Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is the main component in hot peppers, including red chili peppers, jalapenos, and habanero, belonging to the genus Capsicum. Capsaicin is a potent antioxidant that interferes with free radical activities. In the present study, the possible protective effect of capsaicin was studied against methyl methanesulphonate (MMS) induced toxicity in third instar larvae of transgenic Drosophila melanogaster (hsp70-lacZ)Bg. The third instar was allowed to feed on the diet having different doses of capsaicin and MMS separately and in combination. The results suggested that the exposure of third instar larvae to the diet having MMS alone showed significant hsp70 expression as well as tissue DNA and oxidative damage, whereas the larvae feed on the diet having MMS and capsaicin showed a decrease in the toxic effects for 48-h of exposure. In conclusion, capsaicin showed a dose-dependent decrease in the toxic effects induced by MMS in the third instar larvae of transgenic Drosophila melanogaster.
Acetylcholinesterase ; metabolism ; Animals ; Animals, Genetically Modified ; Anticarcinogenic Agents ; pharmacology ; Capsaicin ; pharmacology ; DNA Damage ; drug effects ; Drosophila melanogaster ; drug effects ; Larva ; drug effects ; Methyl Methanesulfonate ; antagonists & inhibitors

OBJECTIVETo investigate the role of capsaicin in regulating permeation of P-gp substrate rhodamine 123 (R123) across the jejunum, ileum and colon membranes of rats.

METHODSThe permeability of R123 or fluorescein sodium (CF) across the jejunum, ileum and colon membranes of male SD rats was evaluated using a Ussing chamber. The concentration of R123 or CF in the receptor was determined using fluorospectrophotometry to calculate the apparent permeability coefficient (Papp).

RESULTSCompared with the blank control group, capsaicin increased the permeability of R123 across jejunal membranes in the mucosal-to-serosal (M-S) direction and decreased its permeability in the serosal-to-mucosal (S-M) direction, but produced no obvious effect on R123 transport across the ileum or colon membranes. Capsaicin caused a regional increase in the permeability of CF across the jejunal membranes compared with the control group, but CF transport across the ileum and colon membranes was not affected.

CONCLUSIONCapsaicin can affect the transport of R123 and CF across rat jejunal membranes, and this effect is shows an obvious intestine segment-related difference probably because of the different distribution of P-gp or tight junction in the intestines. This finding suggests that capsaicin is a weak P-gp inhibitor and an improver of mucous membrane channels.

ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Animals ; Capsaicin ; pharmacology ; Colon ; metabolism ; Fluorescein ; pharmacokinetics ; Ileum ; metabolism ; Intestinal Absorption ; Jejunum ; metabolism ; Male ; Permeability ; Rats ; Rats, Sprague-Dawley ; Rhodamine 123 ; pharmacokinetics

To further uncover the scientific significance and molecular mechanism of the Chinese herbs with pungent hot or warm natures, endogenous and exogenous expression systems were established by isolation of dorsal root ganglion (DRG) neurons and transfection of HEK293 cells with TRPV1 channel gene separately. On this basis, the regulation action of capsaicin, one main ingredient from chili pepper, on TRPV1 channel was further explored by using confocal microscope. Besides, the three-sites one-unit technique and method were constructed based on the brown adipose tissue (BAT), anal and tail skin temperatures. Then the effect of capsaicin on mouse energy metabolism was evaluated. Both endogenous and exogenous TRPV1 channel could be activated and this action could be specifically blocked by the TRPV1 channel inhibitor capsazepine. Simultaneously, the mice's core body temperature and BAT temperature fall down and then go up, accompanied by the increase of temperature of the mice's tail skin. Promotion of the energy metabolism by activation of TRPV1 channel might be the common way for the pungent-hot (warm) herbs to demonstrate their natures.
Adipose Tissue, Brown ; drug effects ; physiology ; Animals ; Capsaicin ; analogs & derivatives ; pharmacology ; Energy Metabolism ; Ganglia, Spinal ; cytology ; HEK293 Cells ; Humans ; Mice ; Neurons ; drug effects ; physiology ; Plants, Medicinal ; chemistry ; TRPV Cation Channels ; physiology ; Temperature ; Thermogenesis

Airway remodeling is an important pathological feature of asthma and the basis of severe asthma. Proliferation of airway smooth muscle cells (ASMCs) is a major contributor to airway remodeling. As an important Ca(2+) channel, transient receptor potential vanilloid 1 (TRPV1) plays the key role in the cell pathological and physiological processes. This study investigated the expression and activity of TRPV1 channel, and further clarified the effect of TRPV1 channel on the ASMCs proliferation and apoptosis in order to provide the scientific basis to treat asthmatic airway remodeling in clinical practice. Immunofluorescence staining and reverse transcription polymerase chain reaction (RT-PCR) were used to detect the expression of TRPV1 in rat ASMCs. Intracellular Ca(2+) was detected using the single cell confocal fluorescence microscopy measurement loaded with Fluo-4/AM. The cell cycles were observed by flow cytometry. MTT assay and Hoechst 33258 staining were used to detect the proliferation and apoptosis of ASMCs in rats respectively. The data showed that: (1) TRPV1 channel was present in rat ASMCs. (2) TRPV1 channel agonist, capsaicin, increased the Ca(2+) influx in a concentration-dependent manner (EC50=284.3±58 nmol/L). TRPV1 channel antagonist, capsazepine, inhibited Ca(2+) influx in rat ASMCs. (3) Capsaicin significantly increased the percentage of S+G2M ASMCs and the absorbance of MTT assay. Capsazepine had the opposite effect. (4) Capsaicin significantly inhibited the apoptosis, whereas capsazepine had the opposite effect. These results suggest that TRPV1 is present and mediates Ca(2+) influx in rat ASMCs. TRPV1 activity stimulates proliferation of ASMCs in rats.
Animals ; Antipruritics ; pharmacology ; Apoptosis ; physiology ; Bronchi ; cytology ; metabolism ; Calcium Signaling ; drug effects ; physiology ; Capsaicin ; analogs & derivatives ; pharmacology ; Cell Proliferation ; Myocytes, Smooth Muscle ; cytology ; metabolism ; Rats ; Rats, Sprague-Dawley ; TRPV Cation Channels ; antagonists & inhibitors ; metabolism

The purpose of this study was to investigate the differences in subjective acute effects of alcohol and naltrexone among those who prefer spicy food to varying degrees. Acute biphasic alcohol effects scale (BAES), visual analogue scale for craving (VAS-C), blood alcohol concentration (BAC) and food preference scale were measured in 26 men. Repeated measures ANOVA (2 preference groupsx4 time blocks) on the stimulative subscale of BAES revealed a significant group by block interaction in naltrexone condition (N+) (P<0.001), but not in non-naltrexone condition (N-). Furthermore, repeated measures ANOVA (2 drug groupsx4 time blocks) on the stimulative subscale of BAES revealed a significant group by block interaction in strong preference for spicy food (SP) (P<0.001), but not in lesser preference for spicy food (LP). The paired t-test revealed that significant suppression of the stimulative subscale of BAES was observed at 15 min (P<0.001) and 30 min (P<0.001) after drinking when N+ compared with N- in SP. For those who prefer spicy food, the stimulative effect of acute alcohol administration was suppressed by naltrexone. This result suggests that the effect of naltrexone may vary according to spicy food preference.
Adult ; Alcohol Drinking/*adverse effects ; Alcoholism/*drug therapy ; Capsaicin/pharmacology ; Food Preferences/*drug effects ; Humans ; Male ; Naltrexone/adverse effects/*therapeutic use ; Narcotic Antagonists/adverse effects/*therapeutic use ; Questionnaires ; Sensory System Agents/pharmacology ; Young Adult

OBJECTIVETo observe the descending modulation of cardiac nociception by the rostral ventromedial medulla (RVM) in rats.

METHODSA rat model of cardiosomatic motor reflex (CMR) was established by injecting capsaicin into the pericardial sac to induce cardiac nociception, and the electromyogram (EMG) response of the dorsal spinotrapezius muscle was studied. The RVM was electrically stimulated (25, 75 and 100 µA) or destroyed to examine whether RVM exerted descending modulation on cardiac nociception.

RESULTSElectrical stimulation of the RVM at 8 sites produced intensity-dependent inhibition of EMG responses to noxious cardiac stimulus (F[2,21]=43.188, P=0.001). Electrical stimulation at 3 sites caused facilitated EMG responses, but the increased magnitude of the EMG was not dependent on stimulation intensity (F[2,6]=0.884, P=0.461). Stimulation at 11 sites produced biphasic effects: at a low intensity (25 µA), the elicited EMG magnitude was significantly larger than baseline (P<0.05), and at greater intensities (75/100 µA), the stimulation caused suppression of the EMG magnitude to a level significantly lower than the baseline (P<0.05). Electrolytic lesion of the RVM resulted in significantly increased EMG responses compared with the baseline and sham lesion group.

CONCLUSIONCardiac nociception evoked by capsaicin stimulation is subjected to descending biphasic modulation by the RVM, which produces predominantly descending inhibition on heart pain.

Animals ; Capsaicin ; pharmacology ; Electric Stimulation ; Electromyography ; drug effects ; Male ; Medulla Oblongata ; physiology ; Nociception ; Nociceptors ; drug effects ; physiology ; Pain ; physiopathology ; Pericardium ; drug effects ; physiology ; Rats ; Rats, Sprague-Dawley ; Sensory System Agents ; pharmacology

OBJECTIVETo evaluate the effect of capsaicin on nude mice xenografted with colorectal carcinoma cells, and to explore its mechanism of action.

METHODSA nude mouse model of colorectal cancer was established by subcutaneous inoculation of human colorectal carcinoma HT-29 cells. Terminal deoxynucleotidyl transferase-mediated nicked labeling assay (TUNEL) was undertaken to detect the cell proliferation and apoptosis in the xenograft tissue in nude mice. Immunohistochemical (IHC) staining and Western blot were used to detect the expression of HSP27, Cyt-C and active caspase-3.

RESULTSThe tumor growth of the groups C10 and C20 was significantly slower than that of the group NS. The integrated optical density (IOD) of both the group C5 (2532.14 ± 578.11) and group C10 (6364.03 ± 1137.98) was significantly higher than that of the group NS (760.12 ± 238.05), (P < 0.05). The integrated optical density (IOD) of the group C20 was (15743.96 ± 1855.95), significantly higher than that of the groups C10, C5 and NS (all were P < 0.01). Immunohistochemistry showed that the cytoplasmic expression of HSP27 was strongly positive in the group NS, and significantly reduced with the increasing dose of capsaicin in the treated groups. The expression of active caspase-3 and Cyt-C in the group NS was weakly positive, and was significantly increased with the increasing dose of capsaicin in the groups C5 and C10 (P < 0.05), and the expression of active caspase-3 and Cyt-C of the group C20 was significantly higher than that of the groups C5, C10 and NS (P < 0.01). Western blot analysis showed that both the expressions of HSP27 of the group C5 (0.73 ± 0.05) and the group C10 (0.41 ± 0.03) were significantly lower than that of the group NS (P < 0.05). The expression of HSP27 of the group C20 (0.22 ± 0.06) was significantly lower than that of the groups C5, C10 and NS (P < 0.01). The expressions of active-caspase-3 and Cyt-C in the group C5 were (2.57 ± 0.34) and (2.03 ± 0.38), significantly higher than those of the group NS (P < 0.05). The expressions of active-caspase-3 and Cyt-C in the group C10 were (4.23 ± 0.45) and (3.13 ± 0.44), also significantly higher than those of the group NS (P < 0.05). The expressions of active-caspase-3 and Cyt-C in the group C20 were (5.78 ± 0.48) and (4.92 ± 0.52), significantly higher than those of the group C5, C10 and NS (P < 0.01). TUNEL analysis showed that there was a significant difference of cell apoptosis in comparison of each two groups. The higher dose of capsaicin was used, the more apoptosis was observed.

CONCLUSIONSCapsaicin can significantly inhibit the tumor growth and induce cell apoptosis in the colorectal carcinoma xenograft in nude mice. Its mechanism of action is possibly related with the down-regulation of HSP27 expression and up-regulation of expression of active caspase-3 and Cyt-C in the colorectal carcinoma xenograft in nude mice.

Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacology ; Apoptosis ; drug effects ; Capsaicin ; administration & dosage ; pharmacology ; Caspase 3 ; metabolism ; Cell Proliferation ; drug effects ; Cytochrome c Group ; metabolism ; Dose-Response Relationship, Drug ; Female ; HSP27 Heat-Shock Proteins ; metabolism ; HT29 Cells ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Random Allocation ; Tumor Burden ; Xenograft Model Antitumor Assays

OBJECTIVETo investigate the vasodilating effect of capsaicin (CAP) on rat mesenteric artery and its mechanism.

METHODSThe third branch of the superior mesenteric artery in male Sprague-Dawley rat (250-350 g) was excised, the periadventitial fat and connective tissue were removed and the mesenteric artery was dissected into 2 mm rings. Each ring was placed in a 5 ml organ bath of DMT 610M system and the tension was recorded.

RESULTSCAP (10(-9)-10(-5) mol/L) relaxed endothelium-intact and endothelium-denuded mesenteric artery pre-constricted by phenylephrine (10(-5) mol/L), and the vasodilation in endothelium-intact mesenteric artery was stronger than that in endothelium-denuded one. Pretreatment with either L-NAME (3 X10(-4) mol/L), an inhibitor of nitric oxide synthase(NOS), or CGRP8-37 (2 X 10(-6) mol/L), an antagonist of calcitonin gene-related peptide (CGRP), for 30 min significantly attenuated the relaxation of endothelium-intact mesenteric artery induced by CAP. CGRP (10(-10)-3 X10(-8) mol/L) relaxed endothelium-intact and endothelium-denuded mesenteric artery pre-constricted by phenylephrine, and the vasodilation in endothelium-intact mesenteric artery was stronger than that in endothelium-denuded one. Substance P did not relax the mesenteric artery pre-constricted by phenylephrine.

CONCLUSIONCAP has partial endothelium-dependent relaxation effect on rat mesenteric artery, which may be mediated by activating the endothelial NOS-NO pathway. The endothelium-independent relaxation in rat mesenteric artery induced by CAP may be mediated by CGRP.

Animals ; Calcitonin Gene-Related Peptide ; metabolism ; Capsaicin ; pharmacology ; In Vitro Techniques ; Male ; Mesenteric Arteries ; drug effects ; physiology ; Peptide Fragments ; metabolism ; Rats ; Rats, Sprague-Dawley ; Vasodilation ; drug effects

OBJECTIVETo assess the inhibitory modulation of blood pressure by stimulation of the deep peroneal nerve (DPN) and to determine the involvement of nociceptive fibers in the modulation.

METHODSAll the animals were divided into six groups (A-F). The rats in groups A and B received no pretreatment. The rats in groups C and D received subcutaneous injection of capsaicin or control vehicle, respectively, near the DPN for 2 days. Those in groups E and F had the DPN exposed to capsaicin or control vehicle, respectively, for 20 min. Subsequently, pressor responses were induced by stimulation of paraventricular nucleus (PVN) either electrically (groups A and C C-F) or chemically via injection of glutamate (group B). After two stable pressor responses (baseline), all groups were subject to 5-min DPN stimulation followed by PVN stimulation for 10 s. Arterial blood pressure, heart rate, and electrocardiogram were recorded. The pressor response was calculated as the difference in the mean arterial pressure (MAP) before and after PVN stimulation, and changes from baseline in pressor response after DPN stimulation were compared between the groups.

RESULTSIncreases of MAP of 22.88±2.18 mm Hg and 20.32±5.25 mm Hg were induced by electrical (group A) or chemical (group B) stimulation of the PVN, respectively. These pressor responses were inhibited by stimulation of the DPN, and the MAP was reduced to 12.00±2.10 mm Hg in group A (n=6, P<0.01) and 7.00±2.85 mm Hg in group B (n=6, P<0.01). Subcutaneous injection of capsaicin (125 mg/kg) near the DPN in group C (n=7) had no effect on the inhibitory effect of DPN stimulation compared with the group D (n=9), and neither did blockade of nociceptive fibers with capsaicin in group E (n=6) compared with group F (n=8).

CONCLUSIONStimulation of the DPN mimicking acupuncture has an inhibitory effect on the pressor response, and the effect is mediated by capsaicin-insensitive afferent fibers in the DPN.

Acupuncture Therapy ; Anesthesia ; Animals ; Blood Pressure ; drug effects ; Capsaicin ; administration & dosage ; pharmacology ; Electric Stimulation ; Injections, Subcutaneous ; Male ; Paraventricular Hypothalamic Nucleus ; cytology ; drug effects ; Peroneal Nerve ; drug effects ; physiology ; Pressoreceptors ; drug effects ; physiology ; Rats ; Rats, Sprague-Dawley

PURPOSE: To investigate the anti-tumor effect of capsaicin on human pharyngeal squamous carcinoma cells (FaDu). MATERIALS AND METHODS: The expression of apoptosis/cell cycle-related proteins (or genes) was examined by reverse transcriptase-polymerase chain reaction, western blotting and ELISA methods, while the apoptotic cell population, cell morphology and DNA fragmentation levels were assessed using flow cytometry, fluorescence microscopy and agarose gel electrophoresis. RESULTS: Capsaicin was found to inhibit the growth and proliferation of FaDu cells in a dose- and time-dependent manner. Apoptotic cell death was confirmed by observing increases in nuclear condensation, nuclear DNA fragmentation and sub-G1 DNA content. The observed increase in cytosolic cytochrome c, activation of caspase 3 and PARP (p85) levels following capsaicin treatment indicated that the apoptotic response was mitochondrial pathway-dependent. Gene/protein expression analysis of Bcl-2, Bad and Bax further revealed decreased anti-apoptotic Bcl-2 protein and increased pro-apoptotic Bad/Bax expression. Furthermore, capsaicin suppressed the cell cycle progression at the G1/S phase in FaDu cells by decreasing the expression of the regulators of cyclin B1 and D1, as well as cyclin-dependent protein kinases cdk-1, cdk-2 and cdk-4. CONCLUSION: Our current data show that capsaicin induces apoptosis in FaDu cells and this response is associated with mitochondrial pathways, possibly by mediating cell cycle arrest at G1/S.
Apoptosis/drug effects ; Blotting, Western ; Capsaicin/*pharmacology ; Carcinoma, Squamous Cell/*metabolism ; Cell Cycle/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Humans ; Microscopy, Fluorescence ; Pharyngeal Neoplasms/*metabolism ; Proto-Oncogene Proteins c-bcl-2/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; bcl-2-Associated X Protein/genetics/metabolism ; bcl-Associated Death Protein/genetics/metabolism