Synthetic Drugs and Natural Product Combinations

Conventional pharmacological treatments aim to achieve homeostasis via specific drug interactions within target cells. However, this often results in cellular damage to non-targeted cells, which clinically manifests as adverse side effects. This is particularly significant in the case of chronic diseases for which curative treatment options are not available, dose increments are needed, and patients' adaptive capacity is limited. To reduce such side effects, single-agent pharmacotherapy may involve the usage of partial agonists, selective receptor modulators (SERM), or pharmaceutical strategies designed to restrict drug distribution and spare sensitive tissues. However, in most cases, additive or synergistic combination therapies are needed to improve therapeutic efficacy and reduce adverse side effects. Historically, purified natural products paved the way for modern physiology and, later, pharmacology. This was followed by the revolutionary and efficient production of synthetic drugs, enabled by combinatorial chemistry, advances in molecular biology, and high-throughput screening. Today's integrative approach favors a tendency toward the usage of natural drugs in drug combinations, not only as isolated natural molecules but also as complex plant extracts. These plant extracts consist of a combination of numerous chemical compounds that can have synergistic and antagonistic effects on specific biological processes. The growing number of ongoing and completed clinical trials across diverse disease settings continues to enhance our understanding of the efficacy and safety of natural product- drug combinations. This literature review offers a concise overview of the existing literature on these "synthetic-natural" pairings. By highlighting key preclinical findings and significant clinical trials, we explore how these hybrid strategies are poised to become the next frontier in medicine.