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The convenient and highly compliant route for the delivery of active pharmaceutical ingredients is the tablet. A versatile platform of tablets is available for the delivery of therapeutic agents to the gastrointestinal tract. This study aimed to prepare gastro retentive drug delivery floating tablets of silymarin to improve its oral bioavailability and solubility. Hydroxypropyl methylcellulose (HPMCK4M and HPMCK15), Carbopol 934p and sodium bicarbonate were used as a matrix, floating enhancer and gas generating agent, respectively. The prepared tablets were evaluated for physicochemical parameters such as hardness, weight variation, friability, floating properties (floating lag time, total floating time), drug content, stability study, in vitro drug release, in vivo floating behavior and in vivo pharmacokinetics. The drug–polymer interaction was studied by Differential Scanning Calorimetry (DSC) thermal analysis and Fourier transform infrared (FTIR). The floating lag time of the formulation was within the prescribed limit (12 h. The dissolution can be described by zero-order kinetics (r2 = 0.979), with anomalous diffusion as the release mechanism (n = 0.65). An in vivo pharmacokinetic study showed that Cmax and AUC were increased by up to two times in comparison with the conventional dosage form. An in vivo imaging study showed that the tablet was present in the stomach for 12 h. It can be concluded from this study that the combined matrix system containing hydrophobic and hydrophilic polymers min imized the burst release of the drug from the tablet and achieved a drug release by zero-order kinetics, which is practically difficult with only a hydrophilic matrix. An in vivo pharmacokinetic study elaborated that the bioavailability and solubility of silymarin were improved with an increased mean residence time.

Plants’ bioactives are well-known safe drugs for vital diseases. Flavones and Flavonoid-rich dietary supplements are known to exhibit neuroprotective potential. In this study, we isolated a flavone 2-(3,4-dimethoxyphenyl)-3,7-dihydroxy-4H-chromen-4-one from Notholirion thomsonianum and it was evaluated against various targets of the oxidative stress-related neurological disorders. The compound showed excellent acetyl and butyrylcholinesterase inhibitions in its profile, giving IC50 values of 1.37 and 0.95 μM, respectively. Similarly, in in-vitro MAO-B assay, our flavone exhibited an IC50 value of 0.14 μM in comparison to the standard safinamide (IC50 0.025 μM). In in-vitro anti-inflammatory assay, our isolated compound exhibited IC50 values of 7.09, 0.38 and 0.84 μM against COX-1, COX-2 and 5-LOX, respectively. The COX-2 selectivity (SI) of the compound was 18.70. The compound was found safe in animals and was very effective in carrageenan-induced inflammation. Due to the polar groups in the structure, a very excellent antioxidant profile was observed in both in-vitro and in-vivo models. The compound was docked into the target proteins of the respective activities and the binding energies confirmed the potency of our compound. Furthermore, absorption, distribution, metabolism, excretion, and toxicity (ADMET) results showed that the isolated flavone has a good GIT absorption ability and comes with no hepatic and cardiotoxicity. In addition, the skin sensitization test, in-vitro human cell line activation test (h-CLAT) and KeratinoSens have revealed that isolated flavone is not skin sensitive with a confidence score of 59.6% and 91.6%. Herein, we have isolated a natural flavone with an effective profile against Alzheimer’s, inflammation and oxidative stress. The exploration of this natural flavone will provide a baseline for future research in the field of drug development.

Based on the pharmacological importance of different species of fragaria, this research was carried out for the isolation of bioactive compounds from Fragaria × ananassa. Using the conventional gravity column chromatography followed by small analytical column purification, two major components were isolated from the plant materials. The structures of both compounds (1 and 2) were accurately confirmed with GC-MS analysis by comparison of the fragmentation pattern within the library of the instrument. Further, the NMR analysis was also used to supplement the structural evidence. Compound 1 was observed to be 4,22-cholestadien-3-one, while compound 2 was identified as stigmast-4-en-3-one. Both compounds were evaluated for anticholinesterase, COX/LOX inhibitions and antioxidant assays. Compound 1 exhibited the IC50 values of 20.29, 27.35, 10.70, 80.10 and 7.40 μg/mL against acetylcholinesterase, butyrylcholinesterase, COX-2, COX-1 and 5-LOX, respectively. Similarly, the IC50 values of compound 2 against the same targets were 14.51, 10.65, 8.45, 109.40 and 8.71 μg/mL. Similarly, both compounds were less potent in ABTS and DPPH targets with IC50 values in the range of 185.83–369.86 μg/mL. Despite the low potencies of these compounds in antioxidant targets, they can be considered as supplementary targets in Alzheimer and inflammation. The molecular docking studies for the in vitro anti-Alzheimer and anti-inflammatory targets were also performed, which showed excellent binding interactions with the respective target proteins. In conclusion, the isolated phytosteroids from Fragaria × ananassa were evaluated scientifically for anti-Alzheimer and anti-inflammatory activities using in vitro and molecular docking approaches.

Cardiac and hepatotoxicities are major concerns in the development of new drugs. Better alternatives to other treatments are being sought to protect these vital organs from the toxicities of these pharmaceuticals. In this regard, a preclinical study is designed to investigate the histopathological effects of a new succinimide derivative (Comp-1) on myocardial and liver tissues, and the biochemical effects on selected cardiac biomarkers, hepatic enzymes, and lipid profiles. For this, an initially lethal/toxic dose was determined, followed by a grouping of selected albino rats into five groups (each group had n = 6). The control group received daily oral saline for 8 days. The 5-FU (5-Fluorouracil) group received oral saline daily for 8 days, added with the administration of a single dose of 5-FU (150 mg/kg I.P.) on day 5 of the study. The atenolol group received oral atenolol (20 mg/kg) for 8 days and 5-FU (150 mg/kg I.P.) on day 5 of the protocol. Similarly, two groups of rats treated with test compound (Comp-1) were administered with 5 mg/kg I.P. and 10 mg/kg I.P. for 8 days, followed by 5-FU (150 mg/kg I.P.) on day 5. Toxicity induced by 5-FU was manifested by increases in the serum creatinine kinase myocardial band (CK-MB), troponin I (cTnI) and lactate dehydrogenase (LDH), lipid profile, and selected liver enzymes, including ALP (alkaline phosphatase), ALT (alanine transaminase), AST (aspartate aminotransferase), BT (bilirubin total), and BD (direct bilirubin). These biomarkers were highly significantly decreased after the administration of the mentioned doses of the test compound (5 mg/kg and 10 mg/kg). Similarly, histological examination revealed cardiac and hepatic tissue toxicity by 5-FU. However, those toxic effects were also significantly recovered/improved after the administration of Comp-1 at the said doses. This derivative showed dose-dependent effects and was most effective at a dose of 10 mg/kg body weight. Binding energy data computed via docking simulations revealed that our compound interacts toward the human beta2-adrenergic G protein-coupled receptor (S = −7.89 kcal/mol) with a slight stronger affinity than the calcium channel T-type (S = −7.07 kcal/mol). In conclusion, the histological and biochemical results showed that the test compound (Comp-1) had prominent cardioprotective, hepatoprotective, and lipolytic effects against 5-FU-induced toxicity in the subjected animal model.