Research and development of botanicals obtained from local medicinal plant, potentially active in skin aging by air pollution

Environmental air pollution encompasses various particulate matter (PM) consisting in solid and/or liquid particles of different sizes and compositions, including mineral dust, metals, metalloids, sea salts, ammonium nitrate and sulfate, organic compounds, elemental carbon. The increasing of the environmental PM caused by human activity is documented to be associated with morbidity and mortality worldwide, presenting one of the most severe pollution related problems. Recent epidemiological studies on the impact of PM showed that its high level is closely related to the development of inflammatory skin diseases and respiratory problems. PM also induces oxidative stress through the production of reactive oxygen species (ROS) and the secretion of pro-inflammatory cytokines such as TNF-α, IL-1 and IL-6. In addition, the increased production of ROS such as superoxide and hydroxyl radicals by PM exposure increases the activity of metalloprotease (MMP) and of other extracellular matrix degrading enzymes. These processes increase inflammatory skin impairments and accelerated skin aging; the first line of intervention are drugs and functional cosmetics topically administered. Anti-oxidant and anti-inflammatory drugs are primarily considered for the treatment of skin diseases induced by PM. In the last years, phytotherapy has focused its research on the field of anti aging and aging-related skin diseases, proving to be a particularly useful discipline in the management and prevention of skin health. This interest in herbal products in the field of skin protection is also very active in Italy, but it is amazing how in our country there is still a little regard to the ethnobotanical tradition and the knowledge of species typical of the area. The results of bibliographic and ethnobotanical research allowed us to identify four interesting and novel species: Calluna vulgaris (L.) Hull. and Cistus creticus L. subsp. eriocephalus (Viv.) Greuter & Burdet, used in Tuscany for skin care, but currently scarcely investigated, and Juglans regia L. and Castanea sativa Mill., very interesting for the potentiality of their by-products, namely leaves collected after fruit harvesting. Optimized extracts, with the highest yield in polyphenols were obtained after having taken into account the collecting time and extraction procedures. A multistep experimental protocol, consisting in cell free and cell-based tests was set up and validated in order to investigate the biological activities of selected extracts in stress models that mimed all the main skin impairments related to aging and pollution exposure. All the selected extracts proved to be interesting candidates for a development in the field of dermatology for skin protection. By-products, C. sativa and J. regia leaves hydroethanolic extracts, as well as C. vulgaris flowering tops water extract showed more likely specific skin protective activities, whereas C. creticus aerial parts hydroethanolic extract resulted effective in all performed tests. C. sativa leaves extract proved to be the most effective extract for its activity in counteracting urban dust-induced MAPK activation. J. regia leaves extract proved to be effective in protecting fibroblasts from immunosuppressive lowered viability and keratinocytes from dehydrative stress probably related to the promotion of occluding expression. C. vulgaris flowering tops extract shared the most important biological characteristic with J. regia extract but it exerted a markedly higher protective activity in UVA-induced keratinocytes damage and in acute and slow oxidative stress. Tuscan C. creticus, taken into account mostly being a species of ethnobotanical interest very scarcely investigated in the field of skin protection, provided the most unexpected and positive results. Indeed, the extract, rich in ellagitannins and flavonols, exerted the best cell-free antiradicalic/antioxidant profile and a strong activity against urban dust-induced keratinocytes stress, both oxidative and inflammatory, accompanied by the best inhibitory effect on elastase, collagenase and hyaluronidase activity. The very positive results obtained in in vitro tests prompted us to perform a small clinical trial on J. regia extract and a formulative development on C. sativa and C. vulgaris extracts