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

Codonopsis lanceolata has been widely used as an anti-inflammatory and anti-lipogenic agent in traditional medicine. Recently, C. lanceolata was reported to prevent hypertension by improving vascular function. This study evaluated the effects of C. lanceolata and its major component lancemaside A on cytosolic calcium concentration in vascular endothelial cells and vascular smooth muscle cells. Cytosolic calcium concentration was measured using fura-2 AM fluorescence. C. lanceolata or lancemaside A increased the cytosolic calcium concentration by releasing Ca2+ from the endoplasmic reticulum and sarcoplasmic reticulum and by Ca2+ entry into endothelial cells and vascular smooth muscle cells from extracellular sources. The C. lanceolata- and lancemaside A-induced cytosolic calcium concentration increases were significantly inhibited by lanthanum, an inhibitor of non-selective cation channels, in both endothelial cells and vascular smooth muscle cells. Moreover, C. lanceolata and lancemaside A significantly inhibited store-operated Ca2+ entry under pathological extracellular Ca2+ levels. In Ca2+-free extracellular fluid, increases in the cytosolic calcium concentration induced by C. lanceolata or lancemaside A were significantly inhibited by U73122, an inhibitor of phospholipase C, and 2-APB, an inositol 1,4,5-trisphosphate receptor antagonist. In addition, dantrolene treatment, which inhibits Ca2+ release through ryanodine receptor channels, also inhibited C. lanceolata- or lancemaside A-induced increases in the cytosolic calcium concentration through the phospholipase C/inositol 1,4,5-trisphosphate pathway. These results suggest that C. lanceolata and lancemaside A increase the cytosolic calcium concentration through the non-selective cation channels and phospholipase C/inositol 1,4,5-trisphosphate pathways under physiological conditions and inhibit store-operated Ca2+ entry under pathological conditions in endothelial cells and vascular smooth muscle cells. C. lanceolata or lancemaside A can protect endothelial cells and vascular smooth muscle cells by maintaining cytosolic calcium concentration homeostasis, suggesting possible applications for these materials in diets for preventing vascular damage.

Beneficial effects of Codonopsis lanceolata extract on systolic blood pressure levels in prehypertensive adults: A double-blind, randomized controlled trial.

Codonopsis lanceolata (CL) extract was shown to have antihypertensive effects in hypertensive rats. This randomized controlled trial was designed to investigate the ability of CL extract to prevent hypertension (HTN) in prehypertensive subjects. Eighty subjects aged 19-60 years with a systolic blood pressure (BP) of 120-139 mmHg and a diastolic BP of 80-89 mmHg were recruited over 3 months. Subjects were randomized 1:1 to a CL group and a placebo (PL) group and administered CL extract and starch, respectively, for 6 weeks. (BP) was measured and blood sampled at baseline and at the end of the trial. Relative to baseline, systolic BP was significantly decreased, and catalase activity was significantly increased following CL treatment in both the elevated systolic BP and stage 1 HTN subgroups. In the elevated systolic BP subgroup, serum nitrite concentration relative to baseline was significantly increased in CL compared to PL treated subjects (p = .038). In subjects with stage 1 HTN, high sensitivity C-reactive protein (p = .020) and malondialdehyde (p = .039) showed significantly greater reductions from baseline in the CL than in the PL group. In summary, CL was effective in preventing endothelial dysfunction, inflammation, and lipid peroxidation in prehypertensive subjects, with these effects differing according to baseline systolic BP levels.

Codonopsis lanceolata extract prevents hypertension in rats.

BACKGROUND: Codonopsis lanceolata, a plant with antioxidant, anti-cancer, anti-inflammatory and blood lipid improving effects, has been widely used as a therapeutic agent in traditional medicine. PURPOSE: The present study investigated the ability of an ethanol extract of Codonopsis lanceolata (ECL) to prevent hypertension in hypertensive rats. METHODS: Rats were orally administered daily doses of 0 mg/kg, 200 mg/kg and 400 mg/kg ECL for 3 weeks. As a positive control, rats were orally administered 10 mg/kg/day nifedipine. Hypertension was induced by immobilization stress for 2 h/day and by administration of 0.8 mg/kg/day nicotine for 3 weeks, followed by injection of 3 mg/kg nicotine on the day of sacrifice. Blood pressure and heart rate were measured using a volume pressure recording system. Vasoconstriction and vasodilation of aortic cross sections were measured with a physiological recorder. Neutrophil counts in bronchoalveolar lavage fluid were estimated with an automated cell counter. RESULTS: Treatment with both dosages of ECL significantly reduced systolic blood pressure (SBP) in hypertensive rats. Both doses of ECL tended to increase ACh- and SNP-induced vascular relaxation in hypertensive rats. Treatment with 200 mg/kg ECL significantly reduced neutrophil in hypertensive rats. CONCLUSIONS: These results suggest that ECL is effective in reducing SBP and inflammation in hypertensive conditions.

Foeniculum vulgare Mill. increases cytosolic Ca2+ concentration and inhibits store-operated Ca2+ entry in vascular endothelial cells.

This study assessed the effects of essential oil of Foeniculum vulgare Mill. (fennel oil) and of trans-anethole, the main component of fennel oil, on extracellular Ca2+-induced store-operated Ca2+ entry (SOCE) into vascular endothelial (EA) cells and their mechanisms of action. Components of fennel oil were analyzed by gas chromatography-mass spectrometry. Cytosolic Ca2+ concentration ([Ca2+]c) in EA cells was determined using Fura-2 fluorescence. In the presence of extracellular Ca2+, fennel oil significantly increased [Ca2+]c in EA cells; this increase was significantly inhibited by the Ca2+ channel blockers La3+ and nifedipine. In contrast, fennel oil induced [Ca2+]c was significantly lower in Ca2+-free solution, suggesting that fennel oil increases [Ca2+]c mainly by enhancing Ca2+ influx into EA cells. [Ca2+]c mobilization by trans-anethole was similar to that of fennel oil. Moreover, SOCE was suppressed by fennel oil and trans-anethole. SOCE was also attenuated by lanthanum (La3+), a non-selective cation channel (NSC) blocker; 2-aminoethoxydiphenyl borane (2-APB), an inositol 1,4,5-triphosphate (IP3) receptor inhibitor and SOCE blocker; and U73122, an inhibitor of phospholipase C (PLC). Further, SOCE was more strongly inhibited by La3+ plus fennel oil or trans-anethole than by La3+ alone. These findings suggest that fennel oil and trans-anethole significantly inhibit SOCE-induced [Ca2+]c increase in vascular endothelial cells and that these reactions may be mediated by NSC, IP3-dependent Ca2+ mobilization, and PLC activation.