(±)-Praeruptorin A (PA) is the di-esterified product of ciskhellactone (CKL) and the major active ingredient in Peucedani Radix and exhibits dramatically anti-hypertensive effect typically through acting as a calcium channel blocker. (±)-Praeruptorin A is revealed anti-inflammatory activity typically by inhibiting the activation of NF-B pathway[1]. (±)-Praeruptorin A also shows great therapeutic potential for the treatment of allergic asthma[2].
In vitro, (±)-Praeruptorin A (0-40μM; 24h) dose-dependently inhibited the LPS (1μg/mL)-induced increases in the mRNA and protein expression levels of inflammatory factors, including TNF-α, IL-1β, IL-6, IL-8, MCP-2, and VCAM-1, in HUVECs[3]. (±)-Praeruptorin A (0-50μM; 24h) dose-dependently inhibited the proliferation, migration, and invasion of HeLa and SiHa cells, accompanied by the downregulation of Matrix Metalloproteinase-2 (MMP-2) and Extracellular signal-Regulated Kinase 1/2 (ERK1/2) signaling-related expression[4]. (±)-Praeruptorin A (0-30μM; 24h) dose-dependently inhibited the migration and invasion of hepatocellular carcinoma cell[5].
In vivo, treatment with (±)-Praeruptorin A (30, 60, 120mg/kg/d; p.o.; 5 days) dose-dependently reduced airway hyperresponsiveness and eosinophilic airway inflammation in mice with allergic asthma, improved lung pathological injury, decreased the levels of interleukin (IL)-4, IL-5, IL-13, and LTC4 in bronchoalveolar lavage fluid as well as serum immunoglobulin E (IgE) levels, and inhibited pulmonary eotaxin production and mRNA expression, IκBα degradation, NF-κB nuclear translocation, NF-κB DNA-binding activity, and RelA/p65 phosphorylation[6]. (±)-Praeruptorin A (2mg/kg; i.v.; once) reduced serum IL-6 levels and the expression of Fas, Bax, and Bcl-2, increased the Bcl-2/Bax ratio, and alleviated inflammatory cell infiltration in rats subjected to 30min of ischemia followed by 120min of reperfusion[7].
References:
[1] Song, Yue-Lin et al. “Metabolic characterization of (±)-praeruptorin A in vitro and in vivo by high performance liquid chromatography coupled with hybrid triple quadrupole-linear ion trap mass spectrometry and time-of-flight mass spectrometry.” Journal of pharmaceutical and biomedical analysis vol. 90 (2014): 98-110.
[2] Xiong, Youyi et al. “Effects of (±)-praeruptorin A on airway inflammation, airway hyperresponsiveness and NF-κB signaling pathway in a mouse model of allergic airway disease.” European journal of pharmacology vol. 683,1-3 (2012): 316-24.
[3] Chang H, Zhang J, Yang C, Qi Z. Pd-Ia exerts anti-inflammatory effects by activating PPAR-α in human umbilical vein endothelial cells. J Transl Sci. 2019;5:1-7.
[4] Wu, Min-Hua et al. “Praeruptorin A Inhibits Human Cervical Cancer Cell Growth and Invasion by Suppressing MMP-2 Expression and ERK1/2 Signaling.” International journal of molecular sciences vol. 19,1 10. 21 Dec. 2017.
[5] Wang, Qiongxiao et al. “The traditional uses, pharmacology, and phytochemistry of Peucedanum praeruptorum Dunn.” Frontiers in pharmacology vol. 15 1352657. 3 Apr. 2024.
[6] Xiong, Youyi et al. “Effects of (±)-praeruptorin A on airway inflammation, airway hyperresponsiveness and NF-κB signaling pathway in a mouse model of allergic airway disease.” European journal of pharmacology vol. 683,1-3 (2012): 316-24.
[7] Chang, Tian-Hui et al. “Effects of dl-praeruptorin A on interleukin-6 level and Fas, bax, bcl-2 protein expression in ischemia-reperfusion myocardium.” Acta pharmacologica Sinica vol. 23,9 (2002): 769-74.