Researchers worldwide frequently use in vitro or in silico models instead of using animal models. It is noteworthy that these studies have limitations, mainly the impossibility of evaluating complex biological interactions as well as the dependence on artificial conditions. In this way, new methodologies are constantly being introduced and improved, and although the intention is to replace animal models, in professional lab research these methodologies complement each other. 

In recent decades, we have observed a significant increase in the pressure to boycott the use of animals in biomedical research. Thus, alternative models that meet more humanitarian criteria have come to the fore throughout the scientific community. Three-D cell culture technologies such as organoids, spheroids, and more recently organ-on-a-chip and human-on-a-chip, are being increasingly explored as alternative methods to increase the “bench to bedside” translation. Thus, although there is a long way to go before animal models can be replaced, alternative methods can be used to reduce the use of animals, as they can be adopted in the initial screening of new drugs and treatments. 

In this Special Issue, we would like to invite investigators to submit alternative methods and preclinical studies focusing on in silico, cell culture, and innovative animal models to evaluate the potential of natural products for the prevention and treatment of diseases. We will consider both original research and review articles. 

Potential topics include but are not limited to the following:

• In silico models in natural products preclinical research 
• In vitro models in natural products preclinical research 
• 2D and 3D cell culture technologies (organoids, spheroids, organ-on-a-chip, and human-on-a-chip) in natural products preclinical research 
• Zebrafish as model organisms for studying natural products 
• Innovative animal models for studying natural products 
• Systematic review of alternative models in biomedical research 
• Molecular interaction of natural products with their targets