Jaehoon Kim1, Young Hye Seo2, Jihyun Kim1, Nayeon Goo1, Yongwoo Jeong1, Ho Jung Bae1, Seo Yun Jung1, Jun Lee3, Jong Hoon Ryu4. 1. Department of Life and Nanopharmaceutical Science, Kyung Hee University, Seoul, 02447, Republic of Korea. 2. Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine (KIOM), Naju, 58245, Republic of Korea. 3. Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine (KIOM), Naju, 58245, Republic of Korea. Electronic address: junlee@kiom.re.kr. 4. Department of Life and Nanopharmaceutical Science, Kyung Hee University, Seoul, 02447, Republic of Korea; Department of Oriental Pharmaceutical Science, Kyung Hee University, Seoul, 02447, Republic of Korea. Electronic address: jhryu63@khu.ac.kr.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: The fruit of Vitex rotundifolia L. (Verbenaceae) has been used in traditional medicine as sedative or analgesic agent for headache. Recent population-based cohort studies have shown that headache including migraines is a risk factor for dementia. Thus, the fruit of V. rotundifolia may be useful for treating cognitive dysfunction observed in dementia. AIM OF THE STUDY: We had previously found that the ethanolic extract of the fruit of V. rotundifolia ameliorated cognitive dysfunction and isolated casticin as an active compound. In the present study, we studied the effect of casticin on a mouse model of cognitive impairment induced by scopolamine. MATERIALS AND METHODS: Mice were treated with the ethanolic extract of the fruit of V. rotundifolia (EEVR; 30, 100 or 300 mg/kg, p.o.) or casticin (0.3, 1 or 3 mg/kg, p.o.). We examined the effect of casticin or EEVR using the passive avoidance test, the Morris water maze test and the novel object recognition test. Scopolamine (1 mg/kg, i.p.) was used to induce cognitive impairment by blocking cholinergic neurotransmitter system. We investigated the effects of casticin on acetylcholinesterase (AchE) activity and the phosphorylation levels of extracellular signal-regulated kinase (ERK), cAMP response element binding protein (CREB), and the expression levels of brain-derived neurotrophic factor (BDNF). RESULTS: EEVR (100 and 300 mg/kg, p.o.) significantly ameliorated the latency in the passive avoidance test, and casticin (1 and 3 mg/kg, p.o.) also significantly improved the latency in the passive avoidance test, novel object preference in the novel object recognition test, and swimming time in the target quadrant of the Morris water maze test. Casticin also decreased AChE activity in ex vivo analysis and increased the phosphorylation levels of memory-related signaling molecules, such as ERK, CREB and BDNF in the cortex. CONCLUSION: These results suggest that casticin ameliorates cholinergic blockade-induced cognitive impairment, in part, through the inhibition of AChE and the activation of the ERK-CREB-BDNF signaling pathway. Taken together, the results suggest that casticin may be useful for treating the cognitive dysfunction observed during cholinergic impairment.
ETHNOPHARMACOLOGICAL RELEVANCE: The fruit of Vitex rotundifolia L. (Verbenaceae) has been used in traditional medicine as sedative or analgesic agent for headache. Recent population-based cohort studies have shown that headache including migraines is a risk factor for dementia. Thus, the fruit of V. rotundifolia may be useful for treating cognitive dysfunction observed in dementia. AIM OF THE STUDY: We had previously found that the ethanolic extract of the fruit of V. rotundifolia ameliorated cognitive dysfunction and isolated casticin as an active compound. In the present study, we studied the effect of casticin on a mouse model of cognitive impairment induced by scopolamine. MATERIALS AND METHODS:Mice were treated with the ethanolic extract of the fruit of V. rotundifolia (EEVR; 30, 100 or 300 mg/kg, p.o.) or casticin (0.3, 1 or 3 mg/kg, p.o.). We examined the effect of casticin or EEVR using the passive avoidance test, the Morris water maze test and the novel object recognition test. Scopolamine (1 mg/kg, i.p.) was used to induce cognitive impairment by blocking cholinergic neurotransmitter system. We investigated the effects of casticin on acetylcholinesterase (AchE) activity and the phosphorylation levels of extracellular signal-regulated kinase (ERK), cAMP response element binding protein (CREB), and the expression levels of brain-derived neurotrophic factor (BDNF). RESULTS: EEVR (100 and 300 mg/kg, p.o.) significantly ameliorated the latency in the passive avoidance test, and casticin (1 and 3 mg/kg, p.o.) also significantly improved the latency in the passive avoidance test, novel object preference in the novel object recognition test, and swimming time in the target quadrant of the Morris water maze test. Casticin also decreased AChE activity in ex vivo analysis and increased the phosphorylation levels of memory-related signaling molecules, such as ERK, CREB and BDNF in the cortex. CONCLUSION: These results suggest that casticin ameliorates cholinergic blockade-induced cognitive impairment, in part, through the inhibition of AChE and the activation of the ERK-CREB-BDNF signaling pathway. Taken together, the results suggest that casticin may be useful for treating the cognitive dysfunction observed during cholinergic impairment.