Targeted Dereplication of Microbial Natural Products by High-Resolution MS and Predicted LC Retention Time

A new strategy for the identification of known compounds in Streptomyces extracts that can be applied in the discovery of natural products is presented. The strategy incorporates screening a database of 5555 natural products including 5098 structures from Streptomyces sp., using a high-throughput LCMS data processing algorithm that utilizes HRMS data and predicted LC retention times (tR) as filters for rapid identification of known compounds in the natural product extract. The database, named StrepDB, contains for each compound the structure, molecular formula, molecular mass, and predicted LC retention time. All identified compounds are annotated and color coded for easier visualization. It is an indirect approach to quickly assess masses (which are not annotated) that may potentially lead to the discovery of new or novel structures. In addition, a spectral database named MbcDB was generated using the ACD/Spectrus DB Platform. MbcDB contains 665 natural products, each with structure, experimental HRESIMS, MS/MS, UV, and NMR spectra. StrepDB was used to screen a mutant Streptomyces albus extract, which led to the identification and isolation of two new compounds, legonmaleimides A and B, the structures of which were elucidated with the aid of MbcDB and spectroscopic techniques. The structures were confirmed by computer-assisted structure elucidation (CASE) methods using ACD/Structure Elucidator Suite. The developed methodology suggests a pipeline approach to the dereplication of extracts and discovery of novel natural products

ANTI-DIARRHEAL ACTIVITY OF ETHANOL AND CHLOROFORM SEED EXTRACT OF COLA NITIDA IN EXPERIMENTALLY INDUCED DIARRHEA

Objective: Cola nitida has been used in traditional medicine to treat diverse ailments including diarrhea. This study is carried out to investigate the antidiarrheal activity of the ethanol and chloroform seed extract of Cola nitida in Wistar albino rats. Methods: The ethanol and chloroform extracts of Cola nitida were evaluated with different doses (100mg/kg, 300mg/kg and 650mg/kg of animal weight) orally for antidiarrheal activity using castor oil induced-diarrhea, gastrointestinal motility test and castor oil-induced gastroenteropooling in Wistar albino rats. The observed activity was compared to standard antidiarrheal drug Lopermaide hydrochloride (2mg/kg) and to distilled water (10ml/kg) which served as the negative control. Results: Cola nitida ethanol extract at 150, 300 and 650mg/kg showed 55.64%, 59.73%, and 71.34% inhibition in gastrointestinal motility respectively. A significant reduction in diarrheal episodes (p<0.0001) was also observed with 650mg/kg of both extracts showing 100% inhibition. A reduction in the volume of fluid in the small intestine was also seen, this was however not significant. The chloroform extract of Cola nitida on the other hand produced a significant reduction in volume and weight of small intestinal content (p<0.05) with 650mg/kg showing a 92.73% inhibition of intestinal fluid accumulation. Conclusion: The ethanol and chloroform extract of Cola nitida showed anti-diarrheal activity in animal model by decreasing the frequency of defecation and by reducing gastrointestinal motility and intraluminal fluid accumulation in the intestine.                              Peer Review History: Received 15 October 2019;   Revised 31 October; Accepted 3 November, Available online 15 November 2019 Academic Editor: Dr. Ali Abdullah Al-yahawi, Al-Razi university, Department of Pharmacy, Yemen, [email protected] UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file:                Reviewer's Comments: Average Peer review marks at initial stage: 6.0/10 Average Peer review marks at publication stage: 8.0/10 Reviewer(s) detail: Prof. Dr. Hüsniye Kayalar, Ege University, Turkey, [email protected] Prof. Dr. Ali Gamal Ahmed Al-kaf, Sana'a university, Yemen, [email protected] Similar Articles: EPIDEMICITY OF VIBRIO CHOLERA IN SANA’A CITY, YEMEN: PREVALENCE AND POTENTIAL DETERMINANT

Evaluation of the Knowledge, Attitude and Perception of Healthcare Students on Antibiotics and Antibiotic Resistance: A Study in Central University, Ghana

Students undergoing programmes in healthcare will play an important role in the management of antibiotic resistance which is still a global problem. Their knowledge and attitude should be adequately documented. This study is carried out to evaluate the knowledge, attitudes and perceptions of antibiotic use and antibiotic resistance among healthcare students in Central University, Ghana. In this study, 1027 students offering courses in pharmacy, nursing and physician assistantship participated in a survey to evaluate their knowledge, attitudes and perception on antibiotic use and antibiotic resistance. Data obtained was analyzed using STATA statistics DATA analysis software version 12.0. Descriptive statistics and chi-squared test was employed. Students displayed very good knowledge of antibiotic use and antibiotic resistance with students studying physician assistantship and nursing showing greater knowledge. The attitude of the respondents on the use of antibiotics was slightly above average. There was a significant difference (p = 0.029) between students’ programme of study and how they obtained their last course of antibiotics. Students displayed average knowledge on antibiotic use and antibiotic resistance but there is a need for more education to improve their perception and attitudes in order to contribute towards curbing the global problem of antibiotic resistance

Betulin and Crinum asiaticum L. bulbs extract attenuate pulmonary fibrosis by down regulating pro-fibrotic and pro-inflammatory cytokines in bleomycin-induced fibrosis mice model

Background: Pulmonary fibrosis (PF) is a lung disease characterized by scaring of lung tissue that impairs lung functions. The estimated survival time of patients with pulmonary fibrosis is 3–5 years. Bleomycin (BLM) is used clinically in the treatment of Hodgkin lymphoma and testicular germ-cell tumors. Bleomycin’s mechanism of action is the inhibition of DNA and protein synthesis. This happens when leukocytes induce the release of cytokines and chemokines which increase the pro-fibrotic and pro-inflammatory cytokines such as IL-6, TNF-alpha, IL-13, IL-1β and transforming growth factor-beta 1 (TGF-β). Crinum asiaticum L. bulbs (CAE) are widely found in parts of Africa, Asia and Indian Ocean Island. It is also prevalent in southern part of Ghana and traditionally used by the indigenes to treat upper respiratory tract infections, and for wound healing. Betulin (BET) is found in the bulbs of Crinum asiaticum L. but widely isolated from the external bark of birches and sycamore trees. Betulin as a lupine type triterpenes has been researched for their pharmacological and biological activities including anticancer, anti-inflammatory, antimicrobial activities and anti-liver fibrosis effects.Aim of the study: The aim was to study the anti-pulmonary fibrosis effect of Crinum asiaticum L. bulbs extract and betulin in bleomycin-induced pulmonary fibrosis in mice. Materials and method: There was a single oropharyngeal administration of bleomycin (80 mg/kg) in mice followed by the treatment of CAE and BET after 48 h of exposure to BLM. Results: There was increased survival rate in CAE and BET treatment groups compared to the BLM induced group. There was a marked decreased in the levels of hydroxyproline, collagen I and III in the CAE and BET treatment groups compared to BLM-treated group. The treatment groups of CAE and BET significantly down regulated the levels of pro-fibrotic and pro-inflammatory cytokines concentrations such as TGF-β1, MMP9, IL-6, IL-1β and TNF-alpha compared to an increased in the BLM treated groups. The histological findings of the lungs suggested the curative effects of CAE and BET following BLM induced pulmonary fibrosis in mice, the study showed improved lung functions with wide focal area of viable alveolar spaces and few collagen fibers deposition on lungs of treatment groups. Conclusion: CAE and BET attenuated pulmonary fibrosis by down regulating pro-fibrotic and pro-inflammatory cytokines as well as improving lung function. This could be a lead in drug discovery where compounds with anti-fibrotic effects could be developed for the treatment of lung injury

The Phytochemistry and Pharmacology of Tulbaghia, Allium, Crinum and Cyrtanthus: ‘Talented’ Taxa from the Amaryllidaceae

Amaryllidaceae is a significant source of bioactive phytochemicals with a strong propensity to develop new drugs. The genera Allium, Tulbaghia, Cyrtanthus and Crinum biosynthesize novel alkaloids and other phytochemicals with traditional and pharmacological uses. Amaryllidaceae biomolecules exhibit multiple pharmacological activities such as antioxidant, antimicrobial, and immunomodulatory effects. Traditionally, natural products from Amaryllidaceae are utilized to treat non-communicable and infectious human diseases. Galanthamine, a drug from this family, is clinically relevant in treating the neurocognitive disorder, Alzheimer’s disease, which underscores the importance of the Amaryllidaceae alkaloids. Although Amaryllidaceae provide a plethora of biologically active compounds, there is tardiness in their development into clinically pliable medicines. Other genera, including Cyrtanthus and Tulbaghia, have received little attention as potential sources of promising drug candidates. Given the reciprocal relationship of the increasing burden of human diseases and limited availability of medicinal therapies, more rapid drug discovery and development are desirable. To expedite clinically relevant drug development, we present here evidence on bioactive compounds from the genera Allium, Tulgbaghia, Cyrtanthus and Crinum and describe their traditional and pharmacological applications