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Blastocystis sp., Parasite Associated with Gastrointestinal Disorders: An Overview of its Pathogenesis, Immune Modulation and Therapeutic Strategies

Kumarasamy V, Anbazhagan D, Subramaniyan V, Vellasamy S

Curr Pharm Des, 2018;24(27):3172-3175.
PMID: 30084327 DOI: 10.2174/1381612824666180807101536

Blastocystis sp. is a unicellular parasitic microorganism commonly found in the gastrointestinal tracts of humans and animals. It causes symptomatic or asymptomatic infection and its route of transmission is via fecal-oral. High prevalence of Blastocystis infection in developing countries is usually due to poor hygiene practices, exposure to animals infected with the parasite and intake of contaminated water or food. Blastocystis infected individuals often suffer from diarrhea, abdominal pain, nausea, and stomach bloating. Even though pathogenicity of Blastocystis is unclear, it is commonly associated with irritable bowel syndrome. In this review, we have analysed the evidence that shows the association between this microorganism and gastrointestinal disorders. There have been a number of studies which showed that the pathogenicity of Blastocystis is related to its different STs. The pathogenicity is speculated to be due to cysteine proteases formation which stimulates mucosal cells to release interleukin-8 which has been associated with extreme dehydration and gut inflammation. In vitro studies on human colonic epithelial cells revealed that incubation of Blastocystis modulated the host immune response by stimulating the formation of pro-inflammatory cytokines and granulocyte macrophage colonystimulating factor. Metronidazole is found to be the first-line drug of choice. Another treatment option is the combination therapy with trimethoprim/sulfamethoxazole.
Potential action of Rumex vesicarius (L.) against potassium dichromate and gentamicin induced nephrotoxicity in experimental rats

Subramaniyan V, Shaik S, Bag A, Manavalan G, Chandiran S

Pak J Pharm Sci, 2018 Mar;31(2):509-516.
PMID: 29618442

To determine the ameliorative potential of the active fraction from different extracts of Rumex vesicarius against potassium dichromate and gentamicin induced nephrotoxicity in experimental rats and its possible mechanism of action. Both sex wistar rats were divided into 6 groups (n=6/group) were fed with a control, potassium dichromate and gentamicin supplemented with different extracts at the doses of 200 and 400mg/kg respectively. Oral administration of EERV offered a significant (p<0.01 and p<0.001) dose dependent protection against PD and GN induced nephrotoxicity. Potassium dichromate and gentamicin nephrotoxicity assessed in terms of body weight, kidney weight, creatinine, urea, uric acid, BUN, albumin and total protein. Thus the present study revealed that EERV phytochemical constituents play an important role in protection against kidney damage.
Fulltext Alcohol-induced liver injury in signalling pathways and curcumin's therapeutic potential

Subramaniyan V, Lubau NSA, Mukerjee N, Kumarasamy V

Toxicol Rep, 2023 Dec;11:355-367.
PMID: 37868808 DOI: 10.1016/j.toxrep.2023.10.005

Confronting the profound public health concern of alcohol-induced liver damage calls for inventive therapeutic measures. The social, economic, and clinical ramifications are extensive and demand a comprehensive understanding. This thorough examination uncovers the complex relationship between alcohol intake and liver damage, with a special emphasis on the pivotal roles of the Toll-like receptor 4 (TLR4)/NF-κB p65 and CYP2E1/ROS/Nrf2 signalling networks. Different alcohol consumption patterns, determined by a myriad of factors, have significant implications for liver health, leading to a spectrum of adverse effects. The TLR4/NF-κB p65 pathway, a principal regulator of inflammation and immune responses, significantly contributes to various disease states when its balance is disrupted. Notably, the TLR4/MD-2-TNF-α pathway has been linked to non-alcohol related liver disease, while NF-κB activation is associated with alcohol-induced liver disease (ALD). The p65 subunit of NF-κB, primarily responsible for the release of inflammatory cytokines, hastens the progression of ALD. Breakthrough insights suggest that curcumin, a robust antioxidant and anti-inflammatory compound sourced from turmeric, effectively disrupts the TLR4/NF-κB p65 pathway. This heralds a new approach to managing alcohol-induced liver damage. Initial clinical trials support curcumin's therapeutic potential, highlighting its ability to substantially reduce liver enzyme levels. The narrative surrounding alcohol-related liver injury is gradually becoming more intricate, intertwining complex signalling networks such as TLR4/NF-κB p65 and CYP2E1/ROS/Nrf2. The protective role of curcumin against alcohol-related liver damage marks the dawn of new treatment possibilities. However, the full realisation of this promising therapeutic potential necessitates rigorous future research to definitively understand these complex mechanisms and establish curcumin's effectiveness and safety in managing alcohol-related liver disorders.
Exosome-mediated PROTACs delivery to target viral infections

Mukerjee N, Maitra S, Ghosh A, Subramaniyan V, Sharma R

Drug Dev Res, 2023 Sep;84(6):1031-1036.
PMID: 37391892 DOI: 10.1002/ddr.22091

Exosome-based targeted delivery of Proteolysis-Targeting Chimeras (PROTACs) is an innovative approach that provides a promising solution for addressing the complex issues of viral diseases. This strategy significantly mitigates the off-target effects associated with traditional therapeutics by facilitating targeted delivery of PROTACs, which in turn enhances the overall therapeutic outcomes. Challenges like poor pharmacokinetics and unintended side effects, commonly observed with conventional PROTACs usage, are effectively managed with this approach. Emerging evidence affirms the potential of this delivery mechanism in curbing viral replication. However, it is crucial to undertake more comprehensive investigations for optimizing exosome-based delivery systems and conducting stringent safety and efficacy assessments within preclinical and clinical settings. The advancements in this field could potentially redefine the therapeutic landscape for viral diseases, opening new vistas for their management and treatment.
Impact of COVID-19 in public health: Prevalence and preventive approaches

Subramaniyan V, Chakravarthi S, Seng WY, Kayarohanam S, Fuloria NK, Fuloria S

Pak J Pharm Sci, 2020 Jul;33(4):1739-1745.
PMID: 33583811

The outbreak of CoVID-19 infection rapidly increases worldwide. Most of the continents affecting from CoVID-19 and still widening its burden disease (Jones DS, 2020; Lai et al., 2020). Along with its fatality rates, CoVID-19 has caused physiological disturbances in the society and termed as "coronophobia". CoVID-19 with renal failure, severe pneumonia and respiratory syndrome patients have been reported to increase the severity of disease conditions (Sevim et al., 2020). Also, CoVID-19 with cancer patients increase the higher risk of infections. Currently, there is no vaccine or specific treatment against CoVID-19 and drug research centres continuously investigating the potential drug against CoVID-19 (Osama and Amer, 2020). For the past 20 years two major coronavirus epidemics have occurred in public includes SARS-CoV approximately 8000 cases and 800 deaths and MERS-CoV 2,500 cases and 800 deaths and these continuing sporadically (Cascella et al., 2020).
Fulltext Chemical Modification of Banana Trunk Fibers for the Production of Green Composites

Sathasivam KV, Haris MRHM, Fuloria S, Fuloria NK, Malviya R, Subramaniyan V

Polymers (Basel), 2021 Jun 11;13(12).
PMID: 34208069 DOI: 10.3390/polym13121943

Natural fibers have proven to be excellent reinforcing agents in composite materials. However, a critical disadvantage of natural fibers is their hydrophilic nature. In this study, banana trunk fibers were mechanically damaged using a high-speed blender, and the resulting fibers (MDBTF) were treated with (i) stearic acid (SAMDBTF) and (ii) calcium carbonate coated with 5% (wt/wt) stearic acid (SACCMDBTF). The moisture sorption, oil sorption and thermal properties of the fibers were determined. The morphology, roughness and the functional groups present were also investigated. Study data of the present study indicate that SACCMDBTF exhibited a faster oil sorption capacity than SAMDBTF. Fast uptake of the oil occurred during the first 5 min, whereby the quantity of oil sorbed in SAMDBTF and SACCMDBTF was 5.5 and 15.0 g oil g-1 fiber, respectively. The results of a used engine oil uptake study revealed that SAMDBTF and SACCMDBTF sorbed 9.5 and 18.3 g/g-1 fiber, respectively, at equilibrium. The obtained results suggest that the mechanically damaged process improved the thermal stability of the fibers. This work reveals that the inclusion of stearic-acid-coated calcium carbonate into the interstices of MDBTF yields is environmentally safe for green hydrophobic composites. SACCMDBTF are used as efficient adsorbents for the removal of spilled oil on aqueous media.
Fulltext Antiarthritic Activity of Achyranthes Aspera on Formaldehyde - Induced Arthritis in Rats

Chinnasamy V, Subramaniyan V, Chandiran S, Kayarohanam S, Kanniyan DC, Velaga VSSR, et al.

Open Access Maced J Med Sci, 2019 Sep 15;7(17):2709-2714.
PMID: 31844425 DOI: 10.3889/oamjms.2019.559

AIM: To determine the ameliorative potential of aqueous extract of Achyranthesaspera(AEAA) against arthritis using swiss albino mice and Wistar rats, and its possible mechanism of action.
METHODS: Swiss albino mice (25-30 g) and Wistar rats (150-180 g) under standard controlled conditions (24 ± 2°C, 50-70 humidity and 12 h light/dark cycle). The groups were divided into 6 groups (n = 6/group) and assigned as control, negative control, standard and, formaldehyde supplemented with two different test dose groups of A. aspera for 4 weeks. Arthritis induced by subplantar administration of 0.1 ml formaldehyde (2% v/v) into the left hind paw in all groups except normal control. Arthritis was assessed using serum Hb, ESR, paw volume, joint diameter, radiological and histopathological investigation.
RESULTS: Oral administration of AEAA shown a significant (p < 0.01) dose-dependent protection against formaldehyde induced arthritis. At 21st day, A.asperashown an inhibition of paw volume in the different doses of 250 mg/kg and 500 mg/kg were found to be 30% and, 38.33% respectively. At 14th day the joint swelling was found to be 27.2% and 36.36 respectively. Diclofenac (10 mg/kg) had an effect of 36.61% inhibition of arthritis and joint swelling at 21st and 14th day.
CONCLUSION: Thus, the present study revealed that the aqueous extract of A. aspera offered significant protection against arthritis and joint inflammation.
Mucoadhesive microspheres of glutaraldehyde crosslinked mucilage of Isabgol husk for sustained release of gliclazide

Sharma VK, Sharma PP, Mazumder B, Bhatnagar A, Subramaniyan V, Fuloria S, et al.

J Biomater Sci Polym Ed, 2021 08;32(11):1420-1449.
PMID: 33941041 DOI: 10.1080/09205063.2021.1925389

Mucoadhesive microspheres have their own significant amongst the various sustained release drug delivery systems. The prolonged residence time of these delivery devices at drug absorption site results in steep concentration gradient and enhanced bioavailability. In this study, the mucilage of Isabgol husk was applied as polymeric backbone to develop gliclazide loaded microspheres by crosslinking with glutaraldehyde. The formulations were studied for surface morphology, swelling behavior, particle size, in vitro release, release kinetics, in vitro mucoadhesion and gamma scintigraphy in rabbits. The release of gliclazide from microspheres was controlled by swelling of crosslinked microspheres followed by diffusion. Gamma scintigraphic images acquired for microspheres retention in gastrointestinal track of rabbits indicated the residence of formulation upto 24 h after oral administration. Gliclazide retained its integrity in polymeric matrix of microspheres as observed by Fourier transform infrared spectroscopy, differential scanning calorimetry and powder X-ray diffractometry. The sustained release of gliclazide and prolonged retention of microspheres in gastrointestinal track disclosed the rationality of mucoadhesive Isabgol husk microspheres in controlling the hyperglycemia in diabetes.
Isolation of new phytometabolites from Alpinia galanga willd rhizomes

Sharma PK, Fuloria S, Ali M, Singh A, Kushwaha SP, Sharma VK, et al.

Pak J Pharm Sci, 2021 Jul;34(4):1397-1401.
PMID: 34799313

The current research was aimed to isolate newer phyto-metabolites from rhizomes of Alpinia galanga plant. Study involved preparation of Alpinia galanga rhizome methanolic extract, followed by normal phase column chromatography assisted isolation of new phytometabolites (using different combinations of chloroform and methanol), and characterization (by UV, FTIR, 13C-NMR, 1H-NMR, COSY, DEPT and Mass spectrometry). The isolation and characterization experiment offered two phytometabolites: an ester (Ag-1) and tetrahydronapthalene type lactone (Ag-2). Present study concludes and reports the two phytometabolites, benzyl myristate (Ag-1) and 3-Methyl-6α, 8β-diol-7-carboxylic acid tetralin-11, 9β-olide (Ag-2) for the first time in Alpinia galanga rhizome. The study recommends that these phytometabolites Ag-1 and Ag-2 can be utilized as effective analytical biomarkers for identification, purity and quality control of this plant in future.
Fulltext Pertinence of nutriments for a stalwart body

Kaur R, Sood A, Kanotra M, Arora S, Subramaniyan V, Bhatia S, et al.

Environ Sci Pollut Res Int, 2021 Oct;28(39):54531-54550.
PMID: 34435290 DOI: 10.1007/s11356-021-16060-1

Nutrition plays a significant role in the prevention and treatment of common diseases. Some superb dietary choices such as functional foods and nutriments can surely help fight against certain diseases and provide various advantages to an individual's health. Plants have been regarded as a primary source of highly effective conventional drugs leading to the development of potential novel agents, which may boost the treatment. Growing demand for functional foods acts as an aid for the producers to expand in agriculture and pave the way for innovation and research by the nutraceutical industry. The given review highlights how various functional foods such as tomatoes, chocolates, garlic and flaxseed are currently being defined, their sources, benefit in treating various ailments and the challenges with their use.
Fulltext Alcohol-associated liver disease: A review on its pathophysiology, diagnosis and drug therapy

Subramaniyan V, Chakravarthi S, Jegasothy R, Seng WY, Fuloria NK, Fuloria S, et al.

Toxicol Rep, 2021;8:376-385.
PMID: 33680863 DOI: 10.1016/j.toxrep.2021.02.010

One of the global burdens of health care is an alcohol-associated liver disease (ALD) and liver-related death which is caused due to acute or chronic consumption of alcohol. Chronic consumption of alcohol damage the normal defense mechanism of the liver and likely to disturb the gut barrier system, mucosal immune cells, which leads to decreased nutrient absorption. Therapy of ALD depends upon the spectrum of liver injury that causes fatty liver, hepatitis, and cirrhosis. The foundation of therapy starts with abstinence from alcohol. Corticosteroids are used for the treatment of ALD but due to poor acceptance, continuing mortality, and identification of tumor necrosis factor-alpha as an integral component in pathogenesis, recent studies focus on pentoxifylline and, antitumor necrosis factor antibody to neutralize cytokines in the therapy of severe alcoholic hepatitis. Antioxidants also play a significant role in the treatment but till today there is no universally accepted therapy available for any stage of ALD. The treatment aspects need to restore the gut functions and require nutrient-based treatments to regulate the functions of the gut system and prevent liver injury. The vital action of saturated fatty acids greatly controls the gut barrier. Overall, this review mainly focuses on the mechanism of alcohol-induced metabolic dysfunction, contribution to liver pathogenesis, the effect of pregnancy, and targeted therapy of ALD.
Fulltext Dietary glucosinolates derived isothiocyanates: chemical properties, metabolism and their potential in prevention of Alzheimer's disease

Khan F, Joshi A, Devkota HP, Subramaniyan V, Kumarasamy V, Arora J

Front Pharmacol, 2023;14:1214881.
PMID: 37554984 DOI: 10.3389/fphar.2023.1214881

Alzheimer's disease (AD) is the most prevalent form of dementia affecting millions of people worldwide. It is a progressive, irreversible, and incurable neurodegenerative disorder that disrupts the synaptic communication between millions of neurons, resulting in neuronal death and functional loss due to the abnormal accumulation of two naturally occurring proteins, amyloid β (Aβ) and tau. According to the 2018 World Alzheimer's Report, there is no single case of an Alzheimer's survivor; even 1 in 3 people die from Alzheimer's disease, and it is a growing epidemic across the globe fruits and vegetables rich in glucosinolates (GLCs), the precursors of isothiocyanates (ITCs), have long been known for their pharmacological properties and recently attracted increased interest for the possible prevention and treatment of neurodegenerative diseases. Epidemiological evidence from systematic research findings and clinical trials suggests that nutritional and functional dietary isothiocyanates interfere with the molecular cascades of Alzheimer's disease pathogenesis and prevent neurons from functional loss. The aim of this review is to explore the role of glucosinolates derived isothiocyanates in various molecular mechanisms involved in the progression of Alzheimer's disease and their potential in the prevention and treatment of Alzheimer's disease. It also covers the chemical diversity of isothiocyanates and their detailed mechanisms of action as reported by various in vitro and in vivo studies. Further clinical studies are necessary to evaluate their pharmacokinetic parameters and effectiveness in humans.
Fulltext Nanotechnological synergy of mangiferin and curcumin in modulating PI3K/Akt/mTOR pathway: a novel front in ovarian cancer precision therapeutics

Alharbi HM, Alqahtani T, Alamri AH, Kumarasamy V, Subramaniyan V, Babu KS

Front Pharmacol, 2023;14:1276209.
PMID: 38239204 DOI: 10.3389/fphar.2023.1276209

Background: Ovarian cancer, colloquially termed the "silent killer" among gynecological malignancies, remains elusive due to its often-asymptomatic progression and diagnostic challenges. Central to its pathogenesis is the overactive PI3K/Akt/mTOR signaling pathway, responsible for various cellular functions, from proliferation to survival. Within this context, the phytochemical compounds mangiferin (derived from Mangifera indica) and curcumin (from Curcuma longa) stand out for their potential modulatory effects. However, their inherent bioavailability challenges necessitate innovative delivery systems to maximize therapeutic benefits. Objective: This study seeks to synergize the merits of nanotechnology with the therapeutic properties of mangiferin and curcumin, aiming to bolster their efficacy against ovarian cancer. Methods: Employing specific nanotechnological principles, we engineered exosomal and liposomal nano-carriers for mangiferin and curcumin, targeting the PI3K/Akt/mTOR pathway. Molecular docking techniques mapped the interactions of these phytochemicals with key proteins in the pathway, analyzing their binding efficiencies. Furthermore, molecular dynamics simulations, spanning 100 nanoseconds, verified these interactions, with additional computational methodologies further validating our findings. The rationale for the 100 nanoseconds time span lies in its sufficiency to observe meaningful protein-ligand interactions and conformational changes. Notably, liposomal technology provided an enhancement in drug delivery by protecting these compounds from degradation, allowing controlled release, and improving cellular uptake. Results: Our computational investigations demonstrated notable binding affinities of mangiferin and curcumin: PI3K at -11.20 kcal/mol, Akt at -15.16 kcal/mol, and mTOR at -10.24 kcal/mol. The adoption of exosome/liposome-mediated delivery significantly amplified the bioavailability and cellular uptake of these nano-formulated compounds, positioning them as potential stalwarts in ovarian cancer intervention. A brief explanation of exosome/liposome-mediated delivery involves the use of these vesicles to encapsulate and transport therapeutic agents directly to the target cells, enhancing drug delivery efficiency and minimizing side effects. Conclusion: Addressing ovarian cancer's intricacies, dominated by the erratic PI3K/Akt/mTOR signaling, mandates innovative therapeutic strategies. Our pioneering approach converges nanotechnological liposomal delivery with mangiferin and curcumin's natural efficacies. This confluence, validated by computational insights, heralds a paradigm shift in ovarian cancer treatment. As our findings underscore the collaborative potential of these phytochemicals, it beckons further exploration in translational studies and clinical applications, ensuring the best intersection of nature and technology for therapeutic advantage.
Fulltext Generative artificial intelligence in drug discovery: basic framework, recent advances, challenges, and opportunities

Gangwal A, Ansari A, Ahmad I, Azad AK, Kumarasamy V, Subramaniyan V, et al.

Front Pharmacol, 2024;15:1331062.
PMID: 38384298 DOI: 10.3389/fphar.2024.1331062

There are two main ways to discover or design small drug molecules. The first involves fine-tuning existing molecules or commercially successful drugs through quantitative structure-activity relationships and virtual screening. The second approach involves generating new molecules through de novo drug design or inverse quantitative structure-activity relationship. Both methods aim to get a drug molecule with the best pharmacokinetic and pharmacodynamic profiles. However, bringing a new drug to market is an expensive and time-consuming endeavor, with the average cost being estimated at around $2.5 billion. One of the biggest challenges is screening the vast number of potential drug candidates to find one that is both safe and effective. The development of artificial intelligence in recent years has been phenomenal, ushering in a revolution in many fields. The field of pharmaceutical sciences has also significantly benefited from multiple applications of artificial intelligence, especially drug discovery projects. Artificial intelligence models are finding use in molecular property prediction, molecule generation, virtual screening, synthesis planning, repurposing, among others. Lately, generative artificial intelligence has gained popularity across domains for its ability to generate entirely new data, such as images, sentences, audios, videos, novel chemical molecules, etc. Generative artificial intelligence has also delivered promising results in drug discovery and development. This review article delves into the fundamentals and framework of various generative artificial intelligence models in the context of drug discovery via de novo drug design approach. Various basic and advanced models have been discussed, along with their recent applications. The review also explores recent examples and advances in the generative artificial intelligence approach, as well as the challenges and ongoing efforts to fully harness the potential of generative artificial intelligence in generating novel drug molecules in a faster and more affordable manner. Some clinical-level assets generated form generative artificial intelligence have also been discussed in this review to show the ever-increasing application of artificial intelligence in drug discovery through commercial partnerships.
Biomedicine and pharmacotherapeutic effectiveness of combinatorial atorvastatin and quercetin on diabetic nephropathy: An in vitro study

Dh HS, Sultana R, Prabhu A, S R P, Mohanto S, Subramaniyan V

Biomed Pharmacother, 2024 Apr 03;174:116533.
PMID: 38574626 DOI: 10.1016/j.biopha.2024.116533

INTRODUCTION: Diabetic nephropathy is a type of kidney disorder that develops as a complication of multifactorial diabetes. Diabetic nephropathy is characterized by microangiopathy, resulting from glucose metabolism, oxidative stress, and changes in renal hemodynamics. This study strived to evaluate the in vitro cytoprotective activity of atorvastatin (ATR), and quercetin (QCT) alone and in combination against diabetic nephropathy.
METHODS: The MTT assay was utilized to analyze the effects of the test compounds on NRK-52E rat kidney epithelial cells. The detection of apoptosis and ability to scavenge free radicals was assessed via acridine orange-ethidium bromide (AO-EB) dual fluorescence staining, and 2,2-diphenyl-1-picrylhydrazyfree assay (DPPH), respectively. The ability of anti-inflammatory effect of the test compounds and western blot analysis against TGF-β, TNF-α, and IL-6 further assessed to determine the combinatorial efficacy.
RESULTS: Atorvastatin and quercetin treatment significantly lowered the expression of TGF-β, TNF-α, and IL-6 indicating the protective role in Streptozotocin-induced nephrotoxicity. The kidney cells treated with a combination of atorvastatin and quercetin showed green fluorescing nuclei in the AO-EB staining assay, indicating that the combination treatment restored cell viability. Quercetin, both alone and in combination with atorvastatin, demonstrated strong DPPH free radical scavenging activity and further encountered an anti-oxidant and anti-inflammatory effect on the combination of these drugs.
CONCLUSION: Nevertheless, there is currently no existing literature that reports on the role of QCT as a combination renoprotective drug with statins in the context of diabetic nephropathy. Hence, these findings suggest that atorvastatin and quercetin may have clinical potential in treating diabetic nephropathy.
Fulltext Immunomodulatory and AntiOxidant Potential of Polyherbal Dhatryadi Rasayana in the Form of Churna and Granules

Rani S, Sharma U, Deshmukh MP, Kumar V, Sharma KC, Malik MK, et al.

ACS Omega, 2024 Apr 02;9(13):14781-14790.
PMID: 38585048 DOI: 10.1021/acsomega.3c06784

Dhatryadi Rasayana revitalizes the human body and helps in maintaining health with the elimination of ill effects of various diseases. The effective delivery systems for Rasayana may affect the profound effect of active principles in the body. The present study deals with investigation and evaluation of phytochemical constituents, physicochemical characteristics, along with antioxidant and immunomodulatory effects of Dhatryadi Rasayana in churna (powder) and granule formulations. Dhatryadi Rasayana churna and its granules were studied for various physicochemical parameters, e.g., moisture content, ash-value, acid-insoluble ash content, water-soluble extractive, alcohol-soluble extractive, bulk density, tapped density, angle of repose, Carr's index, Hausner's ratio, total sugar, reducing sugar, non-reducing sugar, heavy metals, total microbial load, etc. In vitro antioxidant potential of Dhatryadi Rasayana churna and its granules was determined by scavenging the DPPH and FRAP assays. The immunomodulatory activities of Dhatryadi Rasayana churna and its granules were studied in Wistar albino rats and the complete blood count (CBC), delayed-type hypersensitivity reaction (DTH), and hemagglutination antibody titer were assessed. Dhatryadi Rasayana churna contained alkaloids (0.50 ± 0.298% w/w), tannins (9.84 ± 1.527% w/w), saponins (4.18 ± 2.126% w/w), and flavonoids (9.34 ± 1.026% w/w), while its granules contained 11.08 ± 2.468% w/w total tannins, 2.40 ± 1.132% w/w alkaloids, and 12.46 ± 2.645% w/w total flavonoids. The DPPH scavenging effect was determined by IC50 (churna - 23.89 μg/mL; granules - 9.33 μg/mL), and the antioxidant capacity assessed by FRAP was 77.0 mmol/100 g equivalent of ascorbic acid for churna and 50 mmol/100 g equivalent of ascorbic acid for granules. Dhatryadi Rasayana churna and its granules reflected a significant immunostimulatory effect on both the cell-mediated and humoral immune systems in Wistar albino rats. Moreover, churna and granules of Dhatryadi Rasayana revealed significant antioxidant and immunomodulatory activities and these may be applied for treating different diseases as well as improving the immunity of the body.
Fulltext A Comprehensive Review on Source, Types, Effects, Nanotechnology, Detection, and Therapeutic Management of Reactive Carbonyl Species Associated with Various Chronic Diseases

Fuloria S, Subramaniyan V, Karupiah S, Kumari U, Sathasivam K, Meenakshi DU, et al.

Antioxidants (Basel), 2020 Nov 02;9(11).
PMID: 33147856 DOI: 10.3390/antiox9111075

Continuous oxidation of carbohydrates, lipids, and amino acids generate extremely reactive carbonyl species (RCS). Human body comprises some important RCS namely hexanal, acrolein, 4-hydroxy-2-nonenal, methylglyoxal, malondialdehyde, isolevuglandins, and 4-oxo-2- nonenal etc. These RCS damage important cellular components including proteins, nucleic acids, and lipids, which manifests cytotoxicity, mutagenicity, multitude of adducts and crosslinks that are connected to ageing and various chronic diseases like inflammatory disease, atherosclerosis, cerebral ischemia, diabetes, cancer, neurodegenerative diseases and cardiovascular disease. The constant prevalence of RCS in living cells suggests their importance in signal transduction and gene expression. Extensive knowledge of RCS properties, metabolism and relation with metabolic diseases would assist in development of effective approach to prevent numerous chronic diseases. Treatment approaches for RCS associated diseases involve endogenous RCS metabolizers, carbonyl metabolizing enzyme inducers, and RCS scavengers. Limited bioavailability and bio efficacy of RCS sequesters suggest importance of nanoparticles and nanocarriers. Identification of RCS and screening of compounds ability to sequester RCS employ several bioassays and analytical techniques. Present review describes in-depth study of RCS sources, types, properties, identification techniques, therapeutic approaches, nanocarriers, and their role in various diseases. This study will give an idea for therapeutic development to combat the RCS associated chronic diseases.
Fulltext Chemical Characterization and Anti-Inflammatory Activity of Phytoconstituents from Swertia alata

Bajaj S, Fuloria S, Subramaniyan V, Meenakshi DU, Wakode S, Kaur A, et al.

Plants (Basel), 2021 May 31;10(6).
PMID: 34072717 DOI: 10.3390/plants10061109

Swertia alata C.B Clarke (Gentianaceae) is a well-reported plant in the traditional system of medicine. The present study was intended to isolate the phytoconstituents from the ethanolic extract of the aerial parts of S. alata; and evaluate for in vitro COX-1/COX-2 inhibition activity, in vivo anti-inflammatory and ulcerogenic activity. Phytoisolation involved partitioning of S. alata ethanolic extract into petroleum ether and chloroform soluble fractions using silica gel-based column chromatography. The isolation afforded two phytoisolates, namely oleanolic acid (SA-1) and 3-hydroxylup-12-(13)-ene-17-carboxylic acid (SA-4). Phytoisolates structures were established by melting point, ultraviolet (UV), attenuated total reflection-Fourier-transform infrared (ATR-FTIR), nuclear magnetic resonance (1H-NMR, 13C-NMR and HMBC) and mass spectrometry. Phytoisolates were further evaluated for in vitro cyclooxygenase (COX-1/COX-2) inhibitory activity, in vivo anti-inflammatory and ulcerogenic activity. The study revealed SA-4 (COX-1/COX-2 inhibition activity of 104/61.68 µM with % inhibition of 61.36) to be more effective than SA-1 (COX-1/COX-2 inhibition activity of 128.4/87.25 µM, with % inhibition of 47.72). SA-1 and SA-4, when subjected to ulcerogenic study, exhibited significant gastric tolerance. The current study reports chromatographic isolation and spectrometric characterization of SA-1 and SA-4. The present study concludes that compound SA-4 possess significant anti-inflammatory activity and less irritant property over gastric mucosa with no significant ulcerogenicity in comparison to indomethacin.
Fulltext Potential of Marine Terpenoids against SARS-CoV-2: An In Silico Drug Development Approach

Sahoo A, Fuloria S, Swain SS, Panda SK, Sekar M, Subramaniyan V, et al.

Biomedicines, 2021 Oct 20;9(11).
PMID: 34829734 DOI: 10.3390/biomedicines9111505

In an emergency, drug repurposing is the best alternative option against newly emerged severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. However, several bioactive natural products have shown potential against SARS-CoV-2 in recent studies. The present study selected sixty-eight broad-spectrum antiviral marine terpenoids and performed molecular docking against two novel SARS-CoV-2 enzymes (main protease or Mpro or 3CLpro) and RNA-dependent RNA polymerase (RdRp). In addition, the present study analysed the physiochemical-toxicity-pharmacokinetic profile, structural activity relationship, and phylogenetic tree with various computational tools to select the 'lead' candidate. The genomic diversity study with multiple sequence analyses and phylogenetic tree confirmed that the newly emerged SARS-CoV-2 strain was up to 96% structurally similar to existing CoV-strains. Furthermore, the anti-SARS-CoV-2 potency based on a protein-ligand docking score (kcal/mol) exposed that the marine terpenoid brevione F (-8.4) and stachyflin (-8.4) exhibited similar activity with the reference antiviral drugs lopinavir (-8.4) and darunavir (-7.5) against the target SARS-CoV-Mpro. Similarly, marine terpenoids such as xiamycin (-9.3), thyrsiferol (-9.2), liouvilloside B (-8.9), liouvilloside A (-8.8), and stachyflin (-8.7) exhibited comparatively higher docking scores than the referral drug remdesivir (-7.4), and favipiravir (-5.7) against the target SARS-CoV-2-RdRp. The above in silico investigations concluded that stachyflin is the most 'lead' candidate with the most potential against SARS-CoV-2. Previously, stachyflin also exhibited potential activity against HSV-1 and CoV-A59 within IC50, 0.16-0.82 µM. Therefore, some additional pharmacological studies are needed to develop 'stachyflin' as a drug against SARS-CoV-2.
Disruption of the biological activity of protease-activated receptors2/4 in adults rather than children in SARS CoV-2 virus-mediated mortality in COVID-19 infection

Singh Y, Fuloria NK, Fuloria S, Subramaniyan V, Almalki WH, Gupta G, et al.

Drug Dev Res, 2021 Dec;82(8):1075-1078.
PMID: 34469011 DOI: 10.1002/ddr.21874

One of the most remarkable results in 2019 is the reduced prevalence and death of children from coronavirus infection (COVID-19). In 2019, a worldwide pandemic impacted around 0.1 billion individuals, with over 3.5 million mortality reported in the literature. There is minimal knowledge on SARS-CoV-2 infection immunological responses in kids. Studies have been focused mostly on adults and children since the course of pediatric sickness is often short. In adults, severe COVID-19 is related to an excessive inflammatory reaction. Macrophages and monocytes are well known to contribute to this systemic response, although numerous lines are indicative of the importance of neutrophils. An increased number of neutrophils and neutrophil to lymphocyte ratios are early signs of SARS-CoV-2 and a worse prognosis. In this study that it is crucial to monitor PAR2 and PAR4 expression and function (since nursing children have elevated levels) and the inhibiting the normal physiology through the use of anticoagulants may exacerbate the problem in adults. Thus, in COVID-19 infection, we propose the use of antiplatelet (thromboxane A2 inhibitors), if required rather than anticoagulants (FXa and thrombin Inhibitors).

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