6. Natural extracts as a source of active compounds: from ancient to modern times

Scientific reports directed to the discovery of novel natural photoprotective ingredients often describe only the UV-filtering activity (step 1), which is a necessary but not sufficient condition to support the speculation of the effectiveness if inserted into a sunscreen tested on volunteers. The same issue can be referred to the in vitro bioactivity studies (step 2). The hardest challenge is to enhance the already approved findings as models, mentioned in step 3. An extract or natural compound needs to be fully characterized also for its effect in humans in the final product. Without this, it will remain restricted to a scientific investigation, which will be seen as useless to understand the potential of application in substitution of synthetic or mineral filters. Finally, in order to demonstrate real "green" claims, we recommend completing the product development with aquatic ecotoxicity assay. This step is becoming quite relevant [31, 32] and could be a significant benefit for a new sunscreen product.

Natural extracts have often been used as a source of inspiration in the development of new drugs rather than drugs themselves. Thus, while the discovery of synthetic ingredients is based on a rational systematic approach, which takes into account "step-by-step" modifications driven by chemical-physical parameter, the approach to the discovery of herbal ingredients, to be used as extracts, is "experience driven" and mainly based on traditional uses. A step-by-step procedure applied to natural extract would imply (I) the preparation of extracts and eventually phytochemicals from herbs, (II) the phytochemical study of extracts of herbal preparation or compound isolation, (III) the structure/composition elucidation, (IV) the in vitro biological activity evaluation, (V) the compound characterization and principal activity investigation, (VI) and the in vivo proof of the in vitro elucidated activities.

Furthermore, on the one hand, a central government agency of countries with high biodiversity should consider establishing research projects that involve ecological ethics, such as the managing, care, and preservation of the environment. However, on the other hand, the discovery of such ingredients could lead to improving agriculture or farming of these plants which may become an important job opportunity, especially in countries where the land is not favorable for the traditional farming. Finally, biotechnology in fields of plants is already a precious source of ingredients (i.e., secondary metabolites), which can be obtained from cell culture rather than traditional farming, thus saving biodiversity and land to be dedicated to plants for food. This has already been proven possible in the field of medicinal plants (i.e., Artemisia annua) [33].

Due to the growing interest in herbal remedies, there is also a significant amount of data available on herbal ingredients (i.e., public databases containing analysis, efficacy tests, extracts preparation) even in relation to their molecular targets [33].

It is already possible, based on existing proofs, to envisage a stage of discovery from herbal ingredients, which includes the preparation of extract (by the same standardized methods) eventual isolation, structure/composition elucidation, and in vitro bioactivity evaluation. In the case of sunscreens, the class of compounds behaving abilities of solar radiation absorption and antioxidant capacities are well known (i.e., polyphenols); what is not known is how much the mixture of other ingredients present in the extract may contribute to the sunscreen activity with complementary mechanisms (i.e., booster activity). This implies that the evaluation of activity in vivo must be conducted for each single extract. As recently reviewed by Si-Yuan Pan et al., the herbal preparation may contain "hundreds" of active compounds, and in addition, the concentrations of some of them might be exceedingly low and thus insufficient for conducting in vivo studies on isolated molecules. They report that from 1960 to 1982 and from over 100,000 crude tested extracts (deriving from more than 30.00 plants) only two compounds, Taxol and camptothecin, were developed into marketable therapeutics [33].

Based on the experience from random trials and observations in animals, ancient people acquired the knowledge of using herbs to treat illnesses. However, herbs used in traditional medicines constitute only a small portion of naturally occurring plants; thus, a large part of work still remains to be developed.
