Archeal Di-O-geranylgeranyl Glyceryl Phosphate Synthase of a UbiA Superfamily Member Provides Insight into the Multiple Human Diseases.

One of the unique characteristic features of the domain archaea, are the lipids that form the hydrophobic core of their cell membrane. These membrane lipids are characterized by distinctive isoprenoid biochemistry and the building blocks are two core lipid structures, sn-2,3- diphytanyl glycerol diether (archaeol) and sn-2,3-dibiphytanyl diglycerol tetraether (caldarchaeol). Archaeol has two phytanyl chains (C20) in a bilayer structure connected to the glycerol moiety by an ether bond. The enzyme involved in this bilayer formation is Di-O-Geranylgeranyl Glyceryl Phosphate Synthase (DGGGPS), which is a member of a very versatile superfamily of enzymes known as UbiA superfamily. Multiple sequence analysis of the typical members of the UbiA superfamily indicates that the majority of conserved residues are located around the central cavity of these enzymes. Interestingly few of these conserved residues in the human homologs are centrally implicated in several human diseases, on basis of the major mutations reported against these diseases in the earlier clinical studies. It remains to be investigated about the role of these conserved residues in the biochemistry of these enzymes. The binding and active site of these enzymes found to be similar architecture but have different substrate affinities ranging from aromatic to linear compounds. So further investigation of UbiA superfamily may be translated to novel therapeutic and diagnostic application of these proteins in human disease management.

Patho-physiological evaluation of Duranta erecta for the treatment of urolithiasis.

BACKGROUND: Urolithiasis is the third common disorder of the urinary system affecting 10-15% of the general population. In recent years, search for new antilithiatic drugs from natural sources has assumed greater importance. OBJECTIVES: This study was performed to investigate the anti-urolithiatic activity of methanolic extract of Duranta erecta leaves by in vitro and in vivo analysis. MATERIALS AND METHODS: The study was designed to determine presence of phytochemicals in D. erecta, its yield in percentage, antioxidant activity against 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and anti-microbial property against few bacteria. In vitro analysis was carried out study anti-urolithiatic property of D. erecta by nucleation assay and synthetic urine assay for inhibition of calcium oxalate and calcium oxalate monohydrate crystals formation. An in vivo experiment was performed on Wistar rats for confirmation of anti-urolithiatic property of D. erecta in animal model. RESULTS: D. erecta has the presence of primary and secondary metabolites like glycoside, saponins, sterols, flavonoids, phenols, tannins, alkaloids, carbohydrates and proteins. Methanolic extract of D. erecta gave a very good yield (60%). D. erecta proved its antioxidant potential by 93.51% inhibition of DPPH radical at a concentration of 1000 µg/mL where ascorbic showed 94.71% of DPPH radical at the same concentration. In vitro tests like nucleation assay and synthetic urine assay showed that D. erecta inhibits formation of calcium oxalate and calcium oxalate monohydrate crystals. It also showed the anti-microbial property by formation of zone of inhibition against few bacteria. An in vivo experiment on Wistar rat animal model confirmed the anti-urolithiatic property of D. erecta L. leaves extract. CONCLUSIONS: Based on the results, we reported that D. erecta may treat calcium oxalate crystal deposition in the kidney by preventing hyperoxaluria-induced peroxidative damage to the renal tubular membrane surface (lipid peroxidation). It has anti-microbial potential so it may also inhibit the secondary bacterial infection in kidney. Based on the data, it can be concluded that this herb can be used as a potential anti-urolithiasis agent for kidney stone removal.