Dr. Willmar Schwabe GmbH & Co. KG

Ginkgo biloba leaf extract EGb 761® has shown clinical efficacy in patients with mild cognitive impairment and dementia. However, the pharmacological action of EGb 761® in Alzheimer's disease (AD) remains unclear and molecular mechanisms targeted in the brain are not completely understood.

We aimed to investigate 1) the potential sex-dependent effects of oral administration of EGb 761® in 5xFAD mice, an AD mouse model, and 2) the underlying microglial subtype responsible for the observed anti-inflammatory effects in the brain.

Eight-week old 5xFAD and wild type mice received EGb 761®-supplemented diet or control diet for eight weeks. The study investigated changes in cognitive function as well as amyloid plaque load, expression of AD-related genes, and anti-inflammatory effects. Moreover, we used organotypic brain slices for confirmation and assessment of concentration-dependency of the observed EGb 761® effects and performed single cell RNA sequencing on the prefrontal cortex of male mice with focus on microglia.

We demonstrate that EGb 761® treatment improves cognitive function in 5xFAD mice in several behavioral tests. Analysis of the brain tissue from these animals indicated a reduction in amyloid plaque load in the prefrontal cortex (PFC). This brain area was further investigated to assess the molecular changes that occurred following EGb 761® intake. Alterations in the expression of genes related to AD were highly sex-specific with effects on the cholinergic system, the γ-secretase complex, and neuroinflammation. Anti-inflammatory effects of EGb 761® with a particularly pronounced reduction of the TNFα-response could be shown for the PFC but also peripherally in the serum of 5xFAD mice of both sexes. Single-cell RNA sequencing revealed that EGb761® mainly affected disease-associated microglia stage 2 (DAM2), which are thought to have a detrimental role in AD.

EGb 761® shows efficacy in the treatment of cognitive deficits in the 5xFAD mouse model via multimodal activity, including sex-specific and sex-unrelated mechanisms including the normalization of neuroinflammatory parameters.

Real-world data (RWD) is becoming increasingly relevant for evaluating safety and effectiveness of medicinal products, including non-prescription medicines and herbal medicinal products in particular. In order to use real-world data for regulatory decision-making in the field of herbal medicinal products, it is crucial to have an accurate description the herbal substances and preparations, as herbal medicinal products, in contrast to chemically defined medicinal products, contain a complex mixture of natural compounds. However, it remains challenging to get standardised information on herbal products from current literature. This publication gives a brief overview of necessary information of herbal medicinal products in scientific literature and data sources to ensure high-quality real-world data.

Pharmacologic activity of proanthocyanidins in Ginkgo biloba leaf extract has recently been reported. The objective of the present study was to screen proanthocyanidin contents in herbal medicinal products containing Ginkgo extracts. A recently published HPLC method for quantification of proanthocyanidins in G. biloba leaf extract EGb 761 was adopted to also be suitable for finished herbal medicinal products. The method was applied to 14 products from the German market. For each product, a set of three individual batches was purchased and analyzed. Substantial differences in proanthocyanidins contents were found among distinct products, ranging from 0.30 to 5.86%. The batch-to-batch variability within each product was low. The highest concentrations are in a similar range as, for example, the amount of Ginkgo terpene trilactones specified in the monograph for G. biloba leaf extract in the European Pharmacopeia. Although it has not yet been established whether and to what extent proanthocyanidins contribute to the overall pharmacological or clinical efficacy of Ginkgo extracts, a potential impact on the purported benefits of different contents in proanthocyanidins cannot be ruled out. Quality assessment of different Ginkgo extracts in the future may include proanthocyanidins.