hypericum and Ischemia

To investigate the effect of St John's wort (SJW) and its active constituents hypericin and hyperforin on detrusor smooth muscle contractility and their possible neuroprotective role against ischaemic-like conditions, which could arise during overactive bladder disease.. In whole bladders, intrinsic nerves underwent electrical field stimulation (EFS). The effect of drugs on the contractile response and its recovery in reperfusion phase (R) was monitored at different concentrations during 1 or 2 h of anoxia-glucopenia (A-G) and the first 30 min of R. The effects of the drugs were also investigated on rat detrusor muscle strips contracted with carbachol, KCl and electrically.. SJW has spasmolytic activity, which increases with increasing concentration and it worsens the damage induced by A-G/R on rat urinary bladder. Hypericin and hyperforin had no effect during ischemic-like conditions but they both exert a dual modulation of rat detrusor strips contraction. At high micromolar concentrations they showed a relaxing effect, but at submicromolar range hypericin increased the plasma membrane depolarisation and hyperforin showed a stimulatory effect on the cholinergic system.. The results of our study showed that SJW and its constituents could modulate urinary bladder contractility and even worsen A-G/R injury.

Topics: Animals; Anthracenes; Carbachol; Cell Membrane; Dose-Response Relationship, Drug; Electric Stimulation; Glucose; Hypericum; Hypoxia; Ischemia; Male; Muscle Contraction; Muscle, Smooth; Parasympatholytics; Parasympathomimetics; Perylene; Phloroglucinol; Plant Extracts; Potassium Chloride; Rats; Rats, Sprague-Dawley; Terpenes; Urinary Bladder; Urinary Bladder Diseases; Urinary Bladder, Overactive

Ocular neovascularization is a leading cause of blindness in ischemic retinopathies. Hypericin is an active ingredient in the medical herb St. John's Wort (SJW). Because hypericin inhibits intracellular signaling pathways that are believed to participate in the regulation of angiogenesis, we investigated the actions of hypericin and SJW in retinal neovascularization, using a mouse model of oxygen-induced retinopathy (OIR).. C57BL/6 neonatal mice were exposed to a 75% concentration of oxygen from postnatal day 7 (P7) to P12 and returned to room air from P12 to P17 to induce retinal neovascularization. SJW (15 mg/kg/day), hypericin (15, 45, or 135 mug/kg/day), or vehicle was given by gavage once a day for five days from P12 to P17. To quantify the area of retinal neovascularization and vasoobliteration, we stained retinas with isolectin B4 at P17. Phosphorylation of extracellular signal-regulated kinase (ERK) in ischemic retinas was determined by western blot analysis. To estimate retinal vascularization, we stained retinas with isolectin B4 at P7 after treatment with SJW, hypericin, or vehicle from P3 to P7.. Gavage administration of hypericin or SJW significantly inhibited the degree of retinal neovascularization, but did not affect the area of retinal vasoobliteration in a mouse model of OIR. Both SJW and hypericin had no effect on normal vascularization over the treatment time course. Treatment with SJW or hypericin reduced phosphorylation of ERK in the retina.. These data suggest that hypericin and SJW reduce pathological retinal neovascularization and that administration of these agents could have clinical utility for treatment of ischemic retinopathies.

Topics: Angiogenesis Inhibitors; Animals; Anthracenes; Disease Models, Animal; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases; Female; Hypericum; Ischemia; Mice; Mice, Inbred C57BL; Neovascularization, Physiologic; Oxygen; Perylene; Phosphorylation; Retina; Retinal Diseases; Retinal Neovascularization