Scientia Pharmaceutica — Open Access Journal

Our previous study showed that water-soluble fiber from bengkoang (Pachyrizus erosus (L.) Urban) fiber extract (BFE) and bengkoang fiber fraction B (BFE-B) have phagocytic activity and modulation of cytokine production in vitro. The present study evaluates the immunomodulatory effects of water-soluble fibers BFE and BFE-B on male mice induced by hepatitis B vaccine. Thirty mice were divided into six groups and induced by hepatitis B vaccine intraperitoneally on days 7 and 14. The mice were then treated with BFE, BFE-B, levamisole, or sodium carboxymethyl cellulose for 18 days. At the end of the treatments (day 19), phagocytic activity, lymphocyte proliferation, spleen index, cytokine, and immunoglobulin G (IgG) production were determined. The results showed that the water-soluble fiber treatment could significantly increase phagocytic capacity, nitric oxide production, and spleen index. However, BFE-B could modulate tumor necrosis factor (TNF)-α and interleukin (IL)-10 secretion, BFE demonstrated no such effect on cytokine production. Lymphocyte proliferation assay revealed that treatment with 50 mg/kg body weight (BW) BFE and 50 mg/kg BW BFE-B could significantly enhance lymphocyte proliferation. Treatment with 25 and 50 mg/kg BW BFE-B stimulated IgG production. In conclusion, BFE and BFE-B similarly have immunomodulatory effects on innate immune responses. BFE-B further demonstrated immunomodulatory effects on adaptive immune responses. Full article

The aim of this study is to investigate the Thymus vulgaris essential oil (TVEO) as an antifungal agent in aromatherapy and/or as an active ingredient in the prevention or management of topical inflammatory diseases. The chemical composition of TVEO was determined with gas chromatography and revealed the presence of 25 compounds. Carvacrol was found to be the major component (56.8%). Antifungal action of TVEO was determined in vitro by using different methods. By the disc diffusion method, TVEO showed more potent antifungal activity against Candida strains than the positive control. The diameter of inhibition zone (DIZ) varied from 34 to 60 mm for Candida yeasts. Significantly higher antifungal activity was observed in the vapor phase at lower quantities. Candida albicans and C. parapsilosis were the most susceptible strains to the oil vapor with DIZ varying from 35 to 90 mm. The minimum inhibitory concentrations (MIC) of yeast were determined with an agar dilution method and revealed that MIC varied from 0.3 to 0.15 µL/mL for yeast species. The topical anti-inflammatory potential of TVEO was also explored in vivo with the croton oil-induced ear edema assay. TVEO exhibited a potent anti-inflammatory effect at all doses (100, 10 and 2 mg/kg), which were statistically similar (p > 0.05) to the positive control. This activity was also confirmed at the cellular level with histopathology analysis. Our results suggest the potential application of this carvacrol-rich TVEO in the prevention and management of fungal infections and topical inflammation and deserve further investigation for clinical applications. Furthermore, while the mode of action remains mainly undetermined and should be studied. Full article

Breast cancer is one of the most common cancers worldwide, which makes it a very impactful malignancy in the society. Breast cancers can be classified through different systems based on the main tumor features and gene, protein, and cell receptors expression, which will determine the most advisable therapeutic course and expected outcomes. Multiple therapeutic options have already been proposed and implemented for breast cancer treatment. Nonetheless, their use and efficacy still greatly depend on the tumor classification, and treatments are commonly associated with invasiveness, pain, discomfort, severe side effects, and poor specificity. This has demanded an investment in the research of the mechanisms behind the disease progression, evolution, and associated risk factors, and on novel diagnostic and therapeutic techniques. However, advances in the understanding and assessment of breast cancer are dependent on the ability to mimic the properties and microenvironment of tumors in vivo, which can be achieved through experimentation on animal models. This review covers an overview of the main animal models used in breast cancer research, namely in vitro models, in vivo models, in silico models, and other models. For each model, the main characteristics, advantages, and challenges associated to their use are highlighted. Full article

Current antileishmanial drugs are toxic, expensive, and resistance to them has emerged. Several studies have focused on natural products as alternatives. In the present work, the chemical composition, in vitro antileishmanial activity, cytotoxicity effects, and the influence on mitochondrial function of the essential oil from Tagetes lucida Cav. was determined, as well its main compound estragole. Forty-nine compounds were detected in the oil by gas chromatography-mass spectrometry (GC-MS), of which estragole was the main constituent (97%). The oil showed inhibition of the promastigotes of L. tarentolae and L. amazonensis (IC₅₀ = 61.4 and 118.8 µg/mL, respectively), decreased oxygen consumption of L. tarentolae, disrupted mitochondrial membrane potential in L. amazonensis, inhibitory activity on the intracellular amastigote of L. amazonensis (IC₅₀ = 14.2 ± 1.6 µg/mL), and cytotoxicity values ranging from 80.8 to 156 µg/mL against murine macrophages and J774 cells. Estragole displayed higher activity on promastigotes (IC₅₀ = 28.5 and 25.5 µg/mL, respectively), amastigotes (IC₅₀ = 1.4 ± 0.1 µg/mL), and cytotoxicity values ranging from 20.6 to 14.5 µg/mL, respectively, while on mitochondria, it caused a decrease of the membrane potential but did not inhibit oxygen consumption. The potential antileishmanial activity of the essential oil from T. lucida and estragole makes these compounds favorable candidates for exploration in further studies. Full article

Age-related macular degeneration (AMD) will be responsible for the vision impairment of more than five million late-aged adults in the next 30 years. Current treatment includes frequent intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents. However, there are methods of drug delivery that can decrease the frequency of intravitreal injections by sustaining drug release. MPEG-PCL ((methoxypoly(ethylene glycol) poly(caprolactone)) has been reported as biocompatible and biodegradable. Polymeric micelles of MPEG-PCL can be useful in efficiently delivering anti-VEGF drugs such as sunitinib to the posterior segment of the eye. In this study, the novel micellar formulation exhibited an average dynamic light scattering (DLS) particle size of 134.2 ± 2.3 nm with a zeta potential of −0.159 ± 0.07 mV. TEM imaging further confirmed the nanoscopic size of the micelles. A sunitinib malate (SM)-MPEG-PCL formulation exhibited a sustained release profile for up to seven days with an overall release percentage of 95.56 ± 2.7%. In addition to their miniscule size, the SM-MPEG-PCL formulation showed minimal cytotoxicity onto the ARPE-19 human retinal pigment epithelial cell line, reporting a percent viability of more than 88% for all concentrations tested at time intervals of 24 h. The SM-MPEG-PCL micelles also exhibited exceptional performance during an anti-VEGF ELISA that decreased the overall VEGF protein expression in the cells across a 24–72 h period. Furthermore, it can be concluded that this type of polymeric vehicle is a promising solution to symptoms caused by AMD and improving the management of those suffering from AMD. Full article

At the beginning of 2020, the world was swept with a wave of a new coronavirus disease, named COVID-19 by the World Health Organization (WHO 2). The causative agent of this infection is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The data available on one of the promising therapeutic agents—nucleotide analog remdesivir (Gilead Sciences number GS-5734)—were evaluated. These data were concerned with remdesivir activation from the prodrug to the active molecule—triphosphate containing 1′-cyano group and modified nucleobase. This triphosphate competes with the natural substrate adenosine triphosphate. Additionally, its mechanisms of action based on RNA and proofreading exonuclease inhibition, leading to the delayed RNA chain termination of infected cells, and basic pharmacological data were assessed. Additionally, the analytical determination of remdesivir and its metabolites in cells and body liquids and also some data from remdesivir use in other RNA infections—such as Ebola, Nipah virus infection, and Middle East Respiratory Syndrome (MERS)—were summarized. More recent and more detailed data on the clinical use of remdesivir in COVID-19 were reported, showing the intensive efforts of clinicians and scientists to develop a cure for this new disease. Remdesivir as such represents one of the more promising alternatives for COVID-19 therapy, however the current understanding of this disease and the possible ways of dealing with it requires further investigation. Full article

Objective: This study evaluated the effect of melatonin on the response of patients suffering from metabolic syndrome (MEBS) treated with metformin. Design: This study used two-armed groups in a double-blind, randomized controlled clinical trial. Materials and Methods: A randomized double-blind placebo-controlled study was carried out on female patients diagnosed as having MEBS, according to the International Diabetes Federation (IDF) diagnosing criteria of MEBS (2005), from the outpatient clinic in Al-Zahraa Teaching Hospital/Kut, Iraq. They were diagnosed utilizing laboratory and clinical investigations, then randomized into two groups. The first group (group A) was treated with metformin (500 mg) twice daily, in addition to a placebo formula once daily at bedtime for three months. The second group (group B) was treated with metformin (500 mg) twice daily after meals, in addition to melatonin (10 mg) once daily at bedtime for three months. Results: The treatment of patients with MEBS using metformin–melatonin showed an improvement in most MEBS components such as fasting serum glucose (FSG), lipid profile, and body mass index (BMI), in addition to a reduction in insulin resistance and hyperinsulinemia. Simultaneously, there were increments in serum uric acid (UA), leptin, prolactin (PRL), and estradiol levels, while serum progesterone level decreased. Furthermore, patients treated with metformin–placebo showed less improvement in the studied parameters compared to that produced due to the inclusion of melatonin in the treatment protocol. Conclusion: Melatonin improves the effect of metformin on several components of MEBS such as FSG, lipid profile, and BMI, in addition to insulin resistance and hyperinsulinemia, compared to metformin alone. Full article

The skin is constantly exposed to various environmental stresses, in particular to the damage caused by pollution and ultraviolet radiation (UV), and as a consequence, the horny extract can be negatively impacted by the harmful influence of some of its surface components. The mechanisms involved in the degradation processes promoted by UV radiation are driven by the direct absorption of radiation via cellular chromophores, the formation of excited states and the consequent chemical reactions, or even by the photosensitization mechanisms, in which UV light is absorbed by the sensitizers that are excited and their reactions promote the formation of reactive oxygen species (ROS). The mechanisms of polluting agents are not yet fully understood, however, they indicate that one of the main mechanisms involved is oxidative stress by lipid peroxidation, with the ability to promote damage to the composition of sebum, the quality of the stratum corneum and also, promote aging skin. Recent studies demonstrate the potential of antioxidant agents, with an emphasis on products of natural origin, which try to promote the maintenance of the physiological balance of the skin. Full article

Medicinal plants hold a significant place as alternative treatments available for inflammatory diseases, with many phytoconstituents being frequently tested in vitro for their biological activities. In the current study, we investigated the in vivo anti-inflammatory properties of a novel active gel formulation, combining Achillea millefolium and Taxodium distichum essential oils with extracts of Aesculus hippocastanum seeds and Plantago lanceolata leaves. The toxicity of the obtained extracts and volatile oils was determined using the invertebrate model based on Daphnia magna. Anti-inflammatory potential was evaluated by the plethysmometric method on Wistar rats, expressed as the inhibition of the inflammatory oedema (%IIO), while the antinociceptive response was determined on NMRI mice, according to the tail-flick latency method. The tested gel’s efficacy was similar to the 5% diclofenac standard (maximal %IIO of 42.01% vs. 48.70%, respectively), with the anti-inflammatory effect being observed sooner than for diclofenac. Our active gel also produced a significant prolongation of tail-flick latencies at both 60 and 120 min, comparable to diclofenac. Consequently, we can imply that the active constituents present in vivo anti-inflammatory properties, and the prepared gel may be suited for use as an alternative treatment of topical inflammatory conditions. Full article

The pharmacotherapy of critically ill patients is challenging due to the variety of drugs that have to be applied. As the majority of pharmaceuticals must be administered intravenously because of the critical condition of the patients, the compatibility of co-applied intravenous drugs is crucial for a safe and successful infusion therapy. Antihypertensive therapy was reported by health care professionals to be ineffective in association with concomitant application of dihydralazine and metamizole (dipyrone). As both drugs are administered in German intensive care units, we analyzed their compatibility, examined the mechanisms of underlying dihydralazine degradation, and identified reaction products of dihydralazine and metamizole. Binary combinations were prepared at the high and the low end of the nominal administration concentration. Validated high performance liquid chromatography/ultraviolet absorption (HPLC-UV) analysis was conducted to quantify drug amount and high performance liquid chromatography/mass spectrometry (HPLC-MS) was used to analyze degradation products. The combinations of dihydralazine and metamizole proved to be incompatible as dihydralazine concentration decreased immediately and considerably. Metamizole also slightly decreased over time. Specific degradation products of dihydralazine were identified and a degradation pathway was postulated. Our findings demonstrate that the intravenous co-administration of dihydralazine and metamizole should be strictly avoided due to the incompatibility of these two drugs. Full article

Developed methods for routine analysis of medicines should be considered in terms of analytical efficiency, economic cost, as well as their environmental impact. Different chromatographic methods for the routine quantitative analysis of hederacoside C in ivy leaf extract and its original dosage forms (capsules and syrup) are developed. The performance of HPLC and UPLC methods should be done using ACE C18 (150 mm × 4.6 mm, 5.0 μm) and ACQUITY UPLC BEH C18 (50 mm × 2.1 mm, 1.7 μm) columns, respectively, and both of them require a mixture of water and acetonitrile in the ratio 71/29 as a mobile phase. The HPTLC procedure is carried out using the stationary phase pre-coated silica gel 60 F₂₅₄ glass sheets and a mixture of anhydrous formic acid/acetone/methanol/ethyl acetate (4:20:20:30 v/v). The most suitable conditions of preparation for each sample are established, for instance, the solid-phase extraction (SPE) for the analysis of syrup is applied. Analytical methods are compered by analytical accuracy, calculation of expenses, and assessment of their influence on ecology. All methods are recognized as accurate, precise, and reliable. However, the assessment of the environmental impact shows that HPTLC is the less green method. On the another hand, it is found to be the cheapest, the costs of performing HPTLC are 2.3 and 1.6 times lower than for HPLC and UPLC, respectively. Full article

Essential oils are volatile fragrance liquids extracted from plants, and their compound annual growth rate is expected to expand to 8.6% from 2019 to 2025, according to Grand View Research. Essential oils have several domains of application, such as in the food and beverage industry, in cosmetics, as well as for medicinal use. In this study, Michelia alba essential oil was extracted from leaves and was rich in linalool components as found in lavender and jasmine oil. The effects of inhaling michelia oil on human brainwaves still need to be elucidated. Ten male and ten female subjects were recruited. Thirty-two-channel electroencephalography was recorded. The raw data were spectrally analyzed for slow alpha, fast alpha, low beta, mid beta, and high beta activities. The results demonstrate that michelia leaf oil could reduce the alertness level observed by beta wave decrease and fast alpha wave activity increase. The inhalation of pure linalool showed virtually identical responses as the michelia oil inhalation. In conclusion, the sedative effects of michelia oil inhalation might originate from its major linalool component. Full article

Several topical products have been developed to avoid the harmful effects from ultraviolet (UV) radiation, such as sunscreens. Research for actives from natural sources is increasing due to the fact that chemical filters could induce adverse events. The microalgae Botryococcus braunii has potential interest in cosmetic applications. Specialized literature reported that B. braunii aqueous extract induced a reduction in skin dehydration and collagen production and promoted antioxidant activity. This research aimed to produce B. braunii biomass and to investigate its contribution regarding photoprotection. Formulations containing B. braunii dry biomass, with or without UV filters into vehicles composed of an emulsifying polymer or a self-emulsifying base, were evaluated in vitro by means of photoprotective activity and photostability. B. braunii dry biomass did not provide adequate photoprotection efficacy; however, it was observed that the self-emulsifying base promoted better sun protection factor (SPF) in comparison with the emulsifying polymer. Full article

The objectives of this study were to prepare and characterize a novel piperine–succinic acid multicomponent crystal phase and to evaluate the improvement in the solubility and dissolution rate of piperine when prepared in the multicomponent crystal formation. The solid-state characterization of the novel multicomponent crystal was performed by powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform-infrared (FT-IR) spectroscopy. Solubility and dissolution rate profiles were evaluated in distilled water. The physical stability was evaluated under high relative humidity (75% and 100% RH). The determination of the single crystal X-ray diffraction structure revealed that this novel multicomponent crystal was a cocrystalline phase of piperine–succinic acid (2:1 molar ratio). The differential scanning calorimetry thermogram of the cocrystal showed a single and sharp endothermic peak at 110.49 °C. The cocrystal resulted in greater solubility and a faster dissolution rate of piperine than intact piperine. This improvement was a result of the formation of a channel structure in the cocrystal. In addition, the cocrystal was stable under a humid condition. Full article

3-O-ethyl l-ascorbic acid (EA), an ether derivative of Vitamin C, is widely used in skincare formulations. Previously, we reported the effects of neat solvents on EA percutaneous absorption and observed that 0.6–7.5% of the applied EA was delivered through the skin over 24 h. In this work, we designed complex formulations using combinations of solvents that may act synergistically and examined their impact on EA permeation in porcine skin in vitro under finite dose conditions. Binary combinations of propylene glycol (PG) with propylene glycol monolaurate (PGML) were effective in enhancing skin permeation of EA compared with individual solvents (p < 0.05). Combining PGML with 1,2-hexanediol (HEX) did not result in significantly higher EA permeation compared with the neat solvents (p > 0.05). Addition of the volatile solvent isopropyl alcohol (IPA) to PG solutions also did not improve EA skin delivery compared with neat PG. Ternary solvent systems containing PG:PGML were subsequently prepared by the addition of a lipophilic solvent, either isopropyl myristate (IPM), medium-chain triglycerides (MCT) or isostearyl isostearate (ISIS). The optimum vehicle, PG:PGML:IPM, promoted up to 70.9% skin delivery of EA. The PG:PGML:ISIS vehicles also promoted EA permeation across the skin, but to a significantly lesser extent than the IPM-containing vehicles. No enhancement of EA delivery was noted for the PG:PGML:MCT mixtures. These results will inform the development of targeted formulations for EA in the future. Full article

Recently, we identified the promising anticancer potential of the synthetic 4-thiazolidinone-based anticancer lead compound Les-3833 which demonstrated tumor-suppressing action in vitro and in vivo. Based on the results of previous studies, the aim of this research was to investigate the cytotoxicity in vitro and the biodistribution in laboratory mice to support the biotherapeutic drug development of Les-3833. Les-3833 (2.5 mg/kg) was intravenously injected into male Balb/c mice. Measurements were performed at 5 min, 15 min, 1 h, 4 h, and 24 h time points in blood plasma, brain, liver, and kidney using high-performance liquid chromatography/tandem mass spectrometry. After the administration of Les-3833, the maximum level of this compound was observed in plasma at 2.08 min. In the brain, the mean maximum concentration of Les-3833 was 7.17 ng/mL at 5 min, while after 15 min, it was not found. In the liver, at 5 min, the maximum concentration was 1190 ng/g. At 15 min, concentration of Les-3833 in the liver decreased by 14.3%; at 6 h by 22.8%; and after 24 h by 64.7%. Its maximum concentration in kidney was 404 ng/g within 5–15 min, at 1 h it decreased by 36.1%, and after 24 h by 49.3%. Thus, Les-3833 was rapidly taken up by different organs from the bloodstream, partially metabolized in the liver, and excreted mainly through the kidneys, while in the brain, a very low concentration could be observed for only a short period of time. Full article

Self-emulsifying drug delivery systems (SEDDSs) originated as an oral lipid-based drug delivery system with the sole purpose of improving delivery of highly lipophilic drugs. However, the revolutionary drug delivery possibilities presented by these uniquely simplified systems in terms of muco-adhesiveness and zeta-potential changing capacity lead the way forward to ground-breaking research. Contrarily, SEDDSs destined for topical/transdermal drug delivery have received limited attention. Therefore, this review is focused at utilising principles, established during development of oral SEDDSs, and tailoring them to fit evaluation strategies for an optimised topical/transdermal drug delivery vehicle. This includes a detailed discussion of how the authentic pseudo-ternary phase diagram is employed to predict phase behaviour to find the self-emulsification region most suitable for formulating topical/transdermal SEDDSs. Additionally, special attention is given to the manner of characterising oral SEDDSs compared to topical/transdermal SEDDSs, since absorption within the gastrointestinal tract and the multi-layered nature of the skin are two completely diverse drug delivery territories. Despite the advantages of the topical/transdermal drug administration route, certain challenges such as the relatively undiscovered field of skin metabolomics as well as the obstacles of choosing excipients wisely to establish skin penetration enhancement might prevail. Therefore, development of topical/transdermal SEDDSs might be more complicated than expected. Full article

Here, we describe the synthesis and anticonvulsant activity of thiazole-bearing hybrids based on 2-imino-4-thiazolidinone and 2,4-dioxothiazolidine-5-carboxylic acid cores. The structure of target compounds was based on the following: (i) A combination of two thiazole cores; (ii) similarity to ralitolin’s structure; (iii) the compliance with structural requirements for the new anticonvulsants. Target compounds were synthesized via known approaches based on Knoenavegel reaction, alkylation reaction, and one-pot three-component reaction. Anticonvulsant properties of compounds were evaluated in two different models—pentylenetetrazole-induced seizures and maximal electroshock seizure tests. Among the tested compounds 5Z-(3-nitrobenzylidene)-2-(thiazol-2-ylimino)-thiazolidin-4-one Ib, 2-[2,4-dioxo-5-(thiazol-2- ylcarbamoylmethyl)-thiazolidin-3-yl]-N-(2-trifluoromethylphenyl)acetamide IId and (2,4-dioxo-5- (thiazol-2-ylcarbamoylmethylene)-thiazolidin-3-yl)acetic acid ethyl ester IIj showed excellent anticonvulsant activity in both models. The directions of compounds modification based on SAR aspects were discussed. The results of the study provide a basis for further study of the anticonvulsant properties of selected thiazole-thiazolidinones. Full article