TY - JOUR
T1 - Genistein, a potent inhibitor of secretory phospholipase A2
T2 - A new insight in down regulation of inflammation
AU - Dharmappa, Kattepura K.
AU - Mohamed, Riyaz
AU - Shivaprasad, Holenarasipura V.
AU - Vishwanath, Bannikuppe Sannanaik
N1 - Funding Information:
Acknowledgments The authors are grateful to: The University of Mysore, Dharmappa. K.K. CSIR-SRF (Order number DV-8/114/ CSIR/Grants 90-91), Council of Scientific and Industrial Research, CSIR (Order no 9/119 (158), 2005 EMR-1 dated 01/07/2005), New Delhi, India, for the financial support. We are thankful to Prof. Meva Singh, Dept of Psychology, University of Mysore, India. for assistance in biostatistical analysis.
Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2010/2
Y1 - 2010/2
N2 - 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.
AB - 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.
KW - Anti-inflammatory
KW - Antioxidant activity
KW - Genistein
KW - Human pleural fluid
KW - Human synovial fluid
KW - Phospholipase A
KW - Snake venom
UR - http://www.scopus.com/inward/record.url?scp=75949083696&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=75949083696&partnerID=8YFLogxK
U2 - 10.1007/s10787-009-0018-8
DO - 10.1007/s10787-009-0018-8
M3 - Article
C2 - 19894024
AN - SCOPUS:75949083696
SN - 0925-4692
VL - 18
SP - 25
EP - 31
JO - Inflammopharmacology
JF - Inflammopharmacology
IS - 1
ER -