Thai medicinal plants modulate nitric oxide and tumor necrosis factor-alpha in J774.2 mouse macrophages

Centella asiatica (CA) and Rhinacanthus nasutus (RN) are Thai medicinal plants traditionally used to treat a variety of disorders including inflammatory conditions and infections. Nitric oxide (NO) produced from activated macrophages plays a role in both inflammatory and anti-inflammatory processes. This study examined whether CA and RN modulate the production of NO and tumour necrosis factor-alpha (TNF-alpha) by J774.2 mouse macrophages. Expression of the inducible nitric oxide synthase (iNOS) and TNF-alpha genes was also analysed. With CA (water extract) NO production was increased in a dose-dependent manner. An increase also occurred when CA was administered with lipopolysaccharide (LPS), a known macrophage activator. In contrast, an ethanol extract of CA had no effect on NO, and when administered with LPS the extract suppressed production. With RN, neither water nor ethanol extracts alone had an effect on NO, although when the ethanol extract of RN was used in combination with LPS, production was increased. TNF-alpha secretion was correlated with NO production and increases were associated with an elevation in TNF-alpha mRNA. The only effect on iNOS gene expression was an inhibition with the CA ethanol extract in the presence of LPS, consistent with the reduction in NO under these conditions. These studies show that CA and RN extracts can either increase or decrease NO production by macrophages and that these effects are predominantly mediated through an effect on TNF-alpha expression. These data contribute to a better mechanistic understanding of the medicinal properties of these Thai plants.