Apigenin mitigates oxidative stress, neuroinflammation, and cognitive impairment but enhances learning and memory in aluminum chloride-induced neurotoxicity in rats

Abstract

Introduction: Aluminum chloride (AlCl₃) exposure has been linked to neurotoxicity in various animal models, presenting significant concern to human health due to its potential implications in neurodegenerative diseases. Aluminum chloride is a widely recognized neurotoxin and has been used as an animal model of Alzheimer's disease via mechanisms linked with oxidative stress and inflammation. The study investigated the potential ameliorative effect of apigenin on AlCl₃-induced neurotoxicity in rats.

Methods: Forty adult male Wistar rats were randomly divided into four different groups - control, AlCl₃ (100 mg/kg), apigenin (50 mg/kg) plus AlCl₃, and apigenin (50 mg/kg) alone administered orally for 14 days.

Results: Our findings revealed AlCl₃ exposure induced significant neurobehavioral deficits, oxidative stress, neuroinflammation, and loss of the Purkinje cell layer of the cerebellum. Treatment with apigenin attenuated neuroinflammation and enhanced learning and memory with significant improvement in recognition index.

Discussion: Apigenin demonstrates promising ameliorative effects against AlCl₃-induced neurotoxicity in rats.

Highlights: Aluminum chloride toxicity caused significant reduction in learning, exploration, and memory. Aluminum chloride toxicity induced neurotoxicity, increased biomarkers of oxidative stress, neuroinflammation, and precipitated cognitive impairment. Apigenin improved brain antioxidant, enhanced learning, exploration, and memory.

Keywords: Apigenin; cognitive impairment; neurotoxicity; oxidative stress.

FIGURE 1

(A) Structure of apigenin (4′,5,7,‐trihydroxyflavone). (B) Structure of aluminum chloride (AlCl₃).

FIGURE 2

Effects of aluminum chloride‐induced neurotoxicity on body weight, brain weight, and relative brain weight. Letter a indicates significant difference compared with control, while letter b indicates significant difference compared with AlCl₃, and letter c indicates significant difference compared with AlCl₃ + apigenin. Mean ± SD (n = 6).

FIGURE 3

Effects of aluminum chloride‐induced neurotoxicity on recognition index. Letter a indicates significant difference compared with control, while letter b indicates significant difference compared with AlCl₃. Mean ± SD (n = 6).

FIGURE 4

Effects of aluminum chloride‐induced neurotoxicity on brain nitric oxide (NO) level and acetylcholinesterase (AChE) activity. Letter a indicates significant difference compared with control. letter b indicates significant difference compared with AlCl₃, while letter c indicates significant difference compared with AlCl₃ + apigenin. Mean ± SD (n = 6).

FIGURE 5

Effects of aluminum chloride‐induced neurotoxicity on brain malondialdehyde (MDA) levels and content of hydrogen peroxide generation. Letter a indicates significant difference compared with control, while letter b indicates significant difference compared with AlCl₃. Mean ± SD (n = 6).

FIGURE 6

Effects of aluminum chloride‐induced neurotoxicity on brain glutathione S‐transferase and superoxide dismutase activity. Letter a indicates significant difference compared with control. Letter b indicates significant difference compared with AlCl₃, while letter c indicates significant difference compared with AlCl₃ + apigenin. Mean ± SD (n = 6).

FIGURE 7

Cerebellum, cresyl violet stain. Note loss of Purkinje cell layer (red arrows) in AlCl₃ group. These were rescued with concurrent administration of apigenin. Scale bar, 50 µm.