• YAKHAK HOEJI
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• v.25 no.3
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• pp.101-108
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• 1981

Quantitative determination of capsaicin in biological fluid was investigated. The pharmacokinetic study of capsaicin in rabbits was performed by high-pressure liquid chromatography, equipped with a microparticulate reversed-phase column and a fixed wavelength detector. Elution was carried out using methanolwater(70:30). It allows the quantitative determination at 8-400 ng level. When single dose of capsaicin(4mg/kg) was given to rabbits intravenously, the elimination phase was extremely short with average half-life to 17.35 minute. Urine excretion of capsaicin itself during first 2 hours after intravenous administration (4mg/kg) was 0.004-0.04% of the administered amount. The maximum plasma concentration of capsaicin after oral administration (300mg/kg) was $4{\times}10^{-7}$g/ml at 40 minutes. The $LD_{50}$ of capsaicin in mouse was 0.40mg/kg (i.v.) and 47.2 mg/kg (p.o.) which was determined by Litchfield and Wilcoxon's method, suggesting that the gastrointestinal absorption of capsaicin is poor.

• Journal of environmental and Sanitary engineering
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• v.10 no.3
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• pp.16-28
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• 1995

Influences of capsaicin on the activities of cytochrome P45O of liver cell were studied in rats. Rats were provided food and water ad libitum and capsaicin and methylcellulose were gavaged for 6 days. Body weight gain and liver weight/body weight ratio, microsomal protein content and serum HDL- cholesterol content, the activity of cytochrome P450 and erythromycin demethylase, the activities of ethoxyresorufin and pentoxyresorufin O- dealkylase were determined. Capsaicin increased body weight gain but showed no significant changes on liver weight as compared with control group. Capsaicin increased the microsomal protein significantly but decreased the serum HDL- cholesterol. Capsaicin decreased the microsomal cytochrome P4SO significantly and did not show any influences on erythromycin demethylase ( cytochrome P45O III A ). Capsaicin increased the activity of pentoxyresorufin O- dealkylase ( cytochrome P45O II B) and decreased the activity of ethoxyresorufin O-dealkylase ( cytochrome P45O I A). It might be concluded that capsaicin reduced the microsomal cytochrome P45O and induced the CYP III and inhibited the CYP I A. It also might be concluded that capsaicin had no influence on CYP III A and decreased serum HDL- cholesterol. In these results capsaicin can not be used as an anti- atherosclerotic agent by increasing the CYP III A and HDL- cholesterol but it is considered that the more precise study on these theme is necessary.

• Archives of Pharmacal Research
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• v.28 no.1
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• pp.73-80
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• 2005

The effect of capsaicin on apoptotic cell death was investigated in HepG2 human hepatoma cells. Capsaicin induced apoptosis in time- and dose-dependent manners. Capsaicin induced a rapid and sustained increase in intracellular $Ca^{2+}$ concentration, and BAPTA, an intracellular $Ca^{2+}$ chelator, significantly inhibited capsaicin-induced apoptosis. The capsaicin-induced increase in the intracellular $Ca^{2+}$ and apoptosis were not significantly affected by the extracellular $Ca^{2+}$ chelation with EGTA, whereas blockers of intracellular $Ca^{2+}$ release (dantrolene) and phospholipase C inhibitors, U-73122 and manoalide, profoundly reduced the capsaicin effects. Interestingly, treatment with the vanilloid receptor antagonist, capsazepine, did not inhibit either the increased capsaicin-induced $Ca^{2+}$ or apoptosis. Collectively, these results suggest that the capsaicin-induced apoptosis in the HepG2 cells may result from the activation of a PLC-dependent intracellular $Ca^{2+}$ release pathway, and it is further suggested that capsaicin may be valuable for the therapeutic intervention of human hepatomas.

• The Korean Journal of Physiology
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• v.25 no.1
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• pp.87-99
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• 1991

In order to elucidate whether capsaicin applied topically acts as a pain-producing subastance or as a tastant, neuronal activities of the chorda tympani nerve(CN), lingual nerve(LN), solitary tract nucleus(STN), and trigeminal nucleus(TGN) were recorded while thermal and taste stimuli, and capsaicin were being applied topically, and algesics intra-arterially to the tongue of cats anesthetized with ${\alpha}-chloralsoe$. In addition, the STN neurons were examined after wheat germ agglutinin-horseradish peroxidase(WGA-HRP) was applied to the CN. The CN fibers responded to taste and thermal stimuli, algesics, and capsaicin. Responses to capsaicin were significantly correlated with those to taste and thermal stimuli. The LN fibers mainly responded to mechanical and thermal stimuli, algesics, and capsaicin. Responses to capsaicin were significantly correlated with those to algesics. The STN neurons responded to taste and thermal stiumli, algesics, and capsaicin. Responses to capsaicin were significantly correlated with those to taste and thermal stiumli in somewhat different fashion from those of the CN fibers. The TGN neurons mainly responded to mechanical stimuli, algesics, and capsaicin. Correlations between responses to capsaicin and any others were not significant. After WGA-HRP was applied to the CN, the STN neurons which receive input from the CN were identified largely in the medio-ventral portion to the solitary tract. These results suggest that capsaicin produce taste as well as pain sensation. Sensory information evoked by capsaicin can be conveyed to the STN, especially medio-ventral portion, via the CN as gustatory information on the one hand, and to the STN or TGN via the LN as noxious information on the other. In addiation, the noxious information may be conveyed to the STN via the CN.

• Restorative Dentistry and Endodontics
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• v.26 no.5
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• pp.436-442
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• 2001

Neuropeptide such as calcitonin gene-related peptide and substance P may mediate neurogenic inflammation, but little is known about the regulation of neuropeptide release from rat spinal cord. Eugenol has been reported to reduce odontogenic pain and is known to have a structure similar to capsaicin, a potent stimulant of certain nociceptors. This study was done to examine the effect of capsaicin and eugenol on immunoreactive calcitonin gene-related peptide (iCGRP) release from rat spinal cord and whether eugenol regulates capsaicin-sensitive release of iCCRP or it evokes capsaicin-sensitive release of iCGRP. The dor-sal half of rat lumbar spinal cord was chopped into 200$\mu$m slices. They were superfused (500$\mu$l/min) in vitro with an oxygenated Kreb's buffer. The EC$_{50}$ of capsaicin on iCGRP release was measured. Eugenol (600$\mu$M and 1.2mM) and vehicle (0.02% 2-hydroxyl-$\beta$-cyclodextrin) were administered prior to stimulation of rat lumbar spinal cord with capsaicin. The amount of iCGRP release from rat lumbar spinal cord was measured by radioimmunoassay. The results were as follows : 1. iCGRP release from rat lumbar spinal cord was dependent on concentration of capsaicin. The EC$_{50}$ of capsaicin on iCGRP release was 3$\mu$M. 2. In the vehicle treated group, capsaicin (3$\mu$M) evoked a 14-fold increase over basal iCGRP level. 3. Administration of 600$\mu$M and 1.2mM eugenol evoked a 2.2-fold increase and a 2.3-fold increase over basal iCGRP level respectively. 4. Administration of 600$\mu$M and 1.2mM eugenol increased capsaicin evoked release of iCGRP by more than 50%. These results indicate that eugenol evoke CGRP release from central nervous system and potentiate the pain-inducing action of capsaicin on it.

• Journal of Pharmacopuncture
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• v.11 no.1
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• pp.149-162
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• 2008

Objectives : The purpose of this study is to investigate the effects of hot pepper extract and capsaicin on the adipogenesis in 3T3-L1 cells, lipolysis in rat epididymal adipocytes and histological changes in porcine adipose tissue. Methods : Inhibiton of preadipocyte differentiation and/or stimulation of lipolysis play important roles in reducing obesity. 3T3-L1 preadipocytes were differentiated with adipogenic reagents by incubating for 3 days in the absence or presence of hot pepper extract or capsaicin ranging from 0.01 to $1mg/m{\ell}$. The effects of hot pepper extract and capsaicin on adipogenesis were examined by measuring GPDH activity and by Oil Red O staining. Mature adipocytes from rat epididymal fat pad was incubated with hot pepper extract or capsaicin ranging from 0.01 to $1mg/m{\ell}$ for 3 hrs. The effects of hot pepper extract and capsaicin on lipolysis were examined by measuring free glycerol released. Fat tissue from pig skin was injected with hot pepper extract or capsaicinCFP ranging from 0.1 to $10mg/m{\ell}$ to examine the effects of hot pepper extract and capsaicin on histological changes under light microscopy. Results : The following results were obtained from present study on adipogenesis of preadipocytes, lipolysis of adipocytes and histological changes in fat tissue. 1. Hot pepper extract and capsaicin inhibited adipogenic differentiation at the concentration of 0.1 and $0.01mg/m{\ell}$, respectively, indicating that capsaicin was more effective in inhibiting adipogenesis than hot pepper extract. 2. Hot pepper extract and capsaicin decreased the activity of glycerol-3-phosphate dehydrogenase(GPDH) at the concentration of 0.1 and $0.01mg/m{\ell}$, respectively, indicating that capsaicin was more effective in inhibiting adipogenic differentiation than hot pepper extract. 3. Hot pepper extract and capsaicin increased glycerol release at the concentration of $0.1mg/m{\ell}$. There was no difference in lipolytic activity between hot pepper extract and capsaicin at the corresponding concentration. 4. Hot pepper extract and capsaicin caused shrinkage of fat cells, resulting in cell death at the concentration of $1.0mg/m{\ell}$, although capsaicin exerted this action over wide area than hot pepper extract. Conclusions : These results suggest that hot pepper extract and capsaicin efficiently inhibited adipogenesis, increased lipolysis of adipocytes and caused to shrink fat cells. Future studies are needed to make use of hot pepper extract pharmacopuncture for the treatment of obesity.

• Journal of the Korean Society of Food Science and Nutrition
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• v.14 no.4
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• pp.409-418
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• 1985

The contents of capicin according to the growth of fresh red peppers (Capsicum annum) and to-brewing of 'kochujang' (fermented hot peper-soybean paste) and 'kimchi' (a group of Korean seasoned pickles) were quantified by High Pressure Liquid Chromatography. Colors of the peppers were evaluated by Hunter Value and quantity of capsanthin. The content and chemical structure of capsaicin after heat treatment were traced by HPLC, GCMS, UV and NMR. It was found that the capsaicin content of red peper was highest 6 to 7 weeks after flowering and that peppers with high Hunter Value contained higher level of capsanthin. The content of capsaicin of kochujang and kimchi declined by 20% and 17% respectively, as they are brewed. Capsaicin content was decreased by heating. However, change in its chemical strtcure was not occurred.

• IMMUNE NETWORK
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• v.1 no.3
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• pp.203-212
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• 2001

Background: Rapid advances in neuroendocrine immunology have established the concept of bidirectional communication between the immune and neuroendocrine systems. Capsaicin suppresses the immune function by destroying substance P acting as mediatior of neuroendocrine immune system. Methods and Results: In this study, effect of capsaicin on mature murine lymphocyte functions and lymphoid tissue morphology was examined. Formally, capsaicin showed the strong cytotoxic effect on splenocyte over $10{\mu}g/ml$ concentration in citro. And proliferation and Th1-cytokine expression of splenic cells in mice that received high dose of capsaicin ($100{\mu}g/mouse$) were significantly diminished. However, low dose of capsaicin treatment did not influence these responses in vivo($1{\mu}g/mouse$) and in vitro (under $5{\mu}g/ml$). And the morphology of spleen and lymph nodes after capsaicin treatment was observed. In the spleen of mice injected with high dose of capsaicin (100, $200{\mu}g/mouse$), the size of white pulp was significantly decreased and the length of red pulp was increased, Moreover, vascularity index was diminished in a dose dependent manner. Conclusion: These results implies that immunosuppressive effect of capsaicin is associated with cytotoxic activity on lymphocyte, Th1-cytokine down-regulation and lymphoid tissue abnormalization, and this report is expected to give a hand to the study for the mechanism of action of neurotoxin of the immune system.

• Biomolecules & Therapeutics
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• v.5 no.2
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• pp.150-157
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• 1997

Capsaicin cream has been used to attenuate the pain associated with diabetic neuropathy, rheum-atoid arthritis, osteoarthritis and postherpetic neuralgia. But its common side effect, local irritation, limits the use of it and there is still a need for a new analgesic devoid of this side effect. This study was conducted to compare the local irritant effect of DA-5018, a new capsaicin derivative, with that of capsaicin in various animal models and human beings. Capsaicin, applied topically to the mouse ear, produced dose-dependent increase of ear volume and the frequency of ear scratching behavior in mice. Neither ear volume nor scratching behavior was affected by DA-5018. In eye wiping test of rat, DA-5018 was 10 times less irritant than capsaicin. Capsaicin administered intradermally into the rat paw elicited paw lick/lift response with a potency which was three times that of DA-5018. Zostrix-HP (0.075% capsaicin cream), but not DA-50180.3% cream, increased ear volume of rat and induced thermal hyperalgesia in normal and carrageenan inflamed paws. Six day-treatment of Zostrix-HP failed to develop tolerance against this thermal hyperalgesia. In human beings, Zostrix-HP produced burning sensation and itching in more than 90% of volunteers involved and its maximum irritant effect was significantly higher than that of DA-5018 cream. These results suggest that local irritation and burning sensation produced by DA-5018 is much less than capsaicin.

• Archives of Pharmacal Research
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• v.27 no.11
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• pp.1147-1153
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• 2004

Bladder cancer is a common cancer with high risk of recurrence and mortality. Intravesicle chemotherapy after trans-urethral resection is required to prevent tumor recurrence and progression. It has been known that antioxidants enhance the antitumor effect of bacillus Calmette-Guerin (BCG), the most effective intravesical bladder cancer treatment. Capsaicin, the major pungent ingredient in genus Capsicum, has recently been tried as an intravesical drug for overactive bladder and it has also been shown to induce apoptotic cell death in many cancer cells. In this study, we investigated the apoptosis-inducing effect and alterations in the cellular redox state of capsaicin in MBT-2 murine bladder tumor cells. Capsaicin induced apoptotic MBT-2 cell death in a time- and dose-dependent manner. The capsaicin-induced apoptosis was blocked by the pretreatment with Z-VAD-fmk, a broad-range caspase inhibitor, or Ac-DEVD-CHO, a caspase-3 inhibitor. In addition to the caspase-3 activation, capsaicin also induced cytochrome c release and decrease in Bcl-2 protein expression with no changes in the level of Bax. Furthermore, capsaicin at the concentration of inducing apoptosis also markedly reduced the level of reactive oxygen species and lipid peroxidation, implying that capsaicin may enhance the antitumor effect of BCG in bladder cancer treatment. These results further suggest that capsaicin may be a valuable intravesical chemotherapeutic agent for bladder cancers.