Rodboon Teerapat, Sirilun Sasithorn, Okada Seiji, Kariya Ryusho, Chontananarth Thapana, Suwannalert Prasit
Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand.
Res Pharm Sci. 2020 Oct 19;15(5):491-502. doi: 10.4103/1735-5362.297852. eCollection 2020 Oct.
Excessive melanin production caused by overactive tyrosinase (TYR) enzyme results in several dermatological problems. The TYR inhibitor, derived from metabolite changes during fermentation, has been well recognized for pigmentation control.
This study is interested in alternative anti-melanogenic agents from bio-modified Riceberry rice through fermentation. Modified Riceberry rice extract (MRB) was evaluated for its cytotoxicity, melanin content, melanin excretion, and TYR activity in B16 cells. TYR and their melanogenesis-related molecules such as TYR-related proteins-1 and -2, and microphthalmia-associated transcription factor (MITF) were determined. The anti-melanogenic activity and toxicity were also tested using the embryonic zebrafish model. Furthermore, comprehensive genotoxicity testing was verified by cytokinesis-block micronucleus cytome assay.
FINDINGS/RESULTS: The study found that non-cytotoxic concentrations of MRB at 20 and 40 mg/mL inhibited melanogenesis and melanin excretion by interfering B16 cell morphology. Cellular TYR enzymatic activity was also suppressed in the treated cells. The mRNA transcription and protein expression levels of TYR and MITF decreased by dose-dependent and time-dependent manners with MRB treatment. In the animal model, MRB was found to be safe and potent for melanogenesis-related TYR inhibition in embryonic zebrafish at 20 and 30 mg/mL. The toxicity of effective doses of MRB showed no genotoxicity and mutagenicity.
This study suggests that MRB has anti-melanogenesis potential through TYR and its-related protein inhibitions. MRB is also safe for applications and maybe a promising anti-melanogenic agent for hyperpigmentation control.
酪氨酸酶(TYR)活性过高导致黑色素生成过多,会引发多种皮肤问题。源自发酵过程中代谢产物变化的TYR抑制剂,在色素沉着控制方面已得到广泛认可。
本研究关注通过发酵对生物改性红米稻进行替代抗黑色素生成剂的研究。对改性红米稻提取物(MRB)在B16细胞中的细胞毒性、黑色素含量、黑色素排泄及TYR活性进行了评估。测定了TYR及其与黑色素生成相关的分子,如TYR相关蛋白-1和-2,以及小眼相关转录因子(MITF)。还使用斑马鱼胚胎模型测试了抗黑色素生成活性和毒性。此外,通过胞质分裂阻滞微核细胞分析法验证了全面的遗传毒性测试。
研究发现,20和40 mg/mL的非细胞毒性浓度的MRB通过干扰B16细胞形态抑制黑色素生成和黑色素排泄。处理后的细胞中细胞TYR酶活性也受到抑制。MRB处理后,TYR和MITF的mRNA转录和蛋白质表达水平呈剂量依赖性和时间依赖性下降。在动物模型中,发现20和30 mg/mL的MRB对斑马鱼胚胎中与黑色素生成相关的TYR抑制是安全且有效的。有效剂量的MRB的毒性未显示出遗传毒性和致突变性。
本研究表明,MRB通过抑制TYR及其相关蛋白具有抗黑色素生成潜力。MRB在应用中也是安全的,可能是一种有前景的用于控制色素沉着的抗黑色素生成剂。