Effect Of Sal A On Regulating Intracellular Calcium, Scavenging Free Radicals, Memory, Signal Transduction, C-fos Expression And SIV Infection.

Salvianolic acids are depsides isolated from traditional Chinese herb-Salvia miltirrhiza and theirsynthetic derivatives. This paper deals with the influence of salvianolic acids, especially salvianolic acids A (Sal,A) on the following five aspects: 1. the effect of the salvianolic acids on lipidperoxidation, anti-oxidative mechanisms and structure-activity relationship. 2. the effect of Sal A on anisodine induced impairment of mouse memory and the influence of the drug on monoamines of brain cortex. 3. the influence of Sal A on signal transduction system such as intracellular calcium , cAMP, PKC activity and protein phosphorylation. 4. the effect of Sal A on c-fos expression in brain in vivo, 5. the influence of Sal A, B and Sal AA on SIVmac infection.Salvianolic acids could significantly inhibit rat brain and liver lipidperoxidation, the order of inhibitory effect was Sal A = Sal B > Sal C = Sal AA > Ros A >> Sal M = Dan, among them Sal A showed the most potent effect which is about 100 times more potent than that of Vit E and is one of the strongest natural anti-oxidant products known up to date. Further study showed that these compounds could inhibit NBT reduction induced by both xanthine oxidase and non-enzyme generated superoxide anion, and their efficacy order was basically in correspondence with that on lipidperoxidation. The IC₅₀ ranged from 1 to 10 and 10 to 100 umol/L respectively. The inhibitory effect of these compounds on xanthine oxidase was obtained but the IC₅₀ was 100-300 umol/L, about 10-100 times higher than that on NBT reduction in xanthineoxidase system, and the dose range of analogues was nearly the same, indicating that the compounds could directly scavenge superoxide anion. Using HPLC detection withsalicylic acid as probe, we found that salvianolic acids significantly inhibited hydroxylation of salicylic acid in both Fe²⁺-EDTA-H₂O₂ and Fe²⁺-Vit C-H₂O₂ systems. In the former system, these compounds dose-dependently inhibited salicylic acid hydroxylation except Sal A which, like Vit C, inhibit salicylic acid hydroxylation at high concentration(higher than 10^-4mol/L) while promoted salicylic acid hydroxylation at low (lower than 10^-4mol/L) concentration. In the later system, all compounds tested dose-dependently inhibited hydroxylation of salicylic acid and the IC₅₀ range was about 1-10 umol/L. This suggested that Salvianolic acids could scavenge hydroxyl free...