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Large-scale computational screening of Indian medicinal plants reveals Cassia angustifolia to be a potentially anti-diabetic.
Devaraji, V, Sivaraman, J, Prabhu, S
Journal of biomolecular structure & dynamics. 2024;(1):194-210
Abstract
Researchers are investigating the medicinal properties of herbal plants throughout the world, which often leads to the discovery of novel plants and their chemicals for prophylactic needs of humans. Natural phytochemicals continue to be sought as alternative treatments for various diseases because of their non-toxic and therapeutic properties. In recent years, computational phytochemistry has enabled large-scale screening of phytochemicals, enabling researchers to pursue a wide range of therapeutic research alternatives to traditional ethnopharmacology. We propose to identify an anti-diabetic plant by computational screening on Indian herbal plants in conjunction with experimental characterization and biological validation. The methodology involves the creation of an in-house Indian herbal plant database. Molecular docking is used to screen against alpha amylase for anti-diabetic prophylaxis. Cassia angustifolia was chosen because its phytochemicals are able to bind to alpha amylase. Plants were experimentally extracted, botanically studied and their biological activity was evaluated. Further, the use of molecular dynamics was then applied to pinpoint the phytochemicals responsible for the affinity of alpha amylase. Results in the phytochemical analysis of the extracts revealed strong presence of alkaloids, flavonoids and cardiac glycosides. Moreover, alpha amylase biological activity with C. angustifolia extracts of chloroform, hexane and ethyl acetate demonstrated activity of 3.26, 8.01 and 30.33 µg/ml validating computational predictions. In conclusion, this study developed, validated computational predictions of identifying potential anti-diabetic plants 'Cassia angustifolia' from house herbal databases. Hope this study shall inspire explore plant therapeutic repurposing using computational methods of drug discovery.Communicated by Ramaswamy H. Sarma.
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Dental Perspective on Mucormycosis in COVID-19: a Literature Review.
Prabhu, S, In, A, Balakrishnan, D
Current oral health reports. 2022;(4):211-214
Abstract
PURPOSE OF REVIEW The purpose of this paper is to gain an understanding of existing knowledge and attain familiarity on mucormycosis for early diagnosis and treatment. It highlights the systematic factors, signs and symptoms, diagnostic tests and treatment procedure for mucormycosis from dentistry point of view. PubMed/ Medline, Scopus, Web of Science were the search engine used. Study selection encompassed systematic reviews, critical reviews and case reports related to mucormycosis in COVID-19 patients and only mucormycosis. 19 articles were selected between Years 2001 to 2021. Analysis was done based on patient's comorbidity, site of mucormycosis infection, use of steroids and its effect on people with COVID -19 infection. RECENT FINDINGS Rhino-orbito-cerebral mucormycosis is the most common of all systemic manifestations of mucormycosis. Diabetes mellitus and long-term corticosteroid therapy are the leading risk factors with pre-existing diabetes mellitus accounting for almost 80% cases. Elements that facilitate the growth of mucor in COVID-19 patients are the presence of low oxygen levels, high blood glucose levels, acidic media, high levels of iron, immunosuppression, and episodes of prolonged hospitalization. Mucormycosis is heterogenic in nature. Its management requires an individualized plan that considers the immunity status of the host, stage of the infection, systemic disease, early diagnosis and susceptibility to anti-fungal agents. Supervised use of corticosteroids and betadine gargle prevent the occurance of mucormycosis. SUMMARY The paper sheds some light on the warning signs and diagnostic tests that can help in early identification of infection by a dentist. This enables the timely implementation of therapy resulting in good prognosis of the treatment.
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Coexistent Dedifferentiated Endometrioid Carcinoma of the Uterus and Adenocarcinoma of the Bladder in Lynch Syndrome: Case Report and Review of the Literature.
Groth, JV, Prabhu, S, Periakaruppan, R, Ohlander, S, Emmadi, R, Kothari, R
Applied immunohistochemistry & molecular morphology : AIMM. 2020;(3):e26-e30
Abstract
Lynch syndrome is an autosomal dominant disorder, caused by an abnormality in DNA mismatch repair genes and characterized by the development of a variety of cancers. Upper urinary tract urothelial carcinoma is well characterized in Lynch syndrome; however, support for the inclusion of bladder urothelial carcinoma is limited, except for MSH2 mutation carriers. Urologic adenocarcinoma has not been documented in Lynch syndrome. Here we report, to the best of our knowledge, the first case of bladder adenocarcinoma, synchronous with uterine endometrioid dedifferentiated endometrioid adenocarcinoma in a patient with Lynch syndrome. We present a 47-year-old woman with an MLH1 gene mutation (G133X 397G>T) who presented with menorrhagia. Eleven family members have this mutation, 6 with carcinoma: 5 colorectal and 1 with a gynecologic primary of unknown type. Colonoscopy and endoscopy were unremarkable. Positron emission and computed tomography revealed a 3 cm anterior dome bladder mass without additional extrauterine disease or uterine connection. She underwent partial cystectomy, laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and lymphadenectomy. The uterus demonstrated a dedifferentiated endometrioid adenocarcinoma, immunohistochemically positive for vimentin, ER, CK7, MSH2, MSH6, and p53 (focally) and negative for CEA, CDX2, CK20, β-catenin, MLH1, and PMS2. The bladder demonstrated a well-differentiated, enteric-type adenocarcinoma without muscularis propria invasion, positive for CEA, CDX2, CK20, p53, MSH2, and MSH6 and negative for vimentin, ER, CK7, MLH1, and PMS2. Eleven nodes were negative for carcinoma. The morphologic, immunohistochemical, and clinical findings support synchronous bladder adenocarcinoma, enteric type, and uterine dedifferentiated endometrioid adenocarcinoma, in a patient with Lynch syndrome.
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A randomized, double blind, placebo controlled, multicenter clinical trial to assess the efficacy and safety of Emblica officinalis extract in patients with dyslipidemia.
Upadya, H, Prabhu, S, Prasad, A, Subramanian, D, Gupta, S, Goel, A
BMC complementary and alternative medicine. 2019;19(1):27
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Plain language summary
Emblica officinalis (Amla or Indian gooseberry) is a fruit that has been traditionally used in Ayurvedic medicine. It has been shown to be effective in the management of dyslipidemia (abnormal fat metabolism), a risk factor for heart disease, in animal models and in pilot clinical studies without major side effects. This multicenter, randomised, placebo controlled, double blind clinical trial was designed to evaluate the efficacy and safety of a proprietary full spectrum amla extract (containing pulp and seeds) in patients with dyslipidemia. 98 patients were enrolled and all completed the 12 week study. None of them were taking any medication for their dyslipidaemia. All the patients enrolled in the study were also asked to initiate lifestyle changes (healthy diet with exercise at least 4 days a week). Apart from conventional lipid parameters, the investigators also measured a number of other parameters relevant to heart disease, including the atherogenic index of plasma (AIP, a marker of heart disease risk). Compared to the placebo group the amla group had significantly greater reductions in triglycerides, LDL-cholesterol, VLDL-cholesterol and the atherogenic index of plasma (AIP, a better predictor of heart disease risk). There were no significant changes in HDL-cholesterol, CoQ10 (lowering of CoQ10 is a concern with many cholesterol lowering drugs), homocysteine, thyroid stimulating hormone (TSH) or fasting blood glucose. Four non-serious adverse events were observed: mild headache, mild fever, two times gastritis (all resolved with standard treatment), three were in the placebo group, one in the amla group. There were no changes in routine blood tests and vital signs (blood pressure, heart rate, temperature, respiratory rate). The authors conclude that the amla extract has significant potential to improve dyslipidaemia without side effects commonly seen with cholesterol lowering drugs.
Abstract
BACKGROUND Dyslipidemia is one of the most frequently implicated risk factors for development of atherosclerosis. This study evaluated the efficacy of amla (Emblica officinalis) extract (composed of polyphenols, triterpenoids, oils etc. as found in the fresh wild amla fruit) in patients with dyslipidemia. METHODS A total of 98 dyslipidemic patients were enrolled and divided into amla and placebo groups. Amla extract (500 mg) or a matching placebo capsule was administered twice daily for 12 weeks to the respective group of patients. The patients were followed up for 12 weeks and efficacy of study medication was assessed by analyzing lipid profile. Other parameters evaluated were apolipoprotein B (Apo B), apolipoprotein A1 (Apo A1), Coenzyme Q10 (CoQ10), high-sensitive C-reactive protein (hsCRP), fasting blood sugar (FBS), homocysteine and thyroid stimulating hormone (TSH). RESULTS In 12 weeks, the major lipids such as total cholesterol (TC) (p = 0.0003), triglyceride (TG) (p = 0.0003), low density lipoprotein cholesterol (LDL-C) (p = 0.0064) and very low density lipoprotein cholesterol (VLDL-C) (p = 0.0001) were significantly lower in amla group as compared to placebo group. Additionally, a 39% reduction in atherogenic index of the plasma (AIP) (p = 0.0177) was also noted in amla group. The ratio of Apo B to Apo A1 was reduced more (p = 0.0866) in the amla group as compared to the placebo. There was no significant change in CoQ10 level of amla (p = 0.2942) or placebo groups (p = 0.6744). Although there was a general trend of FBS reduction, the numbers of participants who may be classified as pre-diabetes and diabetes groups (FBS > 100 mg/dl) in the amla group were only 8. These results show that the amla extract used in the study is potentially a hypoglycaemic as well. However, this needs reconfirmation in a larger study. CONCLUSIONS The Amla extract has shown significant potential in reducing TC and TG levels as well as lipid ratios, AIP and apoB/apo A-I in dyslipidemic persons and thus has scope to treat general as well as diabetic dyslipidemia. A single agent to reduce cholesterol as well as TG is rare. Cholesterol reduction is achieved without concomitant reduction of Co Q10, in contrast to what is observed with statins. TRIAL REGISTRATION Registered with Clinical Trials Registry- India at www.ctri.nic.in (Registration number: CTRI/2015/04/005682 ) on 8 April 2015 (retrospectively registered).
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Effect of Dietary Factors on Cardiac Rhythm.
Voskoboinik, A, Prabhu, S, Sugumar, H, Kistler, PM
The American journal of cardiology. 2018;(7):1265-1271
Abstract
The interaction between arrhythmias and certain lifestyle factors such as obesity and alcohol consumption is well-established. There is significant public and professional interest in the role of various diets, vitamins, and minerals in cardiovascular health. However, many widely held beliefs are not supported by the literature. There is limited evidence for routine magnesium and omega-3 poly-unsaturated fatty acids supplementation, while coffee, tea, nuts, antioxidant vitamins, and even chocolate may have some antiarrhythmic properties. Saturated fat, added salt, and excessive energy drink consumption appear to be harmful for patients with rhythm disorders. However most recommendations are based on observation studies, and this remains a fertile area for further research.
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Potential therapeutic targets and the role of technology in developing novel cannabinoid drugs from cyanobacteria.
Vijayakumar, S, Manogar, P, Prabhu, S
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2016;:362-371
Abstract
Cyanobacteria find several applications in pharmacology as potential candidates for drug design. The need for new compounds that can be used as drugs has always been on the rise in therapeutics. Cyanobacteria have been identified as promising targets of research in the quest for new pharmaceutical compounds as they can produce secondary metabolites with novel chemical structures. Cyanobacteria is now recognized as a vital source of bioactive molecules like Curacin A, Largazole and Apratoxin which have succeeded in reaching Phase II and Phase III into clinical trials. The discovery of several new clinical cannabinoid drugs in the past decade from diverse marine life should translate into a number of new drugs for cannabinoid in the years to come. Conventional cannabinoid drugs have high toxicity and as a result, they affect the efficacy of chemotherapy and patients' life very much. The present review focuses on how potential, safe and affordable drugs used for cannabinoid treatment could be developed from cyanobacteria.
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Aged Garlic Extract Reduces Low Attenuation Plaque in Coronary Arteries of Patients with Metabolic Syndrome in a Prospective Randomized Double-Blind Study.
Matsumoto, S, Nakanishi, R, Li, D, Alani, A, Rezaeian, P, Prabhu, S, Abraham, J, Fahmy, MA, Dailing, C, Flores, F, et al
The Journal of nutrition. 2016;(2):427S-432S
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Abstract
BACKGROUND Although several previous studies have demonstrated that aged garlic extract (AGE) inhibits the progression of coronary artery calcification, its effect on noncalcified plaque (NCP) has been unclear. OBJECTIVE This study investigated whether AGE reduces coronary plaque volume measured by cardiac computed tomography angiography (CCTA) in patients with metabolic syndrome (MetS). METHODS Fifty-five patients with MetS (mean ± SD age: 58.7 ± 6.7 y; 71% men) were prospectively assigned to consume 2400 mg AGE/d (27 patients) or placebo (28 patients) orally. Both groups underwent CCTA at baseline and follow-up 354 ± 41 d apart. Coronary plaque volume, including total plaque volume (TPV), dense calcium (DC), NCP, and low-attenuation plaque (LAP), were measured based upon predefined intensity cutoff values. Multivariable linear regression analysis, adjusted for age, gender, number of risk factors, hyperlipidemia medications, history of coronary artery disease, scan interval time, and baseline %TPV, was performed to examine whether AGE affected each plaque change. RESULTS The %LAP change was significantly reduced in the AGE group compared with the placebo group (-1.5% ± 2.3% compared with 0.2% ± 2.0%, P = 0.0049). In contrast, no difference was observed in %TPV change (0.3% ± 3.3% compared with 1.6% ± 3.0%, P = 0.13), %NCP change (0.2% ± 3.3% compared with 1.4% ± 2.9%, P = 0.14), and %DC change (0.2% ± 1.4%, compared with 0.2% ± 1.7%, P = 0.99). Multivariable linear regression analysis found a beneficial effect of AGE on %LAP regression (β: -1.61; 95% CI: -2.79, -0.43; P = 0.008). CONCLUSIONS This study indicates that the %LAP change was significantly greater in the AGE group than in the placebo group. Further studies are needed to evaluate whether AGE has the ability to stabilize vulnerable plaque and decrease adverse cardiovascular events. This trial was registered at clinicaltrials.gov as NCT01534910.
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Anionic Host Defence Peptides from the Plant Kingdom: Their Anticancer Activity and Mechanisms of Action.
Harris, F, Prabhu, S, Dennison, SR, Snape, TJ, Lea, R, Mura, M, Phoenix, DA
Protein and peptide letters. 2016;(8):676-87
Abstract
It is becoming increasingly clear that plants ranging across the plant kingdom produce anionic host defence peptides (AHDPs) with potent activity against a wide variety of human cancers cells. In general, this activity involves membrane partitioning by AHDPs, which leads to membranolysis and / or internalization to attack intracellular targets such as DNA. Several models have been proposed to describe these events including: the toroidal pore and Shai-Matsuzaki-Huang mechanisms but, in general, the mechanisms underpinning the membrane interactions and anticancer activity of these peptides are poorly understood. Plant AHDPs with anticancer activity can be conveniently discussed with reference to two groups: cyclotides, which possess cyclic molecules stabilized by cysteine knot motifs, and other ADHPs that adopt extended and α-helical conformations. Here, we review research into the anticancer action of these two groups of peptides along with current understanding of the mechanisms underpinning this action.
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Cardiovascular aspect of Beta-thalassaemia.
Taksande, A, Prabhu, S, Venkatesh, S
Cardiovascular & hematological agents in medicinal chemistry. 2012;(1):25-30
Abstract
Beta-thalassaemia major is a genetic blood disorder caused by the reduced synthesis of beta globin chain. The consequences of the resulting chronic anaemia are also common and include growth retardation, bone marrow expansion, extramedular hematopoiesis, splenomegaly, increased intestinal iron absorption, susceptibility to infections, and hypercoagulability. Transfusional iron overload can affect heart function by directly damaging tissue through iron deposition or via iron-mediated effects at other sites. Cardiac dysfunction is common in patients with thalassaemia and is the leading cause of mortality. The main cardiac abnormalities reported in patients with thalassaemia major (TM) and iron overload are left ventricular systolic and diastolic dysfunction, pulmonary hypertension, valvulopathies, arrhythmias and pericarditis. These cardiac abnormalities are a consequence of the general co-morbid conditions in thalassaemia but are closely related to concomitant endocrine deficiencies, hypercoagulability state and inflammatory milieu. Iron's toxicity within cells arises from its capacity to catalyse the production of reactive oxygen species that cause lipid peroxidation and organelle damage, which lead ultimately to cell death and fibrosis. With the introduction of new technologies such as cardiac magnetic resonance T2* , the early detection of cardiac iron overload and associated cardiac dysfunction is now possible, allowing time for reversal through iron chelation therapy.
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Ultrafast genome-wide scan for SNP-SNP interactions in common complex disease.
Prabhu, S, Pe'er, I
Genome research. 2012;(11):2230-40
Abstract
Long-range gene-gene interactions are biologically compelling models for disease genetics and can provide insights on relevant mechanisms and pathways. Despite considerable effort, rigorous interaction mapping in humans has remained prohibitively difficult due to computational and statistical limitations. We introduce a novel algorithmic approach to find long-range interactions in common diseases using a standard two-locus test that contrasts the linkage disequilibrium between SNPs in cases and controls. Our ultrafast method overcomes the computational burden of a genome × genome scan by using a novel randomization technique that requires 10× to 100× fewer tests than a brute-force approach. By sampling small groups of cases and highlighting combinations of alleles carried by all individuals in the group, this algorithm drastically trims the universe of combinations while simultaneously guaranteeing that all statistically significant pairs are reported. Our implementation can comprehensively scan large data sets (2K cases, 3K controls, 500K SNPs) to find all candidate pairwise interactions (LD-contrast ) in a few hours-a task that typically took days or weeks to complete by methods running on equivalent desktop computers. We applied our method to the Wellcome Trust bipolar disorder data and found a significant interaction between SNPs located within genes encoding two calcium channel subunits: RYR2 on chr1q43 and CACNA2D4 on chr12p13 (LD-contrast test, ). We replicated this pattern of interchromosomal LD between the genes in a separate bipolar data set from the GAIN project, demonstrating an example of gene-gene interaction that plays a role in the largely uncharted genetic landscape of bipolar disorder.