Lancemaside A from Codonopsis lanceolata prevents hypertension by inhibiting NADPH oxidase 2-mediated MAPK signalling and improving NO bioavailability in rats

Abstract

Shin and Han contributed equally to this work. AbstractObjectives This study investigated whether lancemaside A (LMA) can prevent hypertension and assessed the mechanisms of action of LMA in rats. Methods Hypertension was induced by chronic immobilization stress and nicotine administration. Hypertensive vehicle rats were treated with LMA (1, 20, or 40 mg/kg) or nifedipine (10 mg/kg) as a positive control daily for 3 weeks. Key findings In hypertensive vehicle rats, LMA dose-dependently reduced systolic blood pressure. LMA doses of 20 and 40 mg/kg reduced the aortic expression of nicotinamide adenine dinucleotide phosphate oxidase (NOX)2 (both P < 0.01), and 40 mg/kg LMA reduced serum malondialdehyde (P < 0.01). Serum nitrite levels were significantly higher in LMA treated rats than in hypertensive vehicle rats, with LMA doses of 20 and 40 mg/kg reducing the expression of endothelial nitric oxide synthase in rat aortas (P < 0.001 and P < 0.01, respectively). LMA also reduced the aortic levels of nuclear factor kappa B and the activation of the three isoforms of mitogen-activated protein kinase (MAPK). Conclusions Lancemaside A prevents hypertension in rats by inhibiting the activation of MAPK signalling and the impairment in nitric oxide bioavailability due to NOX2-mediated oxidative stress. Thus, LMA may act as a preventive agent for hypertension.

Codonopsis lanceolata Contributes to Ca2+ Homeostasis by Mediating SOCE and PLC/IP3 Pathways in Vascular Endothelial and Smooth Muscle Cells

“…Previous studies have shown that CL and LMA have antioxidant [14] and anti-inflammatory effects [11] and even antihypertensive effects [15,16]. In addition, the findings that CL and LMA reduce peripheral resistance [15] or improve vascular endothelial function [17]…”

“…In addition, in prehypertensive adults, CL has been shown to reduce blood pressure by improving serum nitrite and catalase activity and reducing high-sensitivity C-reactive protein and malondialdehyde [16]. LMA has also been reported to exert an antihypertensive effect by increasing the bioavailability of nitric oxide through the inhibition of nicotinamide adenine dinucleotide phosphate oxidase 2 [17]. Additionally, LMA enhances nitric oxide synthesis in human umbilical vein endothelial cells [18].…”

A systematic review of the mechanism of action and potential medicinal value of codonopsis pilosula in diseases

“…In addition to CPPs, which are the main constituents and the most abundantly studied active ingredients in the last 5 years, Lobetyolin, lancemaside A, Saponins, Luteolin, Alkaloids and other constituents have also been studied by researchers. Among the diseases related to the action of these active ingredients ( Table 2 ), Lobetyolin ( He et al, 2020 ; Cheng et al, 2023 ), Luteolin ( Yu et al, 2023 ; Liu et al, 2024 ), polyacetylenes ( Wang M.-C. et al, 2022 ), Isorhamnetin ( Luan et al, 2019 ) and molecule compound D6 ( Tang X. et al, 2021 ) mainly act in the treatment of cancer, saponins act in digestive diseases ( Liu X. F. et al, 2021 ; Li et al, 2023 ), lancemaside A ( Lee et al, 2019 ; Shin et al, 2019 ) and atractylodesin III( Cao M. et al, 2019 ) act in cardiovascular diseases. In addition, in a mouse model of non-alcoholic fatty liver disease (NAFLD), Alkaloids attenuate lipid deposition in NAFLD by improving energy metabolism, reducing oxidative stress and endoplasmic reticulum stress, and thus act as hepatoprotective agents ( Fan C. et al, 2023 ).…”

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“…Kidney and testes were prepared for histopathatologic evaluation by fixing in a 10% solution of formalin and subsequently embedding the tissues in paraffin wax. Thereafter, the paraffin wax embedded tissues were sectioned, stained with Haematoxylin and Eosin, and examined microscopically (Shin et al, 2019).…”