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Published in: BMC Complementary Medicine and Therapies 1/2019

Open Access 01-12-2019 | Hypertension | Research article

Lancemaside A, a major triterpene saponin of Codonopsis lanceolata enhances regulation of nitric oxide synthesis via eNOS activation

Authors: Young Seok Lee, HeeEun Kim, Jinhye Kim, Geun Hee Seol, Kwang-Won Lee

Published in: BMC Complementary Medicine and Therapies | Issue 1/2019

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Abstract

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 13C-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.
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Literature
1.
go back to reference Lee YG, Kim JY, Lee JY, Byeon SE, Hong EK, Lee J, et al. Regulatory effects of Codonopsis lanceolata on macrophage-mediated immune responses. J Ethnopharmacol. 2007;112:180–8.CrossRefPubMed Lee YG, Kim JY, Lee JY, Byeon SE, Hong EK, Lee J, et al. Regulatory effects of Codonopsis lanceolata on macrophage-mediated immune responses. J Ethnopharmacol. 2007;112:180–8.CrossRefPubMed
2.
go back to reference Lee J-H. Immunostimulative effect of hot-water extract from Codonopsis lanceolata on lymphocyte and clonal macrophage. Korean J Food Sci Technol. 2002;34:732–6. Lee J-H. Immunostimulative effect of hot-water extract from Codonopsis lanceolata on lymphocyte and clonal macrophage. Korean J Food Sci Technol. 2002;34:732–6.
3.
go back to reference Cho K, Kim S-J, Park S-H, Kim S, Park T. Protective effect of Codonopsis lanceolata root extract against alcoholic fatty liver in the rat. J Med Food. 2009;12(6):1293–301.CrossRefPubMed Cho K, Kim S-J, Park S-H, Kim S, Park T. Protective effect of Codonopsis lanceolata root extract against alcoholic fatty liver in the rat. J Med Food. 2009;12(6):1293–301.CrossRefPubMed
4.
go back to reference Kim MH, Lee J, Yoo DS, Lee YG, Byeon SE, Hong EK, et al. Protective effect of stress-induced liver damage by saponin fraction from Codonopsis lanceolata. Arch Pharm Res. 2009;32:1441–6.CrossRefPubMed Kim MH, Lee J, Yoo DS, Lee YG, Byeon SE, Hong EK, et al. Protective effect of stress-induced liver damage by saponin fraction from Codonopsis lanceolata. Arch Pharm Res. 2009;32:1441–6.CrossRefPubMed
5.
go back to reference Choi H-K, Won E-K, Jang YP, Choung S-Y. Antiobesity effect of Codonopsis lanceolata in high-calorie/high-fat-diet-induced obese rats. Evid-Based Compl Alt. 2013;2013. Choi H-K, Won E-K, Jang YP, Choung S-Y. Antiobesity effect of Codonopsis lanceolata in high-calorie/high-fat-diet-induced obese rats. Evid-Based Compl Alt. 2013;2013.
6.
go back to reference Han C, Li L, Piao K, Shen Y, Piao Y. Experimental study on anti-oxygen and promoting intelligence development of Codonopsis lanceolata in old mice. J Chinese Med Mater. 1999;22:136–8. Han C, Li L, Piao K, Shen Y, Piao Y. Experimental study on anti-oxygen and promoting intelligence development of Codonopsis lanceolata in old mice. J Chinese Med Mater. 1999;22:136–8.
7.
go back to reference Weon JB, Lee B, Yun B-R, Lee J, Lee HY, Park D-S, et al. Memory enhancing effect of Codonopsis lanceolata by high hydrostatic pressure process and fermentation. Korean J Pharmacogn. 2013;44:41–6. Weon JB, Lee B, Yun B-R, Lee J, Lee HY, Park D-S, et al. Memory enhancing effect of Codonopsis lanceolata by high hydrostatic pressure process and fermentation. Korean J Pharmacogn. 2013;44:41–6.
8.
go back to reference Cho Y, Kim S, Yoon H, Hong S, Ko H, Park E, et al. Anti-tumor effects of Codonopsis lanceolata extracts on human lung and ovarian cancer. Food Eng Prog. 2011. Cho Y, Kim S, Yoon H, Hong S, Ko H, Park E, et al. Anti-tumor effects of Codonopsis lanceolata extracts on human lung and ovarian cancer. Food Eng Prog. 2011.
9.
go back to reference Ichikawa M, Ohta S, Komoto N, Ushijima M, Kodera Y, Hayama M, et al. Simultaneous determination of seven saponins in the roots of Codonopsis lanceolata by liquid chromatography–mass spectrometry. J Nat Med. 2009;63(1):52–7.CrossRefPubMed Ichikawa M, Ohta S, Komoto N, Ushijima M, Kodera Y, Hayama M, et al. Simultaneous determination of seven saponins in the roots of Codonopsis lanceolata by liquid chromatography–mass spectrometry. J Nat Med. 2009;63(1):52–7.CrossRefPubMed
10.
go back to reference Simeonova R, Vitcheva V, Kondeva-Burdina M, Krasteva I, Nikolov S, Mitcheva M. Effect of purified saponin mixture from Astragalus corniculatus on enzyme-and non-enzyme-induced lipid peroxidation in liver microsomes from spontaneously hypertensive rats and normotensive rats. Phytomedicine. 2010;17(5):346–9.CrossRefPubMed Simeonova R, Vitcheva V, Kondeva-Burdina M, Krasteva I, Nikolov S, Mitcheva M. Effect of purified saponin mixture from Astragalus corniculatus on enzyme-and non-enzyme-induced lipid peroxidation in liver microsomes from spontaneously hypertensive rats and normotensive rats. Phytomedicine. 2010;17(5):346–9.CrossRefPubMed
11.
go back to reference Pan C, Huo Y, An X, Singh G, Chen M, Yang Z, et al. Panax notoginseng and its components decreased hypertension via stimulation of endothelial-dependent vessel dilatation. Curr Vasc Pharmacol. 2012;56(3):150–8.CrossRef Pan C, Huo Y, An X, Singh G, Chen M, Yang Z, et al. Panax notoginseng and its components decreased hypertension via stimulation of endothelial-dependent vessel dilatation. Curr Vasc Pharmacol. 2012;56(3):150–8.CrossRef
12.
go back to reference Hiwatashi K, Shirakawa H, Hori K, Yoshiki Y, Suzuki N, Hokari M, et al. Reduction of blood pressure by soybean saponins, renin inhibitors from soybean, in spontaneously hypertensive rats. Biosci Biotechnol Biochem. 2010;74(11):2310–2.CrossRefPubMed Hiwatashi K, Shirakawa H, Hori K, Yoshiki Y, Suzuki N, Hokari M, et al. Reduction of blood pressure by soybean saponins, renin inhibitors from soybean, in spontaneously hypertensive rats. Biosci Biotechnol Biochem. 2010;74(11):2310–2.CrossRefPubMed
13.
go back to reference Han AY, Lee YS, Kwon S, Lee HS, Lee KW, Seol GH. Codonopsis lanceolata extract prevents hypertension in rats. Phytomedicine. 2018;39:119–24.CrossRefPubMed Han AY, Lee YS, Kwon S, Lee HS, Lee KW, Seol GH. Codonopsis lanceolata extract prevents hypertension in rats. Phytomedicine. 2018;39:119–24.CrossRefPubMed
14.
go back to reference Kim E, Yang WS, Kim JH, Park JG, Kim HG, Ko J, et al. Lancemaside A from Codonopsis lanceolata modulates the inflammatory responses mediated by monocytes and macrophages. Mediat Inflamm. 2014;2014. Kim E, Yang WS, Kim JH, Park JG, Kim HG, Ko J, et al. Lancemaside A from Codonopsis lanceolata modulates the inflammatory responses mediated by monocytes and macrophages. Mediat Inflamm. 2014;2014.
15.
go back to reference Joh E-H, Lee I-A, Han S-J, Chae S, Kim D-H. Lancemaside A ameliorates colitis by inhibiting NF-κB activation in TNBS-induced colitis mice. Int J Color Dis. 2010;25(5):545–51.CrossRef Joh E-H, Lee I-A, Han S-J, Chae S, Kim D-H. Lancemaside A ameliorates colitis by inhibiting NF-κB activation in TNBS-induced colitis mice. Int J Color Dis. 2010;25(5):545–51.CrossRef
16.
go back to reference Jeong Y-H, Jung J-S, Van Le TK, Kim D-H, Kim H-S. Lancemaside A inhibits microglial activation via modulation of JNK signaling pathway. Biochem Biophys Res Commun. 2013;431:369–75.CrossRefPubMed Jeong Y-H, Jung J-S, Van Le TK, Kim D-H, Kim H-S. Lancemaside A inhibits microglial activation via modulation of JNK signaling pathway. Biochem Biophys Res Commun. 2013;431:369–75.CrossRefPubMed
17.
go back to reference Li X, Li J, Li Z, Sang Y, Niu Y, Zhang Q, et al. Fucoidan from Undaria pinnatifida prevents vascular dysfunction through PI3K/Akt/eNOS-dependent mechanisms in the L-NAME-induced hypertensive rat model. Food Funct. 2016;7:2398–408.CrossRefPubMed Li X, Li J, Li Z, Sang Y, Niu Y, Zhang Q, et al. Fucoidan from Undaria pinnatifida prevents vascular dysfunction through PI3K/Akt/eNOS-dependent mechanisms in the L-NAME-induced hypertensive rat model. Food Funct. 2016;7:2398–408.CrossRefPubMed
18.
go back to reference Kobayashi N, Ohno T, Yoshida K, Fukushima H, Mamada Y, Nomura M, et al. Cardioprotective mechanism of telmisartan via PPAR-gamma-eNOS pathway in dahl salt-sensitive hypertensive rats. Am J Hypertens. 2008;21:576–81.CrossRefPubMed Kobayashi N, Ohno T, Yoshida K, Fukushima H, Mamada Y, Nomura M, et al. Cardioprotective mechanism of telmisartan via PPAR-gamma-eNOS pathway in dahl salt-sensitive hypertensive rats. Am J Hypertens. 2008;21:576–81.CrossRefPubMed
19.
go back to reference Urano T, Ito Y, Akao M, Sawa T, Miyata K, Tabata M, et al. Angiopoietin-related growth factor enhances blood flow via activation of the ERK1/2-eNOS-NO pathway in a mouse hind-limb ischemia model. Arterioscler Thromb Vasc Biol. 2008;28(5):827–34.CrossRefPubMed Urano T, Ito Y, Akao M, Sawa T, Miyata K, Tabata M, et al. Angiopoietin-related growth factor enhances blood flow via activation of the ERK1/2-eNOS-NO pathway in a mouse hind-limb ischemia model. Arterioscler Thromb Vasc Biol. 2008;28(5):827–34.CrossRefPubMed
20.
go back to reference Lee SH, Lee YJ, Song CH, Ahn YK, Han HJ. Role of FAK phosphorylation in hypoxia-induced hMSCS migration: involvement of VEGF as well as MAPKS and eNOS pathways. Am J Physiol Cell Physiol. 2010;298:C847–56.CrossRefPubMed Lee SH, Lee YJ, Song CH, Ahn YK, Han HJ. Role of FAK phosphorylation in hypoxia-induced hMSCS migration: involvement of VEGF as well as MAPKS and eNOS pathways. Am J Physiol Cell Physiol. 2010;298:C847–56.CrossRefPubMed
21.
go back to reference Shiojima I, Walsh K. Role of Akt signaling in vascular homeostasis and angiogenesis. Circ Res. 2002;90:1243–50.CrossRefPubMed Shiojima I, Walsh K. Role of Akt signaling in vascular homeostasis and angiogenesis. Circ Res. 2002;90:1243–50.CrossRefPubMed
22.
go back to reference Lin MI, Fulton D, Babbitt R, Fleming I, Busse R, Pritchard KA, et al. Phosphorylation of threonine 497 in endothelial nitric-oxide synthase coordinates the coupling of L-arginine metabolism to efficient nitric oxide production. J Biol Chem. 2003;278:44719–26.CrossRefPubMed Lin MI, Fulton D, Babbitt R, Fleming I, Busse R, Pritchard KA, et al. Phosphorylation of threonine 497 in endothelial nitric-oxide synthase coordinates the coupling of L-arginine metabolism to efficient nitric oxide production. J Biol Chem. 2003;278:44719–26.CrossRefPubMed
23.
go back to reference Beleslin-Cokic BB, Cokic VP, Yu X, Weksler BB, Schechter AN, Noguchi CT. Erythropoietin and hypoxia stimulate erythropoietin receptor and nitric oxide production by endothelial cells. Blood. 2004;104:2073–80.CrossRefPubMed Beleslin-Cokic BB, Cokic VP, Yu X, Weksler BB, Schechter AN, Noguchi CT. Erythropoietin and hypoxia stimulate erythropoietin receptor and nitric oxide production by endothelial cells. Blood. 2004;104:2073–80.CrossRefPubMed
24.
go back to reference Xia T, Guan W, Fu J, Zou X, Han Y, Chen C, et al. Tirofiban induces vasorelaxation of the coronary artery via an endothelium-dependent NO-cGMP signaling by activating the PI3K/Akt/eNOS pathway. Biochem Biophys Res Commun. 2016;474:599–605.CrossRefPubMed Xia T, Guan W, Fu J, Zou X, Han Y, Chen C, et al. Tirofiban induces vasorelaxation of the coronary artery via an endothelium-dependent NO-cGMP signaling by activating the PI3K/Akt/eNOS pathway. Biochem Biophys Res Commun. 2016;474:599–605.CrossRefPubMed
25.
go back to reference Liu D-H, Chen Y-M, Liu Y, Hao B-S, Zhou B, Wu L, et al. Ginsenoside Rb1 reverses H2O2-induced senescence in human umbilical endothelial cells: involvement of eNOS pathway. J Cardiovasc Pharmacol Ther. 2012;59:222–30.CrossRef Liu D-H, Chen Y-M, Liu Y, Hao B-S, Zhou B, Wu L, et al. Ginsenoside Rb1 reverses H2O2-induced senescence in human umbilical endothelial cells: involvement of eNOS pathway. J Cardiovasc Pharmacol Ther. 2012;59:222–30.CrossRef
26.
go back to reference Leung KW, Cheng Y-K, Mak NK, Chan KK, David Fan T, Wong RN. Signaling pathway of ginsenoside-Rg1 leading to nitric oxide production in endothelial cells. FEBS Lett. 2006;580:3211–6.CrossRefPubMed Leung KW, Cheng Y-K, Mak NK, Chan KK, David Fan T, Wong RN. Signaling pathway of ginsenoside-Rg1 leading to nitric oxide production in endothelial cells. FEBS Lett. 2006;580:3211–6.CrossRefPubMed
27.
go back to reference Ushijima M, Komoto N, Sugizono Y, Mizuno I, Sumihiro M, Ichikawa M, et al. Triterpene glycosides from the roots of Codonopsis lanceolata. Chem Pharm Bull. 2008 Mar;56:308–14.CrossRefPubMed Ushijima M, Komoto N, Sugizono Y, Mizuno I, Sumihiro M, Ichikawa M, et al. Triterpene glycosides from the roots of Codonopsis lanceolata. Chem Pharm Bull. 2008 Mar;56:308–14.CrossRefPubMed
28.
go back to reference Du YE, Lee JS, Kim HM, Ahn J-H, Jung IH, Ryu JH, Choi, J-H, Jang DS. Chemical constituents of the roots of Codonopsis lanceolata. Arch Pharm Res. 2018;41:1082–1091.CrossRefPubMed Du YE, Lee JS, Kim HM, Ahn J-H, Jung IH, Ryu JH, Choi, J-H, Jang DS. Chemical constituents of the roots of Codonopsis lanceolata. Arch Pharm Res. 2018;41:1082–1091.CrossRefPubMed
29.
go back to reference Li J-P, Liang Z-M, Yuan Z. Triterpenoid saponins and anti-inflammatory activity of Codonopsis lanceolata. Pharmazie. 2007;62:463–6.PubMed Li J-P, Liang Z-M, Yuan Z. Triterpenoid saponins and anti-inflammatory activity of Codonopsis lanceolata. Pharmazie. 2007;62:463–6.PubMed
30.
go back to reference Hyam SR, Jang S-E, Jeong J-J, Joh E-H, Hand MJ, Kim D-H. Echinocystic acid, a metabolite of lancemaside A, inhibits TNBS-induced colitis in mice. Int Immunopharmacol. 2013;15:433–41.CrossRefPubMed Hyam SR, Jang S-E, Jeong J-J, Joh E-H, Hand MJ, Kim D-H. Echinocystic acid, a metabolite of lancemaside A, inhibits TNBS-induced colitis in mice. Int Immunopharmacol. 2013;15:433–41.CrossRefPubMed
31.
go back to reference Komoto N, Ichikawa M, Ohta S, Nakano D, Nishihama T, Ushijima M, et al. Murine metabolism and absorption of lancemaside A, an active compound in the roots of Codonopsis lanceolata. J Nat Med. 2010;64:321–9.CrossRefPubMed Komoto N, Ichikawa M, Ohta S, Nakano D, Nishihama T, Ushijima M, et al. Murine metabolism and absorption of lancemaside A, an active compound in the roots of Codonopsis lanceolata. J Nat Med. 2010;64:321–9.CrossRefPubMed
32.
go back to reference Ichikawa M, Ohta S, Komoto N, Ushijima M, Kodera Y, Hayama M, et al. Rapid identification of triterpenoid saponins in the roots of Codonopsis lanceolata by liquid chromatography-mass spectrometry. J Nat Med. 2008;62:423–9.CrossRefPubMed Ichikawa M, Ohta S, Komoto N, Ushijima M, Kodera Y, Hayama M, et al. Rapid identification of triterpenoid saponins in the roots of Codonopsis lanceolata by liquid chromatography-mass spectrometry. J Nat Med. 2008;62:423–9.CrossRefPubMed
33.
go back to reference Shirota O, Nagamatsu K, Sekita S, Komoto N, Kuroyanagi M, Ichikawa M, Ohta S, Ushijima M. Preparative separation of the saponin lancemaside A from Condonopsis lanceolata by centrifugal partition chromatography. Phytochem Anal. 2008;19:403–10.CrossRefPubMed Shirota O, Nagamatsu K, Sekita S, Komoto N, Kuroyanagi M, Ichikawa M, Ohta S, Ushijima M. Preparative separation of the saponin lancemaside A from Condonopsis lanceolata by centrifugal partition chromatography. Phytochem Anal. 2008;19:403–10.CrossRefPubMed
34.
go back to reference Han E, Cho S. Effect of Codonopsis lanceolata water extract on the activities of antioxidative enzymes in carbon tetracholoride treated rats. J Korean Soc Food Sci Nutr. 1997;26:1181–6. Han E, Cho S. Effect of Codonopsis lanceolata water extract on the activities of antioxidative enzymes in carbon tetracholoride treated rats. J Korean Soc Food Sci Nutr. 1997;26:1181–6.
35.
go back to reference Lee K-W, Jung H-J, Park H-J, Kim D-G, Lee J-Y, Lee K-T. Beta-D-xylopyranosyl-(1→3)-β-D-glucuronopyranosyl echinocystic acid isolated from the roots of Codonopsis lanceolata induces caspase-dependent apoptosis in human acute promyelocytic leukemia HL-60 cells. Biol Pharm Bull. 2005;28:854–9.CrossRefPubMed Lee K-W, Jung H-J, Park H-J, Kim D-G, Lee J-Y, Lee K-T. Beta-D-xylopyranosyl-(1→3)-β-D-glucuronopyranosyl echinocystic acid isolated from the roots of Codonopsis lanceolata induces caspase-dependent apoptosis in human acute promyelocytic leukemia HL-60 cells. Biol Pharm Bull. 2005;28:854–9.CrossRefPubMed
36.
go back to reference Xu L-P, Wang H, Yuan Z. Triterpenoid saponins with anti-inflammatory activity from Codonopsis lanceolata. Planta Med. 2008;74:1412–5.CrossRefPubMed Xu L-P, Wang H, Yuan Z. Triterpenoid saponins with anti-inflammatory activity from Codonopsis lanceolata. Planta Med. 2008;74:1412–5.CrossRefPubMed
37.
go back to reference Wang L, Xu ML, Hu JH, Rasmussen SK, Wang M-H. Codonopsis lanceolata extract induces G0/G1 arrest and apoptosis in human colon tumor HT-29 cells–involvement of ROS generation and polyamine depletion. Food Chem Toxicol. 2011;49:149–54.CrossRefPubMed Wang L, Xu ML, Hu JH, Rasmussen SK, Wang M-H. Codonopsis lanceolata extract induces G0/G1 arrest and apoptosis in human colon tumor HT-29 cells–involvement of ROS generation and polyamine depletion. Food Chem Toxicol. 2011;49:149–54.CrossRefPubMed
38.
go back to reference Byeon SE, Choi WS, Hong EK, Lee J, Rhee MH, Park H-J, et al. Inhibitory effect of saponin fraction from Codonopsis lanceolata on immune cell-mediated inflammatory responses. Arch Pharm Res. 2009;32:813–22.CrossRefPubMed Byeon SE, Choi WS, Hong EK, Lee J, Rhee MH, Park H-J, et al. Inhibitory effect of saponin fraction from Codonopsis lanceolata on immune cell-mediated inflammatory responses. Arch Pharm Res. 2009;32:813–22.CrossRefPubMed
39.
go back to reference Lee K-T, Choi J, Jung W-T, Nam J-H, Jung H-J, Park H-J. Structure of a new echinocystic acid bisdesmoside isolated from Codonopsis lanceolata roots and the cytotoxic activity of prosapogenins. J Agric Food Chem. 2002;50:4190–3.CrossRefPubMed Lee K-T, Choi J, Jung W-T, Nam J-H, Jung H-J, Park H-J. Structure of a new echinocystic acid bisdesmoside isolated from Codonopsis lanceolata roots and the cytotoxic activity of prosapogenins. J Agric Food Chem. 2002;50:4190–3.CrossRefPubMed
40.
go back to reference Joh EH, Kim DH. Lancemaside A inhibits lipopolysaccharide-induced inflammation by targeting LPS/TLR4 complex. J Cell Biochem. 2010;111:865–71.CrossRefPubMed Joh EH, Kim DH. Lancemaside A inhibits lipopolysaccharide-induced inflammation by targeting LPS/TLR4 complex. J Cell Biochem. 2010;111:865–71.CrossRefPubMed
41.
go back to reference Park H-J, Zhang Y, Georgescu SP, Johnson KL, Kong D, Galper JB. Human umbilical vein endothelial cells and human dermal microvascular endothelial cells offer new insights into the relationship between lipid metabolism and angiogenesis. Stem Cell Rev. 2006;2:93–101.CrossRefPubMed Park H-J, Zhang Y, Georgescu SP, Johnson KL, Kong D, Galper JB. Human umbilical vein endothelial cells and human dermal microvascular endothelial cells offer new insights into the relationship between lipid metabolism and angiogenesis. Stem Cell Rev. 2006;2:93–101.CrossRefPubMed
43.
go back to reference Gusarov I, Shatalin K, Starodubtseva M, Nudler E. Endogenous nitric oxide protects bacteria against a wide spectrum of antibiotics. Science. 2009;325:1380–4.CrossRefPubMedPubMedCentral Gusarov I, Shatalin K, Starodubtseva M, Nudler E. Endogenous nitric oxide protects bacteria against a wide spectrum of antibiotics. Science. 2009;325:1380–4.CrossRefPubMedPubMedCentral
44.
go back to reference Mukai Y, Sato S. Polyphenol-containing azuki bean (Vigna angularis) extract attenuates blood pressure elevation and modulates nitric oxide synthase and caveolin-1 expressions in rats with hypertension. Nutr Metab Cardiovasc Dis. 2009;19:491–7.CrossRefPubMed Mukai Y, Sato S. Polyphenol-containing azuki bean (Vigna angularis) extract attenuates blood pressure elevation and modulates nitric oxide synthase and caveolin-1 expressions in rats with hypertension. Nutr Metab Cardiovasc Dis. 2009;19:491–7.CrossRefPubMed
45.
go back to reference Huang PL, Huang Z, Mashimo H, Bloch KD. Hypertension in mice lacking the gene for endothelial nitric oxide synthase. Nature. 1995;377:239–42.CrossRefPubMed Huang PL, Huang Z, Mashimo H, Bloch KD. Hypertension in mice lacking the gene for endothelial nitric oxide synthase. Nature. 1995;377:239–42.CrossRefPubMed
46.
go back to reference Förstermann U, Münzel T. Endothelial nitric oxide synthase in vascular disease. Circulation. 2006;113(13):1708–14.CrossRefPubMed Förstermann U, Münzel T. Endothelial nitric oxide synthase in vascular disease. Circulation. 2006;113(13):1708–14.CrossRefPubMed
47.
go back to reference Taguchi K, Matsumoto T, Kamata K, Kobayashi T. Akt/eNOS pathway activation in endothelium-dependent relaxation is preserved in aortas from female, but not from male, type 2 diabetic mice. Pharmacol Res. 2012;65:56–65.CrossRefPubMed Taguchi K, Matsumoto T, Kamata K, Kobayashi T. Akt/eNOS pathway activation in endothelium-dependent relaxation is preserved in aortas from female, but not from male, type 2 diabetic mice. Pharmacol Res. 2012;65:56–65.CrossRefPubMed
Metadata
Title
Lancemaside A, a major triterpene saponin of Codonopsis lanceolata enhances regulation of nitric oxide synthesis via eNOS activation
Authors
Young Seok Lee
HeeEun Kim
Jinhye Kim
Geun Hee Seol
Kwang-Won Lee
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2019
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-019-2516-6

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