Unraveling the Novel Protective Effect of Patchouli Alcohol Against Helicobacter pylori-Induced Gastritis: Insights Into the Molecular Mechanism in vitro and in vivo

Abstract

Patchouli alcohol (PA), a natural tricyclic sesquiterpene extracted from Pogostemon cablin (Blanco) Benth. (Labiatae), has been found to exhibit anti-Helicobacter pylori and anti-inflammatory properties. In this study, we investigated the protective effect of PA against H. pylori-induced gastritis in vitro and in vivo, and determined the underlying mechanism. In the in vivo experiment, a C57BL/6 mouse model of gastritis was established using H. pylori SS1, and treatments with standard triple therapy or 5, 10, and 20 mg/kg PA were performed for 2 weeks. Results indicated that PA effectively attenuated oxidative stress by decreasing contents of intracellular reactive oxygen species (ROS) and malonyldialdehyde (MDA), and increasing levels of non-protein sulfhydryl (NP-SH), catalase and glutathione (GSH)/glutathione disulphide (GSSG). Additionally, treatment with PA significantly attenuated the secretions of interleukin 1 beta (IL-1β), keratinocyte chemoattractant and interleukin 6 (IL-6). PA (20 mg/kg) significantly protected the gastric mucosa from H. pylori-induced damage. In the in vitro experiment, GES-1 cells were cocultured with H. pylori NCTC11637 at MOI = 100:1 and treated with different doses of PA (5, 10, and 20 μg/ml). Results indicated that PA not only significantly increased the cell viability and decreased cellular lactate dehydrogenase (LDH) leakage, but also markedly elevated the mitochondrial membrane potential and remarkably attenuated GES-1 cellular apoptosis, thereby protecting gastric epithelial cells against injuries caused by H. pylori. PA also inhibited the secretions of pro-inflammatory factors, such as monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor-α (TNF-α) and IL-6. Furthermore, after PA treatment, the combination of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) and cysteine-aspartic proteases 1 (CASPASE-1), the expression levels of NLRP3 inflammasome-related proteins, such as thioredoxin-interacting protein (TXNIP), pro-CASPASE-1, cle-CASPASE-1, and NLRP3 and genes (NLRP3 and CASPASE1) were significantly decreased as compared to the model group. In conclusion, treatment with PA for 2 weeks exhibited highly efficient protective effect against H. pylori-induced gastritis and related damages. The underlying mechanism might involve antioxidant activity, inhibition of pro-inflammatory factor and regulation of NLRP3 inflammasome function. PA exerted anti-H. pylori and anti-gastritis effects and thus had the potential to be a promising candidate for treatment of H. pylori-related diseases.

Astaxanthin n-Octanoic Acid Diester Ameliorates Insulin Resistance and Modulates Gut Microbiota in High-Fat and High-Sucrose Diet-Fed Mice

“…At the genus level, we found that Bilophila, Helicobacter, Clostridium, Dehalobacterium, and SMB53 were significantly increased after treatment with HFD. The genus Helicobacter, a potential producer of intracellular reactive oxygen species and MDA, induces gastric inflammation and gastrointestinal infection [37,38]. Moreover, an elevated abundance of Clostridium and SMB53 due to an HFD was in agreement with a previous report [39].…”

Arrestin domain containing 3 promotes Helicobacter pylori–associated gastritis by regulating protease-activated receptor 1

“…We have screened the expression of arrestin family members in human primary gastric mucosa of H. pylori-infected and uninfected donors, and we found that 2 arrestins (ARRDC3 and TXNIP) are increased and 2 other arrestins (ARB1 and ARRDC5) are decreased. It is previously reported that TXNIP is slightly increased in H. pylori-infected GECs (19), which may promote inflammation by binding to NLRP3 inflammasome (20). In addition, nonhematopoietic ARB1 has been reported to inhibit inflammation in a murine model of polymicrobial sepsis through inhibiting NF-κB signaling (21).…”

“…It is previously reported that TXNIP is slightly increased in H . pylori –infected GECs ( 19 ), which may promote inflammation by binding to NLRP3 inflammasome ( 20 ). In addition, nonhematopoietic ARB1 has been reported to inhibit inflammation in a murine model of polymicrobial sepsis through inhibiting NF-κB signaling ( 21 ).…”

Potential benefits of patchouli alcohol in prevention of human diseases: A mechanistic review

“…1 ). Diverse health beneficial activities have been documented for PA, including: anti-influenza virus [10] , [11] , [12] , [13] , anti-inflammatory [14] , [15] , [16] , [17] , anti-oxidative [18] , anti-ulcerogenic [19] , [20] , anti-colitis [21] , [22] , anti-mucositis [23] and protective activities against brain and lung injuries [24] , [25] . Most recently, the effects of PA on cancer and metabolic disorders including obesity, fatty liver and gut microbiota have come under investigation [26] , [27] , [28] , [29] .…”