Perspectives on organ-on-a-chip technology for natural products evaluation

Natural products have always been a treasure trove for clinical drug development and a source of inspiration for lead compounds in the process of new drug discovery. However, two-dimensional cell cultures and animal models in the traditional drug development model have serious limitations in generalizing human physiopathology and cannot accurately predict the real clinical response of the human body to drugs, which brings obstacles and challenges to drug evaluation. Organ-on-a-chip (OoC) is an emerging technology based on microfluidic platforms and in vitro cell culture that can mimic the physiological environment and function of human organs for disease modeling and drug evaluation. In this review, we explore several major examples of how human single-OoC systems can be used to simulate complex disease models and outline recent advances in organoids for natural drug screening. Finally, we summarize the challenges and future trends that OoCs must overcome in drug discovery and development. Overall, this review highlights that OoCs, instead of animal models, open new avenues for natural drug development and evaluation, therapeutic innovation, and in vivo embodiment of personalized medicine.