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Natural medicines(NMs)are indispensable sources for the development of modern drugs.However,the targets for most natural compounds are unknown and the current pharmacokinetic evaluation systems developed for target-defined drugs may not be directly applicable to NM-based drug discovery,which is a major bottleneck in bringing natural compounds to the clinic.We propose the concept of "reverse pharmacokinetics" and discuss how a "reverse pharmacokinetics" perspective could help clarify key questions in modern drug discovery from NMs with validated clinical benefits,thereby strengthening the translational potential.Reverse pharmacokinetics can provide physiologically relevant clues to the target identification and mechanistic study of NMs,which may also innovate drug discovery for complex diseases.We anticipate that an evolving deep understanding of the novel mode of action of natural compounds with a reverse pharmacokinetic insight may improve discovery of both single ingredient and multiple-component modern drugs from NMs.