Elsevier

Journal of Ethnopharmacology

Volume 138, Issue 1, 31 October 2011, Pages 156-161
Journal of Ethnopharmacology

Effects of an isopropanolic-aqueous black cohosh extract on central body temperature of ovariectomized rats

https://doi.org/10.1016/j.jep.2011.08.076Get rights and content

Abstract

Ethnopharmacological relevance

Black cohosh (Cimicifuga racemosa) is widely used in menopause symptoms strategy.

Aim of the study

The aim of this study was to examine the effect of isopropanolic black cohosh extract (iCR) on the central body temperature (CBT) of ovariectomized rats (OVX) and elaborate its possible effects in alleviating menopause related hot flushes.

Materials and methods

64 female Sprague-Dawley rats, weighing 230 ± 10 g and aged 6–8 weeks, were divided into four groups: ovariectomy (OVX), sham, ovariectomy plus estradiol valerate (OVX + E), and ovariectomy plus iCR (OVX + ICR). The sham group underwent a sham surgery without ovariectomies, while the other three groups underwent bilateral ovariectomies under sterile conditions and a temperature implant was embedded in the abdominal cavity of all four groups. After 2-week recovery period, the temperature of all animals was monitored for 6 weeks.

Results

CBT of four groups maintained a normal circadian rhythm, with a low day CBT and a high night CBT. CBTs of the sham group were lower than that of the other three groups. The day CBTs of the (OVX + E) group and (OVX + ICR) group were lower than that of the OVX group from day 2 and day 22 respectively. For the difference between day and night CBT, the sham group was smallest, while (OVX + E) and (OVX + ICR) groups were higher than that of OVX group. The amplitude of day and night CBT, CBT fluctuation frequency at 5 min intervals, were higher for the OVX group than the sham group; the amplitude of day and night CBT of (OVX + E) group and the amplitude of night CBT of (OVX + ICR) group were higher than those of OVX group; while the amplitude of day CBT of (OVX + ICR) group was lower than that of OVX group; CBT fluctuation frequency at 5 min intervals was higher for the (OVX + E) and (OVX + ICR) groups than the OVX group.

Conclusions

Ovariectomized rats had abnormal thermoregulation, demonstrating an increase in day and night CBT, greater difference between day and night CBT, higher amplitude of day and night CBT, and more CBT fluctuation frequency. For the herbal extract iCR, the onset of affecting abnormal thermoregulation took longer than that of estradiol valerate. ICR had a significant effect on day CBT but was only little effective on night CBT of ovariectomized rats.

Introduction

The hot flush associated with the menopause is an unique symptom and causes considerable distress and impairment of quality of life. Menopausal hot flush occurs in as many as 74% of menopausal women (Kritz-Silverstein et al., 2000), and for some 40% the symptom is troublesome enough to seek for medical help. The underlying mechanism of hot flushes is still unclear. However, one long-standing assumption has been that hot flashes involve dysregulation of the thermoregulatory system, triggering homeostatic heat loss mechanisms to return the system to normal (Kronenberg, 2010).

It is well known that preoptic anterior hypothalamus (PO/AH), which contains warmth-sensitive/cold-sensitive neurons, receives input from peripheral and deep tissue thermal receptors when core body temperature (CBT) is low/high. Normal homeostasis operates to keep the core body temperature within a very narrow range, sweating and cooling thresholds, which is called the thermoneutral zone (Cabanac and Massonnet, 1977).

Freedman has demonstrated that women with hot flushes have an increased core temperature and a reduced thermoneutral zone (Freedman, 2001, Freedman and Subramanian, 2005) compared with their asymptomatic counterparts indicated that women with significant peri-menopausal symptoms have abnormal thermoregulation, with a raised cooling threshold, lowered sweating threshold and narrowed thermoneutral zone, which is recognized as the mechanism of hot flushes. Currently, estrogen treatment is still the most effective method of alleviating peri-menopausal hot flushes (Nelson, 2008). However, its use has been seriously challenged since the announcement of the Women's Health Initiative (WHI) results in 2002. Therefore, studies of non-estrogen treatments for peri-menopausal hot flushes have been aroused wide-spread concern. Black cohosh (Cimicifuga racemosa) has gained wide clinical attention in alleviating peri-menopausal symptoms, and its efficacy and safety have been confirmed by many randomized controlled trials (Liske et al., 2002, Frei-Kleiner et al., 2005, Bai et al., 2007). There was one study aimed to examine the underlying mechanism of black cohosh, found that black cohosh had no estrogenic effect on the uterine weight of ovariectomized rats, but could specifically bind to the 5-hydroxytryptamine receptors, 5-HT1AR and 5-HT7R (Burdette et al., 2003). The two serotonin receptor subtypes are mainly distributed in the hypothalamus—the central integrator of thermoregulation (Bruck and Zeisberger, 1987). Based on this finding one can assume that black cohosh might alleviate peri-menopausal hot flushes by acting on the thermoregulation center through various neurotransmitter pathways.

In recent years, researches confirmed that ethanolic black cohosh extract can reduce hot flush frequency and subcutaneous temperature in ovariectomized rats (Winterhoff et al., 2003, Kapur et al., 2010). However, there is no report reveals how black cohosh preparations affect the CBT of ovariectomized rats. Because CBT directly determines whether the thermoregulation center issues temperature adjustment signals, the effect of black cohosh preparations on CBT is crucial to explain the underlying mechanism of peri-menopausal hot flushes.

We aimed to study the effect of isopropanolic black cohosh extract on CBT of ovariectomized rats by telemetric measurement system, to further explore possible mechanisms of black cohosh in temperature modulation which might support our understanding of the mechanisms in alleviating hot flushes during the peri-menopausal period.

Section snippets

Drugs

Isopropanolic-aqueous black cohosh extract (Remifemin® tablets) used in this study was manufactured by Schaper & Brümmer GmbH & Co. KG, Germany (bulk batch number 824821) and available on the Chinese drug market. With reference to the active ingredients in each tablet: 0.018–0.026 mL liquid extract corresponded to, on average, 2.5 mg dry extract and to 20 mg crude drug (extraction agent isopropanol 40%, v/v). Estradiol valerate used in this study was manufactured by the Guandong Branch of Bayer

Results

The rats were in a good physical state after the operation. The vaginal smear showed that ovariectomies of the 3 group animals in this study were 100% successful.

Discussion

Decrease in all reproductive hormones in menopause has been shown to cause thermoregulatory dysfunction. Freedman has demonstrated that women with hot flushes have an increased core temperature and a reduced thermoneutral zone. Here, we present 6-week's central body temperature (CBT) of ovariectomized rats and obtained reliable data. Many previous animal studies about peri-menopausal hot flushes have monitored tail temperature of rats (Berendsen et al., 2001, Pan et al., 2001). However, there

Conclusion

Ovariectomized rats had abnormal thermoregulation, demonstrating an increase in day and night CBT, greater difference between day and night CBT, higher amplitude of day and night CBT, and more CBT fluctuation frequency. For the herbal extract iCR, the onset of affecting abnormal thermoregulation took longer than that of estradiol valerate. ICR had a significant effect on day CBT but was only little effective on night CBT of ovariectomized rats. The mechanisms of ICR alleviating menopausal

Funding

This paper is the National Natural Science Funds Project. Funding coding is No. 81070462.

Conflicts of interest

The authors do not have any potential conflicts of interest of a financial or other nature.

Ethical approval

The study was approved by the Ethics Committee for Animal Experimentation of the Faculty of Medicine of Peking University Health Science Center in March, 2009 and the approval number was J200903.

Acknowledgment

Sincere thanks go to Professor Zheng Shurong from the Gynecology Department of the First Hospital of Peking University, who has provided enormous support for this research.

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