capsaicin

Capsaicin is a TRPV1 agonist with an EC50 of 0.29 μM in HEK293 cells.

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Membrane Transporter/Ion Channel >> TRP Channel

Natural Products >> Alkaloid

Research Areas >> Cancer

EC50: 290 nM (hTRPV1, in HEK293 cell)[1]

Capsaicin is an agonist of transient receptor potential vanilloid subtype 1 (TRPV1), which is expressed in nociceptive sensory neurons and a range of secretory epithelia, including salivary glands. Capsaicin activates TRPV1, which modulates the permeability of tight junctions (TJ) by regulating the expression and function of putative intercellular adhesion molecules in an ERK-dependent manner[2]. Capsaicin is found to inhibit the growth and proliferation of FaDu cells in a dose- and time-dependent manner. Cells treated with 50, 100, 200, and 300 µM Capsaicin show an augmented decrease in cell growth as the Capsaicin dose increases. In addition, the percentage of viable cells decreases as the incubation time increases. The observed IC50 value is around 150 µM[3].

Capsaicin (CAP)-treated animals (Group IV) show increased DNA fragmentation suggesting apoptosis when compare with B(a)P-induced lung cancer-bearing animals (Group II) that show reduced DNA fragmentation. CAP-treated Group IV animals show markedly increased expressions of p53, Bax and caspase-3 with remarkable decrease in the levels of anti-apoptotic protein Bcl-2, when compare with B(a)P-administered lung cancer animals of Group II[4]. Capsaicin causes a dose-dependent reduction of tear secretion in female Wistar/ST rats. Significant effects are observed at doses of 20, 50 and 100 mg/kg. In addition, Capsaicin also causes corneal lesions, and significant effects are observed at doses of 50 and 100 mg/kg[5].

FaDu cells are plated at a density of 1×105 cells/well on 24-well plate. After overnight growth, the cells are treated with various concentrations of Capsaicin (0 μM, 50 μM, 100 μM, 150 μM, 200 μM, 250 μM, 300 μM, and 350 μM) for 24, 48 and 72 hours, with medium replacement every 24 hours. At the end of treatment, 30 µL of the tetrazolium compound MTT, and 270 µL of fresh medium are added. After further incubation for 4 hours at 37°C, 200 µL of 0.1 N HCl in 10% SDS is added into each well to dissolve the tetrazolium crystals. Finally, the absorbance at a wavelength of 540 nm is recorded using an ELISA plate reader[3].

Mice[4] Healthy male Swiss albino mice weighing 20-25 g (8-10 weeks old) are divided into four groups of six mice each as follows. Group I: control animals receive olive oil throughout the course of the experiment. Group II: animals are administered with Benzo(a)pyrene (B(a)P) (50 mg/kg body weight dissolved in olive oil) orally twice a week for four successive weeks. Group III: animals receive Capsaicin alone (10 mg/kg body weight dissolved in olive oil) intraperitoneally once in a week for 14 weeks to assess the cytotoxicity (if any) induced by Capsaicin. Group IV: animals receive B(a)P (as in Group II) along with Capsaicin (10 mg/kg b.wt dissolves in olive oil) intraperitoneally. Capsaicin treatment is started one week prior to the first dose of B(a)P administration and continued for 14 weeks. Rats[5] Female Wistar/ST rats, 4 d of age, are used. On postnatal day 4, rats are given a single subcutaneous injection of Capsaicin at a dose of 50 mg/kg (or 20 and 100 mg/kg for the dose-response test) dissolved in physiological saline containing 10% ethanol and 10% Tween 80. Vehicle-treated rats receive the vehicle solution alone. The injected rats are housed with their mothers, who are fed standard rat chow and maintained under normal conditions. At 4 weeks of age, the injected rats are separated and housed in cages, and maintained under normal conditions until the initiation of experiments.

[1]. McNamara FN, et al. Effects of piperine, the pungent component of black pepper, at the human vanilloid receptor (TRPV1). Br J Pharmacol. 2005 Mar;144(6):781-90.

[2]. Shin YH, et al. The Effect of Capsaicin on Salivary Gland Dysfunction. Molecules. 2016 Jun 25;21(7).

[3]. Le TD, et al. Capsaicin-induced apoptosis of FaDu human pharyngeal squamous carcinoma cells. Yonsei Med J. 2012 Jul 1;53(4):834-41.

[4]. Anandakumar P, et al. Capsaicin provokes apoptosis and restricts benzo(a)pyrene induced lung tumorigenesis in Swiss albino mice. Int Immunopharmacol. 2013 Jun 6;17(2):254-259.

[5]. Kagawa Y, et al. Investigation of capsaicin-induced superficial punctate keratopathy model due to reduced tear secretion in rats. Curr Eye Res. 2013 Jul;38(7):729-35.

[6]. Wang J, et al. Anti-inflammatory and retinal protective effects of capsaicin on ischaemia-induced injuries through the release of endogenous somatostatin. Clin Exp Pharmacol Physiol. 2017 Jul;44(7):803-814.

Capsazepine | EIPA | Diphenyleneiodonium chloride | HC-030031 | SKF-96365 | HC 067047 | AMG 9810 | GSK-1016790A | SAR7334 | PF-4840154 | RN-1734 | AMG-517 | SB-366791 | IcilinAG-3-5 | ML204

DATA ITEMS CITED :

23

MOLECULAR FORMULA :

C18-H27-N-O3

MOLECULAR WEIGHT :

305.46

WISWESSER LINE NOTATION :

1OR BQ E1MV5U1Y1&1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

9500 ug/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - excitement Behavioral - muscle contraction or spasticity

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

47200 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Administration onto the skin

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

>512 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

6500 ug/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - excitement Behavioral - muscle contraction or spasticity

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

9000 ug/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - excitement Behavioral - muscle contraction or spasticity

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

400 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intramuscular

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

7800 ug/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - excitement Behavioral - muscle contraction or spasticity

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intratracheal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1600 ug/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - excitement Behavioral - muscle contraction or spasticity

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Rectal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

>218 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - cat

DOSE/DURATION :

1600 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

>50 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

1100 ug/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - excitement Behavioral - muscle contraction or spasticity

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - hamster

DOSE/DURATION :

>120 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

2400 mg/kg/2W-I

TOXIC EFFECTS :

Behavioral - food intake (animal) Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

3318 mg/kg/5W-C

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Gastrointestinal - tumors

TYPE OF TEST :

Micronucleus test

TYPE OF TEST :

DNA inhibition

TYPE OF TEST :

Sister chromatid exchange

MUTATION DATA

TYPE OF TEST :

Mutation in microorganisms

TEST SYSTEM :

Rodent - hamster Lung

DOSE/DURATION :

5 mg/L

REFERENCE :

CALEDQ Cancer Letters (Shannon, Ireland). (Elsevier Scientific Pub. Ireland Ltd., POB 85, Limerick, Ireland) V.1- 1975- Volume(issue)/page/year: 48,109,1989 *** U.S. STANDARDS AND REGULATIONS *** EPA FIFRA 1988 PESTICIDE SUBJECT TO REGISTRATION OR RE-REGISTRATION FEREAC Federal Register. (U.S. Government Printing Office, Supt. of Documents, Washington, DC 20402) V.1- 1936- Volume(issue)/page/year: 54,7740,1989