b1;-lipoic acid: An inhibitor of secretory phospholipase Ab>2b> with anti-inflammatory activity

详细信息	查看全文 | 推荐本文 |

• 作者：Noor Mohamed Jameel ; Mysore A. Shekhar ; Bannikuppe S. Vishwanath
• 关键词：Secretory phospholipase Ab>2b> ; Anti-inflammatory ; b1 ; -lipoic acid
• 刊名：Life Sciences
• 出版年：2006
• 期刊代码：62_00243205
• 类别：imm
• 出版时间：14 December 2006
• 卷：80
• 期：2
• 页码：146-153
• 文件大小：449 K

摘要

b1;-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 PLAb>2b> enzymes from inflammatory fluids and snake venoms. In vitro enzymatic inhibition of sPLAb>2b> from Vipera russellii, Naja naja and partially purified sPLAb>2b> 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 sPLAb>2b> was studied by fluorescent spectral analysis and circular dichroism studies. In vivo anti-inflammatory activity was checked using sPLAb>2b> induced mouse paw edema model. ALA but not DHLA inhibited purified sPLAb>2b> 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. ICb>50b> value calculated for these enzymes ranges from 0.75 to 3.0 bc;M. The inhibition is independent of calcium and substrate concentration. Inflammatory sPLAb>2b> enzymes are more sensitive to inhibition by ALA than snake venom sPLAb>2b> enzymes. ALA quenched the fluorescence intensity of sPLAb>2b> enzyme in a dose dependent manner. Apparent shift in the far UV-CD spectra of sPLAb>2b> with ALA indicated change in its b1;-helical confirmation and these results suggest its direct interaction with the enzyme. ALA inhibits the sPLAb>2b> induced mouse paw edema in a dose dependent manner and confirms the sPLAb>2b> inhibitory activity in vivo also. These data suggest that ALA may act as an endogenous regulator of sPLAb>2b> enzyme activity and suppress inflammatory reactions.