Displaying publications 1 - 20 of 30 in total

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  1. Moorthy R, Bhattamisra SK, Pandey M, Mayuren J, Kow CS, Candasamy M
    Expert Rev Endocrinol Metab, 2024 Mar;19(2):141-154.
    PMID: 38347803 DOI: 10.1080/17446651.2024.2307526
    INTRODUCTION: Type 2 diabetes (T2D) presents significant global health and economic challenges, contributing to complications such as stroke, cardiovascular disease, kidney dysfunction, and cancer. The current review explores the crucial role of mitochondria, essential for fuel metabolism, in diabetes-related processes.

    AREAS COVERED: Mitochondrial deficits impact insulin-resistant skeletal muscles, adipose tissue, liver, and pancreatic β-cells, affecting glucose and lipid balance. Exercise emerges as a key factor in enhancing mitochondrial function, thereby reducing insulin resistance. Additionally, the therapeutic potential of mitochondrial uncoupling, which generates heat instead of ATP, is discussed. We explore the intricate link between mitochondrial function and diabetes, investigating genetic interventions to mitigate diabetes-related complications. We also cover the impact of insulin deficiency on mitochondrial function, the role of exercise in addressing mitochondrial defects in insulin resistance, and the potential of mitochondrial uncoupling. Furthermore, a comprehensive analysis of Mitochondrial Replacement Therapies (MRT) techniques is presented.

    EXPERT OPINION: MRTs hold promise in preventing the transmission of mitochondrial disease. However, addressing ethical, regulatory, and technical considerations is crucial. Integrating mitochondrial-based treatments requires a careful balance between innovation and safety. Ethical dimensions and regulatory aspects of MRT are examined, emphasizing collaborative efforts for the responsible advancement of human health.

  2. Choudhury H, Pandey M, Saravanan V, Mun ATY, Bhattamisra SK, Parikh A, et al.
    Biomater Adv, 2023 Oct;153:213556.
    PMID: 37478770 DOI: 10.1016/j.bioadv.2023.213556
    Cancer at the lower end of the digestive tract, colorectal cancer (CRC), starts with asymptomatic polyps, which can be diagnosed as cancer at a later stage. It is the fourth leading cause of malignancy-associated mortality worldwide. Despite progress in conventional treatment strategies, the possibility to overcome the mortality and morbidity issues with the enhancement of the lifespan of CRC patients is limited. With the advent of nanocarrier-based drug delivery systems, a promising revolution has been made in diagnosis, treatment, and theranostic purposes for cancer management. Herein, we reviewed the progress of miniaturized nanocarriers, such as liposomes, niosomes, solid lipid nanoparticles, micelles, and polymeric nanoparticles, employed in passive and active targeting and their role in theranostic applications in CRC. With this novel scope, the diagnosis and treatment of CRC have proceeded to the forefront of innovation, where specific characteristics of the nanocarriers, such as processability, flexibility in developing precise architecture, improved circulation, site-specific delivery, and rapid response, facilitate the management of cancer patients. Furthermore, surface-engineered technologies for the nanocarriers could involve receptor-mediated deliveries towards the overexpressed receptors on the CRC microenvironment. Moreover, the potential of clinical translation of these targeted miniaturized formulations as well as the possible limitations and barriers that could impact this translation into clinical practice were highlighted. The advancement of these newest developments in clinical research and progress into the commercialization stage gives hope for a better tomorrow.
  3. Lin HL, Mohamed Shukri FN, Yih ES, Sha GH, Jing GS, Jin GW, et al.
    Panminerva Med, 2023 Sep;65(3):362-375.
    PMID: 31663302 DOI: 10.23736/S0031-0808.19.03655-3
    Diabetes mellitus is a chronic metabolic condition characterized by an elevation of blood glucose levels, resulting from defects in insulin secretion, insulin action, or both. The prevalence of the disease has been rapidly rising all over the globe at an alarming rate. Despite advances in the management of diabetes mellitus, it remains a growing epidemic that has become a significant public health burden due to its high healthcare costs and its complications. There is no cure has yet been found for the disease, however, treatment modalities include insulin and antidiabetic agents along with lifestyle modifications are still the mainstay of therapy for diabetes mellitus. The treatment spectrum for the management of diabetes mellitus has rapidly developed in recent years, with new class of therapeutics and expanded indications. This article focused on the emerging therapeutic approaches other than the conventional pharmacological therapies, which include stem cell therapy, gene therapy, siRNA, nanotechnology and theranostics.
  4. Tan SC, Rajendran R, Bhattamisra SK, Krishnappa P, Davamani F, Chitra E, et al.
    J Pharm Pharmacol, 2023 Aug 01;75(8):1034-1045.
    PMID: 37402616 DOI: 10.1093/jpp/rgad063
    OBJECTIVES: Madecassoside (MAD) is a triterpenoid constituent of Centella asiatica (L.) Urb., an ethnomedical tropical plant, extracts of which were shown to reduce blood glucose in experimental diabetes. This study examines MAD for its anti-hyperglycaemic effects and tests the hypothesis that it reduces the blood glucose in experimentally induced diabetic rats by protecting the β-cells.

    METHODS: Diabetes was induced using streptozotocin (60 mg/kg, i.v.) followed by nicotinamide (210 mg/kg, intraperitoneal (i.p.)). MAD (50 mg/kg) was administered orally for 4 weeks, commencing 15 days after induction of diabetes; resveratrol (10 mg/kg) was used as a positive control. Fasting blood glucose, plasma insulin, HbA1c, liver and lipid parameters were measured, along with antioxidant enzymes and malondialdehyde as an index of lipid peroxidation; histological and immunohistochemical studies were also undertaken.

    KEY FINDINGS: MAD normalized the elevated fasting blood glucose levels. This was associated with increased plasma insulin concentrations. MAD alleviated oxidative stress by improving enzymatic antioxidants and reducing lipid peroxidation. Histopathological examination showed significant recovery of islet structural degeneration and an increased area of islets. Immunohistochemical staining showed increased insulin content in islets of MAD-treated rats.

    CONCLUSIONS: The results demonstrate an antidiabetic effect of MAD associated with preservation of β-cell structure and function.

  5. Elhassan SA, Wong YH, Bhattamisra SK, Candasamy M
    Minerva Med, 2022 Oct;113(5):896-897.
    PMID: 32683846 DOI: 10.23736/S0026-4806.20.06611-2
  6. Elhassan SAM, Candasamy M, Ching TS, Heng YK, Bhattamisra SK
    Nat Prod Res, 2021 Nov;35(22):4627-4631.
    PMID: 31797687 DOI: 10.1080/14786419.2019.1696794
    Currently, type 2 diabetes mellitus (T2D) has emerged as global burden disease. Herbal drugs with antidiabetic activities are attracting the attention. Madecassoside and catalpol are herbal compounds having strong antioxidant and glucose lowering activity. Madecassoside and catalpol were investigated for their effect on insulin sensitivity using pancreatic INS-1E cells. Cytotoxicity of these compounds was evaluated by MTT assay. Glucose-stimulated insulin secretion (GSIS) and expression of insulin signalling proteins were studied in presence of madecassoside and catalpol. Results revealed that madecassoside and catalpol enhanced the GSIS without cytotoxic effect. Madecassoside (30 µM) and catalpol (40 µM) increased the insulin secretion in response to high glucose (16.7 mM) stimulation. Subsequently, madecassoside and catalpol showed elevated expression of p-IRS-1, Akt, and p-Akt proteins. Madecassoside and catalpol after 24 h of incubation in pancreatic INS-1E cells with high glucose concentration (30 mM) ameliorated the insulin secretion.
  7. Wong YH, Wong SH, Wong XT, Yi Yap Q, Yip KY, Wong LZ, et al.
    Panminerva Med, 2021 Oct 05.
    PMID: 34609116 DOI: 10.23736/S0031-0808.21.04285-3
    According to the International Diabetes Federation, the number of adults (age of 20-79) being diagnosed with Diabetes Mellitus (DM) have increased from 285 million in year 2009 to 463 million in year 2019 which comprises of 95% Type 2 DM patient (T2DM). Research have claimed that genetic predisposition could be one of the factors causing T2DM complications. In addition, T2DMcomplications cause an incremental risk to mortality. Therefore, this article aims to discuss some complications of T2DM in and their genetic association. The complications that are discussed in this article are diabetic nephropathy, diabetes induced cardiovascular disease, diabetic neuropathy, Diabetic Foot Ulcer (DFU) and Alzheimer's disease. According to the information obtained, genes associated with diabetic nephropathy (DN) are gene GABRR1 and ELMO1 that cause injury to glomerular. Replication of genes FRMD3, CARS and MYO16/IRS2 shown to have link with DN. The increase of gene THBS2, NGAL, PIP, TRAF6 polymorphism, ICAM-1 encoded for rs5498 polymorphism and C667T increase susceptibility towards DN in T2DM patient. Genes associated with cardiovascular diseases are Adiponectin gene (ACRP30) and Apolipoprotein E (APOE) polymorphism gene with ξ2 allele. Haptoglobin (Hp) 1-1 genotype and Mitochondria Superoxide Dismutase 2 (SOD2) plays a role in cardiovascular events. As for genes related to diabetic neuropathy, Janus Kinase (JAK), mutation of SCN9A and TRPA1 gene and destruction of miRNA contribute to pathogenesis of diabetic neuropathy among T2DM patients. Expression of cytokine IL-6, IL-10, miR-146a are found to cause diabetic neuropathy. Besides, A1a16Va1 gene polymorphism, an oxidative stress influence was found as one of the gene factors. Diabetic retinopathy (DR) is believed to have association with Monocyte Chemoattractant Protein-1 (MCP-1) and Insulin-like Growth Factor 1 (IGF1). Over-expression of gene ENPP1, IL-6 pro-inflammatory cytokine, ARHGAP22's protein rs3844492 polymorphism and TLR4 heterozygous genotype are contributing to significant pathophysiological process causing DR, while research found increases level of UCP1 gene protects retina cells from oxidative stress. Diabetic Foot Ulcer (DFU) is manifested by slowing in reepithelialisation of keratinocyte, persistence wound inflammation and healing impairment. Reepithelialisation disturbance was caused by E2F3 gene, reduction of Tacl gene encoded substance P causing persistence inflammation while expression of MMp-9 polymorphism contributes to healing impairment. A decrease in HIF-1a gene expression leads to increased risk of pathogenesis, while downregulation of TLR2 increases severity of wound in DFU patients. SNPs alleles has been shown to have significant association between the genetic dispositions of T2DM and Alzheimer's disease (AD). The progression of AD can be due to the change in DNA methylation of CLOCK gene, followed with worsening of AD by APOE4 gene due to dyslipidaemia condition in T2DM patients. Insulin resistance is also a factor that contributes to pathogenesis of AD.
  8. Wong YL, Pandey M, Choudhury H, Lim WM, Bhattamisra SK, Gorain B
    Polymers (Basel), 2021 Aug 18;13(16).
    PMID: 34451309 DOI: 10.3390/polym13162770
    Hidradenitis suppurativa (HS) has been considered an orphan disease with limited treatments available. The available topical treatment for this condition is clindamycin lotion; however, short retention and frequent application are the main setbacks. Thus, the present study aimed to attain an optimized antibacterial in situ spray formulation for the hidradenitis suppurativa skin condition, which gels once in contact with the skin surface at around 37 °C and possesses bioadhesion as well as sustained-release properties of the incorporated drug. Different concentrations of thermo-reversible gelling polymer, Pluronic F-127, were investigated along with the selected bioadhesive polymers, HPMC and SA. The optimized formulation F3 consisting of 18% Pluronic F-127 with 0.2% HPMC and 0.2% SA was characterized based on various physicochemical properties. The gelation temperature of F3 was found to be 29.0 ± 0.50 °C with a gelation time of 1.35 ± 0.40 min and a pH of 5.8. F3 had the viscosity of 178.50 ± 5.50 cP at 25 °C and 7800 ± 200 cP at 37 °C as the gel set. The optimized formulation was found to be bioadhesive and cytocompatible. Cumulative drug release was 65.05% within the time-frame of 8 h; the release pattern of the drug followed zero-order kinetics with the Higuchi release mechanism. The average zone of inhibition was found to be 43.44 ± 1.34 mm. The properties of F3 formulation reflect to improve residence time at the site of application and can enhance sustained drug release. Therefore, it could be concluded that optimized formulation has better retention and enhanced antimicrobial activity for superior efficacy against HS.
  9. Verma RK, Pandey M, Chawla P, Choudhury H, Mayuren J, Bhattamisra SK, et al.
    PMID: 33982657 DOI: 10.2174/1871527320666210512014505
    BACKGROUND: The complication of Alzheimer's disease (AD) has made the development of its therapeutic a challenging task. Even after decades of research, we have achieved no more than a few years of symptomatic relief. The inability to diagnose the disease early is the foremost hurdle behind its treatment. Several studies have aimed to identify potential biomarkers that can be detected in body fluids (CSF, blood, urine, etc) or assessed by neuroimaging (i.e., PET and MRI). However, the clinical implementation of these biomarkers is incomplete as they cannot be validated.

    METHOD: To overcome the limitation, the use of artificial intelligence along with technical tools has been extensively investigated for AD diagnosis. For developing a promising artificial intelligence strategy that can diagnose AD early, it is critical to supervise neuropsychological outcomes and imaging-based readouts with a proper clinical review.

    CONCLUSION: Profound knowledge, a large data pool, and detailed investigations are required for the successful implementation of this tool. This review will enlighten various aspects of early diagnosis of AD using artificial intelligence.

  10. Pandey M, Choudhury H, D/O Segar Singh SK, Chetty Annan N, Bhattamisra SK, Gorain B, et al.
    Molecules, 2021 May 05;26(9).
    PMID: 34062995 DOI: 10.3390/molecules26092704
    A single ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that causes inflammation of the colonic mucosa at the distal colon and rectum. The mainstay therapy involves anti-inflammatory immunosuppression based on the disease location and severity. The disadvantages of using systemic corticosteroids for UC treatment is the amplified risk of malignancies and infections. Therefore, topical treatments are safer as they have fewer systemic side effects due to less systemic exposure. In this context, pH sensitive and enzymatically triggered hydrogel of pectin (PC) and polyacrylamide (PAM) has been developed to facilitate colon-targeted delivery of budesonide (BUD) for the treatment of UC. The hydrogels were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), swelling ratio, and drug release. FT-IR spectroscopy confirmed the grafting as well loading of BUD in hydrogel. XRD showed the amorphous nature of hydrogel and increment in crystallinity after drug loading. On the other hand, SEM showed that the hydrogels exhibited a highly porous morphology, which is suitable for drug loading and also demonstrated a pH-responsive swelling behaviour, with decreased swelling in acidic media. The in-vitro release of BUD from the hydrogel exhibited a sustained release behaviour with non-ficken diffusion mechanism. The model that fitted best for BUD released was the Higuchi kinetic model. It was concluded that enzyme/pH dual-sensitive hydrogels are an effective colon-targeted delivery system for UC.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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.

  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. 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.
  20. 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 
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