Genistein, a potent inhibitor of secretory phospholipase A2: A new insight in down regulation of inflammation

Kattepura K. Dharmappa, Riyaz Mohamed, Holenarasipura V. Shivaprasad, Bannikuppe Sannanaik Vishwanath

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Objectives: Some of the legumes, spices and medicinal herbs rich in genistein are known for their anti-inflammatory properties. Anti-inflammatory property of these herbs is determined by subjecting secretory phospholipase A2 (sPLA2) inhibition, a key enzyme in the inflammatory reactions by genistein. Materials and methods: Genistein was assessed for inhibition of sPLA2 activity using 14C-oleate radiolabelled Escherichia coli membrane as substrate. The enzyme-inhibitor interaction was established by intrinsic fluorescence and circular dichroism studies. The in vivo anti-inflammatory activity was tested by injecting sPLA2, Vipera russelli venom phospholipase-V (VRV-PL-V) with different concentrations of genistein in the range of 3-21 μM into intra plantar surface of right hind footpad of mice. Systemic effect was tested by administering the genistein (21 μM) i.p. 30 min before and immediately after sPLA2 injection. Result: Genistein inhibited sPLA2 enzymes of inflammatory exudates (human synovial fluid and human pleural fluid) and snake venoms (VRV-PL-V and Naja naja phospholipase-I) in a concentration dependent manner with IC50 values ranging from 5.75 to 11.75 μM. Increasing the calcium (Ca2+) concentration from 2.5 to 15 mM and substrate concentration up to 120 nM did not alter the level of inhibition. Genistein alters the intrinsic fluorescence intensity and shown apparent shift in far ultra violet-circular dichroism spectra of VRV-PL-V, indicating the direct interaction with enzyme. Genistein also inhibited the VRV-PL-V induced mouse paw oedema in a concentration dependent manner. The genistein at 21 μM concentration administered immediately after the VRV-PL-V injection, effectively neutralized the oedema inducing activity. Conclusion: Genistein inhibited sPLA2 activity of both inflammatory exudates and snake venoms in a concentration dependent manner and sPLA2 induced mouse paw oedema. The study partially explains the observed anti-inflammatory property of several medicinal herbs which containing genistein.

Original languageEnglish (US)
Pages (from-to)25-31
Number of pages7
JournalInflammopharmacology
Volume18
Issue number1
DOIs
StatePublished - Feb 2010
Externally publishedYes

Keywords

  • Anti-inflammatory
  • Antioxidant activity
  • Genistein
  • Human pleural fluid
  • Human synovial fluid
  • Phospholipase A
  • Snake venom

ASJC Scopus subject areas

  • Immunology
  • Pharmacology
  • Pharmacology (medical)

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