I) Inhibition of LPS induced release of NO, IL-1 β and IL-6.

Pro-inflammatory cytokines are the cytokines that promotes systemic inflammation. Inflammation is a beneficial host response to a foreign challenge or tissue injury that ultimately leads to the restoration of normal tissue structure and function. Prolonged inflammation contributes to the pathogenesis of many inflammatory diseases. The main pro-inflammatory mediators include cytokines, primarily TNF- α, IL-β, and IL-6. We have studied the effect of GutGard^® on the release of IL-1 β, IL-6 and NO in LPS-induced murine macrophages.

a)Inhibition of LPS-induced production of NO

High levels of NO are produced in response to inflammatory stimuli and mediate pro-inflammatory and destructive effects like hypotension, vascular leakage syndrome, and tissue injury in septic shock. GutGard^® showed significance inhibition in the in LPS-induced NO production, the median inhibitory concentrations (IC₅₀) was observed at 24µg/ml.

b)Inhibition of LPS-induced production of IL-1 β & IL-6.

Interleukin- 1 (IL- 1) is a polypeptide cytokine produced during inflammation and injury, it possess a wide spectrum of immunologic and non-immunologic activities and plays a significant role as an inflammatory mediator in the pathology of chronic and acute coronary diseases.
GutGard^® showed significance inhibition in the in LPS-induced IL-1 β & IL-6 production, the median inhibitory concentrations (IC₅₀) was observed at10 µg/ml (30.8 µM) and 37µg/ml respectively.

Reference: Thiyagarajan P et al., Inflammopharmacology 2011; 19:235-241.

II) Inhibition of COX and LOX products

Cycloxygenase and lipoxygenase are both key enzymes involved in the earachidionic acid cascade leading to the formation of inflammatory mediator’s prostagladins (PGs) and leukoterin (LT4) in the body. PGs and LT4 plays major role in inflammatory reactions and are responsible for the characteristic of inflammatory symptoms. GutGard^® exhibited significant inhibition of PGE₂, TXB₂, and LTB₄ production. GutGard^® acts as a dual inhibitor towards both COX and LOX products.
Compared to individual inhibitors of COX or LOX pathways which exhibits side effects (gastrointestinal erosin) , dual inhibitors present a major advantage by acting on the two major arachidonic acid metabolic pathways which possess a wide range of anti-inflammatory activity.

COX and LOX inhibitory potential of GutGard^® was studied in J774.1 murine macrophages at different concentrations (2.5-40µg/ml).

G.glabra and its major active principle glabridin exhibited significant inhibition of PGE₂, TXB₂, and LTB₄ production, while isoliquiritigenin actively suppressed the PGE₂ and TXB₂ levels. Glycyrrhizin (data not shown) did not demonstrate any inhibitory effect. Based on the inhibitory activity towards both COX and LOX products, G. glabra could be designated as a dual inhibitor. The inhibitory propensity of G. glabra extract towards COX and LOX products is mainly attributed to glabridin and isoliquiritigenin and is not influenced by glycyrrhizin.

GutGard^® showed a significant anti-ulcer activity in pylorus ligation, cold stress and indomethacin induced ulcer model.

Reference: Chandrashekaran CV et al., Phytomedicine 2011; 18: 278-284.