Luteolin (LUT) is a natural flavonoid with low oral bioavailability with restricted clinical applications due to its low solubility. LUT shows significant anti-tumor activity in many cancer cells, including hepatocellular carcinoma (HCC). The most recent trend in pharmaceutical innovations is the application of phospholipid vesicles to improve the solubility of such hydrophobic drugs. Ethosomes are one of the most powerful phospholipid vesicles used to achieve that that target. In this study, LUT-loaded ethosomal nanoparticles (LUT-ENPs) were prepared by the cold method. Full factorial design and response surface methodology were used to analyze and optimize the selected formulation variables. Drug entrapment efficiency, vesicle size, zeta potential, Fourier transform infra-red spectroscopy, scanning electron microscopy, and cumulative percent drug released was estimated. The selected LUT-ENPs were subjected to further investigations as estimation of hepatic gene expression levels of GPC3, liver biomarkers, and oxidative stress biomarkers. The prepared LUT-ENPs were semi-spherical in shape with high entrapment efficiency. The prepared LUT-ENPs have a small particle size with high zeta potential values. The in vitro liver biomarkers assay revealed a significant decrease in the hepatic tissue nitric oxide (NO), malondialdehyde (MDA) content, and the expression of the GPC3 gene. Results showed a high increase in the hepatic tissue levels of glutathione (GSH) and superoxide dismutase (SOD). Histopathological examination showed a small number of hepatic adenomas and a significant decrease of neoplastic hepatic lesions after treatment with LUT-ENPs. Our results firmly suggest the distinctive anti-proliferative activity of LUT-ENPs as an oral drug delivery system for the treatment of HCC.

Microtubules are protein biopolymers created by polymerizing heterodimers of α and β-tubulins. Microtubule disruption induces G2/M cell cycle arrest and abnormal mitotic spindle formation. Their significance in cell division makes microtubules an appealing target for anticancer drug discovery. Several naturally occurring compounds, such as vinblastine, paclitaxel, combretastatin, and colchicine exert their activity by changing tubulin dynamics, such as polymerization and depolymerization. Tubulin, an essential tumor therapy target, is one of the hotspots in the area of antineoplastic drugs, and it is of a significance importance to design novel inhibitors for this target. Both natural and synthetic scaffolds are the main tubulin inhibitors sources. In this article, the main structural features and motifs tubulin polymerization inhibitors are reviewed. Thus, it provides a theoretical basis for target optimization of new inhibitors of tubulin polymerization. In addition, we highly recommend implementing PROTAC-based multi-acting tubulin polymerization inhibotrs for obtaining better potency.

Phytochemical investigation of Ficus pandurata Hance (Moraceae) fruits has led to the isolation of two new triterpenoids, ficupanduratin A [1β-hydroxy-3β-acetoxy-11α-methoxy-urs-12-ene] (11) and ficupanduratin B [21α-hydroxy-3β-acetoxy-11α-methoxy-urs-12-ene] (17), along with 20 known compounds: α-amyrin acetate (1), α-amyrin (2), 3β-acetoxy-20-taraxasten-22-one (3), 3β-acetoxy-11α-methoxy-olean-12-ene (4), 3β-acetoxy-11α-methoxy-12-ursene (5), 11-oxo-α-amyrin acetate (6), 11-oxo-β-amyrin acetate (7), palmitic acid (8), stigmast-4,22-diene-3,6-dione (9), stigmast-4-ene-3,6-dione (10), stigmasterol (12), β-sitosterol (13), stigmast-22-ene-3,6-dione (14), stigmastane-3,6-dione (15), 3β,21β-dihydroxy-11α-methoxy-olean-12-ene (16), 3β-hydroxy-11α-methoxyurs-12-ene (18), 6-hydroxystigmast-4,22-diene-3-one (19), 6-hydroxystigmast-4-ene-3-one (20), 11α,21α-dihydroxy-3β-acetoxy-urs-12-ene (21), and β-sitosterol-3-O-β-D-glucopyranoside (22). Compound 21 is reported for the first time from a natural source. The structures of the 20 compounds were elucidated on the basis of IR, 1D (1H and 13C), 2D (1H–1H COSY, HSQC, HMBC and NOESY) NMR and MS spectroscopic data, in addition to comparison with literature data. The isolated compounds were evaluated for their anti-microbial, anti-malarial, anti-leishmanial, and cytotoxic activities. In addition, their radioligand displacement affinity on opioid and cannabinoid receptors was assessed. Compounds 4, 11, and 15 exhibited good affinity towards the CB2 receptor, with displacement values of 69.7, 62.5 and 86.5 %, respectively. Furthermore, the binding mode of the active compounds in the active site of the CB2 cannabinoid receptors was investigated through molecular modelling.

Objective: The present study was carried out to evaluate the anticancer property of ethanol extract of Annona muricata L. Leaves and fruit against Ehrlich ascites carcinoma in Swiss albino mice. Materials and Methods: The experimental animals were divided into five groups. Group I: (Normal group) Normal mice were received (0.2 ml Saline), Group II: (Cancer group) 20 mice were intraperitoneally received EAC cells (2×10 6 cells/mouse I.P.), Group III: (EAC + leaves extract) 20 mice were orally treated after 48 hours from injection of EAC cell with a dose of 200mg/kg body weight daily for 9 consecutive days, Group IV: (EAC + fruit extract) mice were orally treated after 48 hours from injection of EAC cell with a dose of 200mg/kg body weight daily for 9 consecutive days, Group V: (EAC+ cisplatin), 20 mice were intraperitoneally treated with cisplatin after 48 hours from injection with EAC at a daily dose of 2 mg/kg body weight for 9 consecutive days. Total experimental period was 11 days, after 24 h from the last dose, 8 mice in each group were anesthetized by diethyl ether and sacrificed for the histopathological examination of liver tissue. Results: The extracts showed residual tumor growth on the surface of the liver without infiltration and mild inflammation. Conclusion:From the result it can be found that the ethanol extract of Annona muricata L. Leaves and fruit showed anticancer effect when compared to the tumor group.

Rheumatoid arthritis (RA) is an autoimmune disease with difficulty to diagnose. The association of natural resistance-associated macrophage protein-1 (NRAMP-1) gene polymorphisms with rheumatoid arthritis (RA) is the aim of this study. Methods: Two hundred individuals who were divided into two groups: RA patients group (100 Patients with RA) and control group: (100 apparently healthy subjects). NRAMP1 polymorphisms were determined by the polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) method, including D543N. Results: Rheumatoid arthritis patients demonstrated significant increase in C-reactive protein (CRP), Rheumatoid Factor Ab, Human cartilage oligomeric matrix protein (COMP) and Anti-Cyclic Citrullinated Peptide (anti-CCP) in comparison to normal. Clinical disease activity index (CDAI) and the radiological erosion score of joints in RA patients were 29.8 ± 5.3 and 60.03 ± 38.71 respectively. The G/G, G/A and A/A genotypes were 64, 33, and 3% respectively in RA patients and were 60, 25, and 15% respectively in controls with a significant difference between RA patients and controls. The CDAI and radiological erosion score of joints had the least values in NN followed by DN while DD patients had the highest levels. The patients with phenotype DD had a grade III of disease in 40 patients and grade IV in 21 patients while grade II found in three patients. However, in patients with phenotype DN, the grading of disease II, III and IV were found to be 10, 20 and 3 respectively. All patients with NN phenotype showed a grade II of disease. There was a significant difference in percentage between RA patients and controls as regard to G or A alleles distribution. The nodule associated with G/G genotype in 58.8% while bone erosion associated with G/G genotype in 65% of RA patients. Conclusion: The present study showed that NRAMP1 1703G (543D) is a risk factor for the development of RA. The estimated NRAMP1 1703G haplotype is associated with susceptibility to RA. In RA patients with 1703A, development of rheumatoid nodule is absent.