Current Pharmaceutical Biotechnology - Volume 20, Issue 5, 2019

Background: Worldwide, the progress in reducing neonatal mortality has been very slow. The rate of preterm birth has increased over the last 20 years in low-income and middle-income countries. Its association with increased mortality and morbidity is based on experimental studies and neonatal outcomes from countries with socioeconomic differences, which have considered implementing alternative healthcare strategies to prevent and reduce preterm births. Methods: Currently, there is no widely effective strategy to prevent preterm birth. Pharmacological therapies are directed at inhibiting myometrial contractions to prolong parturition. Some drugs, medicinal plants and microorganisms possess myorelaxant, anti-inflammatory and immunomodulatory properties that have proved useful in preventing preterm birth associated with inflammation and infection. Results: This review focuses on the existing literature regarding the use of different drugs, medicinal plants, and microorganisms that show promising benefits for the prevention of preterm birth associated with inflammation and infection. New alternative strategies involving the use of PDE-4 inhibitors, medicinal plants and probiotics could have a great impact on improving prenatal and neonatal outcomes and give babies the best start in life, ensuring lifelong health benefits. Conclusion: Despite promising results from well-documented cases, only a small number of these alternative strategies have been studied in clinical trials. The development of new drugs and the use of medicinal plants and probiotics for the treatment and/or prevention of preterm birth is an area of growing interest due to their potential therapeutic benefits in the field of gynecology and obstetrics.

Background: Fenoldopam mesylate is a selective agonist of DA-1 receptors. It is currently used for the in-hospital treatment of severe hypertension. DA-1 receptors have high density in renal parenchyma and for this reason, a possible reno-protective role of Fenoldopam mesylate was investigated. Methods: We examined all studies regarding the role of Fenoldopam mesylate in Acute Kidney Injury (AKI); particularly, those involving post-surgical patients, intensive care unit patients and contrastinduced nephropathy. Results: Fenoldopam mesylate was found to be effective in reducing the onset of postoperative AKI, when used before the development of the kidney damage. Positive results were also obtained in the management of intensive care unit patients with AKI, although the clinical studies investigated were few and conducted on small samples. Conclusion: Conflicting results were achieved in contrast-induced nephropathy.

Background: Decalepis arayalpathra (J. Joseph and V. Chandras.) Venter is used primarily for nutrition besides its therapeutic values. Traditional preparations/formulations from its tuber are used as a vitalizer and blood purifier drink. The folklore medicinal uses cover inflammation, cough, wound healing, antipyretic, and digestive system management. A comprehensive review of the current understanding of the plant is required due to emerging concerns over its safety and efficacy. Objective: The systematic collection of the authentic information from different sources with the critical discussion is summarised in order to address various issues related to botanical identity, therapeutic medicine, nutritional usage, phytochemical, and pharmacological potentials of the D. arayalpathra. Current use of traditional systems of medicine can be used to expand future research opportunities. Materials and Methods: Available scripted information was collected manually, from peered review research papers and international databases viz. Science Direct, Google Scholar, SciFinder, Scopus, etc. The unpublished resources which were not available in database were collected through the classical books of ‘Ayurveda’ and ‘Siddha’ published in regional languages. The information from books, Ph.D. and MSc dissertations, conference papers and government reports were also collected. We thoroughly screened the scripted information of classical books, titles, abstracts, reports, and full-texts of the journals to establish the reliability of the content. Results: Tuber bearing vanilla like signature flavor is due to the presence of 2-hydroxy-4-methoxybenzaldehyde (HMB). Among five other species, Decalepis arayalpathra (DA) has come under the ‘critically endangered’ category, due to over-exploitation for traditional, therapeutic and cool drink use. The experimental studies proved that it possesses gastro-protective, anti-tumor, and antiinflammatory activities. Some efforts were also made to develop better therapeutics by logical modifications in 2-Hydroxy-4-methoxy-benzaldehyde, which is a major secondary metabolite of D. arayalpathra. ‘Amruthapala’ offers the enormous opportunity to develop herbal drink with health benefits like gastro-protective, anti-oxidant and anti-inflammatory actions. Conclusion: The plant has the potential to generate the investigational new lead (IND) based on its major secondary metabolite i.e. 2-Hydroxy-4-methoxy-benzaldehyde. The present mini-review summarizes the current knowledge on Decalepis arayalpathra, covering its phytochemical diversity, biological potentials, strategies for its conservation, and intellectual property rights (IPR) status. Chemical Compounds: 2-hydroxy-4-methoxybenzaldehyde (Pubchem CID: 69600), α-amyrin acetate (Pubchem CID: 293754), Magnificol (Pubchem CID: 44575983), β-sitosterol (Pubchem CID: 222284), 3-hydroxy-p-anisaldehyde (Pubchem CID: 12127), Naringenin (Pubchem CID: 932), Kaempferol (Pubchem CID: 5280863), Aromadendrin (Pubchem CID: 122850), 3-methoxy-1,2-cyclopentanedione (Pubchem CID: 61209), p-anisaldehyde (Pubchem CID: 31244), Menthyl acetate (Pubchem CID: 27867), Benzaldehyde (Pubchem CID: 240), p-cymene (Pubchem CID: 7463), Salicylaldehyde (Pubchem CID: 6998), 10-epi-γ-eudesmol (Pubchem CID: 6430754), α -amyrin (Pubchem CID: 225688), 3-hydroxy-4-methoxy benzaldehyde (Pubchem CID: 12127).

Background: The efficient analytical method for the analysis of nonsteroidal antiinflammatory drugs (NSAIDs) in a biological fluid is important for determining the toxicological aspects of such long-term used therapies. Methods: In the present work, multi-walled carbon nanotubes reinforced into a hollow fiber by chitosan sol-gel assisted-solid/ liquid phase microextraction (MWCNTs-HF-CA-SPME) method followed by the high-performance liquid chromatography-diode array detection (HPLC–DAD) was developed for the determination of three NSAIDs, ketoprofen, diclofenac, and ibuprofen in human urine samples. MWCNTs with various dimensions were characterized by various analytical techniques. The extraction device was prepared by immobilizing the MWCNTs in the pores of 2.5 cm microtube via chitosan sol-gel assisted technology while the lumen of the microtube was filled with few microliters of 1-octanol with two ends sealed. The extraction device was operated by direct immersion in the sample solution. Results: The main factors influencing the extraction efficiency of the selected NSAIDs have been examined. The method showed good linearity R2 ≥ 0.997 with RSDs from 1.1 to 12.3%. The limits of detection (LODs) were 2.633, 2.035 and 2.386 μg L-1, for ketoprofen, diclofenac, and ibuprofen, respectively. The developed method demonstrated a satisfactory result for the determination of selected drugs in patient urine samples and comparable results against reference methods. Conclusion: The method is simple, sensitive and can be considered as an alternative for clinical laboratory analysis of selected drugs.

Background: World Health Organization has estimated that 1 in 10 people fall ill and 4, 20, 000 die every year from eating contaminated food. Food pathogens like Escherichia, Salmonella, Staphylococcus and Listeria pose a serious threat to human health. Objective: The objective was to isolate microbes from meat stored at refrigerated conditions and evaluate the antimicrobial activity of the cell-free supernatant against food pathogens. Methods: Chicken and Pork samples were procured and stored at refrigerated conditions (4-7ºC) for 2 weeks. The samples were plated on to Nutrient agar (NA) and De Man, Rogosa and Sharpe (MRS) agar for isolation of aerobic and lactic acid bacteria. Cell-free supernatants of the isolates were screened for antimicrobial activity against Escherichia coli, Salmonella typhimurium, Listeria monocytogenes and Staphylococcus aureus by microtiter plate assay. The 5 most - effective strains were screened for hemolytic activity and identified by 16s rRNA sequencing. Results: A total of 110 strains were isolated, out of which the top 5 most - effective strains were all from MRS agar. They showed 88-90% inhibition against E. coli and S. typhimurium, whereas 60 to 70 % against S. aureus and L. monocytogenes. These strains were found to be non - hemolytic and were identified as Leuconostoc spp. namely, L. mesenteroides subsp. mesenteroides J18, CP003101; L. mesenteroides LM2; L. mesenteroides ATCC 8293, CP000414; L. gelidum subsp. gasicomitatum LM G 18811 and L. mesenteroides; LM2, AY675249. Conclusion: Leuconostoc are known to be effective in controlling foodborne pathogens and therefore, these strains have the potential for application in food and human.

Background: Bacterial ureases have been the cause of various human and animal pathogenicity including hepatic encephalopathy, hepatic coma urolithiasis, gastric and peptic ulcers, pyelonephritis, and urinary catheter encrustation by the production of ammonia. Hence, in view of the side effects of existing drugs, there is a strong need to discover, more safe, effective and potent compounds for the treatment of infections caused by urease. Methods: For this purpose, several natural phenolic compounds have been screened by molecular modelling techniques, wherein the phenolic compounds were docked to the active site of Jack bean urease (PDB ID 3LA4) using the Schrodinger docking software. Results: The lead compounds were identified via in-silico screening technique where docking score, binding energy, ADME and toxicity data were considered to screen the lead compounds as compared with the available standard drugs. From the docking study of screened natural phenolic compounds, five compounds diosmin, morin, chlorogenic acid, capsaicin and resveratrol were selected based upon their better affinity towards the receptor and were considered for further wet lab studies. Conclusion: The in-silico results were confirmed by in vitro experiments by use of the Jack bean urease using Weatherburn method.

Background: Tanshinone IIA (Tan IIA) and Omentin-1 have a protective role in the cardiovascular system. However, if and how Tan IIA and Omentin-1 regulate cholesterol metabolism in macrophages has not been fully elucidated. Objective: To investigate the possible mechanisms of Tan IIA and Omentin-1 on preventing macrophage cholesterol accumulation and atherosclerosis development. Methods: The effect of Tan IIA on the protein and mRNA levels of Omentin-1 and ATP-binding cassette transporter A1 (ABCA1) in macrophages was examined by Western blot and qRT-PCR assay, respectively. Cholesterol efflux was assessed by liquid scintillation counting (LSC). Cellular lipid droplet was measured by Oil Red O staining, and intracellular lipid content was detected by high performance liquid chromatography (HPLC). In addition, the serum lipid profile of apoE−/− mice was measured by enzymatic method. The size of atherosclerotic lesion areas and content of lipids and collagen in the aortic of apoE−/− mice were examined by Sudan IV, Oil-red O, and Masson staining, respectively. Results: Tan IIA up-regulated expression of Omentin-1 and ABCA1 in THP-1 macrophages, promoting ABCA1-mediated cholesterol efflux and consequently decreasing cellular lipid content. Consistently, Tan IIA increased reverse cholesterol transport in apoE−/− mice. Plasma levels of high-density lipoprotein cholesterol (HDL-C), ABCA1 expression and atherosclerotic plaque collagen content were increased while plasma levels of low-density lipoprotein cholesterol (LDL-C) and atherosclerotic plaque sizes were reduced in Tan IIA-treated apoE−/− mice. These beneficial effects were, however, essentially blocked by knockdown of Omentin-1. Conclusion: Our results revealed that Tan IIA promotes cholesterol efflux and ameliorates lipid accumulation in macrophages most likely via the Omentin-1/ABCA1 pathway, reducing the development of aortic atherosclerosis.

Background: Currently, the treatment of infectious diseases has not always been successful due to the emergence of microbial resistance worldwide. Objectives: This study aimed to evaluate the antioxidant activity, content of total phenolic compounds and flavonoids, antifungal potential and antibacterial action of six medicinal plants found in the Cerrado, leaf extracts of Boldo (Peumus boldus), Goiaba (Psidium guajava), Assa-Peixe (Vernonia polysphaera), Abacate (Persea americana), Eucalipto (Eucalyptus citriodora) and raw sap of Bálsamo (Jatropha multifida). Methods: The antioxidant activity was also determined through the DPPH, ABTS and phosphomolybdenum assays. In addition, the total phenolic content and flavonoid dosage were analyzed using the Folin- Ciocalteu method and the aluminum chloride test, respectively. Results: All extracts, except from Assa-Peixe, showed promising values against Staphylococcus aureus, with halos varying from 13-20 mm. Analysis of the minimum inhibitory concentration (MIC) values of the six medicinal plants revealed inhibitory activity of S. aureus, with concentrations varying from 3.12-12.5 mg/mL, which is a significant result considering that S. aureus is one of the main causes of hospital infections. Conclusion: In the analysis of the phytochemical profile, Goiaba contained the best yield of phenolic compounds and total flavonoids, as well as higher antioxidant activity by DPPH and phosphomolybdenum, demonstrating that this species contains antioxidant components that can sequester free radicals under in vitro conditions. Therefore, the crude extracts investigated are promising and their antibacterial and antioxidant actions should be thoroughly studied.