Screening of 100 plant extracts as tyrosinase and elastase inhibitors, two enzymatic target of cosmetic interest
Manuela Mandrone, PhD, Bologna University, Italy



  Abstract
Statement of the Problem: Skin ageing processes are generally divided into intrinsic, irremediably tied to the passage of time, and extrinsic, which are caused by environmental factors (i.e. chronic exposure to sunlight, pollutants) and miscellaneous lifestyle components. Plants are a precious resource for skincare, both as antioxidants and inhibitors of enzymes involved in the ageing process. In this context, elastase and tyrosinase are target of remarkable importance, and their inhibitors find applications as skin whitening, anti-wrinkle, anti-sagging agents, and in the treatment of dermatological disorders. Methodology: The plant sources were from: India (Rajasthan), Africa (Burkina Faso) and Mediterranean area. Hydroalcoholic extracts were prepared, dried and dissolved in water for the assays or in water-d2 phosphate buffer (90 mM; pH 6.0) for 1H NMR analysis. Findings: Seventeen plants resulted endowed with strong bioactivity and leaves of Pistacia lentiscus emerged as the most potent sample on both enzymes (IC50 of 7.18 ±1.37 and 42.04±1.94 ?g/mL against elastase and tyrosinase, respectively). Interestingly, two, out of the 17 most active plants, are endemic of Sardinia Island (Italy), namely: Hypericum scruglii and Limonium morisianum. Moreover, the 17 most active extracts resulted also generally enriched in polyphenols and flavonoids, which confer them additional value, due to their antioxidant potential. Lastly, 1H NMR metabolomics profile of the extracts were measured, compared by multivariate data analysis and correlated to the abovementioned results by OPLS model, showing a positive correlation between spectral signal of aromatic compounds and the potency of enzymatic inhibition. Conclusion & Significance: This bioscreening allowed the selection of 17 plant extracts, promising as cosmetic ingredients, which safety is also supported by the ethnobotanical uses. Nine of them proved active both against tyrosinase and elastase and as shown by the OPLS model their aromatic phytoconstituents play a key role in conferring these bioactivities.
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Recent Publications 
1. Imokawa G, Ishida K (2015) Biological mechanisms underlying the ultraviolet ?radiation-induced formation of skin wrinkling and sagging I: reduced skin elasticity, highly associated with enhanced dermal elastase activity, triggers wrinkling and sagging. International Journal of Molecular Sciences 16: 7753-7775.
2. Liyanaarachchi GD, Samarasekera JK, Mahanama KR, Hemalal KD. (2018) Tyrosinase, elastase, hyaluronidase, inhibitory and antioxidant activity of Sri Lankan medicinal plants for novel cosmeceuticals. Industrial Crops and Products 111:597-605.
3. Mukherjee PK, Maity N, Nema NK, Sarkar BK (2011) Bioactive compounds from natural resources against skin aging. Phytomedicine 19:64-73.
4. Pillaiyar T, Manickam M, Namasivayam V. (2017) Skin whitening agents: medicinal chemistry perspective of tyrosinase inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry 32:403-25
5. Yuliana ND, Khatib A, Choi YH, Verpoorte R. (2011) Metabolomics for bioactivity assessment of natural products. Phytotherapy Research 25:157-69. 




              Biography 
Manuela Mandrone currently works at Bologna University, Department of Pharmacology and Biotechnology, and she is Junior Researcher since 2016. Dr. Mandrone investigates in plant science and in particular, her research is focused on natural-product based drug discovery inspired by traditional medicine knowledge and studies of plant-environment interactions, in particular related to crops. She has expertise in identification of active principles responsible for biological activities of medicinal plants, finding of biomarkers and quality control of botanicals. These lines of research lie on canonical phytochemical studies as well as on novel approaches such as: metabolomics coupled with chemometrics, which has been a subject of her PhD thesis. She has expertise also in biological activities screening, in particular antioxidant and enzymatic inhibitory assays.
                                                                                                Email: manuela.mandrone2@unibo.it



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