Fig 1.
Rats induced with AlCl3 showed a significant (P<0.05) decrease in body weight when compared with control rats.
Oral treatment with FSP to AlCl3 induced rats significantly (P<0.05) increased the body weight dose dependently. There are no significant changes in weight gain of FSP alone treated rats when compared with control rats. Data are expressed as mean ± SEM (one-way ANOVA followed by DMRT) for six rats in each group. Values not sharing the same symbols differ significantly.
Fig 2.
AlCl3 treated rats exhibited increased step-through latency (STL) in passive avoidance test.
AlCl3 induced STL was reduced dose dependently by FSP co-treatment. Data are expressed as mean ± SEM (one-way ANOVA followed by DMRT) for six rats in each group. Values not sharing the same symbols differ significantly−*p < 0.05 compared to the control, #p < 0.05 compared to the AlCl3 treated rats, @p < 0.05 compared to the AlCl3 + FSP (2.5%).
Fig 3.
AlCl3 rats took more time to reach both the visible (on day 20) and hidden (on day 21 and 42) indicating memory deficits.
Co-treatment of FSP (5%) significantly enhanced memory performance on day 20, 21 and 42 in both training and retention phase. Data are expressed as mean ± SEM (a repeated-measured ANOVA followed by DMRT) for six rats in each group. Values not sharing the same symbols differ significantly−*p < 0.05 compared to the control, #p < 0.05 compared to the AlCl3 treated rats.
Fig 4.
AlCl3 animals exhibited enhanced levels of Al in hippocampus and cortex.
Cotreatment of FSP (2.5, 5 and 10%) dose dependently attenuated the AlCl3 mediated Al burden. Data are expressed as mean ± SEM (one-way ANOVA followed by DMRT) for six rats in each group. Values not sharing the same symbols differ significantly−*p < 0.05 compared to the control, #p < 0.05 compared to the AlCl3 treated rats.
Fig 5.
AlCl3 group showed significantly enhanced AChE activity in hippocampus and cortex.
However, FSP (2.5,5 and 10%) co-treatment significantly attenuated the AChE hyperactivity in both regions of brain. It was observed that 5% and 10% FSP treatment showed similar reduction in Al levels and AChE activity, but more significant than 2.5% FSP. As a consequence, we have chosen the optimum dose (5% FSP) for our further study. Data are expressed as mean ± SEM (one-way ANOVA followed by DMRT) for six rats in each group. Values not sharing the same symbols differ significantly−*p < 0.05 compared to the control, #p < 0.05 compared to the AlCl3 treated rats.
Fig 6.
AlCl3 treatment significantly enhanced the protein expressions of APP, Aβ1–42, β and γ secretases and favours amyloid biosynthesis.
Coadministration of FSP attenuated the AlCl3 mediated amyloid biosynthesis. Data are expressed as mean ± SEM (one-way ANOVA followed by DMRT) for three rats in each group. Values not sharing the same symbols differ significantly−*p < 0.05 compared to the control, #p < 0.05 compared to the AlCl3 treated rats.
Fig 7.
Chronic treatment of AlCl3 significantly increased the protein expressions of Bax, Bad, cyto c, caspases -9 and cyto c (mitochondrial fraction) and decreased the expressions of Bcl-2, Bcl—xL and cyto c (cytosolic fraction) in the hippocampus and cortex and favours apoptosis.
However, FSP supplementation (5%) attenuated the AlCl3 induced apoptosis. No-significant changes in the expressions of pro-caspase-3 (32 kDa) were found in control and experimental groups. The activated caspase-3 (17 kDa) expression is enhanced following aluminum treatment and inhibited by the FSP co-treatment, which further proves the antiapoptotic property of FSP. Data are expressed as mean ± SEM (one-way ANOVA followed by DMRT) for three rats in each group. Values not sharing the same symbols differ significantly−*p < 0.05 compared to the control, #p < 0.05 compared to the AlCl3 treated rats.
Fig 8.
AlCl3 rats exhibited significantly lowered the expressions of pAkt and pGSK-3β in hippocampus and cortex.
Western blot studies indicated that their expressions were significantly attenuated by co-treatment with FSP (5%). Data are expressed as mean ± SEM (one-way ANOVA followed by DMRT) for three rats in each group. Values not sharing the same symbols differ significantly−*p < 0.05 compared to the control, #p < 0.05 compared to the AlCl3 treated rats.