Co-option of the same ancestral gene family gave rise to mammalian and reptilian toxins

Background Evolution can occur with surprising predictability when organisms face similar ecological challenges. For most traits, it is difficult to ascertain whether this occurs due to constraints imposed by the number of possible phenotypic solutions or because of parallel responses by shared genetic and regulatory architecture. Exceptionally, oral venoms are a tractable model of trait evolution, being largely composed of proteinaceous toxins that have evolved in many tetrapods, ranging from reptiles to mammals. Given the diversity of venomous lineages, they are believed to have evolved convergently, even though biochemically similar toxins occur in all taxa. Results Here, we investigate whether ancestral genes harbouring similar biochemical activity may have primed venom evolution, focusing on the origins of kallikrein-like serine proteases that form the core of most vertebrate oral venoms. Using syntenic relationships between genes flanking known toxins, we traced the origin of kallikreins to a single locus containing one or more nearby paralogous kallikrein-like clusters. Additionally, phylogenetic analysis of vertebrate serine proteases revealed that kallikrein-like toxins in mammals and reptiles are genetically distinct from non-toxin ones. Conclusions Given the shared regulatory and genetic machinery, these findings suggest that tetrapod venoms evolved by co-option of proteins that were likely already present in saliva. We term such genes ‘toxipotent’—in the case of salivary kallikreins they already had potent vasodilatory activity that was weaponized by venomous lineages. Furthermore, the ubiquitous distribution of kallikreins across vertebrates suggests that the evolution of envenomation may be more common than previously recognized, blurring the line between venomous and non-venomous animals.

Study of the vasodilatory effect of extract from tissue culture biomass of Rauwolfia serpentina Benth.

Design of novel herbal drugs with a wide range of activity is an important object of pharmacology. Herbal remedies having antiarrhythmic, cardiotonic and vasodilatory effects are useful for treatment of heart arrhythmias. Vasodilating drugs are prescribed for medication of hypertension and migraine. Also they are a part of comprehensive treatment of various diseases such as disturbed peripheral blood circulation and atherosclerosis of arteries of extremities as well as problems with urination and potency. Search for novel herbal preparations with vasorelaxant activity in our view is a promising matter of current interest. This work is aiming in study of vasodilatory activity of methanol extract of strain K-27 tissue culture of Rauwolfia serpentina. Evaluation of vasodilatory activity extract of high-productive strain K-27 tissue culture of Rauwolfia serpentina has been carried out by the method of auxotonic mechanography of vascular smooth muscles. Strength and frequency of spontaneous contractions of portal vein as well as relaxation of aortic smooth muscles activated with phenylephrine were evaluation indicators of extract activity. In order to estimate working concentration of extract of strain K-27 tissue culture of Rauwolfia serpentina we have studied vascular activity at sequentially increasing concentrations of extract solution on the portal vein. Overlay of sequence of growing concentrations exhibited decrease in basal level of venous tone and dose-dependent suppression of phasic contractions with complete inhibition of spontaneous activity of portal vein at 1.44 mg/ml concentration and uprise of toxicity at higher concentrations. It has been shown dose-dependent relaxation of vascular preparations followed by development of α-adrenoceptor blocking effect and loss of sensibility to phenylephrine at the end of experiment. After discontinuing exposure with a substance the activating effect of phenylephrine remained not renewed during 30-50 minutes, at the same time contractile activity of aorta on the response to the other type activation (60 mM K+) took place. It was found that at the studied range of concentrations: 0.0288 μg/ml–28.8 μg/ml the extract of strain K-27 tissue culture of Rauwolfia serpentina has distinct vasodilatory effect. Also it was discovered α-adrenoceptor blocking effect of that extract, so it can find wide application in therapy as vasorelaxant and α-blocker, for instance in treatment of prostate diseases.

Anti-hypertensive vasodilatory action of Gynura procumbens mediated by kaempferol 3-O-rutinoside

Introduction: Gynura procumbens (GP), otherwise known as longevity spinach or “Sambung Nyawa” in Malay, is an evergreen herb found in Africa and Southeast Asian countries (including Brunei) used traditionally to treat various diseases such as fever, diabetes and hypertension. We examined GP’s vasodilatory action to determine its possible role via the cholinergic-mediated pathway. Methods: GP leaves were prepared by filtration and evaporation to obtain the aqueous (AEGP) and methanol (MEGP) extracts followed by screening for phytochemical constituents. The total phenol, total flavonoid and flavonol contents were determined using the corresponding Folin–Ciocalteau, and aluminium colorimetric methods and the presence of kaempferol 3-O-rutinoside in the extracts was detected using HPLC analysis. Organ bath studies were conducted to determine the vasodilatory activity using intact and denuded isolated rat aortic rings by exposure to either increasing concentration of extracts (0.25, 0.5, 1.0, and 2.0 mg/mL) or 10 µg/mL kaempferol 3-O-rutinoside in the presence or absence of acetylcholine (ACh) after pre-contraction by noradrenaline (NA). Results: MEGP contained more phytochemical constituents and higher content of total flavonoid and total flavonol but less phenolic content than AEGP. Furthermore, MEGP yielded a 20% elevated amount of kaempferol 3-O-rutinoside than AEGP. Both extracts significantly amplified ACh-endothelium dependent vasodilation and mediated relaxation at 1 mg/mL in endothelium-intact and endothelium-denuded aortic rings with MEGP as a more effective vasodilator than AEGP. Overall, these results imply the involvement of extracts in potentiating cholinergic pathway, which might be mediated by kaempferol, as shown by its vasorelaxation effects in endothelium-intact and –denuded aorta. Conclusions: The present findings demonstrate that the vasodilatory activities of the two Gynura procumbens extracts, AEGP and MEGP, in thoracic aorta rings isolated from rats are potentially mediated via a cholinergic pathway through the action of a flavonoid particularly kaempferol 3-O-rutinoside.

EFFECT OF ACUPUNCTURE IN HEART AURICULAR POINT IN TWO INDEXES OF DIGITAL VOLUME PULSE IN HEALTHY SUBJECTS

Objective: The aim of the study was to determine the changes in two indices derived from the digital volume pulse (DVP) elicited by acupuncture in auricular heart acupoint in healthy subjects. Methods: Eighteen healthy subjects aged 26.22±2.98 years (mean±standard deviation) were assigned to receive auricular acupuncture in auricular heart acupoint in the right ear. The DVP was recorded by photoplethysmography. RIDVP was determined by the relative amplitudes of systolic and diastolic components of the DVP and SIDVP, by the relative timing of these components. Auricular acupoint heart was stimulated by manual acupuncture. The RIDVP and SIDVP indices were calculated for basal and post-acupuncture conditions. Results: Both RIDVP (p=0.0375) and SIDVP (p=0.0063) were significantly decreased by acupuncture of the right auricular acupoint heart when comparing the pre- and post-acupuncture values. Conclusions: These results indicate that manual acupuncture of auricular acupoint heart produces acute effects on vascular physiology. RIDVP and SIDVP indices can be used to assess and demonstrate a vasodilatory activity of auricular acupoint heart.

A Review of Endothelium-Dependent and -Independent Vasodilation Induced by Phytochemicals in Isolated Rat Aorta

This review discusses the contribution of the use of the isolated rat aorta (IRA) as a model for the evaluation of extracts and metabolites produced by plants with a vasodilator effect in animals. This model continues to be a valuable approach for the search and development of new phytochemicals consumed as medicinal plants or foods. In most cases, the sources of phytochemicals have been used in folk medicine to treat ailments that include hypertension. In this model, the endothelium is emphasized as a key component that modulates the vessel contractility, and therefore the basal tone and blood pressure. Based on the functional nature of the model, we focused on studies that determined the endothelium-dependent and -independent vasodilatory activity of phytochemicals. We describe the mechanisms that account for aorta contraction and relaxation, and subsequently show the vasoactive effect of a series of phytochemicals acting as vasodilators and its endothelium dependence. We highlight information regarding the cardiovascular benefits of phytochemicals, especially their potential antihypertensive effect. On this basis, we discuss the advantages of the IRA as a predictive model to support the research and development of new drugs that may be of help in the prevention and treatment of cardiovascular diseases, the number one cause of death worldwide.