期刊
PHARMACEUTICAL BIOLOGY
卷 61, 期 1, 页码 1175-1185出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/13880209.2023.2244176
关键词
Dyskinesia; neurotransmitters; dopaminergic neurons; nardosinone; molecular docking; oxidative stress; neuroinflammation; >
The combination of Nardostachys jatamansi (NJ) and levodopa has a synergistic effect in alleviating Parkinson's disease (PD), which is achieved by activating the Nrf2 pathway and inhibiting oxidative stress and the NLRP3 pathway.
Context Levodopa combined with traditional Chinese medicine has a synergistic effect on Parkinson's disease (PD). Recently, we demonstrated that Nardostachys jatamansi (D. Don) DC. [syn. Patrinia jatamansi D.Don, N. grandiflora DC.] (Valerianaceae) (NJ) can alleviate PD. Objective To explore the synergistic effect of NJ combined with levodopa against PD. Materials and methods The PD model was established by injecting rotenone. Eighty-four Sprague-Dawley rats were randomly divided into seven groups: sham, model, different doses of NJ (0.31, 0.62, or 1.24 g/kg) combined with levodopa (25 mg/kg), and levodopa alone (25 and 50 mg/kg) groups. The synergistic effect of the combination was investigated by pharmacodynamic investigation and detection of expression of nuclear factor erythro2-related factor 2 (Nrf2) and NLR family proteins containing Pyrin-related domain 3 (NLRP3) pathways. Results Compared with the model group, NJ + levodopa (1.24 g/kg + 25 mg/kg) increased the moving distance of PD rats in the open field (2395.34 & PLUSMN; 668.73 vs. 1501.41 & PLUSMN; 870.23, p < 0.01), enhanced the stay time on the rotating rod (84.86 & PLUSMN; 18.15 vs. 71.36 & PLUSMN; 17.53, p < 0.01) and the combination was superior to other treatments. The synergistic effects were related to NJ + levodopa (1.24 g/kg + 25 mg/kg) increasing the neurotransmitter levels by 38.80%-88.67% in PD rats, and inhibiting oxidative stress and NLRP3 pathway by activating Nrf2 pathway. Discussion and conclusions NJ combined with levodopa is a promising therapeutic candidate for PD, which provides a scientific basis for the subsequent clinical combination therapy of levodopa to enhance the anti-PD effect.
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