Scientia Pharmaceutica

The genus Porophyllum (family Asteraceae) is native to the western hemisphere, growing in tropical and subtropical North and South America. Mexico is an important center of diversification of the genus. Plants belong of genus Porophyllum have been used in Mexican traditional medicine to treat kidney and intestinal diseases, parasitic, bacterial, and fungal infections and anti-inflammatory and anti-nociceptive activities. In this sense, several trials have been made on its chemical and in vitro and in vivo pharmacological activities. These studies were carried on the extracts and isolated compounds and support most of their reported uses in folk medicine as antifungal, antileishmanial, anti-inflammatory, anti-nociceptive and burn repair activities, and as a potential source of new class of insecticides. Bio guided phytochemical studies showed the isolation of thiophenes, terpenes and phenolics compounds, which could be responsible for the pharmacological activities. However, more pre-clinical assays that highlight the mechanisms of action of the compounds involved in pharmacological function are lacking. This review discusses the current knowledge of their chemistry, in vitro and in vivo pharmacological activities carried out on the plants belonging to the Porophyllum genus. Full article

Coronavirus Disease 2019 (COVID-19) has spread globally with the number of cases exceeding seventy million. Although trials on potential treatments of COVID-19 Acute Respiratory Distress Syndrome (ARDS) are promising, the introduction of an effective therapeutic intervention seems elusive. In this review, we explored the potential therapeutic role of volatile anesthetics during mechanical ventilation in the late stages of the disease. COVID-19 is thought to hit the human body via five major mechanisms: direct viral damage, immune overactivation, capillary thrombosis, loss of alveolar capillary membrane integrity, and decreased tissue oxygenation. The overproduction of pro-inflammatory cytokines will eventually lead to the accumulation of inflammatory cells in the lungs, which will lead to ARDS requiring mechanical ventilation. Respiratory failure resulting from ARDS is thought to be the most common cause of death in COVID-19. The literature suggests that these effects could be directly countered by using volatile anesthetics for sedation. These agents possess multiple properties that affect viral replication, immunity, and coagulation. They also have proven benefits at the molecular, cellular, and tissue levels. Based on the comprehensive understanding of the literature, short-term sedation with volatile anesthetics may be beneficial in severe stages of COVID-19 ARDS and trials to study their effects should be encouraged. Full article

Diabetes mellitus is a pathology with increasing frequency in society, being one of the main causes of death worldwide. For this reason, new therapeutic targets have been studied over the years. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is an enzyme responsible for reducing cortisone to its active form cortisol, which can lead to metabolic changes such as insulin resistance and hyperglycemia. Therefore, 11β-HSD1 inhibition may offer a new therapeutic approach for type 2 diabetes mellitus. This work intends to systematically review the available scientific evidence on this subject. For this, a search was conducted in three databases and 15 clinical and in vivo preclinical studies were included in this review. Despite the high inhibitory and selectivity levels achieved with several molecules and the demonstrated clinical efficacy in diabetes treatment, no phase III clinical trials have yet been conducted. This is important because the long-term effects of 11β-HSD1 inhibitors including the consequences in hypothalamic–pituitary–adrenal axis must be evaluated. However, this enzyme remains a promising target for drug development, including due to its effectiveness in controlling various factors that constitute the metabolic syndrome and its potential for multiple indications in patients with diabetes, including wound healing and weight loss. Full article

A series of triterpenic acid amides were synthesized incorporating a 2-ethoxy-3-phenylpropanoic acid pharmacophore fragment. The synthesized compounds were tested for their ability to improve glycemic control and to counter lipid abnormalities in C57BL/6 mice placed on a high-fat/high-cholesterol diet. Of all tested compounds, the dihydrobetulonic derivative (16b) had the most pronounced effect in decreasing blood glucose levels, total cholesterol (TC), and high-density lipoproteins (HDL). All the synthesized compounds displayed a relatively safe profile in the animal studies carried out in this work. Full article

While contraceptive drugs have enabled many people to decide when they want to have a baby, more than 100 million unintended pregnancies each year in the world may indicate the contraceptive requirement of many people has not been well addressed yet. The vagina is a well-established and practical route for the delivery of various pharmacological molecules, including contraceptives. This review aims to present an overview of different contraceptive methods focusing on the vaginal route of delivery for contraceptives, including current developments, discussing the potentials and limitations of the modern methods, designs, and how well each method performs for delivering the contraceptives and preventing pregnancy. Full article

Combating the COVID-19 pandemic warrants the exploitation of all the available tools and implies a major focus on both the biological and the physical properties of the causing virus (SARS-CoV2). We hereby introduce a new prophylaxis hypothesis by decreasing the viral load in the body entrances such as the nose and the mouth using pharmaceutical and cosmeceutical preparations that incorporate viral electrostatic repulsive nanofibers fabricated from an abundant marine-derived or a fermentation product polymer; Ԑ-poly-l-lysine was prepared using the electrospinning technique. Full article

Antibiotic-resistant infection is a major health problem, and a limited number of drugs are currently approved as antibiotics. Soil bacteria are promising sources in the search for novel antibiotics. The aim of the present study is to isolate and assess soil bacteria with anti-MRSA activity and improve their capabilities by UV mutagenesis. Soil samples from the upper south of Thailand were screened for antibacterial activity using the cross-streak method. Agar well diffusion was used to examine the activity of isolates against a spectrum of human pathogens. The most active isolate was identified by 16S rRNA sequencing, and the production kinetics and stability were investigated. The most promising isolate was mutated by UV radiation, and the resulting activity and strain stability were studied. The results show that isolates from the cross-streak method could inhibit Staphylococcus aureus TISTR 517 (94 isolates) and Escherichia coli TISTR 887 (67 isolates). Nine isolates remained active against S. aureus TISTR 517 and MRSA, and eight isolates inhibited the growth of E. coli TISTR 887 as assessed using agar well diffusion. The most active strain was Brevibacillus sp. SPR-20, which had the highest activity at 24 h of incubation. The active substances in culture supernatants exhibited more than 90% activity when subjected to treatments involving various heat, enzymes, surfactants, and pH conditions. The mutant M201 showed significantly higher activity (109.88–120.22%) and strain stability compared to the wild-type strain. In conclusion, we demonstrate that soil Brevibacillus sp. is a potential resource that can be subjected to UV mutagenesis as a useful approach for improving the production of anti-MRSA in the era of antibiotic resistance. Full article

Alzheimer’s disease (AD) is a common chronic neurodegenerative disorders. Melatonin (MLT) has been reported to be neuroprotective agent, and its modified structures exhibit potent antioxidant and anti-inflammation activities. Therefore, the activity of MLT and its derivatives against AD was investigated. Herein, the targeted enzymes, such as β-secretase (BACE1) and acetylcholinesterase (AChE), as well as the neuroprotective and neuritogenic effects on P19-derived neurons were evaluated. All the derivatives (1–5), including MLT, displayed potent inhibitory activity for BACE1, with inhibition values of more than 75% at 5 µM. A molecular docking study predicted that MLT, 5-MT, and 5 bound with BACE1 at catalytic amino acids Asp32 and the flap region, whereas 1–4 interacted with allosteric residue Thr232 and the flap region. The additional π-π interactions between 2, 3, and 5 with Tyr71 promoted ligand-enzyme binding. In addition, MLT, 1, 3, and 5 significantly protected neuron cells from oxidative stress by increasing the cell viability to 97.95, 74.29, 70.80, and 69.50% at 1 nM, respectively. Moreover, these derivatives significantly induced neurite outgrowth by increasing the neurite length and number. The derivatives 1, 3, and 5 should be thoroughly studied as potential AD treatment and neuroprotective agents. Full article

A new series of amino acid derivatives of quinolines was synthesized through the hydrolysis of amino acid methyl esters of quinoline carboxamides with alkali hydroxide. The compounds were purified on silica gel by column chromatography and further characterized by TLC, NMR and ESI-TOF mass spectrometry. All compounds were screened for in vitro antimicrobial activity against different bacterial strains using the microdilution method. Most of the synthesized amino acid-quinolines show more potent or equipotent inhibitory action against the tested bacteria than their correspond esters. In addition, many of them exhibit fluorescent properties and could possibly be utilized as fluorophores. Molecular docking and simulation studies of the compounds at putative bacterial target enzymes suggest that the antimicrobial potency of these synthesized analogues could be due to enzyme inhibition via their favorable binding at the fluoroquinolone binding site at the GyrA subunit of DNA gyrase and/or the ParC subunit of topoisomerase-IV. Full article

Vaccination is one of the main methods for the specific prevention of infectious diseases. The disadvantage of vaccination is the use of pathogens (live or attenuated viruses and bacteria) that can lead to the development of a disease. Recombinant technologies are capable of producing specific DNA or protein molecules that possess antigenic properties and do not cause disease. However, individual antigen molecules are low-immunogenic, and therefore, require conjugation with a compound possessing stronger immunogenic properties. In this study, we examined the immunogenic properties of the new anionic copolymer consisting of glycidyl methacrylate, butyl acrylate, triethylene glycol dimethacrylate, and acrylic acid, in mice. The experimental polymer induced a stronger immunogenic response than aluminum hydroxide. The histological studies have established that immunization both with aluminum hydroxide and the polymer studied does not cause damage to the liver, kidneys, or the spleen. No negative side effects were observed. It has been concluded that the new synthetic anionic polyelectrolyte hydrogel (PHG) has a potential as an adjuvant for vaccine development. Full article

The World Health Organization (WHO) officially announced coronavirus disease 2019 (COVID-19) as a pandemic in March 2020. Unfortunately, there are still no approved drugs for either the treatment or the prevention of COVID-19. Many studies have focused on repurposing established antimalarial therapies, especially those that showed prior efficacy against Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV), such as chloroquine and hydroxychloroquine, against COVID-19 combined with azithromycin. These classes of drugs potentially induce prolongation of the QT interval, which might lead to lethal arrhythmia. Beta-blockers, as a β-adrenergic receptor (β-AR) antagonist, can prevent an increase in the sympathetic tone, which is the most important arrhythmia trigger. In this literature review, we aimed to find the effect of administering azithromycin, chloroquine, and hydroxychloroquine on cardiac rhythm disorders and our findings show that bisoprolol, as a cardio-selective beta-blocker, is effective for the management of the QT (i.e., the start of the Q wave to the end of the T wave) interval prolongation in COVID-19 patients. Full article

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a coronavirus that causes the pandemic Coronavirus Disease 2019 (COVID-19). There is no current specific treatment for this new coronavirus. In this study, we employed a virtual screening repurposing strategy to search for potential SARS-CoV-2 Mpro inhibitors. The databases PDB, ChEMBL, BindingDB and DrugBank were queried with several filtering steps based on ligand-based and structure-based approaches. As a result, we obtained 58 molecules (37 from ChEMBL and 21 from DrugBank) that potentially inhibit SARS-CoV-2 Mpro. These molecules have on their chemical structure functional groups that favor stronger docking scores than the inhibitor N3. Several of these molecules are reported experimentally as SARS-CoV Mpro inhibitors. Hence, a combined virtual screening strategy allowed finding chemical compounds with a high potential for the inhibition of SARS-CoV-2 Mpro. Full article

Glochidion wallichianum (GW) is a good source of antioxidants, including gallic acid, promoting its development as a microemulsion. We constructed five pseudo-ternary phase diagrams comprising isopropyl myristate (IPM), water, and surfactant mixture (Smix)—i.e., Labrasol^®:HCO-40^® (1:1) with Transcutol^® (1:1, 2:1, 3:1), and Tween80:Span80 (3:2) with Transcutol^® or propylene glycol:ethanol (1:1). Additionally, blank and GW extract-loaded microemulsions were prepared at an IPM:Water:Smix ratio of 10:30:60 (high water content) and 30:10:60 (high oil content) from each Smix. The physical characteristics, skin permeation, and disposition were evaluated. The formulations with high water content and conductivities provided higher gallic acid permeation and disposition than those with high oil content. The Smix of Labrasol^®:HCO-40^® (1:1) and Transcutol^® (1:1) promoted the highest gallic acid permeation (enhancement ratio 1.78 ± 0.12) and was suitable for transdermal delivery. However, the 1% hydroxypropyl methylcellulose control gel, the microemulsion with Smix of Labrasol^®:HCO-40^® (1:1) with Transcutol^® (2:1), and Smix of Tween80:Span80 (3:2) with propylene glycol:ethanol (1:1) could provide higher skin accumulation of gallic acid than that with other formulations. The microstructures, ratio of surfactant:cosurfactant, and compositions of microemulsions were found to affect the skin permeation and disposition of gallic acid and require optimization to act as transdermal or topical delivery carriers. Full article

Glimepiride is an antidiabetic drug which is one of the third generation sulfonylureas. It belongs to class II, according to the BCS (Biopharmaceutical Classification System), which is characterized by low solubility and high permeability. The aim of this work was to formulate glimepiride as solid dispersion using water-soluble carriers to enhance its aqueous solubility and thus enhance its bioavailability. Nine formulations of glimepiride solid dispersion were prepared by a solvent evaporation technique using three different carriers (mannitol, polyethylene glycol 6000, and β-cyclodextrin) with three different drug carrier ratio (1:1, 1:3, and 1:6). Formulation variables were optimized using 3² full factorial design. The prepared formulations were evaluated for production yield, drug content, micromeritic properties, thermal analysis, in-vitro release, and in-vivo hypoglycemic effect. All prepared formulations showed high production yield ranged from 98.4 ± 2.8 to 99.8 ± 2.2% and high drug content in the range of 97.2 ± 3.2 to 99.6 ± 2.1%. The micromeritic properties revealed that all prepared glimepiride formulations showed good flowability. The differential scanning calorimetry study revealed the presence of the drug in the more soluble amorphous form. In accordance with the results of in vitro release study, it was found that the solubility of glimepiride was increased by increasing the drug carrier ratio, compared with the pure form of the drug. It was found that F9 showed a high and rapid reduction in blood glucose levels in diabetic rats, which indicated the success of a solid dispersion technique in improving the solubility and hence the bioavailability of glimepiride. Full article

Intestinal and hepatic function have been investigated in phase II metabolic reactions and elimination of p-nitrophenol (PNP) in the rat. A jejunal loop was cannulated and recirculated with isotonic solutions containing PNP in different concentrations (0, 20, 100, 500, 1000 µM). Samples were obtained from the perfusate at given intervals. To investigate the metabolic and excretory functions of the liver, the bile duct was cannulated, and the bile was collected. Metabolites of PNP were determined by validated HPLC (high pressure liquid chromatography) methods. The results demonstrated the relative importance of the small intestine and the liver in phase II metabolic transformations and elimination of PNP. There were significant differences between the luminal and biliary appearances of p-nitrophenol-glucuronide (PNP-G) and p-nitrophenol–sulfate (PNP-S). The PNP-G appeared in the intestinal lumen at the lower PNP concentrations (20 µM and 100 µM) at higher rate than in the bile. No significant difference was found between the intestinal and the biliary excretion of PNP-G when PNP was administered at a concentration of 500 µM. However, a reverse ratio of these parameters was observed at the administration of 1000 µM PNP. The results indicated that both the small intestine and the liver might play an important role in phase II metabolic reactions and elimination of PNP. However, the relative importance of the small intestine and the liver can be dependent on the dose of drugs. Full article

Cariprazine (Car) is a recently approved second generation antipsychotic (SGA) with unique pharmacodynamic profile, being a partial agonist at both dopamine D_2/3 receptor subtypes, with almost 10 times greater affinity towards D₃. SGAs are known to increase body weight, alter serum lipids, and stimulate adipogenesis but so far, limited information about the adverse effects is available with this drug. In order to study this new SGA with such a unique mechanism of action, we compared Car to substances that are considered references and are well characterized: olanzapine (Ola) and aripiprazole (Ari). We studied the effects on body weight and also assessed the adipogenesis in rats. The drugs were self-administered in two different doses to female, adult, Wistar rats for six weeks. Weekly body weight change, vacuole size of adipocytes, Sterol Regulatory Element Binding Protein-1 (SREBP-1) and Uncoupling Protein-1 (UCP-1) expression were measured from the visceral adipose tissue (AT). The adipocyte’s vacuole size, and UCP-1 expression were increased while body weight gain was diminished by Car. by increasing UCP-1 might stimulate the thermogenesis, that could potentially explain the weight gain lowering effect through enhanced lipolysis. Full article

Helichrysum petiolare (Asteraceae family) is part of the Helichrysum genus which comprises of an estimated 600 species. Several parts of the plant have been used traditionally for the treatment of various ailments, such as cough, infection, asthma, chest problems, diabetes and wounds. Given its various chemical constituents with anticancer properties, there has been no scientific evidence of its usage for the treatment of cancer. This study aims to investigate the anti-proliferative and genotoxic activities of H. petiolare methanol extract. The cytotoxic effect and cell cycle analysis of mouse melanoma cells (B16F10) and human melanoma cells (MeWo) were assessed using the ImageXpress Micro XLS Widefield High-Content Analysis System. The genotoxic potential of the extract towards Vero cells was also assessed using the micronucleus assay. The extract displayed cytotoxicity towards B16F10 and MeWo skin melanoma cells, thereby showing a dose-dependent decrease in cell density. This was preceded by cell cycle arrest in B16F10 cells at the S phase and MeWo cell arrest at the early M phase with a significant increase in apoptosis in both cells. Furthermore, the extract displayed genotoxic potential at the tested concentrations (12.5–200 μg/mL). Overall, the results revealed that H. petiolare extract may have the potential to eradicate skin cancer. Full article

The prevalence of obesity is increasing worldwide and is commonly associated with comorbidities. The use of several drugs is often necessary, which leads to Potential Drug Interactions (PDI) that may increase the morbidity and mortality. This study aimed to analyze the prevalence of drug interaction and its association with socio-demographics, health status, and drug use in severely obese individuals. Baseline data from a randomized clinical trial registered at Clinicaltrial.gov (NCT02463435) were used. A total of 150 individuals aged 18–65 years with a body mass index of 35 kg/m² were included. The outcome variable was the presence of PDI, and the explanatory variables were divided into the following four levels: socio-demographic, lifestyle, health, and medication use. The prevalence of PDI was 50% (n = 75) (95% CI 41–58). The variables associated with drug–drug interactions in the multiple analyses were arterial hypertension (PR 1.83, 95%, CI 1.10–3.04), polypharmacy (PR 3.12, 95%, CI 2.17–4.50), and diabetes mellitus (PR 0.60, 95%, CI 0.45–0.81). The risk factors for the occurrence of drug interaction were the presence of diabetes mellitus, hypertension, and polypharmacy. Full article

(1) Background: this research aims at studying the nephroprotective properties of BNO 2103 in a model of chromate-induced renal failure in rats and at proving the possibility of using BNO 2103 in clinical practice for the complex treatment of chronic kidney disease (CKD). (2) Methods: fifty rats divided into five groups were studied. The drugs BNO 2103, Prednisolone and Lespephril were administered within 20 days. The excretory function and the functional state of kidneys, blood biochemical parameters and indicators of nitrogen metabolism were determined. (3) Results: under the influence of BNO 2103, there was a significant improvement in renal excretory function, in nitrogen metabolism and blood biochemical parameters compared with the control pathology group. BNO 2103 also outperformed the comparators in most indicators. (4) Conclusions: BNO 2103 has demonstrated nephroprotective, hypoazotemic and diuretic effects; and can be used to implement to the combined therapy of CKD. Full article