Ginkgo biloba extract 761 reduces vascular permeability of the ovary and improves the symptom of ovarian hyperstimulation syndrome in a rat model

Abstract

Aims

Ginkgo biloba extract (EGb) has been widely applied in the treatment of cerebrovascular and neurological diseases. However, the effect of EGb761 on ovarian hyperstimulation syndrome (OHSS), a vascular disorder and life-threatening complication of In Vitro Fertilization and Intracytoplasmic Sperm Injection therapy (IVF/ICSI), has not been evaluated.

Materials and methods

Forty female Wistar rats aged 22-days old (D22) were divided into eight groups: Control rats received intraperitoneal injection of saline for 5 consecutive days (D22-D26); OHSS model group received 10 IU equine chorionic gonadotropin (eCG) for 4 consecutive days (D22-D25) and 30 IU of human chorionic gonadotropin (hCG) on the 5th day (D26); Prophylactic treatment group received three doses of EGb761 (50, 100, and 200 mg/kg/d) one hour before injection of eCG (hCG) for 7 consecutive days; Therapeutic treatment group received three doses of EGb761 (50, 100, and 200 mg/kg/d) 48 h after injection of eCG (hCG) for 7 consecutive days.

Results

All three doses of EGb761 therapeutic medication significantly reduced ovarian mass index in the OHSS model (p ≤ .01). Further, the therapeutic treatment group exhibited improved vascular permeability, decreased estradiol and progesterone levels, lower corpus luteum, and higher follicle numbers compared with the OHSS model. Elevated protein expression of vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) in both ovary and kidney of the OHSS model was restrained by EGb761 therapeutic treatment.

Conclusions

EGb761 therapeutic medication decreases vascular permeability in OHSS rat model by inhibiting VEGF and VEGFR expression, which may contribute to the treatment of OHSS.

银杏叶提取物761 降低卵巢过度刺激综合征大鼠模型中卵巢血管通透性并改善症状 摘要

目标：银杏叶提取物( EGb )已广泛应用于脑血管和神经系统疾病的治疗。卵巢过度刺激综合征( OHSS )血管功能紊乱, 是体外受精和卵胞浆内单精子显微注射技术 ( IVF / ICSI )危及生命的并发症。但目前尚无关于EGb761对OHSS影响的研究。

材料与方法：40只22日龄（D22）雌性Wistar大鼠分为8组：对照组连续5天腹腔注射生理盐水（D22-D26）； OHSS模型组连续4天（D22-D25）注射10 IU马绒毛膜促性腺激素（eCG）, 第5天（D26）注射30 IU人绒毛膜促性腺激素（hCG）； 预防性用药组在注射eCG（hCG）前1小时接受3种剂量的EGb761（50、100和200mg/kg/d）, 连续7天； 治疗性用药组在连续 7 天注射 eCG (hCG) 后 48 小时接受3种剂量的 EGb761（50、100 和 200 mg/kg/d）。

结果：3种剂量的EGb761治疗性用药组均显着降低了 OHSS 模型中的卵巢质量指数 (p≤.01)。 此外, 与 OHSS 模型相比, 治疗性用药组表现出血管通透性改善、雌二醇和孕酮水平降低、黄体数量减少和卵泡数量增多。 EGb761治疗抑制了OHSS模型卵巢和肾脏中血管内皮生长因子（VEGF）和VEGF受体（VEGFR）蛋白表达升高。

结论：EGb761治疗性用药通过抑制VEGF和VEGFR表达降低OHSS大鼠模型的血管通透性, 可能有助于OHSS的治疗。

Keywords:

• Ginkgo biloba extract
• EGb761
• ovarian hyperstimulation syndrome
• OHSS
• vascular permeability
• VEGF
• VEGFR

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by Dalian Medical Science Research Project [Grant Number: 18Z1001].