Abstract

The concept of “blood stasis” – called yū xiě in Chinese, Oketsu in Japanese – is one of the unique pathophysiology of traditional medicine that originated in China and inherited in Korea and Japan. This concept is related to the multiple aspects of hemodynamic disorders brought on by quantitative and qualitative changes. It theorizes that the quantitative changes of “blood stasis” are related to peripheral circulatory insufficiency. When chronic qualitative changes of “blood stasis” produce stagnant blood that turns into a pathological product, it could cause inflammation and lead to organic changes. Trauma induced hematomas, that are considered to be a quantitative change of blood, are also a form of blood stasis. The basic medicine research on Keishibukuryogan (KBG)–a Japanese name in Traditional Japanese Medicine (Kampo) for one of the most common anti- “blood stasis” prescriptions, also known as gui-zhi-fu-ling-wan (GFW) in Chinese in Traditional Chinese Medicine (TCM)–indicated that the initiation of quantitative changes was closely related to loss of redox balances on endothelial function induced by oxidative stress. The following qualitative changes were related to coagulopathy, hyper viscosity; anti-platelet aggregation, lipid metabolism; a regulation of systemic leptin level and/or lipid metabolism, inflammatory factor; cyclooxygenase-1,2 (COX-1, 2), interleukin-6, 8 tumor necrosis factor-α, macrophage infiltration, hyperplasia, tissue fibrosis and sclerosis caused by transforming growth factor-β1 and fibronectin, the dysfunction of regulated cell deaths, such as, apoptosis, autophagy, ferroptosis and ovarian hormone imbalance. Clinically, KBG was often used for diseases related to Obstetrics and Gynecology, Endocrine Metabolism, Rheumatology and Dermatology. In this review, we give an overview of the mechanism and its current clinical application of KBG through a summary of the basic and clinical research and discuss future perspective.

Highlights

  • The concept of “blood stasis” -called yu xiein Chinese, Oketsu in Japanese–is one of the unique pathophysiology of traditional medicine that originated in China and inherited in Korea and Japan

  • Et al reported that long-term daily oral administration of KBG (300 mg/kg) in rats for 14 days decreased plasma levels of LH, follicle stimulating hormone (FSH) and E2 by 94%, 67% and 64% that of controls, respectively and KBG enhanced luteinizing hormone-releasing hormone (LH-RH)-induced increase in plasma LH and FSH levels 1.2- and 2.5-fold respectively, as compared with controls. He concluded that the results indicate that KBG may act as a LH-RH antagonist and /or a weak anti-estrogen [43]

  • KBG did not affect the lower concentration of plasma estradiol and the decreased uterine weight due to ovariectomy, the hormone replacement of 17 beta-estradiol restored them. They concluded that these results suggested that KBG, which does not confer estrogen activity on plasma, may be useful for the treatment of hot flashes in patients for whom estrogen replacement therapy in contraindicated, as well as menopausal women [49]

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Summary

A Review on the Mechanism and Application of Keishibukuryogan

The concept of “blood stasis” – called yuxiein Chinese, Oketsu in Japanese – is one of the unique pathophysiology of traditional medicine that originated in China and inherited in Korea and Japan. This concept is related to the multiple aspects of hemodynamic disorders brought on by quantitative and qualitative changes. The basic medicine research on Keishibukuryogan (KBG)–a Japanese name in Traditional Japanese Medicine (Kampo) for one of the most common anti- “blood stasis” prescriptions, known as gui-zhi-fu-ling-wan (GFW) in Chinese in Traditional Chinese Medicine (TCM)–indicated that the initiation of quantitative changes was closely related to loss of redox balances on endothelial function induced by oxidative stress.

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