In-vitro Anti-cercarial activity of extracts and steroidal alkaloids from the stem bark of Holarrhena floribunda (G. Don) Dur. & Schinz

Context: Schistosomiasis continues to be the leading cause of morbidity and mortality among the neglected tropical diseases. Apart from the high cost of chemotherapy, concerns over drug resistance and tolerance have been raised in the past decade. Objective: The aim of the study was to evaluate the anticercarial activity of extracts and compounds from the stem bark of Holarrhena floribunda on cercaria of Schistosoma haematobium. Methods: Hydroethanolic and alkaloidal extracts from the stem bark of H. floribunda were tested on cercaria at concentrations between 500.00 and 15.625 μg/mL for 180 minutes and assessing the percentage viability at time intervals of 0, 15, 30, 60, 120 and 180 minutes. Praziquantel, used as reference drug, and the isolated compounds were tested at similar concentrations. The cercaria mortalities and IC50 of extracts and compounds were estimated after 30 minutes of incubation. Results: The 70 %v/v ethanol extract showed the highest activity (IC50=20.09±1.11 μg/mL) with praziquantel giving IC50 of 695.50±1.12. The alkaloids holonamine, holadienine and conessine, isolated from the stem bark, showed considerable cercaricidal activity with the latter recording an IC50 of 33.28±1.04. Conclusion: The study gives first-hand knowledge of the anti-cercarial activity of H. floribunda and its steroidal alkaloids. This gives credence to the traditional uses of the plant as an anti-parasitic agent

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

In Vivo Antiplasmodial Activity of Different Solvent Extracts of Myrianthus libericus Stem Bark and Its Constituents in Plasmodium berghei-Infected Mice

The emergence and resurgence of P. falciparum resistance to generations of antimalarial drugs have prompted the search for new, effective, and safe antimalarial agents. This study aimed at investigating the in vivo antiplasmodial activity of the 70% hydroethanolic extract and constituents of the stem bark of Myrianthus libericus based on its ethnomedicinal use as an antimalarial agent. The antiplasmodial activity was assessed in Swiss albino mice employing the 4-day suppressive and Rane’s tests. MLB significantly (p<0.0001) suppressed parasitaemia by 52.26%, 65.40%, and 77.11% at 50, 100, and 200 mg·kg−1 doses, respectively, in the 4-day suppressive test. In Rane’s test, the highest parasitaemia suppression of 72.50% was recorded at a dose of 200 mg·kg−1 of the extract. Fractionation of the bioactive ethyl acetate fraction by solvent-solvent partitioning and column chromatography led to the isolation of friedelan-3-one and stigmasterol being reported for the first time from this species. The compounds demonstrated remarkable antiplasmodial activity by suppressing parasitaemia by 65–72% in the suppressive test and 61–70% in the curative test at doses of 10–30 mg·kg−1. Both the extract and the isolated compounds significantly prolonged the survival time of infected mice and averted the cardinal signs associated with P. berghei-induced malaria including weight loss, hypothermia, and haemolysis. The results obtained confirm the prospect of M. libericus as an important source of new antimalarial compounds and justifies its folkloric use as an antimalarial agent

Myrianthus libericus: Possible mechanisms of hypoglycaemic action and in silico prediction of pharmacokinetics and toxicity profile of its bioactive metabolite, friedelan-3-one

The hypoglycaemic and anti-hyperlipidaemic effects of the 70% ethanol stem bark extract of Myrianthus libericus (MLB), used traditionally in the management of diabetes in Ghana, was evaluated in this study using streptozotocin (45 mg/kg)-induced diabetic rats. In vitro hypoglycaemic activities of the extract and one of its principal compounds, friedelan-3-one were then investigated using α-amylase inhibitory and glucose uptake assay in C2C12 myotubes. In silico analysis of the pharmacokinetic and toxicity properties of the compound was also performed. MLB significantly (p < 0.001) reduced the elevated blood glucose levels and corrected considerably (p < 0.01) the altered serum lipid profiles of the diabetic rats which was comparable to glibenclamide (5 mg/kg). Together with friedelan-3-one, the extract markedly inhibited the activity of α-amylase and promoted glucose uptake in C2C12 cells. Whereas MLB significantly (p < 0.001) up-regulated PI3K and PPARγ transcripts with a corresponding increase in GLUT-4 transcripts within the muscle cells, friedelan-3-one only up-regulated PI3K and GLUT-4 transcripts to promote glucose transport. Friedelan-3-one was shown to be non-carcinogenic, non-hepatotoxic, has decent oral bioavailability and a good compound for optimisation into a drug candidate. The study has demonstrated that MLB possess hypoglycaemic and anti-hyperlipidaemic activities and could be used as a therapeutic agent in the management of diabetes mellitus