Author: Dr. Paul Lawrence, Executive Director of Research and Discovery | Biocogent, LLC
Abstract:
Botanically derived materials with beneficial properties are extremely popular within the cosmetic care industry, driving considerable momentum to identify and launch new products infused with plant-based bio-active ingredients. There is also a great deal of interest in finding ways to leverage the power of epigenetics – the modulation in gene expression without any alteration of the genetic code – to improve skin health. Both endeavors dovetail with a novel extract produced from two different plants that promotes skin rejuvenation via epigenetic mechanisms.
Agrimonia eupatoria or agrimony is a flowering plant with a history steeped in folklore with reports of panacea-like qualities dating back to the Middle Ages, lending to its use in teas and tinctures. The plant can be found throughout the Middle East, Europe, and parts of Northern Africa. It is enriched in a multitude of phytochemicals known to exert health benefits, most notably dihydromyricetin and myricetin. Ampelopsis grossedentata found in Southeast Asia has a similar history and also exhibits particularly high concentrations of myricetin and dihydromyricetin that is sometimes referred to as “ampelopsin”. Intriguingly, in recent years, these compounds have shown to be particularly effective at disrupting aspects of the SARS-CoV2 replication cycle.
Laboratory assays demonstrated that the combined extract possessed both potent antioxidant and anti-inflammatory activity. Indeed, the extract showed dose-dependent scavenging of singlet
oxygen molecules as well as a concentration-dependent reduction in lipid peroxidation. Also, an array of inflammatory mediators was surveyed for diminished activity in response to application
of the dual extract that saw four molecules substantially decreased: monocyte chemoattractant protein-1 (MCP-1), macrophage colony-stimulating factor (M-CSF), interferon-induced
protein-10 (IP-10), and macrophage inflammatory protein-1 beta (MIP-1β).
Beyond traditional cosmetic care ingredient properties, the combination botanical extract was shown to an epigenetic “powerhouse”, revealed to be a naturally occurring inhibitor of histone deacetylases (HDACs). HDACs repress expression of many genes, some of which are associated with anti-inflammatory effects. One of the best characterized natural HDAC inhibitors (HDACi) is trichostatin A, which the dual extract outperformed in a biochemical assay.
Furthermore, microRNA profiling of a three-dimensional skin model 72 hours after application of the material showed a signature upregulation of 17 different microRNAs that epigenetically regulate a series of beneficial gene pathways. Finally, gene expression testing of the same tissue post-application found increased expression of multiple ameliorative genes, including but not limited to 4 different collagens, fibrillin, fibronectin, and hyaluronan synthase.
Further characterization of the epigenetic activity of the dual extract was determined to promote skin health and combat intrinsic aging by eliminating senescent cells or so-called “zombie cells”. While refusing to succumb to natural cell death, zombie cells initiate the “senescence associated secretory phenotype” (SASP) that spurs the release of a variety of inflammatory mediators that damage the surrounding tissue. These zombie cells derive their name from their inability to naturally turnover and their capacity to transform normal healthy cells into senescent cells via the SASP. The reduction in zombie cells was demonstrated via an experiment where two sets of normal human keratinocytes were treated with the double botanical extract followed by one set of cells receiving a sub-lethal dose of ultraviolet (UV) light. Subsequent viability testing revealed that the extract promoted natural programmed cell death in the UV exposed cells with later examination demonstrating that it was driven by selective activation of p53. The control set of keratinocytes showed no impact on cell viability.
Cumulatively, these findings indicate that the dual extract of A. eupatoria and A. grossedentata has a profoundly beneficial impact on human skin. The positive effects include potent antioxidant and anti-inflammatory activities, epigenetic stimulation of beneficial gene products, and the selective elimination of toxic senescent cells in the skin. Such material has the potential be useful in a topical regimen seeking skin rejuvenation and repair.
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