|
1
|
Varadharajan V, Balu AK, Sinclair BJ, Perinbarajan GK, Jenifer A D, Ganesan Sudha H, Ramaswamy A, Venkidasamy B, Thiruvengadam M. Comprehensive analysis of Syzygium cumini L. pomace extract as an α-amylase inhibitor: In vitro inhibition, kinetics, and computational studies. Bioorg Chem 2025; 161:108498. [PMID: 40339502 DOI: 10.1016/j.bioorg.2025.108498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 04/12/2025] [Accepted: 04/19/2025] [Indexed: 05/10/2025]
Abstract
Type 2 diabetes mellitus (T2DM) is a widespread metabolic disorder characterized by impaired regulation of blood glucose levels. Jamun (Syzygium cumini L.) fruits and seeds have been traditionally used in Ayurveda to manage diabetes. While fruit and seed extracts have been extensively studied for their anti-α-amylase properties, pomace, a byproduct of juice extraction, remains under explored. This study investigated the α-amylase inhibitory potential of jamun pomace (JP) extract by using in vitro and in silico methods. Enzyme inhibition assays revealed an half-maximal inhibitory concentration (IC₅₀) value of 85.68 ± 5.22 μg/mL for the JP extract, comparable to acarbose (64.28 ± 7.15 μg/mL). The extract exhibited mixed-mode inhibition, whereas acarbose showed competitive mode inhibition. At 10 μg/mL, the Vmax of JP extract was half that of acarbose, demonstrating significant inhibition. GC-MS analysis identified 11 volatile compounds (R1-R11) in the JP extract. Density Functional Theory (DFT) and ADMET analyses confirmed the chemical reactivity of the volatiles, drug-like properties, and low toxicity. Molecular docking revealed a high binding score for R11 (-8.0 kcal/mol), similar to acarbose (-8.2 kcal/mol). Molecular dynamics simulations further demonstrated the stability of α-amylase complexes with R11, R3, and R8, with R11 showing the lowest binding energy (-28.75 ± 6.25 kcal/mol). These findings suggest that R11 and JP extracts hold promise as anti-diabetic agents. Utilizing JP extract as a nutraceutical offers the dual benefit of diabetes management and sustainable waste valorization in jamun juice production.
Collapse
Affiliation(s)
| | - Ashwath Kumar Balu
- Department of Biotechnology, PSG College of Technology, Peelamedu, Coimbatore, India; Department of Biotechnology, Indian Institute of Technology, Hyderabad, India
| | - Bruce Joshua Sinclair
- Departmet of Electronics and Communication Engineering, PSG College of Technology, Coimbatore, India
| | - Gopi Krishna Perinbarajan
- Departmet of Electronics and Communication Engineering, PSG College of Technology, Coimbatore, India
| | - Dharshini Jenifer A
- Department of Chemical Engineering, National Institute of Technology, Surathkal, Karnataka, India
| | | | - Arulvel Ramaswamy
- Department of Biotechnology, K S Rangasamy College of Technology, Tiruchengode, Namakkal District, Tamil Nadu 637 215, India
| | - Baskar Venkidasamy
- Centre for Biosciences and Biotechnology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai 600077, Tamil Nadu, India.
| | - Muthu Thiruvengadam
- Department of Applied Bioscience, College of Life and Environmental Science, Konkuk University, Seoul, Republic of Korea.
| |
Collapse
|
|
2
|
Weng J, Chen Y, Zeng Y, Jin W, Ji Y, Zhang W, Wang S, Li H, Yi M, Niu X, Deng X, Huang J, Su X, Chen L. A novel hydrogel loaded with plant exosomes and stem cell exosomes as a new strategy for treating diabetic wounds. Mater Today Bio 2025; 32:101810. [PMID: 40391025 PMCID: PMC12088786 DOI: 10.1016/j.mtbio.2025.101810] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2025] [Revised: 04/08/2025] [Accepted: 04/26/2025] [Indexed: 05/21/2025] Open
Abstract
Diabetic wound healing is constrained by various factors, including chronic inflammation, sustained oxidative stress, impaired angiogenesis, and abnormal wound microenvironments. Exosomes derived from mesenchymal stem cells (MSC-exo) contain a wealth of bioactive substances that play a positive role in promoting diabetic wound healing. Plant-derived exosomes, as a novel therapeutic approach, are continuously being explored. Momordica charantia (MC) has been shown to possess blood glucose-lowering effects, and its exosomes are of significant relevance for treating diabetic wounds. However, direct application of exosomes to wounds faces challenges such as poor stability and short retention time, limiting their therapeutic effectiveness and clinical applicability. Encapsulating exosomes in hydrogels is an effective strategy to preserve their bioactivity. In this study, we fabricated a hydrogel loaded with MSC-exo and MC exosomes (MC-exo) by photopolymerization of methacrylated gelatin (GelMA) and dopamine (MEMC-Gel). The resulting MEMC-Gel exhibited favorable mechanical properties, adhesion, degradability, absorbency, and biocompatibility. In vitro, MEMC-Gel demonstrated the ability to resist inflammation, counter oxidative stress, promote fibroblast migration, support endothelial cell angiogenesis, and regulate macrophage polarization. In a diabetic mouse wound model, MEMC-Gel accelerated wound healing by inhibiting inflammation and oxidative stress, modulating macrophage immune responses and hyperglycemia within the microenvironment, promoting angiogenesis, and enhancing epithelialization. In conclusion, MEMC-Gel is an outstanding hydrogel dressing that synergistically promotes repair by loading MSC-exo and MC-exo, significantly accelerating diabetic wound healing through multiple mechanisms. This multifunctional hydrogel, based on exosomes from two different sources, provides an innovative therapeutic strategy for diabetic wound repair with broad clinical application potential.
Collapse
Affiliation(s)
- Jialu Weng
- Department of Anesthesia, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China
| | - Yizhang Chen
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325000, PR China
| | - Yuhan Zeng
- Department of Anesthesia, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325000, PR China
| | - Wenzhang Jin
- Department of Anesthesia, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China
- Department of Colorectal Surgery, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310000, PR China
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China
| | - Ying Ji
- Department of Nephrology, The First Affiliated Hospital of Ningbo University, Ningbo, 315010, PR China
| | - Wa Zhang
- Department of Colorectal Surgery, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310000, PR China
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China
| | - Shunfu Wang
- Department of Anesthesia, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China
| | - Haobing Li
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China
| | - Meilin Yi
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China
| | - Xiaoying Niu
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China
| | - Xuchen Deng
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China
| | - Jiancheng Huang
- Department of Nephrology, The First Affiliated Hospital of Ningbo University, Ningbo, 315010, PR China
| | - Xiang Su
- Department of Anesthesia, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China
- Department of Vascular Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China
| | - Lulu Chen
- Department of Anesthesia, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China
- Department of Vascular Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, PR China
| |
Collapse
|
|
3
|
Derosa G, D’Angelo A, Angelini F, Belli L, Cicero AFG, Da Ros R, De Pergola G, Gaudio GV, Lupi A, Sartore G, Vignati FA, Maffioli P. Nutraceuticals and Supplements in Management of Prediabetes and Diabetes. Nutrients 2024; 17:14. [PMID: 39796448 PMCID: PMC11723399 DOI: 10.3390/nu17010014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Revised: 10/06/2024] [Accepted: 12/10/2024] [Indexed: 01/13/2025] Open
Abstract
Dysglycemia is a condition preceding diabetes mellitus. The two situations inherent in this condition are called impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). If one of these situations is found in the patient, after the advice of an appropriate diet and physical activity, the addition of nutraceuticals or supplements can be considered, which can stop or delay the progression to diabetes mellitus over time. The purpose was to compile a systematic review about the use of nutraceuticals for treating diabetes and prediabetes and to offer a valuable resource for colleagues working on this crucial subject, thereby improving patient health. The added value of the paper compared to other reviews is that it was written by experts appointed by five different scientific societies dealing with diabetes, nutrition, and complications.
Collapse
Affiliation(s)
- Giuseppe Derosa
- SINut—Società Italiana di Nutraceutica, Via Guelfa, 9, 40138 Bologna, Italy; (A.D.); (A.F.G.C.); (P.M.)
- CFC—Collegio Federativo di Cardiologia, Via Paolo Maspero, 5, 21100 Varese, Italy; (G.V.G.); (A.L.)
- Department of Internal Medicine and Therapeutics, University of Pavia, Via Aselli, 43/45, 27100 Pavia, Italy
| | - Angela D’Angelo
- SINut—Società Italiana di Nutraceutica, Via Guelfa, 9, 40138 Bologna, Italy; (A.D.); (A.F.G.C.); (P.M.)
| | - Fabrizio Angelini
- SINseB—Società Italiana Nutrizione, Sport e Benessere, Via Morimondo 26, 20143 Milano, Italy; (F.A.); (L.B.)
| | - Luca Belli
- SINseB—Società Italiana Nutrizione, Sport e Benessere, Via Morimondo 26, 20143 Milano, Italy; (F.A.); (L.B.)
| | - Arrigo F. G. Cicero
- SINut—Società Italiana di Nutraceutica, Via Guelfa, 9, 40138 Bologna, Italy; (A.D.); (A.F.G.C.); (P.M.)
| | - Roberto Da Ros
- AMD—Associazione Medici Diabetologi, Viale delle Milizie, 96, 00192 Roma, Italy; (R.D.R.); (G.S.)
| | - Giovanni De Pergola
- SIO—Società Italiana Obesità, Corso Italia, 115, 56125 Pisa, Italy; (G.D.P.); (F.A.V.)
| | - Giovanni V. Gaudio
- CFC—Collegio Federativo di Cardiologia, Via Paolo Maspero, 5, 21100 Varese, Italy; (G.V.G.); (A.L.)
| | - Alessandro Lupi
- CFC—Collegio Federativo di Cardiologia, Via Paolo Maspero, 5, 21100 Varese, Italy; (G.V.G.); (A.L.)
| | - Giovanni Sartore
- AMD—Associazione Medici Diabetologi, Viale delle Milizie, 96, 00192 Roma, Italy; (R.D.R.); (G.S.)
| | - Federico A. Vignati
- SIO—Società Italiana Obesità, Corso Italia, 115, 56125 Pisa, Italy; (G.D.P.); (F.A.V.)
| | - Pamela Maffioli
- SINut—Società Italiana di Nutraceutica, Via Guelfa, 9, 40138 Bologna, Italy; (A.D.); (A.F.G.C.); (P.M.)
| |
Collapse
|
|
4
|
Derosa G, D'Angelo A, Maffioli P. The role of selected nutraceuticals in management of prediabetes and diabetes: An updated review of the literature. Part II. Phytother Res 2024; 38:5490-5532. [PMID: 39363526 DOI: 10.1002/ptr.8312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Revised: 07/14/2024] [Accepted: 07/19/2024] [Indexed: 10/05/2024]
Abstract
We have already published a review about the results of clinical trials evaluating the effects of selected nutraceuticals on glycemia in humans. In this second part, we describe the role of other nutraceuticals involved in dysglycemia. The available evidence showed promising hypoglycemic effects of the nutraceuticals reviewed both for their efficacy and safety profile. However, contradictory results as regard the efficacy of some supplements such as Allium sativum, Juglans regia, and Lycium barbarum on glucose homeostasis have emerged from some clinical studies. Other nutraceuticals including Aloe vera, Amorphophallus Konjac, Bauhinia forficata, Coccinia, Ganoderma lucidum, Ipomoea batatas, and Lupinus mutabilis require larger and long-term studies rigorously designed to confirm their hypoglycemic effects due to the scarce data available and the poor quality of clinical trials. Further studies are also required for Cinnamomum, Cynara scolymus, Momordica charantia, Olea europaea, and Opuntia streptacantha. Moreover, well-designed large and long-term clinical trials including the use of standardized nutraceutical preparations are necessary for Phaseolus vulgaris and Vaccinium myrtillus.
Collapse
Affiliation(s)
- Giuseppe Derosa
- Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
- Centre of Diabetes, Metabolic Diseases, and Dyslipidemias, University of Pavia, Pavia, Italy
- Regional Centre for Prevention, Surveillance, Diagnosis and Treatment of Dyslipidemias and Atherosclerosis, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
- Laboratory of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Angela D'Angelo
- Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
- Laboratory of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Pamela Maffioli
- Centre of Diabetes, Metabolic Diseases, and Dyslipidemias, University of Pavia, Pavia, Italy
- Regional Centre for Prevention, Surveillance, Diagnosis and Treatment of Dyslipidemias and Atherosclerosis, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| |
Collapse
|
|
5
|
Sun K, Ding M, Fu C, Li P, Li T, Fang L, Xu J, Zhao Y. Effects of dietary wild bitter melon (Momordica charantia var. abbreviate Ser.) extract on glucose and lipid metabolism in HFD/STZ-induced type 2 diabetic rats. JOURNAL OF ETHNOPHARMACOLOGY 2023; 306:116154. [PMID: 36634725 DOI: 10.1016/j.jep.2023.116154] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 12/18/2022] [Accepted: 01/05/2023] [Indexed: 06/17/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Plant-based extracts to interfere with the onset of diabetes may be a promising approach towards type 2 diabetes mellitus (T2DM). Bitter gourd (Momordica charantia L.) is popularly consumed as an edible and medicinal resource with hypoglycemic effect in China. Wild bitter gourd (Momordica Charantia var. abbreviata Ser.) is a variant of bitter gourd, but there are relatively few studies on it. AIM OF THE STUDY The purpose of the experiment is to first screen out the most effective extraction part of Momordica charantia L. and Momordica Charantia var. abbreviata Ser. through the hypoglycemic activity experiment in vitro, and by using a high-fat and high-sugar diet with STZ-induced diabetic rat model in vivo to explore the possible mechanism of action against diabetes. MATERIALS AND METHODS This study first performed α-glucosidase, PTP1B and lipase activities inhibition experiments on the alcohol and water extracts of Momordica charantia L. and Momordica Charantia var. abbreviata Ser. Sprague Dawley rats were either given normal feed or a high sugar and fat diet for four weeks, followed STZ (25 mg/kg, via i. p.) was given. Rats with fasting blood glucose ≥11.1 mmol/l after one week were deemed to be diabetic, treatments were administered for four weeks, and then blood samples were used to evaluate hematological and biochemical indicators, and liver was removed for post-analysis. The expression levels of p-AMPK, AMPK, p-PI3K, PI3K, p-AKT, AKT, p-GSK3β, GSK3β, p-IRS-1, IRS-1, GLUT2 were determined by Western blot. At the same time, the chemical components was identified by liquid-mass spectrometry. RESULTS Data showed that the ethanol extract of wild bitter gourd (WBGE) had the best ability to regulate glucose and lipid metabolism in vitro. Therefore, we further investigated the antidiabetic effects of oral consumption of WBGE on high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM in SD rats. WBGE effectively reduced blood glucose and lipid levels, alleviated glucose intolerance and insulin resistant. Moreover, WBGE consumption could also inhibited oxidant responses and inflammatory damage. Mechanism studies have shown that WBGE may act by regulating AMPK/PI3K signaling pathway. On the other hand, the content of total phenol, total flavonoids, total saponins and total polysaccharide were measured by UV, 27 compounds were identified by LC-MS. CONCLUSIONS These studies explored the role and mechanism of WBGE in regulating glucose and lipid metabolism, and may support the utilization and further investigation of wild bitter gourd as a dietary intervention strategy to prevent diabetes and related metabolic abnormalities.
Collapse
Affiliation(s)
- Kai Sun
- School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin, China.
| | - Meng Ding
- College of Chemistry and Chemical Engineering, Cangzhou Normal University, Cangzhou, 061000, Hebei, China.
| | - Chaofan Fu
- School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, 110016, China.
| | - Pingya Li
- School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin, China.
| | - Tao Li
- College of Life Sciences and Biological Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
| | - Linlin Fang
- College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian, 116044, China.
| | - Jing Xu
- School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, 110016, China.
| | - Yuqing Zhao
- Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji, 133002, China.
| |
Collapse
|
|
6
|
Relevance of Indian traditional tisanes in the management of type 2 diabetes mellitus: a review. Saudi Pharm J 2023; 31:626-638. [PMID: 37181144 PMCID: PMC10172608 DOI: 10.1016/j.jsps.2023.03.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Accepted: 03/01/2023] [Indexed: 03/09/2023] Open
Abstract
Background Tisanes are a potential source of phytochemicals to reduce disease risk conditions and are used to protect from non-communicable diseases, globally. A few tisanes have gained more popularity than others depending on their chemical composition based on the geographical origin of the used herb. Several Indian tisanes have been claimed to have traits beneficial to people with or at a high risk of type 2 diabetes mellitus. Under the concept, the literature was reviewed and compiled into a document to highlight the chemical uniqueness of popular Indian traditional tisanes to be more informative and potent as per modern medicine to overcome type 2 diabetes mellitus. Methods An extensive literature survey was conducted using computerized database search engines, such as Google Scholar, PubMed, ScienceDirect, and EMBASE (Excerpta Medica database) for herbs that have been described for hyperglycemia, and involved reaction mechanism, in-vivo studies as well as clinical efficacies published since 2001 onwards using certain keywords. Compiled survey data used to make this review and all findings on Indian traditional antidiabetic tisanes are tabulated here. Results Tisanes render oxidative stress, counter the damage by overexposure of free radicals to the body, affect enzymatic activities, enhance insulin secretion, etc. The active molecules of tisanes also act as anti-allergic, antibacterial, anti-inflammatory, antioxidant, antithrombotic, antiviral, antimutagenicity, anti-carcinogenicity, antiaging effects, etc. WHO also has a strategy to capitalize on the use of herbals to keep populations healthy through effective and affordable alternative means with robust quality assurance and strict adherence to the product specification.
Collapse
|
|
7
|
Identification of two novel dipeptidyl peptidase-IV inhibitory peptides from sheep whey protein and inhibition mechanism revealed by molecular docking. FOOD BIOSCI 2022. [DOI: 10.1016/j.fbio.2022.101733] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
|
|
8
|
Udrea AM, Gradisteanu Pircalabioru G, Boboc AA, Mares C, Dinache A, Mernea M, Avram S. Advanced Bioinformatics Tools in the Pharmacokinetic Profiles of Natural and Synthetic Compounds with Anti-Diabetic Activity. Biomolecules 2021; 11:1692. [PMID: 34827690 PMCID: PMC8615418 DOI: 10.3390/biom11111692] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 11/06/2021] [Accepted: 11/08/2021] [Indexed: 12/12/2022] Open
Abstract
Diabetes represents a major health problem, involving a severe imbalance of blood sugar levels, which can disturb the nerves, eyes, kidneys, and other organs. Diabes management involves several synthetic drugs focused on improving insulin sensitivity, increasing insulin production, and decreasing blood glucose levels, but with unclear molecular mechanisms and severe side effects. Natural chemicals extracted from several plants such as Gymnema sylvestre, Momordica charantia or Ophiopogon planiscapus Niger have aroused great interest for their anti-diabetes activity, but also their hypolipidemic and anti-obesity activity. Here, we focused on the anti-diabetic activity of a few natural and synthetic compounds, in correlation with their pharmacokinetic/pharmacodynamic profiles, especially with their blood-brain barrier (BBB) permeability. We reviewed studies that used bioinformatics methods such as predicted BBB, molecular docking, molecular dynamics and quantitative structure-activity relationship (QSAR) to elucidate the proper action mechanisms of antidiabetic compounds. Currently, it is evident that BBB damage plays a significant role in diabetes disorders, but the molecular mechanisms are not clear. Here, we presented the efficacy of natural (gymnemic acids, quercetin, resveratrol) and synthetic (TAK-242, propofol, or APX3330) compounds in reducing diabetes symptoms and improving BBB dysfunctions. Bioinformatics tools can be helpful in the quest for chemical compounds with effective anti-diabetic activity that can enhance the druggability of molecular targets and provide a deeper understanding of diabetes mechanisms.
Collapse
Affiliation(s)
- Ana Maria Udrea
- Laser Department, National Institute for Laser, Plasma and Radiation Physics, 077125 Maurele, Romania; (A.M.U.); (A.D.)
- Earth, Environmental and Life Sciences Section, Research Institute of the University of Bucharest, University of Bucharest, 1 B. P. Hașdeu St., 50567 Bucharest, Romania;
| | - Gratiela Gradisteanu Pircalabioru
- Earth, Environmental and Life Sciences Section, Research Institute of the University of Bucharest, University of Bucharest, 1 B. P. Hașdeu St., 50567 Bucharest, Romania;
| | - Anca Andreea Boboc
- “Maria Sklodowska Curie” Emergency Children’s Hospital, 20, Constantin Brancoveanu Bd., 077120 Bucharest, Romania;
- Department of Pediatrics 8, “Carol Davila” University of Medicine and Pharmacy, Eroii Sanitari Bd., 020021 Bucharest, Romania
| | - Catalina Mares
- Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, 91–95 Splaiul Independentei, 050095 Bucharest, Romania; (C.M.); (S.A.)
| | - Andra Dinache
- Laser Department, National Institute for Laser, Plasma and Radiation Physics, 077125 Maurele, Romania; (A.M.U.); (A.D.)
| | - Maria Mernea
- Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, 91–95 Splaiul Independentei, 050095 Bucharest, Romania; (C.M.); (S.A.)
| | - Speranta Avram
- Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, 91–95 Splaiul Independentei, 050095 Bucharest, Romania; (C.M.); (S.A.)
| |
Collapse
|
|
9
|
Liu Y, Mu S, Chen W, Liu S, Cong Y, Liu J, Jia N. Saponins of Momordica charantia increase insulin secretion in INS-1 pancreatic β-cells via the PI3K/Akt/FoxO1 signaling pathway. ENDOCRINOL DIAB NUTR 2021; 68:329-337. [PMID: 34556263 DOI: 10.1016/j.endien.2021.08.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Accepted: 05/06/2020] [Indexed: 11/16/2022]
Abstract
Saponins are the main bioactive substances with anti-hyperglycemic activities of Momordica charantia. This study aimed to verify the effects of M. charantia saponins on insulin secretion and explore the potential underlying mechanisms in INS-1 pancreatic β-cells. We injured INS-1 cells with 33.3mM glucose and then treated them with saponins. Saponins improved cell morphology and viability as demonstrated by inverted microscopy and CCK8 detection and significantly increased insulin secretion in a concentration-dependent manner as shown by ELISA. Thus, we obtained the optimal concentration for the subsequent experiments. Potential mechanisms were explored by immunofluorescence, western blotting, and RT-qPCR techniques. First, saponins increased the mRNA and protein levels of IRS-2 but decreased the serine 731 phosphorylation level of IRS-2. Moreover, saponins increased the phosphorylation of Akt protein and decreased the protein level of FoxO1, which were both reversed by the PI3K inhibitor ly294002. Furthermore, saponins increased the protein level of the downstream molecule and insulin initiating factor PDX-1, which was also reversed by ly294002. Saponins also increased Akt and PDX-1 mRNA and decreased FoxO1 mRNA, which were both reversed by ly294002. Saponins increased glucose-stimulated insulin secretion (GSIS) and intracellular insulin content, which were reversed by ly294002, as determined by ELISA. The immunofluorescence results also confirmed this tendency. In conclusion, our findings improve our understanding of the function of saponins in INS-1 pancreatic β-cells and suggest that saponins may increase insulin secretion via the PI3K/Akt/FoxO1 signaling pathway.
Collapse
Affiliation(s)
- Yufan Liu
- Traditional Chinese Medicine College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Shumin Mu
- Department of Endocrinology, Hospital Affiliated to Shandong Traditional Chinese Medicine University, Jinan, China.
| | - Wenbin Chen
- Scientific Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
| | - Shiyin Liu
- First Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Yuxuan Cong
- Department of Endocrinology, Weihai Hospital of Traditional Chinese Medicine, Weihai, China
| | - Jiajia Liu
- Department of Endocrinology, People's Hospital of Gaotang County, Liaocheng, China
| | - Ning Jia
- Department of Traditional Chinese Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
| |
Collapse
|
|
10
|
Salami MS, Bahrami G, Arkan E, Izadi Z, Miraghaee S, Samadian H. Co-electrospun nanofibrous mats loaded with bitter gourd (Momordica charantia) extract as the wound dressing materials: in vitro and in vivo study. BMC Complement Med Ther 2021; 21:111. [PMID: 33827547 PMCID: PMC8028699 DOI: 10.1186/s12906-021-03284-4] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Accepted: 03/22/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Interactive dressings are innovatively designed to interact with the wound surface and alter the wound environment to promote wound healing. In the current study, we integrated the physicochemical properties of Poly (caprolactone)/ Poly (vinyl alcohol)/Collagen (PCL/PVA/Col) nanofibers with the biological activities of Momordica charantia pulp extract to develop an efficient wound dressing. The electrospinning method was applied to fabricate the nanofibers, and the prepared wound dressings were thoroughly characterized. RESULTS SEM imaging showed that the nanofibers were uniform, straight, without any beds with a diameter in the range of 260 to 480 nm. Increasing the concentration of the extract increased the diameter of the nanofibers and also the wettability characteristics while reduced the ultimate tensile strength from 4.37 ± 0.90 MPa for PCL/PVA/Col to 1.62 ± 0.50 MPa for PCL/PVA/Col/Ex 10% (p < 0.05). The in vivo studies showed that the application of the wound dressings significantly enhanced the healing process and the highest wound closure, 94.01 ± 8.12%, was obtained by PCL/PVA/Col/Ex 10% nanofibers (p < 0.05). CONCLUSION The incorporation of the extract had no significant effects on nanofibers' porosity, water vapor permeability, and swelling characteristics. The in vitro evaluations showed that the fabricated nanofibers were hemocompatible, cytocompatible, and prevent bacterial penetration through the dressing. These findings implied that the PCL/PVA/Col/Ex nanofibers can be applied as the wound dressing materials.
Collapse
Affiliation(s)
- Mohammad Saeid Salami
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Gholamreza Bahrami
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Elham Arkan
- Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Zhila Izadi
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Shahram Miraghaee
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Hadi Samadian
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
- Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
| |
Collapse
|
|
11
|
Cortez-Navarrete M, Méndez-Del Villar M, Ramos-González EJ, Pérez-Rubio KG. Momordica Charantia: A Review of Its Effects on Metabolic Diseases and Mechanisms of Action. J Med Food 2021; 24:1017-1027. [PMID: 33733863 DOI: 10.1089/jmf.2020.0206] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
The global rise in the prevalence of metabolic diseases such as diabetes, obesity, and dyslipidemia is a serious public health issue. The search for safe and effective complementary and alternative therapies to treat metabolic disorders is a key field of research. Momordica charantia (MC) is a tropical and subtropical vine of the Cucurbitaceae family used as a medicinal plant since ancient times. Although MC has been widely studied for its hypoglycemic potential, hypolipidemic and antiobesity effects have also been reported in preclinical studies and clinical trials. This study aims to review the metabolic effects of MC reported in clinical trials as well as its mechanisms of action.
Collapse
Affiliation(s)
- Marisol Cortez-Navarrete
- Instituto de Terapéutica Experimental y Clínica, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México
| | - Miriam Méndez-Del Villar
- Departamento de Ciencias Biomédicas, Centro Universitario de Tonalá, Universidad de Guadalajara, Guadalajara, Tonalá, Jalisco, México
| | - Elsy Janeth Ramos-González
- Unidad de Investigación Biomédica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas, Zacatecas, México
| | - Karina G Pérez-Rubio
- Instituto de Terapéutica Experimental y Clínica, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México
| |
Collapse
|
|
12
|
Hou H, Wang J, Wang J, Tang W, Shaikh AS, Li Y, Fu J, Lu L, Wang F, Sun F, Tan H. A Review of Bioactive Peptides: Chemical Modification, Structural Characterization and Therapeutic Applications. J Biomed Nanotechnol 2021; 16:1687-1718. [PMID: 33485398 DOI: 10.1166/jbn.2020.3001] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
In recent years, the development and applications of protein drugs have attracted extensive attention from researchers. However, the shortcomings of protein drugs also limit their further development. Therefore, bioactive peptides isolated or simulated from protein polymers have broad application prospects in food, medicine, biotechnology, and other industries. Such peptides have a molecular weight distribution between 180 and 1000 Da. As a small molecule substance, bioactive peptide is usually degraded by various enzymes in the organism and have a short half-life. At the same time, such substances have poor stability and are difficult to produce and store. Therefore, these active peptides may be modified through phosphorylation, glycosylation, and acylation. Compared with other protein drugs, the modified active peptides are more easily absorbed by the body, have longer half-life, stronger targeting, and fewer side effects in addition to higher bioavailability. In the light of their functions, bioactive peptide can be divided into antimicrobial, anti-tumour, anti-angiogenic, antioxidant, anti-fatigue, and anti-hypertensive peptides. This article mainly focuses on the introduction of several promising biologically active peptides functioning as antimicrobial, anti-tumour, antiangiogenic, and antioxidant peptides from the three aspects modification, structural characteristics and mechanism of action.
Collapse
|
|
13
|
Liu Z, Gong J, Huang W, Lu F, Dong H. The Effect of Momordica charantia in the Treatment of Diabetes Mellitus: A Review. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2021; 2021:3796265. [PMID: 33510802 PMCID: PMC7826218 DOI: 10.1155/2021/3796265] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 12/02/2020] [Accepted: 12/18/2020] [Indexed: 12/29/2022]
Abstract
In recent years, many studies of Momordica charantia (MC) in the treatment of diabetes mellitus (DM) and its complications have been reported. This article reviewed the effect and mechanism of MC against diabetes, including the results from in vitro and in vivo experiments and clinical trials. The common side effects of MC were also summarized. We hope that it might open up new ideas for further mechanism exploration and clinical application as well as provide a scientific theoretical basis for the development of drugs or foods derived from MC.
Collapse
Affiliation(s)
- Zhuo Liu
- Grade 2016 of Integrated Traditional Chinese and Western Clinical Medicine, Huazhong University of Science and Technology, Wuhan, China
| | - Jing Gong
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wenya Huang
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Fuer Lu
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hui Dong
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| |
Collapse
|
|
14
|
Zhang C, Qiao S, Wu J, Xu W, Ma S, Zhao B, Wang X. A new insulin-sensitive enhancer from Silene viscidula, WPTS, treats type 2 diabetes by ameliorating insulin resistance, reducing dyslipidemia, and promoting proliferation of islet β cells. Pharmacol Res 2021; 165:105416. [PMID: 33412277 DOI: 10.1016/j.phrs.2020.105416] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2020] [Revised: 12/20/2020] [Accepted: 12/29/2020] [Indexed: 12/15/2022]
Abstract
Wacao pentacyclic triterpenoid saponins (WPTS) is a newly discovered insulin sensitivity enhancer. It is a powerful hypoglycemic compound derived from Silene viscidula, which has a hypoglycemic effect similar to that of insulin. It can rapidly reduce blood glucose levels, normalizing them within 3 days of administration. However, its mechanism of action is completely different from that of insulin. Thus, we aimed to determine the pharmacological effects and mechanism of activity of WPTS on type 2 diabetes to elucidate the main reasons for its rapid effects. The results showed that WPTS could effectively improve insulin resistance in KKAy diabetic mice. Comparative transcriptomics showed that WPTS could upregulate the expression of insulin resistance-related genes such as glucose transporter type 4 (Glut4), insulin receptor substrate 1 (Irs1), Akt, and phosphoinositide 3-kinase (PI3K), and downregulate the expression of lipid metabolism-related genes such as monoacylglycerol O-acyltransferase 1 (Moat1), lipase C (Lipc), and sphingomyelin phosphodiesterase 4 (Smpd4). The results indicated that the differentially expressed genes could regulate lipid metabolism via the PI3K/AKT metabolic pathway, and it is noteworthy that WPTS was found to upregulate Glut4 expression, decrease blood glucose levels, and attenuate insulin resistance via the PI3K/AKT pathway. Q-PCR and western blotting further validated the transcriptomics findings at the mRNA and protein levels, respectively. We believe that WPTS can achieve a rapid hypoglycemic effect by improving the lipid metabolism and insulin resistance of the diabetic KKAy mice. WPTS could be a very promising candidate drug for the treatment of diabetes and deserves further research.
Collapse
Affiliation(s)
- Caijuan Zhang
- School of Life Science, Beijing University of Chinese Medicine, China
| | - Sanyang Qiao
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, China
| | - Jiahui Wu
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, China
| | - Wenjuan Xu
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, China
| | - Shuangshuang Ma
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, China
| | - Baosheng Zhao
- Beijing Institute of Chinese Medicine, Beijing University of Chinese Medicine, China
| | - Xueyong Wang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, China; Beijing Institute of Chinese Medicine, Beijing University of Chinese Medicine, China.
| |
Collapse
|
|
15
|
Chang CI, Cheng SY, Nurlatifah AO, Sung WW, Tu JH, Lee LL, Cheng HL. Bitter Melon Extract Yields Multiple Effects on Intestinal Epithelial Cells and Likely Contributes to Anti-diabetic Functions. Int J Med Sci 2021; 18:1848-1856. [PMID: 33746602 PMCID: PMC7976585 DOI: 10.7150/ijms.55866] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Accepted: 01/04/2021] [Indexed: 12/16/2022] Open
Abstract
The intestines have been recognized as important tissues for metabolic regulation, including glycemic control, but their vital role in promoting the anti-diabetic effects of bitter melon, the fruit of Momordica charantia L, has seldom been characterized, nor acknowledged. Evidence suggests that bitter melon constituents can have substantial interactions with the intestinal epithelial cells before circulating to other tissues. We therefore characterized the effects of bitter melon extract (BME) on intestinal epithelial cells. BME was found to contain substantial amounts of carbohydrates, proteins, and triterpenoids. TNF-α induced insulin resistance in an enterocyte cell line of IEC-18 cells, and BME promoted glucose utilization of the insulin-resistant cells. Further analysis suggested that the increased glucose consumption was a result of the combined effects of insulin sensitizing and insulin substitution functions of BME. The functions of insulin substitution were likely generated due to the activation of AMP-activated protein kinase. Meanwhile, BME acted as a glucagon-like peptide 1 (GLP-1) secretagogue on enteroendocrine cells, which may be mediated by the activation of bitter-taste receptors. Therefore, BME possesses insulin sensitizing, insulin substitution, and GLP-1 secretagogue functions upon intestinal cells. These effects of BME on intestinal cells likely play a significant part in the anti-diabetic action of bitter melon.
Collapse
Affiliation(s)
- Chi-I Chang
- Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan
| | - Shi-Yie Cheng
- Department of Life Sciences, National University of Kaohsiung, Kaohsiung 811, Taiwan
| | - Annisa Oktafianti Nurlatifah
- Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan.,Department of Agroindustrial Biotechnology, Brawijaya University, Jalan, Veteran Malang 65145, Indonesia
| | - Wei-Wen Sung
- Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan
| | - Jing-Hong Tu
- Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan
| | - Lin-Lee Lee
- Department of English, National Kaohsiung Normal University, Kaohsiung 80201, Taiwan
| | - Hsueh-Ling Cheng
- Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan
| |
Collapse
|
|
16
|
Kapoor N, Ghorai SM, Kushwaha PK, Shukla R, Aggarwal C, Bandichhor R. Plausible mechanisms explaining the role of cucurbitacins as potential therapeutic drugs against coronavirus 2019. INFORMATICS IN MEDICINE UNLOCKED 2020; 21:100484. [PMID: 33251326 PMCID: PMC7685940 DOI: 10.1016/j.imu.2020.100484] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2020] [Revised: 11/20/2020] [Accepted: 11/20/2020] [Indexed: 02/06/2023] Open
Abstract
In the year 2019, the potent zoonotic virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began to rage globally, which resulted in the World Health Organization (WHO) declaring it as a pandemic on March 11th, 2020. Although extensive research is currently ongoing worldwide to understand the molecular mechanism and disease pathogenicity of SARS-CoV-2, there are still many nuances to elucidate. Therefore, developing an appropriate vaccine or therapeutic drug to combat coronavirus 2019 (COVID-19) is exceedingly challenging. Such scenarios require multifaceted approaches to identify suitable contenders for drugs against COVID-19. In this context, investigating natural compounds found in food, spices, and beverages can lead to the discovery of lead molecules that could be repurposed to treat COVID-19. Sixteen cucurbitacin analogues were investigated for activity against the SARS-CoV-2 main protease protein (Mpro), angiotensin-converting enzyme 2 (ACE2) binding receptor, nonstructural protein 12 (NSP12) RNA-dependent RNA polymerase (RdRp), NSP13 helicase, and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway using several relevant tools and simulated screening methods. All key proteins were found to bind efficiently only with cucurbitacin G 2-glucoside and cucurbitacin H with the lowest global energy. Further, the absorption, distribution, metabolism, and excretion (ADME) of all the cucurbitacins were analysed to explore their drug profiles. Cucurbitacin G 2-glucoside and H showed the best hits and all the analogues showed no adverse properties that would diminish their drug-likeness abilities. The encouraging results of the current study may lay the foundation for future research and development of effective measures and preventive medications against SARS-CoV-2.
Collapse
Affiliation(s)
- Neha Kapoor
- Department of Chemistry, Hindu College, University of Delhi, Delhi, 110007, India
| | - Soma Mondal Ghorai
- Department of Zoology, Hindu College, University of Delhi, Delhi, 110007, India
| | - Prem Kumar Kushwaha
- Department of Chemistry, Birla Institute of Technology, Mesra, Ranchi, 835215, India
| | - Richa Shukla
- Department of Applied Science, Indian Institute of Information Technology, Allahabad, 211015, India
| | - Charu Aggarwal
- Department of Zoology, Hindu College, University of Delhi, Delhi, 110007, India
| | - Rakeshwar Bandichhor
- Integrated Product Development, Innovation Plaza, Dr. Reddy's Laboratories Ltd, Bachupally, Qutubullapur, Hyderabad, Telangana, 500090, India
| |
Collapse
|
|
17
|
Saponins of Momordica charantia increase insulin secretion in INS-1 pancreatic β-cells via the PI3K/Akt/FoxO1 signaling pathway. ACTA ACUST UNITED AC 2020; 68:329-337. [PMID: 33069631 DOI: 10.1016/j.endinu.2020.05.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Revised: 05/06/2020] [Accepted: 05/06/2020] [Indexed: 12/20/2022]
Abstract
Saponins are the main bioactive substances with anti-hyperglycemic activities of Momordica charantia. This study aimed to verify the effects of M. charantia saponins on insulin secretion and explore the potential underlying mechanisms in INS-1 pancreatic β-cells. We injured INS-1 cells with 33.3mM glucose and then treated them with saponins. Saponins improved cell morphology and viability as demonstrated by inverted microscopy and CCK8 detection and significantly increased insulin secretion in a concentration-dependent manner as shown by ELISA. Thus, we obtained the optimal concentration for the subsequent experiments. Potential mechanisms were explored by immunofluorescence, western blotting, and RT-qPCR techniques. First, saponins increased the mRNA and protein levels of IRS-2 but decreased the serine 731 phosphorylation level of IRS-2. Moreover, saponins increased the phosphorylation of Akt protein and decreased the protein level of FoxO1, which were both reversed by the PI3K inhibitor ly294002. Furthermore, saponins increased the protein level of the downstream molecule and insulin initiating factor PDX-1, which was also reversed by ly294002. Saponins also increased Akt and PDX-1 mRNA and decreased FoxO1 mRNA, which were both reversed by ly294002. Saponins increased glucose-stimulated insulin secretion (GSIS) and intracellular insulin content, which were reversed by ly294002, as determined by ELISA. The immunofluorescence results also confirmed this tendency. In conclusion, our findings improve our understanding of the function of saponins in INS-1 pancreatic β-cells and suggest that saponins may increase insulin secretion via the PI3K/Akt/FoxO1 signaling pathway.
Collapse
|
|
18
|
mcIRBP-19 of Bitter Melon Peptide Effectively Regulates Diabetes Mellitus (DM) Patients' Blood Sugar Levels. Nutrients 2020; 12:nu12051252. [PMID: 32354072 PMCID: PMC7281988 DOI: 10.3390/nu12051252] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Revised: 04/23/2020] [Accepted: 04/26/2020] [Indexed: 01/18/2023] Open
Abstract
This study was conducted to test the effectiveness of a particular bitter melon peptide (BMP), with a specific sequence of 19 amino acids (mcIRBP-19), in regulating diabetic patients' blood glucose. In order to test the product with the specially processed BMP, a total of 142 diabetic patients were solicited as study subjects, of which 64 were assigned to an experiment group and 78 to a control group. Biochemical data were compared with a paired t-test to verify the significance of changes over different time periods. The clinical results showed that BMP started to improve the subjects' glycated hemoglobin (HbA1c) levels at the end of the second month (T2), with mean values being significantly lowered from 7.8 ± 1.4% (T0) to 7.5 ± 1.4% (T2) (p = 0.004). The values reduced continuously, eventually reaching 7.4 ± 1.1% (p = 0.000) at the end of the experiment (T3). HbA1c levels for the control group were 7.5 ± 1.2% in T0 and 7.5 ± 1.1% (T3), and not significantly different (p = 0.852) over the same period. This study provides clinical evidence that helps to verify the effectiveness of the new BMP product in regulating diabetic patients' blood sugar levels.
Collapse
|
|
19
|
Probiotics Fermented Bitter Melon Juice as Promising Complementary Agent for Diabetes Type 2: Study on Animal Model. J Nutr Metab 2020; 2020:6369873. [PMID: 32190386 PMCID: PMC7064845 DOI: 10.1155/2020/6369873] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Revised: 12/03/2019] [Accepted: 01/06/2020] [Indexed: 02/08/2023] Open
Abstract
Background and Aim. Bitter melon (Momordica charantia/MC) contains charantin that has antidiabetic properties as an α-glucosidase inhibitor and antioxidative properties. Lactic acid fermentation using Lactobacillus fermentum LLB3 increased its antioxidative properties. The study was aimed to analyse the difference of the treatment that influences blood glucose and SOD level before and after treatment compared to acarbose. Experimental procedure. A total of 24 male Sprague-Dawley rats were used. Diabetes type 2 was induced by a single dose (60 mg/kg) of streptozotocin (STZ) and 120 mg/kg of nicotinamide, intraperitoneally. Following three days of STZ induction, the animals were randomly divided into four groups. Groups 1, 2, 3, and 4 were given acarbose 40 mg/100 g feed, MC 10 ml/kg body weight, fermented MC 10 ml/kg body weight, and distilled water, respectively, for 28 days. Glucose and SOD values were measured by spectrophotometer and ELISA, respectively. The difference between pretest and posttest data was analysed using the pair t-test. Data were analysed using ANOVA and Tukey HSD for post hoc analysis. Level of significance was set at 0.05.
Collapse
|
|
20
|
Francini F, Schinella GR, Ríos JL. Activation of AMPK by Medicinal Plants and Natural Products: Its Role in Type 2 Diabetes Mellitus. Mini Rev Med Chem 2019; 19:880-901. [PMID: 30484403 DOI: 10.2174/1389557519666181128120726] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2018] [Revised: 07/04/2018] [Accepted: 11/22/2018] [Indexed: 12/26/2022]
Abstract
Type-2 Diabetes (T2D) is a metabolic disease characterized by permanent hyperglycemia, whose development can be prevented or delayed by using therapeutic agents and implementing lifestyle changes. Some therapeutic alternatives include regulation of glycemia through modulation of different mediators and enzymes, such as AMP-activated protein kinase (AMPK), a highly relevant cellular energy sensor for metabolic homeostasis regulation, with particular relevance in the modulation of liver and muscle insulin sensitivity. This makes it a potential therapeutic target for antidiabetic drugs. In fact, some of them are standard drugs used for treatment of T2D, such as biguanides and thiazolidindiones. In this review, we compile the principal natural products that are activators of AMPK and their effect on glucose metabolism, which could make them candidates as future antidiabetic agents. Phenolics such as flavonoids and resveratrol, alkaloids such as berberine, and some saponins are potential natural activators of AMPK with a potential future as antidiabetic drugs.
Collapse
Affiliation(s)
- Flavio Francini
- Centro de Endocrinologia Experimental y Aplicada, (CONICET-CCT La Plata-UNLP FCM, CEAS CICPBA), Argentina
| | - Guillermo R Schinella
- Cátedra de Farmacología Básica, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Argentina.,Comisión de Investigaciones Científicas de la Provincia de Buenos Aires, La Plata, Argentina
| | - José-Luis Ríos
- Departament de Farmacologia, Facultat de Farmacia, Universitat de Valencia, Valencia, Spain
| |
Collapse
|
|
21
|
Antioxidative and Antimelanogenesis Effect of Momordica charantia Methanol Extract. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2019; 2019:5091534. [PMID: 31186660 PMCID: PMC6521336 DOI: 10.1155/2019/5091534] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Accepted: 04/07/2019] [Indexed: 01/19/2023]
Abstract
Despite a large number of studies reporting a variety of biological and pharmacological activities of Momordica charantia, its skin protective properties are poorly understood. The present study aimed to explore the skin protective properties of Momordica charantia methanol extract (Mc-ME) and the underlying mechanism in keratinocytes, fibroblasts, and melanocytes. Mc-ME exhibited an antioxidative property by decreasing radical levels in HaCaT keratinocytes and a cytoprotective property in H2O2-damaged HaCaT cells, which was mediated by increasing the expression or activation of Kelch-like ECH-associated protein 1 (KEAP1), HO-1, p85/PI3K, and AKT. Mc-ME was also active against wrinkle formation by regulating the activity or expression of tissue remodeling factors such as elastase, type 1 collagen, and matrix metalloproteinase (MMP)-1 and -9 and tissue-protecting enzymes such as hemeoxygenase-1 (HO-1) and sirtuin 1 (SIRT1) in NIH3T3 fibroblasts and HaCaT cells, in addition to increasing the proliferation of HaCaT cells. Mc-ME also showed antidehydration properties by inducing the expression of natural moisturizing factors such as filaggrin (FLG), transglutaminase-1 (TGM-1), and hyaluronic acid synthase (HAS)-1, -2, and -3 in HaCaT cells. Moreover, Mc-ME showed an antimelanogenic property by inhibiting the synthesis and secretion of melanin from B16F10 melanoma cells via suppression of tyrosinase activity. Taken together, these results suggest that Mc-ME plays a skin protective role through its antioxidative, cytoprotective, skin remodeling, moisturizing, and antimelanogenic properties and might be a new and promising skin protective cosmeceutical.
Collapse
|
|
22
|
Aljohi A, Matou-Nasri S, Liu D, Al-Khafaji N, Slevin M, Ahmed N. Momordica charantia extracts protect against inhibition of endothelial angiogenesis by advanced glycation endproducts in vitro. Food Funct 2019; 9:5728-5739. [PMID: 30318521 DOI: 10.1039/c8fo00297e] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Diabetes mellitus characterized by hyperglycemia favors formation of advanced glycation endproducts (AGEs) capable of triggering vascular complications by interfering with imbalanced inflammation and angiogenesis to eventually impede wound-healing. Momordica charantia (MC, bitter melon) has been shown to prevent AGE formation and to promote angiogenesis in diabetic wounds in animal models. However, the mechanism underlying its effects on angiogenesis is unclear. We investigated the effects of methanolic extracts of MC pulp (MCP), flesh (MCF) and charantin (active component of MC) using an in vitro model of angiogenesis. MC extracts or low concentrations of bovine serum albumin-derived AGEs (BSA-AGEs) stimulated proliferation, migration (using wound-healing assay) and tube formation (using Matrigel™-embedded 3D culture) of bovine aortic endothelial cells (BAEC) together with increases in the phosphorylation of extracellular signal-regulated kinase (ERK)1/2, the key angiogenic signaling cytoplasmic protein. Blocking the receptor for AGEs (RAGE) inhibited low BSA-AGE- and MC extract-induced ERK1/2 phosphorylation and tube formation, indicating the crucial role of RAGE in the pro-angiogenic effects of MC extracts. Moreover, inhibitory effects of high BSA-AGE concentration on cell proliferation and migration were reduced by the addition of MC extracts, which reversed the BSA-AGE anti-angiogenic effect on tube formation. Thus, MC extracts exert direct pro-angiogenic signaling mediated via RAGE to overcome the anti-angiogenic effects of high BSA-AGEs, highlighting the biphasic RAGE-dependent mechanisms involved. This study enhances our understanding of the mechanisms underlying the pro-angiogenic effects of MC extracts in improvement of diabetes-impaired wound-healing.
Collapse
Affiliation(s)
- Ali Aljohi
- School of Healthcare Science, Manchester Metropolitan University, Manchester M1 5GD, UK.
| | | | | | | | | | | |
Collapse
|
|
23
|
Antioxidant effect, glucose uptake activity in cell lines and cytotoxic potential of Melicope lunu-ankenda leaf extract. J Herb Med 2018. [DOI: 10.1016/j.hermed.2018.06.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
|
|
24
|
Bitter melon seed oil increases mitochondrial content in gastrocnemius muscle and improves running endurance in sedentary C57BL/6J mice. J Nutr Biochem 2018; 58:150-157. [DOI: 10.1016/j.jnutbio.2018.05.008] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2018] [Revised: 04/16/2018] [Accepted: 05/12/2018] [Indexed: 11/17/2022]
|
|
25
|
Mozaniel SDO, Wanessa ADC, Fernanda WFB, Marilena EA, Gracialda CF, Raul NDCJ. Phytochemical profile and biological activities of Momordica charantia L. (Cucurbitaceae): A review. ACTA ACUST UNITED AC 2018. [DOI: 10.5897/ajb2017.16374] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
|
|
26
|
Saeed F, Afzaal M, Niaz B, Arshad MU, Tufail T, Hussain MB, Javed A. Bitter melon (Momordica charantia): a natural healthy vegetable. INTERNATIONAL JOURNAL OF FOOD PROPERTIES 2018. [DOI: 10.1080/10942912.2018.1446023] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Farhan Saeed
- Institute of Home and Food Sciences, Government College University Faisalabad, Faisalabad, Pakistan
| | - Muhammad Afzaal
- Institute of Home and Food Sciences, Government College University Faisalabad, Faisalabad, Pakistan
| | - Bushra Niaz
- Institute of Home and Food Sciences, Government College University Faisalabad, Faisalabad, Pakistan
| | - Muhammad Umair Arshad
- Institute of Home and Food Sciences, Government College University Faisalabad, Faisalabad, Pakistan
| | - Tabussam Tufail
- Institute of Home and Food Sciences, Government College University Faisalabad, Faisalabad, Pakistan
| | - Muhammad Bilal Hussain
- Institute of Home and Food Sciences, Government College University Faisalabad, Faisalabad, Pakistan
| | - Ahsan Javed
- Institute of Home and Food Sciences, Government College University Faisalabad, Faisalabad, Pakistan
| |
Collapse
|
|
27
|
Cortez-Navarrete M, Martínez-Abundis E, Pérez-Rubio KG, González-Ortiz M, Méndez-del Villar M. Momordica charantia Administration Improves Insulin Secretion in Type 2 Diabetes Mellitus. J Med Food 2018; 21:672-677. [DOI: 10.1089/jmf.2017.0114] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Affiliation(s)
- Marisol Cortez-Navarrete
- Institute of Experimental and Clinical Therapeutics, Department of Physiology, Health Science University Center, University of Guadalajara, Guadalajara, Mexico
| | - Esperanza Martínez-Abundis
- Institute of Experimental and Clinical Therapeutics, Department of Physiology, Health Science University Center, University of Guadalajara, Guadalajara, Mexico
| | - Karina G. Pérez-Rubio
- Institute of Experimental and Clinical Therapeutics, Department of Physiology, Health Science University Center, University of Guadalajara, Guadalajara, Mexico
| | - Manuel González-Ortiz
- Institute of Experimental and Clinical Therapeutics, Department of Physiology, Health Science University Center, University of Guadalajara, Guadalajara, Mexico
| | - Miriam Méndez-del Villar
- Institute of Experimental and Clinical Therapeutics, Department of Physiology, Health Science University Center, University of Guadalajara, Guadalajara, Mexico
| |
Collapse
|
|
28
|
Bhat GA, Khan HA, Alhomida AS, Sharma P, Singh R, Paray BA. GLP-I secretion in healthy and diabetic Wistar rats in response to aqueous extract of Momordica charantia. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2018; 18:162. [PMID: 29776414 PMCID: PMC5960212 DOI: 10.1186/s12906-018-2227-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/04/2017] [Accepted: 05/02/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND Diabetes mellitus is one of the major global health disorders increasing at an alarming rate in both developed and developing countries. The objective of this study was to assess the effect of aqueous extract of Momordica charantia (AEMC) on fasting blood glucose (FBG), tissue glycogen, glycosylated haemoglobin, plasma concentrations of insulin and GLP-1 hormone (glucagon-like peptide 1) in healthy and diabetic wistar rats. METHODS Male Wistar rats (both normal and diabetic) were treated with AEMC by gavaging (300 mg/kg body wt/day for 28 days). RESULTS AEMC was found to increase tissue glycogen, serum insulin and GLP-1 non-significantly (P > 0.05) in normal, significantly (P < 0.01) in diabetic Wistar rats, whereas decrease in FBG and Glycosylated haemoglobin non-significantly (P > 0.05) in normal, significantly (P < 0.01) in diabetic Wistar rats. The elevation of GLP-1 level in normal and diabetic treated groups may be due to the L-cell regeneration and proliferation by binding with L-cell receptors and makes a conformational change, resulting in the activation of a series of signal transducers. The polar molecules of M. charantia also depolarize the L-cell through elevation of intracellular Ca2+ concentration and which in turn releases GLP-1. GLP-1 in turn elevates beta-cell proliferation and insulin secretion. CONCLUSION The findings tend to provide a possible explanation for the hypoglycemic action of M. charantia fruit extracts as alternative nutritional therapy in the management and treatment of diabetes.
Collapse
Affiliation(s)
- Gulzar Ahmad Bhat
- Department of Zoology, HNB Central University Garhwal, Srinagar, Uttarakhand 249161 India
| | - Haseeb A. Khan
- Department of Biochemistry, College of Science, King Saud University, Riyadh, 11451 Saudi Arabia
| | - Abdullah S. Alhomida
- Department of Biochemistry, College of Science, King Saud University, Riyadh, 11451 Saudi Arabia
| | - Poonam Sharma
- Department of Zoology, Indira Gandhi National Tribal University, (A Central University), Amarkantak, M.P 484887 India
| | - Rambir Singh
- Department of Biological Sciences, Bundelkhand University, Jhansi, UP India
| | - Bilal Ahmad Paray
- Zoology Department, College of Science, King Saud University, PO Box 2455, Riyadh, 11451 Saudi Arabia
| |
Collapse
|
|
29
|
Sung HC, Liu CW, Hsiao CY, Lin SR, Yu IS, Lin SW, Chiang MH, Liang CJ, Pu CM, Chen YC, Lin MS, Chen YL. The effects of wild bitter gourd fruit extracts on ICAM-1 expression in pulmonary epithelial cells of C57BL/6J mice and microRNA-221/222 knockout mice: Involvement of the miR-221/-222/PI3K/AKT/NF-κB pathway. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2018; 42:90-99. [PMID: 29655703 DOI: 10.1016/j.phymed.2018.03.023] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/07/2017] [Revised: 01/22/2018] [Accepted: 03/12/2018] [Indexed: 06/08/2023]
Abstract
BACKGROUND The extracts from wild bitter gourd fruit (WBGE) were reported to possess numerous pharmacological activities. However, the anti-inflammatory effects of WBGE on human lung epithelial cells and the underlying mechanisms have not been determined. PURPOSE To evaluate the molecular basis of the effects of WBGE on intercellular adhesion molecule-1 (ICAM-1) expression in alveolar epithelial (A549) cells, C57BL/6 wild-type (WT) mice and microRNA (miR)-221/-222 knockout (KO) mice with or without tumor necrosis factor (TNF-α; 3 ng/ml) treatment. STUDY DESIGN/METHODS WT mice and miR-221/-222 KO mice were fed a control diet and divided into four groups (C: control mice; T: treated with TNF-α alone; WBGE/T: pretreated with WBGE and then stimulated with TNF-α; WBGE: treated with WBGE alone). The effects of WBGE on ICAM-1 expression and the related signals in A549 cells and mice with or without TNF-α treatment were examined by Western blot and immunofluorescent staining. RESULTS WBGE significantly decreased the TNF-α-induced ICAM-1 expression in A549 cells through the inhibition of phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT)/ nuclear factor- kappa B (NF-κB)/ inhibitor of NF-κB (IκB) phosphorylation and decreased leukocyte adhesion. In addition, WBGE reduced endogenous ICAM-1 expression and upregulated miR-221/-222 expression. The overexpression of miR-222 decreased PI3K/AKT/NF-κB/IκB and ICAM-1 expression, which resulted in reducing monocyte adhesion. Moreover, WBGE reduced ICAM-1 expression in lung tissues of WT mice with or without TNF-α treatment and upregulated miR-221/222. WBGE did not affect the miR-221/-222 level and had little effect on ICAM-1 expression in miR-221/-222 KO mice. CONCLUSIONS These results suggest that WBGE reduced ICAM-1 expression both under in vitro and in vivo conditions. The protective effects were mediated partly through the miR-221/-222/PI3K/AKT/NF-κB pathway.
Collapse
Affiliation(s)
- Hsin-Ching Sung
- Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Anatomy, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chen-Wei Liu
- Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Chien-Yu Hsiao
- Department of Nutrition and Health Sciences, Research Center for Food and Cosmetic Safety, and Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan; Aesthetic Medical Center, Department of Dermatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Shu-Rung Lin
- Department of Bioscience Technology, College of Science, Chung-Yuan Christian University, Taoyuan, Taiwan; Center for Nanotechnology and Center for Biomedical Technology, Chung-Yuan Christian University, Taoyuan, Taiwan
| | - I-Shing Yu
- Laboratory Animal Center, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Shu-Wha Lin
- Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Ming-Hsien Chiang
- Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Chan-Jung Liang
- Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; Center for Lipid Biosciences, Kaohsiung Medical University Hospital, Taiwan
| | - Chi-Ming Pu
- Division of Plastic Surgery, Department of Surgery, Cathay General Hospital, Taipei, Taiwan
| | - Yu-Chen Chen
- Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Ming-Shian Lin
- Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi City, Taiwan; Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi, Taiwan.
| | - Yuh-Lien Chen
- Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
| |
Collapse
|
|
30
|
Cuong DM, Kim JK, Jeon J, Kim TJ, Park JS, Park SU. Expression of Carotenoid Biosynthetic Genes and Carotenoid Biosynthesis during Seedling Development of Momordica charantia. Nat Prod Commun 2018. [DOI: 10.1177/1934578x1801300312] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Carotenoids belong to a large group of secondary metabolites, and have pivotal roles in plants, including photosynthesis and phytohormone synthesis, pigmentation, and membrane stabilization. Additionally, carotenoids are potent antioxidants, and their health benefits are becoming increasingly prominent. In recent years, carotenoids have been studied in many plants. Furthermore, gene expression, as well as carotenoid accumulation in different parts of the bitter melon, has been investigated; however, it has not been studied in bitter melon seedlings. In this study, carotenoid accumulation and transcript levels of McGGPPS1, McGGPPS2, McPSY, McPDS, McZDS, McLCYB, McLCYE1, McLCYE2, McCXHB, and McZEP, involved in carotenoid biosynthesis, were analyzed during seedling development using HPLC and qRT-PCR. The major carotenoids that accumulated in the bitter melon seedlings were lutein and E-β-carotene. The expression of most carotenoid biosynthetic genes increased during seedling development, consistent with the accumulation of violaxanthin, lutein, zeaxanthin, β-cryptoxanthin, 13Z-β-carotene, E-β-carotene, and 9Z-β-carotene in bitter melon seedlings. The results of this study provide a firm basis for comprehending the link between gene expression and carotenoid concentration in bitter melon seedlings.
Collapse
Affiliation(s)
- Do Manh Cuong
- Department of Crop Science, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Korea
| | - Jae Kwang Kim
- Division of Life Sciences and Convergence Research Center for Insect Vectors, Incheon National University, Incheon 22012, Korea
| | - Jin Jeon
- Department of Crop Science, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Korea
| | - Tae Jin Kim
- Division of Life Sciences and Convergence Research Center for Insect Vectors, Incheon National University, Incheon 22012, Korea
| | - Jong Seok Park
- Department of Horticultural Science, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Korea
| | - Sang Un Park
- Department of Crop Science, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Korea
| |
Collapse
|
|
31
|
Yang WS, Yang E, Kim MJ, Jeong D, Yoon DH, Sung GH, Lee S, Yoo BC, Yeo SG, Cho JY. Momordica charantia Inhibits Inflammatory Responses in Murine Macrophages via Suppression of TAK1. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2018; 46:435-452. [PMID: 29463104 DOI: 10.1142/s0192415x18500222] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Momordica charantia known as bitter melon is a representative medicinal plant reported to exhibit numerous pharmacological activities such as antibacterial, antidiabetic, anti-inflammatory, anti-oxidant, antitumor, and hypoglycemic actions. Although this plant has high ethnopharmacological value for treating inflammatory diseases, the molecular mechanisms by which it inhibits the inflammatory response are not fully understood. In this study, we aim to identify the anti-inflammatory mechanism of this plant. To this end, we studied the effects of its methanol extract (Mc-ME) on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Specifically, we evaluated nitric oxide (NO) production, mRNA expression of inflammatory genes, luciferase reporter gene activity, and putative molecular targets. Mc-ME blocked NO production in a dose-dependent manner in RAW264.7 cells; importantly, no cytotoxicity was observed. Moreover, the mRNA expression levels of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 were decreased by Mc-ME treatment in a dose-dependent manner. Luciferase assays and nuclear lysate immunoblotting analyses strongly indicated that Mc-ME decreases the levels of p65 [a nuclear factor (NF)-[Formula: see text]B subunit] and c-Fos [an activator protein (AP)-1 subunit]. Whole lysate immunoblotting assays, luciferase assays, and overexpression experiments suggested that transforming growth factor [Formula: see text]-activated kinase 1 (TAK1) is targeted by Mc-ME, thereby suppressing NF-[Formula: see text]B and AP-1 activity via downregulation of extracellular signal-regulated kinases (ERKs) and AKT. These results strongly suggest that Mc-ME exerts its anti-inflammatory activity by reducing the action of TAK1, which also affects the activation of NF-[Formula: see text]B and AP-1.
Collapse
Affiliation(s)
- Woo Seok Yang
- * Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Eunju Yang
- † Gyeonggi Science High School for the Gifted, Suwon 16297, Republic of Korea
| | - Min-Jeong Kim
- ‡ Department of Radiology, Hallym Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Gyeonggi 14068, Republic of Korea
| | - Deok Jeong
- * Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Deok Hyo Yoon
- § Institute for Bio-Medical Convergence, International St. Mary's Hospital and College of Medicine, Catholic Kwandong University, Incheon 22711, Republic of Korea
| | - Gi-Ho Sung
- § Institute for Bio-Medical Convergence, International St. Mary's Hospital and College of Medicine, Catholic Kwandong University, Incheon 22711, Republic of Korea
| | - Seungihm Lee
- † Gyeonggi Science High School for the Gifted, Suwon 16297, Republic of Korea
| | - Byong Chul Yoo
- ¶ Colorectal Cancer Branch, Research Institute, National Cancer Center, Goyang 10408, Republic of Korea
| | - Seung-Gu Yeo
- ∥ Department of Radiation Oncology, Soonchunhyang University College of Medicine, Soonchunhyang University Hospital, Cheonan 31151, Republic of Korea
| | - Jae Youl Cho
- * Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
- † Gyeonggi Science High School for the Gifted, Suwon 16297, Republic of Korea
| |
Collapse
|
|
32
|
New Insights into the Mechanisms of Chinese Herbal Products on Diabetes: A Focus on the "Bacteria-Mucosal Immunity-Inflammation-Diabetes" Axis. J Immunol Res 2017; 2017:1813086. [PMID: 29164155 PMCID: PMC5661076 DOI: 10.1155/2017/1813086] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2017] [Revised: 06/27/2017] [Accepted: 07/25/2017] [Indexed: 12/25/2022] Open
Abstract
Diabetes, especially type 2, has been rapidly increasing all over the world. Although many drugs have been developed and used to treat diabetes, side effects and long-term efficacy are of great challenge. Therefore, natural health product and dietary supplements have been of increasing interest alternatively. In this regard, Chinese herbs and herbal products have been considered a rich resource of product development. Although increasing evidence has been produced from various scientific studies, the mechanisms of action are lacking. Here, we have proposed that many herbal monomers and formulae improve glucose homeostasis and diabetes through the BMID axis; B represents gut microbiota, M means mucosal immunity, I represents inflammation, and D represents diabetes. Chinese herbs have been traditionally used to treat diabetes, with minimal side and toxic effects. Here, we reviewed monomers such as berberine, ginsenoside, M. charantia extract, and curcumin and herbal formulae such as Gegen Qinlian Decoction, Danggui Liuhuang Decoction, and Huanglian Wendan Decoction. This review was intended to provide new perspectives and strategies for future diabetes research and product.
Collapse
|
|
33
|
Ota A, Ulrih NP. An Overview of Herbal Products and Secondary Metabolites Used for Management of Type Two Diabetes. Front Pharmacol 2017; 8:436. [PMID: 28729836 PMCID: PMC5499308 DOI: 10.3389/fphar.2017.00436] [Citation(s) in RCA: 91] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2016] [Accepted: 06/16/2017] [Indexed: 12/29/2022] Open
Abstract
Diabetes mellitus is a common effect of uncontrolled high blood sugar and it is associated with long-term damage, dysfunction, and failure of various organs. In the adult population, the global prevalence of diabetes has nearly doubled since 1980. Without effective prevention and management programs, the continuing significant rise in diabetes will have grave consequences on the health and lifespan of the world population, and also on the world economy. Supplements can be used to correct nutritional deficiencies or to maintain an adequate intake of certain nutrients. These are often used as treatments for diabetes, sometimes because they have lower costs, or are more accessible or "natural" compared to prescribed medications. Several vitamins, minerals, botanicals, and secondary metabolites have been reported to elicit beneficial effects in hypoglycemic actions in vivo and in vitro; however, the data remain conflicting. Many pharmaceuticals commonly used today are structurally derived from natural compounds from traditional medicinal plants. Botanicals that are most frequently used to help manage blood glucose include: bitter melon (Momordica charantia), fenugreek (Trigonella foenum graecum), gurmar (Gymnema sylvestre), ivy gourd (Coccinia indica), nopal (Opuntia spp.), ginseng, Russian tarragon (Artemisia dracunculus), cinnamon (Cinnamomum cassia), psyllium (Plantago ovata), and garlic (Allium sativum). In majority of the herbal products and secondary metabolites used in treating diabetes, the mechanisms of action involve regulation of insulin signaling pathways, translocation of GLUT-4 receptor and/or activation the PPARγ. Several flavonoids inhibit glucose absorption by inhibiting intestinal α-amylase and α-glucosidase. In-depth studies to validate the efficacies and safeties of extracts of these traditional medicinal plants are needed, and large, well designed, clinical studies need to be carried out before the use of such preparations can be recommended for treatment and/or prevention of diabetes. The main focus of this review is to describe what we know to date of the active compounds in these, along with their glucose-lowering mechanisms, which are either through insulin-mimicking activity or enhanced glucose uptake.
Collapse
Affiliation(s)
| | - Nataša P. Ulrih
- Department of Food Science and Technology, Biotechnical Faculty, University of LjubljanaLjubljana, Slovenia
| |
Collapse
|
|
34
|
Khatib A, Perumal V, Ahmed QU, Uzir BF, Abas F, Murugesu S. Characterization of Antioxidant Activity ofMomordica CharantiaFruit by Infrared-Based Fingerprinting. ANAL LETT 2017. [DOI: 10.1080/00032719.2016.1261877] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- Alfi Khatib
- Department of Pharmaceutical Chemistry, Kulliyah of Pharmacy, International Islamic University Malaysia, Kuantan, Pahang DM, Malaysia
| | - Vikneswari Perumal
- Department of Pharmaceutical Chemistry, Kulliyah of Pharmacy, International Islamic University Malaysia, Kuantan, Pahang DM, Malaysia
| | - Qamar Uddin Ahmed
- Department of Pharmaceutical Chemistry, Kulliyah of Pharmacy, International Islamic University Malaysia, Kuantan, Pahang DM, Malaysia
| | - Bisha Fathamah Uzir
- Department of Pharmaceutical Chemistry, Kulliyah of Pharmacy, International Islamic University Malaysia, Kuantan, Pahang DM, Malaysia
| | - Faridah Abas
- Laboratory of Natural Products, Institute of Bioscience, University Putra Malaysia, Serdang, Malaysia
| | - Suganya Murugesu
- Department of Pharmaceutical Chemistry, Kulliyah of Pharmacy, International Islamic University Malaysia, Kuantan, Pahang DM, Malaysia
| |
Collapse
|
|
35
|
Acute effects of a beverage containing bitter melon extract (CARELA) on postprandial glycemia among prediabetic adults. Nutr Diabetes 2017; 7:e241. [PMID: 28092345 PMCID: PMC5301041 DOI: 10.1038/nutd.2016.51] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2016] [Revised: 10/17/2016] [Accepted: 10/31/2016] [Indexed: 01/16/2023] Open
Abstract
Background: Acute ingestion of bitter melon (BM) has been shown to suppress the postprandial glycemic response in diabetics, but its impact on glucose regulation among individuals with impaired glucose tolerance is unclear. Moreover, one's glucose tolerance level may influence the effectiveness of BM. This study aimed to examine the acute effects of a beverage containing BM extract on blood glucose regulation during an oral glucose tolerance test (OGTT) among prediabetics. Methods: Ten prediabetic adults completed two OGTTs—glucose only (D2) and glucose+BM (D3). Responders were identified as subjects whose area under the glucose curve (AUCglu) during D3 was lower than D2. To compare the acute effects of the beverage among individuals with varying glucose tolerance levels, subjects were grouped by their glucose response pattern—Fastpeak (peak glucose (Glupeak) at 30 min postglucose (30P)) and Slowpeak (Glupeak after 30P). Results: During D3, responders (n=5) experienced a 13.2% reduction in AUCglu (95% confidence interval (CI): −18.1% to −8.3%), 12.2% reduction in mean glucose (95% CI: −17.3% to −7.0%) and 10.6% reduction in Glupeak (95% CI: −17.5% to −3.7%); plasma glucose was reduced by 9.1% at 30P (95% CI: −15.6% to −2.6%), −24.0% at 60P (95% CI: −36.8% to −11.2%) and −20.0% at 90P (95% CI: −35.8% to −4.2%) during D3. No between-trial differences were noted for Fastpeak or Slowpeak. Conclusions: Acute ingestion of BM prior to the second OGTT (D3) led to a reduced postprandial glucose response in 50% of the subjects but did not affect the insulin response. Furthermore, the effectiveness of the beverage was seemingly uninfluenced by the subjects' glucose tolerance level. Although BM has shown to aid blood glucose management in diabetics, it remains uncertain why only a portion of subjects responded positively to the BM extract in the current study.
Collapse
|
|
36
|
Cicero AFG, Colletti A. Role of phytochemicals in the management of metabolic syndrome. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2016; 23:1134-44. [PMID: 26778479 DOI: 10.1016/j.phymed.2015.11.009] [Citation(s) in RCA: 89] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/10/2015] [Revised: 11/14/2015] [Accepted: 11/19/2015] [Indexed: 05/28/2023]
Abstract
BACKGROUND The World Health Organization (WHO) for some years has been focusing on what is now commonly referred to as an "epidemic of obesity and diabetes" ("diabesity"): behind this outbreak, there are several risk factors grouped in what is called "metabolic syndrome" (MetS). The basis of this "epidemic" is either a diet too often characterized by excessive consumption of saturated and trans-esterified fatty acids, simple sugars and salt, either a sedentary lifestyle. PURPOSE The aim of this review is to focus on the phytochemicals that have a more positive effect on the treatment and/or prevention of MetS. CHAPTERS Treatment strategies for MetS include pharmacologic and non-pharmacologic options, with varying degrees of success rate. The first is indicated for patients with high cardiovascular risk, while the second one is the most cost-effective preventive approach for subjects with borderline parameters and for patients intolerant to pharmacological therapy. MetS non-pharmacological treatments could involve the use of nutraceuticals, most of which has plant origins (phytochemicals), associated with lifestyle improvement. The chapter will discuss the available evidence on soluble fibres from psyllium and other sources, cinnamaldehyde, cinnamic acid and other cinnamon phytochemicals, berberine, corosolic acid from banaba, charantin from bitter gourd, catechins and flavonols from green tea and cocoa. Vegetable omega-3 polyunsaturated fatty acids, alliin from garlic, soy peptides, and curcumin from curcuma longa. CONCLUSION Some nutraceuticals, when adequately dosed, should improve a number of the MetS components.
Collapse
Affiliation(s)
- Arrigo F G Cicero
- Diseases Research Center, Medicine & Surgery Dept., Alma Mater Studiorum Atherosclerosis and Metabolic University of Bologna, Bologna, Italy.
| | - Alessandro Colletti
- Diseases Research Center, Medicine & Surgery Dept., Alma Mater Studiorum Atherosclerosis and Metabolic University of Bologna, Bologna, Italy
| |
Collapse
|
|
37
|
Jiang B, Ji M, Liu W, Chen L, Cai Z, Zhao Y, Bi X. Antidiabetic activities of a cucurbitane‑type triterpenoid compound from Momordica charantia in alloxan‑induced diabetic mice. Mol Med Rep 2016; 14:4865-4872. [PMID: 27748816 DOI: 10.3892/mmr.2016.5800] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2015] [Accepted: 09/12/2016] [Indexed: 11/06/2022] Open
Abstract
Momordica charantia has been used to treat a variety of diseases, including inflammation, diabetes and cancer. A cucurbitane‑type triterpenoid [(19R,23E)‑5β, 19‑epoxy‑19‑methoxy‑cucurbita‑6,23,25‑trien‑3 β‑o‑l] previously isolated from M. charantia was demonstrated to possess significant cytotoxicity against cancer cells. The current study investigated the effects of this compound (referred to as compound K16) on diabetes using an alloxan‑induced diabetic mouse model. C57BL/6J mice were intraperitoneally injected with alloxan (10 mg/kg body weight), and those with blood glucose concentration higher than 10 mM were selected for further experiments. Diabetic C57BL/6J mice induced by alloxan were administered 0.9% saline solution, metformine (10 mg/kg body weight), or K16 (25 or 50 mg/kg body weight) by gavage for 4 weeks, followed by analysis of blood glucose level, glucose tolerance, serum lipid levels and organ indexes. The results demonstrated that compound K16 significantly reduced blood glucose (31‑48.6%) and blood lipids (13.5‑42.8%; triglycerides and cholesterol), while improving glucose tolerance compared with diabetic mice treated with saline solution, suggesting a positive improvement in glucose and lipid metabolism following K16 treatment. Furthermore, similarly to metformine, compound K16 markedly upregulated the expression of a number of insulin signaling pathway‑associated proteins, including insulin receptor, insulin receptor substrate 1, glycogen synthase kinase 3β, Akt serine/threonine kinase, and the transcript levels of glucose transporter type 4 and AMP‑activated protein kinase α1. The results of the current study demonstrated that compound K16 alleviated diabetic metabolic symptoms in alloxan‑induced diabetic mice, potentially by affecting genes and proteins involved in insulin metabolism signaling.
Collapse
Affiliation(s)
- Bowen Jiang
- College of Life Science, Liaoning University, Shenyang, Liaoning 110036, P.R. China
| | - Mingli Ji
- Department of Physiology, College of Basic Medicine, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China
| | - Wei Liu
- College of Life Science, Liaoning University, Shenyang, Liaoning 110036, P.R. China
| | - Lili Chen
- College of Life Science, Liaoning University, Shenyang, Liaoning 110036, P.R. China
| | - Zhiyu Cai
- College of Life Science, Liaoning University, Shenyang, Liaoning 110036, P.R. China
| | - Yuqing Zhao
- Department of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, P.R. China
| | - Xiuli Bi
- College of Life Science, Liaoning University, Shenyang, Liaoning 110036, P.R. China
| |
Collapse
|
|
38
|
Martínez-Abundis E, Mendez-del Villar M, Pérez-Rubio KG, Zuñiga LY, Cortez-Navarrete M, Ramírez-Rodriguez A, González-Ortiz M. Novel nutraceutic therapies for the treatment of metabolic syndrome. World J Diabetes 2016; 7:142-52. [PMID: 27076875 PMCID: PMC4824685 DOI: 10.4239/wjd.v7.i7.142] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2015] [Revised: 01/24/2016] [Accepted: 02/14/2016] [Indexed: 02/05/2023] Open
Abstract
Nutraceutic therapies such as berberine, bitter melon, Gymnema sylvestre, Irvingia gabonensis, resveratrol and ursolic acid have been shown to help control metabolic syndrome (MetS). The effect of berberine on glucose and lipid metabolism, hypertension, obesity and MetS has been evaluated in animal models and humans. Most clinical trials involving bitter melon have been conducted to evaluate its effect on glucose metabolism; nevertheless, some studies have reported favorable effects on lipids and blood pressure although there is little information about its effect on body weight. Gymnema sylvestre helps to decrease body weight and blood sugar levels; however, there is limited information on dyslipidemia and hypertension. Clinical trials of Irvingia gabonensis have shown important effects decreasing glucose and cholesterol concentrations as well decreasing body weight. Resveratrol acts through different mechanisms to decrease blood pressure, lipids, glucose and weight, showing its effects on the population with MetS. Finally, there is evidence of positive effects with ursolic acid in in vitro and in vivo studies on glucose and lipid metabolism and on body weight and visceral fat. Therefore, a review of the beneficial effects and limitations of the above-mentioned nutraceutic therapies is presented.
Collapse
|
|
39
|
Chen GC, Su HM, Lin YS, Tsou PY, Chyuan JH, Chao PM. A conjugated fatty acid present at high levels in bitter melon seed favorably affects lipid metabolism in hepatocytes by increasing NAD(+)/NADH ratio and activating PPARα, AMPK and SIRT1 signaling pathway. J Nutr Biochem 2016; 33:28-35. [PMID: 27260465 DOI: 10.1016/j.jnutbio.2016.03.009] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2015] [Revised: 03/09/2016] [Accepted: 03/20/2016] [Indexed: 01/13/2023]
Abstract
α-Eleostearic acid (α-ESA), or the cis-9, trans-11, trans-13 isomer of conjugated linolenic acid, is a special fatty acid present at high levels in bitter melon seed oil. The aim of this study was to examine the effect of α-ESA on hepatic lipid metabolism. Using H4IIEC3 hepatoma cell line, we showed that α-ESA significantly lowered intracellular triglyceride accumulation compared to α-linolenic acid (LN), used as a fatty acid control, in a dose- and time-dependent manner. The effects of α-ESA on enzyme activities and mRNA profiles in H4IIEC3 cells suggested that enhanced fatty acid oxidation and lowered lipogenesis were involved in α-ESA-mediated triglyceride lowering effects. In addition, α-ESA triggered AMP-activated protein kinase (AMPK) activation without altering sirtuin 1 (SIRT1) protein levels. When cells were treated with vehicle control (VC), LN alone (LN; 100μmol/L) or in combination with α-ESA (LN+α-ESA; 75+25μmol/L) for 24h, acetylation of forkhead box protein O1 was decreased, while the NAD(+)/NADH ratio, mRNA levels of NAMPT and PTGR1 and enzyme activity of nicotinamide phosphoribosyltransferase were increased by LN+α-ESA treatment compared to treatment with LN alone, suggesting that α-ESA activates SIRT1 by increasing NAD(+) synthesis and NAD(P)H consumption. The antisteatosis effect of α-ESA was confirmed in mice treated with a high-sucrose diet supplemented with 1% α-ESA for 5weeks. We conclude that α-ESA favorably affects hepatic lipid metabolism by increasing cellular NAD(+)/NADH ratio and activating PPARα, AMPK and SIRT1 signaling pathways.
Collapse
Affiliation(s)
- Gou-Chun Chen
- Department of Nutrition, China Medical University, Taichung, Taiwan
| | - Hui-Min Su
- Graduate Institute of Physiology, National Taiwan University, Taipei, Taiwan
| | - Yu-Shun Lin
- Department of Nutrition, China Medical University, Taichung, Taiwan
| | - Po-Yen Tsou
- Department of Nutrition, China Medical University, Taichung, Taiwan
| | - Jong-Ho Chyuan
- Hualien District Agricultural Research and Extension Station, Hualien, Taiwan
| | - Pei-Min Chao
- Department of Nutrition, China Medical University, Taichung, Taiwan.
| |
Collapse
|
|
40
|
Application of Herbal Medicines with Bitter Flavor and Cold Property on Treating Diabetes Mellitus. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2015; 2015:529491. [PMID: 26557150 PMCID: PMC4628671 DOI: 10.1155/2015/529491] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/23/2015] [Revised: 09/19/2015] [Accepted: 09/29/2015] [Indexed: 12/18/2022]
Abstract
Diabetes mellitus has been a global pandemic. Traditional Chinese Medicine has been used on diabetes mellitus for thousands of years and the modern Chinese medicine studies have found a curative effect of herbal medicine with bitter flavor and cold property on diabetes. This review will introduce the theory summary of flavor and property in TCM, argument basis, the evidences from clinical trails and animal experiments, the possible antidiabetic mechanisms, and advantages on lowering glucose of herbal medicines with bitter flavor and cold property and take rhizome, Chinese rhubarb, and Momordica charantia, the three herbal medicines with bitter flavor and cold property, as examples to illustrate the exact antidiabetic effect. It is hoped that this review can provide some ideas and inspiration for the treatment of diabetes with herbal medicine.
Collapse
|
|
41
|
Beneficial role of bitter melon supplementation in obesity and related complications in metabolic syndrome. J Lipids 2015; 2015:496169. [PMID: 25650336 PMCID: PMC4306384 DOI: 10.1155/2015/496169] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2014] [Accepted: 12/05/2014] [Indexed: 02/06/2023] Open
Abstract
Diabetes, obesity, and metabolic syndrome are becoming epidemic both in developed and developing countries in recent years. Complementary and alternative medicines have been used since ancient era for the treatment of diabetes and cardiovascular diseases. Bitter melon is widely used as vegetables in daily food in Bangladesh and several other countries in Asia. The fruits extract of bitter melon showed strong antioxidant and hypoglycemic activities in experimental condition both in vivo and in vitro. Recent scientific evaluation of this plant extracts also showed potential therapeutic benefit in diabetes and obesity related metabolic dysfunction in experimental animals and clinical studies. These beneficial effects are mediated probably by inducing lipid and fat metabolizing gene expression and increasing the function of AMPK and PPARs, and so forth. This review will thus focus on the recent findings on beneficial effect of Momordica charantia extracts on metabolic syndrome and discuss its potential mechanism of actions.
Collapse
|
|
42
|
Lo HY, Ho TY, Li CC, Chen JC, Liu JJ, Hsiang CY. A novel insulin receptor-binding protein from Momordica charantia enhances glucose uptake and glucose clearance in vitro and in vivo through triggering insulin receptor signaling pathway. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2014; 62:8952-8961. [PMID: 25144709 DOI: 10.1021/jf5002099] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
Abstract
Diabetes, a common metabolic disorder, is characterized by hyperglycemia. Insulin is the principal mediator of glucose homeostasis. In a previous study, we identified a trypsin inhibitor, named Momordica charantia insulin receptor (IR)-binding protein (mcIRBP) in this study, that might interact with IR. The physical and functional interactions between mcIRBP and IR were clearly analyzed in the present study. Photo-cross-linking coupled with mass spectrometry showed that three regions (17-21, 34-40, and 59-66 residues) located on mcIRBP physically interacted with leucine-rich repeat domain and cysteine-rich region of IR. IR-binding assay showed that the binding behavior of mcIRBP and insulin displayed a cooperative manner. After binding to IR, mcIRBP activated the kinase activity of IR by (5.87 ± 0.45)-fold, increased the amount of phospho-IR protein by (1.31 ± 0.03)-fold, affected phosphoinositide-3-kinase/Akt pathways, and consequently stimulated the uptake of glucose in 3T3-L1 cells by (1.36 ± 0.12)-fold. Intraperitoneal injection of 2.5 nmol/kg mcIRBP significantly decreased the blood glucose levels by 20.9 ± 3.2% and 10.8 ± 3.6% in normal and diabetic mice, respectively. Microarray analysis showed that mcIRBP affected genes involved in insulin signaling transduction pathway in mice. In conclusion, our findings suggest that mcIRBP is a novel IRBP that binds to sites different from the insulin-binding sites on IR and stimulates both the glucose uptake in cells and the glucose clearance in mice.
Collapse
Affiliation(s)
- Hsin-Yi Lo
- Graduate Institute of Chinese Medicine, China Medical University , Taichung 40402, Taiwan
| | | | | | | | | | | |
Collapse
|
|
43
|
Antidiabetic Evaluation of Momordica charantia L Fruit Extracts. W INDIAN MED J 2014; 63:294-9. [PMID: 25429471 DOI: 10.7727/wimj.2013.180] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2013] [Accepted: 10/29/2013] [Indexed: 01/03/2023]
Abstract
To investigate hypoglycaemic, hypolipidaemic and pancreatic beta cell regeneration activities of Momordica charantia L fruits(MC). Alloxan induced diabetic rabbits were treated with methanolic and ethanolic MC extract. Effects of plant extracts and the drug glibenclamide on serum glucose, lipid profile and pancreatic beta cell were determined after two weeks of treatment. Serum glucose and lipid profiles were assayed by kit methods. Pancreatic tissue histopathology was performed to study pancreatic beta cells regeneration. Momordica charantia extracts produced significant hypoglycaemic effects (p < 0.05). Hypolipidaemic activity of MC was negligible. Momordica charantia supplementations were unable to normalize glucose and lipid profiles. Glibenclamide, a standard drug, not only lowered the hyperglycaemia and hyperlipidaemia but also restored the normal levels. Regeneration of pancreatic beta cells by MC extracts was minimal, with fractional improvement produced by glibenclamide. The most significant finding of the present study was a 28% reduction in hyperglycaemia by MC ethanol extracts. To determine reliable antidiabetic potentials of MC, identification of the relevant antidiabetic components and underlying mechanisms is warranted.
Collapse
|
|
44
|
Simpson R, Morris GA. The anti-diabetic potential of polysaccharides extracted from members of the cucurbit family: A review. ACTA ACUST UNITED AC 2014. [DOI: 10.1016/j.bcdf.2014.03.003] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
|
|
45
|
Mohamed S. Functional foods against metabolic syndrome (obesity, diabetes, hypertension and dyslipidemia) and cardiovasular disease. Trends Food Sci Technol 2014. [DOI: 10.1016/j.tifs.2013.11.001] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
|
|
46
|
|
|
47
|
Perez JL, Jayaprakasha GK, Patil BS. Separation and Identification of Cucurbitane-Type Triterpenoids from Bitter Melon. ACS SYMPOSIUM SERIES 2014. [DOI: 10.1021/bk-2014-1185.ch003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Jose Luis Perez
- Vegetable and Fruit Improvement Center, Department of Horticultural Sciences, Texas A&M University, College Station, Texas 77845-2119
| | - G. K. Jayaprakasha
- Vegetable and Fruit Improvement Center, Department of Horticultural Sciences, Texas A&M University, College Station, Texas 77845-2119
| | - Bhimanagouda S. Patil
- Vegetable and Fruit Improvement Center, Department of Horticultural Sciences, Texas A&M University, College Station, Texas 77845-2119
| |
Collapse
|
|
48
|
Nkambo W, Anyama NG, Onegi B. In vivo hypoglycemic effect of methanolic fruit extract of Momordica charantia L. Afr Health Sci 2013; 13:933-9. [PMID: 24940315 DOI: 10.4314/ahs.v13i4.11] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Momordica charantia L. is a medicinal plant commonly used in the management of diabetes mellitus. OBJECTIVES We investigated the blood glucose lowering effect of the methanolic fruit extract of the Ugandan variety of M. charantia L. in alloxan-induced diabetic albino rats. METHODS 500g of M. charantia powder were macerated in methanol and the extract administered to two groups of alloxan-induced diabetic rats. The first group received 125mg/kg, the second 375mg/kg and a third group 7mg/kg of metformin. A fourth group received 1ml normal saline. Fasting blood glucose (FBG) levels were measured at 0.5,1,2,3,5,8 and 12 hours and compared using one-way ANOVA. RESULTS There was an initial rise in FBG for 1 hour after administration of extracts followed by steep reductions. Significant reduction in FBG occurred at 2 hours for 125mg/kg of extract (-3.2%, 313±25.9 to 303±25.0mg/dL, p = 0.049), 375mg/kg of extract (-3.9%, 356±19.7 to 342±20.3mg/dL, p = 0.001), and metformin (-2.6%, 344±21.7 to 335±21.1mg/dL, p = 0.003) when compared to normal saline. The maximum percentage reduction in FBG by both extracts occurred between 3 and 12 hours post dose. CONCLUSIONS The methanolic fruit extract of M. charantia exhibits dose dependent hypoglycaemic activity in vivo.
Collapse
Affiliation(s)
- W Nkambo
- Department of Pharmacy, School of Health Sciences, College of Health Sciences, Makerere University, P.O. Box 7072, Kampala, Uganda
| | - N G Anyama
- Department of Pharmacy, School of Health Sciences, College of Health Sciences, Makerere University, P.O. Box 7072, Kampala, Uganda
| | - B Onegi
- Department of Pharmacy, School of Health Sciences, College of Health Sciences, Makerere University, P.O. Box 7072, Kampala, Uganda
| |
Collapse
|
|
49
|
Overview of Botanical Status in EU, USA, and Thailand. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2013; 2013:480128. [PMID: 24228061 PMCID: PMC3818839 DOI: 10.1155/2013/480128] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/09/2013] [Revised: 07/19/2013] [Accepted: 07/26/2013] [Indexed: 01/19/2023]
Abstract
The botanical status in EU, USA, and Thailand is different owing to the regulatory status, the progress of science, and the influence of culture and society. In the EU, botanicals are positioned as herbal medicinal products and food supplements, in the US they are regulated as dietary supplements but often used as traditional medicines, and in Thailand, they are regulated and used as traditional medicines. Information for some of the most popular botanicals from each country is included in this review.
Collapse
|
|
50
|
Uzayisenga R, Ayeka PA, Wang Y. Anti-diabetic potential of Panax notoginseng saponins (PNS): a review. Phytother Res 2013; 28:510-6. [PMID: 23846979 DOI: 10.1002/ptr.5026] [Citation(s) in RCA: 83] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2013] [Revised: 03/18/2013] [Accepted: 05/21/2013] [Indexed: 12/30/2022]
Abstract
Herbal medicines have traditionally played a major role in the management of diabetes in Asian countries for centuries. Panax notoginseng (Burk) F. H. Chen (Araliaceae) known as Tiánqī or san qi is a well-known medicinal herb in Asia for its long history of use in Chinese medicine. Qualified as 'the miracle root for the preservation of life', it has been used in China for 600 years, for treatment of various diseases. Panax notoginseng saponins (PNS) are the key active components. PNS have been widely used in China for treatment of cardiovascular diseases. However, scientific studies have shown a wide range of other pharmacological applications including anti-cancer, neuroprotective and anti-inflammatory agents, immunologic adjuvant and prevention of diabetes complications. Recently, hypoglycemic and anti-obesity properties of PNS have also been demonstrated. The present review highlights the effects of PNS on glucose production and absorption, and on inflammatory processes that seem to play an important role in the development of diabetes.
Collapse
Affiliation(s)
- Rosette Uzayisenga
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 88 Yuquan Road, Tianjin, 300193, PR China; District Pharmacy, Ministry of Health, P.O. Box 84, Kigali, Rwanda
| | | | | |
Collapse
|