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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. To explore the synergistic effect of NJ combined with levodopa against PD. 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. 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 ± 668.73 vs. 1501.41 ± 870.23,  p  &lt; 0.01), enhanced the stay time on the rotating rod (84.86 ± 18.15 vs. 71.36 ± 17.53,  p  &lt; 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. 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.

pharmaceutical biology

Nardostachys jatamansi  and levodopa combination alleviates Parkinson’s disease symptoms in rats through activation of Nrf2 and inhibition of NLRP3 signaling pathways