Nutr Res Pract.  2016 Jun;10(3):274-281. 10.4162/nrp.2016.10.3.274.

Perilla frutescens var. japonica and rosmarinic acid improve amyloid-β25-35 induced impairment of cognition and memory function

• Lee AY
• Hwang BR
• Lee MH
• Lee S
• Cho EJ

• KMID: 2342129
• DOI: http://doi.org/10.4162/nrp.2016.10.3.274

Abstract

BACKGROUND/OBJECTIVES
The accumulation of amyloid-β (Aβ) in the brain is a hallmark of Alzheimer's disease (AD) and plays a key role in cognitive dysfunction. Perilla frutescens var. japonica extract (PFE) and its major compound, rosmarinic acid (RA), have shown antioxidant and anti-inflammatory activities. We investigated whether administration of PFE and RA contributes to cognitive improvement in an Aβ25-35-injected mouse model.
MATERIALS/METHODS
Male ICR mice were intracerebroventricularly injected with aggregated Aβ25-35 to induce AD. Aβ25-35-injected mice were fed PFE (50 mg/kg/day) or RA (0.25 mg/kg/day) for 14 days and examined for learning and memory ability through the T-maze, object recognition, and Morris water maze test.
RESULTS
Our present study demonstrated that PFE and RA administration significantly enhanced cognition function and object discrimination, which were impaired by Aβ25-35, in the T-maze and object recognition tests, respectively. In addition, oral administration of PFE and RA decreased the time to reach the platform and increased the number of crossings over the removed platform when compared with the Aβ25-35-induced control group in the Morris water maze test. Furthermore, PFE and RA significantly decreased the levels of nitric oxide (NO) and malondialdehyde (MDA) in the brain, kidney, and liver. In particular, PFE markedly attenuated oxidative stress by inhibiting production of NO and MDA in the Aβ25-35-injected mouse brain.
CONCLUSIONS
These results suggest that PFE and its active compound RA have beneficial effects on cognitive improvement and may help prevent AD induced by Aβ.

Keyword

Perilla frutescens; rosmarinic acid; amyloid beta; Alzheimer's disease; cognition

MeSH Terms

Administration, Oral
Alzheimer Disease
Animals
Brain
Cognition*
Discrimination (Psychology)
Humans
Kidney
Learning
Liver
Male
Malondialdehyde
Memory*
Mice
Mice, Inbred ICR
Nitric Oxide
Oxidative Stress
Perilla frutescens*
Perilla*
Water
Malondialdehyde
Nitric Oxide
Water

Figure

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  Fig. 1 Behavioral experimental schedule for mice injected with Aβ25-35.

• 

  Fig. 2 Effects of Perilla frutescens var. japonica extract (PFE) and rosmarinic acid (RA) on spontaneous alternation behavior in the T-maze test. Data represent the means ± SD. (n = 8) * P < 0.05 compared with old route. PFE: Perilla frutescens var. japonica extract administered orally at 50 mg/kg/day. RA: rosmarinic acid administered orally at 0.25 mg/kg/day.

• 

  Fig. 3 Effects of Perilla frutescens var. japonica extract (PFE) and rosmarinic acid (RA) on recognition memory in the novel object recognition test. Data represent the means ± SD. (n = 8) * P < 0.05 compared with familiar object. PFE: Perilla frutescens var. japonica extract administered orally at 50 mg/kg/day; RA: rosmarinic acid administered orally at 0.25 mg/kg/day.

• 

  Fig. 4 Effect of Perilla frutescens var. japonica extract (PFE) and rosmarinic acid (RA) on escape latency to platform in the Morris water maze test. Data represent means ± SD. (n = 8) * P < 0.05 compared with normal group, # P < 0.05 compared with Aβ25-35-treated control group. PFE: Perilla frutescens var. japonica extract administered orally at 50 mg/kg/day; RA: rosmarinic acid administered orally at 0.25 mg/kg/day.

• 

  Fig. 5 Effect of Perilla frutescens var. japonica extract (PFE) and rosmarinic acid (RA) on occupancy time in the target quadrant in the Morris water maze test. The percentage of time spent in the target quadrant was calculated in the water maze test on the final test day. Data represent means ± SD. (n = 8) * P < 0.05 compared with normal group, # P < 0.05 compared with Aβ25-35-treated control group. PFE: Perilla frutescens var. japonica extract administered orally at 50 mg/kg/day; RA: rosmarinic acid administered orally at 0.25 mg/kg/day.

• 

  Fig. 6 Effect of Perilla frutescens var. japonica extract (PFE) and rosmarinic acid (RA) on latency to reach hidden platform (A) and exposed platform (B) in the Morris water maze test. Data represent the means ± SD. (n = 8) * P < 0.05 compared with normal group, # P < 0.05 compared with Aβ25-35-treated control group. NS indicates no significant differences among experimental groups. PFE: Perilla frutescens var. japonica extract administered orally at 50 mg/kg/day; RA: rosmarinic acid administered orally at 0.25 mg/kg/day.

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