Bilobalide, a naturally occurring compound found in ginkgo leaves, holds significant pharmacological potential, particularly for neuroprotection. However, its inherent complex chemical structure and rapid degradation within the human body have posed substantial challenges to its development into a viable therapeutic drug. In response to these challenges, a research team from The Chinese University of Hong Kong (CUHK), under the guidance of Professor Billy Ng Wai-lung, has introduced an innovative molecular editing technique that can precisely modify the molecular structure of bilobalide. This advancement has led to the creation of novel bilobalide derivatives, which demonstrate promising pharmacological properties and potential as treatments for neurodegenerative diseases like Alzheimer’s. These findings have been published in the esteemed journal JACS Au.
Ginkgo biloba, also known as the ginkgo tree, is recognised as a “living fossil”, with a lineage that extends back to the Jurassic period. The seeds of the ginkgo tree, commonly referred to as ginkgo nuts, have been traditionally used in food and medicine, particularly in Chinese herbal practices. Beyond the seeds, the leaves of the ginkgo tree have also been utilised in medicinal applications. Among the bioactive compounds extracted from ginkgo leaves, bilobalide, a terpene trilactone, has attracted significant interest due to its potential neuroprotective, anti-inflammatory, anticonvulsant, and antiapoptotic effects.
Despite the pharmacological promise of bilobalide, its development into a therapeutic drug has been hindered by its complex chemical structure and metabolic instability. The rapid decomposition of bilobalide within the human body diminishes its effectiveness, complicating efforts to harness its therapeutic potential. Professor Ng, an expert in chemical modification, noted the challenges associated with bilobalide, stating that while chemists can theoretically modify molecular structures through chemical reactions to create new derivatives, bilobalide’s intricate structure has made this a daunting task.
To overcome these obstacles, Professor Ng and his interdisciplinary team, comprising experts from chemistry, biology, and pharmacy, have pioneered a new molecular editing technology designed to precisely alter the chemical structure of bilobalide. This breakthrough technology allows for the generation of bilobalide derivatives with enhanced stability and improved pharmacological properties. The ability to tailor the molecular structure of bilobalide has resulted in the creation of a diverse library of bilobalide derivatives, which can be used for future drug screening and development.
One of the most notable achievements of this research is the development of a new bilobalide derivative, designated as BB10. This derivative has demonstrated significant neuroprotective effects, particularly in its ability to protect brain cells against ferroptosis – a form of programmed cell death linked to various neurodegenerative diseases and ischemic injuries. BB10 has been shown to effectively reduce the accumulation of toxic lipid peroxidation, a key driver of ferroptosis, and maintain the levels of anti-oxidative enzymes within cells. This dual action helps to suppress excessive brain cell death, making BB10 a promising candidate for the treatment of neurodegenerative disorders.
The innovative molecular editing technology developed by Professor Ng’s team represents a significant advancement in the field of drug discovery, particularly in the optimisation of traditional herbal medicine components. By enabling precise modifications to the molecular structure of natural products like bilobalide, this technology opens new avenues for the exploration and development of novel therapeutic agents derived from Chinese herbs and other natural sources.
The implications of this research extend beyond the immediate development of bilobalide derivatives. It underscores the potential of molecular editing as a tool for enhancing the pharmacological properties of natural products, thereby facilitating their translation into effective therapeutic agents. The successful application of this technology to bilobalide not only highlights the pioneering role of CUHK in the field of drug discovery but also offers new hope for the treatment of neurodegenerative diseases, which remain a significant challenge in modern medicine.
