Anti-inflammatory and antioxidant activities of naringin isolated from Carissa carandas L.: In vitro and in vivo evidence.

BACKGROUND: Carissa carandas L. is known in folk medicine for its anti-inflammatory and hepatoprotective activities. Meanwhile it is an evergreen shrub that constitutes a continuous source of leaves throughout the year.

HYPOTHESIS/PURPOSE: The leaves of Carissa carandas L. may be rich in compounds that can be used as safe anti-inflammatory and antioxidant remedies. The combined antioxidant and anti-inflammatory activities provoked the study of the hepatoprotective effects.

STUDY DESIGN: To isolate major constituents from the leaves of Carissa carandas L. and test their anti-inflammatory and antioxidant activities in-vivo and in-vitro.

METHODS: The leaves of Carissa carandas L. were extracted with 80% MeOH and then defatted with CHCl3 to yield Carissa carandas defatted extract (CCDE). The extract was chemoprofiled using UPLC-MS/MS to stand for major constituents, then subjected to different chromatographic separation steps and naringin (NG) was isolated in a high yield. The anti-inflammatory activity of NG was investigated in-vivo by carrageenan induced hind rat paw edema model at two dose levels (50 and 25 mg/kg). The anti-inflammatory activity was also evaluated in-vitro by measuring its inhibitory effect on LPS induced release of NO from RAW 264.7 macrophages. The antioxidant activity was evaluated by superoxide and DPPH radical scavenging ability. The safety of NG was tested against primary rat hepatocytes. The hepatoprotective effect of CCDE was evaluated by detecting its effects on serum liver function markers and liver cell oxidative stress markers.

RESULTS: NG exhibited potent inhibition of inflammation as compared to indomethacin (20 mg/kg). NG inhibited LPS induced release of NO from macrophages (IC50 , 6.4 μM). NG showed significant antioxidant activity as it scavenged the superoxide radical (EC90 , 10.95 μM) and DPPH radical (EC50 , 11.2 μM). CCDE inhibited the elevation of the serum liver marker enzymes and increased GSH and decreased MDA contents in the liver homogenate. Liver histopathology supported the biochemical findings.

CONCLUSION: C. carandas has potent anti-inflammatory, antioxidant and hepatoprotective activities.