The neuroprotective effect and molecular docking study of sargentol in red vine on PC12 cells
The damage and death of neurons involve a wide range of processes, mainly including oxidative stress, neuroinflammation, excitotoxicity, calcium ion (Ca2+) overload, mitochondrial damage, apoptotic proteins, autophagy, etc. Neuroprotection is a key link in the prevention and treatment of neurological diseases. Natural products such as curcumin, resveratrol, and ginsenosides have shown good neuroprotective effects by regulating ROS, anti-inflammatory effects, and inhibiting excitotoxicity. They have promising applications in combating ischemic brain injury and improving learning and cognitive abilities.
Sargentodoxa cuneta (Oliv.) Rehd Et Wils. is a plant unique to China, which has the effects of detoxification, dispelling carbuncles, promoting blood circulation, relieving pain, and dispelling wind and dampness. The chemical components in red vine mainly include phenolic acids, phenylpropanoids, lignans, etc. Its extracts have pharmacological activities such as anti-inflammatory, antioxidant, and neuroprotective effects. In the preliminary research, our laboratory isolated the phenylpropanoid glycoside compound sargentol (190mg isolated from 6kg plant vine stems) from wild red vines, but there are few reports on the pharmacological activity of this compound. This article aims to evaluate the protective effect of sargentol on PC12 cell injury model and discuss its possible mechanism of action based on molecular docking technology, in order to provide scientific basis for the discovery of neuroprotective active ingredients from traditional Chinese medicine sources.

Fish vine ketone induced damage to PC12 cells is commonly used to establish a cell model of Parkinson’s disease, while NaN3 induced damage to PC12 cells is commonly used for preliminary screening of anti Alzheimer’s disease compounds. In this study, sargentol showed no significant inhibition on PC12 cell damage induced by fisetin and NaN3 (P>0.05), but was most sensitive to the H2O2 injury model and had a significant inhibitory effect on intracellular ROS induced by H2O2 in PC12 cells.
In order to further investigate the neuroprotective mechanism of sargentol, AutoDock Vina software was used to virtually screen its binding target proteins in this study. Considering that ROS effect is a common cause of cell damage or apoptosis in the H2O2 damaged cell model, we selected 14 proteins, mainly ROS effect and inflammation related proteins, for molecular docking.
Based on the binding energy and ratio R, potential targets of sargentol were identified, including TLR2 (5D3I), iNOS (2Y37), PI3K (1E7V), Keap1 (4L7B), and IKK β (3RZF). The Keap1-Nrf2-ARE signaling pathway is one of the most important mechanisms for cell defense against ROS damage. The binding energy between Keap1 (4L7B) and sargentol is -7.2 kcal/mol, indicating that sargentol may have strong activation ability towards the protein Keap1 and potential anti ROS effects based on the Keap1-Nrf2-ARE signaling pathway. This speculation is consistent with the data under Experiment 2.2. TLR2 (5D3I), iNOS (2Y37), and PI3K (1E7V) are important regulatory proteins for ROS and inflammation. In this molecular docking, their binding energies to sargentol were -7.7, -7.7, and -7.3 kcal/mol, respectively. Especially for the former, the binding strength exceeded that of the original ligand (-7.5 kcal/mol). Suggesting that sargentol may exert neuroprotective effects by inhibiting the oxidative stress inflammation oxidative stress cycle. In previous studies, it was found that sargentol can significantly inhibit ear swelling in mice, and its anti-inflammatory activity is consistent with the molecular docking prediction in this study. According to the binding energy, sargentol has a weak ability to inhibit excitotoxicity and regulate apoptosis genes. Future research will focus on the anti-inflammatory activity and mechanism of sargentol.