pungent component in hot chili pepper. It is known that capsaicin induces the increase of energy metabolism through adrenaline activation. The aim of this study was to investigate the mechanism underlying the effect of capsaicin on energy metabolism in human intestinal epithelial cells (Caco-2). To clarify the mechanism, we performed proteomics, real time-PCR, ATP measurement, and MTT in this study. Glycolytic enzymes, namely, phosphoglycerate mutase (PGM) and triosephosphate isomerase (TPI), were overexpressed in capsaicin-treated Caco-2 cells. mRNA expression levels of TPI and PGM were also increased in capsaicin-treated Caco-2 cells. Furthermore, intracellular adenosine triphosphate (ATP) content, which is the end product of glycolysis, was increased. To demonstrate the intracellular ATP production and ATP accumulation, the viability of Caco-2 cells incubated with glucose free medium was measured. The viability of capsaicin pretreated cells was higher than that of untreated cells. All these observations strongly indicate that capsaicin increases energy metabolism in human epithelial cells through the activation of glycolytic enzymes.

Ação nematicida de extratos de alho, mostarda, pimenta malagueta, de óleo de mostarda e de dois produtos à base de capsainóides e alil isotiocianato sobre juvenis de Meloidogyne javanica, (treub) Chitwood, 1949, em casa de vegetação

Neves, W.S; Freitas, L.G.; Coutinho, M.M.; Giaretta-Dallemole, R.; Fabry, C.F.S.; Dhingra, O.D. & Ferraz, S. Atividade nematicida de extratos botânicos de pimenta malagueta (Capsicum frutescens), mostarda (Brassica campestris) e alho (Allium sativum) sobre o nematóide das galhas, Meloidogyne javanica, em casa de vegetação. Summa Phytopathologica, v.35, n.4, p.255-261, 2009 O experimento teve como objetivo avaliar a atividade nematicida de extratos botânicos dos frutos de pimenta malagueta (Capsicum frutescens), plantas de mostarda (Brassica campestris), de bulbos de alho (Allium sativum) e óleo de mostarda sobre o nematóide das galhas, Meloidogyne javanica, em tomateiro em casa de vegetação e posteriormente comparar os extratos que apresentassem maior redução de número de galhas e de ovos com dois produtos à base de capsaicina, capsainóides e alil isotiocianato. Uma mistura peneirada de solo e areia na proporção 1:1 (v:v) foi colocada em vasos de plástico e infestada com 4000 ovos de M. javanica. Quatro dias após 20 mL de cada extrato, na concentração de 1000 ppm, foram espalhados sobre o solo. Apenas água foi derramada sobre o solo infestado no tratamento testemunha. Mudas de tomate com 20 dias de idade foram transplantadas quatro dias após a colocação dos extratos ao solo. Após quarenta e cinco dias avaliou-se o número de ovos e o número de galhas do sistema radicular de cada planta. Os extratos clorofórmico e cetônico de pimenta malagueta e o óleo de mostarda apresentaram melhor controle do nematóide, diferindo estatisticamente da testemunha quanto ao número de galhas. Porém, somente o óleo de mostarda reduziu significativamente o número de ovos quando comparado com a testemunha. Os extratos cetônico e clorofórmico de pimenta e o óleo de mostarda reduziram em 34,5%, 40,4% e 99,9% o número de galhas, respectivamente e o óleo de mostarda reduziu em 99,9% o número de ovos. No experimento seguinte foram avaliados o extrato clorofórmico de pimenta, o óleo de mostarda, o produto comercial Champon® e um produto em desenvolvimento na UFV, chamado DS, a base de capsaicina, capsainóides e alil isotiocianato em diferentes concentrações. Os produtos Champon® e DS e o óleo de mostarda reduziram o número de ovos e galhas quando comparados à testemunha em todas as concentrações testadas. O extrato de pimenta apresentou o melhor resultado na concentração de 400 ppm, reduzindo o número de ovos e galhas em relação à testemunha, porém esse foi bem maior quando comparado com os demais produtos testados.

Determination of banned Sudan dyes in food samples by molecularly imprinted solid phase extraction‐high performance liquid chromatography

A method for molecularly imprinted SPE of banned Sudan azo-dyes from food samples was investigated. The molecularly imprinted polymer was obtained by suspension polymerization using 1-(4-chlorophenyl)azonaphthalen-2-ol as the mimic template. The molecular recognition properties of imprinted beads were evaluated for use as a SPE sorbent, in order to develop a selective extraction protocol for the Sudan class of dyes. The optimized extraction protocol resulted in a reliable molecularly imprinted SPE (MISPE) method suitable for HPLC analysis. It was selective for the main analyte, Sudan I, and the related azo-dyes Sudan II, III, IV, Sudan Red B, and Sudan Red 7B, while the permitted azo-dyes Allura Red AC, Neococcin, and Sunset Yellow FCF were not extracted. The method was tested for Sudan I, II, III, and IV in five different food samples (hot chilli pepper, hot chilli tomato sauce, sausage, tomato sauce, and hard boiled egg yolk) at three concentration levels (15, 100, and 300 microg/g). It demonstrated itself to be insensitive to the presence of different complex matrices, precise, accurate, and with good recovery rates (85-101%). The LOD and LOQ were satisfactory for most analytical determinations.

Capsaicin-induced apoptosis is regulated by endoplasmic reticulum stress- and calpain-mediated mitochondrial cell death pathways

Capsaicin, a pungent compound found in hot chili peppers, induces apoptotic cell death in various cell lines, however, the precise apoptosis signaling pathway is unknown. Here, we investigated capsaicin-induced apoptotic signaling in the human breast cell line MCF10A and found that it involves both endoplasmic reticulum (ER) stress and calpain activation. Capsaicin inhibited growth in a dose-dependent manner and induced apoptotic nuclear changes in MCF10A cells. Capsaicin also induced degradation of tumor suppressor p53; this effect was enhanced by the ER stressor tunicamycin. The proteasome inhibitor MG132 completely blocked capsaicin-induced p53 degradation and enhanced apoptotic cell death. Capsaicin treatment triggered ER stress by increasing levels of IRE1, GADD153/Chop, GRP78/Bip, and activated caspase-4. It led to an increase in cytosolic Ca 2+, calpain activation, loss of the mitochondrial transmembrane potential, release of mitochondrial cytochrome c, and caspase-9 and -7 activation. Furthermore, capsaicin-induced the mitochondrial apoptotic pathway through calpain-mediated Bid translocation to the mitochondria and nuclear translocation of apoptosis-inducing factor (AIF). Capsaicin-induced caspase-9, Bid cleavage, and AIF translocation were blocked by calpeptin, and BAPTA and calpeptin attenuated calpain activation and Bid cleavage. Thus, both ER stress- and mitochondria-mediated death pathways are involved in capsaicin-induced apoptosis.

Capsaicin Reduces Tissue Damage in Experimental Acute Pancreatitis

Calcitonin gene-related peptide (CGRP) is released from perivascular pancreatic nerves. It effects vasomotion and cytokine liberation in inflammatory processes, including acute pancreatitis (AP). Calcitonin gene-related peptide liberation is stimulated by capsaicin, a substance of red hot chili peppers. Aim of the study was to investigate the influence of exogenous capsaicin on experimental AP. Acute pancreatitis was induced in rats by glycodeoxycholic acid and cerulein. Animals were divided into 4 groups: (1) severe AP, (2) severe AP+capsaicin, (3) control without AP, and (4) control+capsaicin. After 24 hours, survival, histology, and CGRP were evaluated (n=6/group). In additional animals, erythrocyte flow and leukocyte activation were evaluated by intravital microscopy 6 hours after AP induction (n=6/group). In the control groups, all animals survived without histological alterations. Mortality in severe AP was 67%. Capsaicin reduced mortality to 16% (P<0.05). Acute pancreatitis animals developed pancreatic inflammation and necrosis, which was significantly less after capsaicin application. Intravital microscopy in severe AP showed reduced erythrocyte velocity and increased leukocyte adhesion, which was nearly normalized by capsaicin (P<0.01). Calcitonin gene-related peptide increased in both capsaicin groups, indicating endogenous CGRP liberation (P<0.01). Capsaicin releases endogenous CGRP with improved pancreatic microcirculation and reduced inflammation in experimental AP. This underlines neuropeptide activity in the pathogenesis of AP.

Capsaicin induces apoptosis by generating reactive oxygen species and disrupting mitochondrial transmembrane potential in human colon cancer cell lines

Although genetic factors are a well-known cause of colorectal cancer, environmental factors contribute more to its development. Despite advances in the fields of surgery, radiotherapy and chemotherapy, the cure rates for colon cancer have not substantially improved over the past few decades. Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), the principal pungent ingredient of hot chili pepper, has exhibited an anti-tumor effect in many cell types. However, the mechanisms responsible for the anti-tumor effect of capsaicin are not yet completely understood. In this study, we investigated whether capsaicin induces apoptosis in colon cancer cell lines. Capsaicin decreased cell viability in a dose-dependent manner in Colo320DM and LoVo cells. In addition, capsaicin produced cell morphology changes and DNA fragmentation, decreased the DNA contents, and induced phosphatidylserine translocation, which is a hallmark of apoptotic cell death. We showed that capsaicin-induced apoptosis is associated with an increase in ROS generation and a disruption of the mitochondrial transmenbrane potential. A possible mechanism of capsaicin-induced apoptosis is the activation of caspase 3, a major apoptosis-executing enzyme. Treatment with capsaicin induced a dramatic increase in caspase 3 activity, as assessed by the cleavage of Ac-DEVD-AMC, a fluorogenic substrate. In conclusion, our results clearly showed that capsaicin induced apoptosis in colon cancer cells. Although the actual mechanisms of capsaicin-induced apoptosis remain uncertain, it may be a beneficial agent for colon cancer treatment and chemoprevention.

Contamination of the organophosphorus insecticide ethion residues in commercial samples of red-hot chilli spice in Kuwait

This study aims to determine the contamination residue levels of ethion in different forms of red-hot chilli samples using gas chromatography analysis with tandem mass spectrometry detection mode. The results of this study clearly demonstrated that the percentage of ethion residue levels decreased remarkably from 81 to 19% of 156 and 384 red chilli samples analysed during 2004 and 2005, respectively. Further results also showed that only 15% of 225 samples analysed in 2006 were found to be contaminated with the residues of ethion pesticide, whereas the decrease in residual ethion contamination percentage level was slightly varied to 16% of 450 samples surveyed in 2007. Mean concentrations of ethion residues were in the range of less than 2 µg kg1 in all tested hot chilli pepper varieties. These results highlighted the necessity to routinely monitor this particular food spice commodity for ethion contamination in order to avoid the exposure to these harmful residues and, moreover, confirmed the importance of such pesticide monitoring programme to reduce the incidence of illegal residues in red chilli peppers.