European review for medical and pharmacological sciences, 2011
BACKGROUND AND OBJECTIVES "In all things of nature there is something of the marvelous"... more BACKGROUND AND OBJECTIVES "In all things of nature there is something of the marvelous". In the present study the anti-hyperglycemic and anti-oxidative potential of aqueous extract of Trigonella foenum graceum (TFG), a traditional medicinal herb was assessed in liver and WBC of alloxan induced diabetic rats. Free radicals can cause oxidative damage, which is balanced by the antioxidants. This has been implicated in aging, and diseases such as diabetes and other chronic conditions. MATERIAL AND METHODS TFG extract was administered orally [500 (LM) and 1000 mg/kg body weight (HM)] for six weeks. The effect of TFG on blood glucose were studied and the levels of lipid peroxidation [MDA (Malondialdehyde)] and antioxidant enzymes [SOD (Superoxide dismutase), GPx (Reduced Glutathione peroxidase)] were estimated and compared with standard drugs glibenclamide and insulin. RESULTS Treatment with TFG, insulin and glibenclamide resulted in significantly reduced blood glucose in LM (8....
Punica granatum L. , ( family Lythraceae) (Pomegranate) is a shrub which attains a height of abou... more Punica granatum L. , ( family Lythraceae) (Pomegranate) is a shrub which attains a height of about 5-8 meters (Middha et al., 2013a). It is believed to have originated in Iran and is cultivated majorly in Meditterranean region, Indian subcontinent, Middle East, Central Asia, Northern Africa and tropical Africa (Akbarpour et al., 2009). The word pomegranate is derived from Latin word ‘pomum’ means ‘apple’ and ‘granatum’ means ‘seeded’. It is variously named thoroughout the globe like grenadine or grantapfel in German, granatapple in Swedish, grenade in French, granda in Spanish and dadim/dadima in India. Pomegranate is used widely in domestic as well as industrial purposes such as cooking, preparation of juice, baking, making of wine and other alcoholic beverages. The fruit is round consisting a crown in the base rendered from the calyx. The texture of the peel is stringy and sturdy, with the colour ranging between yellow to red
Letter to the editor: POMEGRANATE PEEL ATTENUATES HYPERGLYCEMIC EFFECTS OF ALLOXAN-INDUCED DIABETIC RATS
Department of Biochemistry, Maharani Lakshmi Ammanni College For Women, Malleswaram, Bangalore 56... more Department of Biochemistry, Maharani Lakshmi Ammanni College For Women, Malleswaram, Bangalore 560012, India * Corresponding author : Sushil Kumar Middha; Kumaun University, Bhimtal Campus, Nainital, Uttrakhand-263136, India; E-mail: sushil.middha@gmail.com; Phone: (+91)(01594)2248042, Fax: (+91)(01594)2248042 Dear Editor, Diabetes is a major epidemic chronic metabolic ailment worldwide (WHO, 2008). It is characterized by insufficiency of insulin secretion and/or action, insulin resistance, and ab-normal metabolism of glucose, lipid and protein (WHO, 2008; Middha et al., 2011). Today, diabetes has become a pandemic affecting approximately 5 % of people in both developed and developing countries. Globally, diabetes causes high mortality and is the second most common cause of death after cancer (Middha et al., 2012). According to the diabetes atlas, in 2025 India, China and the United States would gain region-wise emphasis as top three coun-tries with people suffering from diabetes (A...
Drug Repurposing Approaches: Existing Leads for Novel Threats and Drug Targets
Current Protein & Peptide Science
Drug Repurposing (DR) is an alternative to the traditional drug discovery process. It is cost and... more Drug Repurposing (DR) is an alternative to the traditional drug discovery process. It is cost and time effective,with high returns and low-risk process that can tackle the increasing need for interventions for varied diseases and new outbreaks. Repurposing of old drugs for other diseases has gained wider attention, as there have been several old drugs approved by the FDA for new diseases. In the global emergency of COVID-19 pandemic, this is one of the strategies implemented in the repurposing of old anti-infective, anti-rheumatic and anti-thrombotic drugs. The goal of the current review is to elaborate the process of DR, its advantages, repurposed drugs for a plethora of disorders, and the evolution of related academic publications. Further, detailed are the computational approaches: literature mining and semantic inference, network-based drug repositioning, signature matching, retrospective clinical analysis, molecular docking and experimental phenotypic screening. We discuss the ...
Potential Cyclooxygenase (COX-2) enzyme inhibitors from Myrica nagi-from in-silico to in-vitro investigation
Pharmacognosy Magazine
Introduction: Myrica nagi Thunb. (family Myricaceae) are actinorhizal plants showing symbiotic in... more Introduction: Myrica nagi Thunb. (family Myricaceae) are actinorhizal plants showing symbiotic interaction with Frankia. Inhibition of cyclooxygenase-2 (COX-2) enzyme is known to be significant in preventing inflammation and in therapeutics. Objectives: Our principal focus was to identify COX-2 enzyme inhibitors, safer and natural anti-inflammatory compounds from M. nagi. Protein–ligand interaction has a significant role in structure-based drug design. Materials and Methods: Sixty-eight phytochemicals were therefore screened and evaluated for their binding energies with COX-2. These phytoconstituents were screened and analyzed for drug Likeliness along with Lipinski's rule of five. The X-ray crystallographic structure of the target COX-2 (protein data bank [PDB] ID: 4PH9), obtained from PDB, was docked with PubChem structures of phytochemicals using AutoDock 4.2 that uses Lamarckian genetic algorithm. Further, myricetin was subjected to in vitro anti-inflammatory assay using RAW-264.7 cell lines and inhibitory concentration (IC50) value was also determined. Results: The myricetin, myricitrin, and corchoionoside-C inhibited COX-2 with − 6.52, −4.94, and − 4.94 Kcal/mol binding energies, respectively, comparable to ibuprofen. Eventually, bioactivity score and absorption distribution metabolism excretion-toxicity properties showed considerable biological activities as G protein-coupled receptor, nuclear receptor, protease inhibitor, and enzyme inhibitors for myricetin, myricitrin, and corchoionoside-C phytochemicals. Molecular docking revealed hydrophobic interactions followed by four, nine, and four numbers of hydrogen bonds between myricetin, myricitrin, and corchoionoside-C, respectively, within the binding site of COX-2. Flavonol myricetin showed 112 μg/mL as IC50 value when it was subjected to in vitro cytotoxicity assay. These results clearly demonstrated that myricetin, myricitrin, and corchoionoside-C could act as highly potential COX-2 inhibitors. Therefore, in silico and in vitro studies revealed that of three best phytochemicals, myricetin could be promising candidate.
Amelioration of antioxidant potential, toxicity, and antihyperglycemic activity of Hippophae salicifolia D. Don leaf extracts in alloxan-induced diabetic rats
3 Biotech
Efficacy of several plant extracts in the clinical research for modulating oxidative stress corre... more Efficacy of several plant extracts in the clinical research for modulating oxidative stress correlated with diabetes mellitus (DM) is well documented. In the present study, we investigated the in vitro antioxidant activity, toxicity, and anti-diabetic activity of methanolic extract of Hippophae salicifolia leaves in normal and alloxan-induced diabetic wistar rats. H. salicifolia leaves were found to be rich in antioxidants. The acute toxicity test of methanolic extract of H. salicifolia leaves revealed that the median lethal dose (LD50) was found to be 3.92 g/kg body weight in mice. Administration of H. salicifolia leaves at 200 mg/kg and 400 mg/kg in alloxan-induced diabetic rats illustrated significant reduction (22% and 39%, respectively) in fasting blood glucose compared to diabetic control. Both the doses were found to be effective when compared to diabetic rats. The Hippophae-treated diabetic rats showed significant increase in the endogenous antioxidant enzymes, superoxide dismutase (50% and 74%, respectively), glutathione peroxidase (57% and 41%, respectively) and decrease in malondialdehyde (33% and 15%, respectively) levels. These results suggested that the methanolic leaf extract of H. salicifolia enhanced the antioxidant defence against reactive oxygen species produced under hyperglycaemic conditions.
Latest evaluation and validation of cancer drugs and their targets has demonstrated the lack and ... more Latest evaluation and validation of cancer drugs and their targets has demonstrated the lack and inadequate development of new and better drugs, based on available protocols. Even though the specificity of drug targets is a great challenge in the pharmaco-proteomics field of cancer biology, for eradicating such hurdles and paving the way for the drugs of future, a novel step has been envisaged here to study the relation between drug target network and the corresponding drug network using the advanced concepts of proteomics and network biology. The literature mining was done for the collection of receptors and the ligands. About 1000 natural compounds were collected and out of those 300 molecules showed anti-cancer activity against colon cancer. Ligand Vs multiple receptor docking was done using the software Quantum 3.3.0; the results were further used for the designing of a well connected Protein Ligand Interaction (PLI) network of colon cancer. The obtained network is then extrapol...
Plants in traditional medicine with special reference to Cyperus rotundus L.: a review
3 Biotech
The nutgrass, Cyperus rotundus L. (Family: Cyperaceae), is a colonial, perennial herb considered ... more The nutgrass, Cyperus rotundus L. (Family: Cyperaceae), is a colonial, perennial herb considered to have originated in India 2000 years ago and widely used in Ayurveda to treat several ailments. In addition to its prehistoric uses, it is used in several systems of medicine for treating variety of diseases. The synergistic actions of the Cyperus’ compounds have added advantage over that of a single constituent. In the past decade, numerous studies proved analgesic, anti-allergic, anti-arthritic, anti-candida, anti-cariogenic, anti-convulsant, anti-diarrheal, anti-emetic, anti-helminthic, anti-histamine, anti-hyperglycemic, anti-hypertensive, anti-inflammatory, anti-malarial, anti-obesity, antioxidant, anti-platelet, anti-pyretic, anti-ulcer, anti-viral, cardioprotective, cytoprotective, cytotoxic, gastroprotective, hepatoprotective, neuroprotective, ovicidal, and larvicidal, wound healing and inhibition of brain Na+ K+ ATPase activities of C. rotundus and its chemical constituents. However, the exact the mechanism of action is not very clear and requires further evaluation. These properties strongly suggest an extensive use of C. rotundus for clinical applications. In this review, we attempted to provide information about the pharmacological effects of Cyperus and its proposed mechanisms of actions.
Anti-Inflammatory, Radical Scavenging Mechanism of New 4-Aryl-[1,3]-thiazol-2-yl-2-quinoline Carbohydrazides and Quinolinyl[1,3]-thiazolo[3,2-b ][1,2,4]triazoles
{"__content__"=>" Antioxidant Potentials of L. Rhizome Extracts and Their Phytochemical Analysis.", "i"=>[{"__content__"=>"In vitro"}, {"__content__"=>"Cyperus rotundus"}]}
Pharmacognosy magazine
L. (family Cyperaceae), native to India, is a multivalent medicinal plant widely used in conventi... more L. (family Cyperaceae), native to India, is a multivalent medicinal plant widely used in conventional medicine. The research reports on bioactive components from L. are scanty. The objective of the study was to optimize the best solvent system and bioprospect the possible phytochemicals in L. rhizome (CRR). The phytochemicals were extracted from the rhizomes of L. by successive Soxhlet technique with solvents of increasing polarity. The resultant extracts were analyzed for their total flavonoid content (TFC), total phenolic content (TPC), total proanthocyanidin content (TPAC), antioxidant potential, and inhibition of lipid peroxidation. The 70% acetone extract of CRR was analyzed using gas chromatography-mass spectrometry (GC-MS) for probable phytochemicals. The TPC, TFC, and TPAC estimates ranged from 0.036 ± 0.002 to 118.924 ± 5.946 μg/mg extract, 7.196 ± 0.359 to 200.654 ± 10.032 μg/mg extract, and 13.115 ± 0.656 to 45.901 ± 2.295 μg/mg extract, respectively. The quantities of TP...
Recent updates on Computer-aided drug discovery: Time for a Paradigm Shift
Current topics in medicinal chemistry, 2018
Computer aided drug designing (CADD) has gained a wide popularity among biologists and chemists a... more Computer aided drug designing (CADD) has gained a wide popularity among biologists and chemists as a part of interdisciplinary drug discovery approach. It plays a vital role in the discovery, design and analysis of drugs in pharmaceutical industry. It is extensively used to reduce cost, time and speed up the early stage development of biologically new active molecules. In the current review we presented a brief review of CADD, merits and demerits, DNA, protein and enzyme as targets, types of CADD: Structure based drug designing (SBDD), ligand based drug designing (LBDD), Pharmacophore based drug designing (PBDD) and fragment based drug designing (FBDD), theory behind the types of CADD and their applications. The review also focuses on the in-silico pharmokinetic, pharmacodynamic and toxicity filters or predictions that play a major role in identifying the drug like molecules. Currently in pharmaceutical sciences computational tools and software are exhibiting imperative role in the ...
Molecular Simulation-based Combinatorial Modeling and Antioxidant Activities of Zingiberaceae Family Rhizomes
Pharmacognosy magazine, 2017
The main aim of this scientific report was to investigate a series of phytochemicals in silico an... more The main aim of this scientific report was to investigate a series of phytochemicals in silico and the pharmacology of four plants found at higher altitude in the ginger family, Zingiberaceae (incl. Costaceae) from North-East India, particularly Sikkim. First, the goal was to determine the biological activities of the four herbs (used under Zingiberaceae family) using antioxidant assays to identify the best species. Second, previously reported compounds in litero were subsequently screened for their anticancerous activities using in silico methods. Using the methanolic extracts of herbs, quantitative detection of phytochemicals such as total phenols and total flavonoids was detected, and the free radical scavenging activity was also studied using 2,2-diphenyl-1-picryl-hydrazyl (DPPH) assay. Docking process was studied, using Discovery Studio version 3.5, to identify suitable molecules at the protein-binding sites through annealing and genetic simulation algorithms. Grids centered on...
Bamboo shoots as a nutritive boon for Northeast India: an overview
3 Biotech
With about 136 species, India is one among the richest countries in bamboo resources that help ma... more With about 136 species, India is one among the richest countries in bamboo resources that help mankind in more than 1500 diverse ways. Although the utilization of juvenile shoots of bamboo in tribal diet of Northeast India is a very old observable fact, its numerous health benefits and potentiality remains uncharted. Apart from being delicious, the bamboo shoots are also rich in minerals and nutrient components such as carbohydrates, proteins, fiber and are low in fat and sugar which could be helpful in mitigating the problem of malnutrition. Few studies also revealed the health benefits of bamboo shoots for the treatment of cancer and cardiovascular diseases, weight loss and to improve digestion. Over and above the nutritional values of different species of bamboo shoots, the increasing inclinations towards health awareness among the consumers have emphasized its utilization in modern diet as a health food for boosting the nutritional security. Thus, in the present review, the nutraceutical potentiality of bamboo shoots is explored alongside its various qualities.
This study investigated and compared the phytochemical constituents and antioxidant property of P... more This study investigated and compared the phytochemical constituents and antioxidant property of Phyllanthus amarus, Vernonia amygdalina, Carica papaya and Jatropha curcus which are commonly used in traditional medicine. This was achieved by evaluating the quantitative and qualitative presence of the phytochemicals and also determining the free radical scavenging potentials of the plant leaf extracts. The results of this study revealed that the leaf extracts of the test plants contain some proportions of important phytochemicals which includes alkaloids, tannins, saponins, flavonoids, phenols, steroids, glycosides, cardiac glycoside. In furtherance, it showed that the selected plants vary significantly in their percentage ferric reducing antioxidant potentials (FRAP) expressed in gallic acid equivalents(GAE) ranging from 63.624 ± 0.14 to 165.076 ± 0.24 mg/100g and all the sample extracts exhibited moderate to significant inhibition of 1,1 diphenyl-2-picryl-hydrazyl (DPPH) activity expressed in trolox equivalent (TAEC) ranging from 1.306±0.20 to 38.943± 0.11/100g. Considering all the parameters assayed, antioxidants capacities were significant in the sequence of P.amarus, V. amygdalina , J. curcas and C. Papaya. This current study shows that the test plants contain useful phytochemicals which makes them employable in traditional medical practices. However more work needs to be done to determine which of these phyto-constituents exert the greatest potency in therapeutic and antioxidant activities.
Bambusa balcooa (Poaceae) is native to India and has been used traditionally by the tribes of Nor... more Bambusa balcooa (Poaceae) is native to India and has been used traditionally by the tribes of Northeast India to treat diabetes. The present investigation was aimed to evaluate the toxicity, anti-diabetic activity along with in vitro antioxidant activity of the leaf of B. balcooa in alloxan-induced diabetic rats and also identify active compounds by using HPLC. The acute toxicity test of aqueous extract of B. balcooa leaf revealed that the median lethal dose (LD 50) of B. balcooa aqueous extract (BAQE) was 5.18 g/kg body weight in mice. Administration of BAQE at 100 and 200 mg/kg in alloxan-induced diabetic rats showed significant reduction in fasting blood glucose and glycated hemoglobin while plasma insulin level was elevated compared to diabetic control. Both the doses were effective when compared to diabetic glibenclamide rats. The BAQE treated diabetic rats showed significant increase in the endogenous antioxidant enzymes superoxide dismutase, glutathione peroxidase and decrease in malondialdehyde levels. HPLC analysis of BAQE showed the presence of rutin, gallic acid and b sitosterol. Thus, it can be inferred from this study that BAQE possess antidiabetic and in vivo antioxidant activity. The overall activity might be possibly due to the presence of potential antioxidants.
We have investigated the anti-oxidative and glucose-lowering effects of 70% methanolic extract of... more We have investigated the anti-oxidative and glucose-lowering effects of 70% methanolic extract of H. heteroclita fruit pulp (MHE). Anti-oxidative property of MHE was assessed by free radical scavenging assays and compound level screening by LC-MS profiling. In silico analysis and in-vivo preclinical validation were also performed using molecular docking and alloxan-induced diabetic model, respectively. MHE showed high anti-oxidant activity in DPPH radical scavenging assay with an IC 50 of 0.37 μg/mL. The LC-MS profile of MHE substantiated the presence of p-hydroxy acids including benzoic,
A study of comparative modelling, simulation and molecular dynamics of CXCR3 receptor with lipid bilayer
Journal of biomolecular structure & dynamics, Jan 14, 2017
The G-coupled receptors seen on the cell surface are composites with a lipid bilayer. The chemoki... more The G-coupled receptors seen on the cell surface are composites with a lipid bilayer. The chemokines are kind of G-coupled receptor which majorly involved in the activation and downstream signalling of the cell. In general, many G-coupled receptors are lack of its 3D structure that become a hurdle in the drug designing process. In this study, comparative modelling of the CXCR3 receptor was carried out, structure evaluation was done using various tools and software's. Additionally, molecular dynamics and docking were performed to prove the structural quality and architecture. Interestingly, the studies like toggle switch mechanism, lipid dynamics, virtual screening were carried out to find the potent antagonist for the CXCR3 receptor. During virtual screening 14303 similar molecules were retrieved among them only four compounds have an ability to interact with a crucial amino acid residue of an antagonist. Hence, these screened compounds can serve as a drug candidate for a CXCR3 ...
An in vitro protocol has been established for clonal propagation of Nothapodytes nimmoniana which... more An in vitro protocol has been established for clonal propagation of Nothapodytes nimmoniana which is an important source of Camptothecin (CPT). Elite source was identified based on the chemical potency to accumulate the optimum level of CPT. Different types and concentrations of plant growth regulators were used to study their effect on inducing multiple shoots from the explants regenerated from embryos of N. nimmoniana. Of these, a combination of N6-benzyladenine (0.2 mg L-1) and Indole-3-butyric acid (IBA) (0.1 mg L-1) proved optimum for differentiating multiple shoots in 90.6 % of the cultures with an average of 10.24 shoots per explant obtained within 8 weeks of inoculation. Nearly, 92 % of the excised in vitro shoots rooted on half strength Murashige and Skoog (MS) medium containing 0.05 % activated charcoal, supplemented with 1-naphthaleneacetic acid and IBA at 0.1 mg L-1 each. The micropropagated plants were evaluated for their genetic fidelity by employing inter simple sequence repeats (ISSR) markers. Ten individuals, randomly chosen from a population of 145 regenerants, were compared with the donor plant. The regenerated plants were also evaluated for their chemical potency using highperformance liquid chromatography (HPLC) analysis of CPT content. The true-to-type nature of the micropropagated plants was confirmed based on their monomorphic banding profiles with that of the mother plants using ISSR markers. Besides, HPLC evaluation of the CPT content confirmed the existence of chemical uniformity among the regenerated plants and the elite mother plant. Keywords Nothapodytes nimmoniana Á Cytokinin Á Genetic fidelity Á Micropropagation Á ISSR Á Camptothecin Abbreviations BA N6-Benzyladenine KN 6-Furfuryl aminopurine NAA 1-Naphthaleneacetic acid IBA Indole-3-butyric acid CPT Camptothecin ISSR Inter simple sequence repeats HPLC High-performance liquid chromatography Electronic supplementary material The online version of this article (
Plants, a therapeutic source are a prehistoric knowledge 1. Past investigations have indicated th... more Plants, a therapeutic source are a prehistoric knowledge 1. Past investigations have indicated that the consumption of natural antioxidants is related with reduced risks of numerous ailments like diabetes 2. Freshly, there is an increasing attention in finding natural antioxidants to substitute manmade ones 3,4. India has a vast biodiversity due to its topographical and climatic circumstances. In India about 139 species of bamboos are encountered belonging to 36 genera 5. North east region holds two third of the countries bamboo reserve with 58 species included in 10 genera. Ethano-pharmacological survey studies in this region have revealed a large number of plant species are traditionally used in North east and surround regions for many ailments 6. There are a few or almost none studies on these plants that have been recorded. Also, these plants were recommended by the natural healers for treatments of diabetic symptoms and its complications 1,7,8. Glucose, Glucose oxidase, Potassium mono hydrogen phosphate, Hydrochloric acid, Potassium dihydrogen phosphate, and EDTA were purchased from Merck and Sigma. All chemicals and reagents used were of the analytical grade and highest commercially available purity. 2.2 Plant collection Leaves of Dendrocalamus hamiltonii (DH), Dendrocalamus sikkimensis (DS), Bambusa balcooa (BB), Bambusa pallida (BP), Bambusa vulgaris (BV) were collected from the Sukna forest after taxonomic identification and authentication. The live accessions are deposited at the Bambusetum in Kurseong Research Range, Sukna, Siliguri 2.3 Extract Preparation After shade dried (Temp<40°C.), plant material was grounded into a moderately coarse powder was boiled with sixteen parts of methanol for a period of 15 minutes 10 and filtered was evaporated under reduced pressure and dried .The yield of the extract was 1.2-2.06% (w/w).
Uploads
Papers by Sushil Middha