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«IN SILICO AND IN VITRO EXPLORATION OF ANTI- INFLAMMATORY ACTIVITY OF ENTADA PURSAETHA BY MOLECULAR DOCKING STUDIES Narasimharao Bhogireddy1, ...»

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World Journal of Pharmaceutical Research

Venkata et al. World Journal of Pharmaceutical Research

SJIF Impact Factor 5.045

Volume 3, Issue 6, 701-717. Research Article ISSN 2277 – 7105

IN SILICO AND IN VITRO EXPLORATION OF ANTI-

INFLAMMATORY ACTIVITY OF ENTADA PURSAETHA BY

MOLECULAR DOCKING STUDIES

Narasimharao Bhogireddy1, Pardhasaradhi Mathi1, Nagavamsikrishna Ambatipudi2, Venkata Raman Bokka3* 1 Department of Biotechnology, K L University, Green fields, Vaddeswaram, Guntur Dist-522 502, AndhraPradesh, India.

2 Department of Biochemistry, Acharya Nagarjuna University, Guntur Dist-522 510, AndhraPradesh, India.

3 Department of Basic Sciences-Chemistry, Madanapalle institute of technology and science, Madanapalle, Chittoor Dist-517 325, AndhraPradesh, India.

ABSTRACT

Article Received on Back ground: Cyclooxygenase (COX), the key enzyme inside the 05 June 2014, conversion process involving arachidonic acid to prostaglandins which Revised on 30 June 2014, Accepted on 25 July 2014 was involved in the pain prone process in living vertebrates.

Cyclooxygenase isoforms are already identified and therefore are called COX-1 in addition to COX-2. Beneath a lot of situation, the *Correspondence for Author actual COX-1 enzyme is usually developed constitutively (i.e., gastric Dr. Venkata Raman Bokka mucosa) in contrast to COX-2 is usually inducible (i.e., sites of Department of Basic Sciences- inflammation). Drug treatments, similar to aspirin, which hinder Chemistry, Madanapalle cyclooxygenase task, are already obtainable in much more towards the institute of technology and general public for approximately 100 years. A single key aim with this science, Madanapalle, Chittoor Dist-517 325, AndhraPradesh, is usually to lay out a good anti-inflammatory molecule having a larger India.

restorative window. This article explores the medicinal values of the Entada pursaetha which is having strong anti-inflammatory and analgesic properties. Materials and methods: Compounds were identified by GC-MS analysis through conventional extraction procedures. Identified lead compound structures were sketched by using chemsketch and marvinsketch software’s. An In silico study has been carried out by using the software Schrödinger maestro. Results and Discussion: The compound oleoyl chloride was found to have great anti-inflammatory action [~ 80 % than

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standard: Diclofenac]. The interactions of the isolated compounds has been proposed based on the docking studies.

KEY WORDS: Cyclooxygenase, GC-MS, Schrödinger, anti-inflammation.

INTRODUCTION

Damage to the human body can inspire an arrangement of chemical changes in the harmed zone. In the first stage, provocative exudates develop because of upgraded vascular porousness and lead to edema. It is followed by diapedesis or extravasation causes the migration of leukocytes and phagocytes from blood vessels to vascular tissues. In the third phase, tissue degradation is followed by fibrosis [1]. Inflammation brings about the liberation of endogenous substances like histamine, serotonin, bradykinin, prostaglandins, and so forth. Prostaglandins are universal substances that show and regulate cell and tissue reactions included in inflammation. These substances even in little amounts can evoke torment reaction. The majority of the anti-inflammatory drugs now accessible are potential inhibitors of the cyclooxygenase (COX) pathways of arachidonic acid metabolism, which generates prostaglandins and leukotrienes. Prostaglandins are hyperanalgesic, pro-pain causing agents, intense vasodialators and help erythema, edema and agony. Subsequently for treating inflammatory pain relieving and anti-inflammatory drugs are in need. These proinflammatory agents contributing different types of rheumatic disorders such as rheumatic fever, rheumatoid arthritis, cancer and other diseases COX-1 & 2 play major role in proinflammatory activity is inhibited by both steroidal and non-steroidal anti-inflammatory drugs (NSAID’s) [2]. Two COX isoforms are known: constitutive COX-1, which is considered to be involved in intercellular signaling and homeostasis maintenance, and COXmostly induced during inflammation [3, 4].

Non steroidal antiinflammatory medications can directly penetrate and initiate concerned genes through binding specifically or indirectly to atomic receptors. Because of the absence of cascading mechanism through action guided operation to limit direct activity of these drugs lead to the development of many undesirable reactions and unrelated responses. In this way it is of incredible enthusiasm to screen disconnect and mimic its system.

When steroids are taken on multiple occasions, more serious side effects may occur. It is for these reasons that the dose and duration of systemic steroids should be minimized whenever possible. Some side effects can be decreased by taking systemic steroids every other day

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instead of daily, even if the total dose is the same. Many of the side effects are reversible if the steroids are stopped, while other side effects may be permanent.

People taking long-term systemic steroids should be closely checked for the symptoms, and should take preventives to forestall osteoporosis. These medications may incorporate supplemental calcium and vitamin D, along with medicines to prevent bone loss called bisphosphonates.





Non-steroidal anti-inflammatory drugs (NSAIDs) are constantly utilized with increasing frequency, because of their potent pain relieving impacts without having symptoms on the central neural system and furthermore because of the large number and varieties of these agents. The analgesic, anti-inflammatory properties and efficacy of NSAIDs in a wide variety of diseases have been already established. NSAIDs can restrain the inflammatory methodology and the structuring of fibrosis, due to their ability to suppress prostaglandin synthesis. It was exhibited in a rat model that breaking strength and collagen fixation at the injury site were less after use of NSAIDs than in the untreated wounds. Regardless of this, NSAIDs are generally utilized as perioperative analgesics.

In spite of the wide utilization of NSAIDS throughout the most recent century, their mechanism of activity was not completely acknowledged until 1971, when Vane published his seminal observations proposing that the capability of NSAIDS to suppress inflammation rests principally on their capacity to inhibit the cyclooxygenase (COX) enzyme. This would confine the generation of proinflammatory prostaglandins (PGs) at a site of injury. Given this, NSAIDS have been utilized by researchers throughout the previous 25 years to dissect the critical part that both the COX enzyme and the eicosanoids inferred from this pathway have in normal and abnormal physiologic states [5].

Entada pursaetha is an immense woody liana among legumes, which produces 90-150 cm long woody giant pods with 5-30 seeds. All parts of this species hold saponins and are accordingly utilized within the soap industry. This species is reported as tribal pulse [6]. Its semi ripe seeds are likewise utilized as a substitute for coffee. The plant material is used by the tribals as a wide range compound. This species might be utilized as an narcotic or as a tonic, etc, or used in curing liver troubles, allaying body pains, in warding off cold, curing eye diseases, arthritis, and paralysis [7]. This species is reported as endangered [8, 9, 10]. In recent times, there has been a deeply felt concern for the preservation and conservation of E. pursaetha germplasm [11] owing

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to an increasing realization of its significance and usefulness. The present piece of work was carried out to investigate the tribal’s knowledge and traditional uses of this species.

In silico research in medicine is thought to have the potential to speed the rate of discovery while reducing the requirement for costly lab work and clinical trials. One approach to accomplish this is by creating and screening drug candidates more effectively. This methodology differs from use of extensive high-throughput virtual screening (HTVS) labs to physically test many differing compounds a day frequently with an expected hit rate on the order of 1% or less with still less expected to be true leads after further testing. Recently docking ligands to receptors utilizing rational drug design is on the increase owing to few problems in the conventional methods of drug designing. Numerous pharmaceutical organizations use this rational drug designing in the advancement of new drugs as this computational method is less time consuming.

Molecular docking has helped important proceedings to drug discovery for long time. One main inspiration in drug discovery is the distinguishing of innovative small molecular scaffolds exhibiting high binding affinity and selectivity for the target together with a reasonable ADME (absorption, distribution, metabolism, and excretion) profile, lead and/or drug likeness. Such chemical entities are likely to have capacity to enter higher phases in the further drug development process. Molecular docking, compared to the fast and successful method of three-dimensional pharmacophore modeling is a rather complex and computerintensive approach to find new compounds by virtual screening. Docking techniques intend to recognize correct poses of ligands in the binding pocket of a protein and to predict the affinity between the ligand and the protein. At the end, docking describes a procedure by which two molecules fit together in three-dimensional space. The crystalline structure of ligands bound to their target receptor is one of the most important sources to gain information about the fundamental mechanism of interaction between the parts constituting the threedimensional complex structure.

MATERIALS AND METHODS

Extraction of Entada pursaetha phytochemical compounds Entada pursaetha seeds were collected from the reserve forest of Srisailam which is located at Western Ghats of Andhra Pradesh, India. The seeds of E. pursaetha were collected, dried and

powdered in a blender to get fine powder. The extract was prepared by using ethanol in 1:3

ratios by using soxhlet apparatus and the filtrate was concentrated under reduced pressure on

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rotavapor under vacuum (BÜCHI, R-3000, Switzerland) at 40oC temperature. The filtrate was used to measure the presence and absence of phytochemical compounds, anti-oxidant activity and for GC-MS studies.

Preliminary phytochemical studies Preliminary phytochemical screening was performed to identify phytochemicals present in the ethanol. Several sophisticated techniques like thin layer chromatography, ultra violet spectroscopy, infrared spectroscopy, nuclear magnetic resonance and HPLC have been used for identification of various groups of phytochemical compounds in plant extracts. In the present investigation, the phytochemical compounds were detected by simple color tests.

These extracts were subjected to preliminary phytochemical tests as described by Mathi PS et al [12], with slight modifications.

Gas Chromatography and Mass Spectroscopy (GC-MS) separation conditions The phytochemicals were analyzed by GC-MS Agilent 5975-C Series instrument employing the electron impact (EI) mode (ionizing potential -70eV) and a capillary column (DB-5ms Agilent) (length 30 m × Diameter 0.25 mm, film thickness 0.25μm) packed with 5% phenyl dimethyl silicone) and the ion source temperature was monitored at 200°C. Further, the GCMS settings were indicated as the initial column temperature was set at 70°C and kept hold for 2 min; the temperature was increased to 300°C at a rate of 10°C/min for 9 min, and placed in isothermal condition for 2 min. The column oven temperature was maintained at 70°C.

Helium was used as carrier gas with 99.9995 % purity. Samples were injected at a temperature of about 250°C with a split ratio of 10: 1 with a flow rate of helium 1.51 ml/min.

Mass scan (m/z): 45-1000, Total MS running time: 36 min. The constituents were identified after comparison with those available in the computer library (NIST ver. year 2005) attached to the instrument and reported.

Structure elucidation of Compounds in plant Structural elucidation of principal compounds was done by GC-MS analysis. Identified lead compounds structures were characterized by using chemdraw and chemsketch software’s.

The three-dimensional models of the plant E. pursaetha molecules under investigation were built by assembling fragments from the software package chemsketch and marvin sketch.

705 www.wjpr.net Vol 3, Issue 6, 2014.

Venkata et al. World Journal of Pharmaceutical Research In-vitro anti-inflammatory activity using bovine serum albumin (BSA) denaturation assay To evaluate the anti-inflammatory activity of phytochemical compounds present in E.

pursaetha, we used an anti-denaturation of BSA assay [13]. In brief the reaction mixture consists of 0.2 ml (10mg/ml) of bovine serum albumin (BSA), 2.8ml of phosphate buffered saline (PBS, pH -6.4), and 2 ml of varying concentrations of ethanol extracts of E. pursaetha 50, 100, 200,400, 800, 1200, 1600, 2000, and 5000 µg ml-1 to a final volume of 5 ml. PBS lacking BSA served as control. The samples were then incubated at 37±2 0C in an incubator for 15 min and then transferred to 700C water bath for 5 min. After cooling the sample, the turbidity was measured at 620 nm using spectrophotometer. The anti-inflammatory activity of phytochemical compounds was determined by plotting the percentage of inhibition with respect to control against treatment condition. In our studies we used Diclofenac as a positive anti-inflammatory drug. The percentage inhibition of protein denaturation was calculated by using the following formula. Percentage (%) of inhibition= 100 × ( v t/vc -1), Where Vt = Absorbance of test Sample, Vc = Absorbance of Control.



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