Aging is an intricate and unavoidable biological process marked by the gradual decline of organ functions over time, influenced by various biochemical reactions and environmental factors. Among the most visible signs of this decline is skin aging, which manifests through symptoms such as skin laxity, wrinkling, dryness, loss of elasticity, pigmentation changes, and thinning. Skin aging encompasses both endogenous aging, driven by genetic and endocrine factors, which reduces dermal fibroblast numbers and the synthesis of collagen and elastin, leading to thinning and fine wrinkles, and exogenous aging, caused by environmental factors like UV radiation, pollution, smoking, temperature, and diet, resulting in deeper wrinkles, laxity, and pigmentation spots.
This study explores the anti-aging potential of fructosazine (FZ) and deoxyfructosazine (DOF), compounds belonging to the polyhydroxyalkylpyrazines (PHAPs) class, previously found in roasted foods and traditional Chinese medicine. While research on PHAPs is limited, FZ and DOF have shown antibacterial activity and potential immunomodulatory effects. FZ was previously observed to exhibit a delaying effect on the natural aging of human embryonic lung diploid cells (2BS cells). Given that 2BS cells are a type of fibroblast and FZ’s multi-hydroxyl structure is similar to the cosmetic ingredient Pro-Xylane, interest arose in exploring FZ, and its structurally similar counterpart DOF, as potential cosmetic raw materials for human skin fibroblast cells (NHDF cells). This research aimed to investigate their anti-aging effects and mechanisms on the skin to provide a scientific basis for their potential use in anti-aging skincare products, addressing the current need for more effective and less irritating options.
Methods
The research employed both in vitro and in vivo approaches. In vitro studies used normal human dermal fibroblast (NHDF) cells to assess viability, the secretion of factors like Type I Collagen (Col I), Hyaluronic Acid (HA), and Matrix Metalloproteinase-1 (MMP-1), as well as intracellular levels of Reactive Oxygen Species (ROS), Catalase (CAT) activity, Malondialdehyde (MDA) content, and Senescence-associated β-galactosidase (SA-β-Gal) expression. An oxidative stress model was established in NHDF cells using H₂O₂. For the in vivo analysis, FZ, DOF, or Pro-xylane were applied topically to the shaved skin on the backs of male Sprague-Dawley rats for three weeks, after which skin samples were collected and stained (Hematoxylin-Eosin, Masson’s trichrome, Elastica van Gieson) to evaluate morphology, collagen, and elastic fibers. Pro-xylane and Vitamin C were used as reference compounds.
Key Findings
The study revealed several promising anti-aging effects of FZ and DOF:
- Enhanced Cell Viability: FZ significantly promoted the viability of NHDF cells, with the most pronounced effect observed at 5 µM, increasing viability to 138.1%. DOF did not show toxicity or enhancement in the tested range.
- Improved Extracellular Matrix: Both FZ and DOF enhanced the secretion of Type I Collagen (Col I) and Hyaluronic Acid (HA), key components for skin elasticity and hydration. They also inhibited the secretion of Matrix Metalloproteinase-1 (MMP-1), an enzyme responsible for collagen breakdown, which is elevated in aged skin. FZ and DOF demonstrated advantages over Pro-xylane in these aspects at the same concentrations.
- Potent Antioxidant Activity: FZ and DOF significantly boosted Catalase (CAT) activity, a crucial antioxidant enzyme, and reduced Malondialdehyde (MDA) content, a marker of lipid peroxidation and cellular damage. Their antioxidant efficacy significantly exceeded that of Vitamin C in normal cultured cells.
- Protection Against Oxidative Stress: Pretreatment with FZ or DOF effectively scavenged Reactive Oxygen Species (ROS) in oxidatively stressed cells. FZ showed superior ROS scavenging compared to DOF. They also effectively suppressed MMP-1 secretion under oxidative stress conditions.
- Reduced Cellular Senescence: FZ and DOF treatments decreased the percentage of senescent cells (identified by SA-β-Gal expression) in oxidatively stressed cells and helped maintain normal cellular morphology, alleviating oxidative damage and delaying senescence.
- In Vivo Skin Improvement: In rat studies, FZ or DOF treatment showed no adverse reactions and had a nourishing effect on the epidermis, suggesting improved skin barrier function. They also increased the content and improved the structure of collagen fibers, making them denser and more regular. Furthermore, they enhanced the content and resilience of elastic fibers, which are critical for skin elasticity and structure.
This study offers valuable insights into the potential anti-aging benefits of FZ and DOF. The novelty of this research lies in specifically investigating the anti-aging properties of these PHAP compounds on the skin, a research gap the study aimed to address. The findings demonstrate that FZ and DOF possess potent multi-mechanistic anti-aging properties, including stimulating fibroblast vitality, promoting ECM component production (Col I, HA), inhibiting collagen degradation (MMP-1), and significantly reducing oxidative stress (ROS, MDA, CAT). Their ability to protect cells from oxidative damage, reduce senescence markers, and improve the structure of collagen and elastic fibers observed in animal studies highlights their comprehensive anti-aging potential.
Notably, FZ and DOF showed performance advantages over Pro-xylane and Vitamin C in certain aspects, particularly in enhancing ECM production and antioxidant activity. These promising results suggest that FZ and DOF could serve as effective active ingredients for the development of novel anti-aging pharmaceuticals and cosmetics, potentially offering multifunctional benefits with low irritation. The study provides a strong scientific basis for their potential application in improving skin health and appearance. However, further research is needed to fully elucidate the specific molecular pathways involved, evaluate their long-term safety, and confirm efficacy in larger and more diverse human populations.
Link to the study:https://www.mdpi.com/1420-3049/30/11/2263
