Daily oral cotreatment with BYA or YP decreased the brain level of TNF-[alpha] compared with that of the D-gal mice to p < 0.05; and cotreatment with BYPA, BYP, BY, or BP decreased the brain level of TNF-[alpha] compared with that of the D-gal mice more extensively to p < 0.01 (Figure 2(a)).
Daily oral cotreatment with BYA, BPA, or YP effectively decreased the brain MDA compared with that of the D-gal mice to p < 0.05; and cotreatment with BYPA, BYP, BY, or BP decreased the brain level of MDA compared with that of the D-gal mice more markedly to p < 0.01 (Figure 2(c)).
In contrast, none of the mice in the Veh group, or in the groups that received D-galactose injections along with an extract from BYPA, BYP, BYA, BPA, or YPA, displayed any loss of whiskers.
As reported earlier , the four-herb BYPA combination induced significant anxiolysis but no sedative effect up to 120 mg/kg (Figures 4 and 5).
The B, Y, A, and BYPA extracts all inhibited the binding of the [GABA.sub.A] receptor benzodiazepine- (BZ-) site agonist [[sup.3]H]-flunitrazepam to rat cerebral cortex membranes with half-inhibition concentration ([IC.sub.50]) values within the same order of magnitude.
Based on the D-galactose-induced accelerated-aging model, the present study showed that extracts of various mixtures of the B, Y, P, and A herbs, especially the BYP, BYA, BY, BP, YP, and BYPA extracts, brought about significant protection against one or more aging effects, including improvement of spatial memory (Figure 1), reduction in neuroinflammation in terms of the brain levels of proinflammatory cytokines TNF-[alpha] and IL-6, or reduction in oxidative stress in the brain in terms of the level of MDA (Figure 2).
Importantly, although each of the B, P, and A herbs when administered alone at 30 mg/kg or 60/mg upwards gave rise to significant sedation, none of the BYP, BPA, BY, BP, BA, YP, YA, and BYPA combinations induced significant sedation at 120 mg/kg (Figure 5).
(III) Two of the mice treated with D-galactose and BYPA, (IV) two of the mice treated with D-galactose and BYP, (V) two of the mice treated with D-galactose and BYA, (VI) two of the mice treated with D-galactose and BPA, and (VII) two of the mice treated with D-galactose and YPA.
Effects of extracts of BYPA (*, black); B (**, green); Y (***, light blue); P (***, dark blue); and A (***, yellow).
The paired columns for herbal combinations BA and BYPA show in each instance that the anxiolytic effect induced by the combination (red column on the right) exceeded the sum of effects induced by the individual component herbs (composite column on the left: B in green, Y in light blue, P in dark blue, and A in yellow); in contrast, the paired columns for YP show that the anxiolytic effects induced by its component herbs Y and P were abolished by antagonisms within the YP combination.