Methanolic extract of Piper nigrum fruits improves memory impairment by decreasing brain oxidative stress in amyloid beta(1-42) rat model of Alzheimer's disease

Abstract

The present study analyzed the possible memory-enhancing and antioxidant proprieties of the methanolic extract of Piper nigrum L. fruits (50 and 100 mg/kg, orally, for 21 days) in amyloid beta(1-42) rat model of Alzheimer's disease. The memory-enhancing effects of the plant extract were studied by means of in vivo (Y-maze and radial arm-maze tasks) approaches. Also, the antioxidant activity in the hippocampus was assessed using superoxide dismutase-, catalase-, glutathione peroxidase-specific activities and the total content of reduced glutathione, malondialdehyde, and protein carbonyl levels. The amyloid beta(1-42)-treated rats exhibited the following: decrease of spontaneous alternations percentage within Y-maze task and increase of working memory and reference memory errors within radial arm-maze task. Administration of the plant extract significantly improved memory performance and exhibited antioxidant potential. Our results suggest that the plant extract ameliorates amyloid beta(1-42)-induced spatial memory impairment by attenuation of the oxidative stress in the rat hippocampus.

Fig. 1

HPLC data for piperine isolated from the Piper nigrum fruits extract

Fig. 2

Representative images of the amyloid plaques in the rat hippocampus in control (a), Aβ(1–42)-treatedgroup (b), Aβ(1–42)+P50-treated group (c) and Aβ(1–42)+P100-treated group (d). Reduced Aβ plaque load in Aβ(1–42)+P50- and Aβ(1–42)+P100-treated groups as compared with Aβ(1–42)-treated group (e) was evidenced. Values are mean ± SEM, ***p < 0.0001 versus Aβ(1–42)-treated group

Fig. 3

Effects of the methanolic extract of Piper nigrum fruits (50 and 100 mg/kg) in the Y-maze on spontaneous alternation % (b) and number of arm entries (a), on the working memory errors (c) and the reference memory errors (d) during 7 days training in radial arm-maze task in the Aβ(1–42)-treated rats. Values are mean ± SEM (n = 10 animals per group), **p < 0.0001 versus Aβ(1–42)-treated group

Fig. 4

Effects of the methanolic extract of Piper nigrum fruits (50 and 100 mg/kg) on SOD (a), GPX (b), and CAT (c) specific activities, on reduced GSH (d), protein carbonyl (e), and MDA (f) levels in the Aβ(1–42)-treated rats. Values are mean ± SEM (n = 10 animals per group), **p < 0.0001, ***p < 0.00001 versus Aβ(1–42)-treated group

Fig. 5

Pearson’s correlation between spontaneous alternation % versus MDA (a), working memory errors versus MDA (b), reference memory errors versus MDA (c), SOD versus MDA (d), GPX versus MDA (e), CAT versus MDA (f), and protein carbonyl versus MDA (g) in control group (circle), Aβ(1–42)-treated group (square), Aβ(1–42)+P50 group (diamond), and Aβ(1–42)+P100 group (triangle)

Fig. 6

Effects of the methanolic extract of Piper nigrum fruits (50 and 100 mg/kg) on DNA fragmentation by agarose (1.5 %) gel electrophoresis. Lane 1 DNA ladder; lane 2 control group; lane 3 Aβ(1–42)-treated group; lane 4 Aβ(1–42)+P50 group; and lane 5 Aβ(1–42)+P100 group