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Background: Major deaths due to colorectal cancer (CRC) arise from the metastatic dissemination of primary tumors, which is related to molecules contributing to metastatic phenotype, the pathways they control, and the genes they regulate. Purpose: To evaluate the effect of eugenol (EUG) and beta-caryophyllene (BCP) in combination with 5-fluorouracil in-vitro cytotoxic activity and in-silico method. Methods: We tested the compounds on human colorectal cancer cell line HCT116 for the combined effect of 5-FU with EUG and BCP in in-vitro MTT assay. The pharmacokinetic assessment was carried out through in-silico ADMET analysis. Compound-Disease-Target (C-D-T) network were constructed against metastatic Colorectal cancer (mCRC) from which the hub proteins were selected for molecular docking studies. Enrichment analysis for the key targets was explored for gene ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways involved in mCRC to explore their functional role in human body for EUG, BCP and 5-FU. Results: ADMET analysis showed that both the compounds follow the rule of five with good bioavailability thus, the compounds were found to be in the acceptable range by following drug-likeness properties. MTT assay revealed in-vitrocytotoxic effects of all three compounds and a significant reduction in IC50 values (p < 0.05) when treated the cells in combination thereby giving synergistic effects (CI < 1) represented by the Fa-CI plot. C-D-T network showed that EUG, BCP, and 5-FU target 58, 24, and 49 proteins of metastatic CRC, out of which 11 target proteins were intersected in the Venn diagram. The merged C-D-T network of these three compounds showed 84 target proteins of CRC from which 16 were selected based on their edge count which includes HSP90AA1, IGF-1R, ESR1, and CASP3. These were further screened in molecular docking which depicted that EUG, BCP, and 5-FU inhibited the C-D-T network’s core target protein HSP90AA1 (Heat shock protein-90 alpha) more effectively than any other proteins. Conclusion: Our data revealed multitarget strategy to increase the effectiveness of the drug 5-FU by reducing its dosage when combined with natural phytocomponents EUG and BCP. Here, the synergism also proved effective against mCRC.

Reactive oxygen species (ROS) may be damaging to any biological system when their levels exceed those of antioxidants. ROS has both positive and negative effects. An imbalance of antioxidants and reactive oxygen species leads to oxidative stress (OS) (ROS. OS, which is more prevalent in elderly persons, is the cause of retinal diseases. Any damage to the retina that results in a reduction in visual acuity is referred to as retinopathy. Age-related macular degeneration (AMD), DR, and other retinal degenerative illnesses are caused by low antioxidant levels. Due to the presence of polyunsaturated fatty acids and photooxidative damage, the retina is especially vulnerable to OS. In vitro and in vivo antioxidant alterations in the retinal pigment epithelium were also noted. The fundamental mechanism must be understood since either OS causes retinopathies or the sickness creates stressful conditions in tissue or cells. We aimed to summarize the latest relationship between lipid peroxidation and retinopathies in the current review article.

Different medicinal products can be used to treat various disorders. Finding promising compounds for both established and new illnesses is the goal of drug development. Finding new therapeutic uses for already-approved, withdrawn-from-use, abandoned, and experimental medications is the process of "drug repurposing." Recently, the medication rosiglitazone (ROSI) was used as an anticancer agent. The status and its application as an anticancer agent are described in the current review. In this review, we outlined the function of ROSI as an anticancer agent and covered a variety of ROSI-related topics, including its molecular mechanism of action, anti-angiogenesis properties, function in oxidative stress and inflammation, function in apoptosis and cell cycle, function in cell migration and invasion, and the use of ROSI in combination therapy with other drug agents.