Effects and mechanism of neuroprotective and neurotherapeutic actions of white Kwao Krua Pueraria mirifica in the hippocampus of estrogen deficient rats were investigated. Serum E2, LH and FSH levels were determined by RIA techniques. The expression of the genes associated with amyloid plaques (App, Adam10 and Bace1) and neurofibrillary tangles (Tau3 and Tau4) in the hippocampus were examined by real-time PCR. Cognitive performance was examined by Morris water maze test. Rats were ovariectomized and kept for 0, 1, 2, 3 and 4 months, or fed with 1 ml/day of distilled water or 100 mg/kg BW/day of P. mirifica (PM) or subcutaneously injected with 7 mg/kg BW/day of puerarin (PU) or 80 mg/kg BW/day of 17beta-estradiol (E2) after ovariectomy for 2 days, 2 and 4 months, respectively, for 4 months, before those parameters were determined. Serum E2 levels were significantly decreased (p<0.005) after 2 weeks of ovariectomy and serum LH and FSH levels were significantly increased (p<0.005) after 1 and 2 months of ovariectomy, respectively. The expression of Tau3 and Tau4 was increased as early as 1 month after ovariectomy while the expression of App, Adam10 and Bace1 was significantly increased after 4 months of ovariectomy. The cognitive impairment was found at 3 and 4 months after ovariectomy. Treatment of PM, PU and E2 in 2-day ovariectomized rats, while serum E2 levels were low, could prevent the cognitive impairment and decreased the expression of App, Adam10, Bace1, Tau3 and Tau4. Treatment of PM, PU and E2 in 2-month ovariectomized rats, while serum estrogen levels were low and serum LH levels were peaked, but the cognitive impairment was yet occurred, the results were similar to those of 2-day ovariectomized rats. However, treatment of PM, PU and E2 in 4-month ovariectomized rats, while cognitive impairment was appeared, could ablate the cognitive impairment in rats, and only the PM fed rats elicited the decreased App mRNA level. Taken together, P. mirifica could exhibit either the neuroprotective or neurotherapeutic effect in ovariectomized rats; however, the neuroprotective effect is more promising than the neurotherapeutics. Thus, treatment of P. mirifica to women should be started during the time of pre- or peri-menopausal period.

Thesis (Ph.D.)--Chulalongkorn University, 2013