Abstract
There have been renewed interests in natural products as drug discovery sources. In particular, natural product combinations have been extensively studied, clinically tested, and widely used in traditional, folk and alternative medicines. But opinions about their therapeutic efficacies vary from placebo to synergistic effects. The important questions are whether synergistic effects can sufficiently elevate therapeutic potencies to drug levels, and by what mechanisms and at what odds such combinations can be assembled. We studied these questions by analyzing literature-reported cell-based potencies of 190 approved anticancer and antimicrobial drugs, 1378 anticancer and antimicrobial natural products, 99 natural product extracts, 124 synergistic natural product combinations, and 122 molecular interaction profiles of the 19 natural product combinations with collective potency enhanced to drug level or by >10-fold. Most of the evaluated natural products and combinations are sub-potent to drugs. Sub-potent natural products can be assembled into combinations of drug level potency at low probabilities by distinguished multi-target modes modulating primary targets, their regulators and effectors, and intracellular bioavailability of the active natural products.
Highlights
Natural products (NP) have been traditional sources of drug discovery and there are renewed interests in them for new drug discovery [1], [2], [3], [4]
While drug potency level can be more rigorously defined by considering these mechanisms, few drugs and NPs have been sufficiently studied for enabling such a consideration
It is more practically feasible to tentatively focus on cell-based activities that reflect the potencies of most drugs and NPs
Summary
Natural products (NP) have been traditional sources of drug discovery and there are renewed interests in them for new drug discovery [1], [2], [3], [4]. NP combinations have been extensively studied [5], [6], tested in clinical trials [7], [8], [9], and widely used in traditional, folk and alternative medicines [10], [11] Their novel multi-targeted mechanisms [8], [12], [13] or molecular scaffolds [14] may be valuable sources for developing multi-targeted therapeutics [15]. One attributes the efficacies of NP combinations to placebo effects [16], [17], [18] based on indications from clinical trials [17], [18] and the findings that bioactive NPs are typically sub-potent to drugs [19], [20]. Another credits the efficacies of NP combinations to synergistic effects [6], [8], [19], [21], [22] based on the findings that some NP combinations produce significantly better effects than equivalent doses of their components [19], [22] and clinical outcomes are not necessarily influenced by positive beliefs [16]
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