Scientia Pharmaceutica

This research sought to optimize the microwave-assisted extraction of Chatuphalathika as an herbal recipe maximizing the active compounds and the antioxidant activity by the Box–Behnken design. Three factors—microwave power, time, and cycle—were varied. Eight responses—extraction yield, total phenolic content, gallic acid content, corilagin content, chebulagic acid, chebulinic acid, IC₅₀ from DPPH assay, and IC₅₀ from FRAP assay—were monitored. Furthermore, cytotoxicity was evaluated to ensure the safety of the extract. After that, the optimized extract was compressed into tablets. The results showed that the optimal condition of the microwave-assisted extraction gave the simultaneous maximum extraction yield, total phenolic content, and antioxidant activity with a microwave power of 450 W for 30 s and 3 cycles. The extract obtained from the optimal condition exhibited a good safety profile although a concentration of 5 mg/mL was used. The optimized tablets were achieved when a compression force of 1500 psi and magnesium stearate of 1% were applied, and no sodium starch glycolate was added. In conclusion, the optimal green extraction method could be used for the extraction of the Chatuphalathika. Furthermore, the fabrication of Chatuphalathika tablets was successful, as the tablets had low friability with a short disintegration time. Full article

The wound healing potential of the aerial parts of Hypericum triquetrifolium Turra (Hypericaceae) was evaluated using an in vivo excision wound model in rats. Adult male Sprague Dawley rats were randomly assigned into seven groups; blank vehicles (olive oil and petroleum jelly), negative control, treatments [H. triquetrifolium ethanolic extract in petroleum jelly (5% and 10%) and H. triquetrifolium olive oil macerate (100 and 200 g/L)], and positive control (MEBO). Treatments were applied topically once daily until the wounds had completely healed. Wound areas and contraction rates were calculated, and full-thickness samples of the healed skin were collected for histopathological examination. H. triquetrifolium ointment (5%) showed the best wound healing activity with statistically significant differences when compared with the MEBO, petroleum jelly, and the negative control groups. Tissue sections were histopathologically examined in terms of re-epithelialization, granulation tissue development, collagen deposition, inflammatory cell infiltration, angiogenesis, and ulcer formation to support the in vivo excision wound model findings. H. triquetrifolium ointment (5%) showed the best histopathological scores in both re-epithelialization and ulcer formation. For quality control purposes, a high-performance liquid chromatography (HPLC) method was used to quantify key marker compounds in the extract, namely hypericin and rutin which showed a content of 0.64% and 4.46% (w/w), respectively. Based on the experimental results, H. triquetrifolium ointment (5%) exhibits remarkable wound healing properties at various stages of the wound healing process. Further investigations to prove its safety and efficacy in different types of wounds and to uncover its cellular mechanisms are warranted. Full article

Essential oils are potential therapeutics for coronavirus disease 2019 (COVID-19), in which some of the volatile compounds of essential oils have been well known for their broad antiviral activities. These therapeutic candidates have been shown to regulate the excessive secretion of pro-inflammatory cytokines, which underlies the pathogenesis of severe COVID-19. We aimed to identify molecular targets of essential oils in disrupting the cell entry and replication of SARS-CoV-2, hence being active as antivirals. Literature searches were performed on PubMed, Scopus, Scillit, and CaPlus/SciFinder (7 December 2022) with a truncated title implying the anti-SARS-CoV-2 activity of essential oil. Data were collected from the eligible studies and described narratively. Quality appraisal was performed on the included studies. A total of eight studies were included in this review; four of which used enzyme inhibition assay, one—pseudo-SARS-CoV-2 culture; two—whole SARS-CoV-2 culture; and one—ACE2-expressing cancer cells. Essential oils may prevent the SARS-CoV-2 infection by targeting its receptors on the cells (ACE2 and TMPRSS2). Menthol, 1,8-cineole, and camphor are among the volatile compounds which serve as potential ACE2 blockers. β-caryophyllene may selectively target the SARS-CoV-2 spike protein and inhibit viral entry. Other interactions with SARS-CoV-2 proteases and RdRp are observed based on molecular docking. In conclusion, essential oils could target proteins related to the SARS-CoV-2 entry and replication. Further studies with improved and uniform study designs should be carried out to optimize essential oils as COVID-19 therapies. Full article

This study aimed to elucidate the anti-inflammatory activity of C. tinctorius leaves by measuring inflammatory parameters such as nitric oxide (NO) production and mRNA expression of iNOS, interleukin-6 (IL-6), and IL-1β in lipopolysaccharide (LPS)-induced HaCaT cells. Further, the effect of C. tinctorius ethanol extract on the MAPKs/NF-κB signaling pathway was examined in HaCaT cells. The phytochemical profile of the ethanol extract of C. tinctorius leaves was determined using UPLC-QTOF-MS/MS. The results indicated that the ethanol extract of C. tinctorius effectively attenuated LPS-induced secretion of NO, IL-6, and IL-1β in HaCaT cells. Further, LPS-stimulated mRNA and protein expressions of iNOS were decreased by pre-treatment with C. tinctorius ethanol extract at the transcriptional level in HaCaT cells. Moreover, the ethanol extract of C. tinctorius suppressed NF-κB signaling in LPS-induced HaCaT cells. This suppression was mediated by MAPKs/NF-κB signaling, inhibiting the phosphorylation of p38 and p65 in HaCaT cells. However, there is no significant effect on the phosphorylation of JNK by the ethanol extract. The QTOF-MS/MS analysis revealed the identification of 27 components in the ethanol extract of C. tinctorius leaves. The data demonstrate that the ethanol extract of C. tinctorius leaves protects the LPS-induced HaCaT cells by inhibiting the expression of iNOS, IL-6, and IL-1β and suppressing the phosphorylation of the p38, p65, p-JNK via inactivation of MAPKs/NF-κB signaling pathway. These results demonstrate that C. tinctorius leaves may serve as a potential candidate to prevent inflammation-related diseases. Full article

Searching for new types of biological activities among preliminarily identified hit compounds is a key challenge in modern medicinal chemistry. In our study, a previously studied 3-[5-(1H-indol-3-ylmethylene)-4-oxo-2-thioxothiazolidin-3-yl]-propionic acid (Les-6614) was screened for antimicrobial, antifungal, anti-allergic, and antitumor activities. Moreover, cytotoxicity, molecular docking, and SwissAdme online target screening were accomplished. It was determined that the Les-6614 has slight antimicrobial and antitumor activity. However, the studied compound decreased IgE levels in sensitized guinea pigs by 33–86% and reduced IgA, IgM, IL-2, and TNF-α, indicating anti-inflammatory and anti-allergic aactivities. According to the SwissADME web tool, target predictions for Les-6614 potentially have an affinity for lysosomal protective protein, Thromboxane-A synthase, and PPARγ. The molecular docking confirmed that the studied 2-thioxo-4-thiazolidinone derivative showed good bonding with LLP and TXAS, leading to stable protein–ligand complexes. Additionally, Les-6614 is a potential PPARγ modulator, which is important in the pathogenesis of allergy, cancer, and cardiovascular diseases. Full article

Background: Combining antiangiogenic drugs with other chemotherapeutic drugs has been found to produce superior therapeutic outcomes and prevent drug resistance in a variety of cancers. Methods: Experimental assays such as the MTT assay, flow cytometry, western blotting, and qPCR have been used to evaluate the efficacy of combination therapy. Results: When compared to controls and monotherapies, the combination treatment of axitinib and idasanutlin demonstrated a substantial decrease in cell viability at lower doses, a significant decrease in migration, and a shift toward early and late apoptosis. This study examined major apoptotic, metastatic, and angiogenic factors, including MDM2, p21, BCL-2, BCL-XL, and MMP9, which have showed differential expressions at the protein and mRNA levels after combination. Axitinib and idasanutlin decreased tumorigenesis and migration in vitro in the MCF-7 cell line when compared to other chemotherapeutic medications. The suggested mechanisms of the antitumorigenic effect of the combination therapy may depend on its capacity to promote the production of apoptotic markers and reduce antiapoptotic markers. Conclusions: Treatments with axitinib and idasanutlin demonstrated effective therapeutic targeting of the primary angiogenic growth factor and, consequently, the pro-metastatic arbitrators. This will not only eliminate cancer cells but also stop other malignant processes and ultimately reduce the metastatic cascade. Full article

Paracetamol (acetaminophen, APAP) is known as a safe pain reliever; however, its negative effects on the central nervous system have gradually been reported. We examined alterations in learning and memory, and brain-derived neurotrophic factor (BDNF) expression in the frontal cortex and hippocampus at different durations of APAP treatment in rats. Novel object recognition (NOR) and Morris water maze (MWM) paradigms were used to assess learning and memory in rats fed with 200 mg/kg APAP at single-dose, 15-day or 30-day treatments. BDNF expression was evaluated through immunohistochemistry and Western blotting. The single-dose APAP treatment did not alter the NOR performance. However, deficits in the NOR and MWM capacities were detected in the rats with longer durations of APAP treatment. An analysis of BDNF expression revealed no significant change in BDNF expression in the single-dose APAP treatment, while rats given APAP for extended periods as treatment showed a significant decrement in this protein in the frontal cortex and hippocampus. Short-term APAP treatment has no effect on learning and memory, or BDNF expression; however, long-term APAP exposure causes cognitive impairment. The diminishment of the BDNF level in the frontal cortex and hippocampus due to the long period of treatment with APAP may at least in part be involved in altered learning and memory in rats. Full article

Funding is often a constraint when planning research, especially in countries where basic research is underfunded. Researchers must take into account these limitations, e.g., in relation to the selection of appropriate reagents, the source of which may affect the study’s final results. The aim of this article was to compare the results of bacteria susceptibility testing using three different sources of antimicrobial: the pure powder available from the supplier and two tablet formulations with different excipients. The chosen substance was furazidin (nitrofuran derivative). The susceptibility was tested on a group of 45 uropathogenic Enterobacterales using both microdilution and disk diffusion methods. The obtained results indicated that despite the relatively higher price, the powder appeared to be the best substance for scientific purposes, especially for quantitative determinations. Full article

Herein, we utilized several deep eutectic solvents (DES) that were based on hydrogen donors and hydrogen acceptors for their antibacterial application. These DES were tested for their bactericidal activities against Gram-positive (Streptococcus pyogenes, Bacillus cereus, Streptococcus pneumoniae, and methicillin-resistant Staphylococcus aureus) and Gram-negative (Escherichia coli K1, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Serratia marcescens) bacteria. Using lactate dehydrogenase assays, DES were evaluated for their cytopathic effects towards human cells. Results from antibacterial tests revealed that DES prepared from the combination of methyl-trioctylammonium chloride and glycerol (DES-4) and DES prepared form methyl-trioctylammonium chloride and fructose (DES-11) at a 2 µL dose showed broad-spectrum antibacterial behavior and had the highest bactericidal activity. Moreover, DES-4 showed 40% and 68% antibacterial activity against P. aeruginosa and E. coli K1, respectively. Similarly, DES-11 eliminated 65% and 61% E. coli K1 and P. aeruginosa, respectively. Among Gram-positive bacteria, DES-4 showed important antibacterial activity, inhibiting 75% of B. cereus and 51% of S. pneumoniae. Likewise, DES-11 depicted 70% B. cereus and 50% S. pneumoniae bactericidal effects. Finally, the DES showed limited cytotoxic properties against human cell lines with the exception of the DES prepared from Methyltrioctylammonium chloride and Citric acid (DES-10), which had 88% cytotoxic effects. These findings suggest that DES depict potent antibacterial efficacies and cause minimal damage to human cells. It can be concluded that the selected DES in this study could be utilized as valuable and novel antibacterial drugs against bacterial infections. In future work, the mechanisms for bactericides and the cytotoxicity effects of these DES will be investigated. Full article

Virtual screening of the potential lead chemotherapeutic phytochemicals from medicinal plants has useful application in the field of in-silico modelling and computer-based drug design by orienting and scoring ligands in the active binding site of a target protein. The phytochemical investigation of the Pterocephalus frutescens extract in n-butanol resulted in the isolation and structure elucidation of three iridoids and four flavonoids which were identified as Geniposide (1), Geniposidic acid (2), Nepetanudoside C (3), Isovitexin (4), Luteolin-7-O-glucoside (5) Isoorientin (6) and Orientin (7), respectively. Molecular docking studies were used to compare the binding energies of the isolated phytochemicals at four biological cancer-relevant targets; namely, aromatase, carbonic anhydrase IX, fatty acid synthase, and topoisomerase II-DNA complex. The docking study concluded that the isolated compounds have promising cytotoxic activities, in particular, Luteolin-7-O-glucoside (5) and Orientin (7) which exhibited high binding affinities among the isolated compounds at the active sites of the target enzymes; Aromatase (−8.73 Kcal/mol), and Carbonic anhydrase IX (−8.92 Kcal/mol), respectively, surpassing the corresponding binding scores of the co-crystallized ligands and the reference drugs at these target enzymes. Additionally, among the isolated compounds, Luteolin-7-O-glucoside (5) showed the most outstanding binding affinities at the active sites of the target enzymes; Fatty acid synthase, and Topisomerase II-DNA complex with binding scores of −6.82, and −7.99 Kcal/mol, respectively. Finally, the SwissADME online web tool predicted that most of these compounds possessed acceptable oral bioavailability and drug likeness characteristics. Full article

In the food and beverage industries, replacing synthetic colorants with plant-based colorants has become popular in recent times. Purple corn (Zea mays L.) is an important source of natural colorants due to its range in color from orange to purple. The whole plant of purple corn has a high amount of anthocyanin content. Anthocyanin is the water-soluble pigment found in various fruits and vegetables. The color pigments are chiefly found in the pericarp or kernels, in addition to corn cobs. Purple corn is rich in various health-promoting compounds, mainly anthocyanins such as cyanidin-3-O-glucoside, perlagonidin-3-O-glucoside, peonidin 3-O-glucoside, and their malonylated forms. This review emphasized recent updates regarding the in vitro and in vivo biological properties of extracts and compounds from purple corn. Purple corn color extracts possess a variety of biological properties, including antioxidant, anti-inflammatory, anticancer, anti-diabetic, anti-obesity, etc. The results of in vitro and in vivo studies of the biological properties of purple corn could lead to the development of different health-promoting products in the near future. Full article

As members of a public trust profession, pharmacists are the most accessible medical team members. Therefore, every pharmacist must know the scope of their professional roles (PR) and professional functions (PF). The study aimed to detail the major PR into a pooled set of PF. The research materials were the provisions of the World Health Organization, the International Pharmaceutical Federation, and scientific works on the PR of pharmacists. Methods of critical analysis, concretization, functional decomposition, and scientific generalization were used. As a result of detailing the 10 main PR according to the “ten-star pharmacist” concept for each, a combined set of partial PFs of the pharmacist was obtained. The decomposition takes into account the principle of complexity limitation, which allowed three to six partial PF for the respective PR to be obtained, namely: three PFs for a life-long-learner, five PFs for a caregiver, a decision-maker, a teacher, a leader, a researcher, an entrepreneur, and an agent of positive change, six PFs for a communicator and a manager. Thus, due to the decomposition of each of the 10 main PR of the pharmacist into three or six corresponding partial PFs, we received a multifunctional verbal model of difficult to organize, professional activities, which is identified by a total of 50 PFs. The importance of using this model in formulating professional competencies and learning outcomes of educational programs for pharmacists is emphasized. Full article

Platelet-rich plasma (PRP) has become an increasingly popular alternative or additional method in treating androgenic alopecia (AGA). AGA is a multifactorial disease, in which testosterone plays a significant role in influencing hair growth. The aim of this study was to evaluate the effectiveness of PRP treatment in AGA affecting men and women. The research was performed using the following databases: PubMed, Embase, and Cochrane Library. The effects were measured with a TrichoScan by comparing the initial and final hair density. A significant difference was observed between the areas of the scalp where PRP injections were made and those where saline was administered. Compared to conventional minoxidil 5% topical PRP, PRP is more effective in treating alopecia. A beneficial outcome of combined therapy with PRP and minoxidil 5% was observed. Therefore, PRP is not only an excellent alternative for patients in whom the minoxidil 5% topical monotherapy did not bring the expected effects or who experienced unacceptable side effects, but can also be used as a complementary therapy. Full article

Zingiberaceae is commonly known as the ginger family and has been extensively studied in the last decades for its pharmacological purposes. The study of ginger includes microorganisms known as endophytes, which raise interest for the research community because they can produce a wide range of secondary metabolites. This review discusses the secondary metabolites of endophytes from the Zingiberaceae family and their pharmacological activities. We detail the group of secondary metabolites, updated for its absolute structures, source and part origins, and, especially, pharmacological divided properties. Zingiberaceae endophytes have 106 volatile compounds and 52 isolated constituents, including 17 polyketides, five nonribosomal peptides, five aromatic compounds, three alkaloids, and 21 terpene-alkaloids. They have antimicrobial, anticancer, antioxidant, and anti-inflammatory activities. Secondary metabolites from plant endophytes of the Zingiberaceae family have the potential to be therapeutic drugs in the future. Research on endophytic bacteria or fungi has been little performed. Therefore, this study supports a new drug discovery from Zingiberaceae endophytes and compares them for future drug development. Full article

Artabotrys sumatranus is one of the Artabotrys species, which lives in Sumatera, Java, and Borneo in Indonesia. No research has been found related to its activity. The objective of this study was to explore the potential of A. sumatranus leaf and twig extracts as the source of an anti-diabetic agent through the α-glucosidase inhibition mechanism, as well as the relationship between the antioxidant and the α-glucosidase inhibition activities in these extracts. Ethanol extracts from leaf and twig A. sumatranus were subjected to several assays: total phenolic content, total flavonoid content, antioxidant activity using DPPH (2,2-diphenyl-1-picrylhydrazyl), radical scavenging activity, and FRAP (ferric reducing antioxidant power) analysis, as well as α-glucosidase inhibition. Later, GC-MS (gas chromatography-mass spectrometer) and LC-MS/MS (liquid chromatography-mass spectrometer/mass spectrometer) analysis were conducted to identify the compounds inside the extracts. The identified compounds were tested for potential α-glucosidase inhibition activity using a molecular docking simulation. As a result, the A. sumatranus leaf extract showed more potential than the twig extract as α-glucosidase inhibitor and antioxidant agent. In addition, from the comparison between the measured quantities, it can be deduced that most of the α-glucosidase active compounds in the A. sumatranus are also antioxidant agents. Several active compounds with a high affinity to α-glucosidase inhibition were identified using the molecular docking simulation. It was concluded that A. sumatranus twig and leaf extracts seem to be potential sources of α-glucosidase inhibitors. Full article

To explore the performance of the cationic nanocarrier leciplex (LPX) in escalating the oral bioavailability of vancomycin hydrochloride (VAN) by promoting its intestinal permeability. With the aid of a D-optimal design, the effect of numerous factors, including lipid molar ratio, cationic surfactant molar ratio, cationic surfactant type, and lipid type, on LPX characteristics, including entrapment efficacy (EE%), particle size (P.S.), polydispersity index (P.I.), zeta potential value (Z.P.), and steady-state flux (Jss) were assessed. The optimized formula was further evaluated in terms of morphology, ex vivo permeation, stability, cytotoxicity, and in vivo pharmacokinetic study. The optimized formula was spherical-shaped with an E.E. of 85.2 ± 0.95%, a P.S. of 52.74 ± 0.91 nm, a P.I. of 0.21 ± 0.02, a Z.P. of + 60.8 ± 1.75 mV, and a Jss of 175.03 ± 1.68 µg/cm²/h. Furthermore, the formula increased the intestinal permeability of VAN by 2.3-fold compared to the drug solution. Additionally, the formula was stable, revealed good mucoadhesive properties, and was well tolerated for oral administration. The in vivo pharmacokinetic study demonstrated that the VAN C_max increased by 2.99-folds and AUC_0-12 by 3.41-folds compared to the drug solution. These outcomes proved the potentiality of LPX in increasing the oral bioavailability of poorly absorbed drugs. Full article

Quercus resinosa leaves are rich in polyphenol compounds, however, they are unstable to several chemical and physical factors that limit their activity. Several methods have been developed to solve such problems, among which bigels can be mentioned and obtained using hydrogels and oleogels. The mechanical characterization of this type of materials is by using rheological methods. Although the use of these methods is well documented, the Carreau-Yasuda model has been little used to evaluate the effect of polyphenols on the mechanical behavior of bigels. Therefore, bigels were obtained from hydrogels (guar gum/xanthan gum, 0.5/0.5% w/v) and oleogels (sesame oil/sorbitan monostearate 10% w/w). Micrographs, linear viscoelasticity range, frequency sweep, and single shear tests were performed. The data were analyzed using ANOVA and Tukey test (p < 0.05); micrographs showed linear relationship between polyphenols concentration and droplet size. Liquid fraction of bigels showed a pseudoplastic behavior, while the parameters of Carreau-Yasuda model showed that the highest value of the complex viscosity at zero shear was at the lowest concentration of extract; the relaxation time presented the lowest value at higher concentrations of extracts. These results indicate that the presence of polyphenols modifyes the mechanical behavior of bigels. Full article

Nanoparticles provide promising advantages in advanced delivery systems for enhanced drug delivery and targeting. The use of a biodegradable polymer such as PLGA (poly lactic-co-glycolic acid) promotes improved nanoparticle safety and, to some extent, provides the ability to modify nanoparticle surface properties. This study compared the effect of altering the surface charge on the translocation of PLGA nanoparticles across excised nasal mucosal tissues. Nanoparticles (average diameter of 60–100 nm) loaded with Nile Red (lipophilic fluorescent dye) were fabricated using a nanoprecipitation method. The effects of nanoparticle surface charge were investigated by comparing the transfer of untreated nanoparticles (negatively charged) and positively charged PLGA nanoparticles, which were modified using PAMAM dendrimer (polyamidoamine, 5th generation). All nanoparticles were able to be transferred in measurable quantities into both nasal respiratory and olfactory mucosae within 30 min. The total nanoparticle uptake was less than 5% of the nanoparticle mass exposed to the tissue surface. The cationic nanoparticles showed a significantly lower transfer into the mucosal tissues where the amount of nanoparticles transferred was 1.8–4-fold lower compared to the untreated negatively charged nanoparticles. The modification of the nanoparticle surface charge can alter the nanoparticle interaction with the nasal epithelial surface, which can result in decreasing the nanoparticle transfer into the nasal mucosa. Full article