22 ANTI-AGEING a


250 200 150 100 50 0


Normal cells


c Normal Cells + Exosomes


+ Exosomes + Scutaline (0.05%)


+ Exosomes + Scutaline (0.075%)


120 100 80 60 40 20 0


Normal cells


Exosomes from SIPS fibroblasts


ns


+130% **


+80% **


SIPS cells


b


-45% ***


6 5 4 3 2 1 0


SIPS cells Scutaline (0.075%)


-42% *


-38% ***


n Normal cells n SIPS cells n SIPS + Scutaline n Scutaline 0.05%


Hyaluronate synthase miR-23a-3P


Collagen I synthesis miR-34a-5P


Exosomes Scutaline (0.05%)


Exosomes Scutaline (0.075%)


Figure 2: Scutaline prevents senescence spreading.NHDF were exposed to H2


O2


for 2h and then left for 3-4 days. Cells were then cultivated in the presence


or in the absence of Scutaline for 48h. The exosomes were then isolated and applied on normal fibroblasts for 72h. a) The number of exosomes produced was then quantified, b) the miRNA they contain were analysed by qRT-PCR, and c) the collagen I production of fibroblasts exposed to exosomes from SIPS fibroblasts was observed by immunofluorescence and quantified (collagen I appears in green and cell nuclei in blue (DAPI)). *** p-value < 0.001, ** p-value < 0.01, * p-value < 0.05 vs SIPS, ns no significant vs normal cells.


SA-ß-Gal activity, treatment with Scutellaria baicalensis root extract (0.1%) decreased the number of senescent cells by 44%. Scutellaria baicalensis root extract thus provided a 65% protection against stress-induced premature senescence (SIPS) (Fig 1). By preventing fibroblasts from entering


into the senescence state, Scutellaria baicalensis root extract maintains their normal function and regulates their redox status, their energy production and their production of MMP-1 (data not shown). Scutellaria baicalensis root extract therefore acts in a preventive mode by limiting the natural process of senescence. This strategy allows skin that is still relatively young to defend itself against stress.


Decreasing the ability of senescent cells to promote senescence and to cause inflamm’aging Senescent cells have the ability to spread senescence. This transmission process is mediated by exosomes which are small excreted vesicles of endoplasmic origin that contain microRNA (miRNA) specific to


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certain genes. Once these exosomes reach a nearby cell, they fuse to the membrane and release their content in this cell. miRNA will then inhibit the expression of specific genes in the target cell, and trigger the senescence phenotype.8-10 In order to assess the ability of


Scutellaria baicalensis root extract to decrease the capacity of senescent cells to further promote senescence, fibroblasts under SIPS were cultivated for 48h in the presence or in the absence of Scutellaria baicalensis root extract. The number of exosomes they produce was quantified and the miRNA they contain was analysed using quantitative RT-PCR (Fig 2A, 2B). Senescent cells secrete twice as many


exosomes as normal cells and they contain high amount of miRNA that will lead to the inhibition of genes involved in key skin parameter such as hyaluronate synthase or collagen I synthesis. Treatment with Scutellaria baicalensis


root extract strongly decreases the number of exosomes secreted by fibroblasts under SIPS and the amount of miRNA they carry (Fig 2A, 2B). Scutellaria baicalensis root


extract therefore reduces the inhibition of several key genes. As a result, target cells maintain an optimal activity such as their ability to produce collagen (Fig 2C). By preventing healthy cells from being


‘contaminated’ by nearby senescent cells, Scutellaria baicalensis root extract maintains an optimal collagen production for a denser and firmer skin. Among all the SASP produced by a


senescent cell, many are pro-inflammatory such as IL-6 and are responsible for inflamm’aging, a low-grade chronic inflammation that can lead to premature ageing. Macrophages are key actors of the


innate immune response. Once activated by a danger message such as the presence of bacteria in the tissue, they secrete high levels of ROS (especially nitric oxide (NO)), pro-inflammatory cytokines, and lipid mediators such as prostaglandin (PGE2


) in


order to obliterate it. However, in the case of a chronic


inflammation, macrophages are recruited even in the absence of pathogen. This creates a micro-environment rich in free


June 2020


Nbr of exosomes (% of control)


Relative miRNA content


Collagen I production (% of control)


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