Blood pressure lowering effect and vascular activity of Phyllanthus niruri extract: The role of NO/cGMP signaling pathway and beta-adrenoceptor mediated relaxation of isolated aortic rings
JOURNAL OF ETHNOPHARMACOLOGY
Authors: Bello, Idris; Usman, Nasiba Salisu; Dewa, Aidiahmad; Abubakar, Kabiru; Aminu, Nafiu; Asmawi, Mohd Zaini; Mahmud, Roziahanim
Abstract
Ethnopharmacological relevance: Phyllanthus niruri have a long history of use in the traditional treatment of various ailments including hypertension. Literature reports have indicated that it is a potent antihypertensive herbal medication used traditionally. Aim of the study: This study was carried out to investigate the antihypertensive and vasodilatory activity of four solvents extracts of P. niruri namely; petroleum ether (PEPN), chloroform (CLPN), methanol (MEPN) and water (WEPN), with the aim of elucidating the mechanism of action and identifying the phytochemical constituents. Materials and methods: Male Spontaneous Hypertensive Rats (SHRs) were given oral gavage of P. niruri extract daily for two weeks and the blood pressure was recorded in vivo. We also determine the vasodilation effect of the extracts on rings of isolated thoracic aorta pre-contracted with phenylephrine (PE, 1 mu M). Endothelium-intact or endothelium-denuded aorta rings were pre-incubated with various antagonists like 1H-(1,2,4] oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ, 10 mu M) and Methylene blue (MB 10 mu M), sGC inhibitors; Nw-Nitro-L-arginine methyl ester hydrochloride (L-NAME, 10 mu M) a nitric oxide synthase (NOS) inhibitor; atropine (10 mu M), a cholinergic receptor blocker; indomethacin (10 mu M), a cyclooxygenase inhibitor and various K+ channel blockers such as glibenclamide (10 mu M) and tetraethyl ammonium (TEA 10 mu M) for mechanism study. Results: SHRs receiving P. niruri extracts showed a significant decrease in their blood pressure (BP) when compared to the baseline value, with PEPN being more potent. The extracts (0.125-4 mg/mL) also induced vasorelaxation on endothelium-intact aorta rings. PEPN elicited the most potent maximum relaxation effect (R-max). Mechanism assessment of PEPN showed that its relaxation effect is significantly suppressed in endothelium-denuded aorta rings. Pre-incubation of aorta rings with atropine, L-NAME, ODQ, indomethacin, and propranolol also significantly attenuated its relaxation effect. Conversely, incubation with TEA and glibenclamide did not show a significant effect on PEPN-induced relaxation. Conclusion: This study indicates that the antihypertensive activity of P. niruri extract is mediated by vasoactive phytoconstituents that dilate the arterial wall via endothelium-dependent pathways and beta-adrenoceptor activity which, in turn, cause vasorelaxation and reduce blood pressure.
Safety of withholding intubation in gamma-hydroxybutyrate- and gamma-butyrolactone-intoxicated coma patients in the emergency department
EUROPEAN JOURNAL OF EMERGENCY MEDICINE
Authors: van Helmond, Lidwien P. F. M.; Gresnigt, Femke M. J.
Abstract
Objective The objective of this study was to determine if supportive care without endotracheal intubation in the emergency department (ED) was safe in the absence of complications in gamma-hydroxybutyrate (GHB)/gamma-butyrolactone (GBL) intoxicated patients with a decreased Glasgow Coma Scale (GCS) score. Methods This was a retrospective chart review of patients presenting to a Dutch tertiary urban ED with a reduced level of consciousness related to alleged GHB/GBL intoxication between April 2011-December 2014. Primary endpoint was major adverse events, defined by: upper airway obstruction not resolved with mayo tube or nasopharyngeal airway, hypoxia not resolved with 15 l of oxygen delivered via non-rebreathing mask, bradypnea not resolved after stimulation, intubation, bradycardia not resolved after intravenous atropine bolus, hypotension for which inotropes were started. Results Data of 209 patients were retrieved. Major adverse events were reported in five patients (2.4%; 95% CI: 0.8-5.5). Intubation with subsequent ICU admission was required for 1.4% of patients (95% CI: 0.3-4.1). The most frequently seen minor adverse events (N = 209) were: airway obstruction (22%), hypothermia (14.8%), hypoxia (12.9%), bradycardia (8.1%), hypotension (6.7%), bradypnea (5.7%), vomiting (5.3%). There were no deaths. None of the patients had signs of aspiration pneumonia or returned to our ED due to complications. Conclusion Our study suggests that conservative airway management for patients with a decreased GCS due to suspected GHB intoxication may be safe. Major adverse events were present in 2.4% of patients, only 1.4% of patients required intubation. All minor adverse events were managed effectively with conservative treatment.