Abstract
Chinese herbal medicines are used by women across the world to treat infertility in natural and assisted reproductive cycles. Randomised control trials and systematic reviews have shown the clinical efficacy of these medicines, but there remains a paucity of information as to the mechanisms by which they exert their effect. The herbal formula in this study, Gui Shao Di Huang Wan comprises eight herbs and is used to treat infertility. It is a base formula from which practitioners create a personalised medicine. The observed fertility benefits may be due to improvements in the receptivity of the endometrium, and a key aspect of this is haematology. The blood is a concept where the western and Chinese perspectives on fertility converge.Aqueous extracts of the whole formula and the individual herbs were used. Prothrombin time and activated partial thromboplastin time were used to evaluate time to clot formation. An MTT assay was used to look at proliferation of human umbilical vein endothelial cells. A 2D differentiation assay was performed on matrigel using human umbilical vein endothelial cells and human uterine microvascular endothelial cells. Lysates of Ishikawa endometrial cells exposed to the herb extracts were used in immunoblotting to explore changes in oestrogen and progesterone receptor expression.Haemostasis, proliferation and differentiation of endothelial cells and expression of steroid receptor proteins on an endometrial cell line have all been shown to be affected by the herb extracts in in vitro assays modelling these functions. Prothrombin time (Welch’s F (8,14.57) =50.21, p<0.0005) and activated partial thromboplastin time (Welch’s F (8,13.77) =38.79, p<0.0005) were both increased. The whole formula led to an increase in proliferation at concentrations between 0.68 and 5.47 μg/mL at 48 and 72 hours.Metrics of tubule number, length, junctions, and mesh size were increased in endothelial cells. All parameters of Human Umbilical Vein Endothelial Cells were statistically significantly increased by the whole formula but not the individual herbs. The Human Uterine Microvascular Endothelial Cell mesh was increased by all herb extracts, total length, and segment number by Radix Paeoniae Alba, Sclerotium Poria.
Cocos, Radix Rehmanniae Preparata, Rhizoma Dioscoreae, Fructus Corni, and Rhizoma Alismatis, total length and junction number for Fructus Corni.Modifications to expression of ERα and PRβ were observed. Downregulation of Estrogen receptor alpha after 24 hour exposure to the herbs for Radix Paeoniae Alba, Radix Angelicae Sinensis, Sclerotium Poria Cocos, and Cortex Moutan. Progesterone receptor beta was upregulated by treatment with Radix Paeoniae Alba, Radix Angelicae Sinensis, Sclerotium Poria Cocos and Radix Rehmanniae Preparata after 48 hours exposure to the herb extract.
trials currently available."
This study adds a new perspective to the limited evidence available through clinical trials which examine Chinese herbal medicines and their potential for use in treating female infertility. The observed effects of the herbs may be mediated by the influence on the identified haematological and vascular processes related to endometrial receptivity.
| Date of Award | Jul 2017 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Asmita Vithaldas Patel (Supervisor) & Helen Fillmore (Supervisor) |