Abstract
The present study investigated the anti-inflammatory effects of a polyherbal decoction comprised of Nigella sativa, Hemidesmus indicus, and Smilax glabra in order to justify its claimed antihepatocarcinogenic activity. Activation of hepatic nuclear factor-kappa B (NF-κB), IκB kinase (IKK α/β) proteins, and TNFα and IL-6 expression was investigated in diethylnitrosamine- (DEN-) induced C3H mice-bearing early hepatocarcinogenic changes. Acute phase inflammatory response was evaluated by carrageenan-induced rat paw edema formation. Anti-inflammatory mechanisms were also assessed by determining effect on (a) membrane stabilization, (b) nitric oxide (NO) inhibitory activity, and (c) inhibition of leukocyte migration. A significant inhibition of the paw edema formation was observed in healthy rats as well as in rats bearing early hepatocarcinogenic changes with oral administration of the decoction. As with the positive control, indomethacin (10 mg/kg b.w.) the inhibitory effect was pronounced at 3rd and 4th h after carrageenan injection. A notable IKK α/β mediated hepatic NF-κB inactivation was associated with a significant hepatic TNFα downregulation among mice-bearing hepatocarcinogenic changes subjected to decoction treatment. Inhibition of NO production, leukocyte migration, and membrane stabilization are possible mechanisms by which anti-inflammatory effect is mediated by the decoction. Overall findings imply that anti-inflammatory activity could be one of the mechanisms by which the decoction mediates its antihepatocarcinogenic effects.
Highlights
Prolonged inflammation is thought to set up a cycle of liver cell destruction and regeneration, resulting in a mitogenic and mutagenic environment that precipitates random genetic and chromosomal damage and leads to the development of HCC [1, 2]
An overall inhibition of rat paw oedema formation was observed with a single oral dose of the decoction (1 g/kg b.w.), the most significant effect was noted at 3rd h after carrageenan injection (32.1% inhibition; P < 0.01)
Epidemiological studies have established that many tumors occur in association with chronic infectious diseases, and it is known that persistent inflammation in the absence of infections increases the risk and accelerates the development of cancer [32]
Summary
Prolonged inflammation is thought to set up a cycle of liver cell destruction and regeneration, resulting in a mitogenic and mutagenic environment that precipitates random genetic and chromosomal damage and leads to the development of HCC [1, 2]. In many Asian countries including Sri Lanka, polyherbal preparations are used traditionally to treat cancer patients despite the lack of evidence from scientifically controlled studies to prove or disprove these claims One such remedy, used by a particular family of ayurvedic physicians in Sri Lanka, is a decoction comprised of Nigella sativa (seeds), Hemidesmus indicus (root), and Smilax glabra (rhizome). The anti-inflammatory effect of the decoction comprised of N. sativa seeds, H. indicus roots, and S. glabra rhizome was evaluated in order to understand the mechanisms by which it mediates the claimed antihepatocarcinogenic effect To achieve this objective, the ability of the decoction to modulate host immune response towards diethylnitrosamine-(DEN-) induced early hepatocarcinogenesis was investigated by evaluating its effect on (a) carrageenan-induced rat paw formation, (b) NO production by rat peritoneal cells, (c) leukocyte migration during carrageenan-induced rat peritonitis, (d) expression of intrahepatic inflammatory mediators (TNFα and IL-6), and (e) key inflammatory regulator; nuclear factor-kappa B (NFκB) activation
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