Future Journal of Pharmaceutical Sciences最新文献

Background

In July 2022, a newly emerged viral infection called Langya virus, a type of Henipavirus identified in febrile patients in China and closely linked to two other henipaviruses (Hendra and Nipah) was considered a potential threat and can lead to the endemic situation. At present, no appropriate vaccine exists. Therefore, this investigation aims to design a multi-epitope vaccine against this infection via an integrated bioinformatics and immunoinformatics approach focusing on attachment glycoprotein and fusion protein.

Results

A total of 26 immunodominant epitopes were carefully chosen for vaccine formulation grounded on their antigenic, nonallergenic and nontoxic features and linked via precise linkers, along with HIV-TAT peptide, PADRE epitope and 6 × His-tag. The intended vaccine is forecast to be immunodominant, with broader population coverage encouraging physicochemical features and highly soluble. The 3D structure was anticipated and verified, and a docking study with toll-like receptors (TLR2, TLR3, TLR8 and TLR9) indicates significant binding with TLR3 and TLR9 based on the highest molecular interaction and high binding affinity score of − 25.2 and − 24.2 kcal mol⁻¹. NMA analysis revealed that vaccines with TLR3 and TLR9 have eigenvalues of 1.953251e−05 and 4.814201e−05, indicating proper molecular motion and flexibility. Further, the simulation (100 ns) showed constancy of complex (vaccine with TLR3 and TLR9). The generated immune activity indicates that the vaccines can trigger an intense immunological response. Furthermore, in silico cloning ensured a significant expression, followed by CAI values of 1 and GC (53.78%) content.

Conclusion

This study successfully designed a promising vaccine with strong immune activity. The vaccine revealed strong activity towards TLR3 and TLR9, with binding affinity of − 25.2 and − 24.2 kcal mol⁻¹, and over 100-ns simulation demonstrated minor deviation followed by the range of RMSD value. Further, the immune stimulation and cloning demonstrated potent activity and suggested the vaccine is able to evoke immune activity. However, experimental and clinical analyses are essential to authenticate these findings.

Background

Analytical quality by design approach is a systematic and scientific method for developing robust analytical procedures. Applying QbD principles in developing stability-indicating HPLC method for quantifying rosuvastatin and bempedoic acid in tablets enhances method understanding by identifying critical method parameters and analytical attributes, ensuring consistent quality.

Method

A two-level seven-factor Plackett–Burman design was employed to screen method parameters. Based on Pareto ranking analysis, the % aqueous (%v/v), buffer pH, and flow rate (ml/min) were identified as critical method parameters, while the retention times of rosuvastatin and bempedoic acid and resolution were selected as critical analytical attributes. Optimization was conducted using a two-level three-factor Box–Behnken design. The final optimized method utilized a Spursil C18 column (5 µm, 150 × 4.6 mm) with a mobile phase consisting of 15 mM ammonium acetate buffer (pH 6.0) and acetonitrile (40:60%v/v), a flow rate of 1 mL/min, and UV detection at 244 nm with an 8-min run time.

Results

Under the above conditions, rosuvastatin and bempedoic acid had retention times of 2.474 min and 3.396 min, respectively. Validation of the optimized method followed ICH Q2 (R1) guidelines and included system suitability, specificity, linearity, accuracy, precision, detection limit, quantitation limit, and robustness assessments. Linearity was observed in the range of 0.8–4.0 µg/mL for rosuvastatin and 3.6–18 µg/mL for bempedoic acid. Additionally, the greenness of the method was evaluated using AGREE software, which provided a score of 0.72, indicating compliance with Green Analytical Chemistry principles.

Conclusion

The developed RP-HPLC method is both sensitive and robust for the quantification of rosuvastatin and bempedoic acid in tablet formulations. The use of Plackett–Burman and Box–Behnken designs facilitated efficient optimization, and the method meets ICH guidelines and greenness criteria, confirming its suitability for routine analysis in quality control laboratories.

Graphical Abstract

Background

Methotrexate is a frequently prescribed antifolate immunosuppressant and antineoplastic agent that has been associated with serious systemic adverse effects including hepatotoxicity. The current investigation explored the efficacy of the peroxisome proliferator activated receptor-gamma (PPAR-γ) agonist, Pioglitazone, in modulating Methotrexate-provoked liver damage then elucidating the underlying molecular mechanisms. Rats were allocated into four groups (n = 6): control group (received saline orally); Pioglitazone-exposed group (administered Pioglitazone 4 mg/kg/day p.o. from day 15 to 28); Methotrexate-treated group, (received Methotrexate 14 mg/kg/week p.o. from day 1 to 14); and Methotrexate and Pioglitazone-treated group (received Methotrexate form day 1 to 14 then received Pioglitazone from day 15 to 28 at the previously specified doses).

Results

The findings of the current work demonstrated that Pioglitazone alleviated Methotrexate-induced liver injury as depicted by correcting Methotrexate-induced elevation of liver enzymes, namely, alanine aminotransferase plus aspartate aminotransferase as well as ameliorating Methotrexate-induced histopathological changes. Accordingly, Pioglitazone administration in Methotrexate-intoxicated rats partially restored the redox homeostasis as manifested by suppressing malondialdehyde alongside elevating reduced glutathione contents. Notably, all previously mentioned parameters were measured using colorimetric assays. Remarkably, the reported hepatoprotective effect is putatively mediated through hindering hepatic inflammation reflected by the reported upregulation of PPAR-γ and hemoxygenase-1 with subsequent suppression of nuclear factor-kappa B and tumor necrosis factor-α. Additionally, current findings revealed modulation of Toll-like receptor 4 following Pioglitazone treatment that was further confirmed by our in silico study.

Conclusions

Therefore, this investigation suggests Pioglitazone as a promising therapeutic intervention in mitigating Methotrexate-induced liver injury.

Background

Euryops arabicus is well known in the Arabian Peninsula as traditional herbal medicine. The plant synthesizes various types of flavonoids, terpenes, and furoermophilanes skeletons in either steroidal or nonsteroidal conformation, and this wide range of chemical compounds might play an increasingly prominent role in medicine. This study aimed to isolate pure secondary metabolites and assess their antibacterial, antiproliferation, and antibiofilm formation properties.

Methods

The organic extract of the areal parts of E. arabicus was chromatographically fractionated to afford pure compounds characterized using NMR, UV, and IR along with mass spectrometry. The activity of the isolated compounds was assessed against three cancer cells and a set of Gram-negative and positive bacteria.

Results

Four specific sesquiterpenoids were identified: 6β-senecioyloxy-1,10-dehydrofuranoeremophilan-9-one (1), 6β-acetoxy-9-oxoeuryopsin (2), 6β-(2′-methyl, 2′,3′-epoxy-butyryloxy)-euryopsin (3), and 6β-angloyloxy-1,10-dehydrofuraoeremophilan-9-one (4). Molecular docking studies indicated the epidermal growth factor receptor and methionyl-tRNA synthetase as probable antibacterial and antiproliferative activities of the compounds. In the in vitro studies, compounds 2 and 4 showed remarkable activity against all examined Gram-negative and positive pathogens with inhibition diameters (mm) ranging from 13.1 ± 0.23 to 19.0 ± 0.44 and 12.9 ± 0.20 to 16.2 ± 0.23, respectively. Compounds 2 and 4 showed moderate biofilm formation inhibition of both Pseudomonas aeruginosa and Staphylococcus aureus with 58% and 79%, respectively. Moreover, the isolated sesquiterpenoids showed potent antiproliferative activities against MCF-7, HepG2, and HCT116 human cancer cells.

Conclusion

Four sesquiterpenoids were isolated from E. arabicus. Compound 2 showed a relatively high antibacterial and cytotoxic activity. Additional studies are recommended to substantiate the observed activities further.

Graphical abstract

Background

Lipidic nanovesicular systems have attracted researchers’ interest for more effective cutaneous delivery and topical pharmacological efficacy. Quercetin (QUT), a polyphenolic flavonoid known for its antioxidant and anti-inflammatory activity, suffers from poor solubility and bioavailability. The aim of this research was to develop an optimized hydrogel formulation comprising QUT-loaded hyaluronic acid (HYA)-modified glycerosomes (glycerohyalurosomes, GHEs) for effective wound management. A combination of glycerol (GLY) and HYA is being used to provide flexibility to the vesicles for better delivery through the skin; these compounds have been reported to provide benefits for wound healing.

Results

D-optimal design suggested fifteen formulations of QUT-GHEs which were prepared using a modified thin-film hydration method. Results showed that particle sizes ranged from 162.33 to 478.49 nm and zeta potential from −57.8 to −18.8 mV. Transmission electron microscopy confirmed successful loading of the drug into the vesicles. QUT-GHEs were integrated into hydrogel (QUT-GHE-GEL) using 1.5% hydroxypropyl methylcellulose. The pH of the QUT-GHE-GEL was recorded as 5.9 ± 0.03, which is acceptable in wound healing. In vivo studies performed on Wistar rats showed that QUT-GHE-GEL accelerated the wound-healing process compared to the untreated control and marketed product (MP)-treated groups, where a significantly higher wound contraction was observed. Histopathological examination of wound tissues revealed that QUT-GHE-GEL-treated and MP-treated groups exhibited newly sprouted capillaries and enhanced fibroblast development.

Conclusions

Thus, the suggested QUT-GHE-GEL formulation shows promise for effective wound-healing management. QUT-GHE-GEL enhances wound contraction and fosters tissue regeneration while modulating inflammation. The results indicate that QUT-GHE-GEL proves a prospective therapeutic option for wound care applications.

Background

Disruption of immune system leads to excessive inflammation and the development of serious autoimmune diseases including atherosclerosis, characterized by the accumulation of oxidized low-density lipoproteins (ox-LDL) and various immune cells, particularly macrophages in the arterial wall. Monocyte chemoattractant protein-1 (MCP-1), stimulated and recognized by ox-LDL and toll-like receptors (TLRs), respectively, triggers intracellular signaling cascades, leading to the excessively released of various cytokines and chemokines. The expression control at any level is of great importance in decreasing the overall cascade of immune responses and inflammation, specifically, atherosclerosis. One of the most promising areas of research in the pathogenesis of inflammation and atherogenesis is herbal medications and its bioactive compounds with better delivery to target the exact cell and tissues with high efficacy and fewer side effects in pharmaceutical exploration. Therefore, the aim of present study was to explore the anti-inflammatory effects of naturally derived compounds, i.e., opuntiol (OP), opuntioside-I (OPG), and opuntiol’s silver nanoparticles (OP-Ag) for achieving optimal therapeutic approach to address the underlying inflammatory processes in atherosclerosis and improving treatment outcomes. Zymosan-induced peritonitis mouse model and ox-LDL was employed to determine the inhibitory potential of these compounds on the expression levels of key cytokines and chemokines allied with the onset of inflammatory events during atherosclerosis.

Results

qRT-PCR and ELISA were employed to check the expression levels of various cytokines (IL-1β, TNF-α, IL-6), chemokines (MCP-1, KC), and a transcription factor (NF-ĸB). Significant reduction was observed in chemotaxis along with decreased expression of key intermediates in response to the natural extracts, i.e., OP, OPG. Its silver-based nanoparticles and OP-Ag in lower concentration enhanced the drug delivery with improved inhibitory roles.

Conclusion

Overall, the present findings hold promise for advancing the potential therapeutic effects of OP, OPG, and its OP-Ag nano-conjugates at minimum concentrations, especially in the inflammation characteristic of atherosclerosis context, by incorporating zymogen-induced ox-LDL model where it interacts with TLRs in triggering inflammatory responses, and subsequently simulate atherosclerotic conditions via upregulation of MCP-1.

Background

Medicinal plants are well known for their health benefits. Syzygium australe (Brush Cherry) is considered a health-promoting food due to its high antioxidant capacity, which may help prevent cancer, cardiovascular diseases, and neurological disorders. Additionally, S. australe exhibits antidiabetic and antiobesity properties.

Aim

This study reviews the antioxidant and antidiabetic activities of S. australe fractions, along with their key phytoconstituents.

Materials and methods

The antioxidant activity of S. australe crude extract and fractions was assessed using DPPH (2,2-diphenyl-1-picrylhydrazyl-hydrate), ABTS (2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)), FIC (ferrozine iron metal chelation), and FRAP (ferric reducing antioxidant power) assays. Their antidiabetic activity was evaluated using α-glucosidase, α-amylase, and lipase inhibition assays. Additionally, their TFC (total flavonoid content) and TPC (total phenolic content) were determined. The secondary metabolites were analysed using Triple TOF UPLC-ESI–MS/MS (ultra-performance liquid chromatography-electrospray ionization-time of flight-mass spectrometry).

Results

Our findings, for the first time, reveal that various S. australe extracts exhibit strong antidiabetic and antioxidant properties. The butanol and ethyl acetate fractions had the highest antidiabetic activity. Their respective IC₅₀ values against α-glucosidase, α-amylase, and lipase were 0.11–0.14 µg/mL, 0.06–0.09 µg/mL, and 26.5–30.79 ng/mL, respectively. Also, they showed powerful antioxidant activity. The IC₅₀ values of the ethyl acetate (19.93 ± 1 μg/mL) and butanol (38.7 μg/mL) fractions were significantly lower than those of the reference compounds, Trolox (24.42 ± 0.87 μg/mL) in the DPPH assay and EDTA (Ethylenediaminetetraacetic acid) (39.7 μg/mL) in the ferrozine iron metal chelation assay, respectively. They had a higher amount of TPC (397.65 ± 14.78, 253.32 ± 10.78 µg GAE/mg sample) and TFC (97.89 ± 4.98, 23.14 ± 1.11 µg RE/mg sample) of ethyl acetate and butanol, respectively. The significant phenolic and flavonoid substances found in these extracts may account for their strong antioxidant activity. Triple TOF UPLC-ESI–MS/MS analysis detected 18 phenolic acids, 19 derivatives, and 39 flavonoids. As a way to prevent or treat various disorders, these two extracts additionally served as a great source of antioxidant phytochemicals.

Conclusion

Ultimately, our findings strongly suggest that the phenolics of S. australe may be valuable for the development of antioxidant and antidiabetic medications.

Background

β-Caryophyllene oxide (BCPO) has wooden odor so widely used as cosmetic and food additives. It is naturally found in various spice and food plant such as basil, black pepper, clove, salvia, and indian bay leaf. It is traditionally used to treat arthritis. The present study anticipated to appraise the anti-inflammatory and anti-arthritic potential of BCPO alone and in combination with methotrexate.

Results

Data from in vitro assays showed that BCPO exerted the highest percentage inhibition at 1600 μg/ml. Complete Freund’s Adjuvant-induced arthritis in Wistar rats treated with BCPO and its combination with methotrexate (MTX) revealed a notable restoration of body weight and reduced pain, arthritic score, oxidative stress, and hematological alterations in contrast to disease control. The histopathological examination showed that BCPO therapy decreased joint inflammation, pannus formation, and bone erosion. Biochemical studies revealed that BCPO alone and in combination not only downregulated the mRNA expression of TNF-α, IL-1β, NF-kB, and COX-2 but also increased the expression of IL-4, and IL-10.

Conclusion

It can be inferred from the finding that BCPO in combination with MTX can be effectively used to manage polyarthritis due to notable anti-inflammatory, antioxidant, and anti-nociceptive activities than monotherapy.

Graphical abstract

Background

Primary percutaneous coronary intervention (PPCI) is the treatment of choice for ST-segment-elevation myocardial infarction (STEMI). Post-PCI induced-oxidative stress, a complication of PCI, is linked to the no-reflow (NR) phenomenon and poor prognosis. A clinical trial involving 70 STEMI patients was conducted to evaluate the impact of alpha lipoic acid (ALA), an antioxidant and anti-inflammatory agent, on oxidative stress and NR. The participants were randomized to standard care (control group) or 600 mg IV infusion of ALA pre/peri PPCI then 600 mg orally once for 28 days plus standard care (ALA group). Outcomes included the degree of myocardial reperfusion by thrombolysis in myocardial infarction (TIMI) flow and myocardial blush grade (MBG), Aldehyde dehydrogenase 2 (ALDH2) and Paroxonase 1 (PON-1) levels, also left ventricular ejection fraction (LVEF), and major adverse cardiac events (MACE).

Results

TIMI flow grade-3 and MBG grade-3 were significantly higher in the ALA group versus controls (97.1% and 62.9%, respectively, P = 0.001, 82.9%, and 45.7%, respectively, P = 0.002). ALDH2 and PON-1 levels were significantly higher in ALA versus controls post-PPCI at all-time points (24 h and 7 days). The ALA group exhibited better LVEF at 7 and 28 days when compared to controls.

Conclusion

ALA supplementation decreased the occurrence of NR, reduced myocardial ischemia–reperfusion injury (IRI) post-PPCI, increased ALDH2, and PON-1 levels, and improved LVEF.

Background

In the present study, a new and sensitive UPLC method for stability-indicating study has been established and validated as per the ICH guidelines. To date, no work has been reported on the forced degradation studies of alpelisib using the UPLC technique. Box–Behnken design was used to study the response surface for method optimisation to achieve a good separation with a minimum number of experimental trials. Three independent parameters selected were mobile phase ratio, flow rate of the mobile phase and temperature of the column. Retention time and tailing factor were taken as two responses to obtain mathematical models.

Results

The chromatography was executed using Waters BEH C₁₈ UPLC column (2.1 × 50 mm, 1.7micron) at wavelength detection of 246 nm. The optimised assay conditions predicted were isocratic mobile solvent system using 0.1% formic acid buffer solution and acetonitrile in the ratio of 50:50 (V/V), with a flow rate of 0.25 mL per min and injection volume of 4 µL. The method has shown a good response with a total run time of 4 min, retention time was found to be 1.49 min and tailing factor was 0.99 for alpelisib, showing good peak symmetry. The linearity of the method developed is at a range of 10–50 µg/mL with R² 0.9955, while the percentage mean recovery for accuracy was of 99.25%. The method developed was precise as % RSD of inter-day and intra-day precision was 0.3 and 0.1, respectively, meeting the specified limits.

Conclusion

The developed UPLC work is quick and simple with an increased level of linearity, precision, specificity and accuracy as per the ICH criteria and can find application in industries as a regular method for quantification of alpelisib.