Capsaicin

PLoS One. 2015 May 1;10(5):e0121538.

Capsaicin Enhances the Drug Sensitivity of Cholangiocarcinoma through the Inhibition of Chemotherapeutic-Induced Autophagy.[Pubmed: 25933112]

Cholangiocarcinoma (CCA), a devastating cancer with a poor prognosis, is resistant to the currently available chemotherapeutic agents. Capsaicin, the major pungent ingredient found in hot red chili peppers of the genus Capsicum, suppresses the growth of several malignant cell lines. Our aims were to investigate the role and mechanism of Capsaicin with respect to the sensitivity of CCA cells to chemotherapeutic agents.
METHODS AND RESULTS:
The effect of Capsaicin on CCA tumor sensitivity to 5-fluorouracil (5-FU) was assessed in vitro in CCA cells and in vivo in a xenograft model. The drug sensitivity of QBC939 to 5-FU was significantly enhanced by Capsaicin compared with either agent alone. In addition, the combination of Capsaicin with 5-FU was synergistic, with a combination index (CI) < 1, and the combined treatment also suppressed tumor growth in the CCA xenograft to a greater extent than 5-FU alone. Further investigation revealed that the autophagy induced by 5-FU was inhibited by Capsaicin. Moreover, the decrease in AKT and S6 phosphorylation induced by 5-FU was effectively reversed by Capsaicin, indicating that Capsaicin inhibits 5-FU-induced autophagy by activating the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway in CCA cells.
CONCLUSIONS:
Taken together, these results demonstrate that Capsaicin may be a useful adjunct therapy to improve chemosensitivity in CCA. This effect likely occurs via PI3K/AKT/mTOR pathway activation, suggesting a promising strategy for the development of combination drugs for CCA.

Gynecol Obstet Invest. 2008;66(1):59-62.

Capsaicin inhibits proliferation of endometriotic cells in vitro.[Pubmed: 18391504 ]

Treatment of immortalized stromal-like and epithelial-like endometriotic cells with Capsaicin resulted in inhibition of proliferation in a concentration-dependent manner. In addition, endometriotic cells are more sensitive to Capsaicin treatment than immortalized endometrial cells, suggesting that Capsaicin may be an admissible drug candidate for treating endometriosis.

Mol Pain. 2015 Apr 22;11(1):22.

Experimental evidence for alleviating nociceptive hypersensitivity by single application of capsaicin.[Pubmed: 25896608]

The single application of high-concentration of Capsaicin has been used as an analgesic therapy of persistent pain. However, its effectiveness and underlying mechanisms remain to be further evaluated with experimental approaches.
METHODS AND RESULTS:
The present study provided evidence showing that the single application of Capsaicin dose-dependently alleviated nociceptive hypersensitivity, and reduced the action potential firing in small-diameter neurons of the dorsal root ganglia (DRG) in rats and mice. Pre-treatment with Capsaicin reduced formalin-induced acute nocifensive behavior after a brief hyperalgesia in rats and mice. The inhibitory effects of Capsaicin were calcium-dependent, and mediated by the Capsaicin receptor (transient receptor potential vanilloid type-1). We further found that Capsaicin exerted inhibitory effects on the persistent nociceptive hypersensitivity induced by peripheral inflammation and nerve injury.
CONCLUSIONS:
Thus, these results support the long-lasting and inhibitory effects of topical Capsaicin on persistent pain, and the clinic use of Capsaicin as a pain therapy.

Molecules . 2016 Jun 25;21(7):835.

The Effect of Capsaicin on Salivary Gland Dysfunction[Pubmed: 27347918]

Abstract Capsaicin (trans-8-methyl-N-vanilyl-6-nonenamide) is a unique alkaloid isolated from hot chili peppers of the capsicum family. 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 has analgesic and anti-inflammatory properties in sensory neurons. Recently, increasing evidence has indicated that Capsaicin also affects saliva secretion and inflammation in salivary glands. Applying Capsaicin increases salivary secretion in human and animal models. Capsaicin appears to increase salivation mainly by modulating the paracellular pathway in 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 (extracelluar signal-regulated kinase) -dependent manner. Capsaicin also improved dysfunction in transplanted salivary glands. Aside from the secretory effects of Capsaicin, it has anti-inflammatory effects in salivary glands. The anti-inflammatory effect of Capsaicin is, however, not mediated by TRPV1, but by inhibition of the NF-κB pathway. In conclusion, Capsaicin might be a potential drug for alleviating dry mouth symptoms and inflammation of salivary glands. Keywords: Capsaicin; NF-κB; Salivary glands; TRPV1.

Nature, 1997, 389(6653):816-24.

The capsaicin receptor.[Reference: WebLink]

Capsaicin, the main pungent ingredient in 'hot' chilli peppers, elicits a s ensation of burning pain by selectively activating sensory neurons that con vey information about noxious stimuli to the central nervous system.
METHODS AND RESULTS:
We hav e used an expression cloning strategy based on calcium influx to Isolate a functional cDNA encoding a Capsaicin receptor from sensory neurons. This re ceptor is a non-selective cation channel that is structurally related to me mbers of the TRP family of ion channels.
CONCLUSIONS:
The cloned Capsaicin receptor Is a lso activated by increases in temperature In the noxious range, suggesting that it functions as a transducer of painful thermal stimuli in vivo.

Arch Oral Biol. 2015 Mar 28;60(7):989-997.

Anxiolytic efficacy of repeated oral capsaicin in rats with partial aberration of oral sensory relay to brain.[Pubmed: 25874812]

This study was conducted to examine if taste over load with oral Capsaicin improves the adverse behavioural effects induced by partial aberration of oral sensory relays to brain with bilateral transections of the lingual and chorda tympani nerves.
METHODS AND RESULTS:
Male Sprague-Dawley rats received daily 1ml of 0.02% Capsaicin or water drop by drop into the oral cavity following the bilateral transections of the lingual and chorda tympani nerves. Rats were subjected to ambulatory activity, elevated plus maze and forced swim tests after 11th, 14th and 17th daily administration of Capsaicin or water, respectively. The basal and stress-induced plasma corticosterone levels were examined after the end of behavioural tests. Ambulatory counts, distance travelled, centre zone activities and rearing were increased, and rostral grooming decreased, during the activity test in Capsaicin treated rats. Behavioural scores of Capsaicin rats during elevated plus maze test did not differ from control rats. Immobility during the swim test was decreased in Capsaicin rats with near significance (P=0.0547). Repeated oral Capsaicin increased both the basal level and stress-induced elevation of plasma corticosterone in rats with bilateral transections of the lingual and chorda tympani nerves.
CONCLUSIONS:
It is concluded that repeated oral administration of Capsaicin reduces anxiety-like behaviours in rats that received bilateral transections of the lingual and chorda tympani nerves, and that the increased corticosterone response, possibly modulating the hippocampal neural plasticity, may be implicated in the anxiolytic efficacy of oral Capsaicin.

J Agric Food Chem. 1999 Jul;47(7):2563-70.

Quantitative HPLC determination of the antioxidant activity of capsaicin on the formation of lipid hydroperoxides of linoleic acid: a comparative study against BHT and melatonin.[Pubmed: 10552527]

The antioxidant activity of Capsaicin, as compared to BHT and melatonin, was determined by the direct measurement of lipid hydroperoxides formed upon linoleic acid autoxidation initiated by AIBN.
METHODS AND RESULTS:
The formation of four isomeric lipid hydroperoxides was detected after reverse-phase HPLC separation. Data from three detectors, UV absorption, glassy carbon electrode electrochemical detection, and postcolumn chemiluminescence using luminol, were compared. Capsaicin was more effective than melatonin in suppressing the formation of lipid hydroperoxides but not as effective as BHT.
CONCLUSIONS:
The formation of Capsaicin and BHT dimers was observed during oxidation, and the dimers were characterized using APCI MS(n).