Development and application of innovative methodologies for the study of the biological activities of Italian and world medicinal plants of ethnobotanical interest

Ethnobotany and traditional uses of medicinal plants by man throughout his history, have and must represent an important source of inspiration and a fundamental starting point for the discovery and development of new therapeutic products; this is because, especially in developing countries, access to drugs and conventional therapy too often turns out to be an insurmountable obstacle and even small wounds can follow important courses, leading to much more serious problems. Although ethnobotany seems to be a growing discipline, the attention given to it and the research facilities are still much lower than those dedicated to scientific research. Added to this is the problem that information and knowledge are mainly transmitted orally, especially by older people and within civilizations that are sometimes remote and difficult to access, a dynamic that could translate, over the next few years, into the loss of this ancient knowledge. Added to all this is the problem of having to confer scientificity to ethnobotanical information, a process that can be difficult for what was previously said and for what can be the costs and timing of pre-clinical experimental research. For these reasons, an integrated in silico/in vitro model was developed and validated, based on what can be considered a very modern computational approach such as Network Pharmacology (NP) and the constant comparison of data from it with data from classic and innovative in vitro experiments. Four species were therefore selected, 2 traditionally used for the healing of skin wounds such as Sedum telephium L. and Carpobrotus acinaciformis (L.) L. Bolus., and two used for immune support, namely Calluna vulgaris (L.) Hull. and Baccharis dracunculifolia DC.. The study of their chemistry has allowed to identify and validate the use of online databases such as LOTUS and, the integration of the respective data, has provided an appropriate number of constituents of the respective phytocomplexes to be used as input in the computational analyses of NP. The latter has provided predictions regarding the various pharmacokinetic and pharmacodynamic processes of the phytocomplexes of the 4 different species, providing guidance for the experiments and reducing their costs. The in vitro analyses have served not only to evaluate the reliability of the NP predictions, but also to justify the traditional uses of the different species, bringing to light what may be the main mechanisms of action and the biological efficacy of S. telephium and C. acinaciformis in skin healing, and of C. vulgaris and B. dracunculifolia in the processes of inflammation and immune support.