Oral administration of Cimicifuga racemosa extract affects immobilization stress-induced changes in murine cerebral monoamine metabolism

Abstract

We investigated the effects of Cimicifuga racemosa (CR) plant extracts on the changes in levels of the cerebral monoamines norepinephrine (NE), dopamine (DA), and serotonin (5-HT), the respective metabolites 3-methoxy-4-hydroxyphenylglycol (MHPG), 3,4-dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA), and plasma corticosterone in mice subjected to acute immobilization stress. Single oral administration of the CR extract (1,000 mg/kg) significantly attenuated plasma corticosterone levels that had been increased as a result of enforced immobilization. Acute immobilization stress caused significant changes in the corresponding amine-to-metabolite ratios in the hypothalamus, hippocampus, and cortex; however, CR-extract treatment significantly attenuated the MHPG/NE change in the hypothalamus, and the 5-HIAA/5-HT changes in each region of the brain. Our results suggest that the CR extract interacts not only with the hypothalamic-pituitary-adrenal (HPA) axis but also with the sympathetic adrenomedullary (SAM) system under stress conditions. Thus the CR extract can alleviate acute stress responses by suppressing the changes of amine-to-metabolite ratio in brain.Cimicifuga racemosa (CR) is a member of the Ranunculaceae family that is indigenous to eastern North America, with a range that extends as far as south Florida. Dried CR rhizomes are known as black cohosh and have been widely used as herbal dietary supplements for almost five decades. Historically, Native American women ingested CR water extract for pain relief during menstruation and childbirth. In recent years, ethanolic and isopropanolic extracts of CR have been used for the treatment of general menopause symptoms including hot flushes, profuse sweating, irritability, and anxiety, and its popularity has grown among women hoping to avoid the potential toxicity of classical hormonereplacement therapy (2). We previously showed that CR extracts had antistress activities in mice in which plasma corticosterone and aspartate aminotransferase (AST) levels were increased as a result of enforced immobilization: a single oral administration of CR extract (1,000 mg/kg) significantly attenuated these increases (23). Previous studies have reported that acute immobilization stress not only elicits activation of the hypothalamic-pituitary-adrenal (HPA) axis but also affects the metabolism of monoamines such as norepinephrine (NE), dopamine (DA), and serotonin (5-HT) in the brain. And these amine-to-metabolite ratios are increased by acute immobilization stress. Furthermore, the relationships among NE, DA, and 5-HT play an important role in regulation of the sympathetic adrenomedullary (SAM) system under stress conditions (5,20,31). Several studies have reported that the neuronal activities of serotonergic and dopaminergic pathways innervating the striatum, hippocampus, hypo-

Oral administration of Cimicifuga racemosa extract attenuates psychological and physiological stress responses

“…Several previous studies have reported that CR extract interacts with neurotransmitters such as 5-HT (6,32,39) and DA (5). In vitro, CR extract acts as agonist of various 5-HT receptors, particularly 5-HT 1A , 5-HT 1D , and 5-HT 7 .…”

“…The stress-induced changes in murine cerebral monoamine metabolism (32). Although many clinical studies reported the efficacy of CR extracts for relieving menopausal symptoms, no investigations have been carried out into their anti-stress properties in humans.…”

Effects of Remifemin Treatment on Bone Integrity and Remodeling in Rats with Ovariectomy-Induced Osteoporosis

“…Because certain extracts of Cimicifuga Racemosa are already recognized as safe and useful for the treatment of certain gynecological disorders [20,27], this study did not include an assessment of the safety of Remifemin; besides, due to the short duration of this experiment and the small number of animals, we were unable to observe the maximum effects of this drug. More studies are needed to fully elucidate Remifemin’s specific mechanisms that affect bone protection, and also regarding its optimal treatment duration and dosage for this additional benefit.…”

Effects of black cohosh on estrogen biosynthesis in hippocampus of non-human primates ex vivo in vitro and in human neuroblastoma cells in vitro

“…Black cohosh, specifically, iCR has been shown to have an impact on brain via modulating neurotransmitter receptors in vitro [20][21][22][23] and in vivo in rodents [14,24] as well as in humans [25,26]. There is pharmacodynamic evidence for bioactivity of iCR-ingredients in brain in vivo, i.e.…”

“…During menopause, the decline of circulating estrogens coincidences with the decline of brain bioenergetics and a shift towards a metabolically compromised phenotype [27]. Oral administration of iCR or E2 for 1 week to ovariectomized rats was able to restore neuronal excitability leading to functional recovery of hypothalamic activity [14,24]. Furthermore, iCR has been shown to upregulate genes related to cell survival under metabolic stress such as hypoxia [28][29][30].…”