RESUMEN
Zhachong-13 pills (ZC-13), as a traditional prescription of Mongolian medicine, are often used in the clinical practice of Mongolian hospitals for the treatment of stroke and rheumatic arthritis. In this experiment, UHPLC-Q-Exactive Orbitrap MS was used to explore the chemical composition of ZC-13. The results showed that 315 compounds were identified or inferred, including 56 alkaloids, 77 2-(2-phenylethyl)chromones, 61 flavonoids, 31 tannins, 8 coumarins, 16 lignans, 21 terpenoids, 5 amino acids, 19 organic acids, and 21 other components. In addition, the pharmacological activities related to anti-cerebral ischemia of these components were summarized. This result laid a foundation for further study on the pharmacodynamic material basis of ZC-13 and provided a scientific basis for the formulation of ZC-13 quality specifications.
RESUMEN
As one of the main marine carotenoids, fucoxanthin has strong antioxidant activity. FoxO3α, a member of the forkhead box O family of transcription factors, plays an important role in DN by regulating oxidative stress. The activity of FoxO3α is related to its phosphorylation and acetylation status, regulated by Akt and Sirt1, a lysine deacetylase. Our study aimed to investigate whether fucoxanthin could alleviate oxidative stress and fibrosis via FoxO3α in DN and whether Akt and Sirt1 were involved. We found that in GMCs cultured in HG, fucoxanthin treatment significantly reduced the expression of FN and collagen IV, as well as reactive oxygen species generation, suggesting that fucoxanthin is beneficial to alleviate both fibrosis and oxidative stress in DN. In addition, we found that fucoxanthin decreased the phosphorylation and acetylation level of FoxO3α, reversed the protein level of FoxO3α inhibited by HG, and then promoted the nuclear transport of FoxO3α. Besides, fucoxanthin promoted the expression of manganese superoxide dismutase, a downstream target of FoxO3α. Furthermore, we found that fucoxanthin reversed the activation of Akt and inhibition of Sirt1. However, the enhancement of fucoxanthin in FoxO3α expression and nuclear transport was significantly decreased by pretreatment with Akt activator SC79 or Sirt1 inhibitor EX527. In summary, our study explored fucoxanthin alleviated oxidative stress and fibrosis induced by HG through Akt/Sirt1/FoxO3α signaling in GMCs, suggesting fucoxanthin is a potential therapeutic strategy for DN.