Culture of plant cells or tissues is a scalable, sustainable, and environmentally friendly approach to obtain extracts and secondary metabolites of uniform quality that can be continuously supplied in controlled conditions, independent of geographical and seasonal variations, environmental factors, and negative biological influences. In addition, tissues and cells can be extracted/obtained from the by-products of other industrial cultivations such as that of Lavandula angustifolia Miller (L. angustifolia), which is largely cultivated for the collection of flowers. Given that, an extract rich in rosmarinic acid was biotechnologically produced starting from cell suspension of L. angustifolia, which was then loaded in hyalurosomes, special phospholipid vesicles enriched with sodium hyaluronate, which in turn are capable of both immobilizing and stabilizing the system. These vesicles have demonstrated to be good candidates for skin delivery as their high viscosity favors their residence at the application site, thus promoting their interaction with the skin components. The main physico-chemical and technological characteristics of vesicles (i.e., mean diameter, polydispersity index, zeta potential and entrapment efficiency of extract in vesicles) were measured along with their biological properties in vitro: biocompatibility against fibroblasts and ability to protect the cells from oxidative stress induced by hydrogen peroxide. Overall, preliminary results disclosed the promising properties of obtained formulations to be used for the treatment of skin diseases associated with oxidative stress and inflammation.

Psoriasis is a chronic inflammatory skin condition characterized by abnormal keratinocyte proliferation and differentiation that is accompanied with dysregulated immune response and abnormal vascularization. Devil’s claw (Harpagophytum procumbens (Burch.) DC. ex Meisn.) tubers extract has been used both systemically and topically for treatment of chronic inflammatory diseases such as arthritis, osteoporosis, inflammatory bowel disease, among others. However, its potential mechanisms of action against psoriasis remains poorly investigated. The human keratinocyte HaCaT cell line is a well-accepted in vitro model system for inflammatory skin disorders such as psoriasis. The present study involved an exploration of the effect of biotechnologically produced H. procumbens (HP) cell suspension extract and pure phenylethanoid glycosides verbascoside (VER) and leucosceptoside A (LEU) in interferon (IFN)-γ/interleukin (IL)-17A/IL-22-stimulated HaCaT cells as a model of psoriasis-like inflammation. Changes in key inflammatory signaling pathways related to psoriasis development were detected by reverse transcription polymerase chain reaction and western blotting. Treatment with LEU, but not VER and HP extract improved psoriasis-related inflammation via suppression of the PI3K/AKT signaling in IFN-γ/IL-17A/IL-22-stimulated HaCaT cells. Our results suggest that LEU may exhibit therapeutic potential against psoriasis by regulating keratinocyte differentiation through inhibition of the PI3K/AKT pathway.

The synthetic 2-cyano-3,12-dioxo-oleana-1,9(11)-dien-28-oic acid methyl ester (CDDO-Me) is a potent activator of the erythroid 2-p45-derived factor 2, Nrf2, a leucine-zipper regulator of the antioxidant response. Herein, we investigated the effect of CDDO-Me on neutrophil function in a murine model of joint damage. Collagenase-induced osteoarthritis (CIOA) was initiated by the intra-articular injection of collagenase in the knee-joint cavity of Balb/c mice. CDDO-Me was administrated intra-articularly twice a week starting at day 7 post-CIOA, and its effect was evaluated at day 14. Neutrophils in blood and bone marrow (BM), cell apoptosis, necrosis, expression of C-X-C chemokine receptor 4 (CXCR4), beta-galactosidase (β-Gal), and Nrf2 levels were measured by flow cytometry. In vitro, CDDO-Me promoted cell survival, reduced cell necrosis, and increased Nrf2 levels by 1.6 times. It decreased surface CXCR4 expression and reduced the frequency of senescent β-Gal+CXCR4+ neutrophils by three times. In vivo, the degree of knee-joint damage in CIOA was correlated with upregulated CXCR4 on CD11b+ neutrophils. CDDO-Me improved the disease histological score, increased the levels of Nrf2, and downregulated surface CXCR4 on mature BM cells. Our data suggest that CDDO-Me may act as a potent regulator of neutrophil senescence during the progression of knee-joint damage.

Chronic and excessive ultraviolet (UVA/UVB) irradiation exposure is known as a major contributor to premature skin aging, which leads to excessive reactive oxygen species generation, disturbed extracellular matrix homeostasis, DNA damage, and chronic inflammation. Sunscreen products are the major preventive option against UVR-induced photodamage, mostly counteracting the acute skin effects and only mildly counteracting accelerated aging. Therefore, novel anti-photoaging and photopreventive compounds are a subject of increased scientific interest. Our previous investigations revealed that the endemic plant Haberlea rhodopensis Friv. (HRE) activates the antioxidant defense through an NRF2-mediated mechanism in neutrophiles. In the present study, we aimed to investigate the photoprotective potential of HRE and two of its specialized compounds—the phenylethanoid glycosides myconoside (MYC) and calceolarioside E (CAL)—in UVA/UVB-stimulated human keratinocytes in an in vitro model of photoaging. The obtained data demonstrated that the application of HRE, MYC, and CAL significantly reduced intracellular ROS formation in UVR-exposed HaCaT cells. The NRF2/PGC-1α and TGF-1β/Smad/Wnt signaling pathways were pointed out as having a critical role in the observed CAL- and MYC-induced photoprotective effect. Collectively, CAL is worth further evaluation as a potent natural NRF2 activator and a promising photoprotective agent that leads to the prevention of UVA/UVB-induced premature skin aging.