Immunomodulatory, Cytotoxic and Antileishmanial Activity of Setaria Megaphylla

Cytotoxic, antioxidative burst and antileishmanial properties of leaf extract and fractions of Setaria megaphylla were investigated to ascertain the folkloric claims of its potency in inflammatory diseases and infections. The leaf extract and fractions of Setaria megaphylla were investigated for anticancer activity against HeLa cells using SRB method and DNA interaction activity using gel electrophoresis. Antioxidative burst activity of the extract in whole blood, neutrophils and macrophages was also investigated using luminol/lucigenin-based chemiluminescence assay. The extract and fractions were similarly screened for antileishmanial activity against promastigotes of Leishmania major in vitro. The GCMS analysis of the most active fraction against HeLa cells was carried out. The leaf extract was found to exert significant anticancer activity with the hexane fraction exhibiting the most pronounced effect. The crude extract and the fractions did not interact with DNA when investigated using electrophoresis. The extract prominently inhibited oxidative burst activity in whole blood, isolated polymorphonuclear cells (PMNs) and mononuclear cells (MNCs) when two different phagocytosis activators (serum opsonizing zymosan-A and PMA) were used. The extract also exhibited moderate antileishmanial activity against promastigotes of Leishmania major in vitro. GCMS analysis of active fraction revealed pharmacologically active compounds. These results suggest that the leaf extract/fractions of S. megaphylla possesses cytotoxic, antioxidative burst and antileishmanial activities and these justify its use in ethnomedicine to treat inflammatory diseases and microbial infections and can be exploited in primary healthcare

IMMUNOMODULATORY ACTIVITIES OF SOME COMMON LICHEN METABOLITES

Objective: To evaluate the immunomodulatory activities of some of the common lichen compounds by using chemiluminescence based cellular assays.Methods: Number of secondary lichen metabolites, representing a breadth of lichen substances, were investigated for their effects on the respiratory burst of human whole blood phagocytes, isolated human polymorphonuclear leukocytes (PMNs) and murine macrophages using luminol or lucigenin-based chemiluminescence probes. Results: This study identify a clear suppressive effect of some lichen metabolites on phagocytosis response upon activation with serum opsonized zymosan by several lichen substances. Amongst the compounds tested, orsellinic acid, methyl orsellinate, methyl haematomate, lecanoric acid and lobaric acid, showed a potent immunomodulatory activity as compared to the standards. The lobaric acid suppressed both the myloperoxidase dependent and myloperoxidase independent, Reactive Oxygen Species (ROS) production in the oxidative burst of polymorphonuclear neutrophils (PMN) at the lowest concentration tested (3.1 µg/ml). Whereas, lecanoric acid, suppressed only the myloperoxidase dependent ROS production with IC50< 3.1µg/ml when compared to the standard sodium diethyldithiocarbamate trihydrate (SDT) (IC50 = 1.3 ± 0.2 µg/ml). Orsellinic acid, methyl orsellinate and methyl haematomate showed a selective myloperoxidase independent pathway with IC50 values; < 3.1µg/ml; 6.1 ± 1.0 µg/ml;  3.3 ± 0.1 µg/ml, respectively, being lower as compared to standard SDT (IC50 = 8.2 ± 1.9 µg/ml). Conclusion: Based on the results obtained it is appropriate to conclude that lichen are not only a good source of antioxidants, but also potent immunomodulators, and thus deserve to be investigated further.Â

Biological activities of a new compound isolated from the aerial parts of Vitex agnus castus L.

A new compound trivially named vitexcarpan was isolated from the ethyl acetate fraction of Vitex agnus castus. The structure of compound was elucidated with the help of spectroscopic techniques: 13C NMR, 1H NMR, heteronuclear multiple bond correlation (HMBC), heteronuclear multiple quantum coherence (HMQC), nuclear overhauser effect spectroscopy (NOESY) and correlation spectroscopy (COSY). The isolated compound was screened for possible urease, chymotrypsin and anti-inflammatory activities. The results showed that the compound possess moderate inhibitory activity against urease (43.3 %) and chymotrypsin (39.8 %) enzymes. Vitexcarpan also showed moderate (48 %) in vitro antiinflammatory activity using activated human neutrophils.Keywords: Vitex agnus castus, vitexcarpan urease, chymotrypsin, anti-inflammator

5,5-Dimethyl-2,2-bis­(pyridin-2-yl)-1,3-diazinane

In the mol­ecule of the title compound, C16H20N4, the 1,3-diazinane ring adopts a chair conformation and the dihedral angle formed by the pyridine rings is 78.64 (8)°. The mol­ecular conformation is stabilized by an intra­molecular C—H⋯N hydrogen bond, forming an S(6) ring motif. In the crystal, centrosymmetrically related mol­ecules are linked into dimers by pairs of N—H⋯N hydrogen bonds, generating rings of R 2 2(10) graph-set motif

Traditional Medicinal Herbs and Food Plants Have the Potential to Inhibit Key Carbohydrate Hydrolyzing Enzymes In Vitro and Reduce Postprandial Blood Glucose Peaks In Vivo

We hypothesized that some medicinal herbs and food plants commonly used in the management of diabetes can reduce glucose peaks by inhibiting key carbohydrate hydrolyzing enzymes. To this effect, extracts of Antidesma madagascariense (AM), Erythroxylum macrocarpum (EM), Pittosporum senacia (PS), and Faujasiopsis flexuosa (FF), Momordica charantia (MC), and Ocimum tenuiflorum (OT) were evaluated for α-amylase and α-glucosidase inhibitory effects based on starch-iodine colour changes and PNP-G as substrate, respectively. Only FF and AM extracts/fractions were found to inhibit α-amylase activity significantly (P < 0.05) and coparable to the drug acarbose. Amylase bioassay on isolated mouse plasma confirmed the inhibitory potential of AM and FF extracts with the ethyl acetate fraction of FF being more potent (P < 0.05) than acarbose. Extracts/fractions of AM and MC were found to inhibit significantly (P < 0.05) α-glucosidase activity, with IC50 comparable to the drug 1-deoxynojirimycin. In vivo studies on glycogen-loaded mice showed significant (P < 0.05) depressive effect on elevation of postprandial blood glucose following ingestion of AM and MC extracts. Our findings tend to provide a possible explanation for the hypoglycemic action of MC fruits and AM leaf extracts as alternative nutritional therapy in the management of diabetes

Drug repurposing: In-vitro anti-glycation properties of 18 common drugs

Drug repositioning or repurposing, i.e. identifying new indications for existing drugs, has gained increasing attention in the recent years. This approach enables the scientists to discover ?new targets? for known drugs in a cost and time efficient manner. Glycation, the non-enzymatic reaction of sugars with proteins or nucleic acids to form early glycation (Amadori or fructosamine) products, is a key molecular basis of diabetic complications. Inhibiting the process of non-enzymatic protein glycation is one of the key strategies to prevent glycation-mediated diabetic complications. The present study focuses on the anti-glycation activity of 18 drugs, commonly used for the treatment of gastrointestinal, central nervous system, inflammatory diseases, bacterial infections, and gout. This study was carried out by using two in-vitro protein anti-glycation assay models. Results revealed that nimesulide (3), a non-steroidal anti-inflammatory drug, possesses a good anti-glycation activity in in-vitro BSA-MG and BSA-glucose glycation models with IC50 values of 330.56 ± 2.90, and 145.46 ± 16.35 μM, respectively. Phloroglucinol dihydrate (11), a drug used for the treatment of gastrointestinal diseases, showed a weak activity in BSA-MG glycation model (IC50 = 654.89 ± 2.50 μM), while it showed a good activity in BSA-glucose assay (IC50 = 148.23 ± 0.15 μM). Trimethylphloroglucinol (9), a drug used for the treatment of pain related to functional disorders of the digestive and biliary tracts, also showed a good antiglycation activity in BSA-MG model (IC50 = 321.15 ± 1.26 μM), while it was found to be inactive in in-vitro BSA-glucose assay (IC50 = 12.95% inhibition). These activities of drugs were compared with the anti-glycation activity of the standard, rutin (IC50 = 294.5 ± 1.50 μM in BSA-MG glycation model, and IC50 = 86.94 ± 0.24 μM in BSA- glucose model). Rest of the drugs exhibited a relatively weak antiglycation activity. This study identifies nimesulide (3), and phloroglucinol dihydrate (11) as new inhibitors of in-vitro protein glycation for further investigations as potential anti-diabetic agents.Fil: Rasheed, Saima. University of Karachi; PakistánFil: Sanchez, Sara Serafina del V.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; ArgentinaFil: Yousuf, Sammer. University of Karachi; PakistánFil: Honore, Stella Maris. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Choudhary, M. Iqbal. King Abdulaziz University; Arabia Saudita. University of Karachi; Pakistá

In vitro and in cellulo anti-diabetic activity of AuI- and AuIII-isothiourea complexes

Authors are grateful to the Higher Education Commission (HEC), Pakistan, for providing financial support under the Indigenous Ph. D. Fellowship for 5000 Scholars Phase-II program for providing financial support.About 100 million people worldwide have type II diabetes (T2D), making it one of the most common metabolic disease. DPP-IV inhibitors are new class of anti-diabetic drug. Gold complexes are known for diverse biological activities. Considering these precedents, and growing interest in developing metal-based enzyme inhibitors, we report here the dipeptidyl peptidase-IV (DPP-IV) inhibitory potential of cationic, and neutral chiral gold (I), and gold (III) isothiourea complexes. Colorimetric assay with recombinant DPP-IV enzyme was employed for initial screening. Kinetic based mechanistic studies were also performed for most active complexes. Efficiency of identified inhibitors in biological environment was assessed in in cellulo assay, using Caco-2 cell line. These complexes showed a good to moderate inhibition of DPP-IV with IC50 values in the range of 22.0 – 99.0 µM, as compared to standard inhibitor, sitagliptin (IC50 = 0.033 ± 0.04 µM). It was observed that steric, and electronic properties of the isothiourea ligands have profound effect on the DPP-IV inhibitory activity of these complexes. To the best of our knowledge this study reports for the first time isothiourea based gold complexes as inhibitors of DPP-IV enzyme. These results thus provide an approach for exploring new insights into the development of effective agents against diabetes using incretin-based therapy.PostprintPeer reviewe

Mechanistic insights into strigolactone biosynthesis, signaling and regulation during plant growth and development

Strigolactones (SLs) constitute a group of carotenoid-derived phytohormones with butenolide moieties. These hormones are involved in various functions, including regulation of secondary growth, shoot branching and hypocotyl elongation, and stimulation of seed germination. SLs also control hyphal branching of arbuscular mycorrhizal (AM) fungi, and mediate responses to both abiotic and biotic cues. Most of these functions stem from the interplay of SLs with other hormones, enabling plants to appropriately respond to changing environmental conditions. This dynamic interplay provides opportunities for phytohormones to modulate and augment one another. In this article, we review our current mechanistic understanding of SL biosynthesis, receptors and signaling. We also highlight recent advances regarding the interaction of SLs with other hormones during developmental processes and stress conditions