Evaluation of the Hypoglycemic Potential of Leaves Extract of Spondias pinnata (L.f.) Kurz. from Nepal

Spondias pinnata (L.f.) Kurz. (family: Anacardiaceae) is a wild deciduous tree indigenous to southeast Asian countries. Different parts of this plant are used traditionally for the treatment and cure of various disorders and illnesses. S. pinnata leaves are used to prevent and treat diabetes in traditional Balinese medicine. However, scientific study on the antihyperglycemic effect of its leaves has not been reported yet. Therefore, this study aims to perform phytochemical screening and investigate the hypoglycemic potential of S. pinnata leaves extract. Preliminary phytochemical screening of the hydroethanolic extract was performed following the standard tests. In vivo hypoglycemic activity of the leaves extract was evaluated using normal and glucose-loaded rats. The results displayed the presence of phytochemical constituents such as saponins, phenolic compounds, flavonoids, and terpenoids. S. pinnata (500 mg/kg) and metformin (100 mg/kg) exhibited a significant (p<0.05) decrease in blood glucose level at 1, 2, and 3 h in normal rats when compared to the control group. Metformin- (100 mg/kg)- and S. pinnata- (500 mg/kg)- treated groups showed a maximum decrease in the blood glucose level at 3 h after single-dose administration in the oral glucose tolerance test (OGTT). In conclusion, S. pinnata leaves possess a significant hypoglycemic activity in the animal model and thus support its traditional use to treat diabetes. Therefore, a detailed mechanism-based study and isolation of bioactive compounds from S. pinnata leaves would be beneficial in the future for the search of new hypoglycemic agents

Structural analysis of the recognition of the -35 promoter element by SigW from Bacillus subtilis.

Sigma factors are key proteins that mediate the recruitment of RNA polymerase to the promoter regions of genes, for the initiation of bacterial transcription. Multiple sigma factors in a bacterium selectively recognize their cognate promoter sequences, thereby inducing the expression of their own regulons. In this paper, we report the crystal structure of the σ4 domain of Bacillus subtilis SigW bound to the -35 promoter element. Purine-specific hydrogen bonds of the -35 promoter element with the recognition helix α9 of the σ4 domain occurs at three nucleotides of the consensus sequence (G-35, A-34, and G'-31 in G-35A-34A-33A-32C-31C-30T-29). The hydrogen bonds of the backbone with the α7 and α8 of the σ4 domain occurs at G'-30. These results elucidate the structural basis of the selective recognition of the promoter by SigW. In addition, comparison of SigW structures complexed with the -35 promoter element or with anti-sigma RsiW reveals that DNA recognition and anti-sigma factor binding of SigW are mutually exclusive

Structural insights into the regulation of Bacillus subtilis SigW activity by anti-sigma RsiW.

Bacillus subtilis SigW is localized to the cell membrane and is inactivated by the tight interaction with anti-sigma RsiW under normal growth conditions. Whereas SigW is discharged from RsiW binding and thus initiates the transcription of its regulon under diverse stress conditions such as antibiotics and alkaline shock. The release and activation of SigW in response to extracytoplasmic signals is induced by the regulated intramembrane proteolysis of RsiW. As a ZAS (Zinc-containing anti-sigma) family protein, RsiW has a CHCC zinc binding motif, which implies that its anti-sigma activity may be regulated by the state of zinc coordination in addition to the proteolytic cleavage of RsiW. To understand the regulation mode of SigW activity by RsiW, we determined the crystal structures of SigW in complex with the cytoplasmic domain of RsiW, and compared the conformation of the CHCC motif in the reduced/zinc binding and the oxidized states. The structures revealed that RsiW inhibits the promoter binding of SigW by interacting with the surface groove of SigW. The interaction between SigW and RsiW is not disrupted by the oxidation of the CHCC motif in RsiW, suggesting that SigW activity might not be regulated by the zinc coordination states of the CHCC motif