The study of skin hydration, anti-wrinkles function improvement of anti-aging cream with alpha-ketoglutarate

Introduction: The tricarboxylic acid (TCA) cycle is a key metabolic pathway for driving the generation of mitochondrial energy in all oxidative organisms. Alpha-ketoglutarate (Alpha-KG), a precursor of glutamine, is known as a crucial intermediate of the TCA cycle and plays a pivotal role in multiple metabolic processes. As a precursor of glutamate and glutamine, AKG acts as an antioxidant agent as it directly reacts with hydrogen peroxide with formation of succinate, water, and carbon dioxide; meanwhile, it discharges plenty of ATP by oxidative decarboxylation. Several studies reported that Alpha-KG is a key participant in the detoxification of reactive oxygen species and acts as an integral part of the oxidative defense machinery. However, few studies have been reported on the efficacy of Alpha-KG in the maintenance of skin functions. This study demonstrated that Alpha-KG has beneficial effects on skin hydration and barrier function and that fermentation is an effective way to enhance the synthesis of Alpha-KG in yeast, which possesses mitochondria. Methods: Evaluation of promoting effects on epidermal keratinocyte proliferation: Keratinocytes were incubated with a test sample, and the degree of proliferation was determined by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Evaluation of promoting effects on mRNA expression of genes related to skin hydration and barrier function: Keratinocytes were incubated with a test sample, and gene expression levels of filaggrin (FLG), serine palmitoyltransferase (SPT), and involucrin (IVL) were analyzed by real-time RT-PCR. Analysis of Alpha-KG in rice fermented liquid: Alpha-KG in rice fermented liquid was quantitatively analyzed by capillary electrophoresis time-of-flight mass spectrometry (CE-TOF-MS). Clinical study testing methods and VISIA testing: After 28 days of treatment use the cream with Alpha-KG and control sample without Alpha-KG, instrumentation measurements were adopted to assess skin wrinkles, texture, elasticity, and firmness, tested by the VISIA-CR. Results: Immediately after using the sample for D0, the skin wrinkles were significantly reduced by 23.64%. After using the sample for D7, the average clinical score of outer corner wrinkles was significantly reduced by 15.23%, and nasolabial groove wrinkles were significantly reduced by 25.68%. After using the sample for D56, the mean clinical evaluation score of crow's feet decreased significantly by 25.42%; the average score of clinical evaluation of skin firmness increased significantly by 41.40%; the skin gloss increased significantly by 28.67%. Conclusion: It was demonstrated that Alpha-KG is expected to promote skin hydration and barrier function by the activation of cell proliferation and the up-regulation of mRNA expression of genes related to the maintenance of epidermal function in in vitro tests. In order to develop a cosmetic ingredient including Alpha-KG, we focused on fermentation with yeast as an efficient production method of Alpha-KG and found that fermentation of rice with yeast efficiently produced Alpha-KG. Taken together, it is considered that rice fermented liquid containing Alpha-KG could be a promising ingredient for skin care products. Through the clinical testing, rice fermented liquid containing Alpha-KG could be a promising cosmetic ingredient for skin care products.