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Chen Z, Xun L, Lu Y, Yang X, Chen M, Yang T, Mei Z, Yang Y, Yang X, Yang Y. The chromosome-scale genomes of two Tinospora species reveal differential regulation of the MEP pathway in terpenoid biosynthesis. BMC Biol 2025; 23:84. [PMID: 40114206 PMCID: PMC11927234 DOI: 10.1186/s12915-025-02185-z] [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: 10/24/2024] [Accepted: 03/04/2025] [Indexed: 03/22/2025] Open
Abstract
BACKGROUND The relationship between gene family expansion and the resulting changes in plant phenotypes has shown remarkable complexity during the evolution. The gene family expansion has contributed to the diversity in plant phenotypes, specifically metabolites through neo-functionalization and sub-functionalization. However, the negative regulatory effects associated with the gene family expansion remain poorly understood. RESULTS Here, we present the chromosome-scale genomes of Tinospora crispa and Tinospora sinensis. Comparative genomic analyses demonstrated conserved chromosomal evolution within the Menispermaceae family. KEGG analysis revealed a significant enrichment of genes related to terpenoid biosynthesis in T. sinensis. However, T. crispa exhibited a higher abundance of terpenoids compared to T. sinensis. Detailed analysis revealed the expansion of genes encoding 1-hydroxy-2-methyl 2-(E)-butenyl 4-diphosphate synthase (HDS), a key enzyme in the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway of terpenoid biosynthesis in T. sinensis. TsiHDS4 retained the ancestral function of converting methylerythritol cyclic diphosphate (MEcPP) to (E)-4-hydroxy-3-methylbut-2-enyl diphosphate (HMBPP). However, the noncanonical CDS-derived small peptide TsiHDS5 was shown to interact with TsiHDS4, inhibiting its catalytic activity. This interaction reduced the levels of HMBPP and isopentenyl pyrophosphate (IPP), which represent key substrates for downstream terpenoid biosynthesis. CONCLUSIONS These findings offer clues to decipher the variations in the MEP pathway of terpenoid biosynthesis between T. crispa and T. sinensis and form a basis for further detailed research on the negative regulation of expanded genes.
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Affiliation(s)
- Zhiyu Chen
- Germplasm Bank of Wild Species, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan, 650201, China
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Lan Xun
- College of Agronomy and Biotechnology, Yunnan Agricultural University, Kunming, 650201, Yunnan, China
| | - Yunyan Lu
- College of Agronomy and Biotechnology, Yunnan Agricultural University, Kunming, 650201, Yunnan, China
| | - Xingyu Yang
- CAS Key Laboratory of Tropical Plant Resources and Sustainable Use, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Mengla, Yunnan, 666303, China
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Minghui Chen
- Yunnan International Joint Laboratory for the Conservation and Utilization of Tropical Timber Tree Species, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Mengla, Yunnan, 666303, China
| | - Tianyu Yang
- Germplasm Bank of Wild Species, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan, 650201, China
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Zhinan Mei
- College of Plant Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China
| | - Yunqiang Yang
- Yunnan International Joint Laboratory for the Conservation and Utilization of Tropical Timber Tree Species, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Mengla, Yunnan, 666303, China.
- CAS Key Laboratory of Tropical Plant Resources and Sustainable Use, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Mengla, Yunnan, 666303, China.
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.
| | - Xuefei Yang
- Key Laboratory of Economic Plants and Biotechnology, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan, 650201, China.
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.
- Southeast Asia Biodiversity Research Institute, Chinese Academy of Sciences, Yezin, Nay Pyi Taw, 05282, Myanmar.
| | - Yongping Yang
- Germplasm Bank of Wild Species, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan, 650201, China.
- Yunnan International Joint Laboratory for the Conservation and Utilization of Tropical Timber Tree Species, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Mengla, Yunnan, 666303, China.
- CAS Key Laboratory of Tropical Plant Resources and Sustainable Use, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Mengla, Yunnan, 666303, China.
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.
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Rai P, Garain T, Gupta D. Phytochemical analysis of Tinospora cordifolia and Withania somnifera and their therapeutic activities with special reference to COVID-19. World J Exp Med 2024; 14:95512. [PMID: 39312696 PMCID: PMC11372741 DOI: 10.5493/wjem.v14.i3.95512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Revised: 07/19/2024] [Accepted: 07/29/2024] [Indexed: 08/29/2024] Open
Abstract
Various important medicines make use of secondary metabolites that are produced by plants. Medicinal plants, such as Withania somnifera and Tinospora cordifolia, are rich sources of chemically active compounds and are reported to have numerous therapeutic applications. The therapeutic use of medicinal plants is widely mentioned in Ayurveda and has folkloric importance in different parts of the world. The aim of this review is to summarize the phytochemical profiles, folkloric importance, and primary pharmacological activity of W. somnifera and T. cordifolia with emphasis on their action against the novel coronavirus.
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Affiliation(s)
- Prateek Rai
- Chemistry, Amity Institute of Applied Sciences, Amity University, Noida 201301, Uttar Pradesh, India
| | - Tanya Garain
- Chemistry, Amity Institute of Applied Sciences, Amity University, Noida 201301, Uttar Pradesh, India
| | - Deepshikha Gupta
- Chemistry, Amity Institute of Applied Sciences, Amity University, Noida 201301, Uttar Pradesh, India
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Chaudhary A, Das R, Mehta K, Mehta DK. Indian herb Tinospora cordifolia and Tinospora species: Phytochemical and therapeutic application. Heliyon 2024; 10:e31229. [PMID: 38813196 PMCID: PMC11133831 DOI: 10.1016/j.heliyon.2024.e31229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Revised: 05/06/2024] [Accepted: 05/13/2024] [Indexed: 05/31/2024] Open
Abstract
Clinical investigations are increasingly focusing on natural materials with medical benefits because, in contrast to medicines, they have extremely few adverse effects. Tinospora species of the Menispermaceae family has many bioactive principles for plant nutraceuticals. A thorough assessment of the existing literature revealed that Indian Tinospora species are an important group of medicinal herbs used for a variety of pharmacological activities. While, Tinospora cordifolia is widely recognized as a significant herb in the Indian System of Medicines (ISM) due to its bioactive components and has been used in the treatment of diabetes, cancer, urinary problems, fever, jaundice, helminthiasis, leprosy, dysentery, skin diseases, and many more. Using the search phrases "phytochemistry," "traditional uses," and "pharmacological evaluation of Indian Tinospora species," appropriate articles were carefully extracted from the MEDLINE/PubMed, Scopus, and WOS databases. Around 180 articles, related to the India Tinospora species, were selected from a pool of 200 papers published between 1991 and 2023. T. cordifolia has received a lot of scientific attention because of its diverse therapeutic characteristics in treating various diseases. Our present study in this review encompasses 1.) Phytochemistry, traditional uses and pharmacological potential of T. cordifolia as well as other Indian Tinospora species. 2.) Safety and toxicity study and available marketed formulation of T. cordifolia for the treatment of various diseases. The chemical constitution and pharmacological characteristics of other Tinospora species must also be investigated, indicating a need for further scientific research.
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Affiliation(s)
- Anu Chaudhary
- Department of Pharmaceutical Chemistry, MM College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, 133207, India
| | - Rina Das
- Department of Pharmaceutical Chemistry, MM College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, 133207, India
| | - Kiran Mehta
- Chitkara Business School, Chitkara University, Rajpura, 140401, India
| | - Dinesh Kumar Mehta
- Department of Pharmaceutical Chemistry, MM College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, 133207, India
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Bhattacharya K, Khanal P, Patil VS, Dwivedi PSR, Chanu NR, Chaudhary RK, Deka S, Chakraborty A. Computational pharmacology profiling of borapetoside C against melanoma. J Biomol Struct Dyn 2024; 42:3233-3248. [PMID: 37203884 DOI: 10.1080/07391102.2023.2213333] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Accepted: 05/04/2023] [Indexed: 05/20/2023]
Abstract
Melanoma,also known as a 'black tumor', begins in the melanocytes when cells (that produce pigment) grows out of control. Immunological dysregulation, which raises the risk for multiple illnesses, including melanoma, may be influenced by stress tiggered through viral infection, long term effects of ultraviolet radiation, environmental pollutants etc. Borapetoside C is one of the phytoconstituents from Tinospora crispa, and its biological source has been reported for its antistress property. Network pharmacology and KEGG pathway analysis of borapetoside C-regulated proteins were conducted to identify the hub genes involved in melanoma development. Further, a molecular docking was performed between borapetoside C and targets involved in melanoma. Further, the top 3 complexes were selected based on the binding energy to conduct molecular dynamics simulations to evaluate the stability of ligand-protein complex followed by principal component analysis and dynamic cross-correlation matrix. In addition, borapetoside C was also screened for its pharmacokinetics and toxicity profile. Network Pharmacology studies and KEGG pathway analysis revealed 8 targets involved in melanoma. Molecular docking between borapetoside C and targets involved in melanoma identified 3 complexes with minimum binding i.e. borapetoside C- MAP2K1, MMP9, and EGFR. Further, molecular dynamics simulations showed a stable complex of borapetoside C with MMP9 and EGFR. The present study suggested that borapetoside C may target MMP9 and EGFR to possess an anti-melanoma property. This finding can be useful in developing a novel therapeutic agent against melanoma from a natural source.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Kunal Bhattacharya
- Pratiksha Institute of Pharmaceutical Sciences, Guwahati, Assam, India
- Royal School of Pharmacy, The Assam Royal Global University, Guwahati, Assam, India
| | - Pukar Khanal
- Department of Pharmacology, NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Nitte (Deemed to be University), Mangalore, India
| | - Vishal S Patil
- KLE College of Pharmacy, KLE Academy of Higher Education and Research, Belagavi, India
| | - Prarambh S R Dwivedi
- Department of Pharmacology, NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Nitte (Deemed to be University), Mangalore, India
| | - Nongmaithem Randhoni Chanu
- Pratiksha Institute of Pharmaceutical Sciences, Guwahati, Assam, India
- Faculty of Pharmaceutical Science, Assam Downtown University, Guwahati, Assam, India
| | - Raushan Kumar Chaudhary
- Department of Pharmacy Practice, NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Nitte (Deemed to be University), Mangalore, India
| | - Satyendra Deka
- Pratiksha Institute of Pharmaceutical Sciences, Guwahati, Assam, India
| | - Arup Chakraborty
- Pratiksha Institute of Pharmaceutical Sciences, Guwahati, Assam, India
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Zuhri UM, Yuliana ND, Fadilah F, Erlina L, Purwaningsih EH, Khatib A. Exploration of the main active metabolites from Tinospora crispa (L.) Hook. f. & Thomson stem as insulin sensitizer in L6.C11 skeletal muscle cell by integrating in vitro, metabolomics, and molecular docking. JOURNAL OF ETHNOPHARMACOLOGY 2024; 319:117296. [PMID: 37820996 DOI: 10.1016/j.jep.2023.117296] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 10/05/2023] [Accepted: 10/06/2023] [Indexed: 10/13/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Tinospora crispa (L.) Hook. f. & Thomson stem (TCS) has long been used as folk medicine for the treatment of diabetes mellitus. Previous study revealed that TCS possesses multi-ingredients and multi-targets characteristic potential as insulin sensitizer activity. However, its mechanisms of action and molecular targets are still obscure. AIM OF THE STUDY In the present study, we investigated the effects of TCS against insulin resistance in muscle cells through integrating in vitro experiment and identifying its active biomarker using metabolomics and in molecular docking validation. MATERIALS AND METHODS We used centrifugal partition chromatography (CPC) to isolate 33 fractions from methanolic extract of TCS, and then used UHPLC-Orbitrap-HRMS to identify the detectable metabolites in each fraction. We assessed the insulin sensitization activity of each fraction using enzyme-linked immunosorbent assay (ELISA), and then used confocal immunocytochemistry microscopy to measure the translocation of glucose transporter 4 (GLUT4) to the cell membrane. The identified active metabolites were further simulated for its molecular docking interaction using Autodock Tools. RESULTS The polar fractions of TCS significantly increased insulin sensitivity, as measured by the inhibition of phosphorylated insulin receptor substrate-1 (pIRS1) at serine-312 residue (ser312) also the increasing number of translocated GLUT4 and glycogen content. We identified 58 metabolites of TCS, including glycosides, flavonoids, alkaloids, coumarins, and nucleotides groups. The metabolomics and molecular docking simulations showed the presence of minor metabolites consisting of tinoscorside D, higenamine, and tinoscorside A as the active compounds. CONCLUSIONS Our findings suggest that TCS is a promising new treatment for insulin resistance and the identification of the active metabolites in TCS could lead to the development of new drugs therapies for diabetes that target these pathways.
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Affiliation(s)
- Ummu Mastna Zuhri
- Doctoral Program in Biomedical Science, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
| | - Nancy Dewi Yuliana
- Department of Food Science and Technology, Bogor Agricultural University, Bogor, Indonesia
| | - Fadilah Fadilah
- Doctoral Program in Biomedical Science, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; Department of Medical Chemistry, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
| | - Linda Erlina
- Department of Medical Chemistry, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
| | - Erni Hernawati Purwaningsih
- Doctoral Program in Biomedical Science, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; Department of Medical Pharmacy, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
| | - Alfi Khatib
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, International Islamic University Malaysia, Kuantan, Malaysia
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Medicinal plants used by rural Thai people to treat non-communicable diseases and related symptoms. Heliyon 2023; 9:e12758. [PMID: 36685400 PMCID: PMC9850000 DOI: 10.1016/j.heliyon.2022.e12758] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Revised: 12/21/2022] [Accepted: 12/29/2022] [Indexed: 01/06/2023] Open
Abstract
Non-communicable diseases (NCDs) are becoming more common in remote regions, whereas previously they were more common in middle-class to wealthy societies. The rising prevalence and severity of NCDs has increased the demand for medical innovation in this space. In this regard, knowledge of traditional medicines used in the treatment of NCDs, by people in the remote communities of Thailand, represents an innovation opportunity. This study aims to use data on ethnomedicinal plants used by local Thai people to identify plant candidates for study of safety and efficacy against a range of specified NCDs. Data were taken from both the literature and interviews from 230 locations in Thailand. The consulted literature was published in the years from 1990 to 2020. Ethnomedicinal field observations were made in person, in villages in Nan and Chiang Rai provinces, in 2021. Data includes names of plants used to target NCDs, and names of target diseases. Important plant species were identified based on the number of use reports and use values together with results from Bayesian approach. A total of 766 plant species were recorded in the treatment of NCDs. Most of the species that were described by informants were used to target diabetes, hypertension, chronic respiratory and renal diseases. This study proposes several plant species that have potential as treatments against NCDs. Many of these important species have insufficient scientific data to support their uses. The study suggests that assessment of efficacy and safety should be the next logical steps.
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Haque E, Bari MS, Khandokar L, Anjum J, Jantan I, Seidel V, Haque MA. An updated and comprehensive review on the ethnomedicinal uses, phytochemistry, pharmacological activity and toxicological profile of Tinospora crispa (L.) Hook. f. & Thomson. PHYTOCHEMISTRY REVIEWS : PROCEEDINGS OF THE PHYTOCHEMICAL SOCIETY OF EUROPE 2022; 22:211-273. [PMID: 36345416 PMCID: PMC9630822 DOI: 10.1007/s11101-022-09843-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Accepted: 10/08/2022] [Indexed: 06/16/2023]
Abstract
Tinospora crispa (L.) Hook. f. & Thomson (Menispermaceae) is a plant indigenous to Africa and South-East Asia. It is widely used in ethnomedicine to alleviate various diseases including hypertension, diabetes, rheumatism, jaundice, inflammation, fever, fractures, scabies, and urinary disorders. A total of 167 phytoconstituents, belonging to 12 different chemical categories, including alkaloids, flavonoids, terpenoids, and phenolic compounds have thus far been isolated from various parts of T. crispa. Numerous in vitro and in vivo investigations have already established the antidiabetic, anticancer, antiparasitic, antimicrobial, immunomodulatory, hepatoprotective, analgesic, antipyretic, antihyperuricemic, and pesticidal activity of this plant, as well as its effects on the cardiac and the central nervous system. Most pharmacological investigations to date have been carried out on plant extracts and fractions. The exact identity of the phytoconstituents responsible for the observed biological effects and their mode of action at the molecular level are yet to be ascertained. Toxicological studies have demonstrated that T. crispa is relatively safe, although dose-dependent hepatotoxicity is a concern at high doses. This review presents a comprehensive update and analysis on studies related to the ethnomedicinal uses, phytochemistry, pharmacological activity and toxicological profile of T. crispa. It provides some critical insights into the current scientific knowledge on this plant and its future potential in pharmaceutical research.
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Affiliation(s)
- Ehfazul Haque
- Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455 USA
| | - Md. Sazzadul Bari
- Department of Chemistry, Purdue University, West Lafayette, IN 47907 USA
| | - Labony Khandokar
- Department of Pharmacy, East West University, Dhaka, 1212 Bangladesh
| | - Juhaer Anjum
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000 Bangladesh
| | - Ibrahim Jantan
- Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia, UKM, Bangi, Selangor Malaysia
| | - Veronique Seidel
- Natural Products Research Laboratory, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK
| | - Md. Areeful Haque
- Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 USA
- Department of Pharmacy, International Islamic University Chittagong, Chittagong, 4318 Bangladesh
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Network pharmacology integrated molecular dynamics reveals the bioactive compounds and potential targets of Tinospora crispa Linn. as insulin sensitizer. PLoS One 2022; 17:e0251837. [PMID: 35737707 PMCID: PMC9223613 DOI: 10.1371/journal.pone.0251837] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Accepted: 11/04/2021] [Indexed: 11/18/2022] Open
Abstract
Insulin resistance is a metabolic disorder characterized by the decreased response to insulin in muscle, liver, and adipose cells. This condition remains a complex phenomenon that involves several genetic defects and environmental stresses. In the present study, we investigated the mechanism of known phytochemical constituents of Tinospora crispa and its interaction with insulin-resistant target proteins by using network pharmacology, molecular docking, and molecular dynamics (MD) simulation. Tinoscorside A, Makisterone C, Borapetoside A and B, and β sitosterol consider the main phytoconstituents of Tinospora crispa by its binding with active sites of main protein targets of insulin resistance potential therapy. Moreover, Tinoscorside A was revealed from the docking analysis as the ligand that binds most strongly to the target protein, PI3K. This finding was strengthened by the results of MD simulation, which stated that the conformational stability of the ligand-protein complex was achieved at 15 ns and the formation of hydrogen bonds at the active site. In conclusion, Tinospora crispa is one of the promising therapeutic agent in type 2 diabetes mellitus management. Regulation in glucose homeostasis, adipolysis, cell proliferation, and antiapoptosis are predicted to be the critical mechanism of Tinospora crispa as an insulin sensitizer.
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Potential of Diterpenes as Antidiabetic Agents: Evidence from Clinical and Pre-Clinical Studies. Pharmacol Res 2022; 179:106158. [PMID: 35272043 DOI: 10.1016/j.phrs.2022.106158] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 02/18/2022] [Accepted: 03/03/2022] [Indexed: 11/20/2022]
Abstract
Diterpenes are a diverse group of structurally complex natural products with a wide spectrum of biological activities, including antidiabetic potential. In the last 25 years, numerous diterpenes have been investigated for antidiabetic activity, with some of them reaching the stage of clinical trials. However, these studies have not been comprehensively reviewed in any previous publication. Herein, we critically discussed the literature on the potential of diterpenes as antidiabetic agents, published from 1995 to September, 2021. In the period under review, 427 diterpenes were reported to have varying degrees of antidiabetic activity. Steviol glycosides, stevioside (1) and rebaudioside A (2), were the most investigated diterpenes with promising antidiabetic property using in vitro and in vivo models, as well as human subjects. All the tested pimaranes consistently showed good activity in preclinical evaluations against diabetes. Inhibitions of α-glucosidase and protein tyrosine phosphatase 1B (PTP 1B) activities and peroxisome proliferator-activated receptors gamma (PPAR-γ) agonistic property, were the most frequently used assays for studying the antidiabetic activity of diterpenes. The molecular mechanisms of action of the diterpenes include increased GLUT4 translocation, and activation of phosphoinositide 3-kinase (PI3K) and AMP-activated protein kinase (AMPK)-dependent signaling pathways. Our data revealed that diterpenes hold promising antidiabetic potential. Stevioside (1) and rebaudioside A (2) are the only diterpenes that were advanced to the clinical trial stage of the drug discovery pipeline. Diterpenes belonging to the abietane, labdane, pimarane and kaurane class have shown promising activity in in vitro and in vivo models of diabetes and should be further investigated.
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Singh B, Nathawat S, Sharma RA. Ethnopharmacological and phytochemical attributes of Indian Tinospora species: A comprehensive review. ARAB J CHEM 2021. [DOI: 10.1016/j.arabjc.2021.103381] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
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Eawsakul K, Panichayupakaranant P, Ongtanasup T, Warinhomhoun S, Noonong K, Bunluepuech K. Computational study and in vitro alpha-glucosidase inhibitory effects of medicinal plants from a Thai folk remedy. Heliyon 2021; 7:e08078. [PMID: 34632145 PMCID: PMC8488491 DOI: 10.1016/j.heliyon.2021.e08078] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 09/06/2021] [Accepted: 09/24/2021] [Indexed: 02/08/2023] Open
Abstract
The number of patients with type 2 diabetes mellitus (T2DM) has increased worldwide. Although an instant cure was achieved with the standard treatment acabose, unsatisfactory symptoms associated with cardiovascular disease after acabose administration have been reported. Therefore, it is important to explore new treatments. A Thai folk recipe has long been used for T2DM treatment, and it effectively decreases blood glucose. However, the mechanism of this recipe has never been proven. Therefore, the potential anti-T2DM effect of this recipe, which is used in Thai hospitals, was determined to involve alpha-glucosidase (AG) inhibition with a half maximal inhibitory concentration (IC50). In vitro experiments showed that crude Cinnamomum verum extract (IC50 = 0.35 ± 0.12 mg/mL) offered excellent inhibitory activity, followed by extracts from Tinospora crispa (IC50 = 0.69 ± 0.39 mg/mL), Stephania suberosa (IC50 = 1.50 ± 0.17 mg/mL), Andrographis paniculate (IC50 = 1.78 ± 0.35 mg/mL), and Thunbergia laurifolia (IC50 = 4.66 ± 0.27 mg/mL). However, the potencies of these extracts were lower than that of acabose (IC50 = 0.55 ± 0.11 mg/mL). Therefore, this study investigated and developed a formulation of this recipe using computational docking. Among 61 compounds, 7 effectively inhibited AG, including chlorogenic acid (IC50 = 819.07 pM) through 5 hydrogen bonds (HBs) and 2 hydrophobic interactions (HIs); β-sitosterol (IC50 = 4.46 nM, 6 HIs); ergosterol peroxide (IC50 = 4.18 nM, 6 HIs); borapetoside D (IC50 = 508.63 pM, 7 HBs and 2 HIs); borapetoside A (IC50 = 1.09 nM, 2 HBs and 2 His), stephasubimine (IC50 = 285.37 pM, 6 HIs); and stephasubine (IC50 = 1.09 nM, 3 HBs and 4 HIs). These compounds bind with high affinity to different binding pockets, leading to additive effects. Moreover, the pharmacokinetics of six of these seven compounds (except ergosterol peroxide) showed poor absorption in the gastrointestinal tract, which would allow for competitive binding to AG in the small intestine. These results indicate that the development of these 6 compounds into oral antidiabetic agents is promising.
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Affiliation(s)
- Komgrit Eawsakul
- School of Medicine, Research Excellence Center for Innovation and Health Product Walailak University, Nakhon Si Thammarat, 80160, Thailand
| | - Pharkphoom Panichayupakaranant
- Phytomedicine and Pharmaceutical Biotechnology Excellence Center, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat-Yai, Songkhla 90112, Thailand
| | - Tassanee Ongtanasup
- School of Medicine, Research Excellence Center for Innovation and Health Product Walailak University, Nakhon Si Thammarat, 80160, Thailand
| | - Sakan Warinhomhoun
- School of Medicine, Research Excellence Center for Innovation and Health Product Walailak University, Nakhon Si Thammarat, 80160, Thailand
| | | | - Kingkan Bunluepuech
- School of Medicine, Research Excellence Center for Innovation and Health Product Walailak University, Nakhon Si Thammarat, 80160, Thailand
- Faculty of Traditional Thai Medicine Prince of Songkla University, Hat Yai, Songkhla, 90112, Thailand
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Chávez-Castillo M, Nuñez V, Rojas M, Ortega Á, Durán P, Pirela D, Marquina M, Cano C, Chacín M, Velasco M, Rojas-Quintero J, Bermúdez V. Exploring Phytotherapeutic Alternatives for Obesity, Insulin Resistance and Diabetes Mellitus. Curr Pharm Des 2021; 26:4430-4443. [PMID: 32611293 DOI: 10.2174/1381612826666200701205132] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Accepted: 05/29/2020] [Indexed: 11/22/2022]
Abstract
At present, the pathologic spectrum of obesity-insulin resistance (IR)-diabetes mellitus (DM) represents not only a pressing matter in public health but also a paramount object of study in biomedical research, as they constitute major risk factors for cardiovascular disease (CVD), and other chronic non-communicable diseases (NCD). Phytotherapy, the use of medicinal herbs (MH) with treatment purposes, offers a wide array of opportunities for innovation in the management of these disorders; mainly as pharmacological research on small molecules accumulates. Several MH has displayed varied mechanisms of action relevant to the pathogenesis of obesity, IR and DM, including immunological and endocrine modulation, reduction of inflammation and oxidative stress (OS), regulation of appetite, thermogenesis and energy homeostasis, sensitisation to insulin function and potentiation of insulin release, among many others. However, the clinical correlates of these molecular phenomena remain relatively uncertain, with only a handful of MH boasting convincing clinical evidence in this regard. This review comprises an exploration of currently available preclinical and clinical research on the role of MH in the management of obesity, IR, and DM.
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Affiliation(s)
- Mervin Chávez-Castillo
- Psychiatric Hospital of Maracaibo, Maracaibo, Venezuela,Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo, Venezuela
| | - Victoria Nuñez
- Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo, Venezuela
| | - Milagros Rojas
- Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo, Venezuela
| | - Ángel Ortega
- Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo, Venezuela
| | - Pablo Durán
- Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo, Venezuela
| | - Daniela Pirela
- Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo, Venezuela
| | - María Marquina
- Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo, Venezuela
| | - Clímaco Cano
- Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo, Venezuela
| | - Maricarmen Chacín
- Universidad Simón Bolívar, Facultad de Ciencias de la Salud, Barranquilla, Colombia
| | - Manuel Velasco
- Clinical Pharmacology Unit, José María Vargas School of Medicine, Central University of Venezuela, Caracas-Venezuela
| | - Joselyn Rojas-Quintero
- Pulmonary and Critical Care Medicine Department, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Valmore Bermúdez
- Universidad Simón Bolívar, Facultad de Ciencias de la Salud, Barranquilla, Colombia
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Andrade C, Gomes NGM, Duangsrisai S, Andrade PB, Pereira DM, Valentão P. Medicinal plants utilized in Thai Traditional Medicine for diabetes treatment: Ethnobotanical surveys, scientific evidence and phytochemicals. JOURNAL OF ETHNOPHARMACOLOGY 2020; 263:113177. [PMID: 32768637 DOI: 10.1016/j.jep.2020.113177] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Revised: 06/23/2020] [Accepted: 07/09/2020] [Indexed: 05/04/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Diabetes mellitus remains the most lethal metabolic disease of contemporaneous times and despite the therapeutic arsenal currently available, research on new antidiabetic agents remains a priority. In recent years, the revitalization of Thai Traditional Medicine (TTM) became a clear priority for the Thai government, and many efforts have been undertaken to accelerate research on herbal medicines and their use in medical services in various hospitals. Additionally, and particularly in rural areas, treatment of diabetes and associated symptomatology frequently relies on herbal preparations recommended by practitioners of TTM. In the current work, medicinal plants used in Thailand for treating diabetes, as well as their hypoglycaemic pharmacological evidences and potential therapeutic use for diabetes-related complications were reviewed. MATERIALS AND METHODS Ethnopharmacological information on the plant materials used in TTM for diabetes treatment was collected through literature search in a range of scientific databases using the search terms: diabetes, folk medicine, Thailand medicinal plants, traditional medicine. Information regarding scientific evidence on the antidiabetic effects of surveyed species was obtained considering not only the most common taxonomic designation, but also taxonomic synonyms, and including the keywords 'diabetes' and 'hypoglycaemic effect'. RESULTS A total of 183 species known to be used for diabetes management in TTM were reviewed, with 30% of them still lacking experimental evidences to support claims regarding the mechanisms and phytochemicals underlying their antidiabetic properties. Moreover, a total of 46 bioactives displaying effective antidiabetic effects have been isolated from 24 species, their underlying mechanism(s) of action being fully or partially disclosed. CONCLUSIONS We deliver the most extensive survey dealing with the ethnomedicinal knowledge of Thai medicinal plants utilized on diabetes management. We are certain that the current review will spark further research on Thai plants for the development of new standardized phytomedicines through drug discovery programmes.
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Affiliation(s)
- Catarina Andrade
- REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade Do Porto, R. Jorge Viterbo Ferreira, Nº 228, 4050-313, Porto, Portugal.
| | - Nelson G M Gomes
- REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade Do Porto, R. Jorge Viterbo Ferreira, Nº 228, 4050-313, Porto, Portugal.
| | - Sutsawat Duangsrisai
- Department of Botany, Faculty of Science, Kasetsart University, Ngam Wong Wang Road, Chatuchak, Bangkok, 10900, Thailand.
| | - Paula B Andrade
- REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade Do Porto, R. Jorge Viterbo Ferreira, Nº 228, 4050-313, Porto, Portugal.
| | - David M Pereira
- REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade Do Porto, R. Jorge Viterbo Ferreira, Nº 228, 4050-313, Porto, Portugal.
| | - Patrícia Valentão
- REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade Do Porto, R. Jorge Viterbo Ferreira, Nº 228, 4050-313, Porto, Portugal.
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Hypoglycemia induced by Plasmodium berghei infection is prevented by treatment with Tinospora crispa stem extract. Parasitol Int 2018; 68:57-59. [PMID: 30343056 DOI: 10.1016/j.parint.2018.10.009] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Revised: 10/14/2018] [Accepted: 10/17/2018] [Indexed: 01/20/2023]
Abstract
During Plasmodium malaria parasite infection in a human, the intraerythrocytic stages lead to the clinical manifestations of the disease, especially hypoglycemia. Hypoglycemia is a recognized feature of severe malaria and linked with a high risk of mortality for children. Hence, the present study aimed to investigate the protective effect of T. crispa stem extract on hypoglycemia induced by P. berghei infection tested with a mouse model. ICR mice were inoculated with 1 × 107 parasitized erythrocytes of P. berghei ANKA (PbANKA) by intraperitoneal injection and given 50, 100, and 200 mg/kg of ethanolic extract for 4-consecutive days. The results showed that T. crispa stem extract exerted a protective effect (100%) on hypoglycemia induced by PbANKA infection at doses of 100 and 200 mg/kg. A significantly (p < .05) prolonged mean survival time (28.0 ± 1.9 days) of the extract treated mice was also observed. Additionally, no effect on blood glucose levels was seen in normal mice treated with all doses of extract. It can be concluded that T. crispa stem extract may have beneficial properties in protecting against hypoglycemia, and in increasing survival time during malaria infection.
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Xu Y, Niu Y, Gao Y, Wang F, Qin W, Lu Y, Hu J, Peng L, Liu J, Xiong W. Borapetoside E, a Clerodane Diterpenoid Extracted from Tinospora crispa, Improves Hyperglycemia and Hyperlipidemia in High-Fat-Diet-Induced Type 2 Diabetes Mice. JOURNAL OF NATURAL PRODUCTS 2017; 80:2319-2327. [PMID: 28742368 DOI: 10.1021/acs.jnatprod.7b00365] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
An insidious increase in the incidence of obesity, insulin resistance, and hyperlipidemia has led to an epidemic of type 2 diabetes worldwide. Tinospora crispa (T. crispa) is a familiar plant traditionally used in herbal medicine for diabetes; however, the major active ingredients of this plant are still unclear. In this study, we identified the therapeutic effects of borapetoside E, a small molecule extracted from T. crispa, in high-fat-diet (HFD)-induced obesity in mice. The therapeutic effects of borapetoside E in HFD-induced obese mice were assessed physiologically, histologically, and biochemically following intraperitoneal injection. Furthermore, we analyzed the expression of glucose and lipid metabolism-related genes and proteins in borapetoside E-treated obese mice. Compared with vehicle-treated mice, borapetoside E markedly improved hyperglycemia, insulin resistance, hepatic steatosis, hyperlipidemia, and oxygen consumption in obese mice, and the effects were comparable to or better than the drug metformin. In addition, borapetoside E suppressed the expression of sterol regulatory element binding proteins (SREBPs) and their downstream target genes related to lipid synthesis in the liver and adipose tissue. Borapetoside E showed beneficial effects in vivo, demonstrating that borapetoside E may be a potential therapy for the treatment of diet-induced type 2 diabetes and related metabolic syndromes.
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Affiliation(s)
- Yuhui Xu
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences , Kunming 650201, People's Republic of China
- University of the Chinese Academy of Sciences , Beijing 100049, People's Republic of China
| | - Yanfen Niu
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences , Kunming 650201, People's Republic of China
- University of the Chinese Academy of Sciences , Beijing 100049, People's Republic of China
- Engineering Research Center, Kunming Medical University , Kunming 650500, People's Republic of China
| | - Yuan Gao
- BioBioPha Co., Ltd , Kunming 650201, People's Republic of China
- Deparment of Chemical Engineering, Yibin University , Yibin 644000, People's Republic of China
| | - Fang Wang
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences , Kunming 650201, People's Republic of China
- University of the Chinese Academy of Sciences , Beijing 100049, People's Republic of China
| | - Wanying Qin
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences , Kunming 650201, People's Republic of China
- University of the Chinese Academy of Sciences , Beijing 100049, People's Republic of China
| | - Yanting Lu
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences , Kunming 650201, People's Republic of China
- University of the Chinese Academy of Sciences , Beijing 100049, People's Republic of China
| | - Jing Hu
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences , Kunming 650201, People's Republic of China
- University of the Chinese Academy of Sciences , Beijing 100049, People's Republic of China
| | - Li Peng
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences , Kunming 650201, People's Republic of China
- University of the Chinese Academy of Sciences , Beijing 100049, People's Republic of China
| | - Jikai Liu
- School of Pharmaceutical Sciences, South-Central University for Nationalities , Wuhan 430074, People's Republic of China
| | - Wenyong Xiong
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences , Kunming 650201, People's Republic of China
- University of the Chinese Academy of Sciences , Beijing 100049, People's Republic of China
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Sun W, Zhuang C, Li X, Zhang B, Lu X, Zheng Z, Dong Y. Varic acid analogues from fungus as PTP1B inhibitors: Biological evaluation and structure-activity relationships. Bioorg Med Chem Lett 2017. [PMID: 28642102 DOI: 10.1016/j.bmcl.2017.06.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Protein tyrosine phosphatase 1B (PTP1B) inhibitors as potential therapies for diabetes and obesity have attracted much attention in recent years. Six varic acid analogues were isolated from two strains of fungi and evaluated for PTP1B inhibition activities. The structure-activity relationships were also characterized and predicted by molecular modeling. Further kinetic studies indicated the reversible and competitive inhibition manner of varic acid analogues. Trivaric acid showed insulin-sensitizing effect not only in vitro but also in vivo, representing a promising lead compound for further optimization.
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Affiliation(s)
- Wenlong Sun
- School of Life Science, Biotechnology, Dalian University of Technology, Dalian, Liaoning 116024, China
| | - Chunlin Zhuang
- School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
| | - Xia Li
- School of Life Science, Biotechnology, Dalian University of Technology, Dalian, Liaoning 116024, China
| | - Bowei Zhang
- School of Life Science, Biotechnology, Dalian University of Technology, Dalian, Liaoning 116024, China
| | - Xinhua Lu
- New Drug Research and Development Center, North China Pharmaceutical Group Corporation and National Microbial Medicine Engineering and Research Center, Shijiazhuang, Hebei 050015, China.
| | - Zhihui Zheng
- New Drug Research and Development Center, North China Pharmaceutical Group Corporation and National Microbial Medicine Engineering and Research Center, Shijiazhuang, Hebei 050015, China
| | - Yuesheng Dong
- School of Life Science, Biotechnology, Dalian University of Technology, Dalian, Liaoning 116024, China.
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17
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Gupta P, Bala M, Gupta S, Dua A, Dabur R, Injeti E, Mittal A. Efficacy and risk profile of anti-diabetic therapies: Conventional vs traditional drugs—A mechanistic revisit to understand their mode of action. Pharmacol Res 2016; 113:636-674. [DOI: 10.1016/j.phrs.2016.09.029] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2016] [Revised: 09/23/2016] [Accepted: 09/23/2016] [Indexed: 12/17/2022]
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18
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Coelho GDP, Martins VS, do Amaral LV, Novaes RD, Sarandy MM, Gonçalves RV. Applicability of Isolates and Fractions of Plant Extracts in Murine Models in Type II Diabetes: A Systematic Review. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2016; 2016:3537163. [PMID: 27843476 PMCID: PMC5098081 DOI: 10.1155/2016/3537163] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/16/2016] [Accepted: 05/11/2016] [Indexed: 12/20/2022]
Abstract
Type II diabetes mellitus is one of the most common public health problems worldwide. Its increasing prevalence in several countries and the difficult metabolic control of individuals with the disease justify studying strategies for primary prevention. The population has sought alternative and cheaper ways to treat the disease, including the use of plants considered medicinal by the population. In this study, we carried out a systematic review on the applicability of isolates and fractions of plant extracts in animal models in type II diabetes. A literature search was performed in MEDLINE/PubMed and Scopus databases. Studies using other experimental animals (horses, rabbits, and monkeys) and humans as well as articles in Chinese, German, and Russian were excluded. We assessed the quality of the studies included by using the criteria described in the ARRIVE guidelines. In general, the animals that received fractions or isolates presented reduced blood glucose levels, normalization of body weight and plasma insulin levels, and reduced total triglycerides and cholesterol. In addition, we observed wide variation among the analyzed parameters, which hindered comparison between the studies found. In further studies, standardized reports and experimental design would help to establish comparable study groups and advance the overall knowledge, thus facilitating translatability from animal data to human clinical conditions.
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Affiliation(s)
| | | | | | - Rômulo Dias Novaes
- Institute of Biomedical Science, Department of Structural Biology, Federal University of Alfenas, Alfenas, MG, Brazil
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19
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Gao Y, Niu YF, Wang F, Hai P, Wang F, Fang YD, Xiong WY, Liu JK. Clerodane Diterpenoids with Anti-hyperglycemic Activity from Tinospora crispa. NATURAL PRODUCTS AND BIOPROSPECTING 2016; 6:247-255. [PMID: 27752986 PMCID: PMC5080211 DOI: 10.1007/s13659-016-0109-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/30/2016] [Accepted: 09/28/2016] [Indexed: 06/06/2023]
Abstract
Four new clerodane diterpenoids, tinosporols A-C (2-4) and tinosporoside A (5), together with six known analogues were isolated from the vines of Tinospora crispa. Their structures were established by extensive spectroscopic analysis. The relative configuration at C-12 in the known diterpenoid borapetoside E (1), the major component of the plant, was firstly established with the aid of molecular model. Compound 1 significantly reduced serum glucose levels at dose-dependent manners in alloxan-induced hyperglycemic mice and db/db type 2 diabetic mice.
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Affiliation(s)
- Yuan Gao
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, Yunnan, People's Republic of China
- Department of Chemical Engineering, Yibin University, Yibin, 644000, People's Republic of China
- BioBioPha Co., Ltd, Kunming, 650201, People's Republic of China
| | - Yan-Fen Niu
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, Yunnan, People's Republic of China
- Graduate University of Chinese Academy of Sciences, Beijing, 100049, People's Republic of China
- Yunnan University, Kunming, 650091, People's Republic of China
| | - Fei Wang
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, Yunnan, People's Republic of China
- BioBioPha Co., Ltd, Kunming, 650201, People's Republic of China
| | - Ping Hai
- Department of Chemical Engineering, Yibin University, Yibin, 644000, People's Republic of China
- BioBioPha Co., Ltd, Kunming, 650201, People's Republic of China
| | - Fang Wang
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, Yunnan, People's Republic of China
- Graduate University of Chinese Academy of Sciences, Beijing, 100049, People's Republic of China
| | - Yin-Dong Fang
- BioBioPha Co., Ltd, Kunming, 650201, People's Republic of China
| | - Wen-Yong Xiong
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, Yunnan, People's Republic of China.
| | - Ji-Kai Liu
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, Yunnan, People's Republic of China.
- School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan, 430074, China.
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20
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Genus Tinospora: Ethnopharmacology, Phytochemistry, and Pharmacology. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2016; 2016:9232593. [PMID: 27648105 PMCID: PMC5018348 DOI: 10.1155/2016/9232593] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/03/2016] [Revised: 07/10/2016] [Accepted: 07/13/2016] [Indexed: 01/19/2023]
Abstract
The genus Tinospora includes 34 species, in which several herbs were used as traditional medicines by indigenous groups throughout the tropical and subtropical parts of Asia, Africa, and Australia. The extensive literature survey revealed Tinospora species to be a group of important medicinal plants used for the ethnomedical treatment of colds, headaches, pharyngitis, fever, diarrhea, oral ulcer, diabetes, digestive disorder, and rheumatoid arthritis. Indian ethnopharmacological data points to the therapeutic potential of the T. cordifolia for the treatment of diabetic conditions. While Tinospora species are confusing in individual ingredients and their mechanisms of action, the ethnopharmacological history of those plants indicated that they exhibit antidiabetic, antioxidation, antitumor, anti-inflammation, antimicrobial, antiosteoporosis, and immunostimulation activities. While the clinical applications in modern medicine are lacking convincing evidence and support, this review is aimed at summarizing the current knowledge of the traditional uses, phytochemistry, biological activities, and toxicities of the genus Tinospora to reveal its therapeutic potentials and gaps, offering opportunities for future researches.
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21
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LIANG GUOQIANG, WANG FEI, SONG XIUDAO, ZHANG LURONG, QIAN ZHEN, JIANG GUORONG. 3-Deoxyglucosone induces insulin resistance by impairing insulin signaling in HepG2 cells. Mol Med Rep 2016; 13:4506-12. [DOI: 10.3892/mmr.2016.5081] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2015] [Accepted: 03/01/2016] [Indexed: 11/06/2022] Open
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22
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Ahmad W, Jantan I, Bukhari SNA. Tinospora crispa (L.) Hook. f. & Thomson: A Review of Its Ethnobotanical, Phytochemical, and Pharmacological Aspects. Front Pharmacol 2016; 7:59. [PMID: 27047378 PMCID: PMC4800188 DOI: 10.3389/fphar.2016.00059] [Citation(s) in RCA: 64] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2015] [Accepted: 02/29/2016] [Indexed: 12/30/2022] Open
Abstract
Tinospora crispa (L.) Hook. f. & Thomson (Menispermaceae), found in the rainforests or mixed deciduous forests in Asia and Africa, is used in traditional medicines to treat numerous health conditions. This review summarizes the up-to-date reports about the ethnobotany, phytochemistry, pharmacological activities, toxicology, and clinical trials of the plant. It also provides critical assessment about the present knowledge of the plant which could contribute toward improving its prospect as a source of lead molecules for drug discovery. The plant has been used traditionally in the treatment of jaundice, rheumatism, urinary disorders, fever, malaria, diabetes, internal inflammation, fracture, scabies, hypertension, reducing thirst, increasing appetite, cooling down the body temperature, and maintaining good health. Phytochemical analyses of T. crispa revealed the presence of alkaloids, flavonoids, and flavone glycosides, triterpenes, diterpenes and diterpene glycosides, cis clerodane-type furanoditerpenoids, lactones, sterols, lignans, and nucleosides. Studies showed that the crude extracts and isolated compounds of T. crispa possessed a broad range of pharmacological activities such as anti-inflammatory, antioxidant, immunomodulatory, cytotoxic, antimalarial, cardioprotective, and anti-diabetic activities. Most pharmacological studies were based on crude extracts of the plant and the bioactive compounds responsible for the bioactivities have not been well identified. Further investigations are required to transform the experience-based claims on the use of T. crispa in traditional medicine practices into evidence-based information. The plant extract used in pharmacological and biological studies should be qualitatively and quantitatively analyzed based on its biomarkers. There should be detail in vitro and in vivo studies on the mechanisms of action of the pure bioactive compounds and more elaborate toxicity study to ensure safety of the plant for human use. More clinical trials are encouraged to be carried out if there are sufficient preclinical and safety data.
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Affiliation(s)
- Waqas Ahmad
- Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia Kuala Lumpur, Malaysia
| | - Ibrahim Jantan
- Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia Kuala Lumpur, Malaysia
| | - Syed N A Bukhari
- Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia Kuala Lumpur, Malaysia
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23
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Thomas A, Rajesh EK, Kumar DS. The Significance of Tinospora crispa
in Treatment of Diabetes Mellitus. Phytother Res 2016; 30:357-66. [DOI: 10.1002/ptr.5559] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 10/22/2015] [Accepted: 12/04/2015] [Indexed: 12/19/2022]
Affiliation(s)
- Alex Thomas
- CARe Keralam Ltd, KINFRA Small Industries Park; KINFRA Park P.O. Koratty 680 309 Kerala India
| | - E. K. Rajesh
- My Holdings Consultancy Pvt Ltd; First Floor, Supriya Tower Chalakudy 680307 Thrissur District, Kerala India
| | - D. Suresh Kumar
- CARe Keralam Ltd, KINFRA Small Industries Park; KINFRA Park P.O. Koratty 680 309 Kerala India
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Liu CY, Hsu YJ, Chien YWE, Cha TL, Tsao CW. Dietary resistant maltodextrin ameliorates testicular function and spermatogenesis in streptozotocin-nicotinamide-induced diabetic rats. Andrologia 2015; 48:363-73. [DOI: 10.1111/and.12454] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/31/2015] [Indexed: 01/22/2023] Open
Affiliation(s)
- C.-Y. Liu
- Department of Nutritional Science; Fu Jen Catholic University; New Taipei City Taiwan
| | - Y.-J. Hsu
- Division of Nephrology; Department of Medicine; Tri-Service General Hospital; National Defense Medical Center; Taipei Taiwan
| | - Y.-W. E. Chien
- School of Nutrition and Health Sciences; Taipei Medical University; Taipei Taiwan
| | - T.-L. Cha
- Division of Urology; Department of Surgery; Tri-Service General Hospital; National Defense Medical Center; Taipei Taiwan
| | - C.-W. Tsao
- Division of Urology; Department of Surgery; Tri-Service General Hospital; National Defense Medical Center; Taipei Taiwan
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25
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Chang CC, Ho SL, Lee SS. Acylated glucosylflavones as α-glucosidase inhibitors from Tinospora crispa leaf. Bioorg Med Chem 2015; 23:3388-96. [DOI: 10.1016/j.bmc.2015.04.053] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2015] [Revised: 04/10/2015] [Accepted: 04/15/2015] [Indexed: 01/07/2023]
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26
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Hamid H, Yusoff M, Liu M, Karim M. α-Glucosidase and α-amylase inhibitory constituents of Tinospora crispa: Isolation and chemical profile confirmation by ultra-high performance liquid chromatography-quadrupole time-of-flight/mass spectrometry. J Funct Foods 2015. [DOI: 10.1016/j.jff.2015.04.011] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
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Liao D, Ma J, Duan XL. Therapeutic effect of Zhuang herb Hanyitai on duck hepatitis B. Shijie Huaren Xiaohua Zazhi 2015; 23:1395-1401. [DOI: 10.11569/wcjd.v23.i9.1395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the therapeutic effect of Zhuang herb Hanyitai on liver function, viral replication, immune regulation and liver inflammation in a duck model infected by duck hepatitis B virus (DHBV).
METHODS: Duck hepatitis B was induced by intraperitoneal injection of DHBV positive serum into one-day-old Guangxi sheldrakes. On the day before treatment (T0), 7 d (T7) and 14 d (T14) during treatment, and 3 d (P3) after treatment, jugular blood and liver tissue samples were collected to detect aspartate aminotransferase (ALT), alanine aminotransferase (AST), interleukin-2 (IL-2), DHBV DNA, and liver pathology.
RESULTS: In the model group, ALT, AST and IL-2 levels were significantly increased after DHBV infection for one week and two weeks (P = 0.028, 0.036; P = 0.005, 0.04; P = 0.045), the amount of virus was relatively stable, and severe fatty degeneration was observed in liver tissues. In the lamivudine group, ALT and IL-2 levels were significantly decreased after treatment for one week and two weeks (P = 0.001, 0.042; P = 0.023), AST level showed no significant changes, the replication of virus was significantly inhibited (P = 0.034; 0.007), without rebounding after medication withdrawal for three days (P = 0.013), and liver tissue pathology showed moderate liver steatosis. In the high dose Hanyitai group, ALT, AST, and IL-2 levels were significantly reduced after treatment for one week and two weeks (P = 0.047, 0.035; P = 0.007, 0.003; P = 0.026, 0.049), the replication of virus was inhibited significantly as the lamivudine group (P = 0.025; P = 0.012; P = 0.011), and liver tissue pathology displayed moderate liver steatosis. In the usual dose Hanyitai group, ALT, AST, and IL-2 levels were significantly reduced after treatment for one week and two weeks (P = 0.015; P = 0.038; P = 0.024, 0.004), but at T14, ALT and AST level rebounded, the replication of virus was inhibited moderately, and moderate or severe steatosis was noted.
CONCLUSION: Hanyitai can reduce transaminase levels, inhibit DHBV DNA replication, and reduce IL-2 secretion in a dose-dependent manner. Hanyitai could protect liver cells, relieve hepatic steatosis, and reduce acute immunological liver injury.
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Cordero-Herrera I, Martín MÁ, Escrivá F, Álvarez C, Goya L, Ramos S. Cocoa-rich diet ameliorates hepatic insulin resistance by modulating insulin signaling and glucose homeostasis in Zucker diabetic fatty rats. J Nutr Biochem 2015; 26:704-12. [PMID: 25814291 DOI: 10.1016/j.jnutbio.2015.01.009] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2014] [Revised: 01/09/2015] [Accepted: 01/20/2015] [Indexed: 01/03/2023]
Abstract
Insulin resistance is the primary characteristic of type 2 diabetes and results from insulin signaling defects. Cocoa has been shown to exert anti-diabetic effects by lowering glucose levels. However, the molecular mechanisms responsible for this preventive activity and whether cocoa exerts potential beneficial effects on the insulin signaling pathway in the liver remain largely unknown. Thus, in this study, the potential anti-diabetic properties of cocoa on glucose homeostasis and insulin signaling were evaluated in type 2 diabetic Zucker diabetic fatty (ZDF) rats. Male ZDF rats were fed a control or cocoa-rich diet (10%), and Zucker lean animals received the control diet. ZDF rats supplemented with cocoa (ZDF-Co) showed a significant decrease in body weight gain, glucose and insulin levels, as well as an improved glucose tolerance and insulin resistance. Cocoa-rich diet further ameliorated the hepatic insulin resistance by abolishing the increased serine-phosphorylated levels of the insulin receptor substrate 1 and preventing the inactivation of the glycogen synthase kinase 3/glycogen synthase pathway in the liver of cocoa-fed ZDF rats. The anti-hyperglycemic effect of cocoa appeared to be at least mediated through the decreased levels of hepatic phosphoenolpyruvate carboxykinase and increased values of glucokinase and glucose transporter 2 in the liver of ZDF-Co rats. Moreover, cocoa-rich diet suppressed c-Jun N-terminal kinase and p38 activation caused by insulin resistance. These findings suggest that cocoa has the potential to alleviate both hyperglycemia and hepatic insulin resistance in type 2 diabetic ZDF rats.
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Affiliation(s)
- Isabel Cordero-Herrera
- Department of Metabolism and Nutrition, Institute of Food Science and Technology and Nutrition, Consejo Superior de Investigaciones Científicas, José Antonio Novais 10, Ciudad Universitaria, 28040 Madrid, Spain
| | - María Ángeles Martín
- Department of Metabolism and Nutrition, Institute of Food Science and Technology and Nutrition, Consejo Superior de Investigaciones Científicas, José Antonio Novais 10, Ciudad Universitaria, 28040 Madrid, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Fernando Escrivá
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, Instituto de Salud Carlos III, 28029 Madrid, Spain; Departamento de Bioquímica y Biología Molecular II, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain
| | - Carmen Álvarez
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, Instituto de Salud Carlos III, 28029 Madrid, Spain; Departamento de Bioquímica y Biología Molecular II, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain
| | - Luis Goya
- Department of Metabolism and Nutrition, Institute of Food Science and Technology and Nutrition, Consejo Superior de Investigaciones Científicas, José Antonio Novais 10, Ciudad Universitaria, 28040 Madrid, Spain
| | - Sonia Ramos
- Department of Metabolism and Nutrition, Institute of Food Science and Technology and Nutrition, Consejo Superior de Investigaciones Científicas, José Antonio Novais 10, Ciudad Universitaria, 28040 Madrid, Spain.
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Tinospora crispa Ameliorates Insulin Resistance Induced by High Fat Diet in Wistar Rats. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2015; 2015:985042. [PMID: 25821506 PMCID: PMC4363645 DOI: 10.1155/2015/985042] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/14/2014] [Revised: 07/17/2014] [Accepted: 07/17/2014] [Indexed: 11/18/2022]
Abstract
The antidiabetic properties of Tinospora crispa, a local herb that has been used in traditional Malay medicine and rich in antioxidant, were explored based on obesity-linked insulin resistance condition. Male Wistar rats were randomly divided into four groups, namely, the normal control (NC) which received standard rodent diet, the high fat diet (HFD) which received high fat diet only, the high fat diet treated with T. crispa (HFDTC), and the high fat diet treated with orlistat (HFDO). After sixteen weeks of treatment, blood and organs were harvested for analyses. Results showed that T. crispa significantly (p < 0.05) reduced the body weight (41.14 ± 1.40%), adiposity index serum levels (4.910 ± 0.80%), aspartate aminotransferase (AST: 161 ± 4.71 U/L), alanine aminotransferase (ALT: 100.95 ± 3.10 U/L), total cholesterol (TC: 18.55 ± 0.26 mmol/L), triglycerides (TG: 3.70 ± 0.11 mmol/L), blood glucose (8.50 ± 0.30 mmo/L), resistin (0.74 ± 0.20 ng/mL), and leptin (17.428 ± 1.50 ng/mL) hormones in HFDTC group. The insulin (1.65 ± 0.07 pg/mL) and C-peptide (136.48 pmol/L) hormones were slightly decreased but within normal range. The histological results showed unharmed and intact liver tissues in HFDTC group. As a conclusion, T. crispa ameliorates insulin resistance-associated with obesity in Wistar rats fed with high fat diet.
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Jayanthy G, Subramanian S. RA abrogates hepatic gluconeogenesis and insulin resistance by enhancing IRS-1 and AMPK signalling in experimental type 2 diabetes. RSC Adv 2015. [DOI: 10.1039/c5ra04605j] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
RA abrogates hyperglycemia and insulin resistance, the primary features of type 2 diabetes (T2DM).
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Affiliation(s)
- G. Jayanthy
- Department of Biochemistry
- University of Madras
- Guindy Campus
- Chennai
- India
| | - S. Subramanian
- Department of Biochemistry
- University of Madras
- Guindy Campus
- Chennai
- India
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Antidiabetic claims of Tinospora cordifolia (Willd.) Miers: critical appraisal and role in therapy. Asian Pac J Trop Biomed 2015. [DOI: 10.1016/s2221-1691(15)30173-8] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
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Abood WN, Fahmi I, Abdulla MA, Ismail S. Immunomodulatory effect of an isolated fraction from Tinospora crispa on intracellular expression of INF-γ, IL-6 and IL-8. Altern Ther Health Med 2014; 14:205. [PMID: 24969238 PMCID: PMC4227069 DOI: 10.1186/1472-6882-14-205] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2014] [Accepted: 06/23/2014] [Indexed: 12/18/2022]
Abstract
Background Immunomodulators are substances that modify immune system response to a threat. Immunomodulators modulate and potentiate the immune system, keeping it highly prepared for any threat. The immunomodulatory effect of the traditional medicine Tinospora crispa is investigated in this work. Methods T. crispa ethanol extract was fractionated by using different solvents. The ethanol extract and effective isolated fraction were used to investigate the potential immunomodulatory effect of different T. crispa doses ranging from 25 μg/mL to 1000 μg/mL on RAW 246.7 cells by detecting intracellular INF-γ, IL-6, and IL-8 expressions. The antioxidant activity of T. crispa was evaluated through FRAP and DPPH. The total phenolic and total flavonoid contents were also quantified. Results Results show that T. crispa extract has higher antioxidant potential than ascorbic acid. The FRAP value of T. crispa extract is 11011.11 ± 1145.42 μmol Fe+2/g, and its DPPH inhibition percentage is 55.79 ± 7.9, with 22 μg/mL IC50. The results also reveal that the total phenolic content of T. crispa extract is 213.16- ± 1.31 mg GAE/g dry stem weight, and the total flavonoid content is 62.07- ± 39.76 mg QE/g dry stem weight. T. crispa crude extract and its isolated fraction significantly stimulate RAW264.7 cell viability (P ≤ 0.05) and intracellular INF-γ, IL-6, and IL-8 expressions. The results of LC-MS show that four of the active compounds detected in the T. crispa isolated fraction are cordioside, quercetin, eicosenoic acid (paullinic acid), and boldine. Conclusions The results of this study obviously indicate that T. crispa has immunomodulatory effects through the stimulation of INF-γ, IL-6, and IL-8 expressions. LC-MS phytochemical analysis showed that the T. crispa fraction has cordioside, quercetin, eicosenoic acid (paullinic acid), and boldine, which may be responsible for the immunostimulator effect of T. crispa.
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Eddouks M, Bidi A, El Bouhali B, Hajji L, Zeggwagh NA. Antidiabetic plants improving insulin sensitivity. ACTA ACUST UNITED AC 2014; 66:1197-214. [PMID: 24730446 DOI: 10.1111/jphp.12243] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2013] [Accepted: 02/23/2014] [Indexed: 12/19/2022]
Abstract
BACKGROUND Globally, the prevalence of diabetes mellitus is increasing at an alarming rate. This chronic pathology gravely troubled the human health and quality of life. Both insulin deficiency and insulin resistance are involved in the pathophysiology of diabetes mellitus. Moreover, insulin resistance is being diagnosed nowadays in a growing population of diabetic and obese patients, especially in industrialized societies. There are lots of conventional agents available to control and to treat diabetes, but total recovery from this disorder has not been reported up to this date. Plants provided a potential source of hypoglycemic drugs and are widely used in several traditional systems of medicine to prevent diabetes. A few reviews with less attention paid to mechanisms of action have been published on antidiabetic plants. OBJECTIVES The present review focuses on the various plants that have been reported to be effective in improving insulin sensitivity associated with diabetes. KEY FINDINGS In this work, an updated systematic review of the published literature has been conducted to review the antidiabetic plants improving insulin sensitivity and 111 medicinal plants have been reported to have a beneficial effect on insulin sensitivity using several in-vitro and in-vivo animal models of diabetes. CONCLUSION The different metabolic and cellular effects of the antidiabetic plants improving insulin sensitivity are reported indicating the important role of medicinal plants as potential alternative or complementary use in controlling insulin resistance associated with diabetes mellitus.
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Affiliation(s)
- Mohamed Eddouks
- Faculty of Sciences and Techniques Errachidia, Moulay Ismail University, Errachidia, Morocco
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Antidiabetic Effect of Oral Borapetol B Compound, Isolated from the Plant Tinospora crispa, by Stimulating Insulin Release. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2013; 2013:727602. [PMID: 24319481 PMCID: PMC3844206 DOI: 10.1155/2013/727602] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/03/2013] [Revised: 08/30/2013] [Accepted: 09/12/2013] [Indexed: 01/22/2023]
Abstract
Aims. To evaluate the antidiabetic properties of borapetol B known as compound 1 (C1) isolated from Tinospora crispa in normoglycemic control Wistar (W) and spontaneously type 2 diabetic Goto-Kakizaki (GK) rats. Methods. The effect of C1 on blood glucose and plasma insulin was assessed by an oral glucose tolerance test. The effect of C1 on insulin secretion was assessed by batch incubation and perifusion experiments using isolated pancreatic islets. Results. An acute oral administration of C1 improved blood glucose levels in treated versus placebo groups with areas under glucose curves 0–120 min being 72 ± 17 versus 344 ± 10 mmol/L (P < 0.001) and 492 ± 63 versus 862 ± 55 mmol/L (P < 0.01) in W and GK rats, respectively. Plasma insulin levels were increased by 2-fold in treated W and GK rats versus placebo group at 30 min (P < 0.05). C1 dose-dependently increased insulin secretion from W and GK isolated islets at 3.3 mM and 16.7 mM glucose. The perifusions of isolated islets indicated that C1 did not cause leakage of insulin by damaging islet beta cells (P < 0.001). Conclusion. This study provides evidence that borapetol B (C1) has antidiabetic properties mainly due to its stimulation of insulin release.
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Ruan CT, Lam SH, Lee SS, Su MJ. Hypoglycemic action of borapetoside A from the plant Tinospora crispa in mice. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2013; 20:667-675. [PMID: 23523259 DOI: 10.1016/j.phymed.2013.02.009] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/30/2012] [Revised: 11/30/2012] [Accepted: 02/21/2013] [Indexed: 06/02/2023]
Abstract
AIM This study explores the hypoglycemic effects of borapetoside A, the most active principle among three major diterpenoids (borapetosides A, B, and C) isolated from ethanol extract of Tinospora crispa vines. METHODS We employed mouse mitogenic C2C12 and hepatocellular carcinoma Hep3B cells in this study. Furthermore, the mice were divided into three groups, including streptozotocin-induced type 1 diabetes mellitus, diet-induced type 2 diabetes mellitus, and normal control. The mice in each group were treated with assigned vehicle control, borapetoside A, or other active agents. RESULTS Borapetoside A was shown to increase the glycogen content and decrease the plasma glucose concentration in a concentration or dose-dependent manner in vitro and in vivo. The hypoglycemic effects in the normal mice and the mice with type 2 diabetes mellitus were associated with the increases of the plasma insulin levels; whereas, the insulin levels remained unchanged in the mice with type 1 diabetes mellitus. Borapetoside A not only attenuated the elevation of plasma glucose induced by an intraperitoneal glucose tolerance test, but also increased the glycogen synthesis of IL-6 treated C2C12 cells. Moreover, the elevated protein expression levels of phosphoenolpyruvate carboxykinase were reversed after borapetoside A treatment twice a day for 7 days. CONCLUSIONS The hypoglycemic effects of borapetoside A were mediated through both the insulin-dependent and the insulin-independent pathways. Furthermore, borapetoside A was shown to increase the glucose utilization in peripheral tissues, to reduce the hepatic gluconeogenesis, and to activate the insulin signaling pathway; they thereby contributed to the lowering of the plasma glucose. Comparison of the structures of three borapetosides suggests clearly that the C-8 stereochemistry plays a key role in hypoglycemic effect since the active borapetoside A and C possess 8R-chirality but the inactive borapetoside B possess 8S-chirality. The location of glycoside at C-3 for borapetoside A but C-6 for borapetoside C and the formation of lactone between C-4 and C-6 for borapetoside A, could account for the different potency in hypoglycemic action for these two compounds.
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Affiliation(s)
- Chi-Tun Ruan
- Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan
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Liao D, Duan XL. In vitro anti-HBV effect of polyherbal medicine of Chuang herb HanYiTai. Shijie Huaren Xiaohua Zazhi 2013; 21:614-618. [DOI: 10.11569/wcjd.v21.i7.614] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To compare the effect of polyherbal medicine and single herb of Chuang herb HanYiTai in resisting HBV by detecting HBV antigen and HBV DNA.
METHODS: Different concentrations of HanYiTai and other compounded herbs were co-incubated with 2215 cells in vitro, and their toxic effects were detected by XTT method to determine the safe concentrations of HanYiTai and other herbs. Polyherbal compounds were matched with a variety of intoxic concentrations of herbs. Culture medium was changed once every 3 d, and supernatants were collected 9 d later. The contents of HBsAg and HBeAg in supernatants were measured using ELISA. Meanwhile, the secretion of HBV-DNA was detected using fluorescent quantitative PCR.
RESULTS: The inhibitory effect of polyherbal medicine on the secretion of HBsAg antigen was slightly stronger than that of single HanYiTai group, but the difference was not statistically significant. The inhibitory effect of polyherbal medicine F3-F5 on the secretion of HBeAg and HBVDNA was significantly stronger than that of corresponding concentrations of single HanYiTai (P = 0.002-0.009; P = 0.038-0.05). Polyherbal medicine at low and middle concentrations (F3-F5) showed stronger inhibitory effect on the secretion of HBVDNA than that at high concentrations (F1-F2) (P = 0.048-0.015).
CONCLUSION: Anti-HBV effect of low concentration of polyherbal medicine was better than that of high concentration of polyherbal medicine and corresponding concentration of HanyiTai single herb. The mutual influence and synergy of various pharmaceutical ingredients can not only reduce the concentration of a single drug but also produce a superimposed synergistic effect.
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Cordero-Herrera I, Martín MA, Bravo L, Goya L, Ramos S. Cocoa flavonoids improve insulin signalling and modulate glucose production via AKT and AMPK in HepG2 cells. Mol Nutr Food Res 2013; 57:974-85. [PMID: 23456781 DOI: 10.1002/mnfr.201200500] [Citation(s) in RCA: 112] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2012] [Revised: 12/17/2012] [Accepted: 12/19/2012] [Indexed: 12/14/2022]
Abstract
SCOPE Cocoa and (-)-epicatechin (EC), a main cocoa flavanol, have been suggested to exert beneficial effects in diabetes, but the mechanism for their insulin-like effects remains unknown. In this study, the modulation of insulin signalling by EC and a cocoa phenolic extract (CPE) on hepatic HepG2 cells was investigated by analysing key proteins of the insulin pathways, namely insulin receptor, insulin receptor substrate (IRS) 1 and 2, PI3K/AKT and 5'-AMP-activated protein kinase (AMPK), as well as the levels of the glucose transporter GLUT-2 and the hepatic glucose production. METHODS AND RESULTS EC and CPE enhanced the tyrosine phosphorylation and total insulin receptor, IRS-1 and IRS-2 levels and activated the PI3K/AKT pathway and AMPK in HepG2 cells. CPE also enhanced the levels of GLUT-2. Interestingly, EC and CPE modulated the expression of phosphoenolpyruvate carboxykinase, a key protein involved in the gluconeogenesis, leading to a diminished glucose production. In addition, EC- and CPE-regulated hepatic gluconeogenesis was prevented by the blockage of AKT and AMPK. CONCLUSION Our data suggest that EC and CPE strengthen the insulin signalling by activating key proteins of that pathway and regulating glucose production through AKT and AMPK modulation in HepG2 cells.
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Affiliation(s)
- Isabel Cordero-Herrera
- Department of Metabolism and Nutrition, Institute of Food Science and Technology and Nutrition (ICTAN), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain
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