Effects of capsaicin on pro-inflammatory and anti-inflammatory signaling in the stomach of transient receptor potential type vanilloid 1 (TRPV1) wild type and knockout mice

Abstract

Gastric cancer is the fourth most common cancer in men and fifth in women, and the second leading cause of cancer mortality in the rate of gastric cancer in the world. There are several factors that contribute to gastric cancer development. These include Helicobacter pylori infection, high salt diet, and smoking. Frequent consumption of hot spicy food has been speculated to be a risk factor for the gastric cancer, but the data in the literature are still conflicting and discordant. Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is a major pungent principle of hot chili pepper which is one of the most frequently consumed spices throughout the world, especially in Korea, Southeast Asian and Latin-American countries. The transient receptor potential type vanilloid 1 (TRPV1) is known as the capsaicin receptor activated not only by capsaicinoids, but also other stimuli including heat (>43℃). However, the roles of TRPV1 and capsaicin in gastric carcinogenesis are still controversial. In the present study, I investigated the effects of capsaicin on gastric inflammation in TRPV1 wild type (WT) and knockout (KO) mice. TRPV1 WT and KO mice were fed normal diet or 0.05% capsaicin diet for 36 weeks. TRPV1 KO mice fed normal diet showed significantly elevated expression of cyclooxygenase-2 (COX-2) than did the WT animals. In contrast, the expression level of heme oxygenase-1 (HO-1) with an anti-inflammatory function was reduced in the TRPV1 KO mice. COX-2 up-regulation and HO- 1 down-regulation in the TRPV1 KO mice were attenuated by capsaicin administration. AMP-activated protein kinase (AMPK), which functions as a cellular energy sensor, has been shown to mediate critical anti-inflammatory effects. The expression level of phosphorylated-AMPK was elevated in capsaicin-treated TRPV1 KO mice. These findings suggest capsaicin may exert antiinflammatory effects in mouse stomach via TRPV1.