Introduction
Stroke is one of the leading causes of disability and mortality worldwide. Thrombolysis and intra-artery therapy, the only two effective strategies, are available to only a minority of patients with stroke due to the limited time window.1 However, a great many stroke survivors suffer from cognitive decline. One cross sectional study performed in 10 countries found that the prevalence of post stroke dementia was approximately 30% determined by Mini-Metal State Examination (MMSE) <27.2 Cognitive decline after stroke can result in vascular cognitive impairment (VCI) and Alzheimer’s disease.3 Thus effective and safe interventions are urgently needed to tackle this public health burden of stroke and VCI.
Ginkgo biloba is an ancient Chinese tree and its extract has long been used in China as a traditional herb for memory, depression, tinnitus and confusion.4 In the UK, Europe, Canada and the USA, Ginkgo biloba extract (GBE) is a commercially available food supplement available without prescription. The ingredients of GBE are complicated, and vary by age, cultivation source and gender of the Ginkgo biloba tree.5 EGb761 is a well defined GBE, produced by Dr Willmar Schwabe Pharmaceuticals in the early 1990s, which contains approximately 24% flavone glycosides (primarily quercetin, kaempferol and isorhamnetin), 6% terpene lactones (ginkgolides A, B and C, and bilobalide), 0.8% Ginkgolide B and <5 ppm harmful ginkgoic acid. Most of the clinical trials to date have been performed based on the standardised EGb761.6 The Ginkgo ketone ester dispersible tablets produced by Jiangsu Shenlong Pharmaceutical Co include 44% flavone glycosides, 10% terpene lactones, 2.5% Ginkgolide B and <2 ppm harmful ginkgoic acid. The chemical structures and chromatograms are presented in the online Supplementary figure S1 and S2. Hence the GBE in this study has more protective chemicals and less harmful constituents and is expected to exert a better therapeutic effect than EGb761.6
It is reported that EGb761 protected against ischaemic brain injury by scavenging free radicals, including superoxide radicals, ONOO-, OH• and NO•, and other lipid peroxide radicals.7–9 EGb761 can also suppress the activity of ACE, thereby inhibiting the contraction of small arteries, dilation of cerebral blood vessels and increase in cerebral blood flow.10 Despite the protective effect of GBE,11 there is still a lack of compelling evidence to recommend its use in the management of ischaemic stroke. Clinical trials focussing on the therapeutic effect of GBE in VCI are lacking.
In this study, we investigated 348 patients with acute stroke with the aim of evaluating the potential use of GBE in the treatment of ischaemic stroke and its secondary effects on cognitive decline. In addition, we evaluated the side effects of an oral dose of GBE 450 mg daily. We also provide more evidence for neurologists regarding the application of GBE.