Activation of peroxisome proliferator-activated receptors (PPAR) α/γ is known to inhibit the increases in matrix metalloproteinase (MMP) and reactive oxygen species (ROS) induced by ultraviolet light (UV). Extracts of natural herbs, such as Kochia scoparia and Rosa multiflora, have a PPAR α/γ dual agonistic effect. Therefore, we investigated whether and how they have an antiaging effect on photoaging skin. Eighteen-week-old hairless mice were irradiated with UVA 14 J/cm2 and UVB 40 mJ/cm2 three times a week for 8 weeks. A mixture of extracts of Kochia scoparia and Rosa multiflora (KR) was topically applied on the dorsal skin of photoaging mice twice a day for 8 weeks. Tesaglitazar, a known PPAR α/γ agonist, and vehicle (propylene glycol:ethanol = 7:3, v/v) were applied as positive and negative controls, respectively. Dermal effects (including dermal thickness, collagen density, dermal expression of procollagen 1 and collagenase 13) and epidermal effects (including skin barrier function, epidermal proliferation, epidermal differentiation, and epidermal cytokines) were measured and compared. In photoaging murine skin, KR resulted in a significant recovery of dermal thickness as well as dermal fibroblasts, although it did not change dermal collagen density. KR increased the expression of dermal transforming growth factor (TGF)-β. The dermal effects of KR were explained by an increase in procollagen 1 expression, induced by TGF-β, and a decrease in MMP-13 expression. KR did not affect basal transepidermal water loss (TEWL) or stratum corneum (SC) integrity, but did decrease SC hydration. It also did not affect epidermal proliferation or epidermal differentiation. KR decreased the expression of epidermal interleukin (IL)-1α. Collectively, KR showed possible utility as a therapeutic agent for photoaging skin, with few epidermal side effects such as epidermal hyperplasia or poor differentiation.
In this study, caviar (sturgeon eggs) was used to elucidate its roles in adiponectin production and skin anti-aging. Recently, caviar has been largely used not only as a nutritional food, but also in cosmetic products. In particular, it has been reported that docosahexaenoic acid (DHA), as one of the main phospholipid components of caviar extract, induces intracellular lipid accumulation and the expression of adiponectin in adipocytes. Although adipocytes are well known to be associated with the skin dermis by secreting various factors (e.g., adiponectin), the effects of caviar extract and DHA on the skin are not well studied. Here, we demonstrate the effects of caviar extract and DHA on adipocyte differentiation and adiponectin production, resulting in a preventive role in UV-irradiated skin aging. Caviar extract and DHA enhanced adipocyte differentiation and promoted the synthesis of transcription factors controlling adipocyte differentiation and adiponectin. In addition, the mRNA expression levels of matrix metalloproteinase-1 (MMP-1) were decreased in UVB-irradiated Hs68 fibroblasts that were cultured in conditioned medium from caviar extract or DHA-treated differentiated adipocytes. Taken together, these results indicate that caviar extract and DHA induce adipocyte differentiation and adiponectin production, thereby inhibiting UVB-induced premature skin aging via the suppression of MMP-1 production.
Centella asiatica, a traditional herb, is widely recognized for its pharmacologically active components, such as asiaticoside, madecassoside, asiatic acid, and madecassic acid. These components render it a highly sought-after ingredient in various industries, including cosmetics and pharmaceuticals. This study aimed to enhance the production and activity of these pharmacological constituents of C. asiatica using the plant growth-promoting rhizobacterium Priestia megaterium HyangYak-01 during its cultivation. To achieve this goal, the researchers conducted field experiments, which revealed an increase in the production of pharmacologically active compounds in C. asiatica cultivated with a P. megaterium HyangYak-01 culture solution. Additionally, quadrupole time-of-flight mass spectrometry (Q-TOF MS) confirmed that the composition ratios of the C. asiatica extract treated with the P. megaterium HyangYak-01 culture solution differed from those of the untreated control and type strain-treated groups. Skin cell experiments indicated that the C. asiatica extract treated with the P. megaterium HyangYak-01 culture solution exhibited greater skin barrier improvement and less pronounced inflammatory responses than those from plants grown without the bacterial culture solution. This study demonstrates that microbial treatment during plant cultivation can beneficially influence the production of pharmacological constituents, suggesting a valuable approach toward enhancing the therapeutic properties of plants.
Alterations in the ceramide (CER) profile have been associated with atopic dermatitis in dogs; however, the specific effects of CER subclasses on canine keratinocytes remain unclear. This study aimed to optimize a CER complex and evaluate its effects on cytokine expression, CER synthesis, and skin barrier formation using canine epidermal keratinocyte progenitor (CPEK) cells and a reconstructed canine epidermis (RCE) model. Among various CER combinations tested, only the mixture of CER [NS] and [EOP] significantly reduced proinflammatory cytokine mRNA levels in Staphylococcus pseudintermedius–stimulated CPEK cells. Further optimization revealed that a 4:1 ratio of CER [NS] to [EOP] (cCER complex) markedly decreased CCL17 and CCL22 mRNA expression while upregulating keratin 10, ceramide synthase 3 (CERS3), and ceramide synthase 4, as well as enzymes involved in both de novo and salvage CER biosynthesis pathways. In the RCE model, cCER administration improved stratum corneum organization and increased the expression of loricrin, CERS3, and CER. In vivo application of cCER in dogs accelerated skin barrier repair and improved hair condition. These findings suggest that a CER [NS]/[EOP] mixture represents a promising therapeutic option with anti-inflammatory and skin barrier-enhancing effects for canine atopic dermatitis.
Injected botulinum neurotoxins (BoNT) reduce dynamic wrinkles by cleaving SNARE proteins at the neuromuscular junction; however, their large size mostly limits their use to injectable procedures. Certain polyphenols, including myricetin, have been shown in neuronal systems to reduce acetylcholine (ACh)-induced muscle contraction via inhibition of SNARE complex zippering, suggesting potential for topical use as modulators of skin cholinergic activity. This study aimed to identify a natural extract blend similarly capable of attenuating ACh release followed by characterization of the activity of this extract on human skin explants, alongside reference molecules BoNT/A, α-bungarotoxin, and myricetin. The natural extract blend (“Blend 1”) inhibited vesicle fusion and attenuated norepinephrine release in a cell culture system, inhibited muscle cell contraction within nerve/muscle co-culture, and attenuated ACh release consistent with myricetin and reference neurotoxins within human skin explants. Bulk transcriptomics of treated ex vivo skin explants revealed that BoNT/A, myricetin and Blend 1 all shared a similar downregulated inflammatory and anti-viral gene profile separate from α-bungarotoxin, but that myricetin and Blend 1 shared a large degree of overlap for upregulated genes associated with skin homeostasis and repair that was not observed for either toxin. These data support Blend 1 as a candidate for topical cosmetic use through modulation of BoNT/A-like cholinergic pathways, alongside activation of additional pathways associated with skin homeostasis and repair.