Iranian Journal of Pharmaceutical Sciences
Volume:17 Issue: 2, Spring 2021

Hematological toxicities are considerable side effects of linezolid, which can restrict its administration. This study aims to evaluate the protective effect of vitamin B6 on linezolid-induced hematological dyscrasia, i.e., thrombocytopenia and anemia in poisoned patients. In this quasi-experimental (non-randomized, non-blinded) study, a number of 28 patients treated with linezolid and vitamin B6 were matched with 50 patients who received only linezolid. The hematological factors, including red blood cells (RBCs), hemoglobin (Hb), hematocrit (Hct), and platelets (PLTs) were assessed at baseline and on days 0, 1, 3, 5, and 7 during the linezolid treatment coarse. There were no considerable differences between the two groups in demographic characteristics, poisoning, vital signs, baseline laboratory test results, and mortality rates. Overall, patients who received linezolid+B6 had significantly higher RBCs, Hb, and Hct than those treated with linezolid alone (P < 0.05). Unexpectedly, patients in the treatment group had lower PLT counts compared to the control group with no significant differences (P > 0.05). According to our findings, the co-administration of vitamin B6 and linezolid was accompanied by a lower risk of anemia but no impact on preventing or reducing thrombocytopenia in patients with gram-positive bacterial infections.

Moringa oleifera has been used in many regions of the world at the level of folk medicine as a remedy for numerous diseases including the treatment of type 2 diabetes. This study aims to investigate the antidiabetic activity of the methanolic extract of M. oleifera leaves in type 2 diabetes mellitus in animal model induced by fat rich diet and the use of the diabetogenic agent, streptozotocin (STZ) in male Wistar rats. A daily dose of 300 mg/kg of M. oleifera extract (MOE) was administered to diabetic male Wistar rats that had been induced by high fat diet feeding for one month followed by intraperitoneal injection of 40mg/kg of streptozotocin. After three weeks of MOE treatment, blood glucose concentration, lipid profile markers, urea, and creatinine were assayed. Food intake was measured daily and body weight was measured weekly. After three weeks of treatment, MOE significantly decreased the blood glucose of the tested rats, and a marked decrease of triglyceride also was noticed. Regarding renal function indicators, MOE significantly decreased the serum urea level of diabetic rats. However, no change has been noticed in the serum creatinine level in all experimental groups. The findings in the present study suggest that M. oleifera can significantly alleviate hyperglycemia, and hyperlipidemia in diabetic rats. M. oleifera could be a potential treatment of type 2 diabetic patients.

Sterol glucosides were biosynthesised in Momordica charantia L. and used as markers for the standardization of M. charantia extracts. The sterol glucoside, charantin, used as a marker consisted of equal amounts of two sterol glucosides, namely, 5, 25-stigmastadienol glucoside (1) and β-sitosterol glucoside (2). Most quantitation methods either mixed up both isomers, namely (1) and stigmasterol glucoside (3) or both the sterol glucosides (1) and (2) were not separated in the quantitation methods. The labelling of individual sterol glucosides needs to be clearly stated in nutraceutical products. This study aimed to resolve the separation of the commonly mixed-up sterol glucosides and further validate a high-performance liquid chromatography-photodiode array detector (HPLC-PDA) method for the quantification of individual sterol glucosides in M. charantia. The HPLC-PDA instrument was used for method development as it is a universal instrument available in most nutraceutical companies. Sterol glucosides (1)-(3) were separated with a Zorbax SB-C18 column and an isocratic HPLC mobile phase system of 88% methanol in deionized water. The wavelength of the PDA detector was set at 200 to 500 nm with a linearity range of 90 to 300 µg/mL and a good correlation coefficient of r2 > 0.99. The validated method was applied to fresh fruits and nutraceutical products. The sterol glucoside (1) is the major constituent in charantin. Hybrid fruits biosynthesised higher content of sterol glucosides compared to non-hybrid fruits. The content of (1)-(3) in the final nutraceutical products fluctuates and dependent on the source of raw material. Thus, standardization of extracts is essential in nutraceutical production to ensure uniform content of secondary metabolites and reproducible therapeutic effect.

Matricaria recutita L. (chamomile) is a well-known medicinal plant. As the main constituents of chamomile, flavonoids, e.g. apigenin, act on benzodiazepine/GABA receptors. This study was designed to determine the protective effect of hydroalcoholic Matricaria recutita (MR) extract (hMRxt) on pentylenetetrazole (PTZ)-induced kindling model and lipid peroxidation in mice. Forty-eight male albino mice (25-30 g) were randomly divided into six groups (n=8). Kindling was induced by 13 PTZ injections (35 mg /kg; i.p.) every other day for 26 days. The seizure score was observed and noted until 30 minutes after the PTZ injection. Finally, the mice were decapitated and their brains were dissected out so as to assess some biochemical factors, namely malondialdehyde (MDA) and nitric oxide metabolites (NOx) in the brain tissue. One-way ANOVA was used for analysis in Prism 6.0. The results showed that hMRxt (400 mg/kg) and valproate (VAP) (150 mg/kg) significantly decreased the progression and duration of seizure induced by PTZ (P <0.001). NOx level in the hMRxt (400 mg / kg), VAP (150 mg / kg) and the combination of hMRxt (50 mg / kg) + VAP (50 mg / kg) groups was significantly reduced compared to the PTZ group. Also, hMRxt (50 and 400 mg/kg) significantly increased the MDA level (P <0.001) compared to PTZ and control groups.This study revealed that hMRxt protects mice against the PTZ-induced epilepsy via NO signaling with no effect on lipid peroxidation.

Allium cepa (A. cepa) is a medicinal plant widely used as spice in food and has been reported to have antiinflammatory, antiulcer, antidiabetic, antihypertensive, anticancer, and antioxidant properties amongst others. The peels from this vegetable also possess antioxidant, antiulcer, antidiabetic, antihypertensive activities to mention few. A. cepa peels is used by traditional healers to treat and or manage different ailments but little is known about the safety of A. cepa peels. This study evaluated the safety of aqueous extract of A. cepa peels (AEACP) in female Wistar albino rats. Oral acute toxicity was evaluated using Organization for Economic Cooperation and Development (OECD) guideline 423, three (3) oral doses of extract (125, 250, and 500 mg/kg) were used for the subacute toxicity study. The effect of AEACP was evaluated on the: body weight, relative organ weight, hematological parameters, hepatic and renal parameters. The effect of AEACP was also evaluated on the histology of the kidney and liver. The median lethal dose (LD50) was estimated to be greater than 2000 mg/kg and administration of AEACP produced no significant (p˂0.05) differences in body weight, relative kidney weight, creatinine, and uric acid when compared with control group. There was a significant (p˂0.05) reduction in relative liver weight, serum sodium, and serum chloride level in 500 mg/kg group and the percentage reduction in comparison with control was 15.24 ± 1.98, 42.45 ± 2.40, and 9. 65 ± 1.07 respectively. The PLT and ALT in 125 mg/kg group was significantly (p˂0.05) lowered by 26.26 ± 2.96 and 39.46 ± 3.04 when compared with control. The WBC, uric acid, Albumin, and D. bilirubin values in 500 mg/kg group were significantly reduced (p˂0.05) compared with 125 mg/kg group with percentage reduction of 32.10 ± 2.31, 7.79 ± 1.03, 17.89 ± 2.34, and 27.37 ± 2.79 respectively. Urea level in groups treated with 125 and 250 mg/kg of AEACP was significantly lower than the control group and the percentage reduction was found to be 54.17 ± 2.10 and 37.15 ± 1.98 respectively. The histopathological examinations showed no traces of toxicity as the architecture of the liver and kidney were preserved. Acute and subacute use of Allium cepa peels produced no toxicity and its folkloric uses is safe and hence encouraged.

The global incidence of resistance to commonly used antibiotics was a challenging public health concern which justifies the urgency in the development of novel antibacterial agents. ATP dependent Mur ligases (MurC, MurD, MurE and MurF) are considered as validated targets in antibacterial drug design. Drug repurposing or drug repositioning is an alternative strategy in identifying new indications for the currently approved drugs. Statins are currently FDA approved drugs used to treat hyperlipidemia. The pleiotropic effects of statins along with their anticipated antibacterial properties encouraged us to investigate them against MurD ligase of Escherichia coli and Staphylococcus aureus. The molecular docking and MMGB-SA studies revealed that amongst all selected statins, pravastatin exhibited higher binding affinity with the catalytic residues of Escherichia coli (-7.24 kcal/mol and -88.36 kcal/mol) and Staphylococcus aureus (-7.47 kcal/mol and -63.75 kcal/mol) MurD ligases. Further 20 ns MD simulation showed stability and favorable interaction pattern of pravastatin with both enzymes.

COVID-19 is an infectious disease that started at the end of 2019 in China then became pandemic worldwide. A number of crystal structures of coronavirus proteins are available in the Protein Data Bank. In this paper, we reported results from the virtual screening of databases including 2701 FDA approved drugs against five known coronavirus protein targets. Our results showed a wide range of scores for different drugs of which some were predicted to be active against one or some of the proteins. Among all of the compounds with higher scores, tannic acid and cobicistat showed to be active against four and two of the studied proteins respectively. Tannic acid which was reported to be an antiviral and potent inhibitor of hepatitis C virus activity and cobicistat with anti- HIV activity, might be useful for the cure of COVID-19. According to the results, we suggest more studies on these valuable potential drugs.

Hypertensive crisis is a severe elevation in blood pressure (BP) that requires urgent reduction in BP to prevent or reduce target organ damage. The antihypertensive effects of nitroglycerin have been proven, but there are limited reports on the effects of various factors on the effectiveness of nitroglycerin in the treatment of hypertensive crisis. The purpose of this study was to evaluate the effects of diabetes, history of hypertension and age as well as gender differences in the effectiveness of nitroglycerin in patients with hypertensive crisis. This study included 76 patients with hypertensive crisis. For management, nitroglycerin initially started at 5 μg/min by intravenous infusion and, if needed, every 3 to 5 min, 5 μg/min was added to the above dose to a maximum of 20 μg/min as long as the blood pressure level reaches to the desired level. The results showed that the mean time of reduction of BP to the desired level in patients with history of hypertension and diabetes alone or both diseases, increased significantly in comparison to patients without these underlying diseases (P<0.01, P<0.01 and P<0.05 respectively). The results also demonstrated that there is a significant difference between patients younger than 45 and over 65 years with patients aged 45-65 (P<0.05). There is no difference between two genders in each group (P>0.05). In conclusion, patients with diabetes and/or history of hypertension are more resistant to pressure lowering effect of nitroglycerin in hypertensive crisis. Patients under 45 years of age as well as the elderly are also resistant. Therefore, it is advisable for physicians to choose the appropriate treatment for the desired outcome, considering the patient's condition.

Neuroinflammation (NI) plays a pivotal role in the pathogenesis of several neurodegenerative diseases. It has been believed that alleviating NI can be a valuable approach in controlling the progress of neurodegenerative diseases. The generation of reactive oxygen and nitrogen species could trigger and deteriorate NI. According to previous studies, rosmarinic acid (RA) could exhibit neuroprotective potential. Therefore, this study aimed to evaluate the effect of RA on hippocampal oxidative stress markers in lipopolysaccharide (LPS)-induced NI in rat brain. A total of 24 adult male Wistar rats were randomly allocated into four equal groups (n=6 each) and NI was induced in three of them by intracerebroventricular (ICV) injection of LPS (50 µg/20µl; 10 µl into each ventricle). RA (2.5-5 mg/kg i.p.) was injected 30 min before the LPS injection and continued once per day up to 48 h. On day 3, animals were sacrificed and their hippocampi were dissected. Then, hippocampal concentrations of malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NOx) were determined. RA prevented hippocampal MDA elevation in a dose-dependent-manner and increased SOD activity but did not affect NOx content. In conclusion, the results of the present study demonstrated that systemic administration of RA could effectively ameliorate oxidative stress induced by LPS in rat’s brain. This potential might be one of the underlying mechanisms through which RA mitigates NI.

Aza analogs of peptides are used in the treatment of cancer and neurodegenerative disorders. The clinical approval of goserelin for the treatment of prostate cancer proves the therapeutic potentiality of azaglycine residue. With this background, a novel approach to functionalizing the azaglycine moiety aimed at compounds possessing C-functionalization with active five membered heterocycles (pyrrole, imidazole, etc thiazolidine-2, 4-dione) and N-functionalization with acyl chains on azaglycine moiety were synthesized. The compounds were evaluated for in vitro MAGL inhibition and cytotoxicity against MCF-7 cell lines. The biological activities were corroborated with molecular docking studies with Cathepsin B and MAGL enzymes. The compounds with prominent in vitro and in silico potential against MAGL were evaluated for antinociceptive activity. This privileged N- and C-functionalization approach in the synthesis of azaglycinyl analogs demonstrated that N-oleoyl and C-thiazolidine-2,4-dione functionalized azaglycinamide derivative 1q, was found to possess moderate cytotoxic and MAGL inhibitory profile.  The active compounds were well accommodated in the binding sites of these targets with good electrostatic complementarity.  The N-oleoyl and C-thiazolidine-2, 4-dione functionalized azaglycine can be envisaged as a novel molecule with potential anticancer and antinociceptive activities.