Research & Development Center, Mageline Biology Tech Co., Ltd., Wuhan, Hubei, China.
J Cosmet Dermatol. 2022 Apr;21(4):1736-1743. doi: 10.1111/jocd.14635. Epub 2021 Nov 24.
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.
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.
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%.
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.
三羧酸(TCA)循环是所有需氧生物中驱动线粒体能量产生的关键代谢途径。α-酮戊二酸(Alpha-KG)是谷氨酰胺的前体,是 TCA 循环的重要中间产物,在多种代谢过程中发挥着关键作用。作为谷氨酸和谷氨酰胺的前体,AKG 作为抗氧化剂直接与过氧化氢反应,形成琥珀酸、水和二氧化碳; 同时,通过氧化脱羧释放大量的 ATP。有几项研究报道称,Alpha-KG 是活性氧解毒的关键参与者,是氧化防御机制的组成部分。然而,关于 Alpha-KG 在维持皮肤功能方面的功效的研究很少。本研究表明,Alpha-KG 对皮肤水合和屏障功能有益,发酵是提高酵母中 Alpha-KG 合成的有效途径,酵母具有线粒体。
评估对表皮角质形成细胞增殖的促进作用:将角质形成细胞与测试样品孵育,并通过 MTT [3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴盐]测定法测定增殖程度。评估对与皮肤水合和屏障功能相关的基因表达的促进作用:将角质形成细胞与测试样品孵育,并通过实时 RT-PCR 分析丝聚合蛋白(FLG)、丝氨酸棕榈酰转移酶(SPT)和内披蛋白(IVL)的基因表达水平。大米发酵液中 Alpha-KG 的分析:通过毛细管电泳飞行时间质谱(CE-TOF-MS)定量分析大米发酵液中的 Alpha-KG。临床研究测试方法和 VISIA 测试:使用含有 Alpha-KG 的面霜和不含 Alpha-KG 的对照样品治疗 28 天后,采用仪器测量评估皮肤皱纹、纹理、弹性和紧致度,采用 VISIA-CR 进行测试。
使用样品后的 D0 时,皮肤皱纹明显减少了 23.64%。使用样品后的 D7 时,外眼角皱纹的平均临床评分显著降低了 15.23%,鼻唇沟皱纹显著降低了 25.68%。使用样品后的 D56 时,鱼尾纹的平均临床评估评分显著降低了 25.42%;皮肤紧致度的平均临床评估评分显著增加了 41.40%;皮肤光泽度显著增加了 28.67%。
在体外试验中,通过激活细胞增殖和维持表皮功能相关基因的 mRNA 表达上调,证明 Alpha-KG 有望促进皮肤水合和屏障功能。为了开发含有 Alpha-KG 的化妆品成分,我们专注于酵母发酵作为 Alpha-KG 的有效生产方法,并发现酵母发酵大米可以有效地生产 Alpha-KG。综上所述,含有 Alpha-KG 的大米发酵液可能是一种有前途的护肤品成分。通过临床测试,含有 Alpha-KG 的大米发酵液可能是一种有前途的护肤品成分。