Blood pressure-reducing activity of Gongronema latifolium Benth. (Apocynaeceae) and the identification of its main phytochemicals by UHPLC Q-Orbitrap mass spectrometry
Justin Atiang BeshelJavier PalaciosFavour Nyoh BeshelC. O. NkuDaniel Udofia OwuMagdalene NwokochaJorge BórquezMario J. SimirgiotisChukwuemeka R. Nwokocha
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Abstract Background Gongronema latifolium Benth. (family Apocynaceae ) leaves ( GL ) has interesting medicinal properties. The effects of extracts from G. latifolium on blood pressure (BP) and the possible mechanisms of action were also investigated. Methods The ultrahigh resolution liquid chromatography orbitrap MS analysis was used to identify the phytochemicals present. Normotensive Wistar rats were anesthetized with sodium pentobarbitone (40 mg/kg) intraperitoneally, and the jugular vein was cannulated for infusion of drugs while the carotid artery was cannulated for direct BP measurement. GL extract (5–20 mg) alone or with nifedipine (10 mg/kg), atropine (2 mg/kg), L-NAME (5 mg/kg), methyl blue (3 mg/kg) and propranolol (1 mg/kg) were administered intravenously to Wistar rats and direct BP measurements were carried out. Results Systolic and diastolic BP levels (128/90 mm Hg; MAP 103 ± 3 mm Hg) and heart rates were all significantly (p < 0.01) decreased after GL administration. Raised mean arterial pressure (MAP) and heart rate by atropine, L-NAME and methyl blue were significantly (p < 0.01) reduced after GL administration, while propranolol significantly (p < 0.01) inhibited hypotension caused by GL. Infusion of GL reduced MAP (95 ± 3 mm Hg) comparable with nifedipine (93 ± 2 mm Hg), a calcium channel blocker. The phytochemicals identified were 34 compounds, including oleanolic acid derivatives, flavonoids, antioxidant fatty acids, 2 coumarins and 2 iridoids. Conclusions These results suggest that G. latifolium has hypotensive properties mediated by the synergistic activity of the compounds, probably via the β-adrenergic blockade mechanism.Indocyanine Green
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Nitroglycerin (drug)
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Objective: To observe the hypotensive effect on DBP with nifedipine tardy-released tablets. Methods Eighty cases of hypertesion in the elderly were randomly divided mifedipine treatmental group and captopril group as control. Results The dffecti of nifedipine was siginficant than captopriil (P0.01).Condusions Nifedipine tardy-released tablet has certain valule in clinical treatment.
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AIM To compare the pharmacokinetics of nifedipine sustained release tablets and nifedipine tablets in healthy volunteers.METHODS Twelve healthy male volunteers were divided into two groups,and received a single oral dose of nifedipine sustained release tablets and nifedipine tablets 20 mg,respectively.The plasma concentrations of nifedipine were determined by HPLC,and the pharmacokinetic parameters were calculated by DAS 2.1 software.RESULTS The pharmacokinetic parameters of nifedipine sustained release tablets and nifedipine tablets were as follows:ρmax were(1 247.8 ± 78.4)μg·L-1 and(1 896.7 ± 109.2)μg·L-1,tmax were(4.6 ± 0.7)h and(2.6 ± 0.9)h,t1/2 were(8.6 ± 2.8)h and(4.8 ± 1.5)h,AUC0-∞ were(5 879.3 ± 176.2)μg·h·L-1 and(3 724.9 ± 121.3)μg·h·L-1,AUC0-t were(4 427.8 ± 131.7)μg·h·L-1 and(2 936.5 ± 75.4)μg·h·L-1 respectively.The tmax and t1/2 of nifedipine sustained release tablets were significantly longer than that of nifedipine tablets,AUC0-t and AUC0-∞ were significantly higher than that of the nifedipine tablets,and ρmax was significantly lower than that of nifedipine tablets.CONCLUSION The nifedipine sustained release tablets have the sustained-release characteristics.
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ObjectiveTo invitro.MethodsPrimarily 在齿龈的成纤维细胞在骨胶原的表示上调查 nifedipine (钙隧道阻滞物) 的效果齿龈的成纤维细胞与 nifedipine (108 μ g/L， 360 μ g /L 和 1200 μ g /L ) 的各种各样的集中有教养、孵化 5 天了。齿龈的成纤维细胞主要是有教养的面对 360 μ g /L nifedipine 源于 nifedipine 应答者和非应答者。连接酶的免疫吸着剂试金被用来评估类型的数量我骨胶原。房间增长被房间与计算骨胶原的 MTT value.ResultsThe 表达式数测量，房间增长在第五天在高集中组和其它之中是显著地不同的，在 360 μg /L 和 1200 个 μg /L 组特别更高、在应答者和骨胶原和房间增长的 non-responders.ConclusionThe 表示可以涉及的 nifedipine 之中也不同为齿龈的增生的生物机制。
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Background: Cyclosporin A and nifedipine cause gingival overgrowth in rat, and the combined use of these drugs increases the overgrowth severity. Objective: The purpose of this study was to compare gingival overgrowth of rats of differents ages treated with cyclosporin A and nifedipine alone or given concurrently. Materials and methods: Rats 15, 30, 60 and 90 d old were treated with 10 mg/kg body weight of cyclosporin A and/or 50 mg/kg body weight of nifedipine in the chow. Results: Young rats showed evident gingival overgrowth with nifedipine, cyclosporin A, and cyclosporin A and nifedipine given concurrently. Adult rats did not show significant gingival alterations when treated with cyclosporin A and nifedipine alone. Nevertheless evident gingival overgrowth with alterations of the epithelium and connective tissue were observed when treated simultaneously with cyclosporin A and nifedipine. Conclusion: These results suggest that the combined effects of cyclosporin A and nifedipine on gingival overgrowth in rat is not age dependent.
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Gingival enlargement is usually noted within one to two months after the initiation of nifedipine therapy. The aetiology of nifedipine-induced gingival overgrowth is uncertain. The aim of this study was to determine the relationship between plasma and gingival crevice fluid (GCF) nifedipine concentrations and the degree of gingival overgrowth in patients treated with nifedipine, and also to assess the correlations between clinical and pharmacological variables.Eighteen patients taking nifedipine in regular doses for at least six months participated in the study. Gingival enlargement was evaluated with two indices to score vertical and horizontal overgrowth. Gingival index (GI), plaque index (PI), gingival bleeding time index (GBTI), probing depth (PD) and clinical attachment level (CAL) were also evaluated. GCF and plasma nifedipine concentrations were determined by using high performance liquid chromatography.There was no significant difference between responders and non-responders for PI, GI and GBTI. The mean concentration of nifedipine in GCF was significantly greater than concentration in plasma. No significant difference was observed for GCF and plasma nifedipine concentration between responders and non-responders.The present study showed that neither GCF nor plasma nifedipine levels appeared to be a risk factor for nifedipine-induced gingival overgrowth. Improving the oral hygiene in patients using nifedipine may help control the degree of drug-induced gingival enlargement.
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Etiology
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Objective To study the prevalence of gingival overgrowth in patients induced by nifedipine. Methods 75 patients treated with nifedipine were periodontally examined while 134 other patients without the agent were regarded as controls. Results The prevalence of gingival overgrowth in the group of nifedipine was significantly higher than that of the controls. Conclusion It is suggested that nifedipine is a risk factor inducing gingival overgrowth.
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