Phytochemical and Safety Evaluations of Finger Lime, Mountain Pepper, and Tamarind in Zebrafish Embryos

Plants play a pivotal role in drug discovery, constituting 50% of modern pharmacopeia. Many human diseases, including age-related degenerative diseases, converge onto common cellular oxidative stress pathways. This provides an opportunity to develop broad treatments to treat a wide range of diseases in the ageing population. Here, we characterize and assess the toxicological effects of finger lime (Citrus australasica), mountain pepper (Tasmannia lanceolata), and small-leaved tamarind (Diploglottis australis) extracts. The characterization demonstrates that these Australian native plants have antioxidant potential and, importantly, they have high concentrations of distinct combinations of different antioxidant classes. Using zebrafish larvae as a high-throughput pre-clinical in vivo toxicology screening model, our experiment effectively discriminates which of these extracts (and at what exposure levels) are suitable for development towards future therapies. The LC50-96h for finger lime and tamarind were >480 mg/L, and 1.70 mg/L for mountain pepper. Critically, this work shows that adverse effects are not correlated to the properties of these antioxidants, thus highlighting the need for combining characterization and in vivo screening to identify the most promising plant extracts for further development. Thus, we present a high-throughput pre-clinical screening that robustly tests natural plant products to utilize the diversity of antioxidant compounds for drug development.