Immunomodulatory Effects of Psyllium Extract on Helicobacter pylori Interaction With Gastric Epithelial Cells.

Plantago ovata (Psyllium, Ispaghul) is a herb of Plantaginaceae family is found widely across the world. Psyllium contains active principals including e.g., 4-O-methylglucuronic acid, aucubin, campesterol, linoleic acid, oleic acid, mucilage, etc, polysaccharides, and arabinoxylans with high gel-forming property Refined Psyllium is used as a prebiotic, in functional bowel disorder, and intestinal inflammation. Plant derived phenolic compounds and flavonoids have reported clinical benefits and pharmacologic effects.  They demonstrate  antiinflammatory activity by modulating the expression levels of cytokines including interleukin- (IL-1), nuclear kappa  B (NF-κB), tumor necrosis factor-alpha (TNF-α), cyclooxygenase (Cox-2), etc.

 Helicobacter pylori (H. pylori) is a Gram negative organism that causes gastritis and is associated with gastrointestinal disorder such as peptic ulcers, gastric malignancies. H. pylori adhere to gastric epithelial cells and stimulate interleukin 8 (IL-8) productions to attract components of the innate and adaptive immune systems. This results in neutrophil infiltration of the gastric epithelium.  H. pylori infection activates NF-κB in gastric epithelial cells in vitro and in vivo. NF-κappa B is a transcriptional regulator of IL-8 production, and its activation is an important defense response in gastrointestinal epithelial cells. Toll-like receptor 2 (TLR2) and TLR5 recognize H. pylori and initiate signaling pathways that activates NF-κB.  H. pylori induced a time-dependent expression of mRNA and protein for IL-8 via activation of NF-κB and increased the levels of IL-8 and IL-6, which were inhibited by NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC). NF-κB activity is inhibited by glucocorticoids and non-steroidal anti-inflammatory agents. In gastric cancer-derived cell line, MKN45 produce an increased amount of IL-8 upon coculture with live H. pylori indicating that IL-8 production requires a direct contact between the cells and H. pylori. H. pylori directly induced IL-8 mRNA expression and protein secretion and cagA positive and negative strains of H. pylori varied in inducing epithelial IL-8 production. Cell lines are used to model and study drug effects, genetic and immune responses, etc as cells can be grown and treated with drugs under the same condition. We determined the effect of Psyllium husk extract on IL-8 and NF-κB secretion by gastric epithelial cell in response to H. pylori. AGS cell line (Human gastric adenocarcinoma cell line) cells were exposed to Psyllium extract in different concentrations before H. pylori infection. ELISA for IL-8 and NF- κB was used to analyze cell culture supernatant. RNA from cells was used for Real-Time-PCR for messenger RNA expression of IL-8. Psyllium extract 5 and 10μg/ml markedly (P<0.001) lowered basal IL-8 by 64.71% and 74.51%, respectively and H. pylori stimulated IL-8 was also (P<0.001) lowered by 41.67% and 66.67%, respectively. Psyllium 5 and 10μg/ml also reduced (P<0.0001) cagA positive H. pylori induced IL-8 mRNA expression by 42.3% and 67.6%, respectively. Psyllium also reduced (P=0.0001) NF-κB in response to H. pylori strains confirming its role as anti-inflammatory agent. This shows that the Psyllium can play a role in the treatment of H. pylori associated diseases. Psyllium contained compounds will prevent H. pylori contact with gastric epithelial cell important for the pathogenecity of the H. pylori with essential contributions by outer membrane proteins e.g., HopQ, BabA, etc. and its virulence marker e.g., cagA, vacA alleles, etc. Treatment of AGS cells with psyllium decreases IL-8 expression in the presence and absence of H. pylori. It prevents H. pylori from eliciting a proinflammatory host cell response via the activation of NF-κB and mitogen activated protein kinases. Hence psyllium keep dendritic cell and T cells function from being modified by H. pylori. The down regulation of proinflammatory responses makes Psyllium useful for diverse indication. This study showed that Psyllium has an immune modifying effect on gastric epithelial cells. However, randomized controlled study is required to establish the efficacy of Psyllium husk in the treatment of H. pylori infection that can effect secretion of IL-8 by H. pylori.