Srinivasan Ramamurthy

Molecular understanding of Epigallocatechin gallate (EGCG) in cardiovascular and metabolic diseases

ETHNOPHARMACOLOGICAL RELEVANCE The compound epigallocatechin-3-gallate (EGCG), the major polyphenolic compound present in green tea [Camellia sinensis (Theaceae], has shown numerous cardiovascular health promoting activity through modulating various pathways. However, molecular understanding of the cardiovascular protective role of EGCG has not been reported. AIM OF THE REVIEW This review aims to compile the preclinical and clinical studies that had been done on EGCG to investigate its protective effect on cardiovascular and metabolic diseases in order to provide a systematic guidance for future research. MATERIALS AND METHODS Research papers related to EGCG were obtained from the major scientific databases, for example, Science direct, PubMed, NCBI, Springer and Google scholar, from 1995 to 2017. RESULTS EGCG was found to exhibit a wide range of therapeutic properties including anti-atherosclerosis, anti-cardiac hypertrophy, anti-myocardial infarction, anti-diabetes, anti-inflammatory and antioxidant. These therapeutic effects are mainly associated with the inhibition of LDL cholesterol (anti-atherosclerosis), inhibition of NF-κB (anti-cardiac hypertrophy), inhibition of MPO activity (anti-myocardial infarction), reduction in plasma glucose and glycated haemoglobin level (anti-diabetes), reduction of inflammatory markers (anti-inflammatory) and the inhibition of ROS generation (antioxidant). CONCLUSION EGCG shows different biological activities and in this review, a compilation of how this bioactive molecule plays its role in treating cardiovascular and metabolic diseases was discussed.

Molecular understanding of the protective role of natural products on isoproterenol-induced myocardial infarction: A review

Modern medicine has been used to treat myocardial infarction, a subset of cardiovascular diseases, and have been relatively effective but not without adverse effects. Consequently, this issue has stimulated interest in the use of natural products, which may be equally effective and better tolerated. Many studies have investigated the cardioprotective effect of natural products, such as plant-derived phytochemicals, against isoproterenol (ISO)-induced myocardial damage; these have produced promising results on the basis of their antioxidant, anti-atherosclerotic, anti-apoptotic and anti-inflammatory activities. This review briefly introduces the pathophysiology of myocardial infarction (MI) and then addresses the progress of natural product research towards its treatment. We highlight the promising applications and mechanisms of action of plant extracts, phytochemicals and polyherbal formulations towards the treatment of ISO-induced myocardial damage. Most of the products displayed elevated antioxidant levels with decreased oxidative stress and lipid peroxidation, along with restoration of ionic balance and lowered expression of myocardial injury markers, pro-inflammatory cytokines, and apoptotic parameters. Likewise, lipid profiles were positively altered and histopathological improvements could be seen from, for example, the better membrane integrity, decreased necrosis, edema, infarct size, and leukocyte infiltration. This review highlights promising results towards the amelioration of ISO-induced myocardial damage, which suggest the direction for future research on natural products that could be used to treat MI.

Production, Characterization and Evaluation of Kaempferol Nanosuspension for Improving Oral Bioavailability

CONTEXT Kaempferol has a large particle size and poor water solubility, leading to poor oral bioavailability. The present work aimed to develop a kaempferol nanosuspension (KNS) to improve pharmacokinetics and absolute bioavailability. METHODS A nanosuspension was prepared using high pressure homogenization (HPH) techniques. The physico-chemical properties of the kaempferol nanosuspension (KNS) were characterized using photon correlation spectroscopy (PCS), transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FTIR) and x-ray diffractometry (XRD). A reversephase high performance liquid chromatography (RP-HPLC) method for the analysis of the drug in rat plasma was developed and validated as per ICH guidelines. In vivo pharmacokinetic parameters of oral pure kaempferol solution, oral kaempferol nanosuspension and intravenous pure kaempferol were assessed in rats. RESULTS AND DISCUSSION The kaempferol nanosuspension had a greatly reduced particle size (426.3 ± 5.8 nm), compared to that of pure kaempferol (1737 ± 129 nm). The nanosuspension was stable under refrigerated conditions. No changes in physico-chemical characteristics were observed. In comparison to pure kaempferol, kaempferol nanosuspension exhibited a significantly (P<0.05) increased in Cmax and AUC(0-∞) following oral administration and a significant improvement in absolute bioavailability (38.17%) compared with 13.03% for pure kaempferol. CONCLUSION These results demonstrate enhanced oral bioavailability of kaempferol when formulated as a nanosuspension.

Phytochemical, Pharmacological and Toxicological Properties ofFicusdeltoidea:A Review of a Recent Research

Ficusdeltoidea(Mas Cotek) is one of the commonly usedmedicinal plants in Malaysia and it belongs to the family of Moraceae. I t is a shrub that reaches a height of six feet, used as anornamental plant in the tropics or in the home and conservatories.Thisplantis native to Southeast Asia and Philiphines.It has beenused to relieve headache, fever, pneumonia, heart problems, migraines, skin diseases,diarrhea, and toothache. It is also used as an aphrodisiac tonic. Decoction of the whole plant has been used as herbal drink by women after birth to strengthen the uterus and vaginal muscles. It also improves blood circulation and regains body strength as well as treats disorders related to menstrual cycle. This plant is basically a Malay traditional medicine which was very popular ever since it has good medicinal properties.Based on ethnobotanical approaches, F. deltoideahas been claimed to possess antidiabetic, antiulcerogenic, antioxidant, anti -melanogenic, anti-inflammatory,analgesic, antihypertensive properties . Recently, there were a lot of investigations that was carried out to isolate some of the chemical constituents in

Early effect of hydroxychloroquine therapy: relationship between cumulative dose and retinal thickness

Abstract Background: Hydroxychloroquine (HCQ) is widely used for long-term treatment of autoimmune diseases such as rheumatoid arthritis. However, its long-term use is known to be associated with visual changes due to retinal damage. Retinal damage associated with long-term HCQ therapy is preventable if the drug is discontinued early when the patients are still asymptomatic. In view of contrasting reports from previous studies, we investigated the association of prolonged HCQ therapy with retinal thickness in macular area. Methods: This study included 48 patients on long-term HCQ therapy and 38 healthy controls. All subjects underwent examination for corrected visual acuity, fundus photography, visual fields and SD-OCT for retinal thickness. Results: Visual acuity, visual fields, fundus photography and SD-OCT did not reveal changes consistent with diagnosis of established HCQ retinopathy in any of the subjects from HCQ group. Retinal thickness in central, parafoveal and perifoveal areas did not show significant differences between HCQ and control groups. However, we observed negative correlation between cumulative dose and retinal thickness in the parafoveal (p = 0.003) and perifoveal areas (p = 0.019) but not in the central area. Conclusions: Correlation of cumulative dose with retinal thickness in parafoveal and perifoveal areas and not the central area is in accordance with the late appearance of HCQ-induced bulls eye retinopathy. Hence screening of asymptomatic patients using OCT seems to be of great importance for early detection of retinal changes.

Current attempts to implement microRNA-based diagnostics and therapy in cardiovascular and metabolic disease: a promising future

MicroRNAs (miRNAs) are small, noncoding RNAs regulating gene expression at the post-translational level. miRNA-based therapeutic agents are important because of the functionality of miRNAs in regulating lipid and glucose metabolism and their role in the pathogenesis of metabolic disorders such as diabetes and obesity, where dysregulation leads to disease; they are also important in angiogenesis. miRNAs additionally serve as biomarkers in the diagnosis, prognosis and risk assessment of disease and in monitoring the response to treatment. Here, we provide a brief overview of progress in miRNA-based therapeutics in the preclinical and clinical setting and highlight the novel outcomes and opportunities in the diagnosis and treatment of metabolic conditions. In addition, we present the role of miRNAs in stem cell therapy which could have great potential in regenerative medicine.

A systematic review of the protective role of swertiamarin in cardiac and metabolic diseases

BACKGROUND Swertiamarin, is a secoiridoid glycoside found in genera of Enicostemma Species (Enicostemma littorale and Enicostemma axillare) belonging to the family of gentianaceae, which has been reported to cure many diseases such as diabetes, hypertension, atherosclerosis, arthritis, malaria and abdominal ulcers. However, to the best of our knowledge, till date systematic studies to understand the molecular basis of cardiac and metabolic disease preventing properties of swertiamarin has not been reported. AIM OF THE REVIEW The present review aims to compile an up-to-date information on the progress made in the protective role of swertiamarin in cardiac and metabolic diseases with the objective of providing a guide for future research on this bioactive molecule. MATERIALS AND METHODS Information on the swertiamarin was collected from major scientific databases (Pubmed, Springer, google scholar, and Web of Science) for publication between1974-2016. In this review, the protective role of swertiamarin on cardiac and metabolic diseases was discussed. RESULTS Swertiamarin reported to exhibit a wide range of biological activities such as anti-atherosclerotic, antidiabetic, anti-inflammatory and antioxidant effects. These activities were mainly due to its effect on various signaling pathways associated with cardiac remodeling events such as inhibition of NF-kB expression, LDL oxidation, apoptosis, inflammatory and lipid peroxidation markers and stimulation of antioxidant enzymes. CONCLUSION Sweriamarin exhibit a wide range of biological activities. This review presents evidence supporting the point of view that swertiamarin should be considered a potential therapeutic agent against cardiac and metabolic diseases, giving rise to novel applications in their prevention and treatment.

Effects of nanosuspension and inclusion complex techniques on the in vitro protease inhibitory activity of naproxen

Mandevilla coccinea (Hook. et Arn.) Woodson, Apocynaceae is a herb native to South America employed in folk medicine as an analgesic, anti-inflammatory and to inhibit snake venom effects. This work was carried out to study the morpho-anatomical characters of the leaf and stem in order to advance knowledge on this medicinal plant and on pharmacognostic quality control. The plant material was fixed and prepared according to light and scanning electron microtechniques. Its leaves are simple, alternate and ovate-obovate. The epidermis is uniseriate and coated with a thick and striate cuticle. The stomata are paracytic and occur on both foliar surfaces. The dorsiventral-like mesophyll has a sub-epidermal parenchymatic layer containing phenolic substances and is traversed by minor collateral vascular bundles. The midrib is biconvex and the petiole is concave-convex, both presenting bicollateral vascular bundles in an open arc. The stem is circular in transverse section and the epidermis remains in incipient secondary growth. A sub-epidermal parenchymatic layer containing phenolic substances, a discontinuous sclerenchymatic sheath of non-lignified fibres and cylinders of external phloem, xylem and internal phloem occur. Numerous branched laticifers and idioblasts with phenolic substances are present in the leaf and stem.