Our results indicated possible decreasing effect of ALA on inflammatory mediators especially in high dose .
& NA ; Alpha‐Lipoic Acid ( ALA ) is a natural antioxidant compound which is naturally found in plant sources .
New evidence revealed that ALA can reduce inflammation .
Our objective in this meta‐ analysis was to conduct a systematic review and meta‐ analysis on r and omized controlled trials to indicate ALA effects on serum inflammatory mediators concentration such as tumor necrosis factor‐alpha ( TNF‐&agr ; ) , c‐reactive protein ( CRP ) , and interleukin‐6 ( IL‐6 ) .
Lipoic Acid Attenuates Inflammation via cAMP and Protein Kinase A Signaling
Background Abnormal regulation of the inflammatory response is an important component of diseases such as diabetes , Alzheimer 's disease and multiple sclerosis ( MS ) . Lipoic acid ( LA ) has been shown to have antioxidant and anti-inflammatory properties and is being pursued as a therapy for these diseases . We first reported that LA stimulates cAMP production via activation of G-protein coupled receptors and adenylyl cyclases . LA also suppressed NK cell activation and cytotoxicity . In this study we present evidence supporting the hypothesis that the anti-inflammatory properties of LA are mediated by the cAMP/PKA signaling cascade . Additionally , we show that LA oral administration elevates cAMP levels in MS subjects . Methodology /Principal Findings We determined the effects of LA on IL-6 , IL-17 and IL-10 secretion using ELISAs . Treatment with 50 µg/ml and 100 µg/ml LA significantly reduced IL-6 levels by 19 and 34 % , respectively , in T cell enriched P BMC s. IL-17 levels were also reduced by 35 and 50 % , respectively . Though not significant , LA appeared to have a biphasic effect on IL-10 production . Thymidine incorporation studies showed LA inhibited T cell proliferation by 90 % . T-cell activation was reduced by 50 % as measured by IL-2 secretion . Western blot analysis showed that LA treatment increased phosphorylation of Lck , a downstream effector of protein kinase A. Pretreatment with a peptide inhibitor of PKA , PKI , blocked LA inhibition of IL-2 and IFN gamma production , indicating that PKA mediates these responses . Oral administration of 1200 mg LA to MS subjects result ed in increased cAMP levels in P BMC s four hours after ingestion . Average cAMP levels in 20 subjects were 43 % higher than baseline . Conclusions / Significance Oral administration of LA in vivo result ed in significant increases in cAMP concentration . The anti-inflammatory effects of LA are mediated in part by the cAMP/PKA signaling cascade . These novel findings enhance our underst and ing of the mechanisms of action of LA
Our results indicated possible decreasing effect of ALA on inflammatory mediators especially in high dose .
& NA ; Alpha‐Lipoic Acid ( ALA ) is a natural antioxidant compound which is naturally found in plant sources .
New evidence revealed that ALA can reduce inflammation .
Our objective in this meta‐ analysis was to conduct a systematic review and meta‐ analysis on r and omized controlled trials to indicate ALA effects on serum inflammatory mediators concentration such as tumor necrosis factor‐alpha ( TNF‐&agr ; ) , c‐reactive protein ( CRP ) , and interleukin‐6 ( IL‐6 ) .