The pharmacodynamic and pharmacological mechanisms underlying nanovesicles of natural products: Developments and challenges.

Natural products such as Traditional Chinese Medicines (TCMs) show great advantages in the treatment and prevention of diseases, but the unclear effective ingredients and mechanisms are key obstacles to restrict their rapid development. Under the guidance of the theoretical guidance of reductionism and the theoretical of allopathic medicine, some researches have indeed achieved some breakthrough results. However, these incomplete methods mainly limited to direct actions or indirect actions (such as the intermediated substances mediated cross-organ or cross-system regulation) mechanism of single active ingredient derived from natural products, which are often inconsistent with Systemism and Harmonizing Medicine and make it difficult to reasonably explain the pharmacodynamics and pharmacological mechanism of most natural products. Actually, effective pharmaceutical ingredients often do not exist in the form of free monomers, but prefer to assembly nanovesicles (NVs) for a combinational pharmacological effect, mainly including self-assembled nanoparticles (SANs) and exosome-like nanoparticles (ELNs). These developments of NVs-based application are a good supplement to existing pharmacological mechanism research. Hence, this review focuses on the developments and strategies of the pharmacodynamics and pharmacological mechanism of NVs-based TCMs under the combining theory of traditional Chinese and western medicine. On this basis, a novel "multidimensional combination" research approach is proposed firstly, which will provide new strategies and directions for breaking through the bottleneck of pharmacological mechanism research, and promote the clinical application of innovative natural products including TCMs.