Evaluation of the Pharmacokinetics of the Pancreastatin Inhibitor PSTi8 Peptide in Rats: Integration of In Vitro and In Vivo Findings

PSTi8 is a pancreastatin inhibitory peptide that is effective in the treatment of diabetic models. This study investigates the pharmacokinetic (PK) properties of PSTi8 in Sprague Dawley rats, for the first time. In vitro and in vivo PK studies were performed to evaluate the solubility, stability in plasma and liver microsomes, plasma protein binding, blood–plasma partitioning, bioavailability, dose proportionality, and gender difference in PK. Samples were analyzed using the validated LC-MS/MS method. The solubility of PSTi8 was found to be 9.30 and 25.75 mg/mL in simulated gastric and intestinal fluids, respectively. The protein binding of PSTi8 was estimated as >69% in rat plasma. PSTi8 showed high stability in rat plasma and liver microsomes and the blood–plasma partitioning was >2. The bioavailability of PSTi8 after intraperitoneal and subcutaneous administration was found to be 95.00 ± 12.15 and 78.47 ± 17.72%, respectively, in rats. PSTi8 showed non-linear PK in dose proportionality studies, and has no gender difference in the PK behavior in rats. The high bioavailability of PSTi8 can be due to high water solubility and plasma protein binding, low clearance and volume of distribution. Our in vitro and in vivo findings support the development of PSTi8 as an antidiabetic agent.     

Modern Approaches in the Discovery and Development of Plant-Based Natural Products and Their Analogues as Potential Therapeutic Agents

Natural products represents an important source of new lead compounds in drug discovery research. Several drugs currently used as therapeutic agents have been developed from natural sources; plant sources are specifically important. In the past few decades, pharmaceutical companies demonstrated insignificant attention towards natural product drug discovery, mainly due to its intrinsic complexity. Recently, technological advancements greatly helped to address the challenges and resulted in the revived scientific interest in drug discovery from natural sources. This review provides a comprehensive overview of various approaches used in the selection, authentication, extraction/isolation, biological screening, and analogue development through the application of modern drug-development principles of plant-based natural products. Main focus is given to the bioactivity-guided fractionation approach along with associated challenges and major advancements. A brief outline of historical development in natural product drug discovery and a snapshot of the prominent natural drugs developed in the last few decades are also presented. The researcher’s opinions indicated that an integrated interdisciplinary approach utilizing technological advances is necessary for the successful development of natural products. These involve the application of efficient selection method, well-designed extraction/isolation procedure, advanced structure elucidation techniques, and bioassays with a high-throughput capacity to establish druggability and patentability of phyto-compounds. A number of modern approaches including molecular modeling, virtual screening, natural product library, and database mining are being used for improving natural product drug discovery research. Renewed scientific interest and recent research trends in natural product drug discovery clearly indicated that natural products will play important role in the future development of new therapeutic drugs and it is also anticipated that efficient application of new approaches will further improve the drug discovery campaign.     

Simultaneous Determination of Caffeine and Paracetamol in Commercial Formulations Using Greener Normal-Phase and Reversed-Phase HPTLC Methods: A Contrast of Validation Parameters

There has been no assessment of the greenness of the described analytical techniques for the simultaneous determination (SMD) of caffeine and paracetamol. As a result, in comparison to the greener normal-phase high-performance thin-layer chromatography (HPTLC) technique, this research was conducted to develop a rapid, sensitive, and greener reversed-phase HPTLC approach for the SMD of caffeine and paracetamol in commercial formulations. The greenness of both techniques was calculated using the AGREE method. For the SMD of caffeine and paracetamol, the greener normal-phase and reversed-phase HPTLC methods were linear in the 50–500 ng/band and 25–800 ng/band ranges, respectively. For the SMD of caffeine and paracetamol, the greener reversed-phase HPTLC approach was more sensitive, accurate, precise, and robust than the greener normal-phase HPTLC technique. For the SMD of caffeine paracetamol in commercial PANEXT and SAFEXT tablets, the greener reversed-phase HPTLC technique was superior to the greener normal-phase HPTLC approach. The AGREE scores for the greener normal-phase and reversed-phase HPTLC approaches were estimated as 0.81 and 0.83, respectively, indicated excellent greenness profiles for both analytical approaches. The greener reversed-phase HPTLC approach is judged superior to the greener normal-phase HPTLC approach based on numerous validation parameters and pharmaceutical assays.     

Synthesis and X-ray crystal structure analysis of (−)-1-menthoxygermatrane

A solvate complex of (−)-1-menthoxygermatrane with chloroform ( 1 ) was obtained by reaction of (−)-menthoxytriethylstannane with 1-bromogermatrane in chloroform. The crystal and molecular structure of 1 was established by X-ray analysis.     

Isolation,Identification and Pharmacological Effects of Mandragora autumnalis Fruit Flavonoids Fraction

Since ancient times, Mandragora autumnalis has been used as a traditional medicinal plant for the treatment of numerous ailments. In light of this, the current study was designed to isolate and identify the chemical constituents of the flavonoids fraction from M. autumnalis ripe fruit (FFM), and evaluate its DPPH scavenging, anti-lipase, cytotoxicity, antimicrobial and antidiabetic effects. An ethyl acetate extract of M. autumnalis was subjected to a sequence of silica gel column chromatography using different eluents with various polarities. The chemical structures of the isolated compounds were identified using different spectral techniques, including ¹H NMR and ¹³C NMR. FFM’s anti-diabetic activity was assessed using a glucose transporter-4 (GLUT4) translocation assay, as well as an inhibition against α-amylase and α-glucosidase using standard biochemical assays. The FFM anti-lipase effect against porcine pancreatic lipase was also evaluated. Moreover, FFM free radical scavenging activity using the DPPH test and antimicrobial properties against eight microbial strains using the micro-dilution method were also assessed. Four flavonoid aglycones were separated from FFM and their chemical structures were identified. The structures of the isolated compounds were established as kaempferol 1, luteolin 2, myricetin 3 and (+)-taxifolin 4, based on NMR spectroscopic analyses. The cytotoxicity test results showed high cell viability (at least 90%) for up to 1 mg/mL concentration of FFM, which is considered to be safe. A dose-dependent increase in GLUT4 translocation was significantly shown (p < 0.05) when the muscle cells were treated with FFM up to 0.5 mg/mL. Moreover, FFM revealed potent α-amylase, α-glucosidase, DPPH scavenging and porcine pancreatic lipase inhibitory activities compared with the positive controls, with IC₅₀ values of 72.44 ± 0.89, 39.81 ± 0.74, 5.37 ± 0.41 and 39.81 ± 1.23 µg/mL, respectively. In addition, FFM inhibited the growth of all of the tested bacterial and fungal strains and showed the greatest antibacterial activity against the K. pneumoniae strain with a MIC value of 0.135 µg/mL. The four flavonoid molecules that constitute the FFM have been shown to have medicinal promise. Further in vivo testing and formulation design are needed to corroborate these findings, which are integral to the pharmaceutical and food supplement industries.     

FNDC5/Irisin: Physiology and Pathophysiology

A sedentary lifestyle or lack of physical activity increases the risk of different diseases, including obesity, diabetes, heart diseases, certain types of cancers, and some neurological diseases. Physical exercise helps improve quality of life and reduces the risk of many diseases. Irisin, a hormone induced by exercise, is a fragmented product of FNDC5 (a cell membrane protein) and acts as a linkage between muscles and other tissues. Over the past decade, it has become clear that irisin is a molecular mimic of exercise and shows various beneficial effects, such as browning of adipocytes, modulation of metabolic processes, regulation of bone metabolism, and functioning of the nervous system. Irisin has a role in carcinogenesis; numerous studies have shown its impact on migration, invasion, and proliferation of cancer cells. The receptor of irisin is not completely known; however, in some tissues it probably acts via a specific class of integrin receptors. Here, we review research from the past decade that has identified irisin as a potential therapeutic agent in the prevention or treatment of various metabolic-related and other diseases. This article delineates structural and biochemical aspects of irisin and provides an insight into the role of irisin in different pathological conditions.     

Quantitative Analysis of Abamectin,Albendazole, Levamisole HCl and Closantel in Q-DRENCH Oral Suspension Using a Stability-Indicating HPLC-DAD Method

Combination therapy of many anthelmintic drugs has been used to achieve fast animal curing. Q-DRENCH is an oral suspension, containing four different active drugs against GIT worms in sheep, commonly used in Australia and New Zeeland. The anti-parasitic drugs are Albendazole (ALB), Levamisole HCl (LEV), Abamectin (ABA), and Closantel (CLO). The main purpose of this study is to present a new simultaneous stability-indicting HPLC-DAD method for the analysis of the four drugs. The recommended liquid system was 1 mL of Triethylamine/L water, adjusting the pH to 3.5 by glacial acetic acid: acetonitrile solvent (20:80, v/v). Isocratic elusion achieved the desired results of separation at a 2 mL/min flow rate using Zorbax C-18 as a stationary phase. Detection was performed at 210 nm. The linearity ranges were 15.15 to 93.75 μg/mL for ALB, 25 to 150 μg/mL for LEV, 30 to 150 μg/mL for ABA, and 11.7 to 140.63 μg/mL for CLO. Moreover, the final greenness score was 0.62 using the AGREE tool, which reflects the eco-friendly nature. Moreover, the four drugs were determined successfully in the presence of their stressful degradation products. This work presents the first chromatographic method for simultaneous analysis for Q-DRENCH oral suspension drugs in the presence of their stressful degradation products.     

Synthesis,Nanoformulations, and In Vitro Anticancer Activity of N-Substituted Side Chain Neocryptolepine Scaffolds

The naturally occurring neocryptolepine (5-Methylindolo [2,3-b]quinoline) and its analogs exhibited prominent anticancer and antimalarial activity. However, the main problem of this class of compounds is their poor aqueous solubility, hampering their bioavailability and preventing their clinical development. To overcome the problem of insolubility and to improve the physicochemical and the pharmacological properties of 5-Methylindolo [2,3-b]quinoline compounds, this work was designed to encapsulate such efficient medical compounds into mesoporous silica oxide nanoemulsion (SiO₂NPs). Thus, in this study, SiO₂NPs was loaded with three different concentrations (0.2 g, 0.3, and 0.6 g) of 7b (denoted as NPA). The findings illustrated that the nanoparticles were formed with a spherical shape and exhibited small size (less than 500 nm) using a high concentration of the synthesized chemical compound (NPA, 0.6 g) and good stabilization against agglomeration (more than −30 mv). In addition, NPA-loaded SiO₂NPs had no phase separation as observed by our naked eyes even after 30 days. The findings also revealed that the fabricated SiO₂NPs could sustain the release of NPA at two different pH levels, 4.5 and 7.4. Additionally, the cell viability of the produced nanoemulsion system loaded with different concentrations of NPA was greater than SiO₂NPs without loading, affirming that NPA had a positive impact on increasing the safety and cell viability of the whole nanoemulsion. Based on these obtained promising data, it can be considered that the prepared NPA-loaded SiO₂NPs seem to have the potential for use as an effective anticancer drug nanosystem.     

Experimental Study of Halloysite Nanofluids in Pool Boiling Heat Transfer

Halloysite nanotube (HNT) which is cheap, natural, and easily accessible 1D clay, can be used in many applications, particularly heat transfer enhancement. The aim of this research is to study experimentally the pool boiling heat transfer (PBHT) performance of novel halloysite nanofluids at atmospheric pressure condition from typical horizontal heater. The nanofluids are prepared from halloysite nanotubes (HNTs) nanomaterials-based deionized water (DI water) with the presence of sodium hydroxide (NaOH) solution to control pH = 12 to obtain stable nanofluid. The nanofluids were prepared with dilute volume concentrations of 0.01–0.5 vol%. The performance of PBHT is studied via pool boiling curve and pool boiling heat transfer coefficient (PBHTC) from the typical heater which is the copper horizontal tube with a thickness of 1 mm and a diameter of 22 mm. The temperatures of the heated tube surface are measured to obtain the PBHTC. The results show an improvement of PBHTC for halloysite nanofluids compared to the base fluid. At 0.05 vol% concentration, HNT nanofluid has the best enhancement of 5.8% at moderate heat flux (HF). This indicates that HNT is a potential material in heat transfer applications.