Background: The Bangladeshi rural and hilly areas people have long tradition to use various medicinal plants for treating different diseases. That's why, the crude methanolic leaf extract of Ardisia solanacea with its different fractions (petroleum ether, carbon tetrachloride, n-hexane and chloroform fractions) were subjected to investigate bioactivities in swiss albino mice; namely analgesic, CNS, and Oral hypoglycemic activities, while in-vitro evaluation of cytotoxicity. Methods: Central nervous system activity was investigated by various method such as Elevated plus maze, Hole board, Hole cross and Open field test apparatus. Analgesic activity was evaluated by both acetic acid induced and tail immersion method. Hypoglycemic activity was evaluated by oral glucose tolerance test and cytotoxicity was evaluated by Brine shrimp lethality bioassay. Results: In CNS activity, among others fractions, ASCF fraction produced a significant anxiolytic activity in both elevated plus maze and Hole board test. During open-field test almost all the fractions of A. solanacea leaves extract display decreased locomotor activities that indicates significant sedative activity. The ASME and ASCF showed significant peripheral analgesic activity at a dose of 200 mg/kg and 400 mg/kg body weight (p < 0.05). In tail immersion method, among others extracts chloroform fractions exhibited significant (p < 0.05) elongation of reaction time 30 min after oral dose of 200 and 400 mg/kg body weight respectively. The methanolic and n-hexane extracts reduced blood glucose level significantly after 90 min with value of 53.94% and 48.15% respectively (p < 0.05). In case of cytotoxicity activity, among other fractions carbon tetrachloride fraction showed lowest LC 50 values. Conclusions: From the above results, it is clear that different fractions of A. solanacea showed significant pharmacological potentiality in different in-vitro and in-vivo study model. So, it will be very much possible source for an isolating lead compound for curing the numerous disorders.

: The molecular etiology of pseudoxanthoma elasticum (PXE), an autosomal recessive connective tissue disorder, has become increasingly complex as not only mutations in the ABCC6 but also ENPP1 and GGCX can cause resembling phenotypes. To get insights common pathway, the overlapping metabolites for these three proteins were predicted through 3D homology modeling and virtual screening. 3D homology models of ABCC6, ENPP1 and GGCX were generated by MODELLER program, which were further validated using RAMPAGE and ERRAT servers. Substrate binding sites of ABCC6 were predicted using blind docking of reported in vitro substrates. Virtual screening against substrate binding site of ABCC6 using metabolites listed in Human Metabolome Databases (HMDB) revealed best possible substrate of ABCC6. Those listed metabolites were further docked against predicted substrate binding sites of GGCX and ENPP1. Molecular docking and virtual screening revealed a list of 133 overlapping metabolites of these three proteins. Most of them are phosphatidylinositol (PI), Phosphatidylserine (PS), Diacylglycerol (DAG), phosphatidic acid, oleanolic acid metabolites and found to have links with calcification. These predicted overlapping metabolites may give novel insights for searching common patho-mechanism for PXE and PXE-like diseases.

Protein quality control is essential for cellular homeostasis. In this study, we examined the effect of improperly folded proteins that do not form amyloid fibrils on mitochondria, which play important roles in ATP production and cell death. First, we prepared domain 3 of the dengue envelope protein in wild type and four mutants with widely different biophysical properties in misfolded/aggregated or destabilized states. The effects of the different proteins were detected using fluorescence microscopy and Western blotting, which revealed that three of the five proteins disrupted both inner and outer membrane integrity, while the other two proteins, including the wild type, did not. Next, we examined the common characteristics of the proteins that displayed toxicity against mitochondria by measuring oligomer size, molten globule-like properties, and thermal stability. The common feature of all three toxic proteins was thermal instability. Therefore, our data strongly suggest that thermally unstable proteins generated in the cytosol can cause cellular damage by coming into direct contact with mitochondria. More importantly, we revealed that this damage is not amyloid-specific.

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Objective: This study aims to uncover the anti-diarrheal, antioxidant, thrombolytic, and anthelmintic activities of methanol extract of A. solanacea (ASME) and its soluble n-hexane fraction in methanol (ASNH).Materials and Methods: The phytochemical assessment of this plant was performed by using the standard method. The anti-diarrheal property was screened by castor oil induced diarrhea in Swiss albino mice and plant extract was administered into mice by oral gavage. The antioxidant property was being investigated by two different in vitro methods such as ferric reducing effect assay and superoxide scavenging activity assay. The thrombolytic activity was evaluated by in vitro clot lysis procedure, and the anthelmintic study was carried out on earthworm Pheretima posthuma.Results: In castor-oil induced diarrhea, ASME and ASNH induced a significant decrease (**P