Ojayeonjonghwan, an oriental medicine composed of five seeds, protects against vasomotor and neurological disorders in estrogen-deficient rats

Abstract

The different ojayeonjonghwan remedies all contain five fruit and seed water extracts, and they have been used for reproductive health in men and women. We hypothesized that the two OJa remedies would differently improve the early menopause-related vasomotor and neurological symptoms in estrogen-deficient animals. Ovariectomized (OVX) rats had either 0.5% dextrin (OVX-control), conjugated equine estrogen (150 μg/kg body weight; positive-control), 0.5% ojayeonjonghwan remedy-1 (OJa1), or 0.5% ojayeonjonghwan remedy-2(OJa2) in high-fat diet for 12 weeks. Normal-control rats (sham operation) were fed the same high-fat diet as OVX-control rats. Tail skin temperature, depressiveness, memory function, and body composition were determined. The mRNA expressions of hippocampal serotonin receptor (5HT)1A and 5HT2A and brain-derived neurotrophic factor(BDNF) were measured. OJa1 and OJa2 groups had lower tail skin temperatures than OVX-control. Bone mineral density (BMD) and lean body mass (LBM) measured by DEXA increased only in OJa2, and were similar to the positive- and normal-controls ( P < 0.05). In the forced swim test immobile time, an index of depressiveness was much lower in OJa1 and OJa2 than the control group. Memory as measured by passive avoidance, water maze, and Y maze tests was impaired in the OVX-control group, compared to the normal-control ( P < 0.05), but normalized in OJa1 comparable to the positive- and normal-control groups. The neurological impairments were associated with serum serotonin levels and 5HT2A mRNA expression in the midbrain, and decreased hippocampal BDNF mRNA and protein expressions in the OVX-control group compared to normal-controls ( P < 0.05). OJa1 increased serum serotonin levels and 5HT2A expression in the midbrain, and hippocampal BDNF expression to similar levels as normal-controls ( P < 0.05). In conclusion, OJa1 and OJa2 improved hot flashes and depression and maintained BMD and LBM. OJa2 prevented the impairment of memory function in OVX rats. OJa1 and OJa2 have the potential to be effective therapies for postmenopausal vasomotor and neurological symptoms. Impact statement Menopausal symptoms impair the quality of life of many women, and although conventional treatments are often effective, their use is limited by adverse effects. Ojayeonjonghwan, OJa, is a traditional Oriental medicine that is used for both male and female reproductive health and has a long history of safe use. We evaluated the effectiveness of two variations of OJa (OJa1 and OJa2) for treating menopausal symptoms in ovariectomized (OVX) rats. Both OJa preparations were effective for relieving indicators of hot flashes and depression, and for preventing loss of bone mineral density and lean body mass. Only OJa 2 prevented memory dysfunction. These results show that the traditional Oriental medicine, Ojayeonjonghwan, has the potential to relieve menopausal symptoms in women and should be further evaluated in human clinical trials as an alternative to convention therapies in women for whom conventional therapies are not indicated or found to be ineffective.