Future Journal of Pharmaceutical Sciences最新文献

Background

Streptozotocin (STZ) is a glucose analogue commonly used for inducing diabetes in experimental animals. This study is intended to investigate the ability of captopril (Cap) pretreatment to augment STZ-induced diabetogenic effect in an experimental rat model. If this hypothesis were proven, Cap administration to rats could reduce the dosage of STZ by augmenting its effect and resulting in a subsequent reduction in STZ cost. Forty-two adult male Wistar rats were randomly divided into seven groups: a control group that fed a normal diet, whereas the other six experimental groups were fed a high-fat diet (HFD). The six groups were then divided into STZ-30, STZ-30-Cap, STZ-40, STZ-40-Cap, STZ-50, and STZ-50-Cap. All Cap-received groups were supplemented with 50 mg/kg Cap orally one hour just before intraperitoneal (I.P.) injection of STZ. 30-STZ, 40-STZ, and 50-STZ-treated groups were injected once with STZ I.P. at doses of 30, 40, and 50 mg/kg, respectively. An intraperitoneal glucose tolerance test (IPGTT) was done. Pancreatic tissue was obtained to measure Tumor necrosis factor alpha (TNF-α), interleukin one beta (IL-1β), and nitric oxide (NO) by enzyme-linked immunosorbent assay (ELISA) and glucose transporter 2 (GLUT2) gene expression by reverse transcription polymerase chain reaction (RT-PCR). Pancreatic sections were examined by hematoxylin and eosin (H&E) stain, and immunohistochemical staining by anti-insulin and anti-TNF-α antibodies.

Results

Results indicated that administration of Cap before STZ in different doses significantly augmented the hyperglycemic state that was evident by intraperitoneal glucose tolerance test, and markedly increased pancreatic pro-inflammatory markers. Histological analysis of islets of Langerhans indicated degeneration with extensive vacuolations associated with a significant decrease in mean area % of insulin immunoreactivity and an increase in optical density of TNF-α immunoreactivity.

Conclusion

These findings pointed to the ability of captopril pretreatment to augment the hyperglycemic state and the diabetogenic response that was induced secondary to STZ injection in an experimental rat model.

Background

The objective of this current research was to enhance the topical delivery of Nadifloxacin (NDFX) by incorporating it into a transethosomal gel formulation. NDFX has limited penetration into the deep layer of the skin because it is poorly water soluble and it has a log p value of 2.47. To optimize the formulation, the “Box–Behnken design” was utilized. The independent variables included phosphatidylcholine 90, tween 80 and ethanol. The produced formulations underwent evaluation for entrapment efficiency, vesicle size and zeta potential. The optimized formulation was then incorporated into suitable gel bases and subjected to further investigation, including in vitro diffusion, ex vivo penetration, in vitro antimicrobial assay and in vivo anti-acne activity.

Results

The optimized formulation exhibited an entrapment efficiency of 80.12%, a vesicle size of 156.1 nm and a zeta potential of − 33.23 mV. TEM images confirmed the presence of encapsulated vesicles with a spherical shape. The in vitro diffusion study demonstrated that the transethosomal gel containing Carbopol 934 (1%) exhibited higher drug release compared to the HPMC K4M gels. Furthermore, the ex vivo permeation study revealed that the optimized transethosomal gel demonstrated increased permeation compared to the commercially available formulation.

Conclusion

The optimized transethosomal formulation displayed enhanced in vitro antimicrobial and in vivo anti-acne effects against Propionibacterium acnes in Wistar albino rats when compared to the marketed formulation.

Background

Pregabalin (PGB) is a medication with anticonvulsant, analgesic and anxiolytic properties, employed in the treatment of epilepsy, neuropathic pain, fibromyalgia, restless leg syndrome, opioid withdrawal syndrome and generalized anxiety disorder. Several spectrofluorimetric techniques have been documented for the determination of PGB in pharmaceutical dosage forms. However, these published methods typically involve the use of expensive and toxic organic solvents and reagents, as well as high reaction temperatures for PGB analysis. These components pose risks to aquatic life and the environment, making them less environmentally friendly and user-friendly. A recent advancement in analytical chemistry has introduced a white analytical approach, providing an economical, eco-friendly and user-friendly method for the development of analytical procedures.

Objectives

Therefore, a green and sensitive spectrofluorimetric determination of PGB, guided by white analytical chemistry principles, has been conducted utilizing distilled water as an environmentally friendly solvent.

Methods

The establishment of the spectrofluorimetric method involved employing the design of experiments approach to ensure a robust, precise and accurate estimation of PGB. Response surface analysis and optimization of critical procedural variables and responses were carried out using the central composite design. The validation of the developed method adhered to the guidelines outlined in ICH (International Council for Harmonization) Q2 (R1) and M10.

Results

The established spectrofluorimetric method was utilized to determine the PGB content in commercially available formulations and human plasma samples spiked with PGB. The obtained results were in accordance with the labeled claim of PGB in the formulations. The recovery of PGB in the spiked human plasma samples ranged from 85 to 90% of the spiked amount.

Conclusions

The greenness profiles of the published and suggested spectrofluorimetric methods for PGB estimation were evaluated and compared using the AGREE calculator, GAPI software and ESA tool. The suggested method demonstrated sensitivity, robustness, environmental friendliness and user-friendliness.

Background

The study seeks to investigate the therapeutic potential of Terminalia arjuna callus in addressing atherosclerosis. In order to get maximum beneficial phytoconstituents from Terminalia arjuna, it is recommended to harvest the bark from Arjuna trees that are at least 15 years old and a gap of minimum 2 years should be kept before harvesting bark from the same plant. The callus culture technique was employed to expedite the process. The callus culture extract was subsequently converted into a nanosuspension with the aim of improving the efficacy of its phytoconstituents. It was then subjected to a comprehensive series of in vitro and in vivo evaluations to ascertain its potential for treatment of atherosclerosis.

Results

Liquid chromatography–mass spectrometry analysis of the callus extract confirmed the presence of flavonoids and terpenoids, known for their antioxidant and anti-inflammatory activities. Some terpenoids were even absent in Arjuna tree naturally. TEM images validated successful entrapment of the extract within the nanoparticles. In vitro analysis for antilipase and antioxidant assay confirmed the antiatherosclerotic potential of the extract. In vivo tests on rat blood serum demonstrated a significant reduction in total cholesterol, low-density lipoprotein, triglycerides, high-density lipoprotein, and very low-density lipoprotein. Histopathological analysis of rat aortas showed additional confirmation of antiatherosclerotic action.

Conclusion

In conclusion, the study highlights the potential of nanosuspension derived from Terminalia arjuna callus extract as a comprehensive therapeutic strategy for atherosclerosis treatment. The research highlights antioxidant, anti-inflammatory, and antiatherosclerotic properties of the callus, hinting at its viability as a potential treatment for atherosclerosis. This interdisciplinary investigation emphasizes the promising role of traditional medicinal plants within modern medical paradigms.

Background

Researchers, prompted by the toxicity and side effects associated with cisplatin, are exploring alternative approaches for developing transition metal-based anticancer agents. Employing a green biochemical approach, we transformed Nickel pyridine dicarboxylic acid compounds into the nanoscale using the aqueous extract of Macrotyloma uniflorum (horse gram).

Results

Characterization of the biosynthesized nanoparticles involved electronic and IR spectroscopy. A scanning electron microscope revealed a predominant spherical shape for most Nickel nanoparticles (Ni-NPs), with XRD patterns indicating particle sizes ranging from approximately 30–150 nm. The nanoparticles were evaluated for their free radical scavenging efficiency and in vitro anti-malignant properties against HeLa and A549 cancer cell lines. Numerical optimization of the DPPH and MTT assays was conducted using response surface methodology (RSM), focusing on the effects of 3,4-pyridine dicarboxylic acid (ML₁), 2,4-pyridine dicarboxylic acid (ML₂), nickel nanoparticles concentration, and temperature. In this investigation, the incorporation of Horse Gram seed extract (Macrotyloma uniflorum) has unveiled its abundance in phenolic and flavonoid compounds, widely acknowledged for their robust antioxidant activity in the existing literature.

Conclusion

The present study highlights the potential for refining the bio-toxicity and biochemical attributes of Ni-NPs to pave the way for a new generation of versatile anticancer agents with clinically established efficacy. Notably, the anticipated data closely corresponds with experimental outcomes, reinforcing the trustworthiness and validity of the RSM model for examining anticancer and antioxidant properties in this context. ML₂ exhibited heightened antioxidant and anticancer activities in comparison to ML₁ nanoparticles.

Graphical abstract

Background

Obesity is a precursor for many co-morbid diseases. One of the main triggering factors for obesity is the abnormal expansion of white adipose tissue characterized by high rates of genesis and differentiation of precursor cells into mature adipocytes. As a result, targeting adipogenesis and adipogenic transcription factors opens new roadmaps for developing novel antiobesity pharmacotherapies. The present study was intended to rationally develop topiramate–phenolic acid conjugate for targeting obesity via inhibition of PPARγ which is often considered as the master regulator of adipogenesis.

Results

2D QSAR models were built to foretell PPARγ inhibitory activity of designed conjugates. The models presented excellent robustness, goodness of fit, and predictive capability compounds. The highest PPARγ inhibitory activity was predicted for T3 (topiramate–caffeic acid conjugate) with a pIC₅₀ value of 7.08 µM. Molecular docking was performed for all the designed conjugates against PPARγ (PDB ID: 3VSO). The highest binding affinity was exhibited by T3 (− 11.27 kcal/mol) and displayed strong and stable interactions with the receptor within the allosteric pocket in comparison to the irreversible PPARγ antagonist, GW9662 (binding affinity, − 9.0 kcal/mol). These results were confirmed by subjecting the best-docked molecules to molecular dynamic simulations. The PPARγ–T3 complex was observed to be most stable with maximum number of hydrogen bonds (maximum observed RMSD = 0.57 Å at 100 ns) in comparison to PPARγ–topiramate and PPARγ–caffeic acid complexes. Consequently, T3 was synthesized and further subjected to in vitro screening. The TR-FRET assay established T3 as a PPARγ antagonist (IC₅₀ = 6.78 µM). T3 also significantly reduced the lipid buildup in the 3T3-L1 adipocytes in a dose-dependent manner. In addition, T3 also reduced the protein expression levels of PPARγ as evidenced from western blot results.

Conclusions

Studies clearly indicated that T3 reduces adipose tissue cell differentiation by downstreaming PPARγ expression at protein levels, thereby emerging as a novel scaffold for antiobesity pharmacotherapy.

Graphical abstract

Background

Tetrapleura tetraptera Taubert (Fabaceae) fruits are employed by herbal practitioners in the management of uterine leiomyoma, but its usage in this regard and level of safety in chronic administration has not been sufficiently established. This study evaluated the toxicity effects of T. tetraptera ethanol fruit extract and explored its antileiomyoma effect in female Sprague Dawley (SD) rats.

Methods

Sub-chronic toxicity test of the extract was done, with biochemical and hematological changes as well as histopathology of organs assessed. Leiomyoma formation was induced in SD rats with monosodium glutamate (MSG) and the extract given at 100, 200 and 400 mg/kg doses, following both the preventive and curative methods. Total serum cholesterol, protein and estradiol were determined, as well as histopathology assessment of the uterus. Phytochemical profiling of the extract was evaluated by analytical high-performance liquid chromatography (HPLC).

Results

No significant alterations were seen in the biochemical and hematological indices in the toxicity test. The vital organs showed no changes at 200 mg/kg, but at 800 mg/kg it appeared to induce multiplication of glandular epithelium and stromal fibrosis in the uterus, and induced perivascular inflammation around the vessels of the heart. Total serum cholesterol and estradiol were significantly elevated (P ≤ 0.05) on treating normal female rats with 800 mg/kg MSG. Preventive and curative treatment of MSG-treated animals with the extract significantly decreased the elevated serum cholesterol (P ≤ 0.01) and estradiol (P ≤ 0.05). Histological studies of the uterus showed an amelioration of the proliferating fibroid cells with administration of the extract, which was more evident in the curative treatment. Result of HPLC analysis of the extract revealed rich composition in bioactive compounds such as umbelliferone, ferulic acid, aridanin, echinocystic acid, naringenin and hentriacontane.

Conclusion

The ethanol fruit extract of T. tetraptera is relatively safe in Sprague Dawley rats in low doses and has antifibroid potential as seen in its significant reduction in the elevated total cholesterol and estradiol content as well as its ability to decrease uterine leiomyoma proliferation, which may be due to its array of phytochemical constituents.

Background

In the first few days of life, jaundice has continued to be a major health concern. It typically manifests as a yellowing of the skin, mucous membranes, and sclera as a result of bilirubin deposition from excessively high concentrations in the body. It affects 80% of preterm and 60% of term new-borns within the first seven days of life, which is of great concern. According to the World Health Organization, the widespread acceptance of traditional medicines can be attributed to their accessibility and affordability. In West African arid savannah, there is a tree called Vitellaria paradoxa (Sapotaceae) that grows naturally. This well-known herb has numerous applications in medicine. Various plant components, including the leaves, roots, seeds, and fruit, have all been used in traditional medicine to cure a variety of illnesses. The purpose of this study is to objectively ascertain the efficacy of V. paradoxa root extracts on jaundice. Rats given phenylhydrazine (PHZ) to induce hyperbilirubinemia were orally administered ethylacetate, n-butanol, n-hexane, and aqueous fractions.

Result

Results indicated the presence of terpenoids, flavonoids, and phenol. n-hexane and ethylacetate fractions showed activity against jaundice in rats. This observation was due to the fact that they significantly improved all biomarkers that were examined, namely body weight change, liver function parameters (total bilirubin, direct bilirubin, aspartate aminotransferase, albumin, and total protein), haematological parameters (white blood cells, haemoglobin, red blood cells, haematocrit, and platelets), and antioxidant enzymes (superoxide dismutase and malondialdehyde).

Conclusion

n-Hexane and ethylacetate fractions of the extract showed significant activity against PHZ-induced jaundice in rats. However, n-hexane fraction was the most active fraction.

Background

Collagen extracted from fish body parts is a promising biological material. It has an important role in many pharmaceutical, medical applications and tissue engineering such as corneal regeneration and stromal replacement. The present work investigates a new trend to extract collagen from the fish cornea, as a prospected substituent of human corneal collagen by characterizing some biochemical and optical properties of the fish corneal collagen.

Results

Examination of the corneal tissue of Nile tilapia; Oreochromis niloticus was conducted using electron microscopy, Fourier transform infrared (FTIR) spectroscopy, UV–visible spectrophotometry, optical properties, and thermal properties. The fish were divided into 10 groups each of which consisted of 5 fish. 2 groups of fish were examined for each technique. Results indicated that the corneal layers of O. niloticus are thin at the center and thicker at the periphery with the stroma consisting of a triple helical structure collagen type I. The fish cornea showed very weak transmission at the UV regions (190 nm) and maximum transmission at the visible regions. The values of transmission (T), reflected light (R) and scattered light (S) were 2.685 mw, 100 × 10⁻³ mw at 45° and 40 × 10⁻³ mw, respectively. Consequently, the percentage of absorbed light is 21.76%. The denaturation temperature of the fish corneal stroma is 22.27 °C.

Conclusions

The method for obtaining fish collagen affects the specific properties of collagen and consequently its further uses as a potential biomedical substituent for mammalian collagen. Specification of the fish species and tissue type is crucial in identifying the quality as well as the physical and functional properties of the extracted collagen.

Background

Liver cancer, a formidable and complex disease, poses a significant global health threat, stemming from various causes, including chronic infections like hepatitis B and C, cirrhosis, and lifestyle factors. In liver cancer treatment, targeted delivery revolutionizes precision therapy, minimizing side effects by directing drugs specifically to cancer cells. This study aims to develop and statistically optimize cubosomal formulations containing piperine and quercetin with the goal of augmenting their activity against hepatocellular carcinoma.

Results

Employing a central-composite design, we utilized Design-Expert® software to guide the experiment. The key formulation variables were the concentration of glyceryl monooleate (GMO) and Poloxamer-407, while the dependent responses were particle size (PS) and entrapment efficiency (EE%). The optimized cubosomal formulation was validated through the utilization of high-resolution transmission electron microscopy (HR-TEM), in vitro release studies, and an in vitro cell proliferation assay conducted on the HepG2 cell line. High-performance liquid chromatography was employed for the determination of piperine and quercetin in the optimized cubosomal nanoparticle. The optimized formulation had a composition of 2.5 (w/w%) GMO and 0.5 (w/w%) Poloxamer 407. The predicted values for PS and EE% were 102.34 and 75.11%, respectively. The cytotoxicity of the optimized cubosomal formulation exhibited enhanced efficacy on the HepG2 cancer cell line, even at lower concentrations, when compared to the standard. Notably, it demonstrated a superior cytotoxic effect on the liver cancer cell line.

Conclusion

The findings of the study indicated that cubosomes exhibit promise as an effective carrier for delivering piperine and quercetin, addressing hepatocellular carcinoma effectively.

Graphical abstract