Displaying publications 1 - 20 of 30 in total

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  1. Patro G, Bhattamisra SK, Mohanty BK, Sahoo HB
    Pharmacognosy Res, 2016;8(1):22-8.
    PMID: 26941532 DOI: 10.4103/0974-8490.171099
    OBJECTIVE: Mimosa pudica Linn. (Mimosaceae) is traditionally used as a folk medicine to treat various ailments including convulsions, alopecia, diarrhea, dysentery, insomnia, tumor, wound healing, snake bite, etc., Here, the study was aimed to evaluate the antioxidant potential of M. pudica leaves extract against 2, 2-diphenyl-1-picrylhydrazyl (DPPH) (in vitro) and its modulatory effect on rat brain enzymes.
    MATERIALS AND METHODS: Total phenolic, flavonoid contents, and in vitro antioxidant potential against DPPH radical were evaluated from various extracts of M. pudica leaves. In addition, ethyl acetate extract of Mimosa pudica leaves (EAMP) in doses of 100, 200, and 400 mg/kg/day were administered orally for 7 consecutive days to albino rats and evaluated for the oxidative stress markers as thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) from rat brain homogenate.
    RESULTS: The ethyl acetate extract showed the highest total phenolic content and total flavonoid content among other extracts of M. pudica leaves. The percentage inhibition and IC50 value of all the extracts were followed dose-dependency and found significant (P < 0.01) as compared to standard (ascorbic acid). The oxidative stress markers as SOD, CAT, and GSH were increased significantly (P < 0.01) at 200 and 400 mg/kg of EAMP treated animals and decreased significantly the TBARS level at 400 mg/kg of EAMP as compared to control group.
    CONCLUSION: These results revealed that the ethyl acetate extract of M. pudica exhibits both in vitro antioxidant activity against DPPH and in vivo antioxidant activity by modulating brain enzymes in the rat. This could be further correlated with its potential to neuroprotective activity due to the presence of flavonoids and phenolic contents in the extract.
    SUMMARY: Total phenolic, flavonoid contents and in-vitro antioxidant potential were evaluated from various extracts of M. pudica leaves. Again, in-vivo antioxidant evaluation from brain homogenate on oxidative stress markers as TBARS, SOD, CAT and GSH from rat was investigated. Our findings revealed that M. pudica possesses both in-vitro and in-vivo antioxidant activity due to presence of phenolics and flavonoids.
    KEYWORDS: 2; 2-diphenyl-1-picrylhydrazyl; Brain homogenate; Flavonoids; Mimosa pudica; Oxidative stress
  2. Tan SY, Mei Wong JL, Sim YJ, Wong SS, Mohamed Elhassan SA, Tan SH, et al.
    Diabetes Metab Syndr, 2018 10 10;13(1):364-372.
    PMID: 30641727 DOI: 10.1016/j.dsx.2018.10.008
    Type 1 and type 2 diabetes mellitus is a serious and lifelong condition commonly characterised by abnormally elevated blood glucose levels due to a failure in insulin production or a decrease in insulin sensitivity and function. Over the years, prevalence of diabetes has increased globally and it is classified as one of the leading cause of high mortality and morbidity rate. Furthermore, diabetes confers a huge economic burden due to its management costs as well as its complications are skyrocketing. The conventional medications in diabetes treatment focusing on insulin secretion and insulin sensitisation cause unwanted side effects to patients and lead to incompliance as well as treatment failure. Besides insulin and oral hypoglycaemic agents, other treatments such as gene therapy and induced β-cells regeneration have not been widely introduced to manage diabetes. Therefore, this review aims to deliver an overview of the current conventional medications in diabetes, discovery of newer pharmacological drugs and gene therapy as a potential intervention of diabetes in the future.
  3. Elhassan SAM, Candasamy M, Chan EWL, Bhattamisra SK
    Diabetes Metab Syndr, 2018 Nov;12(6):1109-1116.
    PMID: 29843994 DOI: 10.1016/j.dsx.2018.05.020
    BACKGROUND: Autophagy is a process devoted to degrade and recycle cellular components inside mammalian cells through lysosomal system. It plays a main function in the pathophysiology of several diseases. In type 2 diabetes, works demonstrated the dual functions of autophagy in diabetes biology. Studies had approved the role of autophagy in promoting different routes for movement of integral membrane proteins to the plasma membrane. But its role in regulation of GLUT4 trafficking has not been widely observed. In normal conditions, insulin promotes GLUT4 translocation from intracellular membrane compartments to the plasma membrane, while in type 2 diabetes defects occur in this translocation.

    METHOD: Intriguing evidences discussed the contribution of different intracellular compartments in autophagy membrane formation. Furthermore, autophagy serves to mobilise membranes within cells, thereby promoting cytoplasmic components reorganisation. The intent of this review is to focus on the possibility of autophagy to act as a carrier for GLUT4 through regulating GLUT4 endocytosis, intracellular trafficking in different compartments, and translocation to cell membrane.

    RESULTS: The common themes of autophagy and GLUT4 have been highlighted. The review discussed the overlapping of endocytosis mechanism and intracellular compartments, and has shown that autophagy and GLUT4 utilise similar proteins (SNAREs) which are used for exocytosis. On top of that, PI3K and AMPK also control both autophagy and GLUT4.

    CONCLUSION: The control of GLUT4 trafficking through autophagy could be a promising field for treating type 2 diabetes.

  4. A/L B Vasanth Rao VR, Tan SH, Candasamy M, Bhattamisra SK
    Diabetes Metab Syndr, 2018 11 30;13(1):754-762.
    PMID: 30641802 DOI: 10.1016/j.dsx.2018.11.054
    Diabetic nephropathy (DN) is a major cause of end-stage renal disease and affects a large number of individuals with diabetes. However, the development of specific treatments for DN has not yet been identified. Hence, this review is concisely designed to understand the molecular pathways leading to DN in order to develop suitable therapeutic strategies. Extensive literature search have been carried in regard with the pathogenesis and pathophysiology of DN, drug targets and updates on clinical trials, the consequences associated with DN and the potential biomarkers for diagnosis and prediction of DN are discussed in this review. DN is characterised by microalbuminuria and macroalbuminuria, and morphological changes such as glomerular thickening, interstitial fibrosis, formation of nodular glomerulosclerosis and decreased endothelial cell fenestration. Besides, the involvement of renin-angiotensin-aldosterone system, inflammation and genetic factors are the key pathways in the progression of DN. In regard with drug development drugs targeted to epidermal growth factor, inflammatory cytokines, ACTH receptor and TGFβ1 receptors are in pipeline for clinical trials whereas, several drugs have also failed in phase III and phase IV of clinical trials due to lack of efficacy and severe adverse effect. The research on DN is limited with respect to its pathogenesis and drug development. Thus, a more detailed understanding of the pathogenesis of DN is very essential to progress in the drug development process.
  5. Pandey M, Choudhury H, Yeun OC, Yin HM, Lynn TW, Tine CLY, et al.
    Curr Pharm Biotechnol, 2018;19(4):276-292.
    PMID: 29874994 DOI: 10.2174/1389201019666180605125234
    BACKGROUND: Targeting chemotherapeutic agents to the tumor tissues and achieving accumulation with ideal release behavior for desired therapy requires an ideal treatment strategy to inhibit division of rapid growing cancerous cells and as an outcome improve patient's quality of life. However, majority of the available anticancer therapies are well known for their systemic toxicities and multidrug resistance.

    METHODS: Application of nanotechnology in medicine have perceived a great evolution during past few decades. Nanoemulsion, submicron sized thermodynamically stable distribution of two immiscible liquids, has gained extensive importance as a nanocarrier to improve chemotherapies seeking to overcome the limitations of drug solubilization, improving systemic delivery of the chemotherapeutics to the site of action to achieve a promising inhibitory in tumor growth profile with reduced systemic toxicity.

    RESULTS AND CONCLUSION: This review has focused on potential application of nanoemulsion in the translational research and its role in chemotherapy using oral, parenteral and transdermal route to enhance systemic availability of poorly soluble drug. In summary, nanoemulsion is a multifunctional nanocarrier capable of enhancing drug delivery potential of cytotoxic agents, thereby, can improve the outcomes of cancer treatment by increasing the life-span of the patient and quality of life, however, further clinical research and characterization of interactive reactions should need to be explored.

  6. Tzeyung AS, Md S, Bhattamisra SK, Madheswaran T, Alhakamy NA, Aldawsari HM, et al.
    Pharmaceutics, 2019 Jan 10;11(1).
    PMID: 30634665 DOI: 10.3390/pharmaceutics11010026
    The objective of the present study was to develop, optimize, and evaluate rotigotine-loaded chitosan nanoparticles (RNPs) for nose-to-brain delivery. Rotigotine-loaded chitosan nanoparticles were prepared by the ionic gelation method and optimized for various parameters such as the effect of chitosan, sodium tripolyphosphate, rotigotine concentration on particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency. The prepared nanoparticles were characterized using photon correlation spectroscopy, transmission electron microscopy, scanning electron microscopy, atomic force microscopy, fourier-transform infrared spectroscopy, and X-ray diffraction. The developed RNPs showed a small hydrodynamic particle size (75.37 ± 3.37 nm), small PDI (0.368 ± 0.02), satisfactory zeta potential (25.53 ± 0.45 mV), and very high entrapment efficiency (96.08 ± 0.01). The 24-h in vitro release and ex vivo nasal permeation of rotigotine from the nanoparticles were 49.45 ± 2.09% and 92.15 ± 4.74% while rotigotine solution showed corresponding values of 95.96 ± 1.79%and 58.22 ± 1.75%, respectively. The overall improvement ratio for flux and permeability coefficient were found to be 4.88 and 2.67 when compared with rotigotine solution. A histopathological study showed that the nanoparticulate formulation produced no toxicity or structural damage to nasal mucosa. Our results indicated that rotigotine-loaded chitosan nanoparticles provide an efficient carrier for nose-to-brain delivery.
  7. Lee ECS, Elhassan SAM, Lim GPL, Kok WH, Tan SW, Leong EN, et al.
    Biomed Pharmacother, 2019 Mar;111:198-208.
    PMID: 30583227 DOI: 10.1016/j.biopha.2018.12.052
    For many years, circular ribonucleic acids (circRNAs) have been counted as aberrant splicing by-products. Advanced bioinformatics analysis and deep sequencing techniques have allowed researchers to discover more interesting facts about circRNAs. Intriguing evidence has shed light on the functions of circRNAs in many tissues. Furthermore, emerging reports showed that circRNAs are found abundantly in saliva and blood samples, suggesting that circRNAs are potential clinical biomarkers for human embryonic development, diseases progression and prognosis, in addition to its role in organogenesis and pathogenesis. The implementation of circRNAs in human developmental stages and diseases would be a tremendous discovery in the science and medical field. Therefore, circRNAs have been studied for its biological function as well as its implication in various human diseases. The aim of this review is to highlight the importance of circRNAs in cardiac, respiratory, nervous, endocrine and digestive systems. In addition, the role and impact of circRNAs in, cardiogenesis, neurogenesis and cancer have been discussed.
  8. Vasanth Rao VRB, Candasamy M, Bhattamisra SK
    Diabetes Metab Syndr, 2019 05 07;13(3):2112-2120.
    PMID: 31235145 DOI: 10.1016/j.dsx.2019.05.004
    Obesity is a complex disorder that is linked to many coexisting disorders. Recent epidemiological data have suggested that the prevalence of obesity is at an all-time high, growing to be one of the world's biggest problems. There are several mechanisms on how individuals develop obesity which includes genetic and environmental factors. Not only does obesity contribute to other health issues but it also greatly affects the quality of life, physical ability, mental strength and imposes a huge burden in terms of healthcare costs. Along with that, obesity is associated with the risk of mortality and has been shown to reduce the median survival rate. Obesity is basically when the body is not able to balance energy intake and output. When energy intake exceeds energy expenditure, excess calories will be stored as fat leading to weight gain and eventually obesity. The therapeutic market for treating obesity is composed of many different interventions from lifestyle intervention, surgical procedures to pharmacotherapeutic approaches. All of these interventions have their respective benefits and disadvantages and are specifically prescribed to a patient based on the severity of their obesity as well as the existence of other health conditions. This review discusses the genetic and environmental causes of obesity along with the recent developments in anti-obesity therapies.
  9. Bhattamisra SK, Yean Yan VL, Koh Lee C, Hui Kuean C, Candasamy M, Liew YK, et al.
    J Tradit Complement Med, 2019 Jul;9(3):206-214.
    PMID: 31193983 DOI: 10.1016/j.jtcme.2018.05.001
    Geraniol, an active constituent of rose and palmarosa essential oils, possesses several pharmacological properties, including antioxidant, antibacterial and antiulcer activity. Geraniol was therefore investigated for its antiulcer and anti-Helicobacter pylori activity in rats. Ulcers were induced by injecting acetic acid into the sub-serosal layer of the stomach followed by orogastric inoculation of H. pylori for 7 days. Geraniol (15 and 30 mg/kg), vehicle and a standard drug combination (amoxicillin, 50 mg/kg; clarithromycin, 25 mg/kg and omeprazole, 20 mg/kg) were administered twice daily for 14 days. All the parameters were measured at the end of treatment. The ulcer index was significantly (P 
  10. Panda BP, Krishnamoorthy R, Bhattamisra SK, Shivashekaregowda NKH, Seng LB, Patnaik S
    Sci Rep, 2019 11 22;9(1):17331.
    PMID: 31758056 DOI: 10.1038/s41598-019-53996-4
    Drug delivery and therapeutic challenges of gliclazide, a BCS class II drug used in type 2 diabetes mellitus (T2DM) can be overcome by exploring smarter carriers of second-generation nanocrystals (SGNCs). A combined method of emulsion diffusion, high-pressure homogenization and solvent evaporation method were employed in the preparation of gliclazide loaded poly (D, L-lactide-co-glycolide) (PLGA) SGNCs. Taguchi experimental design was adopted in fabrication of Gliclazide SGNc using Gliclazide -PLGA ratio at 1:0.5, 1:0.75, 1:1 with stabilizer (Poloxamer-188, PEG 4000, HPMC E15 at 0.5, 0.75, 1% w/v). The formulated gliclazide of SGNCs were investigated for physicochemical properties, in vitro drug release, and in vivo performance studies using type-2 diabetes rat model. The formulation (SGNCF1) with Drug: PLGA 1: 0.5 ratio with 0.5% w/v Poloxamer-188 produced optimized gliclazide SGNCs. SGNCF1 showed spherical shape, small particle size (106.3 ± 2.69 nm), good zeta potential (-18.2 ± 1.30 mV), small PDI (0.222 ± 0.104) and high entrapment efficiency (86.27 ± 0.222%). The solubility, dissolution rate and bioavailability of gliclazide SGNCs were significantly improved compared to pure gliclazide. The findings emphasize gliclazide SGNCs produce faster release initially, followed by delayed release with improved bioavailability, facilitate efficient delivery of gliclazide in T2DM with better therapeutic effect.
  11. Gorain B, Choudhury H, Yee GS, Bhattamisra SK
    Curr Pharm Des, 2019;25(26):2828-2841.
    PMID: 31333092 DOI: 10.2174/1381612825666190716102037
    Adenosine is a ubiquitous signaling nucleoside molecule, released from different cells within the body to act on vasculature and immunoescape. The physiological action on the proliferation of tumour cell has been reported by the presence of high concentration of adenosine within the tumour microenvironment, which results in the progression of the tumour, even leading to metastases. The activity of adenosine exclusively depends upon the interaction with four subtypes of heterodimeric G-protein-coupled adenosine receptors (AR), A1, A2A, A2B, and A3-ARs on the cell surface. Research evidence supports that the activation of those receptors via specific agonist or antagonist can modulate the proliferation of tumour cells. The first category of AR, A1 is known to play an antitumour activity via tumour-associated microglial cells to prevent the development of glioblastomas. A2AAR are found in melanoma, lung, and breast cancer cells, where tumour proliferation is stimulated due to inhibition of the immune response via inhibition of natural killer cells cytotoxicity, T cell activity, and tumourspecific CD4+/CD8+ activity. Alternatively, A2BAR helps in the development of tumour upon activation via upregulation of angiogenin factor in the microvascular endothelial cells, inhibition of MAPK and ERK 1/2 phosphorylation activity. Lastly, A3AR is expressed in low levels in normal cells whereas the expression is upregulated in tumour cells, however, agonists to this receptor inhibit tumour proliferation through modulation of Wnt and NF-κB signaling pathways. Several researchers are in search for potential agents to modulate the overexpressed ARs to control cancer. Active components of A2AAR antagonists and A3AR agonists have already entered in Phase-I clinical research to prove their safety in human. This review focused on novel research targets towards the prevention of cancer progression through stimulation of the overexpressed ARs with the hope to protect lives and advance human health.
  12. Bhattamisra SK, Siang TC, Rong CY, Annan NC, Sean EHY, Xi LW, et al.
    Curr Diabetes Rev, 2019;15(5):382-394.
    PMID: 30648511 DOI: 10.2174/1573399815666190115145702
    BACKGROUND: The incidence of diabetes is increasing steeply; the number of diabetics has doubled over the past three decades. Surprisingly, the knowledge of type 3c diabetes mellitus (T3cDM) is still unclear to the researchers, scientist and medical practitioners, leading towards erroneous diagnosis, which is sometimes misdiagnosed as type 1 diabetes mellitus (T1DM), or more frequently type 2 diabetes mellitus (T2DM). This review is aimed to outline recent information on the etiology, pathophysiology, diagnostic procedures, and therapeutic management of T3cDM patients.

    METHODS: The literature related to T3cDM was thoroughly searched from the public domains and reviewed extensively to construct this article. Further, existing literature related to the other forms of diabetes is reviewed for projecting the differences among the different forms of diabetes. Detailed and updated information related to epidemiological evidence, risk factors, symptoms, diagnosis, pathogenesis and management is structured in this review.

    RESULTS: T3cDM is often misdiagnosed as T2DM due to the insufficient knowledge differentiating between T2DM and T3cDM. The pathogenesis of T3cDM is explained which is often linked to the history of chronic pancreatitis, pancreatic cancer. Inflammation, and fibrosis in pancreatic tissue lead to damage both endocrine and exocrine functions, thus leading to insulin/glucagon insufficiency and pancreatic enzyme deficiency.

    CONCLUSION: Future advancements should be accompanied by the establishment of a quick diagnostic tool through the understanding of potential biomarkers of the disease and newer treatments for better control of the diseased condition.

  13. Furman BL, Candasamy M, Bhattamisra SK, Veettil SK
    J Ethnopharmacol, 2020 Jan 30;247:112264.
    PMID: 31600561 DOI: 10.1016/j.jep.2019.112264
    ETHNOPHARMACOLOGICAL RELEVANCE: The global problem of diabetes, together with the limited access of large numbers of patients to conventional antidiabetic medicines, continues to drive the search for new agents. Ancient Asian systems such as traditional Chinese medicine, Japanese Kampo medicine, and Indian Ayurvedic medicine, as well as African traditional medicine and many others have identified numerous plants reported anecdotally to treat diabetes; there are probably more than 800 such plants for which there is scientific evidence for their activity, mostly from studies using various models of diabetes in experimental animals.

    AIM OF THE REVIEW: Rather than a comprehensive coverage of the literature, this article aims to identify discrepancies between findings in animal and human studies, and to highlight some of the problems in developing plant extract-based medicines that lower blood glucose in patients with diabetes, as well as to suggest potential ways forward.

    METHODS: In addition to searching the 2018 PubMed literature using the terms 'extract AND blood glucose, a search of the whole literature was conducted using the terms 'plant extracts' AND 'blood glucose' AND 'diabetes' AND 'double blind' with 'clinical trials' as a filter. A third search using PubMed and Medline was undertaken for systematic reviews and meta-analyses investigating the effects of plant extracts on blood glucose/glycosylated haemoglobin in patients with relevant metabolic pathologies.

    FINDINGS: Despite numerous animal studies demonstrating the effects of plant extracts on blood glucose, few randomised, double-blind, placebo-controlled trials have been conducted to confirm efficacy in treating humans with diabetes; there have been only a small number of systematic reviews with meta-analyses of clinical studies. Qualitative and quantitative discrepancies between animal and human clinical studies in some cases were marked; the factors contributing to this included variations in the products among different studies, the doses used, differences between animal models and the human disease, and the impact of concomitant therapy in patients, as well as differences in the duration of treatment, and the fact that treatment in animals may begin before or very soon after the induction of diabetes.

    CONCLUSION: The potential afforded by natural products has not yet been realised in the context of treating diabetes mellitus. A systematic, coordinated, international effort is required to achieve the goal of providing anti-diabetic treatments derived from medicinal plants.

  14. Bhattamisra SK, Shak AT, Xi LW, Safian NH, Choudhury H, Lim WM, et al.
    Int J Pharm, 2020 Apr 15;579:119148.
    PMID: 32084576 DOI: 10.1016/j.ijpharm.2020.119148
    Rotigotine, a non-ergoline dopamine agonist, has been shown to be highly effective for the treatment of Parkinson's disease (PD). However, despite its therapeutic potential, its' clinical applications were hindered due to low aqueous solubility, first-pass metabolism and low bioavailability. Therefore, we developed rotigotine-loaded chitosan nanoparticles (RNPs) for nose-to-brain delivery and evaluated its neuronal uptake, antioxidant and neuroprotective effects using cell-based studies. The pharmacological effects of nose-to-brain delivery of the RNPs were also evaluated in an animal model of PD. The average particle size, particle size distribution and entrapment efficiency of the RNPs were found to be satisfactory. Exposure of RNPs for 24 h did not show any cytotoxicity towards SH-SY5Y human neuroblastoma cells. Furthermore, the RNPs caused a decrease in alpha-synuclein (SNCA) and an increase in tyrosine hydroxylase (TH) expression in these cells, suggestion that the exposure alleviated some of the direct neurotoxic effects of 6-OHDA. Behavioral and biochemical testing of RNPs in haloperidol-induced PD rats showed a reversal of catalepsy, akinesia and restoration of swimming ability. A decrease in lactate dehydrogenase (LDH) and an increase in catalase activities were also observed in the brain tissues. The results from the animal model of PD show that intranasally-administered RNPs enhanced brain targeting efficiency and drug bioavailability. Thus, RNPs for nose-to-brain delivery has significant potential to be developed as a treatment approach for PD.
  15. Pandey M, Choudhury H, Fern JLC, Kee ATK, Kou J, Jing JLJ, et al.
    Drug Deliv Transl Res, 2020 08;10(4):986-1001.
    PMID: 32207070 DOI: 10.1007/s13346-020-00737-0
    The involvement of recent technologies, such as nanotechnology and three-dimensional printing (3DP), in drug delivery has become the utmost importance for effective and safe delivery of potent therapeutics, and thus, recent advancement for oral drug delivery through 3DP technology has been expanded. The use of computer-aided design (CAD) in 3DP technology allows the manufacturing of drug formulation with the desired release rate and pattern. Currently, the most applicable 3DP technologies in the oral drug delivery system are inkjet printing method, fused deposition method, nozzle-based extrusion system, and stereolithographic 3DP. In 2015, the first 3D-printed tablet was approved by the US Food and Drug Administration (FDA), and since then, it has opened up more opportunities in the discovery of formulation for the development of an oral drug delivery system. 3DP allows the production of an oral drug delivery device that enables tailor-made formulation with customizable size, shape, and release rate. Despite the advantages offered by 3DP technology in the drug delivery system, there are challenges in terms of drug stability, safety as well as applicability in the clinical sector. Nonetheless, 3DP has immense potential in the development of drug delivery devices for future personalized medicine. This article will give the recent advancement along with the challenges of 3DP techniques for the development of oral drug delivery. Graphical abstract.
  16. Yap KH, Yee GS, Candasamy M, Tan SC, Md S, Abdul Majeed AB, et al.
    Biomolecules, 2020 09 24;10(10).
    PMID: 32987623 DOI: 10.3390/biom10101360
    Catalpol was tested for various disorders including diabetes mellitus. Numerous molecular mechanisms have emerged supporting its biological effects but with little information towards its insulin sensitizing effect. In this study, we have investigated its effect on skeletal muscle mitochondrial respiration and insulin signaling pathway. Type-2 diabetes (T2DM) was induced in male C57BL/6 by a high fat diet (60% Kcal) and streptozotocin (50 mg/kg, i.p.). Diabetic mice were orally administered with catalpol (100 and 200 mg/kg), metformin (200 mg/kg), and saline for four weeks. Fasting blood glucose (FBG), HbA1c, plasma insulin, oral glucose tolerance test (OGTT), insulin tolerance test (ITT), oxygen consumption rate, gene (IRS-1, Akt, PI3k, AMPK, GLUT4, and PGC-1α) and protein (AMPK, GLUT4, and PPAR-γ) expression in muscle were measured. Catalpol (200 mg/kg) significantly (p < 0.05) reduced the FBG, HbA1C, HOMA_IR index, and AUC of OGTT whereas, improved the ITT slope. Gene (IRS-1, Akt, PI3k, GLUT4, AMPK, and PGC-1α) and protein (AMPK, p-AMPK, PPAR-γ and GLUT4) expressions, as well as augmented state-3 respiration, oxygen consumption rate, and citrate synthase activity in muscle was observed in catalpol treated mice. The antidiabetic activity of catalpol is credited with a marked improvement in insulin sensitivity and mitochondrial respiration through the insulin signaling pathway and AMPK/SIRT1/PGC-1α/PPAR-γ activation in the skeletal muscle of T2DM mice.
  17. Bhattamisra SK, Shin LY, Saad HIBM, Rao V, Candasamy M, Pandey M, et al.
    CNS Neurol Disord Drug Targets, 2020;19(3):174-183.
    PMID: 32418534 DOI: 10.2174/1871527319666200518102130
    The interlink between diabetes mellitus and neurodegenerative diseases such as Alzheimer's Disease (AD) and Parkinson's Disease (PD) has been identified by several researchers. Patients with Type-2 Diabetes Mellitus (T2DM) are found to be affected with cognitive impairments leading to learning and memory deficit, while patients with Type-1 Diabetes Mellitus (T1DM) showed less severe levels of these impairments in the brain. This review aimed to discuss the connection between insulin with the pathophysiology of neurodegenerative diseases (AD and PD) and the current therapeutic approached mediated through insulin for management of neurodegenerative diseases. An extensive literature search was conducted using keywords "insulin"; "insulin resistance"; "Alzheimer's disease"; "Parkinson's disease" in public domains of Google scholar, PubMed, and ScienceDirect. Selected articles were used to construct this review. Studies have shown that impaired insulin signaling contributes to the accumulation of amyloid-β, neurofibrillary tangles, tau proteins and α-synuclein in the brain. Whereas, improvement in insulin signaling slows down the progression of cognitive decline. Various therapeutic approaches for altering the insulin function in the brain have been researched. Besides intranasal insulin, other therapeutics like PPAR-γ agonists, neurotrophins, stem cell therapy and insulin-like growth factor-1 are under investigation. Research has shown that insulin insensitivity in T2DM leads to neurodegeneration through mechanisms involving a variety of extracellular, membrane receptor, and intracellular signaling pathway disruptions. Some therapeutics, such as intranasal administration of insulin and neuroactive substances have shown promise but face problems related to genetic background, accessibility to the brain, and invasiveness of the procedures.
  18. Pandey M, Choudhury H, Verma RK, Chawla V, Bhattamisra SK, Gorain B, et al.
    CNS Neurol Disord Drug Targets, 2020;19(9):648-662.
    PMID: 32819251 DOI: 10.2174/1871527319999200819095620
    Alzheimer Association Report (2019) stated that the 6th primary cause of death in the USA is Alzheimer's Disease (AD), which leads to behaviour and cognitive impairment. Nearly 5.8 million peoples of all ages in the USA have suffered from this disease, including 5.6 million elderly populations. The statistics of the progression of this disease is similar to the global scenario. Still, the treatment of AD is limited to a few conventional oral drugs, which often fail to deliver an adequate amount of the drug in the brain. The reduction in the therapeutic efficacy of an anti-AD drug is due to poor solubility, existence to the blood-brain barrier and low permeability. In this context, nasal drug delivery emerges as a promising route for the delivery of large and small molecular drugs for the treatment of AD. This promising pathway delivers the drug directly into the brain via an olfactory route, which leads to the low systemic side effect, enhanced bioavailability, and higher therapeutic efficacy. However, few setbacks, such as mucociliary clearance and poor drug mucosal permeation, limit its translation from the laboratory to the clinic. The above stated limitation could be overcome by the adaption of nanoparticle as a drug delivery carrier, which may lead to prolong delivery of drugs with better permeability and high efficacy. This review highlights the latest work on the development of promising Nanoparticles (NPs) via the intranasal route for the treatment of AD. Additionally, the current update in this article will draw the attention of the researcher working on these fields and facing challenges in practical applicability.
  19. Bhattamisra SK, Koh HM, Lim SY, Choudhury H, Pandey M
    Biomolecules, 2021 02 20;11(2).
    PMID: 33672590 DOI: 10.3390/biom11020323
    Catalpol isolated from Rehmannia glutinosa is a potent antioxidant and investigated against many disorders. This review appraises the key molecular pathways of catalpol against diabetes mellitus and its complications. Multiple search engines including Google Scholar, PubMed, and Science Direct were used to retrieve publications containing the keywords "Catalpol", "Type 1 diabetes mellitus", "Type 2 diabetes mellitus", and "diabetic complications". Catalpol promotes IRS-1/PI3K/AKT/GLUT2 activity and suppresses Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose 6-phosphatase (G6Pase) expression in the liver. Catalpol induces myogenesis by increasing MyoD/MyoG/MHC expression and improves mitochondria function through the AMPK/PGC-1α/PPAR-γ and TFAM signaling in skeletal muscles. Catalpol downregulates the pro-inflammatory markers and upregulates the anti-inflammatory markers in adipose tissues. Catalpol exerts antioxidant properties through increasing superoxide dismutase (sod), catalase (cat), and glutathione peroxidase (gsh-px) activity in the pancreas and liver. Catalpol has been shown to have anti-oxidative, anti-inflammatory, anti-apoptosis, and anti-fibrosis properties that in turn bring beneficial effects in diabetic complications. Its nephroprotective effect is related to the modulation of the AGE/RAGE/NF-κB and TGF-β/smad2/3 pathways. Catalpol produces a neuroprotective effect by increasing the expression of protein Kinase-C (PKC) and Cav-1. Furthermore, catalpol exhibits a cardioprotective effect through the apelin/APJ and ROS/NF-κB/Neat1 pathway. Catalpol stimulates proliferation and differentiation of osteoblast cells in high glucose condition. Lastly, catalpol shows its potential in preventing neurodegeneration in the retina with NF-κB downregulation. Overall, catalpol exhibits numerous beneficial effects on diabetes mellitus and diabetic complications.
  20. Pandey M, Choudhury H, Binti Abd Aziz A, Bhattamisra SK, Gorain B, Su JST, et al.
    Polymers (Basel), 2021 Apr 20;13(8).
    PMID: 33923900 DOI: 10.3390/polym13081340
    Eyesight is one of the most well-deserved blessings, amid all the five senses in the human body. It captures the raw signals from the outside world to create detailed visual images, granting the ability to witness and gain knowledge about the world. Eyes are exposed directly to the external environment; they are susceptible to the vicissitudes of diseases. The World Health Organization has predicted that the number of individuals affected by eye diseases will rise enormously in the next decades. However, the physical barriers of the eyes and the problems associated with conventional ocular formulations are significant challenges in ophthalmic drug development. This has generated the demand for a sustained ocular drug delivery system, which serves to deliver effective drug concentration at a reduced frequency for consistent therapeutic effect and better patient treatment adherence. Recent advancement in pharmaceutical dosage design has demonstrated that a stimuli-responsive in situ gel system exhibits the favorable characteristics for providing sustained ocular drug delivery and enhanced ocular bioavailability. Stimuli-responsive in situ gels undergo a phase transition (solution-gelation) in response to the ocular environmental temperature, pH, and ions. These stimuli transform the formulation into a gel at the cul de sac to overcome the shortcomings of conventional eye drops, such as rapid nasolacrimal drainage and short contact time with the ocular surface This review highlights the recent successful research outcomes of stimuli-responsive in situ gelling systems in treating in vivo models with glaucoma and various ocular infections. Additionally, it also presents the mechanism, recent development, and safety considerations of stimuli-sensitive in situ gel as the potential sustained ocular delivery system for treating common eye disorders.
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