Effects of the traditional Japanese medicine Tokaku-jyoki-to in rat-models for menopausal hot flash.
OBJECTIVE
Luteinizing hormone-releasing hormone (LH-RH) has been suggested as an inducer of centrally mediated elevation of skin temperature, and calcitonin gene-related peptide (CGRP) is one of the potent vasodilator neuropeptides that has been suggested as an inducer of peripherally mediated elevation of skin temperature. We investigate the effect of the Japanese herbal medicine Tokaku-jyoki-to using two rat-models for menopausal hot flash.


METHODS
Tokaku-jyoki-to used in present study was prepared as a spray-dried powder from hot-water extract. Skin temperature was measured by thermister thermometer. Estrogen receptor (ER) binding assay of Tokaku-jyoki-to extract was performed using human recombinant ERalpha or ERbeta.


RESULTS
Oral Tokaku-jyoki-to (1000 mg/kg) restored skin temperature rise induced by LH-RH or CGRP in ovariectomized (OVX) rats as well as subcutaneous 17beta-estradiol (0.010 mg/kg) did. Tokaku-jyoki-to did not affect the lower concentration of plasma estradiol and the decreased uterine weight due to ovariectomy, although the hormone replacement of 17beta-estradiol restored them. In estrogen receptor ligand-binding study, Tokaku-jyoki-to extract bound to human ERalpha poorly and did not bound to human ERbeta.


CONCLUSIONS
These results suggest that Tokaku-jyoki-to, which appears to contain organ-specific selective estrogen receptor modulator, may be useful for the treatment of hot flashes in patients for whom estrogen replacement therapy is contraindicated as well as menopausal women.
Noguchi
Masamichi
M
Tsumura Research Laboratory, Ami-Machi, Inashiki-Gun, Ibaraki, Japan. noguchi_masamichi@mail.tsumura.co.jp
Yuzurihara
Mitsutoshi
M
Ikarashi
Yasushi
Y
Tsuchiya
Naoko
N
Hibino
Tomoko
T
Mase
Akihito
A
Kase
Yoshio
Y
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000627:therapeutic use*; D004958:Estradiol / Q000097:blood / Q000627:therapeutic use; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D019584:Hot Flashes / Q000188:drug therapy*; D007564:Japan; D008518:Medicine, East Asian Traditional; D008593:Menopause / Q000187:drug effects*; D015394:Molecular Structure; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D010936:Plant Extracts / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000187:drug effects; D012881:Skin Temperature / Q000187:drug effects; D014599:Uterus / Q000473:pathology
D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; D011960:Receptors, Estrogen; C112001:tokaku-joki-to; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D015740:Calcitonin Gene-Related Peptide