Background
Many studies on the effect of saponin-rich
Codonopsis lanceolata
as a bioactive source for improving physical health have been performed.
C. lanceolata
contains triterpenoid saponins, including lancemasides. These saponins are known to be particularly involved in the regulation of blood pressure or hypertension. This study investigated whether lancemaside A (LA), a major triterpenoid saponin from
C. lanceolata
, regulates nitric oxide (NO) production via the activation of endothelial NO synthase (eNOS) in human umbilical vein endothelial cells.
Methods
Upon separation with petroleum ether, ethyl acetate, and
n
-butanol, LA was found to be abundant in the
n
-butanol-soluble portion. For further purification of LA, HPLC was performed to collect fraction, and LA was identified using analysis of LC/MSMS and
13
C-NMR values. In in vitro, the effects of LA on NO release mechanism in HUVECs were investigated by Griess assay, quantitative real-time reverse-transcription PCR, and Western blotting.
Results
Our results showed that NO production was efficiently improved by treatment with LA in a dose-dependent manner. In addition, the LA treatment resulted in extensive recovery of the NO production suppressed by the eNOS inhibitor, L-NAME, compared with that in the control group. Additionally, the level of eNOS mRNA was increased by this treatment in a dose-dependent manner. These results suggested that LA is an inducer of NO synthesis via eNOS mRNA expression. Also, the study indicated that LA is involved in activating the PI3K/Akt/eNOS signaling pathway.
Conclusion
These results suggested that LA is an inducer of NO synthesis via eNOS mRNA expression. Also, the study indicated that LA is involved in activating the PI3K/Akt/eNOS signaling pathway. These findings suggest the value of using LA as a component of functional foods and natural pharmaceuticals.
Electronic supplementary material
The online version of this article (10.1186/s12906-019-2516-6) contains supplementary material, which is available to authorized users.
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.
Hiatus hernia (HH) is prevalent in adults with pulmonary fibrosis. We hypothesized that HH would be associated with markers of lung inflammation and fibrosis among community-dwelling adults and stronger among MUC5B (rs35705950) risk allele carriers.In the Multi-Ethnic Study of Atherosclerosis, HH was assessed from cardiac and full-lung computed tomography (CT) scans performed at Exam 1 (2000–2002, n=3342) and Exam 5 (2010–2012, n=3091), respectively. Percentage of high attenuation areas (HAAs, % of voxels with attenuation between −600 and −250 Hounsfield units) was measured from cardiac and lung scans. Interstitial lung abnormalities (ILA) were examined from Exam 5 scans (n=2380). Regression models were used to examine the associations of HH with HAAs, ILA, serum matrix metalloproteinase-7, and adjusted for age, sex, race/ethnicity, educational attainment, smoking, height, weight, and scanner parameters for HAAs analysis.HH detected from Exam 5 scans was associated with a mean % difference in HAAs of 2.23% (95% CI 0.57–3.93) and an increase of 0.48% increase/year (95% CI 0.07–0.89), particularly in MUC5B risk allele carriers (p-value for interaction=0.02). HH was associated with ILA among those younger than 80 years of age (odds ratio for ILA 1.78, 95% CI 1.14–2.80) and higher serum matrix metalloproteinase-7 level among smokers (p-value for interaction=0.04).Hiatus hernia was associated with more HAAs over time, particularly among MUC5B risk allele carriers, and ILA in younger adults and may be a risk factor in the early stages of interstitial lung disease.
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