Pharmaceutical Sciences
Volume:27 Issue: 1, Mar 2021

For the last years, different types of cucurbitacins have been extracted from various species of Cucurbitaceae family. For this review, all related papers were accumulated by searching electronic databases in the English language, including PubMed, Scopus, and Google Scholar. The keywords of cucurbitacin, cucumber anticancer therapy, cytotoxic effects, chemotherapy, and inhibitor effect were searched until February 2020. According to the result of this review, cucurbitacin E as a tetracyclic triterpenes compound, has been exhibited cell cycle arrest, anti-inflammatory and anticancer activities. It showed tumor proliferation prevention, induction of apoptosis or synergistically acts with other established antitumor compounds and cytokines throughout many molecular mechanisms. In a function-structure association manner, cucurbitacin E can inhibit Janus kinas2 (JAK2) phosphorylation, the signal transducer activator of transcription 3 (STAT3) and subsequently block these pathways, which seems to be the main mechanism of its activity. Future studies could target its detection in uninvestigated sources, subsequently its derivatives to improve their anticancer activity

Biological activity of Boswellia extract (BE) has been attributed to its main active ingredients; i.e. Boswellic acids (BAs). BE/BAs possess a promising therapeutic potential in neurodegenerative disorders; including Alzheimer’s disease (AD). The multifactorial nature of AD pathophysiology necessitates the development of the disease-modifying agents (DMA). Recent multi-targeting approaches for the DMAs development have brought more attention to the plant-derived compounds regarding their better human compatibility because of their biological origin. This review addresses the current knowledge on the anti-AD activity of BE/BAs based on the available in silico, in vitro, in vivo studies and clinical trials. The contribution of BE/BAs in inflammatory pathways, Tau and β-amyloid proteins, microtubule functions, oxidative stress, cholinesterase and diabetes/insulin pathways involved in AD have been discussed. BAs efficacy in different AD-related pathways has been confirmed in vitro and in vivo. They can be considered as valuable scaffold/lead compounds for multi-targeted DMAs in anti-AD drug discovery and development.

Cholestatic liver disease primarily affects hepatic tissue. Cholestasis could also influence the function of other organs rather than the liver. Cholestasis-induced kidney injury is a severe clinical complication known as “cholemic nephropathy” (CN). Bile duct ligation (BDL) is a trustworthy experimental model for inducing CN. Although the precise mechanism of renal injury in cholestasis is not fully recognized, several studies revealed the role of oxidative stress in CN. There is no promising pharmacological intervention against CN. Carnosine (CAR) is a peptide extensively investigated for its pharmacological effects. Radical scavenging and antioxidative stress are major features of CAR. The current study aimed to evaluate the role of CAR supplementation on the CN.

CAR was administered (250 and 500 mg/kg, i.p) to BDL rats for 14 consecutive days. Urine and serum markers of renal injury, biomarkers of oxidative stress in the kidney tissue, and renal histopathological alterations were monitored.

Significant elevation in oxidative stress biomarkers, including ROS formation, lipid peroxidation, oxidized glutathione (GSSG) levels, and protein carbonylation were found in the kidney of BDL rats. Moreover, renal tissue antioxidant capacity and reduced glutathione (GSH) levels were significantly decreased in the organ of cholestatic animals. Renal histopathological changes, including tubular atrophy, interstitial inflammation, tissue fibrosis, and cast formation, were detected in the kidney of BDL rats. It was found that CAR administration significantly protected the kidney of cholestatic animals.

The antioxidative properties of this peptide might play a fundamental role in its protective properties during cholestasis.

The carcinogenic substance 7,12-Dimethylbenz[a]anthracene (DMBA) was commonly used to induce tumor formation in rodents. The development of tumor may trigger higher expression of pro-inflammatory cytokines, which in turn supports tumor progression. In this study, we examined the efficacy of Cyperus rotundus extract (CRE) that was reported to have anti-inflammatory properties. We focused on investigating the levels of activated T lymphocytes and the pro-inflammatory cytokines expressed by macrophages.

Female BALB/c were injected with DMBA subcutaneously. The DMBA exposed mice were given CRE orally in three different doses; 63.33, 158.4, and 316.8 mg/kg. After 14 days, the levels of activated T lymphocytes and pro-inflammatory cytokines were analyzed using flow cytometry. Graphical analysis was done with FlowJo v10 and followed by statistical analysis.

The treatment of CRE reduced the population of CD4 and CD8 T cells. The number of activated CD4 and CD8 T cells were also significantly suppressed. The population of macrophages marked by CD11b cells was significantly reduced. Finally, the CRE treatment suppressed the levels of TNF-α, IFN-γ, IL-1β, and IL-6 expressed by macrophages.

Our findings suggest that CRE could be a potential agent useful in therapeutic approachesfor curing the disease caused by aberrant cells.

Osthole, one of the most active components of Cnidium monnieri, has different pharmacological and biological effects such as boosting the immune system, reducing rheumatoid pain, hepatoprotective, and inhibitory effect on osteoporosis. Furthermore, it showed anti-inflammatory, anti-cancer, and antioxidant properties. However, there is little information about the antioxidant effects of osthole using cell-based assays. In the current work, we used in vitro model of 2,2-azobis (2-amidinopropane) dihydrochloride (AAPH)- induced hemolysis of erythrocytes to investigate the protective effects of osthole against oxidative damage of biological membranes.

Erythrocytes were challenged with 2, 2ꞌ-azobis (2-aminopropane) dihydrochloride (AAPH) as a model oxidant in the presence and absence of osthole. The protective effects of osthole on lipid peroxidation, protein carbonyl oxidation, glutathione (GSH) content of erythrocytes were evaluated and compared with control samples.

It was found that osthole has protective effects on erythrocyte hemolysis induced by AAPH at different concentrations in a time-dependent manner. Osthole also suppressed lipid and protein oxidation as well as reductions in GSH content in a concentration and timedependent manner.

Osthole showed protective effects against free radical-induced hemolysis in rat erythrocytes. Therefore, it can be considered as a supplement for the prevention or treatment of a variety of human health problems associated with oxidative stress. However, further investigations are required to illustrate other possible impacts of osthole on cells.

Organophosphate (OP) poisoning leads to atrioventricular node blockade, alterations in ST segment, prolongation of QT interval, alterations in P wave, lethal arrhythmias, and cardiac arrest through the inhibition of acetylcholinesterase and consequent accumulation of free synaptic acetylcholine level. So the present study was aimed to investigate the role of electrocardiographic (ECG) monitoring combined with the introduction of anti-arrhythmic interventions on OPs poisoning outcomes.

41 patients with OPs poisoning were included. Patients with history of heart or liver diseases, cholinesterase deficiency, anemia, and poisoning with other toxins were excluded. Demographic characteristics, the time elapsed between OP ingestion and hospital admission, need for mechanical ventilation, and serum cholinesterase level were recorded. ECG of patients was analyzed for rate, rhythm, ST-T abnormalities, conduction defects, and measurement of PR and QT intervals. Study outcomes were measures of morbidity and mortality.

Of 41 patients, with mean age of 34.76±13 years, 19 were male. For 68.3% of the patients, the time elapsed between ingestion and hospital admission was 3-6 hours. Eight patients were treated with mechanical ventilation. There was a significant correlation between ST segment alterations and poisoning outcomes including uncomplicated discharge, complicated discharge, and death (P=0.02). Thirty one patients were discharged without any complication, 8 with morbidity and 2 expired. ST segment changes were seen in 4 patients. Two percent had PR interval greater than 0.21s and 3% had QT interval longer than 0.45s. The mean serum cholinesterase concentration was 3011.56 U/L.

Due to lethal cardiac arrhythmia caused by OP poisoning, continuous monitoring, managing, and preventing irreparable effects of OP poisoning is highly emphasized.

Epithelial sodium channel (ENaC) is a transmembrane protein involved in maintaining sodium levels in blood plasma. It is also a potential biomarker for the early detection of hypertension since the amount of ENaC is related to the familial history of hypertension. ENaC can be detected by an aptamer, a single-stranded DNA (ssDNA) or RNA which offers advantages over an antibody. This study aimed to obtain an ssDNA aptamer specific to ENaC through virtual screening.

Forty-one aptamers were retrieved from the Protein Data Bank (PDB) and the RNA was converted to ssDNA aptamers. The X-ray crystallographic structure of ENaC protein was remodelled using Modeller 9.20 to resolve missing residues. Molecular docking of aptamers against ENaC was performed using Patchdock and Firedock, then the selected aptamer was subjected to molecular docking against other ion channel proteins to assess its selectivity to ENaC. A molecular dynamics (MD) simulation was also conducted using Amber16 to acquire an in-depth understanding of the interaction within the aptamer-ENaC complex.

The virtual screening suggested that the ssDNA of iSpinach aptamer (PDB: 5OB3) displayed the strongest binding to ENaC (-49.46 kcal/mol) and was selective for ENaC over the other ion protein channels. An MMGBSA calculation on the complex of aptamer-ENaC revealed binding energy of -42,12 kcal/mol.

The iSpinach-based aptamer is a potential probe for detecting ENaC or iDE and may be useful for the development of hypertension early detection systems.

Because of the narrow therapeutic range of tricyclic antidepressant drugs, their determination in biological samples is of great importance. In this work, a fast and environment friendly sample pretreatment method based on a dispersive liquid–liquid microextraction was developed for the extraction and preconcentration of four tricyclic antidepressants including nortriptyline, amitriptyline, desipramine, and clomipramine in urine prior to their determinations by gas chromatography–mass spectrometry.

In the suggested method, an appropriate mixture of Na2 SO4 solution (as phase separation agent and disperser) containing isopropanol (extraction solvent) is rapidly injected into an alkaline aqueous sample solution containing Na2 SO4 and the analytes. As a result, a cloudy mixture is formed and the tiny droplets of the extractant containing the extracted analytes are collected on the surface of the aqueous phase after centrifuging. Finally, an aliquot of the collected organic phase is removed and injected into the separation system for the quantitative analysis.

Under the optimum conditions, the enrichment factors and extraction recoveries were in the ranges of 380–440 and 76–88%, respectively. The limits of detection and quantification were obtained in the ranges of 11–24, and 41–75 ng/L, respectively. The relative standard deviations of the proposed method were ≤ 6.1% for intra– (n=6) and inter–day (n=4) precisions at a concentration of 100 ng/L of each analyte.

The introduced method was satisfactorily utilized for the simultaneous determination of the selected tricyclic antidepressant drugs in the patient’s urine samples.

The low aqueous solubility of three important drugs (betamethasone (BETA), meloxicam (MEL) and piroxicam (PIR)) have been increased by use of deep eutectic solvents (DESs) based choline chloride/urea (ChCl/U), choline chloride/ethylene glycol (ChCl/EG) and choline chloride/glycerol (ChCl/G) as new class of solvents at T = (298.15 to 313.15) K.

DESs were prepared by combination of the ChCl/EG, U and G with the molar ratios: 1:2. The solubility of drugs in the aqueous DESs solutions was measured at different temperatures with shake flask method.

The solubility of the investigated drugs increased with increasing the weight fraction of DESs. The solubility data were correlated by e-NRTL and Wilson models. Also, the thermodynamic functions, Gibbs energy, enthalpy, and entropy of dissolution were calculated.

At the same composition of co-solvents and temperature, the BETA, PIR and MEL solubility was highest in (ChCl/U + water), (ChCl/U + water) and (ChCl/EG + water) respectively. The calculated solubility based on these models was in good agreement with the experimental values. In addition, the results show that, the main contribution for drugs solubility in the aqueous DES solutions is the enthalpy.

Green synthesized nanoparticles (NPs) from agricultural wastes is an area of great interest due to it is eco-friendly and profitable. Zinc oxide is an inorganic UV-filter commonly used as UV-blocker in a different industry.

Zinc oxide nanoparticles (ZnO NPs) were successfully biosynthesized using Zn(NO3 )2 as a substrate by polyphenol enriched fraction (PEF) of pomegranate peel. The biological activity of ZnO NPs was evaluated using MBC and MIC tests for antibacterial and DPPH assay for antioxidant potential. Sunscreen potential of NPs was determined after applying them in water-in-oil emulsions.

UV-Vis and FT-IR spectroscopy techniques confirmed the formation of ZnO NPs. FE-SEM characterized the morphology and purity of the biosynthesized NPs with EDAX and XRD data. The average crystalline size of ZnO NPs was found to be 22 nm. FT-IR spectroscopy revealed the role of phenolic compounds in the formation and stability of ZnO NPs. The antibacterial activity of PEF and its biosynthesized ZnO was evaluated against Staphylococcus aureus and Escherichia coli. The prepared NPs showed a higher antibacterial effect than the commercial ZnO NPs. Interestingly, the antioxidant activity was also detected for obtained NPs. The PEF powder also exhibited higher antibacterial and antioxidant activity than the standards. Furthermore, the in vitro sun protection factors were estimated after applying NPs in water-inoil emulsions.

This study highlighted the possibility of using PEF of pomegranate peel for the biosynthesis of ZnO NPs as well as applying its NPs in sunscreens to achieve a safe alternative to harmful chemical UV-filters commonly used in cosmetics.

Cilostazol is an anti-platelets drug with considerable antithrombotic effects in vivo. Therefore, it is widely used by elderly patients. However, it suffers from poor bioavailability due to its low aqueous solubility. The objective of this work was to enhance the dissolution of cilostazol with the aim of formulating fast dissolving tablets for geriatrics and those of swallowing difficulties.

Ethanol-assisted co-grinding of cilostazol with sugar-based excipients was adopted. Sucralose and mannitol were used for this purpose as hydrophilic excipient as well as taste improving agents. The obtained products were investigated regarding differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction, scanning electron microscope (SEM) and in vitro drug dissolution. Fast disintegrating tablets were prepared and evaluated.

Thermal behavior of the developed products reflected reduced crystallinity, it also suggested possible existence of new crystalline species with sucralose. Eutexia was also suggested for mannitol mixtures, that was supported by X-ray diffraction data. SEM indicated size reduction with the deposition of the drug as submicron particles over the excipient surface. Co-processing markedly improved cilostazol dissolution compared to unprocessed drug. The optimized formulations were successively formulated into fast disintegrating tablets.

This investigation introduced the wet grinding strategy with sugar excipients as a platform for the formulation of easy to use tablets with optimum drug release.

Aquatic microorganisms have an important role in the bioremediation of environmental pollutants. Polycyclic Aromatic Hydrocarbons (PAHs) are described as dangerous pollutants that can bind covalently to the nucleic acids, causing mutations. Therefore, they have carcinogenic and toxic properties. Also, are involved in diseases such as asthma, lung dysfunction, and chronic bronchitis. This study aimed to isolate and characterize aquatic biodegrading bacteria from the world’s largest lake, Khazar, with the ability to use PAHs as only carbon source.

Samples were taken from the estuary of Siah Rud River (Mazandaran province, Iran) and Fereydunkenar beach leading to isolation of twenty-three bacteria on marine agar and sea water media. The isolates were cultured on separate ONR7a medium, each supplemented with only one PAH; as the sole carbon source; including naphthalene, phenanthrene, and anthracene.

Eleven bacterial isolates were able to grow on supplemented media: TBZ-E1, TBZ-E2, TBZ-E3, TBZ-S12, TBZ-S16, TBZ-E20, TBZ-SF2, TBZ-F1, TBZ-F2, TBZ-F3 and TBZ2. These isolates belong to Alteromonas, Marivivens, Pseudoalteromonas, Vibrio, Shewanella, Photobacterium, Mycobacterium and Pseudomonas genera. The qualitative analysis showed that the consortium of isolates TBZ-F1, TBZ-F2, TBZ-F3, TBZ-SF2, and TBZ2 displayed the highest degradation rate for phenanthrene and naphthalene. Naphthalene, phenanthrene, and anthracene were potently degraded by TBZ2 and TBZ-SF2 and accordingly were subjected to measure degradation potential of mentioned PAHs.

The bacterial isolates of Caspian lake have a critical duty in biodegradation of PAHs. These isolates are representative samples of the bacterial population of this lake, participating in the purification process of this habitat.

The excessive generation of ROS in the skin results in oxidative stress that can contribute to premature skin aging, inflammation, and skin carcinogenesis. To prevent these detrimental effects, the development of herbal medicine with a potent antioxidant activity into cosmetic products is required. This study aims to formulate cream that contains a safe and effective concentration of merbau (Intsia bijuga), which has been shown to have a strong antioxidant activity.

Powdered merbau wood was macerated with methanol and the dried extract was evaluated for its cytotoxic effect and antioxidant activity on human keratinocytes cell line using MTS assay. Five cream formulations containing the extract were made and subjected to stability and physical evaluations, including organoleptic, types of cream, pH, viscosity, and homogeneity.

Cytotoxicity assay revealed that merbau extracts had an IC50 of 181.3 μg/mL (95% confidence interval (CI): 165.4 - 200.1 µg/mL). At a concentration of 31.25 μg/mL, the extract exhibited a protective effect against H2 O2 -induced oxidative stress, comparable to vitamin E. Five cream formulas that were developed demonstrated good physical properties that fulfilled the evaluation parameters, including o/w type of cream, homogenous, and stable based on centrifugation and freeze-thaw cycle tests. The pH values were between 5.65 ± 0.067 - 7.4 ± 0.050, while the viscosity values were between 131 ± 1.249 - 56,011 ± 2,729.27 mPa.s. All cream formulas exhibited shear-thinning properties upon increasing shear stress.

Overall, this study has successfully formulated several cream formulations containing merbau extract at a concentration that shows antioxidant activity.

Ferulago angulata (Schltdl.) Boiss. is a herbaceous perennial plant distributed in Iran, Turkey and Iraq. The aromatic aerial parts of this plant are commonly used as antiseptic, sedative, wound healing, analgesic and food additive.

Column chromatography on silica gel (normal phase and RP-18) and Sephadex LH-20, along with recrystallization method were applied to isolation of the phytochemicals extracted from F. angulata fruits. The structures of the isolated compounds were characterized by 1 H-NMR and 13C-NMR spectral analysis. Chemical composition of the fruits essential oil obtained by hydrodistillation (HD) and steam distillation (SD) methods were also analyzed using GC-MS technique.

Six coumarin derivatives; suberosin (1), isoimperatorin (2), imperatorin (3), bergapten (4), tamarin (5) and suberenol (6), a monoterpene glycoside; verbenone-5-O-β-Dglucopyranoside (7), together with five flavonol-3-O-glycosides; isorhamnetin-3-O-rutinoside (narcissin) (8), kaempferol-3-O-rutinoside (nicotiflorin) (9), quercetin-3-O-rutinoside (rutin) (10), isorhamnetin-3-O-β-D-glucuronide (11), isorhamnetin-3-O-β-D-glucopyranoside (12) were isolated from F. angulata fruits. Essential oil extraction using HD and SD methods afforded colorless oils in 4.1 and 1.8% (v/w) yields, respectively. A total of 28 compounds were identified in essential oils, of which (Z)-β-ocimene (HD; 48.97%, SD; 50.02%), α-pinene (HD; 21.32%, SD; 23.06%) and allo-ocimene (HD; 6.98%, SD; 5.61%) were the main compounds.

This study introduces F. angulata fruits as a new source of coumarin derivatives and flavonoid glycosides. The presence of these compounds with known biological properties provides more medicinal potentials for the fruits of F. angulata. The present study also reports hydrodistillation, as an efficient method for extraction of essential oil from these aromatic fruits.