Bio-Potency and Molecular Docking Studies of Isolated Compounds from Grewia optiva J.R. Drumm. ex Burret.

In the study, two novel compounds along with two new compounds were isolated from Grewia optiva. The novel compounds have never been reported in any plant source, whereas the new compounds are reported for the first time from the studied plant. The four compounds were characterized as: 5,5,7,7,11,13-hexamethyl-2-(5-methylhexyl)icosahydro-1H-cyclopenta[a]chrysen-9-ol (IX), docosanoic acid (X), methanetriol mano formate (XI) and 2,2'-(1,4-phenylene)bis(3-methylbutanoic acid (XII). The anticholinesterase, antidiabetic, and antioxidant potentials of these compounds were determined using standard protocols. All the isolated compounds exhibited a moderate-to-good degree of activity against acetylcholinesterases (AChE) and butyrylcholinesterase (BChE). However, compound XII was particularly effective with IC50 of 55 µg/mL (against AChE) and 60 µg/mL (against BChE), and this inhibitory activity is supported by in silico docking studies. The same compound was also effective against DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid) radicals with IC50 values of 60 and 62 µg/mL, respectively. The compound also significantly inhibited the activities of α-amylase and α-glucosidase in vitro. The IC50 values for inhibition of the two enzymes were recorded as 90 and 92 µg/mL, respectively. The in vitro potentials of compound XII to treat Alzheimer's disease (in terms of AchE and BChE inhibition), diabetes (in terms of α-amylase and α-glucosidase inhibition), and oxidative stress (in terms of free radical scavenging) suggest further in vivo investigations of the compound for assessing its efficacy, safety profile, and other parameters to proclaim the compound as a potential drug candidate.

Pharmacological evaluation and in-silico modeling study of compounds isolated from Ziziphus oxyphylla.

Medicines derived from plants are preferred over synthetic therapeutic agents in treating different diseases. Ziziphus oxyphylla (a member of Rhamnaceae family) is a medicinal plant used as a remedy of different diseases in Greek and Ayurveda medical systems. Z. oxyphylla roots were shade dried and then subjected to extraction of bioactive compounds using different solvent systems and silica gel. From ethyl acetate fraction, three compounds viz., p-coumaric acid (V), 3,4-dimethoxy benzoic acid (VI), and 4-heptyloxy benzoic acid (VII) were isolated in pure form. The selection of ethyl acetate fraction for isolation was based on HPLC profiling of crude extract and different fractions. These compounds were characterized by different spectroscopic techniques and evaluated for their in vitro antioxidant, anticholinesterase, α-glucosidase, and α-amylase inhibitory potentials. To find out possible binding interactions of V with AChE and BChE crystals, in-silico docking studies were also carried out. Compound V showed maximum scavenging capabilities of DPPH and ABTS free radicals with IC50 values of 69 and 62 µg/mL respectively. Excellent percent inhibition (83.4 ± 0.5% at highest concentration 1000 µg/mL) of acetylcholinesterase (AChE) was exhibited by compound V (IC50 = 80 µg/mL); whereas, for the mentioned concentration, 83.2 ± 1.1% inhibition (IC50 = 90 µg/mL) of butyrylcholinesterase (BChE) was observed as well. The compound VI exhibited highest % inhibition against α-glucosidase (IC50 = 84 µg/mL) whereas α-amylase was more potently inhibited by compound V (% inhibition = 86.8 % and IC50 = 85 µg/mL). Docking scores of -1.391 Kcal/mol (BChE) and -6.253 Kcal/mol (AChE) were recorded using molecular docking software. Compound V exhibited strong free radical scavenging and anticholinesterase potentials suggesting that it can be effectively used to treat oxidative stress and dementia in human.

Toxicological, anticholinesterase, antilipidemic, antidiabetic and antioxidant potentials of Grewia optiva Drummond ex Burret extracts.

Background In this study, Grewia optiva Drummond ex Burret root extracts were assessed for use as a remedy for oxidative stress, diabetes mellitus and neurological disorders. Methods The antioxidative potentials of the extracts were determined using DPPH and ABTS assays, whereas their enzyme inhibitory potentials were determined against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-glucosidase and α-amylase. In the in vivo experiments, methanol extract was orally administered to mice (n = 5) at four doses of 200, 300, 400 and 500 mg kg-1 for 30 days and its effect on glucose, triglycerides, total cholesterol, etc. were investigated. Results The highest free radical scavenging activities against DPPH and ABTS radicals were recorded for the methanol and ethyl acetate extracts, and their respective IC50 values were 75 and 88 µg/mL. In addition, these two fractions were highly active in inhibiting AChE and BChE, with IC50 values of 120 and 185 µg/mL, respectively. Moderate inhibition (µg/mL) was recorded against α-glucosidase (69.02 ± 1.02 and 64.29 ± 2.41) and α-amylase (65.12 ± 2.02 and 63.29 ± 1.41) and these were comparable to the inhibitory activities exhibited by the standard, acarbose. All the extracts showed high phenolic and flavonoid contents, which correlated with their antioxidant, anticholinesterase, α-glucosidase and α-amylase activities. The phenolic compounds in the crude extract and fractions were determined using the standard HPLC method and bioactive compounds, namely, morin, ellagic acid, kaempferol-3-(p-coumaroyl-diglucoside)-7-glucoside, apigenin-7-O-rutinoside, quercetin-3-(caffeoyl-diglucoside)-7-glucoside, etc., which were detected at various retention times. Significant decrease in cholesterol, triglyceride and blood glucose levels were observed. Conclusion G. optiva is a good source of antioxidants and other phytochemicals, some of which possess anticholinesterase, anti-glucosidase, and anti-amylase activities, and can be used to treat different health conditions such as oxidative stress, neurological disorders, and diabetes mellitus.

Isolation, pharmacological evaluation and molecular docking studies of bioactive compounds from Grewia optiva.

BACKGROUND: Traditionally, Grewia optiva is widely used for the treatment of many diseases like dysentery, fever, typhoid, diarrhea, eczema, smallpox, malaria and cough. METHODS: Shade-dried roots of G. optiva were extracted with methanol. Based on HPLC results, chloroform and ethyl acetate fractions were subjected to silica column isolation and four compounds: glutaric acid (V), 3,5 dihydroxy phenyl acrylic acid (VI), (2,5 dihydroxy phenyl) 3',6',8'-trihydroxyl-4H chromen-4'-one (VII) and hexanedioic acid (VIII) were isolated in pure form. Ellman's assay was used to determine the anticholinesterase potential of isolated compounds while their antioxidant potential was estimated by DPPH and ABTS scavenging assays. RESULTS: Amongst the isolated compounds, VI and VII exhibited excellent percent inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) (83.23±1.11, 82.72±2.20 and 82.11±2.11, 82.23±1.21, respectively, at 1000 µg/mL) with IC50 of 76, 90, 78 and 92 µg/mL, respectively. Highest percent radicals scavenging against DPPH and ABTS (87.41±1.20 and 86.13±2.31) with IC50 of 64 and 65 µg/mL, respectively, were observed for compound VII. Molecular docking studies also supported the binding of compound VI and VII with the target enzyme. The para-hydroxyl group of the phenolic moiety is formed hydrogen bonds with the active site water molecule and the side chain carbonyl and hydroxyl residues of enzyme. CONCLUSION: The isolated compounds inhibited the DPPH and ABTS-free radicals, and AChE and BChE enzymes. It was concluded that these compounds could be used in relieving the oxidative stress and pathological symptoms associated with excessive hydrolysis of acetyl and butyryl choline. The results of the study were supported by docking studies for compounds VI and VII.

HGVA: the Human Genome Variation Archive.

High-profile genomic variation projects like the 1000 Genomes project or the Exome Aggregation Consortium, are generating a wealth of human genomic variation knowledge which can be used as an essential reference for identifying disease-causing genotypes. However, accessing these data, contrasting the various studies and integrating those data in downstream analyses remains cumbersome. The Human Genome Variation Archive (HGVA) tackles these challenges and facilitates access to genomic data for key reference projects in a clean, fast and integrated fashion. HGVA provides an efficient and intuitive web-interface for easy data mining, a comprehensive RESTful API and client libraries in Python, Java and JavaScript for fast programmatic access to its knowledge base. HGVA calculates population frequencies for these projects and enriches their data with variant annotation provided by CellBase, a rich and fast annotation solution. HGVA serves as a proof-of-concept of the genome analysis developments being carried out by the University of Cambridge together with UK's 100 000 genomes project and the National Institute for Health Research BioResource Rare-Diseases, in particular, deploying open-source for Computational Biology (OpenCB) software platform for storing and analyzing massive genomic datasets.

Palmaris Longus Tendon Grafting for Extensor Pollicis Longus Tendon Rupture bScrew Tip after 20 years.

INTRODUCTION: Spontaneous ruptures of extension pollicis longus tendon predominantly occur after undisplaced or minimally displaced distal radial fracture near Lister tubercle. Systemic inflammatory diseases and systemic or local steroid, mechanical causes like bony ridges, presence of bone plate or external fixator pin may precipitate this. Repetitive uses in certain occupation like cooking, cow milking, tailoring and direct trauma in kick boxer are also identified as cause. In this study it is caused by screw tip that also after 20 years. Instead of tendon transfer, interposition tendon grafting is preferred. CADE PRESENTATON: A 36-year-old male manual worker was plated for distal radial shaft fracture of left side. Distal most screw length was 3 mm in excess. After 20 years he developed rupture of extensor pollicislongus spontaneously. After excluding probable other causes and confirming by USG tendon ends were explored through dorsal incision. Offending slotted head screw was removed using hollow mill. Ipsilateral Palmaris longus tendon was grafted. Tension was set by extension of thumb and neutral position of the wrist. Removal of stitch after 2 weeks, short arm cast immobilization for 6 week and intermittent splinting and exercises for another 6 weeks yield excellent result. CONCLUSION: Timely removal of implant when it is applied over tendon rich areas is preferable. In late situation surgeon should be equipped and careful to remove it. To avoid chance of transferring a diseased tendon interposition grafting using Palmaris longus is justified.