Indian Journal of Pharmacology最新文献

Introduction: 4-hydroxy isoleucine (4-HIL), a potent glucose-lowering agent and insulin secretagogue, is widely available in nutraceutical market as fenugreek seed extract formulations. This study aims to elucidate the oral pharmacokinetics (PK) of 4-HIL in healthy human volunteers to standardize its dose and dosing regimen, ensuring its potential for effective diabetes management.

Methodology: Twelve healthy volunteers received a single oral administration of 150 mg of 4-HIL as fenugreek seed extract tablets. Caplillary blood samples were collected at various time points within 24 h and plasma levels of 4-HIL were quantified using liquid chromatography-tandem mass spectrometry. In vitro studies on 4-HIL pharmacodynamics, derived from the literature, were used to calculate the half-minimal effective concentration (EC50). PK assessments based on compartmental modelling and dosage simulation studies were conducted using PKsolver and ModVizPOP, respectively. The PK simulation included three distinct dosage regimens (150 mg thrice daily, 225 mg twice daily, or 450 mg once daily) to evaluate EC50 level attainment.

Results: The best-fit was observed with a two-compartmental model, with maximum 4-HIL plasma concentration (Concentration maximum, 2.42 ± 0.61 µg/mL) observed at 0.5 h (Time maximum). The derived mean EC50 of 4-HIL, needed to reduce blood glucose, was 1.50 ± 0.31 µg/mL. The PK simulation study indicated that daily intake of 450 mg 4-HIL in all three tested dosing regimens had maintained EC50 levels more than 18 h for glucose-lowering effects.

Conclusion: The optimal 4-HIL dose of 450 mg/day up to three divided dosing regimens has proven effective and hence may be considered for future diabetic trials.

Metoclopramide is a dopamine-2 antagonist and is generally used as an antiemetic in clinical practice. Extrapyramidal reactions are the important adverse effects of metoclopramide which are reported in 0.2% of cases. In young children, the incidence can extend up to 25%. Metoclopramide-induced EPS include acute dystonia, tardive dyskinesia, parkinsonism, akathisia, and malignant neuroleptic syndrome. We are reporting a single dose of metoclopramide induced acute dystonia in an adolescent girl, which caused lot of anxiety in the patient and the parents which responded to oral diphenhydramine.

Background: Palmitoylethanolamide (PEA) is an endogenous fatty acid amide signaling molecule that may indirectly modulate the endocannabinoid system. It has poor water solubility and, therefore, is not readily absorbed in the human body. Various formulation techniques have been developed to enhance the rate of dissolution of PEA and minimize the variability of drug absorption when administered orally. The present study compared the pharmacokinetics (PKs) of two different grades of micronized PEA, a water-dispersible PEA, and standard PEA in male Sprague-Dawley rats, following a single oral administration.

Materials and methods: The drug PKs of each form of PEA-micronized (PEA-10µm), micronized PEA 6 µm (PEA-6 µm), and water-dispersible PEA (PEA-WD), were assessed and compared against a standard nonmicronized PEA (PEA-nm) using male Sprague-Dawley rats after a single dose oral administration. PEA plasma concentration (ng/mL) across all groups was determined using the liquid chromatography with tandem mass spectrometry method.

Results: PEA supplementation significantly increased the total area under curve (AUC) in all the groups compared to PEA-nm, with PEA-WD (P < 0.001) exhibiting an exceptionally large effect of > 16 times. In addition, the PEA supplementation raised the maximum concentration (Cmax) from the baseline in all the groups. When Cmax for each group was compared against PEA-nm at a probability level of 0.05, PEA-10 µm indicated no statistically significant difference (P = 0.060), whereas PEA-6 µm (P < 0.001) and PEA-WD (P < 0.001) displayed a statistically significant difference at the aforesaid probability level.

Conclusion: PEA-WD demonstrated a higher total AUC and Cmax, followed by PEA-6 µm and PEA-10 µm compared to nonmicronized form of PEA. This indicates greater bioavailability of water-dispersible PEA, thus making it a promising candidate for enhancing clinical outcomes.

Introduction: The proper allopathy treatment is unavailable, and the recurrent is very commonly observed for urolithiasis; therefore, there is a need to find out phytochemical options to prevent and treat urolithiasis. Our current research focuses on phytochemical alternatives as it was reported that the bean aqueous extract is used for treating kidney stones as a home remedy.

Materials and methods: Nano-aqueous extract of Phaseolus vulgaris (NAPV) suspension was formulated and evaluated for nano-formulation, the mean particle size was 327 nm, and the zeta potential was found to be -5 mV. We inducted urolithiasis by ethylene glycol-induced rat model as a standard model for evaluating anti-urolithiasis activity. Urolithiasis in rats was successfully induced in all 4 treated groups with ethylene glycol except the control group for 4 weeks as approved by CCSEA. The standard group, Test-1, test-2 were treated with aqueous extract of Phaseolus vulgaris (APV), and NAPV, respectively.

Results: The Cystone, APV, and NAPV treated groups normalized the serum, urine biochemical parameters, and kidney function compared to the ethylene glycol-induced disease control group. The kidney tissue anti-oxidants such as catalase, superoxide dismutase, and glutathione were moderately reversed for the treated groups. The histopathological examination demonstrates the cystone, APV, and NAPV-treated groups better recovered from kidney stone injury compared to the disease control group.

Conclusion: The APV and nano-formulation effectively reversed the urolithiasis symptoms similar to standard group cystone. Therefore, the APV is one of the potent phytochemical alternatives for the prevention, treatment, and management of urolithiasis.

Objective: The current study comprised a silver nanocomposite of azithromycin and its action against pseudomonal Gram-negative bacteria.

Materials and methods: First, silver nanoparticles of tulsi extract were prepared by the bottom-up method, and a nanocomposite was fabricated by azithromycin incorporation.

Results and discussion: Silver nanoparticles were subjected to ultraviolet (UV), Fourier transform infra-red (FT-IR), SEM, and X-ray diffraction (XRD) method; and produced satisfactory results. Furthermore, five formulations (NC1-NC5) of nanocomposite were prepared by silver nanoparticle and azithromycin. All nanocomposite formulation was characterized by UV, FT-IR, SEM, XRD, and EDAX. The NC4 formulation was found suitable for further investigation. UV-VIS spectra revealed that the highest absorption band is at 437 nm. FT-IR peaks were observed at 3392.350 cm-1, 1653.456 cm-1 and 1059.043 cm-1. Distinctive silver ion peaks were observed at 670.658 cm-1. Silver nanocomposite showed 2θ values of 38.8°, 44.7°, and 64.9°, and the sizes were 15.218 nm, 6.181 nm, and 14.356 nm for the silver nanocomposite of azithromycin. The average crystalline size of the nanoparticle was computed to be 15.41 nm. The atomic silver component was 60.3% confirmed by the EDAX method. The spherical shape of the nanocomposite was confirmed by an SEM study. NC-4 was further evaluated against the in vitro inhibition of Pseudomonas aeruginosa. Azithromycin was a positive control. LogIC50 was computed as 1.062-2.419 of NC4 against azithromycin. It exhibits the significant inhibition of the bacterial zone (5 mm) in comparison of azithromycin (7 mm).

Conclusion: In most cases, azithromycin gets resistant to bacterial infections. To overcome this issue, the silver nanocomposite of azithromycin could be a better alternative against Pseudomonas and other Gram-negative precarious infections.

Background: Dried Embelia ribes berries can be used to extract Embelin (2,5-Dihydroxy-3-undecylcyclohexa-2,5-diene -1,4-dione), a herbal p-benzoquinone derived from general quinones. This plant shows potential for scientific study that could provide cutting-edge therapeutic compounds. Prior studies have shown that the molecule's transformation into a complex may have increased its bioactivity. Furthermore, it has been shown that inorganic complexes are more versatile than pure organic molecules, which may improve the ability to target sites that are commonly present in the aquatic ecological environment.

Materials and methods: One of the substances with known activity found in the fruits of Embelia ribes, embelin (2, 5-dihydroxy-3- undecyl-p-benzoquinone), was extracted using chloroform solvent and then separated using column chromatography techniques. An Embelin-Sn complex was created using the purified Embelin. The Embelin-Sn complex was synthesized under simple, appropriate conditions that employed room temperature. Using elemental analysis, infrared spectroscopy, mass spectrum analysis, and Proton Nuclear Magnetic Resonance (1H NMR) spectroscopy, the structure of the Embelin-Sn complex has been ascertained.

Results: The phytochemical embelin isolated from Embelia ribes was used to synthesize Embelin-Sn complex, its characterization studied, and its anticancer potential evaluated using the MTT assay and apoptotic assay on the T-47D breast cancer cell line and antibacterial study by disc diffusion method. Sn complex concentration on breast cancer cells (T-47D cell line) were exposed to varied concentrations for 24 hours, including 40, 60, 80, 100, and 120 mg/ml. This result implies that embelin inhibits the proliferation of breast cancer cells. The antibacterial property was determined by measuring the disc's inhibitory zone size.

Conclusion: For the first time, an Embelin-Sn complex was synthesized, and it exhibited zone of inhibition against E. coli and dose-dependent administration of Embelin-Sn complex represents a potential novel strategy which can successfully treat the breast cancer.

Eltrombopag is a thrombopoietin receptor agonist which is used an off-label treatment for thrombocytopenia in chronic liver disease (CLD). It is US Food and Drug Administration approved in the treatment of immune thrombocytopenia. However, the literature review suggests its use is associated with increased risk of venous thrombosis including portal vein thrombosis (PVT). There have been several case reports of developing PVT during treatment with Eltrombopag in patients with CLD of varying etiology. We report the case of nonalcohol steatohepatitis-associated CLD with concomitant immune thrombocytopenia who developed PVT 15 days after starting eltrombopag for thrombocytopenia. Our case suggests the possible causation of PVT by eltrombopag in patients with CLD and the need for caution and continuous vigilance for detection of such a complication.

Objective: The current study sought to assess the anxiolytic effects of a methanolic extract of Biophytum sensitivum (L) DC leaves.

Materials and methods: In vivo screening methods such as the elevated plus maze model, light and dark chamber model, and mirror chamber apparatus were used to study the anxiolytic behavior, using Wistar albino rats. Methanolic extract of B. sensitivum (MEBS) leaves and was administered orally at a dose of 200 mg and 400 mg/kg.

Results: The methanolic extract of the leaves of B. sensitivum exhibited a dose-dependent anxiolytic activity.

Conclusions: The MEBS showed anxiolytic activity and showed results which were comparable to the standard drugs used. The total flavonoid content test confirmed the presence of flavonoids, which may have a role in the anxiolytic activity.