Efficacy of Cyanotis tuberosa (Roxb.) Schult. &Schult. f. root tubers' active fraction as anti-diabetic, antihyperlipidemic and antioxidant in Streptozotocin-induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Cyanotis tuberosa (Roxb.) Schult. &Schult.f. is traditionally used as ethnomedicine for curing several ailments like diabetes, liver problems, ulcers, etc. OBJECTIVE: The present study was designed to evaluate the anti-diabetic potential of Cyanotis tuberosa root tubers (CTRT)in Streptozotocin (STZ) induced diabetic rats. MATERIALS AND METHODS: Anti-hyperglycemic activity of hexane extract of CTRT was investigated in diabetic rats. Silica gel chromatography was used to fractionate the hexane extract and the fraction's antihyperglycemic activity was checked in diabetic rats. Effects of long-term (30 days) treatment with an active fraction (CTAF) were evaluated in diabetic rats for 30 days by measurement of body weights, glycemic control, insulin levels, HbA1c, and serum and tissue lipid profiles. Lipid peroxide levels and antioxidant status were measured in the liver and kidney. Hepatic and Renal functional markers were also measured. Phytochemical characterization of CTAF was carried out by LC-ESI-MS/MS analysis. RESULTS: Hexane extract of CTRT at a dose of 750 mg/kg b.w produced significant antihyperglycemic activity in diabetic rats whereas CTAF has produced maximum antihyperglycemic activity at the dose of 75 mg/kg b.w. Following long-term treatment with CTAF in diabetic rats, significant improvement in glycemic control, (HbA1c) along with decreased insulin resistance (HOMA-IR), increase in body weights, and plasma insulin were observed. Also, CTAF ameliorated the serum and tissue lipid profiles. In addition, CTAF suppressed lipid peroxidation and restored the activities of antioxidant enzymes in the liver and kidney to normal levels. Further, CTAF reversed the liver and kidney functional markers to normalcy. LC-ESI-MS/MS analysis revealed the presence of 7 different phytoconstituents. CONCLUSION: This study confirmed that CTAF exerts antidiabetic effects in diabetic rats by improving insulin secretion, glycemic control, and restoring functional activities of the liver and kidney. Our results suggest that root tubers of Cyanotis tuberosa can be used as a complementary or alternative agent for the treatment of diabetes mellitus.

One-pot synthesis of thiazolo[3,2-a]pyrimidine derivatives, their cytotoxic evaluation and molecular docking studies.

An economical, simple and efficient one-pot method has been developed for the synthesis of thiazolo[3,2-a]pyrimidine hydrobromide derivatives. 2,4-diaryl-6,7,8,9-tetrahydro-4H-benzo[4,5]thiazolo[3,2-a]pyrimidine hydrobromides were synthesized by the α-bromination of cyclohexanone with N-Bromosuccinamide (NBS) and followed by cyclization with 3,4-dihydropyrimidine-2(1H)-thiones, respectively, in the presence of p-toluenesulfonic acid (PTSA) in acetonitrile. However when cyclohexanone was replaced by acetyl acetone and alpha-tetralone gave the corresponding 1-(3-methyl-5,7-diaryl-5H-thiazolo[3,2-a]pyrimidin-2-yl)ethan-1-one hydrobromide and 9,11-diaryl-6,11-dihydro-5H-naphtho[1',2':4,5]thiazolo[3,2-a]pyrimidine hydrobromide derivatives, respectively. The significant features of this method are novel, simple, inexpensive experimental procedure, short reaction time, and good yield. The some of the synthesized compounds were evaluated for cytotoxic activity against human lung adenocarcinoma cell line (A549), human breast carcinoma cell line (MCF-7), human cervical cancer cell line (HeLa) and human neuronal carcinoma cell lines (SKNSH). Tested compounds 5(b-e) showed the excellent anticancer activity against various cell lines. Particularly compound 5c with IC50 value of 2.2 ± 0.6 µM against A549 and compound 5e with IC50 value of 5.6 ± 0.4 µM against HeLa showed best cytotoxic effects. Furthermore, Molecular docking study was performed for some of the synthesized compounds 5(b-e) against topoisomerase-II by using Auto dock method. Docking results of the compounds 5c, 5d, and 5e exhibited higher cytotoxic activity than the standard doxorubicin.

Designing, docking and molecular dynamics simulation studies of novel cloperastine analogues as anti-allergic agents: homology modeling and active site prediction for the human histamine H1 receptor.

The present study predicts a three-dimensional model for the histamine H1 receptor and the design of antihistamine inhibitors using cloperastine as the core molecule by docking studies. In this work, we predicted a three-dimensional structure of the histamine H1 receptor using the MODELLER9V7 software. The protein structure was developed based on the crystal structure of the histamine H1 receptor, the lysozyme chimera of Escherichia virus T4 (PDB ID: 3RZE_A) target collected from the PDB data bank. Using molecular dynamics simulation methods, the final predicted structure is obtained and further analyzed by VERIFY3D and PROCHECK programs, confirming that the final model is reliable. The drug derivatives of cloperastine were designed and docking was performed with the designed ligands along with the drug. The predicted model of the histamine H1 receptor structure is stable and confirms that it is a reliable structure for docking studies. The results indicate that MET 183, THR 184 and ILE 187 in the histamine H1 receptor are important determinant residues for binding as they have strong hydrogen bonding with cloperastine derivatives. The drug derivatives were docked to the histamine H1 receptor protein by hydrogen bonding interactions and these interactions played an important role in the binding studies. The molecule 1-{2-[(4-chlorophenyl) (phenyl) methoxy] ethyl}-4-methylenepiperidine showed the best docking results with the histamine H1 receptor. The docking results predicted the best compounds, which may act as better drugs than cloperastine and in the future, these may be developed for anti-allergy therapy.

In Silico Studies on Anti-Stress Compounds of Ethanolic Root Extract of Hemidesmus indicus L.

BACKGROUND: Alternative medicine is available for those diseases which cannot be treated by conventional medicine. Ayurveda and herbal medicines are important alternative methods in which the treatment is done with extracts of different medicinal plants. This work is concerned with the evaluation of anti-stress bioactive compounds from the ethanolic root extract of Hemidesmus indicus. METHODS: Gas chromatography and Mass Spectrum studies are used to identify the compounds present in the ethanolic extract based on the retention time, area. In order to perform docking studies, Vasopressin model is generated using modeling by Modeller 9v7. Vasopressin structure is developed based on the crystal structure of neurophysin-oxytocin from Bos taurus (PDB ID: 1NPO_A) collected from the PDB data bank. Using molecular dynamics simulation methods, the final predicted structure is obtained and further analyzed by verifying 3D and PROCHECK programs, confirmed that the final model is reliable. The identified compounds are docked to vasopressin for the prediction of anti-stress activity using GOLD 3.0.1 software. RESULTS: The predicted model of Vasopressin structure is stabilized and confirmed that it is a reliable structure for docking studies. The results indicated ARG4, THR7, ASP9, ASP26, ALA32, ALA 80 in Vasopressin are important determinant residues in binding as they have strong hydrogen bonding with phytocompounds. Among the 21 phytocompounds identified and docked, molecule Deoxiinositol, pentakis- O-(trimethylsilyl) showed the best docking results with Vasopressin. CONCLUSION: The identified compounds were used for anti-stress activity by insilico method with Vasopressin which plays an important role in causing stress and hence selected for inhibitory studies with phytocompounds. The phytocompounds are inhibiting vasopressin through hydrogen bodings and are important in protein-ligand interactions. Docking results showed that out of twenty-one compounds, Deoxiinositol, pentakis-O-(trimethylsilyl) showed best docking energy to the Vasopressin.

Antidiabetic activity of root tubers of Asparagus gonoclados Baker in streptozotocin induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Asparagus gonoclados Baker is a traditional folk remedy used for diabetes, diuretic, galactogogue, gastric ulcer activities etc. AIM: The present investigation was intended to evaluate the beneficial effect of the A.gonoclados (Lilliaceae) root tubers against diabetes mellitus. MATERIALS AND METHODS: Different solvent extracts of root tubers of A. gonoclados were used to study the antihyperglycemic activity in streptozotocin (45 mg/kg.wt) induced diabetic rats. Oral glucose tolerance test was performed in diabetic and normal rats treated with A.gonoclados. Total phenolic content (TPC), total flavanoid content (TFC) and total steroidal saponins content (TSSC) were measured in different solvent extracts. Following bioassay guided fractionation method antihyperglycemic active fraction of A. gonoclados (AGAF) was isolated from the ethanol extract (AGEE) by silica gel column chromatography. We further tested relationship between insulin stimulation effect and the influence of active fraction on K+-ATP and Ca2+ channels opening in normal and diabetic rats. The characterization of AGAF was carried out by LC-ESI-MS/MS. RESULTS: Among the different solvent extracts, the ethanol extract (AGEE) at a dose of 500 mg/kg b.wt has produced maximum (67%) reduction in fasting blood glucose levels (FBG) in diabetic treated rats after 6 h of oral administration when compared to the standard drug glibenclamide (40%). AGEE also showed dose-dependent inhibitory effect on the activities of α-glucosidase (74.73%) and α-amylase (76.47%), which is comparable to the activity of standard drug acarbose (88.42%). AGEE was found to have the richest quantity of TPCs (138.4 ±â€¯0.39 µg/mg gallic acid equivalents), TFCs (64.8 ±â€¯0.54 µg/mg quercetin equivalents) and TSSCs (12.9 ±â€¯0.11µg/mg sarasapogenin equivalents). We identified 8 potential antihyperglycemic compounds in AGAF by LC-ESI-MS/MS analysis. CONCLUSION: From our current study we confirm that A. gonoclados root tubers have potent antihyperglycemic activity and it can be a unique drug/formulation for the management of diabetes mellitus.