• Title, Summary, Keyword: Capsaicin

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Capsaicin-Induced Apoptosis and Reduced Release of Reactive Oxygen Species in MBT-2 Murine Bladder Tumor Cells

  • Lee, Ji-Seon;Chang, Jong-Sun;Lee, Ji-Youl;Kim, Jung-Ae
    • 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.

Neurotoxic Desensitizing Effect of Capsaicin on Peripheral Sensory Nerve Endings in Guinea Pig Bronchi (기니픽 기관지 말초신경에 대한 캡사이신의 탈감작 효과)

  • Jung, Yi-Sook;Cho, Tai-Soon;Moon, Chang-Hyun;Shin, Hwa-Sup
    • YAKHAK HOEJI
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    • v.41 no.1
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    • pp.139-146
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    • 1997
  • In the present study, capsaicin-induced desensitization of peripheral sensory nerves were investigated by using guinea pig bronchi, in which these nerves are stimulated with cap saicin to produce a contractile response via the release of sensory neuropeptides such as substance P and neurokinin A. The contractile response to capsaicin was inhibited by the combination of CP96345 and SR 48968 suggesting that the excitatory effect of capsaicin is mediated via both the tachykinin NK-1 and NK-2 receptor. Capsaicin produced in vitro-desensitization in dose-dependent manner, but after this in vitro-desensitization the response to NK-1 and NK-2 receptor agonist did not change. Systemic administration (s.c.) of capsaicin also desensitized significantly bronchial tissues but could not produce any change in the contractile response to the selective agonists of NK-1 and NK-2 receptor. Therefore, the present results suggest that functional desensitization to capsaicin-induced contractile response in guinea pig bronchi does not involve NK-1 and NK-2 receptor, while excitatory effect of capsaicin is mediated via both NK-1 and NK-2 receptor. In conclusion, it is suggested that capsaicin- induced excitation and desensitization involves somewhat different pathways.

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Effect of capsaicin on murine lymphocyte functions and lymphoid tissue morphology

  • Lee, June-Chul;Park, Yeong-Min
    • 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.

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Studies on the quantitative determination of Capsaicin in various species of the genus Capsicum (고추중의 Capsaicin 정량(定量)에 관(關)한 연구(硏究))

  • Lee, Tae-Yeong;Park, Seong-O
    • Applied Biological Chemistry
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    • v.4
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    • pp.23-28
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    • 1963
  • Various species of the genus Capsicum contain in their fruits an intensively sharp and pungent substance, Capsaicin, which was first isolated in an almost pure state by Thresh. Containing the pungent principle, Capsicums are used extensively in food as a spice and in medicine as a rubefacient and carminative. Numerous methods have been proposed for the isolation, the chemical structure and the quantitative determination of Capsaicin. Modifying the several methods described before, the Capsaicin contents in various species of the genus Capsicum were determined as follows. (1) The isolation of pure Capsaicin was the essential first step for the determination of Capsaicin contents. Powdered cayenne pepper was extracted with acetone. By the method of ether alkali partition extraction slightly modified at this laboratory and by the recrystallization with light petroleum ether that was repeated ten times, the pure crystalline Capsaicin was obtained. Using this Capsaicin, the standard absorption curve was drawn with Beckman spectrophotometer model DU for the quantitative determination of Capsaicin. 92) The powdered sample was extracted in a Soxhlet extractor with ether-acetone solvent system(3:1) for 25 hours. Capsaicin in this ether-acetone extracts was efficiently separated in a pure state by paper partition chromatography using 58% methanol solution as developing agent. It was found that 58% methanol was one of the most valuable solvent to separate Capsaicin from impurities such as sterols, fatty acids, waxes and carotenoid pigments. (3) The colorimetric method modifying the Schulte-Kruger's method which consists of measuring the red color produced with diazobenzenesulphonic acid was used. Capsaicin in various species of the genus Capsicum was determined quantitatively with use of Beckman spectrophotometer model DU at $480\;m{\mu}$.

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Capsaicin Induces Acute Spinal Analgesia and Changes in the Spinal Norepinephrine Level (Capsaicin에 의한 척수 수준에서의 급성 진통효과와 Norepinephrine의 변화)

  • Park, Hyoung-SuP;Park, Kyung-Pyo
    • The Korean Journal of Pharmacology
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    • v.29 no.1
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    • pp.33-41
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    • 1993
  • Central analgesic effect of capsaicin was assessed by the tail flick reflex (TFR) test, using male Sprague-Dawley rats under anesthesia with pentobarbital sodium (induction with 40 mg/kg and maintenance with $4{\sim}8\;mg/kg/hr$). Level of norepinephrine in the spinal cord was also measured. Capsaicin, $35{\sim}150\;{\mu}g$, was injected intrathecally, and the TFR latency was measured before, 10, 30, and 60 minutes after the drug administration. TFR latency was increased 100% or more immediately by intrathecal capsaicin, from 2.9 seconds to the maximum of 7.0 seconds at 10 minute after the drug; P<0.01. The increase in TFR latency was maintained during the course of experiment of 2 hours. Concomitant reduction of NE content in the spinal cord was observed; from 16 ng/mg protein to 7 ng/mg protein. On the other hand, subcutaneous injection of capsaicin of 50 mg/kg did not change the TFR latency although the NE content reduced similarly to the case of intrathecal injection. Pretreatment of the animal with 0.5 mg/kg of MK-801 reversed the increase of TFR latency and NE reduction induced by intrathecal capsaicin. These results suggest that capsaicin causes analgesia at the spinal cord level by activating the excitatory amino acid-NE-dorsal horn interneurons axis of the descending inhibitory pain modulation pathway.

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Genotoxicity of Capsaicin in Cultured Human Lymphocytes

  • Lee, Sang-Sup;Park, Young-Ho;Sohn, Yeowon;Ryu, Soo-Jung;Surh, Young-Joon
    • Environmental Mutagens and Carcinogens
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    • v.15 no.2
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    • pp.81-87
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    • 1995
  • The clastogenic activity of capsaicin, a major pungent and irritating constituent of hot chili pepper, was evaluated in cultured human lymphocytes. Capsaicin (125, 250, and 500 $\mu$M) caused cytogenetic damage as determined by increased frequency of chromosome/chromatid aberrations compared to the solvent control. The mitotic indices were also decreased in a concentration-related manner in capsaicin-treated cells. Moreover, capsaicin suppressed [$^3$]thymidine incorporation into lymphocytes. The clastogenicity and cytotoxicity of capsaicin towards human lymphocytes were evident without an external metabolic activation system. Taken together, these findings suggest that capsaicin is a genotoxic agent and may thus represent a potential health hazard in humans.

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Subcellular Localization of Capsaicin-Hydrolyzing Enzyme in Rat Hepatocytes (Capsaicin 가수분해효소의 흰쥐 간세포내 소재확인)

  • Park, Young-Ho;Lee, Sang-Sup
    • YAKHAK HOEJI
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    • v.38 no.1
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    • pp.12-19
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    • 1994
  • Capsaicin(8-methyl-N-vanillyl-6-nonenamide) is the principal pungent component of Capsicum fruits. This work is directed to the capsaicin-hydrolyzing enzyme playing a key role in the rate limiting and critical step of capsaicin metabolism. In order to get precise information on the enzyme's subcellular location, rat liver homogenate was divided into six subcellular fractions by differential centrifugation technique: crude nuclear pellet, PNS(post nuclear supernatant) fraction, lysosomal pellet, cytosol, Tris wash fraction, micrisomes. Capsaicin-hydrolysing enzyme activity was analysed by high performance liquid chromatography(HPLC). This enzyme was found at the highest specific activity in the microsomal fraction and co-distributed with marker enzymes of the endoplasmic reticulum, NADPH-cytochrome c reductase and nucleoside diphosphatase. This is compatible with the result of ninhydrin color reaction of vanillylamine, primary metabolite of capsaicin hydrolysis, on thin layer chromatography(TLC). This enzyme is most active at pH $8.0{\sim}9.0$. Definite subcellular location of this enzyme will make it easy to proceed with further study.

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Involvement of Adenosine in The Spinal Antinociception by Capsaicinoids (캅사이신 유사체들의 척수 진통작용을 매개하는 아데노신)

  • 유은숙;김옥희;손여원;정인경;이상섭
    • YAKHAK HOEJI
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    • v.43 no.1
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    • pp.55-60
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    • 1999
  • To investigate analgesic mechanism of capsaicin and its analogues (capaicinoids) adenosine release was measured by high performance liquid chromatography from rat spinal cord synaptosomes. Exposure of synaptosomes to $K^+$ and morphine produced a dose dependent release of adenosine in the presence of $Ca^{++}$. Capsaicin (0.1, 1, $10{\;}{\mu}M$), and its analogues: NE-19550 (1, 10, $100{\;}{\mu}M$), DMNE (1, 10, $100{\;}{\mu}M$) and KR 25018 (0.1, 1, $10{\;}{\mu}M$) produced a concentration dependent release of adenosine in the presence of $Ca^{++}$. Nifedifine, L-type voltage sensitive calcium channel blocker, inhibited $K^+$ (6, 12 mM)-and morphine ($10{\;}{\mu}M$)-evoked release of adenosine partially. Capsazepine, a novel capsaicin selective antagonist, blocked only capsaicin and capsaicinoids induced release of adenoside. Therefore, it is suggested that the adenosine release by capsaicin and capsaicinoids having antinociceptive effects involves actvation of capsaicin specific receptor and capsaicin sensitive $Ca^{++}$. channel.

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Excitatory effect of KR-25018 and capsaicin on the isolated guinea pig bronchi

  • 정이숙;신화섭;박노상;문창현;조태순
    • Proceedings of the Korean Society of Applied Pharmacology
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    • pp.252-252
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    • 1996
  • We Investigated the peripheral excitatory effect of capsaicin and KR-25018, a newly synthesized capsaicin derivative which was demonstrated to have a potent analgesic activity. KR-25018 and capsaicin were found to be both potent efficacious contractors of isolated guinea pig bronchial smooth muscle. KR-25018 was equipotent with capsaicin and [Sar$\^$9/,Met(O$_2$)$\^$11/]-substance P, 10-fold more potent than histamine and 10-fold less potent than (${\beta}$ -Ala$\^$8/)-neurokinin A(4-10), and their -log(M)EC$\_$50/ values were 6.94${\pm}$0.08, 6.86${\pm}$0.05, 6.96${\pm}$0.07, 5.64${\pm}$0.04, 7.96${\pm}$0.02, respectively. Contractile responses to KR-25018 and capsaicin were potentiated by phosphoramidon (1 ${\mu}$M), an inhibitor of neuropeptide-inactivating endopeptidase, but completely abolished in a calcium-free medium. These responses to KR-25018 and capsaicin were unaffected by the NK-1 antagonist CP96345 (1${\mu}$M), partially inhibited by the NK-2 antagonist SR48968 (1 ${\mu}$M) but almost completely abolished by a combination of the antagonists. A vanilloid receptor antagonist capsazepine competitively antagonized the responses to both KR-25018 and capsaicin (pA$_2$: aganst KR-25018, 5.98${\pm}$0.47; against capsaicin, 5.80${\pm}$0.31), and a capsaicin-sensitive cation channel antagonist ruthenium red caused significant reduction in the maximum responses to KR-25018 and capsaicin (pD'$_2$: against KR-25018, 4.61${\pm}$0.33; against capsaicin 4.96${\pm}$0.21). In conclusion, the present results suggest that KR-25018 and cpasaicin act on the same vanilloid receptor inducing the influx of calcium through ruthenium red-sensitive cation channel and produce contractile responses via the release of tachykinins that act on both NK-1 and NK-2 receptor subtypes.

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Effect of Capsaicin and Its Novel Derivative on the Isolated Guinea Pig Bronchi (캡사이신과 그 합성유도체의 기니픽 기관지 평활근에 대한 작용)

  • 정이숙;이부연;공재양;박노상;조태순;신화섭
    • Journal of Food Hygiene and Safety
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    • v.9 no.3
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    • pp.163-168
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    • 1994
  • In the present study we investigated the peripheral function of capsaicin and KR-25018, a newly synthesized capsaicin derivative, which was demonstrated to have a potent analgesic activity through different mechanism from morphine and nonsteroidal antiinflammatory drugs. Capsaicin (10-8~10-5 M) and KR-25018 (10-8~10-5 M) produced concentration-dependent contractions of the isolated guinea pig bronchi. There were no significant differences in the maximum response and the EC50 values (EC50: 0.137$\pm$0.025 $\mu$M and 0.097$\pm$0.031 $\mu$M for capsaicin and KR-25018, respectively, P>0.05). Phosphoramidon (10 $\mu$M) and indomethacin (10 $\mu$M) had no significant effect on contractile response to the submaximal concentration range of capsaicin and KR-25018 (3$\times$10-9~3$\times$10-7 M). The response to KR-25018, like that to capsaicin, was significantly inhibited by ruthenium red with reduction in the maximum response, which is indicative of non-competitive antagonism. A further common feature of the responses to capsaicin and KR-25018 in the guinea pig bronchi was their sensitivity to capsazepine. Capsazepine caused a rightward parallel shift in concentration-response curves obtained by capsaicin and KR-25018. the pA2 values of capsazepine were 5.90 and 5.99 against capsaicin and KR-25018 response, respectively. In conclusion, KR-25018 and capsaicin exert their contractile effects in the isolated guinea pig bronchial muscle by common mechanisms, probably via the activation of a specific receptor.

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