FORMULATION AND EVALUATION OF ISORHAMNETIN LOADED POLY LACTIC-CO-GLYCOLIC ACID NANOPARTICLES

  Objective: The aim of the present study was formulation and evaluation of isorhamnetin loaded poly lactic-co-glycolic acid (PLGA) polymeric nanoparticles (NPs).Methods: The present study was designed to incorporate the isorhamnetin in PLGA formulation by double emulsion solvent evaporation method, which offers a dynamic and flexible technology for enhancing drug solubility due to their biphasic characteristic, variety in design, composition and assembly. Synthesized isorhamnetin-PLGA NPs were characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and particle size analyzer. We tested the efficacy of isorhamnetin-PLGA NPs in HepG2 cell lines.Results: From the FTIR result, we concluded that -C-N-, -C=C-, N-H, C-N, N-O, O-H, and C-H are the functional groups present in isorhamnetin-PLGA NPs, SEM image shows spherical shape of particles. The particle size analysis result shows 255-342 nm range of particles. Isorhamnetin-PLGA NPs significantly enhanced (p<0.05) the antiproliferative effect when compared to the plain drug.Conclusion: This study concluded that the newly formulated NP drug delivery systems of isorhamnetin provided an insight into the therapeutic effectiveness of the designed formulation for the treatment of chemotherapy

COMPUTATIONAL STUDIES ON DIFFERENT TYPES OF APOPTOTIC PROTEINS DOCKED WITH A DIETARY FLAVONOID ERIODICTYOL IN COLON CANCER

Objective: In this study, to evaluate the computational studies of eriodictyol docked with apoptotic proteins.Methods: AutoDock Vina and Molecular Graphics Laboratory tools were used to determine the interaction between proteins and eriodictyol. Discovery studio visualizer and PyMOL were used to determine the interaction of amino acid residues between apoptotic proteins and eriodictyol.Results: The obtained results revealed more binding affinities of p53, caspase 8, B-cell lymphoma (Bcl)-2, Bcl-2 - associated X protein (BAX), and adenomatous polyposis coli (APC) of −10.6, −10.9, −9.0, −9.5, and 7.2 kcal/mol, respectively. Interaction of hydrophobic polar contacts of amino acid residues of p53 (CYS-277 and ALA-276), caspase 8 [THR-467, THR-337 (2), and GLU-396 (2)], Bcl-2 [ARG-103 (3), ALA-104 (2), and PHE-105, TYR-101], BAX [GLY-108, TRY-107, ASN-106, and GLN-155 (2)], and APC [GLU-40 (2) and LEU-37 (2)] were notified between macromolecules and small molecules. The calculation of root-mean-square deviation of proteins and eriodictyol showed the lower binding energies to be 11.6, 12.5, 15.9, 19.6, and 15.8 and the upper binding energies to be 12.4, 15.3, 16.9, 20.7, and 18, respectively. The homology of binding energies was determined below 2Å which is computationally less expensive and easily determined the hydrophobic polar contacts.Conclusions: The  homology  of  binding  energies  was  determined  below  2Å which  is  computationally  less  expensive  and  easily  determined the hydrophobic polar contacts. The results were proved that the eriodictyol highly interacted with apoptotic proteins. It might be a strong anti-inflammatory activity of colon cancer. In future, computational molecular docking studies should aid further in vitro and in vivo studies.Keywords: AutoDock Vina, p53, Eriodictyol, Caspase 8, B-cell lymphoma-2, Bcl-2 - associated X protein, Adenomatous polyposis coli

IN SILICO DOCKING STUDIES ON KAEMPFERITRIN WITH DIVERSE INFLAMMATORY AND APOPTOTIC PROTEINS FUNCTIONAL APPROACH TOWARDS THE COLON CANCER

Objective: The objective of this research was to formulate the binding energies and interaction of amino acid residues in kaempferitrin with different types of apoptotic and inflammatory proteins of colon cancer.Methods: AutoDock Vina and MGL tool were used for docking calculations. Both programs require the pdbqt input files and allow for flexibility of all the torsional bonds of small molecules. Discovery Studio Visualizer v3.5 was used for removal of water molecules and ligands and the pymol program was used to do analysis of the docking with various apoptotic proteins BAX, Bcl-2, COX-2, Protein kinase B.Results: In our study was developed binding energy scoring function of kaempferitrin docked with different types of inflammatory proteins and apoptotic proteins. Binding score values for-6.9 (BAX),-7.2 (Bcl-2),-7.3 (caspase-3),-8.8 (Cox-2),-7.4 (Cytochrome P450),-6.7 (Proteinase kinase B),-8.0 (TNF-α) and-7.2 (VEGF) kcal/mol, respectively. Amino acid interaction of kaempferitrin with proteins for ARG-25, LEU-52, ASN-54, PHE-55, GLU-17, LYS-14, TRP-22, THR-21 GLY-16 (Protein Kinase B), ASP-102, ASN-48, GLN-52, ASP-104 (BAX), GLU-176, TRP-173, GLU-132, PHE-135 (Bcl-2), SER-249, ASP-2, ASN-208, GLN-217, LEU-242 (Caspase 3), TYR-55, HIS-39, SER-49, GLU-322, GLY-326 (COX-2), SER-95, LEU-94, ARG-82, VAL-123, ALA-96 (TNF-α), ASP-414, LYS-322, GLU-326, GLU-416, GLU-438, ALA-439, GLU-437 (Cytochrome P450) and LEU-47, GLN-46, CYS-61, CYS-60, ASP-63, GLU-67, GLY-65, LEU-66 (VEGF) respectively.Conclusion: The results obtained in this research work clearly indicated the docking scores of apoptotic and Inflammatory proteins imply that kaempferitrin is an effective inhibitory compound for colon cancer

Luteolin promotes mitochondrial protection during acute and chronic periods of isoproterenol induced myocardial infarction in rats

AbstractObjectiveAn attempt has been made to evaluate the mitochondrial protection in acute and chronic periods after isoproterenol (ISO)-induced myocardial-infarction (MI) in male Wistar rats.Materials and methodsLuteolin was supplemented by intra-gastric intubation at a daily dose of 0.3mg/kg body weight for 30days. In the acute MI model, luteolin had been administered once per day to rat groups during 30days. On 29th and 30th days, the rats of the acute MI control groups were administered 85mg/kg body weight, isoproterenol, intra-peritoneally at an interval of 24h. In the chronic MI model luteolin was supplemented to the rat group during 30days. On the 1st and 2nd days, the rats of the chronic MI control and luteolin treatment groups were administered ISO by the same way.ResultsThe isoproterenol-treated rats both in acute and chronic models showed an increase in the level of TBARS and a decrease in the activities of mitochondrial antioxidants in MI rats, an increase in levels of mitochondrial lipid profile except phospholipids and the activities of mitochondrial enzymes were decreased in isoproterenol-treated rats. Oral treatments with luteolin in both acute and chronic models showed a significant decrease in the levels of mitochondrial lipid peroxidation, increase in the mitochondrial antioxidant levels and also decrease in the mitochondrial enzymes.ConclusionThus the present study revealed that luteolin ameliorates mitochondrial damage in isoproterenol induced myocardial infarction by maintaining lipid peroxidation metabolism due to its free radical scavenging, mitochondrial lipids, antioxidants and mitochondrial enzymes. Histopathological observations were also in correlation with the biochemical parameters

Luteolin promotes mitochondrial protection during acute and chronic periods of isoproterenol induced myocardial infarction in rats

Objective: An attempt has been made to evaluate the mitochondrial protection in acute and chronic periods after isoproterenol (ISO)-induced myocardial-infarction (MI) in male Wistar rats. Materials and methods: Luteolin was supplemented by intra-gastric intubation at a daily dose of 0.3 mg/kg body weight for 30 days. In the acute MI model, luteolin had been administered once per day to rat groups during 30 days. On 29th and 30th days, the rats of the acute MI control groups were administered 85 mg/kg body weight, isoproterenol, intra-peritoneally at an interval of 24 h. In the chronic MI model luteolin was supplemented to the rat group during 30 days. On the 1st and 2nd days, the rats of the chronic MI control and luteolin treatment groups were administered ISO by the same way. Results: The isoproterenol-treated rats both in acute and chronic models showed an increase in the level of TBARS and a decrease in the activities of mitochondrial antioxidants in MI rats, an increase in levels of mitochondrial lipid profile except phospholipids and the activities of mitochondrial enzymes were decreased in isoproterenol-treated rats. Oral treatments with luteolin in both acute and chronic models showed a significant decrease in the levels of mitochondrial lipid peroxidation, increase in the mitochondrial antioxidant levels and also decrease in the mitochondrial enzymes. Conclusion: Thus the present study revealed that luteolin ameliorates mitochondrial damage in isoproterenol induced myocardial infarction by maintaining lipid peroxidation metabolism due to its free radical scavenging, mitochondrial lipids, antioxidants and mitochondrial enzymes. Histopathological observations were also in correlation with the biochemical parameters

Cardioprotective effect of fenugreek on isoproterenol-induced myocardial infarction in rats

Objectives : This study is designed to evaluate the cardioprotective effect of fenugreek on isoproterenol- induced myocardial infarction and is investigated by an in vivo method in rats. Materials and Methods : Male Wistar albino rats were divided into four groups (n=10). Group I received 0.5% CMC treated as normal control group. Group II received isoproterenol (85 mg/kg body weight) intraperitoneal (i.p.) for two consecutive days (14 th and 15 th days). Group III received fenugreek (250 mg/kg body weight) intragastric intubation for 15 days. Group IV rats received fenugreek as in Group III and additionally isoproterenol was given for two consecutive days (14 th and 15 th days). Results : The results described the cardioprotective effect that observed in Group IV showed significantly (P< 0.05) decreased levels of TBARS and enhanced the activities of both enzymatic and non-enzymatic antioxidants (SOD, CAT, GPx and GSH) in myocardial infarcted rats when compared to Groups II and III. Histopathological studies were also co-relating with the above biochemical parameters. Conclusion : These findings concluded the cardioprotective effect of fenugreek on lipid peroxidation and antioxidant defense system during isoproterenol-induced myocardial infarction in rats

Orientin, a flavanoid, mitigates 1, 2 dimethylhydrazine-induced colorectal lesions in Wistar rats fed a high-fat diet

Orientin, a c- glycosyl flavonoid found copiously in roobios tea and various medicinal plants is well known for its antioxidant, anti-inflammatory, and antitumor effects. The present study aims to investigate the anti-cancer efficacy of orientin on 1,2 dimethyl hydrazine induced colonic aberrant crypt foci (ACF) and cell proliferation in Wistar rats. Rats were randomly divided into six groups and fed with high fat diet. Group 1 left as untreated control. Group 2 administered with DMH (20 mg/kg body weight) for initial 4 weeks and left untreated. Group 3 received orientin (10 mg/kg body weight) alone for the entire period. Group 4 received orientin along with DMH for initial 4 weeks and left untreated; Group 5 administered DMH for initial 4 weeks and treated with orientin for remaining 12 weeks; Group 6 administered DMH and treated with orientin throughout the entire period. Our preclinical findings suggest that the administration of orientin decreases the occurrence of DMH induced colonic polyps and aberrant crypt foci, augments antioxidant defense and altered the activities of drug metabolizing phase I and phase II enzymes in colonic and hepatic tissues and thereby ensuring the detoxification of carcinogen. Furthermore, orientin attenuates the aberrant crypt foci formation and reinstates the DMH induced cell proliferation, as evident from the AgNORs staining of colonic tissues of experimental rats. Thus, our study emphasizes that orientin may prevent DMH induced precancerous lesions and proven to be a potent antioxidant and antiproliferative agent. Keywords: Colorectal cancer, DMH, Orientin, Aberrant crypt foci, Cell proliferatio