Skin ageing is strictly related to chronic inflammation of the derma and the decay of structural proteins of the extracellular matrix. Indeed, it has become common practice to refer to this phenomenon as inflammageing. Biotech innovation is always in search of new active principles that induce a youthful appearance. In this paper, apple-derived nanovesicles (ADNVs) were investigated as novel anti-inflammatory compounds, which are able to alter the extracellular matrix production of dermal fibroblasts. Total RNA sequencing analysis revealed that ADNVs negatively influence the activity of Toll-like Receptor 4 (TLR4), and, thus, downregulate the NF-κB pro-inflammatory pathway. ADNVs also reduce extracellular matrix degradation by increasing collagen synthesis (COL3A1, COL1A2, COL8A1 and COL6A1) and downregulating metalloproteinase production (MMP1, MMP8 and MMP9). Topical applications for skin regeneration were evaluated by the association of ADNVs with hyaluronic-acid-based hydrogel and patches.

The constant dialogue between the plant world and the animal world (including man among them) has been known since the time of Adam and Eve, where an apple was the origin of the evils of the world. Apart from Snow White—who might have something to object to when it comes to the use of apples—fruits, plants, and natural extracts have been known for millennia as remedies for human health-related ailments. In the light of such evidence, the aim of the present work was to investigate from a biological point of view the potential role of apple exosomes in inflammatory processes on human cells. To this end we isolated and characterized apple exosomes and treated human cells such as macrophages and NCTC L929 as cancer cells in order to evaluate the tumorigenic and anti-inflammatory effect of apple exomes. Microscopic and molecular biology analyses were conducted to characterize exosomes and to assess cell proliferation, death, and miRNA line, as well as gene expression and the uptake of exosomes by cells. The results confirm the absolute biological safety of exosomes and their anti-inflammatory effect, mediated mainly by miRNA146 production by M2 macrophages.

Apple by-products (APs) consist of whole defective fruits discarded from the market and pomace resulting from juice squeezing and puree production, which are currently underutilized or disposed of due to the lack of effective and scalable extraction methods. Bioactive compounds in APs, especially phlorizin, which is practically exclusive to the apple tree, are endowed with preventive and therapeutic potential concerning chronic diseases such as cardiovascular diseases, metabolic diseases, and specific types of cancer. This study investigated the exploitation of APs using hydrodynamic cavitation (HC) for the extraction step and water as the only solvent. High-temperature extraction (>80 °C) was needed to inactivate the polyphenol oxidase; a strict range of the cavitation number (around 0.07) was identified for extraction optimization; less than 20 min were sufficient for the extraction of macro- and micro-nutrients up to nearly their potential level, irrespective of the concentration of fresh biomass up to 50% of the water mass. The energy required to produce 30 to 100 g of dry extract containing 100 mg of phlorizin was predicted at around or less than 1 kWh, with HC contributing for less than 2.5% to the overall energy balance due to the efficient extraction process.

Apple by-products (AP) consist of whole defective fruits discarded from the market and pomace resulting from juice squeezing and puree production, which are currently underutilized or dis-posed of due to the lack of effective and scalable extraction methods. Bioactive compounds in AP, especially phlorizin, which is practically exclusive to the apple tree, are endowed with preventive and therapeutic potential concerning chronic diseases such as cardiovascular, metabolic and specific types of cancer. This study investigated the exploitation of AP using hydrodynamic cavitation (HC) for the extraction step and water as the only solvent. High-temperature extraction (>80°C) was needed to inactivate the polyphenol oxidase; a strict range of the cavitation number (around 0.07) was identified for extraction optimization; less than 20 minutes were sufficient for extraction of macro- and micro-nutrients up to nearly their potential level, irrespective of the concentration of fresh biomass up to 50% of the water mass. The energy required to produce 30 to 100 g of dry extract containing 100 mg of phlorizin was predicted around or less than 1 kWh, with HC contributing for less than 2.5% to the overall energy balance due to the efficient extraction process.