α-lipoic acid: an inhibitor of secretory phospholipase A2 with anti-inflammatory activity

Jameel, Noor Mohamed and Shekhar, M. A. and Vishwanath, B. S. (2006) α-lipoic acid: an inhibitor of secretory phospholipase A2 with anti-inflammatory activity. Life Sciences, 80 (2). 146 - 153. ISSN 1879-0631

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Official URL: https://doi.org/10.1016/j.lfs.2006.08.032

Abstract

α-Lipoic acid (ALA) and its reduced form dihydrolipoic acid (DHLA) are powerful antioxidants both in hydrophilic and lipophylic environments with diverse pharmacological properties including anti-inflammatory activity. The mechanism of anti-inflammatory activity of ALA and DHALA is not known. The present study describes the interaction of ALA and DHALA with pro-inflammatory secretory PLA2 enzymes from inflammatory fluids and snake venoms. In vitro enzymatic inhibition of sPLA2 from Vipera russellii, Naja naja and partially purified sPLA2 enzymes from human ascitic fluid (HAF), human pleural fluid (HPF) and normal human serum (HS) by ALA and DHLA was studied using 14C-oleate labeled Escherichia coli as the substrate. Biophysical interaction of ALA with sPLA2 was studied by fluorescent spectral analysis and circular dichroism studies. In vivo anti-inflammatory activity was checked using sPLA2 induced mouse paw edema model. ALA but not DHLA inhibited purified sPLA2 enzymes from V. russellii, N. naja and partially purified HAF, HPF and HS in a dose dependent manner. This data indicated that ALA is critical for inhibition. IC50 value calculated for these enzymes ranges from 0.75 to 3.0 μM. The inhibition is independent of calcium and substrate concentration. Inflammatory sPLA2 enzymes are more sensitive to inhibition by ALA than snake venom sPLA2 enzymes. ALA quenched the fluorescence intensity of sPLA2 enzyme in a dose dependent manner. Apparent shift in the far UV-CD spectra of sPLA2 with ALA indicated change in its α-helical confirmation and these results suggest its direct interaction with the enzyme. ALA inhibits the sPLA2 induced mouse paw edema in a dose dependent manner and confirms the sPLA2 inhibitory activity in vivo also. These data suggest that ALA may act as an endogenous regulator of sPLA2 enzyme activity and suppress inflammatory reactions.

Item Type: Article
Uncontrolled Keywords: Secretory phospholipase A, Anti-inflammatory, α-lipoic acid
Subjects: C Chemical Science > Biochemistry
Divisions: Department of > Biochemistry
Depositing User: lpa manjunath user
Date Deposited: 08 Aug 2019 05:20
Last Modified: 11 Dec 2019 11:05
URI: http://eprints.uni-mysore.ac.in/id/eprint/6219

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