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  1. Article ; Online: Abrus precatorius Leaf Extract Stimulates Insulin-mediated Muscle Glucose Uptake: In vitro Studies and Phytochemical Analysis.

    Lankatillake, Chintha / Huynh, Tien / Dias, Daniel A

    Planta medica

    2024  Volume 90, Issue 5, Page(s) 388–396

    Abstract: Diabetes mellitus, linked with insulin resistance and hyperglycaemia, is a leading cause of mortality. Glucose uptake through glucose transporter type 4, especially in skeletal muscle, is crucial for maintaining euglycaemia and is a key pathway targeted ... ...

    Abstract Diabetes mellitus, linked with insulin resistance and hyperglycaemia, is a leading cause of mortality. Glucose uptake through glucose transporter type 4, especially in skeletal muscle, is crucial for maintaining euglycaemia and is a key pathway targeted by antidiabetic medication.
    MeSH term(s) Animals ; Insulin/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Abrus/chemistry ; Insulin Receptor Substrate Proteins/metabolism ; Rosiglitazone/metabolism ; Rosiglitazone/pharmacology ; Glucose Transporter Type 4 ; Phosphatidylinositol 3-Kinases ; Muscle, Skeletal/metabolism ; Diabetes Mellitus/drug therapy ; Hypoglycemic Agents/pharmacology ; Insulin Resistance ; Plant Extracts/chemistry ; Hyperglycemia ; Glucose/pharmacology
    Chemical Substances Insulin ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Insulin Receptor Substrate Proteins ; Rosiglitazone (05V02F2KDG) ; Glucose Transporter Type 4 ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Hypoglycemic Agents ; Plant Extracts ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2024-03-15
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 123545-x
    ISSN 1439-0221 ; 0032-0943
    ISSN (online) 1439-0221
    ISSN 0032-0943
    DOI 10.1055/a-2281-0988
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Abrus precatorius Leaf Extract Stimulates Insulin-mediated Muscle Glucose Uptake: In vitro Studies and Phytochemical Analysis

    Lankatillake, Chintha / Huynh, Tien / Dias, Daniel A

    Planta Medica

    2024  Volume 90, Issue 05, Page(s) 388–396

    Abstract: Diabetes mellitus, linked with insulin resistance and hyperglycaemia, is a leading cause of mortality. Glucose uptake through glucose transporter type 4, especially in skeletal muscle, is crucial for maintaining euglycaemia and is a key pathway targeted ... ...

    Abstract Diabetes mellitus, linked with insulin resistance and hyperglycaemia, is a leading cause of mortality. Glucose uptake through glucose transporter type 4, especially in skeletal muscle, is crucial for maintaining euglycaemia and is a key pathway targeted by antidiabetic medication. Abrus precatorius is a medicinal plant with demonstrated antihyperglycaemic activity in animal models, but its mechanisms are unclear. This study evaluated the effect of a 50% ethanolic ( v/v A. precatorius leaf extract on (1) insulin-stimulated glucose uptake and (2) related gene expression in differentiated C2C12 myotubes using rosiglitazone as a positive control, and (3) generated a comprehensive phytochemical profile of A. precatorius leaf extract using liquid chromatography-high resolution mass spectrometry to elucidate its antidiabetic compounds. A. precatorius leaf extract significantly increased insulin-stimulated glucose uptake, and insulin receptor substrate 1 and Akt substrate of 160 kDa gene expression; however, it had no effect on glucose transporter type 4 gene expression. At 250 µg/mL A. precatorius leaf extract, the increase in glucose uptake was significantly higher than 1 µM rosiglitazone. Fifty-five phytochemicals (primarily polyphenols, triterpenoids, saponins, and alkaloids) were putatively identified, including 24 that have not previously been reported from A. precatorius leaves. Abrusin, precatorin I, glycyrrhizin, hemiphloin, isohemiphloin, hispidulin 4′- O β -D-glucopyranoside, homoplantaginin, and cirsimaritin were putatively identified as known major compounds previously reported from A. precatorius leaf extract. A. precatorius leaves contain antidiabetic phytochemicals and enhance insulin-stimulated glucose uptake in myotubes via the protein kinase B/phosphoinositide 3-kinase pathway by regulating insulin receptor substrate 1 and Akt substrate of 160 kDa gene expression. Therefore, A. precatorius leaves may improve skeletal muscle insulin sensitivity and hyperglycaemia. Additionally, it is a valuable source of bioactive phytochemicals with potential therapeutic use for diabetes.
    Keywords Fabaceae ; diabetes mellitus ; LC-HRMS ; hyperglycaemia ; GLUT4
    Language English
    Publishing date 2024-03-15
    Publisher Georg Thieme Verlag KG
    Publishing place Stuttgart ; New York
    Document type Article
    ZDB-ID 123545-x
    ISSN 1439-0221 ; 0032-0943
    ISSN (online) 1439-0221
    ISSN 0032-0943
    DOI 10.1055/a-2281-0988
    Database Thieme publisher's database

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  3. Article: Understanding glycaemic control and current approaches for screening antidiabetic natural products from evidence-based medicinal plants.

    Lankatillake, Chintha / Huynh, Tien / Dias, Daniel A

    Plant methods

    2019  Volume 15, Page(s) 105

    Abstract: Type 2 Diabetes Mellitus has reached epidemic proportions as a result of over-nutrition and increasingly sedentary lifestyles. Current therapies, although effective, are not without limitations. These limitations, the alarming increase in the prevalence ... ...

    Abstract Type 2 Diabetes Mellitus has reached epidemic proportions as a result of over-nutrition and increasingly sedentary lifestyles. Current therapies, although effective, are not without limitations. These limitations, the alarming increase in the prevalence of diabetes, and the soaring cost of managing diabetes and its complications underscores an urgent need for safer, more efficient and affordable alternative treatments. Over 1200 plant species are reported in ethnomedicine for treating diabetes and these represents an important and promising source for the identification of novel antidiabetic compounds. Evaluating medicinal plants for desirable bioactivity goes hand-in-hand with methods in analytical biochemistry for separating and identifying lead compounds. This review aims to provide a comprehensive summary of current methods used in antidiabetic plant research to form a useful resource for researchers beginning in the field. The review summarises the current understanding of blood glucose regulation and the general mechanisms of action of current antidiabetic medications, and combines knowledge on common experimental approaches for screening plant extracts for antidiabetic activity and currently available analytical methods and technologies for the separation and identification of bioactive natural products. Common in vivo animal models, in vitro models, in silico methods and biochemical assays used for testing the antidiabetic effects of plants are discussed with a particular emphasis on in vitro methods such as cell-based bioassays for screening insulin secretagogues and insulinomimetics. Enzyme inhibition assays and molecular docking are also highlighted. The role of metabolomics, metabolite profiling, and dereplication of data for the high-throughput discovery of novel antidiabetic agents is reviewed. Finally, this review also summarises sample preparation techniques such as liquid-liquid extraction, solid phase extraction, and supercritical fluid extraction, and the critical function of nuclear magnetic resonance and high resolution liquid chromatography-mass spectrometry for the dereplication, putative identification and structure elucidation of natural compounds from evidence-based medicinal plants.
    Language English
    Publishing date 2019-09-07
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2203723-8
    ISSN 1746-4811
    ISSN 1746-4811
    DOI 10.1186/s13007-019-0487-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Understanding glycaemic control and current approaches for screening antidiabetic natural products from evidence-based medicinal plants

    Lankatillake, Chintha / Huynh, Tien / Dias, Daniel A

    Plant methods. 2019 Dec., v. 15, no. 1

    2019  

    Abstract: Type 2 Diabetes Mellitus has reached epidemic proportions as a result of over-nutrition and increasingly sedentary lifestyles. Current therapies, although effective, are not without limitations. These limitations, the alarming increase in the prevalence ... ...

    Abstract Type 2 Diabetes Mellitus has reached epidemic proportions as a result of over-nutrition and increasingly sedentary lifestyles. Current therapies, although effective, are not without limitations. These limitations, the alarming increase in the prevalence of diabetes, and the soaring cost of managing diabetes and its complications underscores an urgent need for safer, more efficient and affordable alternative treatments. Over 1200 plant species are reported in ethnomedicine for treating diabetes and these represents an important and promising source for the identification of novel antidiabetic compounds. Evaluating medicinal plants for desirable bioactivity goes hand-in-hand with methods in analytical biochemistry for separating and identifying lead compounds. This review aims to provide a comprehensive summary of current methods used in antidiabetic plant research to form a useful resource for researchers beginning in the field. The review summarises the current understanding of blood glucose regulation and the general mechanisms of action of current antidiabetic medications, and combines knowledge on common experimental approaches for screening plant extracts for antidiabetic activity and currently available analytical methods and technologies for the separation and identification of bioactive natural products. Common in vivo animal models, in vitro models, in silico methods and biochemical assays used for testing the antidiabetic effects of plants are discussed with a particular emphasis on in vitro methods such as cell-based bioassays for screening insulin secretagogues and insulinomimetics. Enzyme inhibition assays and molecular docking are also highlighted. The role of metabolomics, metabolite profiling, and dereplication of data for the high-throughput discovery of novel antidiabetic agents is reviewed. Finally, this review also summarises sample preparation techniques such as liquid–liquid extraction, solid phase extraction, and supercritical fluid extraction, and the critical function of nuclear magnetic resonance and high resolution liquid chromatography–mass spectrometry for the dereplication, putative identification and structure elucidation of natural compounds from evidence-based medicinal plants.
    Keywords animal models ; bioassays ; blood glucose ; computer simulation ; enzyme inhibition ; glycemic control ; glycemic effect ; hypoglycemic agents ; in vitro studies ; insulin ; lifestyle ; liquid chromatography ; liquid-liquid extraction ; mass spectrometry ; mechanism of action ; medicinal plants ; metabolites ; metabolomics ; noninsulin-dependent diabetes mellitus ; nuclear magnetic resonance spectroscopy ; plant extracts ; screening ; solid phase extraction ; supercritical fluid extraction ; traditional medicine
    Language English
    Dates of publication 2019-12
    Size p. 105.
    Publishing place BioMed Central
    Document type Article
    Note Review
    ISSN 1746-4811
    DOI 10.1186/s13007-019-0487-8
    Database NAL-Catalogue (AGRICOLA)

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  5. Article: Screening natural product extracts for potential enzyme inhibitors: protocols, and the standardisation of the usage of blanks in α-amylase, α-glucosidase and lipase assays

    Lankatillake, Chintha / Luo, Shiqi / Flavel, Matthew / Lenon, George Binh / Gill, Harsharn / Huynh, Tien / Dias, Daniel Anthony

    Plant methods. 2021 Dec., v. 17, no. 1

    2021  

    Abstract: BACKGROUND: Enzyme assays have widespread applications in drug discovery from plants to natural products. The appropriate use of blanks in enzyme assays is important for assay baseline-correction, and the correction of false signals associated with ... ...

    Abstract BACKGROUND: Enzyme assays have widespread applications in drug discovery from plants to natural products. The appropriate use of blanks in enzyme assays is important for assay baseline-correction, and the correction of false signals associated with background matrix interferences. However, the blank-correction procedures reported in published literature are highly inconsistent. We investigated the influence of using different types of blanks on the final calculated activity/inhibition results for three enzymes of significance in diabetes and obesity; α-glucosidase, α-amylase, and lipase. This is the first study to examine how different blank-correcting methods affect enzyme assay results. Although assays targeting the above enzymes are common in the literature, there is a scarcity of detailed published protocols. Therefore, we have provided comprehensive, step-by-step protocols for α-glucosidase-, α-amylase- and lipase-inhibition assays that can be performed in 96-well format in a simple, fast, and resource-efficient manner with clear instructions for blank-correction and calculation of results. RESULTS: In the three assays analysed here, using only a buffer blank underestimated the enzyme inhibitory potential of the test sample. In the absorbance-based α-glucosidase assay, enzyme inhibition was underestimated when a sample blank was omitted for the coloured plant extracts. Similarly, in the fluorescence-based α-amylase and lipase assays, enzyme inhibition was underestimated when a substrate blank was omitted. For all three assays, method six [Raw Data - (Substrate + Sample Blank)] enabled the correction of interferences due to the buffer, sample, and substrate without double-blanking, and eliminated the need to add substrate to each sample blank. CONCLUSION: The choice of blanks and blank-correction methods contribute to the variability of assay results and the likelihood of underestimating the enzyme inhibitory potential of a test sample. This highlights the importance of standardising the use of blanks and the reporting of blank-correction procedures in published studies in order to ensure the accuracy and reproducibility of results, and avoid overlooked opportunities in drug discovery research due to inadvertent underestimation of enzyme inhibitory potential of test samples resulting from unsuitable blank-correction. Based on our assessments, we recommend method six [RD − (Su + SaB)] as a suitable method for blank-correction of raw data in enzyme assays.
    Keywords accuracy ; alpha-amylase ; assays ; carboxylic ester hydrolases ; color ; diabetes ; drugs ; enzyme inhibition ; enzyme inhibitors ; literature ; obesity ; plant extracts ; protocols ; reproducibility ; research ; sampling ; screening ; standardization ; variability
    Language English
    Dates of publication 2021-12
    Size p. 3.
    Publishing place BioMed Central
    Document type Article
    ISSN 1746-4811
    DOI 10.1186/s13007-020-00702-5
    Database NAL-Catalogue (AGRICOLA)

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  6. Article: Screening natural product extracts for potential enzyme inhibitors: protocols, and the standardisation of the usage of blanks in α-amylase, α-glucosidase and lipase assays.

    Lankatillake, Chintha / Luo, Shiqi / Flavel, Matthew / Lenon, George Binh / Gill, Harsharn / Huynh, Tien / Dias, Daniel Anthony

    Plant methods

    2021  Volume 17, Issue 1, Page(s) 3

    Abstract: Background: Enzyme assays have widespread applications in drug discovery from plants to natural products. The appropriate use of blanks in enzyme assays is important for assay baseline-correction, and the correction of false signals associated with ... ...

    Abstract Background: Enzyme assays have widespread applications in drug discovery from plants to natural products. The appropriate use of blanks in enzyme assays is important for assay baseline-correction, and the correction of false signals associated with background matrix interferences. However, the blank-correction procedures reported in published literature are highly inconsistent. We investigated the influence of using different types of blanks on the final calculated activity/inhibition results for three enzymes of significance in diabetes and obesity; α-glucosidase, α-amylase, and lipase. This is the first study to examine how different blank-correcting methods affect enzyme assay results. Although assays targeting the above enzymes are common in the literature, there is a scarcity of detailed published protocols. Therefore, we have provided comprehensive, step-by-step protocols for α-glucosidase-, α-amylase- and lipase-inhibition assays that can be performed in 96-well format in a simple, fast, and resource-efficient manner with clear instructions for blank-correction and calculation of results.
    Results: In the three assays analysed here, using only a buffer blank underestimated the enzyme inhibitory potential of the test sample. In the absorbance-based α-glucosidase assay, enzyme inhibition was underestimated when a sample blank was omitted for the coloured plant extracts. Similarly, in the fluorescence-based α-amylase and lipase assays, enzyme inhibition was underestimated when a substrate blank was omitted. For all three assays, method six [Raw Data - (Substrate + Sample Blank)] enabled the correction of interferences due to the buffer, sample, and substrate without double-blanking, and eliminated the need to add substrate to each sample blank.
    Conclusion: The choice of blanks and blank-correction methods contribute to the variability of assay results and the likelihood of underestimating the enzyme inhibitory potential of a test sample. This highlights the importance of standardising the use of blanks and the reporting of blank-correction procedures in published studies in order to ensure the accuracy and reproducibility of results, and avoid overlooked opportunities in drug discovery research due to inadvertent underestimation of enzyme inhibitory potential of test samples resulting from unsuitable blank-correction. Based on our assessments, we recommend method six [RD - (Su + SaB)] as a suitable method for blank-correction of raw data in enzyme assays.
    Language English
    Publishing date 2021-01-06
    Publishing country England
    Document type Journal Article
    ISSN 1746-4811
    ISSN 1746-4811
    DOI 10.1186/s13007-020-00702-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: A Pharmacological Perspective on Plant-derived Bioactive Molecules for Epilepsy.

    Sharifi-Rad, Javad / Quispe, Cristina / Herrera-Bravo, Jesús / Martorell, Miquel / Sharopov, Farukh / Tumer, Tugba Boyunegmez / Kurt, Begum / Lankatillake, Chintha / Docea, Anca Oana / Moreira, Ana Catarina / Dias, Daniel A / Mahomoodally, Mohamad Fawzi / Lobine, Devina / Cruz-Martins, Natália / Kumar, Manoj / Calina, Daniela

    Neurochemical research

    2021  Volume 46, Issue 9, Page(s) 2205–2225

    Abstract: Epilepsy is a related chronic neurological condition of a predisposition for recurrent epileptic seizures, with various manifestations and causes. Although there are antiepileptic drugs, complementary natural therapies are widely used. The purpose of ... ...

    Abstract Epilepsy is a related chronic neurological condition of a predisposition for recurrent epileptic seizures, with various manifestations and causes. Although there are antiepileptic drugs, complementary natural therapies are widely used. The purpose of this systematic review was to analyze the antiepileptic/anticonvulsant pharmacological properties of plant-food derived bioactive molecules. In this regard, a systematic review of the PubMed database was made based on the inclusion criteria. Natural compounds/herbs with scientifically proven antiepileptic properties were selected. Experimental pharmacological studies in vitro and in vivo have shown that flavonoids, alkaloids and terpenoids may have anticonvulsant mechanisms similar to the new generation antiepileptic drugs. The relationships of structure-anticonvulsant effect, pharmacological models, seizure-inducing factors and response, effective dose were also analyzed and discussed. The results of in vitro and in vivo pharmacological studies analyzed in this systematic review support the clinical importance of plant-food-derived bioactive molecules for the complementary treatment of epilepsy. Thus, are opened new perspectives to develop new natural anticonvulsant drugs.
    MeSH term(s) Alkaloids/pharmacology ; Alkaloids/therapeutic use ; Animals ; Anticonvulsants/pharmacology ; Anticonvulsants/therapeutic use ; Epilepsy/drug therapy ; Flavonoids/pharmacology ; Flavonoids/therapeutic use ; Humans ; Phytochemicals/pharmacology ; Phytochemicals/therapeutic use ; Plant Extracts/pharmacology ; Plant Extracts/therapeutic use ; Plants, Medicinal/chemistry ; Seizures/drug therapy ; Terpenes/pharmacology ; Terpenes/therapeutic use
    Chemical Substances Alkaloids ; Anticonvulsants ; Flavonoids ; Phytochemicals ; Plant Extracts ; Terpenes
    Language English
    Publishing date 2021-06-12
    Publishing country United States
    Document type Journal Article ; Systematic Review
    ZDB-ID 199335-5
    ISSN 1573-6903 ; 0364-3190
    ISSN (online) 1573-6903
    ISSN 0364-3190
    DOI 10.1007/s11064-021-03376-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Impact of Natural Compounds on Neurodegenerative Disorders: From Preclinical to Pharmacotherapeutics.

    Sharifi-Rad, Mehdi / Lankatillake, Chintha / Dias, Daniel A / Docea, Anca Oana / Mahomoodally, Mohamad Fawzi / Lobine, Devina / Chazot, Paul L / Kurt, Begum / Tumer, Tugba Boyunegmez / Moreira, Ana Catarina / Sharopov, Farukh / Martorell, Miquel / Martins, Natália / Cho, William C / Calina, Daniela / Sharifi-Rad, Javad

    Journal of clinical medicine

    2020  Volume 9, Issue 4

    Abstract: Among the major neurodegenerative disorders (NDDs), Alzheimer's disease (AD) and Parkinson's disease (PD), are a huge socioeconomic burden. Over many centuries, people have sought a cure for NDDs from the natural herbals. Many medicinal plants and their ... ...

    Abstract Among the major neurodegenerative disorders (NDDs), Alzheimer's disease (AD) and Parkinson's disease (PD), are a huge socioeconomic burden. Over many centuries, people have sought a cure for NDDs from the natural herbals. Many medicinal plants and their secondary metabolites are reported with the ability to alleviate the symptoms of NDDs. The major mechanisms identified, through which phytochemicals exert their neuroprotective effects and potential maintenance of neurological health in ageing, include antioxidant, anti-inflammatory, antithrombotic, antiapoptotic, acetylcholinesterase and monoamine oxidase inhibition and neurotrophic activities. This article review the mechanisms of action of some of the major herbal products with potential in the treatment of NDDs according to their molecular targets, as well as their regional sources (Asia, America and Africa). A number of studies demonstrated the beneficial properties of plant extracts or their bioactive compounds against NDDs. Herbal products may potentially offer new treatment options for patients with NDDs, which is a cheaper and culturally suitable alternative to conventional therapies for millions of people in the world with age-related NDDs.
    Language English
    Publishing date 2020-04-08
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2662592-1
    ISSN 2077-0383
    ISSN 2077-0383
    DOI 10.3390/jcm9041061
    Database MEDical Literature Analysis and Retrieval System OnLINE

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