Reverse Pharmacology: Transdisciplinary Approach of Drug Discovery from Ethnomedicine

Reverse pharmacology is the process of drug discovery that starts with traditional medicine and works backward in search of active compounds and understanding their mechanism of action. The attention of academicians in the late twentieth century was raised in the direction of reverse pharmacology as their pharmaceutical collaborations explored novel methods for medication discovery. Due to the emergence of drug resistance, there was a need for new molecules contending resistance. The cost of overall treatment had been raised by drug resistance. The cost of resistance includes the direct expenses for alternative new therapies, deaths, and health issues produced by the increasing incidence of antibiotic resistance. Switching from cheap chloroquine therapy to artemisinin combination treatment for malaria which is now recommended by the WHO had resulted in a $300–$500 million increase in cost (Howard and Scott 2005). In conventional drug development, molecular targets are identified, and then molecular libraries are searched for molecules interacting with them. In reverse pharmacology, the bed-to-laboratory approach starts with clinical observations or effects of herbal or traditional medications, and then the laboratory finds the underlying mechanism and prospective therapeutic target molecules (Fig. 1). This method establishes a link between the therapeutic impact of a medicine or chemical and the precise target or mechanism of action. Artemisinin extracted from the plant Artemisia annua which has been used for generations to cure fevers in traditional Chinese medicine. Tu Youyou, a Chinese researcher, directed the efforts to identify new antimalarial medications during the Vietnam War. She identified a chemical and named it artemisinin which proved its efficiency against malaria parasites. Tu Youyou’s revolutionary discovery won her Nobel Prize in Physiology or Medicine in 2015. Artemisinin and its derivatives are currently the world’s first-line malaria treatments (Awari et al. 2022). In reverse pharmacology for the discovery of drug targets and the creation of novel therapeutic approaches, various clinical investigation processes include techniques like extraction and isolation of active compounds, in vitro testing using cell cultures, cytokine levels, target identification, animal studies, biomarker identification, clinical trials, patient samples analysis, target validation, optimization and drug development, regulatory approval, and post-marketing surveillance (Fig. 2).