Chronic Cold-Water-Induced Hypothermia Impairs Memory Retrieval and Nepeta menthoides as a Traditional “Hot” Herb Reverses the Impairment

Document Type: Research article


1 Department of Traditional Pharmacy, School of Traditional Medicine, Shahid Beheshti University of Medical Sciences,Tehran, Iran

2 1-Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.2-Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia

3 Department of Pharmacognosy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

4 Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

5 Traditional Medicine and Materia Medica Research center, Shahid Beheshti University of Medical Sciences, Tehran, Iran


Iranian Traditional Medicine (ITM) describes a kind of dementia with similar signs and symptoms of Alzheimer’s disease (AD). It explains the pathology of dementia with cold intemperament of the brain, which means that the brain is colder than its healthy form. ITM strategy for treatment of dementia is to heat the brain up by medical “hot” herbs. Nepeta menthoides (NM) is one of these “hot” herbs. To evaluate the veracity of ITM concept about dementia and its treatment, we first try to examine if coldness of brain can make memory impairment. If so, can NM reverse memory impairment? Rats in cold-water-induced hypothermic (CWH) groups were immersed up to the neck in 3.5°C water, for 5 min during 14 consecutive days. As a control, rats were forced to swim in warm water at the same conditions. To eliminate the impact of forced swimming stress, a group of intact rats was also added. After last swimming in day 14, some groups received drug (100 or 500 mg/kg aqueous extract of NM) or vehicle via i.p. injection. Learning and memory were assessed by Morris water maze, and tau hyperphosphorylation was measured by western blotting. The results showed that CWH impairs learning and memory and induces tau hyperphosphorylation. 100 mg/kg of NM reversed memory impairment as well as tau hyperphosphorylation. ITM theory about the relationship between brain hypothermia and dementia is in accordance with our findings.


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