Nigelladine A among Selected Compounds from Nigella sativa Exhibits Propitious Interaction with Omicron Variant of SARS-CoV-2: An In Silico Study.

COVID-19 has been a threat to the entire world for more than two years since its outbreak in December 2019 in Wuhan city of China. SARS-CoV-2, the causative agent, had been reported to mutate over time exposing new variants. To date, no impeccable cure for the disease has been unveiled. This study outlines an extensive in silico approach to scrutinize certain phytochemical compounds of Nigella sativa (mainly the black cumin seeds) targeting the spike protein and the main protease (Mpro) enzyme of the Omicron variant of SARS-CoV-2. The objective of this study is to investigate the extracted compounds with a view to developing a potential inhibitor against the concerned SARS-CoV-2 variant. The investigation contemplates drug-likeness analysis, molecular docking study, ADME and toxicity prediction, and molecular dynamics simulation which have been executed to elucidate different phytochemical and pharmacological properties of the tested compounds. Based on drug-likeness parameters, a total of 96 phytochemical compounds from N. sativa have been screened in the study. Interestingly, Nigelladine A among the compounds exhibited the highest docking score with both the targets with the same binding affinity which is -7.8 kcal/mol. However, dithymoquinone, kaempferol, Nigelladine B, Nigellidine, and Nigellidine sulphate showed mentionable docking scores. Molecular dynamics up to 100 nanoseconds were simulated under GROMOS96 43a1 force field for the protein-ligand complexes exhibiting the top-docking score. The root mean square deviations (RMSD), root mean square fluctuations (RMSF), radius of gyration (Rg), solvent accessible surface area (SASA), and the number of hydrogen bonds have been evaluated during the simulation. From the findings, the present study suggests that Nigelladine A showed the most promising results among the selected molecules. This framework, however, interprets only a group of computational analyses on selected phytochemicals. Further investigations are required to validate the compound as a promising drug against the selected variant of SARS-CoV-2.

Methotrexate-Loaded Gelatin and Polyvinyl Alcohol (Gel/PVA) Hydrogel as a pH-Sensitive Matrix.

The aim was to formulate and evaluate Gel/PVA hydrogels as a pH-sensitive matrix to deliver methotrexate (MTX) to colon. The primed Gel/PVA hydrogels were subjected to evaluation for swelling behavior, diffusion coefficient, sol-gel characteristic and porosity using an acidic (pH 1.2) and phosphate buffer (PBS) (pH 6.8 & pH 7.4) media. Fourier transform infrared spectroscopy (FTIR) and thermal gravimetric analysis (TGA) were performed to evaluate the chemical compatibility of the Gel/PVA hydrogel. The shape alteration and release of Gel/PVA hydrogel was conducted at pH 1.2, pH 6.8 and pH 7.4. The drug release kinetic mechanism was determined using various kinetic equations. The physicochemical evaluation tests and drug release profile results were found to be significant (p < 0.01). However, it was dependent on the polymers' concentration, the pH of the release media and the amount of the cross-linking agent. Hydrogels containing the maximum amount of gel showed a dynamic equilibrium of 10.09 ± 0.18 and drug release of 93.75 ± 0.13% at pH 1.2. The kinetic models showed the release of MTX from the Gel/PVA hydrogel was non-Fickian. The results confirmed that the newly formed Gel/PVA hydrogels are potential drug delivery systems for a controlled delivery of MTX to the colon.

Role of Citrus medica L. Fruits Extract in Combatting the Hematological and Hepatic Toxic Effects of Carbofuran.

Citrus medica L. is rich in numerous vital bioactive constituents, though it is an underutilized among the citrus genus. Therefore, the aim of the present investigation was to evaluate the protective role of the C. medica fruit (CMF) methanol extract against carbofuran (CF)-induced toxicity in experimental rats. In addition, this work aims at detecting and measuring polyphenolic compounds by means of high-performance liquid chromatography (HPLC) and evaluation of the antioxidant activity of this extract. For this, studies dealing with serum hematological and biochemical parameters, liver endogenous antioxidants, as well as hepatic histo-architectural features have been carried out to assess the protective ability of CMF against CF-induced toxicity. Additionally, total phenol, flavonoid, and antioxidant capability were measured and the antioxidant action was investigated using DPPH and nitric oxide radical scavenging assays as well as reducing power assessments. HPLC results revealed the presence of benzoic acid, cinnamic acid, gallic acid, quercetin, and salicylic acid in CMF extract. Furthermore, results showed that CMF has considerable total phenol, flavonoid, and antioxidant capability and exhibits significant free radical scavenging and reducing potentialities. On the other hand, CF intoxication of rats significantly altered the hematological and serum biochemical parameters with hepatocytes disruption. Carbofuran also caused an upsurge in malondialdehyde (MDA) level and a decline in hepatic cellular antioxidant enzymes levels in rats compared to the control group. Co-administration of CMF amended the anomalies and improved the histo-architectural arrangement of hepatocytes in treated groups. CMF also inhibited the alteration of endogenous antioxidant enzymes and MDA levels as compared to the carbofuran treated group and returned them to their normal state. Taken all together, results from this investigation highlight the protective role of CMF against CF-induced toxicity which might be attributed to the polyphenolic constituents of the extract.

Antioxidant mediated protective effect of Bridelia tomentosa leaf extract against carbofuran induced oxidative hepatic toxicity.

Bridelia tomentosa (B. tomentosa) is a traditional medicinal plant for treating diverse ailments. Hence, we designed our study to scrutinize the protective effect of the methanol extract of B. tomentosa leaf (BTL) against carbofuran-induced oxidative stress-mediated hepato-toxicity in Sprague-Dawley rats for the first time, along with the identification and quantification of phenolic acids and flavonoids by high-performance liquid chromatography (HPLC) and evaluation of antioxidant and antiradical activities of this extract. HPLC analysis confirmed the existence of tannic acid, gallic acid, salicylic acid, and naringin in B. tomentosa leaf extract which showed in-vitro antioxidant potentialities with DPPH, nitric oxide, hydrogen peroxide, and hydroxyl radical scavenging properties. Co-administration of B. tomentosa leaf extract with carbofuran showed dose-dependent significant protective effects of hepatic toxicity on serum markers such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyl-transferase, lactate dehydrogenase, total bilirubin, total protein, albumin, globulin, lipid profile, urea, uric acid, and creatinine. Carbofuran intoxication also revealed an upsurge in malondialdehyde (MDA) and a decline in cellular endogenous antioxidant enzyme levels in rats compared with the control group. However, B. tomentosa leaf extract co-treatment increased the levels of hepatic antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase, and amended the MDA level. Similarly, histopathological evaluation further assured that BTL could keep the hepatocyte from carbofuran-induced damage. Therefore, all of our findings may conclude that the phenolic acids and flavonoids of B. tomentosa leaf extract are responsible to neutralize the toxic free radical-mediated oxidative hepatic damages.

Hepatoprotective and Antioxidant Activities of Justicia gendarussa Leaf Extract in Carbofuran-Induced Hepatic Damage in Rats.

In folk medicines, Justicia gendarussa (J. gendarussa) is used as a depurative herb for treating fever, pain, and cancer and as laxative for constipation. The aim of the present investigation was to evaluate the hepatoprotective effect of the leaf methanol extract of J. gendarussa leaf (J gMe) against carbofuran (CF)-intoxicated liver injuries in Sprague-Dawley rats, along with the antioxidant activity of this extract. For this purpose, levels of serum diagnostic markers, hepatic antioxidant enzymes, and liver histo-architecture were employed to justify the protective efficacy of J gMe. In addition, the phenolic and flavonoid contents of the extract were quantified, and antioxidant activity was investigated using the 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide, hydrogen peroxide, and hydroxyl free radical scavenging assays. Results revealed that the leaf extract caused a significant (<0.05, <0.01) decrease of the level of hepatic enzymes, triglycerides, and bilirubin and an increase of the total protein. J gMe has also significantly (<0.05, <0.01) lowered the level of malonylaldehyde. Carbofuran markedly suppressed hepatic antioxidant enzymes, however, the leaf extract significantly augmented these enzymes. The hepatoprotective effect was demonstrated by the improvement in the histo-architectural features of liver sections of CF-intoxicated rats treated with J gMe at 500 mg/kg dose. In addition, J gMe showed moderate total phenolic and total flavonoid content, whereas the IC50 values of DPPH, nitric oxide, hydrogen peroxide, and hydroxyl free radical scavenging assays were 71.31 ± 0.42, 134.82 ± 0.14, 47.69 ± 0.38, and 118.44 ± 0.30 µg/mL, respectively. In conclusion, the present study suggests the protective role of J gMe against hepatic injury induced by CF, which may be attributed to its higher antioxidant properties and thereby scientifically justifies its traditional use.

Protective Role of Syzygium Cymosum Leaf Extract Against Carbofuran-Induced Hematological and Hepatic Toxicities.

The aim of the present study was to evaluate the protective effect of Syzygium cymosum leaf methanol extract (SCL) against carbofuran (CF)-induced hepatotoxicity in Sprague-Dawley rats, along with the identification and quantification of polyphenolic composition by high-performance liquid chromatography (HPLC). Results revealed the presence of alkaloids, tannins, and flavonoids in SCL. Similarly, HPLC analysis suggests that SCL contains some known important antioxidants, such as rutin, benzoic acid, and salicylic acid that could be responsible for the hepatoprotective activity of the extract. In CF-exposed rats, significant hematological alterations along with histological changes were marked by the presence of necrosis, congestion, and inflammation. CF-intoxication also showed an increase in lipid peroxidation and decrease in cellular antioxidant enzymes (e.g., superoxide dismutase, catalase, and glutathione peroxidase) levels in rats compared with the control group. Furthermore, coadministration of SCL significantly ameliorated the abnormalities and improved the cellular arrangement in experimental animals. SCL also reversed the alteration of hematological and biochemical parameters and brought them back to normal levels as compared to the control group. In conclusion, S. cymosum may be one of the best sources of natural antioxidant compounds that can be used in the treatment of oxidative stress and stress-related diseases and disorders.

General perception and self-practice of complementary and alternative medicine (CAM) among undergraduate pharmacy students of Bangladesh.

BACKGROUND: Complementary and Alternative Medicine (CAM) is a combination of herbal medicine, traditional therapies, and mind-body intervention. This descriptive study was designed to assess the knowledge, attitudes, perception and self-use of CAM among Bangladeshi undergraduate pharmacy students. The study also evaluated their opinions about its integration into the pharmacy course curriculum. METHODS: It was a cross-sectional, questionnaire-based study conducted on 250 pharmacy students of five reputed public universities of Bangladesh. RESULTS: This study revealed that majority of the pharmacy students were using or had previously used at least one type of CAM. Among the students, 59% had used homeopathy followed by Ayurveda (30%), meditation (29%), massage (13%), Unani (9%), yoga (6%) and acupuncture (2%). Students' attitudes towards CAM were influenced by family and friends, books and journals, the internet and to a lesser degree by health practitioners. A significant (p < 0.05) number of students had knowledge about CAM. A majority of the students (90%) had positive, while 10% had negative attitudes towards CAM. Lack of knowledge and trained professionals were found to be the major interruptions to CAM use. 84.45% acknowledged the importance of knowledge about CAM for them as future healthcare practitioners. Furthermore, the majority of the students also believed that ideas and methods of CAM would be beneficial for conventional medicine. CONCLUSIONS: From the findings of the study, it can be recommended that an approach should be taken to educate the students about the fundamentals of CAM use so that it may fulfill the professional needs of our future pharmacists.