The seed coat extract of Tamarindus indica, a polyphenolic flavonoid, has been shown to have antioxidant properties. The present studies investigated the inhibitory effect of the seed coat extract of T. indica on nitric oxide production in vitro using a murine macrophage-like cell line, RAW 264.7, and in vitro and in vivo using freshly isolated B6C3Fl mouse peritoneal macrophages. In vitro exposure of RAW 264.7 cells or peritoneal macrophages to 0.2-200 J.lg/mL ofT. indica extract significantly attenuated (as much as 68%) nitric oxide production induced by lipopolysaccharide (LPS) and interferon gamma (IFN-y) in a concentration dependent manner. In vivo administration ofT. indica extract (100--500 mgjkg) to B6C3Fl mice dose-dependently suppressed TPA, LPS and/or IFN-y induced production of nitric oxide in isolated mouse peritoneal macrophages in the absence of any effect on body weight. Exposure to T. indica extract had no effect on cell viability as assessed by the MTT assay. In B6C3Fl mice, pre liminary safety studies demonstrated a decrease in body weight at only the highest dose tested (1000 mgjkg) without alterations in hematology, serum chemistry or selected organ weights or effects on NK cell activity. A significant decrease in body weight was observed in BALB/c mice exposed to concentrations of extract of 250 mgjkg or higher. Oral exposure of BALB/c mice to T. indica extract did not modulate the development ofT cell-mediated sensitization to DNFB or HCA as measured by the local lymph node assay, or dermal irritation to nonanoic acid or DNFB. These studies suggest that in mice, T. indica extract at concentrations up to
500 mgjkg may modulate nitric oxide production in the absence of overt acute toxicity.
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