Danggui-Shaoyao-San Improves Learning and Memory in Female SAMP8 via Modulation of Estradiol

Abstract

Previous studies showed that Danggui-Shaoyao-San (DSS), a traditional Chinese medicinal prescription, could alleviate cognitive dysfunction of Alzheimer's disease (AD) patients. However, the mechanisms remain unclear; we have now examined the effect of DSS on SAMP8 and elucidated the possible mechanism. Animals were treated with DSS for 2 months, and step-down test and Morris water maze (MWM) test were used to evaluated cognitive abilities. The estradiol (E2), NO, and glycine in blood plasma or in hippocampus were detected to explore the possible mechanisms. The latency of SAMP8 in step-down test was shorter than that of age-matched SAMR1, and DSS increased the latency especially in female animals. In MWM test, we got similar results; SAMP8 spent more time to find the platform, and DSS decreased the time before finding the platform, with little effect on swim velocity, during the training sessions. During test session, DSS increased the time spent in target quadrant especially in female SAMP8. In female SAMP8, plasma E2, NO, and glycine were elevated in plasma or hippocampus tissue. In conclusion, DSS could ameliorate deterioration of cognition in SAMP8, especially in female animals. Increasing E2, NO, and glycine might contribute to the cognitive improvement effect of DSS in female SAMP8.

Herbal Formula Danggui-Shaoyao-San Promotes Neurogenesis and Angiogenesis in Rat Following Middle Cerebral Artery Occlusion

“…A multitude of cellular and molecular mechanisms have been associated with neuroprotection of DSS that include modulation of neurotransmitter, regulation of cerebral blood flow and reduction of NO and malondialdehyde [13,17,19]. In this study, we first reported that DSS improved neuronal outcome through the promotion of angiogenesis and neurogenesis.…”

“…It was reported that DSS modulated the estrogen level in parous ovariectomized rats and stimulated estrogen production in vivo [10,11]. Recent studies found that the function of DSS is not limited to modulation of estrogen level, but is also widely used for the treatment of cognitive impairment and depression [10,[12][13][14][15][16]. Zhou et al reported that DSS reduced infarct size 24 h post-stroke in transient middle cerebral artery occlusion (MCAO) mice [17].…”

“…These materials were purchased from Tongrentang Pharmaceutical Company (Beijing, China), and were then authenticated by Dr. Weipeng Yang in the China Academy of Chinese Medical Sciences. The DSS dilution was prepared as described previously [13]. In brief, the 6 raw herbs were mixed in their dry weight ratios of 3:16:4:4:8:3.…”

Does Infection-Induced Immune Activation Contribute to Dementia?

“…In the MWM test, SAMP8 mice that were administered DSS orally spent less time finding the platform. DSS could increase the estradiol (E2), NO, and glycine, and ameliorate deterioration of cognition in SAMP8 mice, especially in females [71]. After oral administration of DSS for 3 weeks, melatonin level was significantly increased at night.…”

Systems pharmacology-based approach to investigate the mechanisms of Danggui-Shaoyao-san prescription for treatment of Alzheimer’s disease

“…Besides, previous pharmacological studies have deciphered that DSS could exert potentially therapeutic effects for AD via multiple mechanisms such as disrupting the aggregation of Aβ, attenuating inflammatory reaction, and adjusting the mitochondrial membrane permeability ( Table 1 ) . For instance, a study in 2014 has reported that DSS could improve learning and memory capacity in female SAMP8 mice through modulating estrogen, nitric oxide, and glycine in plasma or hippocampal tissue [ 13 ]. Furthermore, Kou et al demonstrated that DSS ameliorated memory dysfunction and protected the ultrastructure of cortex changed by aging, which may be beneficial for the treatment of AD [ 14 ].…”