Publications by authors named "Amita Verma"

47 Publications

Amelioration of diethylnitrosamine (DEN) induced renal oxidative stress and inflammation by embedded silver nanoparticles in rodents.

Toxicol Rep 2021 23;8:636-645. Epub 2021 Mar 23.

Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences, Allahabad, Uttar Pradesh, 211007, India.

Introduction: Inflammation and oxidative stress are the main factors ascribed with interruption in the process of renal tissue impairment. The toxicity of different types of nitrosamine is well recognized in animals and humans. Administration of the smallest quantities of diethylnitrosamine or dimethylnitrosamine either orally or parenterally results into renal damage. Therapeutic effects of phytofabricated silver nanoparticles of aqueous extract has been scrutinised in current study for the assessment of renal cancer activity in animal model.

Methodology: Phytofabricated silver nanoparticles were characterized by using different instrumentation. Nephroprotective activity of silver nanoparticles at different doses was evaluated against N-diethylnitrosamine (200 mg/kg b.w., intraperitoneal) in animal model. Serum and renal homogenate were taken to evaluate the renal toxicity markers, oxidative stress, and antioxidant parameter, proinflammatory cytokines and histopathological study.

Result: Significant outcomes of silver nanoparticles in dose dependent manner down regulated the elevated serum marker, tumour marker enzymes and histopathology observation of repaired tissue assured the renal cancer activity in animals. In addition, profile of enzymatic and non-enzymatic antioxidant, proinflammatory cytokines and tumour promotion marker also favours the anticancer property of silver nanoparticles.

Conclusion: The data of current study reveals silver nanoparticles ameliorates renal oxidative stress and carcinogenesis which was induced by N-diethylnitrosamine and accredited to antioxidant and anticancer activities of phytofabricated nanoparticles by biological approach.
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http://dx.doi.org/10.1016/j.toxrep.2021.03.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039534PMC
March 2021

Design, synthesis, antibacterial evaluation, and computational studies of hybrid oxothiazolidin-1,2,4-triazole scaffolds.

Arch Pharm (Weinheim) 2021 Mar 3:e2000473. Epub 2021 Mar 3.

Bioorganic and Medicinal Chemistry Research Laboratory, Department of Pharmaceutical Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences, Prayagraj, Uttar Pradesh, India.

Bacterial infections are a serious threat to human health due to the development of resistance against the presently used antibiotics. The problem of growing and widespread antibiotic resistance is only getting worse with the shortage of new classes of antibiotics, creating a substantial unmet medical need in the treatment of serious bacterial infections. Therefore, in the present work, we report 18 novel hybrid thiazolidine-1,2,4-triazole derivatives as DNA gyrase inhibitors. The derivatives were synthesized by multistep organic synthesis and characterized by spectroscopic methods ( H and C nuclear magnetic resonance and mass spectroscopy). The derivatives were tested for DNA gyrase inhibition, and the result emphasized that the synthesized derivatives have a tendency to inhibit the function of DNA gyrase. Furthermore, the compounds were also tested for antibacterial activity against three Gram-positive (Bacillus subtilis [NCIM 2063], Bacillus cereus [NCIM 2156], Staphylococcus aureus [NCIM 2079]) and two Gram-negative (Escherichia coli [NCIM 2065], Proteus vulgaris [NCIM 2027]) bacteria. The derivatives showed a significant-to-moderate antibacterial activity with noticeable antibiofilm efficacy. Quantitative structure-activity relationship (QSAR), ADME (absorption, distribution, metabolism, elimination) calculation, molecular docking, radial distribution function, and 2D fingerprinting were also performed to elucidate fundamental structural fragments essential for their bioactivity. These studies suggest that the derivatives 10b and 10n have lead antibacterial properties with significant DNA gyrase inhibitory efficacy, and they can serve as a starting scaffold for the further development of new broad-spectrum antibacterial agents.
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http://dx.doi.org/10.1002/ardp.202000473DOI Listing
March 2021

Molecular dynamics analysis of phytochemicals from against COVID-19 main protease (M) and human angiotensin-converting enzyme 2 (ACE2).

Biocatal Agric Biotechnol 2021 Mar 27;32:101924. Epub 2021 Jan 27.

Bioorganic and Medicinal Chemistry Research Laboratory, Department of Pharmaceutical Sciences, Sam Higginbottom University of Agriculture, Technology and Sciences, Allahabad, 211007, India.

The outbreak of COVID-19 created unprecedented strain in the healthcare system. Various research revealed that COVID-19 main protease (M) and human angiotensin-converting enzyme 2 (ACE2) are responsible for viral replication and entry into the human body, respectively. Blocking the activity of these enzymes gives a potential therapeutic target for the COVID-19. The objective of the study was to explore phytochemicals from against SARS-CoV-2 through studies. In this study, 34 phytochemicals of were docked with M and ACE2 through AutoDock Tools-1.5.6 and their binding affinity was studied. Phytochemicals with higher affinity have been chosen for further molecular dynamics simulations to determine the stability with target protein. Molecular dynamics simulations were studied on GROMACS 5.1.4 version. Furthermore, 5-β-glucosyl-7-demethoxy-encecalin (5GDE) and 2-oxocadinan-3,6(11)-dien-12,7-olide (BODO) were found to be potential blockers with excellent binding affinity with Mpro and ACE2 than their native inhibitors remdesivir and hydroxychloroquine respectively. The drug likeness study and pharmacokinetics of the phytoconstituents present in A. adenophora provide an excellent support for the lead drug discovery against COVID-19.
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http://dx.doi.org/10.1016/j.bcab.2021.101924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839396PMC
March 2021

Hybrid Quinazoline 1,3,5-Triazines as Epidermal Growth Factor Receptor (EGFR) Inhibitors with Anticancer Activity: Design, Synthesis, and Computational Study.

ChemMedChem 2021 Mar 1;16(5):822-838. Epub 2020 Dec 1.

Laboratory of Computational Modelling of Drugs, South Ural State University, Chaikovskogo 20A, Chelyabinsk, 454008, Russia.

We report a series of hybrid quinazoline-1,3,5-triazine derivatives as EGFR inhibitors, which were synthesised and tested by using a variety of in vitro, in silico, and in vivo techniques. The derivatives were found to be active against different cancer cell lines and nontoxic against normal ones, with compounds 7 c, 7 d, 7 e, and 7 j being the most potent ones. The derivatives were also evaluated for angiogenesis inhibition potency in chicken eggs, and molecular docking and dynamics simulation studies were carried out to elucidate the fundamental substituent groups essential for their bioactivity. Additionally, a SAR study of the derivatives was performed for future compound optimisation. These studies suggested that the derivatives have a high affinity towards EGFR with favourable pharmacological properties. The most active compound (7 e) was further evaluated for in vivo anticancer activity against DMBA-induced tumours in female Sprague-Dawley rats as well as its effects on plasma antioxidant status, biotransformation enzymes, and lipid profile. The study suggested that 7 e has lead properties against breast cancer and can serve as a starting compound for further development of anti-EGFR compounds.
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http://dx.doi.org/10.1002/cmdc.202000646DOI Listing
March 2021

Madhuca longifolia embedded silver nanoparticles attenuates diethylnitrosamine (DEN) -induced renal cancer via regulating oxidative stress.

Curr Drug Deliv 2020 Sep 10. Epub 2020 Sep 10.

Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences, Allahabad -211007, Uttar Pradesh. India.

Objective: Madhuca longifolia has been used for the treatment of renal cancer. Therefore, the current study describes the protective effects of biofabricated silver nanoparticles (MLAgNPs) using Madhuca longifolia aqueous leaves extract against diethylnitrosamine (DEN) induced renal cell carcinoma (RCC) in rats.

Methods: Animals were categorized into five groups and treated with doses of silver nanoparticles for 16 weeks. Antineoplastic effect in renal cancer was dose dependent to control the macroscopical variations when compared to DEN induced group. Significant changes were observed in biochemical parameters and dose graded improvement in the level of antioxidants parameters were accountable for its protective nature.

Result: Silver nanoparticles in dose dependent manner was effective to modify the raised levels of pro-inflammatory cytokines and inflammatory mediators during renal cancer. Alteration in renal histopathology were also detected in the silver nanoparticles treated group, which show its safety concern. Biofabricated silver nanoparticles (MLAgNPs) using Madhuca longifolia can convey significant chemo-protective effect against renal cancer by suppressing the IL-6, TNF-α and IL-1β by nuclear factor-kappa B (NF-κB) pathway.

Conclusion: Our outcomes implicates that biofabricated MLAgNPs exhibited a chemoprotective potential in the prevention and intervention of RCC.
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http://dx.doi.org/10.2174/1567201817666200910154301DOI Listing
September 2020

1,2,4-Triazole-conjugated 1,3,4-thiadiazole hybrid scaffolds: A potent ameliorant of carrageenan-induced inflammation by lessening proinflammatory mediators.

Arch Pharm (Weinheim) 2020 Jan 7;353(1):e1900233. Epub 2019 Nov 7.

Laboratory of Computational Modeling of Drugs, Higher Medical and Biological School, South Ural State University, Chelyabinsk, Russia.

Inflammation acts as an alarming signal for the progression of various biological complications. Various reports in the literature have revealed that heterocycle-containing synthetic compounds have a restorative capability against acute and chronic inflammatory stages. In the current study, we synthesized a series of 1,2,4-triazole-conjugated 1,3,4-thiadiazole hybrid scaffolds and evaluated their impacts against carrageenan-induced paw edema and proinflammatory markers in Wistar rats. Further, 3D QSAR study (three-dimensional quantitative structure-activity relationships), ADMET (absorption, distribution, metabolism, and excretion) profiling, and docking studies were performed to determine the possible mechanism of the action of the derivatives. The study shows that the most active derivatives, 13f and 13g, have optimal logP, a higher anti-inflammatory activity score, and poor metabolism at various sites of cytochrome P450. The docking studies recommended that the synthesized compounds have a similar affinity as the ligands A307, 63X, and S58 to interact with tumor necrosis factor-α, COX-1, and COX-2. So, these molecules will definitely hold a promise for the future drug development initiative.
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http://dx.doi.org/10.1002/ardp.201900233DOI Listing
January 2020

Quinazoline based 1,3,5-triazine derivatives as cancer inhibitors by impeding the phosphorylated RET tyrosine kinase pathway: Design, synthesis, docking, and QSAR study.

Arch Pharm (Weinheim) 2019 Sep 5;352(9):e1900053. Epub 2019 Aug 5.

Laboratory of Computational Modeling of Drugs, Higher Medical and Biological School, South Ural State University, Chelyabinsk, Russia.

The present research focused on designing a quinazoline skeleton, framed via 1,3,5-triazine derivatives (QBT) through field mapping and alignment studies. The QBT derivatives were synthesized via time- and cost-effective protocol. The 3D-QSAR study, computational physicochemical properties, and ADME calculation of the derivatives were performed to establish the affinity towards the biological system. Molecular docking in the adenosine triphosphate binding site of the RET tyrosine kinase domain (PDB ID: 7IVU) was studied to elucidate vital structural residues necessary for bioactivity. The derivatives were evaluated for anticancer potency against TPC-1 cells (thyroid cancer), MCF-7 cells (breast cancer), and one normal cell line (human foreskin fibroblasts) via 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide assay followed by an in ovo CAM assay. The entire series of derivatives (8a-o) showed mild to significant anticancer potency against the selected cancer cell lines.
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http://dx.doi.org/10.1002/ardp.201900053DOI Listing
September 2019

Molecular Docking and Cognitive Impairment Attenuating Effect of Phenolic Compound Rich Fraction of Trianthema portulacastrum in Scopolamine Induced Alzheimer's Disease Like Condition.

Neurochem Res 2019 Jul 4;44(7):1665-1677. Epub 2019 Apr 4.

Bioorganic & Medicinal Chemistry Research Laboratory, Department of Pharmaceutical Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences (SHUATS), Allahabad, 211007, India.

Dementia is considered as the frequent cause of neurodegenerative mental disorder such as Alzheimer's disease (AD) amongst elderly people. Free radicals as well as cholinergic deficit neurons within nucleus basalis magnocellularis demonstrated to attribute with aggregation of β amyloid which further acts as an essential hallmark in AD. Various phenolic phytoconstituents exists in Trianthema portulastrum (TP) leaves have been reported as active against various neurological disorders. The current investigation was undertaken to evaluate the antiamnesic potential of butanol fraction of TP hydroethanolic extract (BFTP) by utilizing rodent models of elevated plus maze (EPM) and Hebbs William Maze (HWM) along with in vitro and in vivo antioxidant as well as acetylcholinesterase (AChE) inhibition studies. Molecular docking studies were also performed for evaluation of molecular interaction of existed phenolic compounds in BFTP. In vitro antioxidant study revealed concentration dependant strong ability of BFTP to inhibit free radicals. In vitro AChE inhibition study showed competitive type of inhibition kinetics. BFTP significantly reversed (p < 0.005 versus scopolamine) the damaging effect of scopolamine by reducing TL (Transfer Latency) and TRC (Time taken to recognize the reward chamber) in the EPM and HWM, respectively. BFTP also contributed towards increased (p < 0.005 versus scopolamine) enzymatic antioxidant as well as hippocampal acetylcholine (ACh) levels. Histological studies also supported the results as BFTP pretreated mice significantly reversed the scopolamine induced histological changes in hippocampal region. Docking studies confirmed chlorogenic acid has the most significant binding affinity towards AChE. This research finding concludes that BFTP could be a beneficial agent for management of cognition and behavioral disorders associated with AD.
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http://dx.doi.org/10.1007/s11064-019-02792-7DOI Listing
July 2019

Antioxidant and anti-inflammatory properties of Prosopis cineraria based phenolic rich ointment in wound healing.

Biomed Pharmacother 2018 Dec 9;108:1572-1583. Epub 2018 Oct 9.

Bioorganic & Medicinal Chemistry Research Laboratory, Department of Pharmaceutical Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences (SHUATS), Allahabad, India. Electronic address:

Oxidative stress and inflammation are the critical factors attributed with delay in wound repairing process. Traditionally Prosopis cineraria (L.) Druce (PC) is used for swift healing of cutaneous wounds. Since there is lack of scientific claim of this medicinal plant on wounds, the main focus of present study was to explore the wound healing effect of PC in rats by using excision and incision wound model as well as biochemical estimation along with inflammatory markers. Considering these facts, ethyl acetate, chloroform and butanol fractions of PC hydroethanolic extract (EFPC, CFPC, BFPC, respectively) investigated for determination of antioxidant activity by in vitro method and then strongest activity possessing fraction was further quantitatively analyzed by HPLC-DAD analysis. in vitro anti-inflammatory and enzyme (collagenase and elastase) inhibitory effect of BFPC were investigated to confirm underlying mechanism of action for wound healing process. BFPC was observed as most active fraction against free radicals among all and presence of protocatechuic acid, chlorogenic acid, ferulic acid and caffeic acid was confirmed by HPLC-DAD analysis. Results showed that BFPC has significant anti-inflammatory as well as anti-collagenase and anti-elastase activities. Application of BFPC ointment for 16 consecutive days on the dorsal wound area of rats confirmed the faster wound repairing process, higher hydroxyproline content, reduction in epithelialization period and inflammatory markers in blood as compared to control group. Histological analysis also endorsed the results by promoting collagen formation, re-epithelialization, angiogenesis and mainly the restoration of cutaneous appendages, i. e., hair follicles. Results of current study implicate that BFPC has potential to act as effective cutaneous wound healing agent.
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http://dx.doi.org/10.1016/j.biopha.2018.09.180DOI Listing
December 2018

Attenuation of diethylnitrosamine (DEN) - Induced hepatic cancer in experimental model of Wistar rats by Carissa carandas embedded silver nanoparticles.

Biomed Pharmacother 2018 Dec 21;108:757-765. Epub 2018 Sep 21.

Bio-Organic & Medicinal Chemistry Research Laboratory, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences, Allahabad, 211007, Uttar Pradesh, India. Electronic address:

Objective: Hepatic cancer is well known, and leading cancer around the world and remain asymptomatic diseases. Carissa carandas possess anti-proliferative, antioxidant, hepatoprotective property and used in hepatic cancer. The current study deals to evaluate the chemoprotective and therapeutic property of Carissa carandas embedded silver nanoparticles (CCAgNPs) against diethylnitrosamine (DEN) -induced hepatic cancer.

Material And Method: Wistar rats were divided into six groups and hepatic cancer was induced with diethylnitrosamine at the dose of 200 mg/kg BW. The animals were gastrogavaged with standard drug and CCAgNPs for 16 weeks. Serum biomarkers, haematological profile, antioxidants enzymes, inflammatory markers and membrane bound enzymes were assessed to find the anti-proliferative potential of silver nanoparticles. Histological evaluation and microscopic characterizations were also performed to authenticate the outcomes of the present work.

Results: Biosynthesized CCAgNPs significantly down-regulated the serum marker enzymes of hepatic and non-hepatic parameter, elevated the levels of enzymatic and non-enzymatic antioxidant profile, elevation in membrane bound enzymes and diminish the levels of inflammatory markers (IL-6, TNF-α, and IL-1β) via NF-κB pathway. Histopathological features also showed recovery of a hepatic architecture in cancer-induced rats in a dose-dependent manner.

Conclusion: Our consequences established that such plant mediated silver nanoparticles shown a defensive impact against DEN-induced hepatocarcinogenesis, and serves as a better option to ameliorate the clinical results against hepatocellular carcinoma.
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http://dx.doi.org/10.1016/j.biopha.2018.09.066DOI Listing
December 2018

Phytofabricated silver nanoparticles of Phyllanthus emblica attenuated diethylnitrosamine-induced hepatic cancer via knock-down oxidative stress and inflammation.

Inflammopharmacology 2019 Oct 15;27(5):1037-1054. Epub 2018 Sep 15.

Bio-organic and Medicinal Chemistry Research Laboratory, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom University of Agriculture, Technology and Sciences, Allahabad, Uttar Pradesh, 211007, India.

Oxidative stress and inflammation play a pivotal role in the expansion and progression of hepatic cancer. Nanoparticle-based drug delivery can quickly enhance the restorative capability of hepatic cancer. Silver nanoparticles synthesized from plant source are of great importance due to their small size, economic, non-hazardous and different biomedical applications. In the current study, we have evaluated the impacts of oxidative stress and proinflammatory markers of biosynthesized silver nanoparticles of Phyllanthus emblica (PE) leaves against diethylnitrosamine-induced hepatocellular carcinoma (HCC) in wistar rats till 16 weeks with its underlying mechanism. The physico-chemical properties of biosynthesized silver nanoparticles were determined by ultra-visible spectroscopy, Fourier transform infrared spectroscopy, field emission scanning electron microscope, energy dispersive X-ray analysis, transmission electron microscopy and X-ray diffraction studies. Biofabricated silver nanoparticles (PEAgNPs) significantly enhanced the process of recovery from hepatic cancer in animal models, which was ascertained by increased body weight, reduced hepatic knobs on the outer surface of liver, downregulated serum biochemical parameters (ALT: 134.66 ± 2.60; AST: 120.33 ± 3.18; ALP: 153.33 ± 4.25; AFP: 167.33 ± 3.38), decreased hepatic lipid peroxidation (20.22 ± 1.74), increased membrane-bound enzymes (Na/KATPase: 4.18 ± 0.20; CaATPase: 6.24 ± 0.12), increased antioxidants parameters (CAT: 64.89 ± 4.13; SOD: 6.01 ± 0.11; GPx: 8.55 ± 0.05), alteration in the level of proinflammatory cytokines (TNF-α: 90.15 ± 5.77; NF-κB: 173.29 ± 7.26; IL-6: 178.11 ± 3.16; IL-1β: 48.26 ± 1.89) and histopathological studies. Our outcomes implicate successfully biofabrication of silver nanoparticles and exhibited a chemoprotective potential in the prevention and intervention of hepatocellular carcinoma.
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http://dx.doi.org/10.1007/s10787-018-0525-6DOI Listing
October 2019

Amarogentin as Topical Anticancer and Anti-Infective Potential: Scope of Lipid Based Vesicular in its Effective Delivery.

Recent Pat Antiinfect Drug Discov 2019 ;14(1):7-15

Department of Pharmaceutical Science, Shalom Institute of Health and Allied Sciences, Faculty of Health Sciences, Sam Higginbottom University of Agriculture, Technology and Sciences, Allahabad 211007, Uttar Pradesh, India.

There is a need for the development of liposomes based nanomedicines formulation for better efficacy and safety of the available drugs in the market. Liposomes have various applications in the field of pharmaceutical and medical field for their drug target potential, diagnostic importance and imaging techniques. Natural plant based drugs and their derivatives have been used in the medicine, nutraceuticals, perfumery, cosmetic and beverages industry. More than half of the prescribed drugs in the worldwide are mainly derived from different natural sources. Development of plant derived product is an emerging field of food, pharmaceutical and health industries. Plants belonging to the Gentianaecae family are well known for their bitter taste and Swertia chirata is one of best plants among them. Various active phytochemical of Swertia chirata are bitter secoiridoids like gentiopicroside, amarogentin, swertiamarin, isovitexin and isogentisin. People use different species of Swertia in the form of decoction, infusion, paste and juice for the treatment of fever and enteric diseases. Swertia chirata possesses anticarcinogenic, antioxidative, hypoglycemic, antihepatotoxic, antimalarial, anti-inflammatory and antimicrobial activities. Amarogentin, a bitter secoiridoid glycoside present in Swertia chirata plant is an activator of human bitter taste receptor. Pharmacologically, amarogentin has antibacterial, antihepatitis, anticholinergic and chemopreventive activities, moreover, amarogentin has been proven for their anti-lieshmanial activity. Other studies also suggested that amarogentin acts on liver carcinogenesis, skin carcinogenesis and reduced tumour progression. In the present review, we have collected and compiled the data regarding biological sources, ethnomedicinal uses, phytochemistry, anticancer and anti-infective potential of amarogentin. For better understanding of various aspects of amarogentin, we have also discussed Swertia chirayita in a very concise manner. Further data related to various patents on amarogentin have also been discussed in this manuscript. However, we also admit that new advance biological research will also increase the medicinal and pharmacological value of amarogentin. Information regarding the chemistry of amarogentin, its biological sources, bioavailability as a pharmacological agent for the treatment and management of skin disorders and various forms of cancers will be beneficial to the scientists in the medicinal field.
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http://dx.doi.org/10.2174/1574891X13666180913154355DOI Listing
May 2020

One-pot green synthesis and structural characterisation of silver nanoparticles using aqueous leaves extract of : antioxidant, anticancer and antibacterial activities.

IET Nanobiotechnol 2018 Sep;12(6):748-756

Bio-organic & Medicinal Chemistry Research Laboratory, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences, Allahabad, UP 211007, India.

Facile green synthesis of silver nanoparticles (AgNPs) using an aqueous extract of () leaves was studied. Fabrication of AgNPs was confirmed by the UV-visible spectroscopy which gives absorption maxima at 420 nm. C. carandas leaves are the rich source of the bioactive molecules, acts as a reducing and stabilising agent in AgNPs, confirmed by Fourier transforms infrared spectroscopy. The field emission scanning electron microscope revealed the spherical shape of biosynthesised AgNPs. A distinctive peak of silver at 3 keV was determined by energy dispersive X-ray spectroscopy. X-ray diffraction showed the facecentred cubic structure of biosynthesised AgNPs and thermal stability was confirmed by the thermogravimetric analysis. Total flavonoid and total phenolic contents were evaluated in biosynthesised AgNPs. Biosynthesised AgNPs showed free radical scavenging activities against 2, 2-diphenyl-1-picrylhydrazyl test and ferric reducing antioxidant power assay. cytotoxicity against hepatic cell lines (HUH-7) and renal cell lines (HEK-293) were also assessed. Finally, biosynthesised AgNPs were scrutinised for their antibacterial activity against methicillin-resistant , , and . This study demonstrated the biofabrication of AgNPs by using leaves extract and a potential in vitro biological application as antioxidant, anticancer and antibacterial agents.
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http://dx.doi.org/10.1049/iet-nbt.2017.0261DOI Listing
September 2018

Amelioration of neurodegeneration and cognitive impairment by Lemon oil in experimental model of Stressed mice.

Biomed Pharmacother 2018 Oct 11;106:575-583. Epub 2018 Jul 11.

Natural Product Drug Discovery Laboratory, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences, Allahabad, Uttar Pradesh, 211007, India. Electronic address:

Citrous lemon (Rutaceae) an Indian folk medicine has been used for the treatment of various pathological diseases viz., diabetes, cardiovascular, inflammation, hepatobiliary dysfunction and neurodegenerative disorder. Can lemon oil altered the memory of unstressed and stressed mice, a basic question for which the present work was put on trial. The present investigation was intended to assess the impact of Lemon oil on memory of unstressed and Stressed Swiss young Albino mice. Lemon oil (50 and 100 mg/kg o.r.) and donepezil (10 mg/kg) were guided for three weeks to different groups of stressed and unstressed mice. The nootropic movement was assessed utilizing elevated plus maze and Hebbs Williams Maze. Cerebrum acetylcholinesterase (AChE), plasmacorticosterone, decreased glutathione, lipid per oxidation alongside superoxide dismutase and catalase was surveyed as marker for disease. Histopathology was performed for estimation of drug effects. Acute immobilized stress was induce, lemon oil (100 mg/kg) and donepezil together indicated memory enhancing movement both in stressed and unstressed mice. Lemon oil significantly (p < 0.001) altered and lowered brain AChE activity both in stressed and unstressed mice. Scopolamine induced amnesia was also significantly altered and reversed both in stressed and unstressed mice by lemon oil at a dose of 50 and 100 mg/kg. Lemon oil (50 and 100 mg/kg) was further able to control the corticosterone level in plasma for stressed mice. Lemon oil significantly (p < 0.001) elevated the level of catalase, superoxide dismutase and reduced glutathione levels both in stressed and unstressed animals with respect to controlled group along with TBARS both in stressed and unstressed compared with control group. Hence it can be concluded that memory enhancing activity might be related to reduction in AChE and TBARS activity and by elevated GSH, SOD and catalase through decrease in raised plasma corticosterone levels.
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http://dx.doi.org/10.1016/j.biopha.2018.06.160DOI Listing
October 2018

Comparative Evaluation of (L.) Druce and Its ZnO Nanoparticles on Scopolamine Induced Amnesia.

Front Pharmacol 2018 23;9:549. Epub 2018 May 23.

Bioorganic & Medicinal Chemistry Research Laboratory, Department of Pharmaceutical Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences (SHUATS), Allahabad, India.

Over recent years, utilization of green synthesized nanomaterials has been widely growing on human body because of its special properties. With the increasing acceptance of nanoparticle approach for various clinical treatments, the biosafety and toxicological effects on the vital organs such as central nervous system, have received more concern. Main focus of this study was to evaluate acute exposure of -butanol fraction of (L.) Druce hydroethanolic extract (BuPC) and green synthesized zinc oxide nanoparticles of BuPC (ZnOPC) on spatial cognition behavior, and to assess underlying mechanism by estimation of enzymatic antioxidative status along with acetylcholinesterase (AChE) activity in mice brain. Strongest antioxidant and AChE inhibitory activity exhibiting fraction, BuPC, was examined for inhibition kinetic study by Lineweaver-Burk and Dixon plots. BuPC was further used for fabrication ZnOPC and characterized by UV-visible spectroscopy, Fourier Transform Infrared (FTIR), Field Emission Scanning Electron Microscopy (FESEM), Energy Dispersive X ray (EDX), and Dynamic Light Scattering (DLS) analysis. Old male swiss albino mice were randomly divided into seven groups and treated for 21 days. Subsequently spatial memory was determined by two behavioral models [Elevated plus maze (EPM) and Hebbs William maze (HWM)] and supernatant of brain homogenate was analyzed for enzymatic antioxidant level and AChE inhibitory activity. Zinc content of blood plasma and brain was estimated. Results showed prolonged transfer latency (TL) and time taken to reach reward chamber (TRC) by scopolamine was not ameliorated by the ZnOPC group, whereas BuPC group showed significant reduction in scopolamine induced increase in TL and TRC compared to control and scopolamine treated groups. ZnOPC alleviated enzymatic antioxidant activity and AChE as compared to donepezil and BuPC treated groups. Study concludes that ZnOPC attenuated spatial learning and memory by increase in oxidative stress and decrease in AChE activity at both dose levels. Our results suggest that BuPC exhibited a strong neuroprotective effect on cognitive deficit mice and it may be employed as a strong substance for the treatment of dementia whereas the green synthesized ZnOPC was not proficient to reverse the memory impairment induced by scopolamine.
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http://dx.doi.org/10.3389/fphar.2018.00549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974226PMC
May 2018

Quinazoline clubbed 1,3,5-triazine derivatives as VEGFR2 kinase inhibitors: design, synthesis, docking, in vitro cytotoxicity and in ovo antiangiogenic activity.

Inflammopharmacology 2018 Dec 16;26(6):1441-1453. Epub 2018 Apr 16.

Bioorganic and Medicinal Chemistry Research Laboratory, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom University of Agriculture, Technology and Sciences, Allahabad, Uttar Pradesh, 211007, India.

A series of quinazoline clubbed 1,3,5-triazine derivatives (QCT) were synthesized and evaluated for their in vitro anticancer activity against HeLa (human cervical cancer), MCF-7 (human breast cancer cell), HL-60 (human promyelocytic leukemia cell), HepG2 (human Hepatocellular carcinoma cell), and one normal cell line HFF (human foreskin fibroblasts). In vitro assay result encouraged to further move towards in ovo anticancer evaluation using chick embryo. The series of QCT derivatives showed higher anticancer and antiangiogenic activity against HeLa and MCF-7 cell lines. In the series, synthetic molecule 8d, 8l, and 8m displayed significant activity. Further, these results substantiated by docking study on VGFR2. SAR study concluded that the potency of drugs depends on the nature of aliphatic substitution and the heterocyclic ring system.
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http://dx.doi.org/10.1007/s10787-018-0471-3DOI Listing
December 2018

Development of surface-engineered PLGA nanoparticulate-delivery system of Tet1-conjugated nattokinase enzyme for inhibition of Aβ plaques in Alzheimer's disease.

Int J Nanomedicine 2017 13;12:8749-8768. Epub 2017 Dec 13.

Microbial and Pharmaceutical Biotechnology Laboratory, Centre for Advanced Research in Pharmaceutical Science, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India.

According to the World Health Organization, globally there are around 18 million patients suffering from Alzheimer's disease (AD), and this number is expected to double by 2025. The pathophysiology of AD includes selective deposition of Aβ peptide in the mitochondria of cells, which inhibits uptake of glucose by neurons and key enzyme functions. Current drug treatments for AD are unable to rectify the underlying pathology of the disease; they only provide short-term symptomatic relief, so there is a need for the development of newer treatment regimes. The antiamyloid activity, antifibrinolytic activity, and antithrombotic activity of nattokinase holds potential for the treatment of AD. As nattokinase is a protein, its stability restricts its usage to a greater extent, but this limitation can be overcome by nanoencapsulation. In this work, we successfully synthesized polymeric nanoparticles of nattokinase and characterized its use by different techniques: transmission electron microscopy, scanning electron microscopy, DTS Nano, differential scanning calorimetry, Fourier-transform infrared spectroscopy, thioflavin T-binding assay, in vitro drug release, antifibrinolytic activity, and in vivo antiamyloid activity. As brain targeting of hydrophilic drugs is complicated due to the stringent nature of blood-brain barrier, in the current experimental study, we conjugated poly(lactic--glycolic acid) (PLGA)-encapsulated nattokinase with Tet1 peptide, which exhibits retrograde transportation properties because of its affinity to neurons. Our study suggests that PLGA-encapsulated nattokinase polymeric nanoparticles are able to downregulate amyloid aggregation and exhibit antifibrinolytic activity. The encapsulation of nattokinase in PLGA did not affect its enzyme activity, so the prepared nanoformulation containing nattokinase can be used as an effective drug treatment against AD.
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http://dx.doi.org/10.2147/IJN.S144545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732557PMC
May 2018

Attenuation of dermal wounds via downregulating oxidative stress and inflammatory markers by protocatechuic acid rich n-butanol fraction of Trianthema portulacastrum Linn. in wistar albino rats.

Biomed Pharmacother 2017 Dec 29;96:86-97. Epub 2017 Sep 29.

Bioorganic & Medicinal Chemistry Research Laboratory, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences (SHUATS), Allahabad 211007, India. Electronic address:

Oxidative stress and inflammation contribute as a key factor for retarding the process of dermal wound healing. Trianthema portulcastrum Linn. (TP) leaves reported to possess antioxidant, antifungal, anti-inflammatory and antibacterial properties, which could make TP a promising wound healing agent. The current study was aimed to estimate the antioxidant potential of the fractionated hydroethanolic extract of TP leaves and evaluate wound healing activity by excision and incision wound models along with the assessment of possible underlying mechanism. Ethyl acetate, chloroform and n-butanol fractions of the hydroethanolic extract of TP leaves were examined for in vitro antioxidant ability by DPPH method. Strongest antioxidant activity bearing n-butanol fraction (nBuTP) was further analyzed quantitatively by High Performance Liquid Chromatography coupled with Diode Array Detector (HPLC-DAD). Wound healing potential of nBUTP using excision and incision wound model was studied. Wistar albino rats were randomly divided into four groups, containing six animals in each group; group I served as control treated with simple ointment base, group II was standard group, treated with povidone-iodine ointment USP (5%), group III treated with nBuTP 5% w/w ointment, and group IV treated with nBuTP 10%w/w ointment. All the groups were topically applied their respective ointments, once daily, till the complete healing achieved. Wound healing was assessed by analyzing % wound closure, hydroxyproline content, epithelialization period, tensile strength, enzymatic antioxidative status and inflammatory markers. Total phenolic and flavonoid content of the extract was estimated to be 112.32±1.12 and 84.42±0.47mg/g, respectively. HPLC-DAD of nBuTP confirmed the presence of chlorogenic acid (20.74±0.03), protocatechuic acid (34.45±0.02mg/g), caffeic acid (4.31±0.03mg/g) and ferulic acid (1.43±0.01mg/g). 5% and 10%w/w nBuTP ointment significantly accelerated the wound healing process dose-dependently in both wound models, evidenced by the faster rate of wound contraction, epithelialization, increased hydroxyproline content, high tensile strength, increased antioxidant enzyme activity, decreased the level of inflammatory markers compared to the control group. Histopathological studies also revealed the dose-dependant amelioration of wound healing by re-epithelialization, collagenation and vascularization of wounded skin sample in nBuTP treated groups. These results implicate potential medicinal value of nBuTP to heal dermal wounds.
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http://dx.doi.org/10.1016/j.biopha.2017.09.125DOI Listing
December 2017

Fabrication, optimization, and characterization of umbelliferone β-D-galactopyranoside-loaded PLGA nanoparticles in treatment of hepatocellular carcinoma: in vitro and in vivo studies.

Int J Nanomedicine 2017 11;12:6747-6758. Epub 2017 Sep 11.

Bio-organic and Medicinal Chemistry Research Laboratory, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences, Allahabad, Uttar Pradesh, India.

Umbelliferone β-D-galactopyranoside (UFG), isolated from plants, exhibits promising inhibitory action on numerous diseases. The present research was initiated to develop a suitable delivery system for UFG with an intention to enhance its therapeutic efficacy against diethyl nitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in Wistar rats. UFG-loaded polymeric nanoparticles prepared by sonication were scrutinized for average size, drug loading capacity, zeta potential, and drug release potency in animals. HCC cell lines HuH-7 and Hep G2 were used for in vitro cytotoxic investigation. Several hepatic, nonhepatic, antioxidant, and anti-inflammatory biochemical parameters were estimated to establish the anticancer potential of UFG nanoformulation. Microscopical and histopathological investigations were also undertaken to substantiate the results of our work. Umbelliferone β-D-galactopyranoside-loaded poly(d,l-lactide--glycolide) nanoparticles (UFG-PLGA-NP) with particle size of 187.1 nm and polydispersity index 0.16 were uniform in nature with 82.5% release of the total amount of drug after 48 h. Our study successfully established the development and characterization of UFG-PLGA-NP with noticeable effect against both in vivo and in vitro models. The anticancer potential of UFG-PLGA-NP was brought about by the management of DEN-induced reactive oxygen species generation, mitochondrial dysfunction, proinflammatory cytokines alteration, and induction of apoptosis. Positive zeta potential on the surface of UFG-PLGA-NP would have possibly offered higher hepatic accumulation of UFG, particularly in the electron-dense mitochondria organelles, and this was the take-home message from this study. Our results demonstrated that such polymer-loaded delivery systems of UFG can be a better option and can be further explored to improve the clinical outcomes against hepatic cancer.
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http://dx.doi.org/10.2147/IJN.S136629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5600267PMC
January 2018

Preclinical renal chemo-protective potential of Prunus amygdalus Batsch seed coat via alteration of multiple molecular pathways.

Arch Physiol Biochem 2018 Feb 24;124(1):88-96. Epub 2017 Aug 24.

a Natural Product Drug Discovery Laboratory, Department of Pharmaceutical Sciences, Faculty of Health Sciences , Sam Higginbottom University of Agriculture, Technology & Sciences , Allahabad , India.

Prunus amygdalus Batsch (almond) is a classical nutritive traditional Indian medicine. Along with nutritive with anti-oxidant properties, it is, clinically, used in the treatment of various diseases with underlying anti-oxidant mechanism. This study is an effort to scrutinise the renal protective effect of P. amygdalus Batsch or green almond (GA) seed coat extract and its underlying mechanism in animal model of Ferric nitrilotriacetate (Fe-NTA) induced renal cell carcinoma (RCC). RCC was induced in Swiss Albino Wistar rats by intraperitoneal injection of Fe-NTA. The rats were then treated with ethanolic extract of GA (25, 50 and 100 mg/kg per oral) for 22 weeks. Efficacy of GA administration was evaluated by change in biochemical, renal, macroscopical and histopathological parameters and alterations. Additionally, interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and inflammatory mediator including prostaglandin E2 (PGE), nuclear factor-kappa B (NF-κB) were also observed to explore the possible mechanisms. The oral administration of GA significantly (p < .001) altered the Fe-NTA induced RCC in rats by inhibition of renal nodules, decolourisation of tissues, tumour promoter marker including thymidine [H] incorporation, ornithine decarboxylase, renal parameters and anti-oxidant parameters in serum. Additionally, GA treatment significantly (p < .001) down-regulated the IL-6, IL-1β, TNF-α, inflammatory mediators PGE and NF-κB in a dose-dependent manner. Histopathology observation supported the renal protective effect of GA by alteration in necrosis, size of Bowman capsules and inflammatory cells. Hence, it can be concluded that GA possesses observable chemo-protective action and effect on Fe-NTA induced RCC via dual inhibition mechanism one by inhibiting free radical generation and second by inhibiting inflammation.
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http://dx.doi.org/10.1080/13813455.2017.1364773DOI Listing
February 2018

Umbelliferon-α-d-glucopyranosyl-(2→1)-α-Dglucopyranoside ameliorates Diethylnitrosamine induced precancerous lesion development in liver via regulation of inflammation, hyperproliferation and antioxidant at pre-clinical stage.

Biomed Pharmacother 2017 Oct 10;94:834-842. Epub 2017 Aug 10.

Bio-organic & Medicinal Chemistry Research Laboratory, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences, Allahabad, 211007, Uttar Pradesh, India.

It is well documented that anomalous production of inflammatory proteins linked with most of the toxic expression and genesis of diverse chronic disease including cancer. Diethylnitrosamine (DEN) a well-known hepatotoxin and hepatocarcinogen, can induce oxidative stress and inflammatory reaction in it. Umbelliferone, secondary metabolites, is present in different plants and widely consumed by humans as medicine and food supplements. The aim of the current study was to scrutinize the chemoprotective potential of umbelliferon-α-d-glucopyranosyl-(2→1)-α-d-glucopyranoside (UFD) against DEN-induced hepatocellular carcinoma (HCC) in experimental rats. Single intraperitoneal injection of DEN (200mg/kg) was used for induction of HCC in rats and rats were grouped and orally treated with UFD (5, 10 and 20mg/kg) dose for 22 weeks. Parameters under investigation included hepatic, non-hepatic enzymes, oxidative stress, pro-inflammatory cytokines, COX-2 and NF-κB level along with histopathological examination in HCC rats. UFD exerted protective effect via reduction of oxidative stress, liver and non-liver parameters in a dose-dependent manner. It also reduced the expression of TNF-α, IL-1β, IL-6 and COX-2 in diseased rats. Our result revealed the essential repression of the inflammation cascade through modulation of nuclear factor-kappa B (NF-κB) signaling pathway.
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http://dx.doi.org/10.1016/j.biopha.2017.07.047DOI Listing
October 2017

Design and discovery of novel monastrol-1,3,5-triazines as potent anti-breast cancer agent via attenuating Epidermal Growth Factor Receptor tyrosine kinase.

Sci Rep 2017 07 19;7(1):5851. Epub 2017 Jul 19.

Drug Design & Discovery Laboratory, Department of Pharmaceutical Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences, Allahabad, Uttar Pradesh, 211007, India.

A novel series of hybrid analogues of monastrol-1,3,5-triazine were designed and developed via one-pot synthesis using Bi(NO) as a catalyst. Entire compounds were evaluated for their anticancer activity against HeLa (cervical cancer), MCF-7 (breast cancer), HL-60 (Human promyelocytic leukemia), HepG2 (Hepatocellular carcinoma) and MCF 12A (normal epithelial breast cell line) using MTT assay, where they showed highest inhibitory activity against MCF-7. The molecules were also found to be non-toxic to MCF 12A cells. These molecules showed considerable inhibitory percentage against Epidermal Growth Factor Receptor tyrosine kinase (EGFR-TK), in in-vitro assay. Molecular docking study was carried out on the analogs and reference compound (Erlotinib) into the ATP binding site of EGFR-TK domain (PDB ID:1M17) to elucidate vital structural residues necessary for bioactivity. The effect of most active compound 7l was also estimated in-vivo in DMBA induced mammary tumor in female Sprague-Dawley rats. The effect of anti-breast cancer effect of 7l was quantified on the basis of tumour incidence, body weight and tumor volume in DMBA-induced rats. Its effect on biochemical parameters, such as antioxidant status (SOD, CAT, GPX and GSH) and lipid peroxidation was also studied. The compound 7l showed inhibition of EGFR downstream signalling in the western blot analysis.
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http://dx.doi.org/10.1038/s41598-017-05934-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5517562PMC
July 2017

Triterpenoids principle of Wedelia calendulacea attenuated diethynitrosamine-induced hepatocellular carcinoma via down-regulating oxidative stress, inflammation and pathology via NF-kB pathway.

Inflammopharmacology 2018 Feb 12;26(1):133-146. Epub 2017 Jun 12.

Natural Product Drug Discovery Laboratory, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom Institute of Agriculture, Technology and Sciences (Deemed University), Allahabad, Uttar Pradesh, 211007, India.

The aerial part of Wedelia calendulacea have been used in Ayurveda, Unani, Tibetan, Siddha and other folk medicine systems to protect the liver and renal tissue. Liver is considered as primary metabolizing site of body, which is prone to damage by endogenous and exogenous toxicants. A reason for liver toxicity, and major causes of the hepatocellular carcinoma (HCC). 19-α-Hydroxyurs-12(13)-ene-28 oic acid-3-O-β-D-glucopyranoside (HEG), a triterpenoids found in the higher plants, has been known to possess protective effect against various toxicants. The aim of the current study was to scrutinize the hepatoprotective mechanism of HEG against DEN-induced oxidative stress, hyperproliferation, inflammation and apoptosis tissue injury in Wistar rats. Invitro cell lines study of HEG scrutinized against the Hep-G2 and HuH-7 cells. A single dose of DEN (200 mg/kg) and double dose of phenobarbitol were administered to induce the liver damage in rats; the dose treatment of HEG was terminated at the end of 22 weeks. Macroscopical study was performed for the confirmation of hepatic nodules. The serum and hepatic samples were collected for further biochemical and histopathological analysis. Hepatic; non-hepatic; Phase I and II antioxidant enzymes were also examined. Additionally, we also scrutinized the inflammatory cytokines viz., tumor necrosis factor-α, interlukin-6, interlukin-1β, and Nuclear factor kappa beta (NF-kB), respectively. Histopathological study was also performed for analyzing the changes during the HCC. HEG confirmed the reduction of growth and deoxyribonucleic acid synthesis of both cell lines. DEN successfully induced the HCC in all group, which was significantly (p < 0.001) altered by the HEG in a dose-dependent manner. The decreased level of pro-inflammatory cytokines and altered membrane-bound enzyme activity were also observed. HEG inhibits the phase I, II and antioxidant enzymes at the effective dose-dependent manner, which were considered as the precursor of the HCC. The alteration of phase I, II and antioxidant enzymes confirmed the inhibition of inflammatory reaction and oxidative stress, which directly or indirectly inhibited the NF-kB expression. Collectively, we can conclude that the HEG inhibited the growth of Hepatocellular carcinoma via attenuating the NF-kB pathway.
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http://dx.doi.org/10.1007/s10787-017-0350-3DOI Listing
February 2018

Therapeutic Applications of Liposomal Based Drug Delivery and Drug Targeting for Immune Linked Inflammatory Maladies: A Contemporary View Point.

Curr Drug Targets 2017 ;18(13):1558-1571

Natural Product Drug Discovery Laboratory, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Shalom Institute of Health and Allied Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences (SHUATS), Allahabad. India.

Immune-based inflammatory diseases involve immune related dysregulation in different sites of body, which includes rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, atherosclerosis, etc. Advancements in molecular research have facilitated investigation of their pathogenesis that is involved in inflammatory cytokines cells and several genes. The available drug therapy provides suboptimal therapeutic effects and higher adverse effects. Emergence of liposomal systems of the drugs meant for the above mentioned disease has gained broader importance due to their high treatment efficacy by means of optimal therapeutic drug delivery. Beyond the conventional liposomal formulations, evolution of second generation liposomes including stealth liposomes, cationic liposomes, immuno-liposomes, etc. has gained tremendous attention owing to their drug target potential, diagnostic importance and imaging in treatment of above mentioned immune mediated inflammatory disorders.
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http://dx.doi.org/10.2174/1389450118666170414113926DOI Listing
June 2018

Novel glycoside from Wedelia calendulacea inhibits diethyl nitrosamine-induced renal cancer via downregulating the COX-2 and PEG through nuclear factor-κB pathway.

Inflammopharmacology 2017 Feb 2;25(1):159-175. Epub 2017 Feb 2.

Natural Product Drug Discovery Laboratory, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom University of Agriculture, Technology and Sciences, Allahabad, Uttar Pradesh, 211007, India.

A new compound derivative of glycoside 19-α-hydroxy-ursolic acid glucoside (19-α-hydroxyurs-12(13)-ene-28-oic acid-3-O-β-D-glucopyranoside (HEG) was isolated from whole plant of Wedelia calendulacea (Compositae). The structure was elucidated and established by standard spectroscopy approaches. Diethylnitrosamine (DEN) (200 mg/kg) and ferric nitrilotriacetate (Fe-NTA) (9 mg/kg) were used for induction of renal cell carcinoma (RCC) in the rats. The rats were further divided into different groups and were treated with HEG doses for 22 weeks. Anti-cancer effect in RCC by HEG was dose dependent to restrict the macroscopical changes as compared to DEN + Fe-NTA-control animals. Significant alteration in biochemical parameters and dose-dependent alleviation in Phase I and Phase II antioxidant enzymes were responsible for its chemo-protective nature. HEG in dose-dependent manner was significant to alter the elevated levels of pro-inflammatory cytokines and inflammatory mediators during RCC. The histopathological changes were observed in the HEG pre-treated group, which was proof for its safety concern as far as its toxicity is concerned. The isolated compound HEG can impart momentous chemo-protection against experimental RCC by suppressing the cyclooxygenase (COX-2) and prostaglandin E2 (PGE) expression via nuclear factor-kappa B (NF-κB) pathway.
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http://dx.doi.org/10.1007/s10787-017-0310-yDOI Listing
February 2017

Melastoma malabathricum Linn attenuates complete freund's adjuvant-induced chronic inflammation in Wistar rats via inflammation response.

BMC Complement Altern Med 2016 Dec 7;16(1):510. Epub 2016 Dec 7.

Bio-organic & Medicinal Chemistry Research Laboratory, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom Institute of Agriculture, technology & Sciences (Deemed University), Allahabad, -211007, Uttar Pradesh, India.

Background: Natural products use for arthritis treatment is gaining importance in the medical worldt. Various studies reports medical importance of Melastoma malabathricum Linn. (MM) (Melastomataceae), also known as "putki," has a broad range of health benefits, for its free radical scavenging constituents. The current investigation scrutinizes the antioxidant and anti-inflammatory effect of MM against adjuvant-induced arthritis in experimental rats.

Methods: High-performance thin layer chromatography (HPTLC) was used for estimation of phytochemical-constituents present in the MM extract. Protective effect of MM extract in Wistar rats was estimated using CFA-induced model. The rats were divided into different groups with six rats in each group. All animals received oral administration of MM and indomethacin for 28 days. The body weight and arthritic score were scrutinized at regular intervals. At the end of experimental protocol, the rats were sacrificed, and blood samples were used for antioxidant, hematological parameters, pro-inflammatory and inflammatory mediator, respectively. Histopathological observation was used to evaluate the protective effect of MM extract.

Result & Discussion: Current study confirmed the preventive effect of MM against adjuvant-induced paw edema, paw redness and arthritic progression. MM significantly (P < 0.001) modulated the oxidative stress parameters as well as hematological parameter induced by CFA. The result also altered the distorted level of proinflammatory mediators and inflammatory mediator, which further reinforce the implication of MM in CFA induced arthritis. Histological analyses of joints of rats showed a reduction in the synovial hyperplasia and mononuclear infiltration in the MM treated group which provides evidence for the antiarthritic effect of MM.

Conclusion: From above parameters our study states that the MM is capable of restraining the alteration produced via adjuvant-induced arthritis in aminals. The repressing effect of MM could be attributed, at least in part, to antioxidant, hematological and anti-inflammatory effect. Figure Caption: Melastoma Malabathricum Linn Attenuates Complete Freund's Adjuvant-Induced Chronic Inflammation in Wistar rats by Inflammation Response.
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http://dx.doi.org/10.1186/s12906-016-1470-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5142378PMC
December 2016

Phytoconstituents as pharmacotherapeutics in rheumatoid arthritis: challenges and scope of nano/submicromedicine in its effective delivery.

J Pharm Pharmacol 2017 Jan 24;69(1):1-14. Epub 2016 Oct 24.

Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom Institute of Agriculture, Technology & Sciences (SHIATS), Naini, India.

Objectives: The present review explores the therapeutic application of herbals in rheumatoid arthritis (RA) therapy, and how nano/submicromedicine can be fit in the scope of its therapeutic delivery in RA has been addressed.

Key Findings: Incorporation of bioactive such as polyphenols, thymoquinone, resveratrol, hesperidin, curcumin, celastrol and gambogic acid in a dose-dependent manner showed quite high efficacy for the treatment of RA. It can be attributed to their targeting ability against various inflammatory mediators including nitric oxide (NO), cytokines, chemokines, adhesion molecules, NF-kβ, lipoxygenase (LOXs) and arachidonic acid (AA). Despite the presence of significant merits, the use of these bioactives has several demerits such as poor bioavailability as a function of low aqueous solubility and higher first-pass metabolism upon oral administration. The impact of nano/submicromedicine in the delivery of these bioactives against RA has gained wider attention owing to bioavailability enhancement, higher stability and better efficacy.

Conclusion: Phytoconstituents possess immense potential in RA pharmacotherapy, but the obstacles for their effective delivery can be overcome using nano/submicrocarrier-based drug delivery technologies, which maximize the efficacy of these herbal antirheumatic drugs without any systemic adverse effects.
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http://dx.doi.org/10.1111/jphp.12661DOI Listing
January 2017

Symmetrical peripheral gangrene: Unusual complication of dengue fever.

Adv Biomed Res 2016 26;5:154. Epub 2016 Sep 26.

Department of Geriatric ICU, King George's Medical University, Lucknow, Uttar Pradesh, India.

Symmetrical peripheral gangrene (SPG) is a rare clinical entity, infective, and noninfective both types of etiologies are responsible. The basic underlying pathology in SPG is being disseminated intravascular coagulation and carries a high mortality. Here, we describe a 52-year-old male with dengue fever, who developed bilateral symmetrical dry gangrene of both hand and feet. His dengue IgM antibody was positive. All the peripheral pulses of the affected limbs were palpable. Color Doppler study of upper and lower limb vessels showed normal flow. The patient was managed with intravenous fluids, low molecular weight heparin, and fresh frozen plasma. His general condition was improved within 72 h with no further progression of gangrene. Clinician should suspect the possibility of SPG while dealing a case of dengue fever presenting as peripheral gangrene.
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http://dx.doi.org/10.4103/2277-9175.188940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5046798PMC
September 2016

Chemomodulatory effect Melastoma Malabathricum Linn against chemically induced renal carcinogenesis rats via attenuation of inflammation, oxidative stress, and early markers of tumor expansion.

Inflammopharmacology 2016 Oct 14;24(5):233-251. Epub 2016 Sep 14.

Natural Product Drug Discovery Laboratory, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom Institute of Agriculture, Technology and Sciences (Deemed to be University), Allahabad, 211007, Uttar Pradesh, India.

Melastoma malabathricum Linn (MM) has high valued for its commercial significance. Indian market (northeast) has great demand for the plants, which extended, its use as a traditional home remedy due to its anti-inflammatory effects. In this study, we scrutinize the therapeutic and protective effect of MM against diethylnitrosamine (DEN) and ferric nitrilotriacetate (Fe-NTA)-induced renal carcinogenesis, renal hyperproliferation, and oxidative stress in rats. Liquid chromatography mass spectroscopy (LC-MS) was used for identification of phytoconstituents. Administration of DEN confirmed the initiation the renal carcinogenesis via enhancing the expansion of tumor incidence. Intraperitoneally, administration of Fe-NTA boost the antioxidant enzymes (phase I), viz., superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx) and phase II, viz., quinone reductase (QR) and glutathione-S-transferase (GST). It also increased the content of renal lipid peroxidation (LPO), hydrogen peroxidase (HO) with decrease content in glutathione content (GSH). It also increased the renal biochemical and non-biochemical parameter. It also confirmed the augment the level of thymidine [3H] incorporation into renal DNA, ornithine decarboxylase (ODC) activity and increased the generation of proinflammatory (TNF-α, IL-6 and IL-β) and inflammatory mediator (PGE). We also analyzed the macroscopic and histologic of renal tissue. In addition, the effect of phytoconstituent of MM extract was evaluated in silico and free radical scavenging activity against the DPPH and ABTS free radicals. LC-MS confirmed the presence of quercetin >gallic acid in MM extract. Renal carcinogenesis rats treated with MM (100, 250, and 500 mg/kg) confirmed the significantly (P < 0.001) protective effect via reduction the antioxidant (phase I and phase II) enzymes, biochemical parameter and restore the proinflammatory and inflammatory mediator at dose dependent manner. MM altered the ODC and thymidine activity in renal DNA. The chemoprotective effect of MM was confirmed via decreased the renal tumor incidence, which was confirmed by the macroscopic and histopathological observation. Consequently, our result suggests that MM is a potent chemoprotective agent and suppresses DEN+ Fe-NTA-induced renal carcinogenesis, inflammatory reaction, and oxidative stress injury in Wister rats.
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http://dx.doi.org/10.1007/s10787-016-0276-1DOI Listing
October 2016

Moxifloxacin loaded gelatin nanoparticles for ocular delivery: Formulation and in-vitro, in-vivo evaluation.

J Colloid Interface Sci 2016 Dec 10;483:132-138. Epub 2016 Aug 10.

Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, 259 Mack Ave, Wayne State University, Detroit, MI 48201, United States. Electronic address:

The current research focuses on developing positively charged gelatin nanoparticles loaded with moxifloxacin for its effective ocular delivery and controlled release in corneal eye layer. We selected type A gelatin because of its biodegradable and non-toxic nature as the polymer of choice for fabricating the nanoparticles by a modified two step desolvation technique. The produced nanoparticles were positively charged (+24±0.12mV) with a narrow particle size of 175±1.11nm as measured by dynamic light scattering (DLS). The in-vitro drug release from the nanoformulations exhibited a burst effect in the first hour followed by a controlled release of the drug for the subsequent 12h. The Korsmeyer-Peppas model showed better linearity and the formulations displayed non-Fickian drug release pattern. The optimized formulation was assessed for its utility as an anti-bacterial agent and its effectiveness was tested on the corneal eye surface of rabbits. The in-vivo tolerance tests revealed that the drug loaded nano-formulations was non-irritant to the ocular tissues indicating its safety. The in-vivo anti-bacterial activity of the nanosuspension was more effective against S. aureus than the commercially market product, MoxiGram®. Microbiological efficacy assessed against B. subtilus using cup-plate method suggested that our fabricated nanosuspension possess better anti-microbial activity as compared to the commercial agent, MoxiGram® revealing promising potentials for the currently developed gelatin based nanoformualtions.
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http://dx.doi.org/10.1016/j.jcis.2016.08.018DOI Listing
December 2016