Antidiabetic and pancreas-protective potential of Parthenium Hysterophorous (Carrot grass) in Alloxan induced diabetic rabbits.

Parthenium hysterophorus has been used to cure cancer, fever, malaria, diarrhea, dysentery, and neurologic disorders. This study evaluates the anti-diabetic effects of methanolic extract of P. hysterophorus (MEPH) in alloxan-induced diabetic rabbits. Twenty-five rabbits were divided into 5groups (N=5). Group-I served as a negative control. Groups II to V were injected with freshly prepared alloxan solution 150 mg/kg intraperitoneally to induce diabetes. Group II till V received following treatments orally: Group II: Alloxan 150 mg/kg alone; group III: Alloxan + MEPH (50 mg/kg); group IV: Alloxan + MEPH (100 mg/kg); group V: Alloxan +Glucophage (62.5 mg/kg), respectively for 10 days. The body weight of all animals was recorded on the 1st, 4th, 7th and 10th days. Short-term (1st, 3rd, 5th and 7th hour) and long-term (4th, 7th and 10th day) hypoglycemic effects were also recorded. All animals were sacrificed on the 10th day to isolate the pancreas for histopathological examination. The results showed that MPEH reduced the blood glucose levels in all the groups of alloxan-induced diabetic rabbits. The histopathological studies depicted that 100 mg/kg of MEPH most effectively repaired alloxan-induced pancreatic damage. The study showed that the MPEH is useful for developing effective phytomedicine to treat diabetes mellitus.

Structural and Functional Impact of Damaging Nonsynonymous Single Nucleotide Polymorphisms (nsSNPs) on Human VPS35 Protein Using Computational Approaches.

Parkinson's disease is the second most common progressive neurodegenerative movement disorder. Mutations in retromer complex subunit and VPS35 represent the second most common cause of late-onset familial Parkinson's disease. The mutation in VPS35 can disrupt the normal protein functions resulting in Parkinson's disease. The aim of this study was the identification of deleterious missense Single Nucleotide Polymorphisms (nsSNPs) and their structural and functional impact on the VPS35 protein. In this study, several insilico tools were used to identify deleterious and disease-associated nsSNPs. 3D structure of VPS35 protein was constructed through MODELLER 9.2, normalized using FOLDX, and evaluated through RAMPAGE and ERRAT whereas, FOLDX was used for mutagenesis. 25 ligands were obtained from literature and docked using PyRx 0.8 software. Based on the binding affinity, five ligands i.e., PG4, MSE, GOL, EDO, and CAF were further analyzed. Molecular Dynamic simulation analysis was performed using GROMACS 5.1.4, where temperature, pressure, density, RMSD, RMSF, Rg, and SASA graphs were analyzed. The results showed that the mutations Y67H, R524W, and D620N had a structural and functional impact on the VPS35 protein. The current findings will help in appropriate drug design against the disease caused by these mutations in a large population using in-vitro study.