Natural products have long gained wide acceptance among the public and scientific community in the gastrointestinal ulcerative field. The present study explore the potential effects of aged garlic extract (AGE) on indomethacin-(IN-) induced gastric inflammation in male rats. Animals were divided into six groups (n = 8) control group, IN-induced gastric inflammation group via oral single dose (30 mg/kg to fasted rats) two AGE orally administered groups (100 and 200 mg/kg for 30 consecutive days) two AGE orally administered groups to rats pretreated with IN at the same aforementioned doses. The results declared the more potent effect of the higher AGE dose (200 mg/kg) as compared to that of the 100 mg/kg dose in the gastroprotective effects reflected by significant gastric mucosal healing of damage and reduction in the total microbial induced due to indomethacin administration. In addition to the significant effect to normalize the significant increase in malondialdehyde (MDA), myeloperoxidase (MPO), tumor necrosis factor-α (TNF-α) values, and the significant decrease in the total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) values induced by indomethacin. The results support AGE antioxidant, anti-inflammatory, and antimicrobial potency reflected by the healing of the gastric tissue damage induced by indomethacin.

Nanomedicines have gained popularity due to their potential therapeutic applications, especially cancer treatment. Targeted nanoparticles can deliver drugs directly to cancer cells and enable prolonged drug release, reducing off-target toxicity and increasing therapeutic efficacy. However, translating nanomedicines from preclinical to clinical settings has been difficult. Rapid advancements in nanotechnology promise to enhance cancer therapies. Nanomedicine offers advanced targeting and multifunctionality. Nanoparticles (NPs) have several uses nowadays. They have been studied as drug transporters, tumor gene delivery agents, and imaging contrast agents. Nanomaterials based on organic, inorganic, lipid, or glycan substances and synthetic polymers have been used to enhance cancer therapies. This review focuses on polymeric nanoparticle delivery strategies for anticancer nanomedicines.

Although Annona squamosa Linn. (Annonaceae) has been used in traditional medicine and is known to have several pharmacological properties, its impact on EGFR kinase has not been fully investigated. An assay (biochemical) was used to govern the potential of different A. squamosa seed extracts to scavenge free radicals in petroleum ether, acetone, ethanol, and methanol. We also tested A. squamosa leaf extracts for their ability to inhibit the growth of HEK 293, MCF7, and HepG2 cell lines. The PSE, ASE, ESE, and MSE all contained anti-cancer substances like anethole, cyclopentane, 1,1,3-trimethyl, and phosphonate oxide tributyl, according to phytochemical analysis. ESE extracts from A. squamosa seeds have been selected based on free radical generation probabilities, cytotoxicity studies, and phytochemical analysis. Subsequent insilico studies have been conducted, and the results have shown that interactions between compounds present in ESE extracts and the EGFR kinase are what give these compounds their inhibitory effects. Preliminary phytochemical and pharmacological activities were studied and reported. A. squamosa ESE extracts inhibited the growth of MCF7 cells, and a pharmacokinetic study showed that the compounds anethole, cyclopentane, 1,1,3-trimethyl, and phosphonium oxide tributyl had few undesirable side effects. These substances can be used to both prevent and treat cancer diseases.

Kaposi’s sarcoma associated herpesvirus (KSHV) is causative agent of Kaposi’s sarcoma, Multicentric Castleman Disease and Pleural effusion lymphoma. KSHV-encoded ORF17 encodes a protease which cleaves -Ala-Ala-, -Ala-Ser- or -Ala-Thr-bonds. The protease plays an important role in assembly and maturation of new infective virions. In the present study, we investigated expression pattern of KSHV-encoded protease during physiologically allowed as well as chemically induced reactivation condition. The results showed a direct and proportionate relationship between ORF17 expression with reactivation time. We employed virtual screening on a large database of natural products to identify an inhibitor of ORF17 for its plausible targeting and restricting Kaposi’s sarcoma associated herpesvirus assembly/maturation. A library of 307,814 compounds of biological origin (A total 481,799 structures) has been used as a screen library. 1-oleoyl-2-hydroxy-sn-glycero-3-phospho-(1′-myo-inositol) was highly effective against ORF17 in in-vitro experiments. The screened compound was tested for the cytotoxic effect and potential for inhibiting Kaposi’s sarcoma associated herpesvirus production upon induced reactivation by hypoxia, TPA and butyric acid. Treatment of reactivated KSHV-positive cells with 1-oleoyl-2-hydroxy-sn-glycero-3-phospho-(1′-myo-inositol) resulted in significant reduction in the production of Kaposi’s sarcoma associated herpesvirus. The study identified a lysophosphatidic acid molecule for alternate strategy to inhibit KSHV-encoded protease and target Kaposi’s sarcoma associated herpesvirus associated malignancies.

Human noroviruses (NV) are the most prevalent cause of sporadic and pandemic acute gastroenteritis. NV infections cause substantial morbidity and death globally, especially amongst the aged, immunocompromised individuals, and children. There are presently no authorized NV vaccines, small-molecule therapies, or prophylactics for humans. NV 3 C L protease (3CLP) has been identified as a promising therapeutic target for anti-NV drug development. Herein, we employed a structure-based virtual screening method to screen a library of 700 antiviral compounds against the active site residues of 3CLP. We report three compounds, Sorafenib, YM201636, and LDC4297, that were revealed to have a higher binding energy (BE) value with 3CLP than the control (Dipeptidyl inhibitor 7) following a sequential screening, in-depth molecular docking and visualization, physicochemical and pharmacological property analysis, and molecular dynamics (MD) study. Sorafenib, YM201636, and LDC4297 had BEs of -11.67, -10.34, and -9.78 kcal/mol with 3CLP, respectively, while control had a BE of -6.38 kcal/mol. Furthermore, MD simulations of the two best compounds and control were used to further optimize the interactions, and a 100 ns MD simulation revealed that they form stable complexes with 3CLP. The estimated physicochemical, drug-like, and ADMET properties of these hits suggest that they might be employed as 3CLP inhibitors in the management of gastroenteritis. However, wet lab tests are a prerequisite to optimize them as NV 3CLP inhibitors.