Electrochemical analysis and in silico molecular docking with tropomyosin-related kinase B reveals electron shuttles-mediated neuroprotective potential of mandarin orange pu-erh tea extracts

Abstract

Camellia tea, rich in phytonutrients, holds significant potential in combating oxidative stress linked to neurological diseases. Its phytonutrients include polyphenolic electron shuttles (ES), which majorly stimulate bioenergy through microbial fuel cells (MFC) due to their redox-cycling properties. Previous research highlighted the bioenergy-stimulating and antiviral capabilities of ES in herbal extracts (Tsai, Hsieh et al., 2022; Tsai, Hsueh et al., 2022), yet their neuroprotective role remains unexplored. This study investigates the neuroprotective potential of mandarin orange pu-erh tea (CRPR), a subclass of Camellia tea. Phytochemical contents and antioxidant capacities of CRPR water (CRPR-W) and ethanol (CRPR-E) extracts were assessed. Cyclic voltammetry and MFC were employed to evaluate the electron-shuttling and bioenergy-stimulating characteristics of these extracts. In silico molecular docking analyses with tropomyosin-related kinase B (TrkB) were done to explore the neuroprotective potentials of CRPR's ES. Results indicated that CRPR-E (total polyphenols 224.15 f 0.55 gallic acid mg/g; total flavonoids 18.31 f 0.51 rutin mg/g; amplification 1.88 f 0.34) is better at acquiring antioxidative and bioenergy-stimulating phytochemicals, particularly flavonoids, compared to CRPR-W (total polyphenols 110.66 f 1.05 gallic acid mg/g; total flavonoids 6.26 f 0.13 rutin mg/g; amplification 1.76 f 0.27). Molecular docking revealed that flavonoid ES, such as quercetin (-6.2 kcal/mol), luteolin (-6.0 kcal/ mol), and taxifolin (-5.8 kcal/mol), exhibit favorable binding affinities with TrkB, with quercetin showing the most promise at the active site. Additionally, other ES like luteolin (-6.5 kcal/mol; allosteric site #1) and ellagic acid (-6.4 kcal/mol; allosteric site #2) are likely allosteric modulators of TrkB. In conclusion, the flavonoid-rich CRPR-E emerges as a promising candidate for the ES-mediated neuroprotective potential of CRPR as a medicated diet.