Somasundaram Arumugam
@niperkolkata.edu.in
Assistant Professor, Pharmacology and Toxicology
National Institute of Pharmaceutical Education and Research, Kolkata, India
RESEARCH, TEACHING, or OTHER INTERESTS
Pharmacology, Toxicology and Pharmaceutics, Pharmaceutical Science, Pharmacology, Drug Discovery
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Manoj Limbraj Yellurkar, Vani Sai Prasanna, Pamelika Das, Sulogna Sarkar, Rakesh Matta, Devendra Kumar Dhaked, Ramalingam Peraman, Amit Kumar Taraphdar, Satheesh Kumar Nanjappan, Ravichandiran Velayutham,et al.
Elsevier BV
Shiv Pal, Manoj Limbraj Yellurkar, Pamelika Das, Vani Sai Prasanna, Sulogna Sarkar, Rahul L. Gajbhiye, Amit Kumar Taraphdar, Ravichandiran Velayutham, and Somasundaram Arumugam
Informa UK Limited
Somasundaram Arumugam, Kumaravel Vadivel, Devendra Kumar Dhaked, Vani Sai Prasanna, Manoj Limbraj Yellurkar, Pamelika Das, Raja Manoharan, Austin Jose Thomas, Lalith Singh, Subhas Singh,et al.
Georg Thieme Verlag KG
Abstract Background Coronavirus disease 2019 (COVID-19) is a potentially fatal disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several studies have shown that hydroxychloroquine (HCQ) significantly inhibits SARS-CoV-2 infections in vitro. Objective Since the phytoconstituents of Cinchona officinalis (CO) are similar to those of HCQ, the objective of this study was to test the antiviral potential of different homeopathic formulations of CO. Methods An analysis of the molecular composition of CO was carried out using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry, followed by a detailed docking study. The constituents of CO were docked against various targets of SARS-CoV-2, and the binding potential of the phytoconstituents was compared and quantified. The ligand with the lowest Glide docking score is considered to have the best binding affinity. The cytotoxicity of several homeopathic formulations, including CO mother tincture (CO-MT), was also checked on VeroE6 cells. A known antiviral, remdesivir, was used as a positive control for the in vitro assays to evaluate the effects of CO-MT against SARS-CoV-2-infected VeroE6 cells. Results Molecular docking studies showed that constituents of CO exhibited binding potential to various targets of SARS-CoV-2, including Mpro, PLpro, RdRp, nucleocapsid protein, ACE2 (in host) and spike protein. Quinoline, one of the constituents of CO, can potentially bind the spike protein of SARS-CoV-2. Quinic acid showed better binding capabilities with Mpro, PLpro RdRp, nucleocapsid protein and ACE2 (allosteric site) than other constituents. Quinidine exhibited better binding to ACE2. Compared to HCQ, other phytoconstituents of CO had the equivalent potential to bind the RNA-dependent RNA polymerase, nucleocapsid protein, Mpro, PLpro and spike protein of SARS-CoV-2. In vitro assays showed that homeopathic CO-MT was not cytotoxic and that CO-MT and remdesivir respectively caused 89% and 99% inhibition of SARS-CoV-2 infection in VeroE6 cells. Conclusion Based on this in silico and in vitro evidence, we propose CO-MT as a promising antiviral medicine candidate for treating COVID-19. In vivo investigation is required to clarify the therapeutic potential of CO-MT in COVID-19.
Somasundaram Arumugam, Manoj Limbraj Yellurkar, Vani Sai Prasanna, Pamelika Das, Sulogna Sarkar, Jishna Das, Remya Sreedhar, and Ravichandiran Velayutham
Elsevier
Pavazhaviji Pazhani, Vijaya VaraPrasad Medapati, Somasundaram Arumugam, and Jose Prakash Dharmian
Open Science Publishers LLP
Somasundaram Arumugam, Aiping Lyu, Bey Hing Goh, and Uraiwan Panich
Frontiers Media SA
Ravichandiran Velayutham, Somasundaram Arumugam, Priya Bisht, Neha Dagar, and Nitesh Kumar
Bentham Science Publishers Ltd.
Background: Constipation is one of the most frequent abnormalities of the gastrointesti-nal system that affects the patient’s quality of life. Constipation is more common in women and af-fects them more frequently as they get older. Many constipated patients take over-the-counter drugs for treatment, but some do not respond to these medicines and need newer, more expensive drugs. Still, many patients are not completely satisfied with these medicines. Unlike other areas, constipa-tion research is not given much importance. Objective: This review discusses targets such as ClC-2, CFTR, opioid receptors, and 5HT-4 recep-tors, which are important in constipation therapy. The recent focus is also on the gut microbiome with the help of various randomized controlled trials. Pharmacological advances have also added novel targets such as IBAT, PAR-2, and intestinal NHE-3 for constipation treatment. Methods: This review summarises the research on these targets collected from various databases. ClC-2 and CFTR are involved in intestinal chloride secretion followed by sodium or water, which increases stool passage. Non-cancer pain treatment with opioids targeting opiate receptors is con-sidered in 40-90% of patients, which causes constipation as a side effect. On activation, 5HT-4 re-ceptors increase gastrointestinal motility. IBAT is responsible for transporting bile acid into the liv-er. Bile acid will reach the colon by inhibiting IBAT, stimulating colonic motility, and providing a laxative effect. Activation of the ghrelin receptor results in prokinetic activity in both animals and humans. Intestinal NHE-3 mediates the absorption of Na+ and the secretion of hydrogen into the in-testine. Many reports show that PAR-2 is involved in the pathogenesis of gastrointestinal diseases. The gut microbiota influences the peristaltic action of the intestine. Conclusion: Drugs working on these targets positively impact the treatment of constipation, as do the drugs that are currently in clinical trials acting on these targets. The results from the ongoing clinical trials will also provide some valuable information regarding whether these medications will meet the patients’ needs in the future.
Pamelika Das, Rajarajan A. Thandavarayan, Kenichi Watanabe, Ravichandiran Velayutham, and Somasundaram Arumugam
Springer Science and Business Media LLC
Kenichi Watanabe, Masao Hirayama, Somasundaram Arumugam, Masayoshi Sugawara, Hisanori Kato, Sumiko Nakamura, Ken'ichi Ohtsubo, Hitoshi Matsumoto, Yuri Nomi, Noriyuki Homma,et al.
Elsevier BV
Somasundaram Arumugam, Wawaimuli Arozal, and Koji Ikeda
Frontiers Media SA
Anti-In fl ammatory Agents in the Context of Age-related Cardiometabolic Disease: in metabolic syndrome in addition to the supporting data for the role of Moringa oleifera Lam. on various signaling pathways activated during in fl ammation and oxidative stress. et al. have studied the molecular basis of the effect of ShenLian extract on atherosclerotic plaques in vitro and in vivo . By using the co-culture model, macrophage and smooth muscle cell (SMC) interactions were studied and reported the necessary role of transforming growth factor (TGF)- β in the cross-talk between macrophages and SMC in stabilizing the atherosclerotic plaques. They have reported that ShenLian extract (an herbal decoction consisting of Coptis chinensis Franch. and Panax ginseng C.A.Mey.) could stabilize the vulnerable plaques by increasing plaque collagen and functionally reconstruct the extracellular matrix via increasing TGF- β expression and regulating the STAT3/SOCS3 pathway. Liu et al. and her team reported that the monocyte locomotion inhibitory factor (MLIF), a heat-stable pentapeptide from Entamoeba histolytica , promoted microglia transition toward the M2 phenotype, which contributes to neuronal survival and tissue repair, in vivo and in vitro ischemic stroke model via regulation of eEF1A1/
Pamelika Das, Pappula Mounika, Manoj Limbraj Yellurkar, Vani Sai Prasanna, Sulogna Sarkar, Ravichandiran Velayutham, and Somasundaram Arumugam
MDPI AG
Atopic dermatitis (AD), characterized by rashes, itching, and pruritus, is a chronic inflammatory condition of the skin with a marked infiltration of inflammatory cells into the lesion. It usually commences in early childhood and coexists with other atopic diseases such as allergic rhinitis, bronchial asthma, allergic conjunctivitis, etc. With a prevalence rate of 1–20% in adults and children worldwide, AD is gradually becoming a major health concern. Immunological aspects have been frequently focused on in the pathogenesis of AD, including the role of the epidermal barrier and the consequent abnormal cytokine expressions. Disrupted epidermal barriers, as well as allergic triggers (food allergy), contact allergens, irritants, microbes, aggravating factors, and ultraviolet light directly initiate the inflammatory response by inducing epidermal keratinocytes, resulting in the abnormal release of various pro-inflammatory mediators, inflammatory cytokines, and chemokines from keratinocytes. In addition, abnormal proteinases, gene mutations, or single nucleotide polymorphisms (SNP) affecting the function of the epidermal barrier can also contribute towards disease pathophysiology. Apart from this, imbalances in cholinergic or adrenergic responses in the epidermis or the role played by immune cells in the epidermis such as Langerhans cells or antigen-presenting cells can also aggravate pathophysiology. The dearth of specific biomarkers for proper diagnosis and the lack of a permanent cure for AD necessitate investigation in this area. In this context, the widespread role played by keratinocytes in the pathogenesis of AD will be reviewed in this article to facilitate the opening up of new avenues of treatment for AD.
David Paul, A. Parag, K. S. Aswathi, Dinesh Kumar Chellappan, Somasundaram Arumugam, and Satheesh Kumar Nanjappan
Springer Nature Singapore
Hiroshi Suzuki, Kenichi Watanabe, Somasundaram Arumugam, Manoj Limbraj Yellurkar, Remya Sreedhar, Rejina Afrin, and Hirohito Sone
Begell House
Nonalcoholic steatohepatitis (NASH) is becoming the most common cause of hepatocellular carcinoma (HCC) in developed countries. Oxidative stress plays a major role in the pathogenesis of NASH due to steatosis; hence, novel therapeutic approaches might include natural antioxidants. Ceraceomyces tessulatus strain Basidiomycetes-X (BDM-X), a novel edible mushroom, possesses potent antioxidant activity. This study aimed to investigate the hepato-protective effect of C. tessulatus BDM-X in a novel NASH-HCC mouse model. To prepare this animal model, 2-day-old C57BL/6J male pups were exposed to low-dose streptozotocin (STZ); at 4 weeks of age, they were randomly divided into two groups. The NASH group (NASH) received a high-fat diet (HFD32) up to 14 weeks of age; the C. tessulatus BDM-X group (BDM-X) received HFD32 up to age 10 weeks, followed by HFD32 + 20% BDM-X (percent weight per weight in the diet) up to age 14 weeks. Mice not treated with STZ and fed a normal diet served as a control group. We found that C. tessulatus BDM-X improved serum aminotransferase levels as well as histopathological features such as steatosis, inflammatory foci, and pericellular fibrosis in NASH mice. Hepatic protein expression of sterol regulatory element binding protein isoform SREBP-1 and peroxisome proliferator-activated receptor PPARα was significantly increased in NASH mice. C. tessulatus BDM-X treatment normalized the expression of both proteins. Our data suggest that C. tessulatus BDM-X may protect the liver against lipogenesis in NASH-HCC mice.
Manoj Limbraj Yellurkar, Vibhavana Singh, Vani Sai Prasanna, Pamelika Das, Satheeshkumar Nanjappan, Ravichandiran Velayutham, and Somasundaram Arumugam
Public Library of Science (PLoS)
The compound methyl cinnamoyl catalpol (DAM-1) was isolated from the methanol extract of Dolichandrone atrovirens. Studies have already reported the antioxidant activity of Dolichandrone atrovirens bark extract, but till date the antioxidant activity of the isolated compound DAM-1, remains unexplored. The endogenous process of reactive oxygen species generation which leads to various degenerative diseases, can be broken down using these exogenous moieties from plant origin, herein this study we sought to evaluate the antioxidant potential of the DAM-1 compound using Caenorhabditis elegans (C. elegans), which is the primary model to study the antioxidant activity of compounds. Cytotoxicity assay results showed that DAM-1 treatment in the concentration of 10, 25 and 50 μg/ml has shown 100%, 91%, and 50% survival respectively with overall p<0.0001 (treatment v/s control group). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide–Formazan (MTT) assay results showed that treatment had better survival rates than the control group at different time intervals i.e. 48 h, and 72 h with p<0.01. Mechanosensation (behavioral study) as well as in vivo study results showed that at 0 h, 10 μg/ml of DAM-1 treatment showed a better anti-oxidative activity than the control group, 25 and 50 μg/ml of DAM-1 treated groups with p<0.001 but at 2.5 h incubation with 10, 25, 50 μg/ml of DAM-1 showed an increased anti-oxidative activity than the control group with p<0.001. Thermoresistance assay confirmed that the treatment group had more survival than control group with p<0.001. Absorption study of DAM-1 in C. elegans has shown that the absorption of the drug increases up to 180 mins with a slight decrease after 360 mins and then constant absorption up to 1440 mins. This study paves the way towards the initiative to explore the pharmacological role of DAM-1 in various oxidative stress mediated diseases at molecular levels and the absorption study points out its potential role which could be utilized in the metabolomics and proteomics analysis of this compound in other studies.
Neha Dagar, Pamelika Das, Priya Bisht, Amit Kumar Taraphdar, Ravichandiran Velayutham, and Somasundaram Arumugam
Elsevier BV
Mst. Rejina Afrin, Somasundaram Arumugam, Vigneshwaran Pitchaimani, Vengadeshprabhu Karuppagounder, Rajarajan Amirthalingam Thandavarayan, Meilei Harima, Chowdhury Faiz Hossain, Kenji Suzuki, Hirohito Sone, Yasuhiro Matsubayashi,et al.
Elsevier BV
Vigneshwaran Pitchaimani, Somasundaram Arumugam, Rajarajan Amirthalingam Thandavarayan, Vengadeshprabhu Karuppagounder, Mst Rejina Afrin, Remya Sreedhar, Meilei Harima, Masahiko Nakamura, Kenichi Watanabe, Satoru Kodama,et al.
Elsevier BV
Vijayasree V. Giridharan, Vengadeshprabhu Karupppagounder, Somasundaram Arumugam, Yutaka Nakamura, Ashrith Guha, Tatiana Barichello, Joao Quevedo, Kenichi Watanabe, Tetsuya Konishi, and Rajarajan A. Thandavarayan
MDPI AG
Aging is a predominant risk factor for the development and progression of cardiovascular complications. Physiologically and anatomically, the heart undergoes numerous changes that result in poor cardiac function in the elderly population. Recently, several studies have provided promising results, confirming the ability of the senescence-accelerated mouse-prone 8 (SAMP8) model to accurately model age-related cardiovascular alterations. In this study, using a murine model of senescence, SAMP8, we aimed to investigate the effect of 3,4-dihydroxybenzalacetone (DBL), a catechol-containing phenylpropanoid derivative isolated from Inonotus obliquus (Chaga), on cardiac aging. DBL was administered at the doses of 10 mg/kg and 20 mg/kg by oral gavage to SAMP8 mice to examine aging-mediated cardiac changes, such as oxidative DNA damage, oxygen radical antioxidant capacity (ORAC) value, fibrosis, inflammation, and apoptosis. The treatment with DBL at both doses significantly reduced aging-mediated oxidative DNA damage, and simultaneously increased the ORAC value in the SAMP8 assay. Cardiac fibrosis was assessed with Azan-Mallory staining, and the number of cardiac remodeling markers was found to be significantly reduced after the treatment with DBL. We also observed a decrease in cardiomyocyte apoptosis as measured by the terminal transferase-mediated dUTP nick end labeling (TUNEL) staining method and the caspase-3 levels in SAMP8 mice compared with senescence-resistant control (SAMR1) mice. The findings from this study suggest that DBL has a potentially beneficial effect on aging-mediated myocardial alterations. Further studies are warranted to confirm the promising potential of this catechol compound against aging-associated myocardial dysfunction.
Kenichi Watanabe, Rejina Afrin, Remya Sreedhar, Vengadeshprabhu Karuppagounder, Meilei Harima, Xavier Alexander, Ravichandiran Velayutham, and Somasundaram Arumugam
Begell House
Nonalcoholic steatohepatitis (NASH) is becoming the most common cause of hepatocellular carcinoma (HCC). Natural products including edible mushrooms are gaining attention for the prevention and treatment of lifestyle related disorders. Ceraceomyces tessulatus (strain BDM-X) possesses potent antioxidative stress activity. In this study, we hypothesize that BDM-X treatment protects the liver of mouse with NASH by reducing inflammation in a novel NASH-HCC mouse model. C57BL/6J female pups were exposed to low-dose streptozotocin (STZ) and fed a high-fat diet (HFD) 32 from the age of 4 weeks to 16 weeks. Water extract of BDM-X was given at 500 mg/kg dose daily by oral gavage started at the age of 12 weeks and continued until 16 weeks of age along with HFD feeding. We found that BDM-X improved the histopathological changes, serum aminotransferases, and blood glucose levels in NASH mice. The hepatic protein expressions of SIRT1 and IL-10 were significantly repressed in NASH mice. BDM-X treatment restored these expressions. BDM-X treatment effectively reduced the progression of NASH by suppressing the protein expression of SREBPlc, p-NF-κB, Ep-CAM, and prothrombin in the NASH liver. In conclusion, our data suggest that BDM-X can protect the liver against inflammation and lipogenesis in NASH-HCC mice.
Geetha Kandasamy, Dalia Almaghaslah, Palanisamy Sivanandy, and Somasundaram Arumugam
Wiley
OBJECTIVES
A prospective observational study was carried out with the aim of evaluating the effectiveness of nasal continuous positive airway pressure (nCPAP) therapy on the health-related quality of life (QoL) of patients with obstructive sleep apnea (OSA).
METHODS
The patients included in this study were those recently diagnosed with OSA (AHI > 5) and given nCPAP therapy, as well as being referred to a sleep laboratory for an assessment of their sleep disordered breathing. Prior to the start of nCPAP therapy and polysomnography evaluation, patients were asked to complete the validated Quebec sleep questionnaire (QSQ), and their baseline measurements were recorded.
RESULTS
Among the study population, 14.41% (n = 31) had mild OSA with an apnea and hypopnea index of 5 to 14.9 events/h, while 26.97% (n = 58) had moderate OSA and 40% (n = 86) had severe OSA. The overall average apnea and hypopnea index of the study population was 30.24 ± 9.73 events/h; mild OSA patients had an average apnea and hypopnea index of 10.09 ± 2.65 events/h, moderate OSA patients had 21.48 ± 4.40 events/h, and severe OSA patients had 59.16 ± 22.14 events/h. A significant difference was observed between the scores before treatment and after 6 months of therapy in all domains of the QSQ QoL scores (P < 0.0001).
CONCLUSION
Nasal continuous positive airway pressure treatment improved the QoL for patients with mild, moderate, and severe sleep apnea.
Kenichi Watanabe, Vengadeshprabhu Karuppagounder, Remya Sreedhar, Geetha Kandasamy, Meilei Harima, Ravichandiran Velayutham, and Somasundaram Arumugam
Elsevier BV
Vengadeshprabhu Karuppagounder, Anamika Bajpai, Shu Meng, Somasundaram Arumugam, Remya Sreedhar, Vijayasree V. Giridharan, Ashrith Guha, Arvind Bhimaraj, Keith A. Youker, Suresh S. Palaniyandi,et al.
Public Library of Science (PLoS)
The purpose of this study was to determine whether blocking of G protein βγ (Gβγ) signaling halts heart failure (HF) progression by macrophage phenotype manipulation. Cardiac Gβγ signaling plays a crucial role in HF pathogenesis. Previous data suggested that inhibiting Gβγ signaling reprograms T helper cell 1 (Th1) and Th2 cytokines, suggesting that Gβγ might be a useful drug target for treating HF. We investigated the efficacy of a small molecule Gβγ inhibitor, gallein, in a clinically relevant, experimental autoimmune myocarditis (EAM) model of HF as well as in human macrophage phenotypes in vitro. In the myocardium of HF patients, we observed that G protein coupled receptor kinase (GRK)2 levels were down-regulated compared with healthy controls. In rat EAM, treatment with gallein effectively improved survival and cardiac function, suppressed cardiac remodeling, and further attenuated myocardial protein expression of GRK2 as well as high mobility group box (HMGB)1 and its cascade signaling proteins. Furthermore, gallein effectively inhibited M1 polarization and promoted M2 polarization in vivo in the EAM heart and in vitro in human monocyte-derived macrophages. Taken together, these data suggest that the small molecule Gβγ inhibitor, gallein, could be an important pharmacologic therapy for HF as it can switch the phenotypic reprogramming from M1 to M2 phenotype in a rat model of EAM heart and in human macrophages.
Somasundaram Arumugam, Remya Sreedhar, Vengadeshprabhu Karuppagounder, Meilei Harima, Masahiko Nakamura, Hiroshi Suzuki, Hirohito Sone, and Kenichi Watanabe
Wiley
BACKGROUND
Chronic heart failure (CHF) involves fluid retention and volume overload, leading to impaired cardiac function. In these conditions, diuretic agents are most commonly used to treat edema and thereby reducing the volume load on the failing heart. There are several other beneficial effects of diuretics apart from their action on urinary excretion.
METHODS
To identify the effects of diuretic agents on adverse cardiac remodeling in CHF, this study was carried out, where we have compared the effects of torasemide and spironolactone in a rat model of dilated cardiomyopathy induced by porcine cardiac myosin-mediated experimental autoimmune myocarditis.
RESULTS
Cardiac protein expression levels of inflammation, endoplasmic reticulum stress, and fibrosis markers were upregulated in the hearts of CHF rats, while treatment with either torasemide or spironolactone has downregulated their expression. The effect produced by spironolactone on cardiac fibrosis markers was comparably lesser than torasemide. Further, immunohistochemical analysis and histopathological studies have provided evidence to confirm the beneficial effects of these drugs on adverse cardiac remodeling in rats with CHF.
CONCLUSION
Torasemide treatment has benefits against adverse cardiac remodeling in CHF rats, which was better than the protection offered by spironolactone.
Mst. Rejina Afrin, Somasundaram Arumugam, Md. Azizur Rahman, Vengadeshprabhu Karuppagounder, Meilei Harima, Hiroshi Suzuki, Shizuka Miyashita, Kenji Suzuki, Kazuyuki Ueno, Hiroyuki Yoneyama,et al.
Elsevier BV
Remya Sreedhar, Somasundaram Arumugam, Rajarajan A. Thandavarayan, Vengadeshprabhu Karuppagounder, Yusuke Koga, Takashi Nakamura, Meilei Harima, and Kenichi Watanabe
Elsevier BV