rss_2.0Acta Pharmaceutica FeedSciendo RSS Feed for Acta Pharmaceuticahttps://sciendo.com/journal/ACPHhttps://www.sciendo.comActa Pharmaceutica 's Coverhttps://sciendo-parsed-data-feed.s3.eu-central-1.amazonaws.com/634ee1e9bacc361c9f20ed40/cover-image.jpg?X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Date=20221205T090401Z&X-Amz-SignedHeaders=host&X-Amz-Expires=604800&X-Amz-Credential=AKIA6AP2G7AKP25APDM2%2F20221205%2Feu-central-1%2Fs3%2Faws4_request&X-Amz-Signature=6a4de1cd4e23952c4b7107a8d5bb7261e7c44515dd398c07af4efdb62483811f200300Optimized D-α-tocopherol polyethylene glycol succinate/phospholipid self-assembled mixed micelles: A promising lipid-based nanoplatform for augmenting the antifungal activity of fluconazolehttps://sciendo.com/article/10.2478/acph-2022-0028<abstract> <title style='display:none'>Abstract</title> <p>Fluconazole (FLZ) is the most widely used antifungal agent for treating cutaneous candidiasis. Although oral FLZ has been proved to be effective, the incidence of side effects necessitates the development of an effective formulation that could surpass the pitfalls associated with systemic availability. Accordingly, this research aimed at developing a self-assembled mixed micelles topical delivery system to enhance the topical delivery of the drug. Self-assembled mixed micelles were developed using D-α-tocopheryl polyethylene glycol 1000 succinate and phospholipids and optimized using Box-Behnken design. The optimized formulation with minimized size was then tested <italic>in vivo</italic> for the antifungal activity against <italic>C. albicans</italic> in immunocompromised mice. Treatment with the optimized formulation led to decreased peripheral erythema as well as lesions due to fungal infection in comparison to raw FLZ loaded gel. Therefore, the developed formulation was found to be a promising vehicle for the treatment of cutaneous candidiasis.</p> </abstract>ARTICLE2022-10-18T00:00:00.000+00:00Direct oral anticoagulants (DOACs): From the laboratory point of viewhttps://sciendo.com/article/10.2478/acph-2022-0034<abstract> <title style='display:none'>Abstract</title> <p>Direct oral anticoagulants (DOACs) represent a new generation of drugs that have been increasingly used in the prevention and treatment of thromboembolic states. According to the mechanism of anticoagulant action, DOACs are divided into two groups: direct inhibitors of thrombin (dabigatran) and direct inhibitors of activated factor X (FXa) (rivaroxaban, apixaban, edoxaban, betrixaban). Compared to the vitamin K antagonists, DOACs are superior in terms of onset of action, pharmacokinetic and pharmacodynamics properties and fixed daily dose without the need for routine coagulation monitoring. Despite these advantages, there are clinical conditions in which laboratory measurement of DOACs should be performed. Although DOACs have an impact on screening haemostasis assays (prothrombin time, PT; activated partial thromboplastin time, aPTT; and thrombin time, TT), these tests are not appropriate for quantifying drug levels. Therefore, specific quantitative methods (LC-MS/MS as a gold standard method for all DOACs, coagulometric and chromogenic assays for dabigatran, and chromogenic anti-Xa assays with drug-specific calibrators for inhibitors of FXa) should only be used for determination of DOACs concentration. The aim of this review is to present all aspects of laboratory assessment of DOACs, including pre-analytical, analytical and post-analytical factors in the overall testing process with a special accent on the available specific quantitative methods for measurement of DOACs in circulation.</p> </abstract>ARTICLE2022-10-18T00:00:00.000+00:00Anti-inflammatory effects of NaB and NaPc in -stimulated THP-1 cells TLR-2/NF-κB/ROS/NLRP3 pathwayhttps://sciendo.com/article/10.2478/acph-2022-0036<abstract> <title style='display:none'>Abstract</title> <p>This study evaluated the anti-inflammation effect of the three main short-chain fatty acids (SCFAs) on <italic>Acinetobacter baumannii</italic>-induced THP-1 cells. The three main SCFAs could inhibit <italic>A. baumannii</italic>-stimulated THP-1 cell NF-κB pathway activity and the expressions of NLRP3 inflamma-some and GSDMD, and increase autophagy. The three main SCFAs, especially the sodium butyrate (NaB), had the effect of down-regulation of ROS and <italic>TLR-2</italic> expression in THP-1 cells. NaB and sodium propionate (NaPc), but not sodium acetate (NaAc), dramatically suppressed <italic>IL-1β</italic> and <italic>IFN-γ</italic> expression. The results indicated that NaB and NaPc could significantly inhibit the inflammation of THP-1 cells induced by <italic>A. baumannii</italic>, and the inhibitory effect was in the order of NaB &gt; NaPc &gt; NaAC. NaB and NaPc may inhibit inflammation through TLR-2/NF-κB/ROS/NLRP3 signaling pathway.</p> </abstract>ARTICLE2022-10-18T00:00:00.000+00:00Synergistic action between a synthetic cannabinoid compound and tramadol in neuropathic pain ratshttps://sciendo.com/article/10.2478/acph-2022-0037<abstract> <title style='display:none'>Abstract</title> <p>In the present study the interaction of cannabinoid, PhAR-DBH-Me [(<italic>R</italic>, <italic>Z</italic>)-18-((1<italic>S</italic>,4<italic>S</italic>)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)-18-oxooctadec-9-en-7-ylphenyl-acetate] and tramadol in two neuropathy models, as well as their possible toxic effects, was analyzed. The anti-allodynic effect of PhAR-DBH-Me, tramadol, or their combination, were evaluated in neuropathic rats. Furthermore, the effective dose 35 (as the 35 % of the anti allodynic effect) was calculated from the maximum effect of each drug. Moreover, the isobolographic analysis was performed to determine the type of interaction between the drugs. A plasma acute toxicity study was carried out to assess the hepatic, renal, and heart functions after an individual or combined administration of the drugs, as well as histology using the hematoxylin-eosin or Masson-trichome method. PhAR-DBH-Me, tramadol, and their combination produced an antiallodynic effect on spinal nerve ligation (SNL) and cisplatin-induced neuropathic pain in rats. Moreover, PhAR-DBH-Me and tramadol combination showed a synergistic interaction in neuropathic pain rats induced by SNL but not for cisplatin-induced neuropathy. On the other hand, changes in renal and hepatic functions were not observed. Likewise, analysis of liver, kidney and heart histology showed no alterations compared with controls. Results show that the combination of PhAR-DBH-Me and tramadol attenuates the allodynia in SNL rats; the acute toxicology analysis suggests that this combination could be considered safe in administered doses.</p> </abstract>ARTICLE2022-10-18T00:00:00.000+00:00Therapeutic alliance impact on analgesic outcomes in a real-world clinical setting: An observational studyhttps://sciendo.com/article/10.2478/acph-2022-0035<abstract> <title style='display:none'>Abstract</title> <p>A good therapeutic alliance is relevant for healthcare providers exposed to patients’ suffering, especially since patients and physicians may understand the painful experience differently. Our aim was to explore the impact of therapeutic alliance on analgesic outcomes in a real-world interdisciplinary pain unit (PU). A cross-sectional observational study was conducted on outpatients (<italic>n</italic> = 69) using opioids on a long-term basis for the treatment of chronic non-cancer pain, where clinical pharmacologists and pharmacists advised patients about their opioid treatment. Responses to the patient-doctor relationship questionnaire (PDRQ), sociodemographic and clinical information (pain level, quality of life and hospital use) were collected, whereas pharmacology data (analgesic prescription, adverse events, and compliance) were obtained from electronic health records. Patients were predominantly middle-aged (75 % women, 72 % retired), experiencing moderate pain (VAS 40–70 mm) on average, and under a high morphine equianalgesic dosage (95 ± 88 mg per day, mainly tapentadol or fentanyl). Patients with better PDRQ outcomes, and therefore better therapeutic alliance, showed lower pain intensity than patients with worse PDRQ outcomes (pain intensity: high scores 60 ± 47 mm and medium scores 60 ± 45 mm <italic>vs</italic>. low scores 80 ± 75 mm, <italic>p</italic> &lt; 0.01). Along with this, pain intensity was lower when patients affirmed that, thanks to the health-care providers, they “gained new insight”, “felt better”, or “felt content with their doctor’s treatment”. What´s more, patients who affirmed “I benefit from the treatment” experienced increased pain relief (benefit 40 ± 30 <italic>vs</italic>. non-benefit 19 ± 26 mm, <italic>p</italic> = 0.010) and improved quality of life (benefit 33 ± 25 <italic>vs</italic>. non-benefit 18 ± 16 mm, <italic>p</italic> = 0.031). However, there was a percentage of patients who did not fully understand the provided information, which is something to be taken into account to improve in clinical routine. Therapeutic alliance supported by pharmacist experts on pain management can be an effective strategy to improve analgesic outcomes. Further efforts are needed to improve communication strategies for pain management. Future directions of research should include the analysis of the role of the pharmacist in poly-professional consultations as related to the advice of patients about their medication, and the mutual trust with the patients.</p> </abstract>ARTICLE2022-10-18T00:00:00.000+00:00Punicalagin attenuated allergic airway inflammation regulating IL4/IL-4Rα/STAT6 and Notch- GATA3 pathwayshttps://sciendo.com/article/10.2478/acph-2022-0038<abstract> <title style='display:none'>Abstract</title> <p>Allergic asthma is an inflammatory disease of the airways which has a complex etiology. Punicalagin, a major polyphenol present in pomegranates, is reported to possess various biological properties including antioxidant and antiproliferative effects. The current research aimed to evaluate the antiasthmatic effects of punicalagin in an ovalbumin (OVA)-induced experimental model of asthma in female BALB/c mice. Treatment group animals received punicalagin (12.5, 25 or 50 mg kg<sup>−1</sup> body mass) per day for 21 days from day 1 of OVA injection. Dexamethasone (DEX) was administered to a separate group of mice, as the standard drug control. Inflammatory cell infiltration into the broncho-alveolar lavage fluid (BALF) was substantially decreased in punicalagin-treated mice. Punicalagin reduced Th2-derived cytokines and OVA-specific IgE levels. The IL-4/STAT6 and Notch/GATA3 signalling pathways were regulated on punicalagin administration. The data obtained illustrate the potency of punicalagin as an anti-asthmatic drug. Conclusively, the study’s observations suggest the potential therapeutic efficiency of punicalagin in allergic asthma.</p> </abstract>ARTICLE2022-10-18T00:00:00.000+00:00Effect of gastrointestinal digestion on the chemical composition and antioxidant properties of leaves decoction and commercial capsuleshttps://sciendo.com/article/10.2478/acph-2022-0033<abstract> <title style='display:none'>Abstract</title> <p>In this study <italic>Ginkgo biloba</italic> leaves (GBL) decoction and commercial capsules were digested using an <italic>in vitro</italic> model. Thirty-six active compounds were identified and quantified by HPLC-ESI-MS analysis based on the MS/MS patterns (precursor ions and product ions) and retention times, in comparison with reference standards. Most compounds in GBL showed a significant decrease during intestinal digestion, with an exception of vanillic acid and biflavonoids. Bioaccessibility values of chemical compositions varied between decoction and capsules samples. Also, significant reductions of total flavonoids and total phenolic content was observed after <italic>in vitro</italic> digestion. Both, 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis (3-ethylbenzothiazo-line-6-sulfonic acid (ABTS) scavenging capacity decreased after gastric digestion, but increased during intestinal digestion. Nevertheless, different behaviour was observed in reducing antioxidant power (FRAP) assay. Compared to the pH of digestion, the influence of digestive enzymes on the chemical composition and antioxidant activity of GBL was relatively minor. Overall, these results may help provide a valid foundation for further investigations on bioactive compounds and the pharmacodynamics of GBL.</p> </abstract>ARTICLE2022-10-18T00:00:00.000+00:00Relaxin inhibits Lu-EDTMP associated cell death in osteosarcoma cells through notch-1 pathwayhttps://sciendo.com/article/10.2478/acph-2022-0032<abstract> <title style='display:none'>Abstract</title> <p><sup>177</sup>Lu-EDTMP (Ethylenediamine tetramethylene phosphonic acid) is the most used radioactive agent for pain palliation in bone cancer patients. The present study aims to study the impact of relaxin-2 on the <sup>177</sup>Lu-EDTMP associated cell toxicity and death in osteosarcoma cells. MG63 and Saos-2 cells were cultured with <sup>177</sup>Lu-EDTMP (37 MBq) for 24 h with and without pretreatment of recombinant relaxin 2 (RLXH2) for 12 and 24 h. <sup>177</sup>Lu-EDTMP associated cellular deterioration and death was determined by LDH, MTT, and trypan blue dye assays. ELISA-based kit was used to determine apoptotic DNA fragmentation. Western blotting was used to determine expression levels of apoptotic-related signalling pathway proteins like bcl2, poly(ADP-ribose) polymerase (PARP), and MAPK (mitogen-activated protein kinase). Our results found that RLXH2 counters <sup>177</sup>Lu-EDTMP associated cellular toxicity. Similarly, RLXH2 was able to counter <sup>177</sup>Lu-EDTMP induced cell death in a concentration and time--dependent manner. Furthermore, it was found that RLXH2 treatment prevents apoptosis in <sup>177</sup>Lu-EDTMP challenged cells through activation of the notch-1 pathway in a concentration- and time-dependent manner. We reported that RLXH2 significantly declined cellular toxicity and apoptosis associated with <sup>177</sup>Lu-EDTMP in MG63 and Saos-2 cells through the notch-1 pathway.</p> </abstract>ARTICLE2022-10-18T00:00:00.000+00:00 effects of ascorbic acid on viability and metabolism of patients’ osteosarcoma stem cellshttps://sciendo.com/article/10.2478/acph-2022-0040<abstract> <title style='display:none'>Abstract</title> <p>Stagnation in novelties of osteosarcoma (OS) treatment indicates the need for new therapeutic methods. OS cancer stem cells (OS-CSC) are taught to have the ability to self-renew and develop mechanisms of anticancer drug resistance, and this is why it is difficult to eradicate them. Their metabolism has been recognized as a potential target of therapeutic action. Ascorbic acid (AA) is considered to act pro-oxidative against OS-CSC <italic>in vitro</italic> by oxidative effect and by inhibition of glycolysis. This study examined an <italic>in vitro</italic> impact of AA on OS-CSC metabolism isolated from patients’ biopsies, with the aim of better understanding of OS-CSC metabolism and the action of AA on OS-CSC. OS-CSC were isolated using a sphere culture system and identified as stem cells using Hoechst 33342 exclusion assay. Determination of the dominant type of metabolism of OS-CSC, parental OS cells, human mesenchymal stem cells (hMSC) and U2OS OS lineage before and after AA treatment was done by Seahorse XF (Agilent). Cytotoxicity of high-dose AA was confirmed by the MTT test and was proven for all the examined cell types as well as HEK293. Seahorse technology showed that OS-CSC can potentially use both glycolysis and oxidative phosphorylation (OXPHOS), and can turn to glycolysis and slow metabolic potential in unfavorable conditions such as incubation in AA.</p> </abstract>ARTICLE2022-10-18T00:00:00.000+00:00MicroRNA-140-5p inhibits cellular proliferation, migration and invasion by downregulating AKT/STAT3/NF-κB pathway in breast carcinoma cellshttps://sciendo.com/article/10.2478/acph-2022-0039<abstract> <title style='display:none'>Abstract</title> <p>MicroRNA-140-5p (miR-140-5p) plays a pivotal role in human cancers. However, its role and molecular mechanisms in breast carcinoma are not fully explored. Using miR-140-5p transfected breast cancer cell line MDA-MB-231, several <italic>in vitro</italic> experiments were performed and described in this paper. They consist of the cell proliferation assay, wound healing assay, transwell assay, colony formation assays and qRTPCR. Expression levels of target proteins were determined using Western blotting. In addition, experiments on animal models were performed to study the possible role of miR-140-5p in tumorigenesis of breast carcinoma cells. The induction of experimental breast tumor in mice model was achieved through the incorporation of MDA-MB-231 tumor cells subcutaneously into the middle left side of the mice. The results showed that miR-140-5p up-regulation significantly suppresses proliferation, cellular invasion and migration of breast carcinoma cells. Furthermore, miR-140-5p up-regulation stops breast cancer cells at G0/G1 phase. The results of the animal model indicated that up-regulation of miR-140-5p suppresses its tumorigenic ability. Moreover, we also found that miR-140-5p up-regulation reduces the phosphorylation level of STAT3, p65, and AKT. In addition, miR-140-5p overexpression significantly decreases CDK2 expression while increasing E-cadherin expression level. These data revealed that miR-140-5p suppressed tumor progression of breast carcinoma cells through inhibition of the AKT/STAT3/NF-κB pathway. Taken the present study results together, we can conclude that miR-140-5p may act as a novel target in microRNA-targeting anticancer strategy for the treatment of breast cancer.</p> </abstract>ARTICLE2022-10-18T00:00:00.000+00:00Design and development of novel 1,2,3-triazole chalcone derivatives as potential anti-osteosarcoma agents inhibition of PI3K/Akt/mTOR signalling pathwayhttps://sciendo.com/article/10.2478/acph-2022-0026<abstract> <title style='display:none'>Abstract</title> <p>Osteosarcoma (OS) is an uncommon tumour that mainly affects bone in children and adolescents. The current treatment options of OS are of limited significance due to their immense side effects. In the present manuscript, we have developed a novel series of 1,2,3-triazole chalcone derivatives as potential agents against OS. The compounds were synthesized and evaluated for their PI3K and mTOR inhibitory activity using luminescent kinase assay, and Lance ultra assay, resp. The entire set of compounds showed significant to moderate inhibition of both kinases in the nanomolar range. The three most active compounds: <bold>4e</bold> (<italic>N</italic>-(4-(3-(1-(4-bromophenyl)-1<italic>H</italic>-1,2,3-triazol-4-yl)acryloyl)phenyl)-4-nitrobenzamide), <bold>4f</bold> (<italic>N</italic>-(4-(3-(1-(4-bromophenyl)-1<italic>H</italic>-1,2,3-triazol-4-yl)acryloyl)phenyl)-4-chlorobenzamide) and <bold>4g</bold> (4-bromo-<italic>N</italic>-(4-(3-(1-(4-bromophenyl)-1<italic>H-</italic>1,2,3-triazol-4-yl)acryloyl)phenyl)benzamide), were evaluated for anticancer activity against human OS cancer cell line (MG-63), liver cancer cell line (HepG2), lung cancer cell line (A549) and cervical cancer (HeLa), using MTT assay. Among the tested series, compound <bold>4e</bold> showed a better inhibitory profile than gedatolisib against PI3K and was approximately comparable to that of gedatolisib against mTOR. The most significant inhibitory activity was observed for compound <bold>4e</bold> against all cell lines (MG-63, HepG2, A549 and HeLa), still somewhat lower to comparable to that of gedatolisib, but with the highest potency against MG-63 cells. Compound <bold>4e</bold> was further tested for anti-cancer activity against other OS cells and showed to be equipo-tent to gedatolisib against U2OS and Saos-2 cells. Moreover, it was also found non-toxic to normal cells (BEAS-2B and MCF 10A). The effect of compound <bold>4e</bold> was further determined on apoptosis of Saos-2 cells by Annexin-PI assay, where it significantly amplified the percentage of apoptotic cells. Novel 1,2,3-triazole chalcone derivatives are potential agents against OS.</p> </abstract>ARTICLE2022-04-13T00:00:00.000+00:00Polyphenol content and antioxidant activity of phytoestrogen containing food and dietary supplements: DPPH free radical scavenging activity by HPLChttps://sciendo.com/article/10.2478/acph-2022-0031<abstract> <title style='display:none'>Abstract</title> <p>Soy, red clover, chaste tree, hop and flax have all been found to contain a wide range of phytoestrogenic compounds, and a large number of dietary supplements contain their extracts as principal ingredients. This study is aimed to evaluate the total polyphenolic content and antioxidant activity of phytoestrogen-containing food and formulated dietary supplements. The HPLC-DPPH method was applied for DPPH free radical scavenging activity testing of various phytoestrogen-containing samples. Polyphenol content and antioxidant activity in dietary supplements were higher than in functional food samples; multiple-botanical-source preparations showed higher polyphenol content and antioxidant activity than the mono-botanical counterparts. Furthermore, the correlation between polyphenol content and anti-oxidant activity was strongly statistically significant, so it might be concluded that antioxidant activity is proportional to the content of these secondary metabolites. The most striking batch-to-batch deviations were represented by one chaste berry-based product (RSD 41.3 %) and one red clover derived product (RSD 57.9 %). The results of this study contribute to a better understanding of the phenolic profile and antioxidant properties of phytoestrogen containing food and dietary supplements.</p> </abstract>ARTICLE2022-04-13T00:00:00.000+00:00Potential anti-ageing effects of probiotic-derived conditioned media on human skin cellshttps://sciendo.com/article/10.2478/acph-2022-0027<abstract> <title style='display:none'>Abstract</title> <p>In this study, the protective functions of bacteria-free conditioned media from <italic>Bifidobacterium</italic> and <italic>Lactobacillus</italic> species against ultraviolet radiation-induced skin ageing and associated cellular damage were investigated. The effects of ultraviolet radiation-induced reactive oxygen species production were suppressed by all conditioned media; particularly, the loss of cell viability and downregulation of collagen gene expression were significantly reversed by the conditioned media from <italic>B. longum</italic> and <italic>B. lactis</italic>. Further exa mination of potential anti-pigmentation effects revealed that the <italic>B. lactis</italic>-derived conditioned media significantly inhibited tyrosinase activity and alpha-melanocyte-stimulating hormone-induced melanin production in human epidermal melanocytes. Further, the conditioned media suppressed the phosphorylation of extracellular signal- related kinase, which functions as an upstream regulator of melanogenesis. Therefore, <italic>B. lactis</italic>-derived conditioned media can potentially protect against cellular damage involved in skin-ageing processes.</p> </abstract>ARTICLE2022-04-13T00:00:00.000+00:00Fingolimod exerts anticancer activity against hepatocellular carcinoma cell lines YAP/TAZ suppressionhttps://sciendo.com/article/10.2478/acph-2022-0029<abstract> <title style='display:none'>Abstract</title> <p>Hepatocellular carcinoma (HCC) remains a notably global health challenge with high mortality rates and poor prognosis. The deregulation of the Hippo signalling pathway, especially the overexpression and activation of downstream effector Yes-associated protein (YAP), has been demonstrated to result in the rapid malignant evolution of HCC. In this context, multiple efforts have been dedicated to targeting YAP for HCC therapy, but effective YAP inhibitors are still lacking. In this study, through a YAP-TEAD (8×GTIIC) luciferase reporter assay, we identified fingolimod, an immunomodulatory drug approved for the treatment of multiple sclerosis, as a novel YAP inhibitor. Fingolimod suppressed the proliferation of HCC cell lines by downregulating the protein levels as well as the trans-activating function of YAP. Overall, our current study not only identifies fingolimod as a novel YAP-targeting in hibitor, but also indicates that this clinically-approved drug could be utilized as a potential and feasible therapeutic drug for HCC.</p> </abstract>ARTICLE2022-04-13T00:00:00.000+00:00Metabolomics reveal the mechanism for anti-renal fibrosis effects of an -butanol extract from https://sciendo.com/article/10.2478/acph-2022-0023<abstract> <title style='display:none'>Abstract</title> <p>To reveal the mechanism of anti-renal fibrosis effects of an <italic>n</italic>-butanol extract from <italic>Amygdalus mongolica,</italic> renal fibrosis was induced with unilateral ureteral obstruction (UUO) and then treated with an <italic>n</italic>-butanol extract (BUT) from <italic>Amygdalus mongolica</italic> (Rosaceae). Sixty male Sprague-Dawley rats were randomly divided into the sham-operated, renal fibrosis (RF) model, benazepril hydrochloride-treated model (1.5 mg kg<sup>−1</sup>) and BUT-treated (1.75, 1.5 and 1.25 g kg<sup>−1</sup>) groups and the respective drugs were administered intragastrically for 21 days. Related biochemical indices in rat serum were determined and histopathological morphology observed. Serum metabolomics was assessed with HPLC-Q-TOF-MS. The BUT reduced levels of blood urea nitrogen, serum creatinine and albumin and lowered the content of malondialdehyde and hydroxyproline in tissues. The activity of superoxide dismutase in tissues was increased and an improvement in the severity of RF was observed. Sixteen possible biomarkers were identified by metabolomic analysis and six key metabolic pathways, including the TCA cycle and tyrosine metabolism, were analyzed. After treatment with the extract, 8, 12 and 9 possible biomarkers could be detected in the high-, medium- and low-dose groups, respectively. Key biomarkers of RF, identified using metabolomics, were most affected by the medium dose. <italic>A. mongolica</italic> BUT extract displays a protective effect on RF in rats and should be investigated as a candidate drug for the treatment of the disease.</p> </abstract>ARTICLE2022-04-13T00:00:00.000+00:00Evaluation and molecular modelling of bis-Schiff base derivatives as potential leads for management of diabetes mellitushttps://sciendo.com/article/10.2478/acph-2022-0019<abstract> <title style='display:none'>Abstract</title> <p>Developing a medication to cure and manage diabetes mellitus complications is of interest in medicinal chemistry. Toward this end, six bis-biphenyl-salicylaldehyde Schiff base derivatives have been evaluated for their α-glucosidase inhibition, antiglycation and anti-inflammation potentials. Four compounds (compounds <bold>2</bold>–<bold>5</bold>) showed an excellent α-glucosidase inhibitory effect superior to that produced by acarbose. Additionally, the docking study revealed that these compounds are anchored within the binding pocket of α-glucosidase <italic>via</italic> hydrogen bonding, π-stacking and hydrophobic interactions, comparable to a high number of hydrogen bonding involved in anchoring acarbose. Interestingly, all tested compounds showed varying degrees of antiglycation activity with superior activity for two of them (compound <bold>1</bold> and compound <bold>6</bold>) compared to the standard rutin. Moreover, the results indicated an outstanding anti-inflammatory activity for two compounds (compounds <bold>1</bold> and <bold>6</bold>) compared to ibuprofen.</p> </abstract>ARTICLE2022-04-13T00:00:00.000+00:00Dasatinib enhances curcumin-induced cytotoxicity, apoptosis and protective autophagy in human schwannoma cells HEI-193: The role of Akt/mTOR/p70S6K signalling pathwayhttps://sciendo.com/article/10.2478/acph-2022-0025<abstract> <title style='display:none'>Abstract</title> <p>The present study was carried out in human schwannoma cells (HEI-193) to determine the combined anti-cancer effect of curcumin and dasatinib. Cells were treated with curcumin only, dasatinib only, or the combination of curcumin and dasatinib for 24 hours. Cellular toxicity, cell proliferation, and cell death were determined by LDH, MTT, and trypan blue dye assays, respectively. ELISA based kit was used to determine apoptotic cell death. Western blotting was used to determine the expression of apoptotic and autophagy-associated protein markers. Similarly, expression levels of Akt/mTOR/p70S6K signalling pathway-related proteins were studied using Western blotting. Cell death and apoptosis were significantly higher in HEI-193 cells treated with curcumin and dasatinib combination compared to individual controls. The combination of curcumin and dasatinib significantly enhances autophagy markers compared to individual controls. Furthermore, the combination of curcumin and dasatinib significantly activates Akt/mTOR/p70S6K signalling pathway compared to individual controls. In conclusion, our results suggest that the combination of curcumin and dasatinib significantly enhances cytotoxicity, apoptosis, and protective autophagy in HEI-193 cells through Akt/mTOR/p70S6K signalling pathway.</p> </abstract>ARTICLE2022-04-13T00:00:00.000+00:00AXL inhibitors selected by molecular docking: Option for reducing SARS-CoV-2 entry into cellshttps://sciendo.com/article/10.2478/acph-2022-0024<abstract> <title style='display:none'>Abstract</title> <p>The COVID-19 pandemic is ongoing and the benefit from vaccines is still insufficient since COVID-19 continues to be dia g-nosed in vaccinated individuals. It is, therefore, necessary to propose specific pharmacological treatments against COVID-19. A new therapeutic target on the human cellular membrane is AXL (<italic>anexelekto</italic>), proposed as an independent pathway by which interaction with the S protein of SARS-CoV-2 allows the virus to enter the cell, without the participation of ACE2. AXL serves as another gate through which SARS-CoV-2 can enter cells. Therefore, any stage of COVID-19 could be ameliorated by hindering the interaction between AXL and SARS-CoV-2. This study proposes ten compounds (<bold>1–10</bold>), selected by mole-cu lar docking and using a library of nearly 500,000 compounds, to develop a new drug that will decrease the interaction of AXL with the S protein of SARS-CoV-2. These compounds have a specific potential site of interaction with AXL, between Glu59, His61, Glu70 and Ser74 amino acids. This site is necessary for the interaction of AXL with the S protein. With this, we propose to develop a new adjuvant treatment against COVID-19.</p> </abstract>ARTICLE2022-04-13T00:00:00.000+00:00Bivalirudin exerts antiviral activity against respiratory syncytial virus-induced lung infections in neonatal micehttps://sciendo.com/article/10.2478/acph-2022-0022<abstract> <title style='display:none'>Abstract</title> <p>Respiratory syncytial virus (RSV) is the most common cause of small airways inflammation in the lungs (bronchiolitis) in neonates and immunocompromised adults. The deregulation of cellular and plasma components leads to increased morbidity and mortality. The activation of the clotting cascade plays a key role in the progression of disease severity during viral infection. The current investigation studied the effect of bivalirudin (BR) on the progression and cellular effects of RSV-induced infection in the neonatal mice model. Mice (5–7 days old) were inoculated intranasally with RSV with or without BR administration (2 mg kg<sup>−1</sup> day<sup>−1</sup>, <italic>i.v.</italic>) for 2 weeks. Tissue histopathology, inflammatory signalling genes such as TLR, and cytokines were analyzed. The results showed pneumocytes exhibiting nuclear pyknosis, cellular infiltration in lung tissue and increased lung titers in RSV-infected mice compared to the control. Furthermore, RSV-infected mice demonstrated altered clotting parameters such as D-dimer, soluble thrombomodulin, and increased inflammatory cytokines IL-5, 6, IFN-γ, IL-13, and CXCL1. Additionally, the mRNA expression analysis displayed increased levels of IL-33, TLR3, and TLR7 genes in RSV-infected lung tissue. Further, to delineate the role of micro RNAs, the qRT-PCR analysis was done, and the results displayed an increase in miR-136, miR-30b, and let-7i. At the same time, the down-regulated expression of miR-221 in RSV-infected mice compared to the control. BR treatment reduced the cellular infiltration with reduced inflammatory cytokines and normalized clotting indices. Thus, the study shows that RSV infection induces specific changes in lung tissue and the clotting related signalling mechanism. Additionally, BR treatment significantly reduces bronchiolitis and prevents the severity of the infections suggesting that BR can possibly be used to reduce the viral-mediated infections in neonates.</p> </abstract>ARTICLE2022-04-13T00:00:00.000+00:00The effectiveness of dexamethasone as a combination therapy for COVID-19https://sciendo.com/article/10.2478/acph-2022-0030<abstract> <title style='display:none'>Abstract</title> <p>Coronavirus disease 2019 (COVID-19) was reported as a global pandemic in March 2020 after invading many countries and leaving behind tens of thousands of infected patients in a brief time span. Approval of a few vaccines has been obtained and their efficacy of varying degrees established. Still, there is no effective pharmaceutical agent for the treatment of COVID-19 though several drugs are undergoing clinical trials. Recent studies have shown that dexamethasone, a corticosteroid, can reduce the rate of COVID-19-related mortality in the intensive care unit by 35 % for patients who are on mechanical ventilation. Although variable efficacy of other combination therapies has been reported for treating COVID-19 associated with acute respiratory distress syndrome (ARDS), dexamethasone is an extensively used drug in many treatment regimens against COVID-19. The current review aims to explore the role of dexamethasone as an efficient combination treatment for COVID-19.</p> </abstract>ARTICLE2022-04-13T00:00:00.000+00:00en-us-1