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Kaur M, Kumar D, Kaur N, Muthuraman AM, Devi S, Gupta S. Therapeutic Potential of 3-(4-Chlorophenyl)-4-(2-Hydroxyphenyl) 1,3-Oxazetidin-2-One in STZ-Induced Diabetic Neuropathic Pain in Rats. Fundam Clin Pharmacol 2025; 39:e70026. [PMID: 40421777 DOI: 10.1111/fcp.70026] [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: 05/03/2025] [Accepted: 05/05/2025] [Indexed: 05/28/2025]
Abstract
The present study was designed to investigate the therapeutic potential of oxazetidin-2-one derivatives in a rat model of streptozotocin (STZ)-induced diabetic neuropathic pain. A single dose of STZ (i.e., 75 mg/kg; i.p.) was administered to induce diabetes-associated neuropathic pain in rats. The serum glucose level was estimated on days 0, 3, 42, and 45. A battery of behavioral tests, i.e., hot plate, plantar, tail immersion, and tail flick tests, were performed to assess the degree of thermal hyperalgesia in the paw and tail regions at different time intervals, i.e., 42nd and 44th day. Total protein, thiobarbituric acid reactive substances (TBARS), nitrite, reduced glutathione (GSH), and total calcium levels in sciatic nerve tissue were also estimated on the 45th day of the experiment. The test compound (CHO; 5, 10, or 15 mg/kg; p.o.) and pregabalin (10 mg/kg; p.o.) were administered for three consecutive days beginning on the 42nd day after STZ administration. STZ significantly induced diabetic neuropathic pain, as indicated by thermal hyperalgesia in the paw and tail along with increases in the TBARS, nitrite, and total calcium levels and a decrease in the GSH level. Administration of CHO attenuated STZ-induced behavioral and biochemical changes in a dose-dependent manner compared to those in the pregabalin-treated group. The attenuating effect of CHO (15 mg/kg) on STZ-induced diabetic neuropathic pain may be attributed to its neuroprotective potential via multiple pharmacological actions, including anti-lipid peroxidation, free radical scavenging, and inhibition of intracellular calcium accumulation.
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Affiliation(s)
- Manpreet Kaur
- Department of Chemistry, Mata Gujri College, Fatehgarh Sahib, Punjab, India
| | - Dhruva Kumar
- Department of Chemistry, Guru Nanak College, Budhlada, Punjab, India
| | - Navjeet Kaur
- Department of Physics, Mata Gujri College, Fatehgarh Sahib, Punjab, India
| | - A M Muthuraman
- Department of Pharmacology, Akal Toxicology Research Centre, Akal College of Pharmacy & Technical Education, Sangrur, Punjab, India
- Toxicology and Basic Health Sciences Unit, Faculty of Pharmacy, AIMST University, Bedong, Kedah, Malaysia
| | - Sushma Devi
- Chitkara College of Pharmacy, Chitkara University, Rajpura
| | - Saurabh Gupta
- Department of Microbiology, Mata Gujri College, Fatehgarh Sahib, Punjab, India
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Singh P, Singh DP, Patel MK, Binwal M, Kaushik A, Mall M, Sahu M, Khare P, Shanker K, Bawankule DU, Sundaresan V, Mani DN, Shukla AK. Vindoline is a key component of Catharanthus roseus leaf juice extract prepared through an Ayurveda-based method for ameliorating insulin-resistant type 2 diabetes. PROTOPLASMA 2025; 262:667-681. [PMID: 39794517 DOI: 10.1007/s00709-024-02026-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Accepted: 12/22/2024] [Indexed: 01/13/2025]
Abstract
Catharanthus roseus leaves have been traditionally described to possess potent antidiabetic activity and some leaf-specific alkaloids, including vindoline, have been studied for their antidiabetic potential. The aim of the present study was to validate the antidiabetic property of the plant with special reference to vindoline. An Ayurveda-based method was used to prepare the Swaras [leaf juice extract (LJE)] of three familial C. roseus genotypes differing in their vindoline content [CIM-Sushil (CS) > Dhawal (D) > Nirmal (N)]. In vivo experiments using LJE were performed in Charles Foster rats, whereby metformin (M100, 100 mg/kg BW) and vindoline (V20, 20 mg/kg BW) were used for comparison. OGTT-based screening for LJE doses (N100, N300, N500, D100, D200, D300, CS100, CS200, CS300 mg/kg BW) was carried out. Further analysis of the effective doses (D100, D200, D300, CS100, CS200, CS300) in streptozotocin-induced diabetic rats indicated highest blood glucose depletion in D300 (52.51%) and CS200 (64.55%) together with V20 (56.96%) on the 14th day. CS-LJE was found to be safe up to 2000 mg/kg BW. The role of LJE/vindoline in maintaining glucose homeostasis in liver was found to be mediated through the expression of insulin pathway genes (IRS-1, PI3K, AKT, GLUT2). TNF-α-induced insulin resistance in L6 skeletal muscle cells was used to analyze the effect of LJE/vindoline through glucose uptake assay and expression analysis of insulin pathway genes (IRS-1, PI3K, AKT, GLUT4). The results indicated that the antidiabetic effect of LJE/vindoline is mediated through activation of IRS/PI3K/AKT/GLUT signaling pathway.
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Affiliation(s)
- Pooja Singh
- CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Lucknow, 226015, Uttar Pradesh, India
| | - Dewasya P Singh
- CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Lucknow, 226015, Uttar Pradesh, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, Uttar Pradesh, India
| | - Manish K Patel
- CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Lucknow, 226015, Uttar Pradesh, India
| | - Monika Binwal
- CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Lucknow, 226015, Uttar Pradesh, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, Uttar Pradesh, India
| | - Amit Kaushik
- CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Lucknow, 226015, Uttar Pradesh, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, Uttar Pradesh, India
| | - Maneesha Mall
- CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Lucknow, 226015, Uttar Pradesh, India
| | - Mridula Sahu
- CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Lucknow, 226015, Uttar Pradesh, India
| | - Puja Khare
- CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Lucknow, 226015, Uttar Pradesh, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, Uttar Pradesh, India
| | - Karuna Shanker
- CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Lucknow, 226015, Uttar Pradesh, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, Uttar Pradesh, India
| | - Dnyaneshwar U Bawankule
- CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Lucknow, 226015, Uttar Pradesh, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, Uttar Pradesh, India
| | - Velusamy Sundaresan
- CSIR-Central Institute of Medicinal and Aromatic Plants, Research Centre, Allalasandra, GKVK Post, Bengaluru, 560065, Karnataka, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, Uttar Pradesh, India
| | - Daya N Mani
- CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Lucknow, 226015, Uttar Pradesh, India.
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, Uttar Pradesh, India.
| | - Ashutosh K Shukla
- CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Lucknow, 226015, Uttar Pradesh, India.
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, Uttar Pradesh, India.
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Li C, Lin K, Xiao L, Dilixiati Y, Huo Y, Zhang Z. Evaluation of cadmium effects on the glucose metabolism on insulin resistance HepG2 cells. Heliyon 2024; 10:e37325. [PMID: 39296152 PMCID: PMC11408151 DOI: 10.1016/j.heliyon.2024.e37325] [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: 06/03/2024] [Revised: 08/11/2024] [Accepted: 09/01/2024] [Indexed: 09/21/2024] Open
Abstract
Cadmium (Cd) is an environmental endocrine disruptor. Despite increasing research about the metabolic effects of Cd on HepG2 cells, information about the metabolic effects of Cd on insulin resistance HepG2 (IR-HepG2) cells is limited. Currently, most individuals with diabetes are exposed to Cd due to pollution. Previously, we reported that Cd exposure resulted in decreased blood glucose levels in diabetic mice, the underlying mechanism deserves further study. Therefore, we used palmitic acid (0.25 mM) to treat HepG2 cells to establish IR-HepG2 model. IR-HepG2 cells were exposed to CdCl2 (1 μM and 2 μM). Commercial kits were used to measure glucose production, glucose consumption, ROS and mitochondrial membrane potential. Western blot and qRT-PCR were used to measure the proteins and genes of glucose metabolism. In the current study setting, we found no significant changes in glucose metabolism in Cd-exposed HepG2 cells, but Cd enhanced glucose uptake, inhibited gluconeogenesis and activated the insulin signaling pathway in IR-HepG2 cells. Meanwhile, we observed that Cd caused oxidative stress and increased the intracellular calcium concentration and inhibited mitochondrial membrane potential in IR-HepG2 cells. Cd compensatingly increased glycolysis in IR-HepG2 cells. Collectively, we found Cd ameliorated glucose metabolism disorders in IR-HepG2 cells. Furthermore, Cd exacerbated mitochondrial damage and compensatory increased glycolysis in IR-HepG2 cells. These findings will provide novel insights for Cd exposure in insulin resistant individuals.
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Affiliation(s)
- Changhao Li
- School of Public Health, Soochow University, Suzhou, 215123, China
| | - Ke Lin
- Center for Disease Control and Prevention of Xishan District, Wuxi, 214000, Jiangsu, China
| | - Liang Xiao
- School of Public Health, Soochow University, Suzhou, 215123, China
| | | | - Yuan Huo
- School of Public Health, Soochow University, Suzhou, 215123, China
| | - Zengli Zhang
- School of Public Health, Soochow University, Suzhou, 215123, China
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Rashmi P, Urmila A, Likhit A, Subhash B, Shailendra G. Rodent models for diabetes. 3 Biotech 2023; 13:80. [PMID: 36778766 PMCID: PMC9908807 DOI: 10.1007/s13205-023-03488-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Accepted: 01/19/2023] [Indexed: 02/11/2023] Open
Abstract
Diabetes mellitus (DM) is associated with many health complications and is potentially a morbid condition. As prevalence increases at an alarming rate around the world, research into new antidiabetic compounds with different mechanisms is the top priority. Therefore, the preclinical experimental induction of DM is imperative for advancing knowledge, understanding pathogenesis, and developing new drugs. Efforts have been made to examine recent literature on the various induction methods of Type I and Type II DM. The review summarizes the different in vivo models of DM induced by chemical, surgical, and genetic (immunological) manipulations and the use of pathogens such as viruses. For good preclinical assessment, the animal model must exhibit face, predictive, and construct validity. Among all reported models, chemically induced DM with streptozotocin was found to be the most preferred model. However, the purpose of the research and the outcomes to be achieved should be taken into account. This review was aimed at bringing together models, benefits, limitations, species, and strains. It will help the researcher to understand the pathophysiology of DM and to choose appropriate animal models.
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Affiliation(s)
- Patil Rashmi
- Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth (Deemed to be University), Paud Road, Erandwane, Pune, 411038 India
| | - Aswar Urmila
- Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth (Deemed to be University), Paud Road, Erandwane, Pune, 411038 India
| | - Akotkar Likhit
- Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth (Deemed to be University), Paud Road, Erandwane, Pune, 411038 India
| | - Bodhankar Subhash
- Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth (Deemed to be University), Paud Road, Erandwane, Pune, 411038 India
| | - Gurav Shailendra
- Department of Pharmacognosy, Goa College of Pharmacy, Goa University, Panaji, Goa India
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Khadka D, Pandey K. Exploring the Crucial Role of Plant Growth-Promoting Rhizobacteria (PGPR) in Plant Secondary Metabolite Production and Diabetes Management. Fungal Biol 2022. [DOI: 10.1007/978-3-031-04805-0_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/15/2022]
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Zhang J, Teng F, Pan L, Guo D, Liu J, Li K, Yuan Y, Li W, Zhang H. Circulating adipsin is associated with asymptomatic carotid atherosclerosis in obese adults. BMC Cardiovasc Disord 2021; 21:517. [PMID: 34696714 PMCID: PMC8543967 DOI: 10.1186/s12872-021-02329-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Accepted: 10/13/2021] [Indexed: 12/30/2022] Open
Abstract
Background Adipsin has been identified as a secreted adipokine that plays a critical pathogenic role in metabolic disorders. However, it is not clear regarding the association of circulating adipsin with cardiovascular disease (CVD). This study will explore the association between circulating adipsin and asymptomatic carotid atherosclerosis in Chinese obese adults. Methods A total of 483 obese adult subjects (aged 40 years or older) were enrolled in this study. Serum adipsin concentrations and carotid intima-media thickness (CIMT) were measured to determine these associations. Results Individuals with increased CIMT and asymptomatic carotid atherosclerosis had lower levels of circulating adipsin than controls (both p < 0.05). The prevalence of asymptomatic carotid atherosclerosis was significantly higher in subjects with lower levels of serum adipsin than those with higher values (42.5% vs. 36.7%, p < 0.05). Notably, subjects in the lowest quartile of serum adipsin were 1.94 times (p = 0.059) more likely to have increased CIMT and 2.91 times (p = 0.03) more likely to have asymptomatic carotid atherosclerosis than those in the highest quartile in multivariable logistic regression analyses, adjusting for age, gender, current smoking, alcohol consumption, physical activity, BMI, systolic BP, fasting glucose, total cholesterol, HDL-c, and HOMA-IR. However, such associations with circulating adipsin were not noted for atherosclerotic plaque. Conclusions These findings suggest that circulating adipsin concentrations are a potential marker of risks of increased CIMT and asymptomatic carotid atherosclerosis in obese Chinese adults.
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Affiliation(s)
- Jinhua Zhang
- Key Laboratory of Functional and Clinical Translational Medicine, Department of General Medicine, Xiamen Medical College, Xiamen, China
| | - Fei Teng
- Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Road, Guangzhou, 510515, China.,The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Lingling Pan
- Department of Endocrinology and Metabolism, Tongji Hospital, Tongji University, Shanghai, China
| | - Dan Guo
- Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Road, Guangzhou, 510515, China
| | - Jianfang Liu
- Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Road, Guangzhou, 510515, China
| | - Kangli Li
- Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Road, Guangzhou, 510515, China
| | - Youwen Yuan
- Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Road, Guangzhou, 510515, China
| | - Wenyuan Li
- Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Road, Guangzhou, 510515, China.
| | - Huijie Zhang
- Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Road, Guangzhou, 510515, China. .,The First Affiliated Hospital of Xiamen University, Xiamen, China. .,Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
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Wickramasinghe ASD, Kalansuriya P, Attanayake AP. Herbal Medicines Targeting the Improved β-Cell Functions and β-Cell Regeneration for the Management of Diabetes Mellitus. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2021; 2021:2920530. [PMID: 34335803 PMCID: PMC8298154 DOI: 10.1155/2021/2920530] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Accepted: 07/05/2021] [Indexed: 12/12/2022]
Abstract
There is an increasing trend of investigating natural bioactive compounds targeting pancreatic β-cells for the prevention/treatment of diabetes mellitus (DM). With the exploration of multiple mechanisms by which β-cells involve in the pathogenesis of DM, herbal medicines are gaining attention due to their multitasking ability as evidenced by traditional medicine practices. This review attempts to summarize herbal medicines with the potential for improvement of β-cell functions and regeneration as scientifically proven by in vivo/in vitro investigations. Furthermore, attempts have been made to identify the mechanisms of improving the function and regeneration of β-cells by herbal medicines. Relevant data published from January 2009 to March 2020 were collected by searching electronic databases "PubMed," "ScienceDirect," and "Google Scholar" and studied for this review. Single herbal extracts, polyherbal mixtures, and isolated compounds derived from approximately 110 medicinal plants belonging to 51 different plant families had been investigated in recent years and found to be targeting β-cells. Many herbal medicines showed improvement of β-cell function as observed through homeostatic model assessment-β-cell function (HOMA-β). Pancreatic β-cell regeneration as observed in histopathological and immunohistochemical studies in terms of increase of size and number of functional β-cells was also prominent. Increasing β-cell mass via expression of genes/proteins related to antiapoptotic actions and β-cell neogenesis/proliferation, increasing glucose-stimulated insulin secretion via activating glucose transporter-2 (GLUT-2) receptors, and/or increasing intracellular Ca2+ levels were observed upon treatment of some herbal medicines. Some herbal medicines acted on various insulin signaling pathways. Furthermore, many herbal medicines showed protective effects on β-cells via reduction of oxidative stress and inflammation. However, there are many unexplored avenues. Thus, further investigations are warranted in elucidating mechanisms of improving β-cell function and mass by herbal medicines, their structure-activity relationship (SAR), and toxicities of these herbal medicines.
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Affiliation(s)
| | - Pabasara Kalansuriya
- Department of Biochemistry, Faculty of Medicine, University of Ruhuna, Galle, Sri Lanka
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Abd El-Hameed AM, Yousef AI, Abd El-Twab SM, El-Shahawy AAG, Abdel-Moneim A. Hepatoprotective Effects of Polydatin-Loaded Chitosan Nanoparticles in Diabetic Rats: Modulation of Glucose Metabolism, Oxidative Stress, and Inflammation Biomarkers. BIOCHEMISTRY (MOSCOW) 2021; 86:179-189. [PMID: 33832416 DOI: 10.1134/s0006297921020061] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Polydatin (PD) has a broad range of pharmacological activities; however, its effects on diabetic liver damage are poorly studies. This work is aimed to explore possible protective effects of polydatin-loaded chitosan nanoparticles (PD-CSNPs) or PD against liver damage associated with diabetes. Diabetes was induced in rats using nicotinamide/streptozotocin treatment. Diabetic rats were then divided into six groups: normal control rats, diabetic control rats, and rats orally treated with PD, PD-CSNPs, equivalent unloaded CSNPs, or metformin daily for 4 weeks. Treatment with PD and PD-CSNPs significantly reduced the blood glucose content, lipid peroxidation in the liver, and activities of serum transaminases and carbohydrate metabolism enzymes (including succinate dehydrogenase and pyruvate kinase); by contrast, liver glycogen content, glutathione concentration, and activities of the antioxidant enzymes (superoxide dismutase, glutathione peroxidase, catalase, and glucose-6-phosphate dehydrogenase) were markedly increased compared with the control diabetic rats. Furthermore, expression of the tumor necrosis factor α and interleukin-1β mRNAs was significantly downregulated, while expression of glucose transporter 2 and glucokinase mRNAs was strongly upregulated vs. control diabetic rats. We concluded that PD-CSNPs and PD ameliorate diabetic liver damage by modulating glucose transporter 2 expression, affecting the activity of carbohydrate metabolism enzymes, and suppressing oxidative stress and inflammation, PD-CSNPs being more efficient than PD, probably due to higher bioavailability and prolonged release.
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Affiliation(s)
- Abeer M Abd El-Hameed
- Chemistry Department, Faculty of Science, Taibah University, Al-Madinah Al-Munawarah, 30002, Saudi Arabia.
| | - Ahmed I Yousef
- Molecular Physiology Division, Faculty of Science, Beni-Suef University, Beni-Suef, 62511, Egypt.
| | - Sanaa M Abd El-Twab
- Molecular Physiology Division, Faculty of Science, Beni-Suef University, Beni-Suef, 62511, Egypt.
| | - Ahmed A G El-Shahawy
- Materials Science and Nanotechnology Department, Faculty of Postgraduate Studies for Advanced Sciences (PSAS), Beni-Suef University, Beni-Suef, 62511, Egypt.
| | - Adel Abdel-Moneim
- Molecular Physiology Division, Faculty of Science, Beni-Suef University, Beni-Suef, 62511, Egypt.
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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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Apaya MK, Kuo TF, Yang MT, Yang G, Hsiao CL, Chang SB, Lin Y, Yang WC. Phytochemicals as modulators of β-cells and immunity for the therapy of type 1 diabetes: Recent discoveries in pharmacological mechanisms and clinical potential. Pharmacol Res 2020; 156:104754. [DOI: 10.1016/j.phrs.2020.104754] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2019] [Revised: 03/07/2020] [Accepted: 03/10/2020] [Indexed: 12/19/2022]
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Uchenna UE, Shori AB, Baba AS. Tamarindus indica seeds improve carbohydrate and lipid metabolism: An in vivo study. J Ayurveda Integr Med 2018; 9:258-265. [PMID: 29203351 PMCID: PMC6318079 DOI: 10.1016/j.jaim.2017.06.004] [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: 12/28/2016] [Revised: 03/10/2017] [Accepted: 06/01/2017] [Indexed: 11/02/2022] Open
Abstract
BACKGROUND The tamarind seeds have a lot of nutrients that may be used to control cholesterol or glucose levels. OBJECTIVE(S) The effects of tamarind seeds (T) on lipid and carbohydrate metabolism in rats were studied. Rats were offered basal diet (BD) with T (2%, 4% or 8%) or without T. MATERIALS AND METHODS Feeding and growth performance in rats were measured and samples of liver and blood were analyzed for glycogen content and levels of cholesterol and glucose respectively. RESULTS The inclusion of T in the diet influences the feeding and growth performance in rats. The serum cholesterol level was reduced (p < 0.05) in Sprague Dawley (SD) rats fed on basal diet (BD) containing 4% and 8% T (0.24 ± 0.14 g/l and 0.31 ± 0.06 g/l respectively) compared to control (0.79 ± 0.04 g/l). The serum glucose levels in the spontaneous hypertensive rats (SHR) was lower (50.74 ± 2.50 mg/dl; p < 0.05) than control (93.52 ± 10.83 mg/dl) at 4% T. Incorporation of increasing doses of T resulted in linear increase of glycogen storage in livers of SD rats fed on BD and high sucrose diet. CONCLUSION Tamarind seeds can lower blood glucose and serum cholesterol and enhance storage of glycogen in rats.
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Affiliation(s)
- Uzukwu Emmanuel Uchenna
- Biomolecular Research Group, Division of Biochemistry, Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia
| | - Amal Bakr Shori
- King Abdulaziz University, Faculty of Science, Department of Biological Sciences, Jeddah 21589, Saudi Arabia.
| | - Ahmad Salihin Baba
- Biomolecular Research Group, Division of Biochemistry, Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia
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Sathasivampillai SV, Rajamanoharan PRS, Munday M, Heinrich M. Plants used to treat diabetes in Sri Lankan Siddha Medicine - An ethnopharmacological review of historical and modern sources. JOURNAL OF ETHNOPHARMACOLOGY 2017; 198:531-599. [PMID: 27448453 DOI: 10.1016/j.jep.2016.07.053] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/12/2016] [Revised: 06/21/2016] [Accepted: 07/18/2016] [Indexed: 05/13/2023]
Abstract
INTRODUCTION AND BACKGROUND In recent decades diabetes mellitus has become a considerable health problem in countries like Sri Lanka and results in an increasing economic burden hampering the social and economic development of these countries. About 60% to 70% of the rural population in Sri Lanka rely on indigenous medicinal systems as their main source for primary health care. Siddha (Tamil) Medicine is one of the four Sri Lankan traditional medicinal systems and it is practised mostly in the eastern and northern provinces of Sri Lanka where the majority of Tamils reside. AIM The foundation of this study is a documentation of plant species recorded in historical and modern Sri Lankan Siddha Medical documents used to treat diabetes. Based on the systematic documentation and analysis of Siddha concepts about diabetes and its signs and preparations used to treat diabetes in Sri Lankan Siddha Medicine, the plant species included in these preparations (excluding globally or very widely used, very well studied species) were evaluated in terms of the current state-of-the-art about these species' pharmacology and effectiveness in order to lay a foundation for their further development. METHOD Historic and modern Sri Lankan university texts books in Tamil were used as sources for information on diabetes Siddha concepts and antidiabetic Sri Lankan Siddha Medicine preparations. Information on the known antidiabetic effects of extracts and compounds obtained from these species were used in order to assess the current state of the art of these species. RESULTS AND DISCUSSION Information of ingredients, preparation methods, amount of ingredients used, and dosages of 60 antidiabetic Sri Lankan Siddha Medicine preparations were obtained. Animal parts including marine organisms, inorganic substances, and plants are the three types of ingredients used. Overall 171 plant species in 73 families were documented. Senna auriculata (L.) Roxb. (Fabaceae) was identified as the most frequently cited species. Globally distributed and very well studied plants were excluded in the pharmacological and clinical literature review which includes 123 plant species. The majority (48%) of the plant species reviewed were studied up to in vivo level as the current maximum level of scientific evidence available. Followed by 41% of species have not been studied for antidiabetic activities or did not show antidiabetic activity. Moreover, 6% and 5% were studied up to in vitro and in clinical levels, respectively. The majority of the species were studied only in the models that represent type 1 diabetes. CONCLUSION This is the first study systematically assessing the importance of preparations and plants used in antidiabetic Sri Lankan Siddha Medicine preparations. Antidiabetic plants are a crucial health care resource in Sri Lankan Siddha Medicine. This study also identified a wide range of methodological problems in the studies conducted so far. More and better type 2 diabetes models should be employed in future studies. This comprehensive review creates the basis for a more systematic study of these local resources.
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Affiliation(s)
| | - Pholtan R S Rajamanoharan
- Planning Unit, Provincial Department of Indigenous Medicine, Trincomalee, Eastern Province, Sri Lanka
| | - Michael Munday
- Research Cluster 'Biodiversity and Medicines', UCL School of Pharmacy, University of London, United Kingdom
| | - Michael Heinrich
- Research Cluster 'Biodiversity and Medicines', UCL School of Pharmacy, University of London, United Kingdom.
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Improvement in glycemia after glucose or insulin overload in leptin-infused rats is associated with insulin-related activation of hepatic glucose metabolism. Nutr Metab (Lond) 2016; 13:19. [PMID: 26937247 PMCID: PMC4774133 DOI: 10.1186/s12986-016-0079-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2015] [Accepted: 02/25/2016] [Indexed: 11/16/2022] Open
Abstract
Background Insulin regulates glucose homeostasis through direct effects on the liver, among other organs, with leptin modulating insulin’s hepatic actions. Since central leptin may modify insulin signaling in the liver, we hypothesized that leptin infusion activates hepatic glycogen synthesis following peripheral administration of a bolus of glucose or insulin, thus regulating glycemia. Findings Oral glucose and intraperitoneal insulin tolerance tests were performed in control, intracerebroventricular leptin-treated and pair-fed rats during 14 days. An improvement in glycemia and an increase in hepatic free glucose and glycogen concentrations after glucose or insulin overload were observed in leptin-treated rats. In order to analyze whether the liver was involved in these changes, we studied activation of insulin signaling by Western blotting and multiplex bead immunoassay after leptin infusion. Our studies revealed an increase in phosphorylation of insulin receptor substrate-1 and Akt in leptin-treated rats. Examination of parameters related to glucose uptake and metabolism in the liver revealed an augment in glucose transporter 2 and a decrease in phosphoenolpyruvate carboxylase protein levels in this group. Conclusions These results indicate that central leptin increases hepatic insulin signaling, associated with increased glycogen concentrations after glucose or insulin overload, leading to an improvement in glycemia.
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Burgos-Ramos E, Canelles S, Rodríguez A, Gómez-Ambrosi J, Frago LM, Chowen JA, Frühbeck G, Argente J, Barrios V. Chronic central leptin infusion modulates the glycemia response to insulin administration in male rats through regulation of hepatic glucose metabolism. Mol Cell Endocrinol 2015; 415:157-72. [PMID: 26296906 DOI: 10.1016/j.mce.2015.08.014] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2015] [Revised: 08/06/2015] [Accepted: 08/09/2015] [Indexed: 10/23/2022]
Abstract
Leptin and insulin use overlapping signaling mechanisms to modify hepatic glucose metabolism, which is critical in maintaining normal glycemia. We examined the effect of an increase in central leptin and insulin on hepatic glucose metabolism and its influence on serum glucose levels. Chronic leptin infusion increased serum leptin and reduced hepatic SH-phosphotyrosine phosphatase 1, the association of suppressor of cytokine signaling 3 to the insulin receptor in liver and the rise in glycemia induced by central insulin. Leptin also decreased hepatic phosphoenolpyruvate carboxykinase levels and increased insulin's ability to phosphorylate insulin receptor substrate-1, Akt and glycogen synthase kinase on Ser9 and to stimulate glucose transporter 2 and glycogen levels. Peripheral leptin treatment reproduced some of these changes, but to a lesser extent. Our data indicate that leptin increases the hepatic response to a rise in insulin, suggesting that pharmacological manipulation of leptin targets may be of interest for controlling glycemia.
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Affiliation(s)
- Emma Burgos-Ramos
- Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, E-28009, Spain; IMDEA Food, CEI UAM+CSIC, Carretera de Cantoblanco 8, Madrid, E-28049, Spain
| | - Sandra Canelles
- Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, E-28009, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, E-28009, Spain
| | - Amaia Rodríguez
- Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, E-28009, Spain; Metabolic Research Laboratory, Clínica Universidad de Navarra, IdiSNA, Pamplona, E-31008, Spain
| | - Javier Gómez-Ambrosi
- Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, E-28009, Spain; Metabolic Research Laboratory, Clínica Universidad de Navarra, IdiSNA, Pamplona, E-31008, Spain
| | - Laura M Frago
- Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, E-28009, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, E-28009, Spain
| | - Julie A Chowen
- Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, E-28009, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, E-28009, Spain
| | - Gema Frühbeck
- Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, E-28009, Spain; Metabolic Research Laboratory, Clínica Universidad de Navarra, IdiSNA, Pamplona, E-31008, Spain
| | - Jesús Argente
- Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, E-28009, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, E-28009, Spain
| | - Vicente Barrios
- Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, E-28009, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, E-28009, Spain.
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Al-Shaqha WM, Khan M, Salam N, Azzi A, Chaudhary AA. Anti-diabetic potential of Catharanthus roseus Linn. and its effect on the glucose transport gene (GLUT-2 and GLUT-4) in streptozotocin induced diabetic wistar rats. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2015; 15:379. [PMID: 26490765 PMCID: PMC4618145 DOI: 10.1186/s12906-015-0899-6] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/10/2015] [Accepted: 10/06/2015] [Indexed: 12/13/2022]
Abstract
BACKGROUND Catharanthus roseus is an important Ayurvedic medication in traditional medicine. It is potentially used in countries like India, South Africa, China and Malaysia for the healing of diabetes mellitus. Although, the molecular mechanisms behind this effect are yet to be exclusively explored. Due to the great antidiabetic and hyperlipidemic potential of c. roseus, we hypothesized that the insulin mimetic effect of ethanolic extract of c. roseus might add to glucose uptake through improvement in the expression of genes of the glucose transporter (GLUT) family messenger RNA (mRNA) in liver. METHODS STZ-induced diabetic rats treated by ethanolic extract of c. roseus 100 mg/kg and 200 mg/kg; and one group treated with Metformin (100 mg/kg). After final administration of treatment of 4 weeks, blood samples were collected under fasting conditions, and the body weights (BWs) were measured. Total RNA from liver was extracted with the Qiagen RNEasy Micro kit (GERMANY) as described in the manufacturer's instructions. First-strand complementary DNA (cDNA) was synthesized at 40 °C by priming with oligo-dT12-18 (Invitrogen, USA) and using Super ScriptII reverse transcriptase according to the protocol provided by the manufacturer (Invitrogen, USA). Real-time polymerase chain reaction (PCR) amplifications for GLUT-4 (gene ID: 25139) were conducted using Light-Cycler 480 (Roche, USA) with the SyBr® I nucleic acid stain (Invitrogen, USA) according to the manufacturer's instructions. Polymerase chain reaction products of β-actin primer gene were used as an internal standard. RESULTS The proposed study was framed to look at the antidiabetic efficacy of ethanolic extract of c. roseus and an expression of GLUT-2 and GLUT-4 gene in streptozotocin induced diabetic wistar rats. The doses were administered orally at a rate of 100 and 200 mg/kg and detrain the glucose transport system in liver for 4 weeks. The observed results showed a good positive correlation between intracellular calcium and insulin release levels in isolated islets of Langerhans. The supplementation of ethanolic extract of c. roseus significantly amplified the expression of GLUT gene mRNA by Real Time PCR in liver of diabetic rats. CONCLUSIONS We conclude that the observed antidiabetic effect of c. roseus on STZ induced diabetes was a result of complex mechanisms of GLUT gene mRNA expression. The findings are very encouraging and greatly advocate its candidature for the design of a novel herbal drug to cure deadly diabetes.
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Affiliation(s)
- Waleed M Al-Shaqha
- College of Medicine, Al-Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, 13317-7544, Kingdom of Saudi Arabia (KSA)
| | - Mohsin Khan
- Department of Energy and Environmental sciences, Chaudhary Devi Lal University, Sirsa, Haryana, 125055, India
| | - Nasir Salam
- College of Medicine, Al-Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, 13317-7544, Kingdom of Saudi Arabia (KSA)
| | - Arezki Azzi
- College of Medicine, Al-Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, 13317-7544, Kingdom of Saudi Arabia (KSA)
| | - Anis Ahmad Chaudhary
- College of Medicine, Al-Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, 13317-7544, Kingdom of Saudi Arabia (KSA).
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El-Abhar HS, Schaalan MF. Phytotherapy in diabetes: Review on potential mechanistic perspectives. World J Diabetes 2014; 5:176-197. [PMID: 24748931 PMCID: PMC3990312 DOI: 10.4239/wjd.v5.i2.176] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2013] [Revised: 01/07/2014] [Accepted: 03/14/2014] [Indexed: 02/05/2023] Open
Abstract
Diabetes mellitus (DM) is a widely spread epidemic disease that results from the absence of insulin, decreased secretion and/or impaired function. Since DM is a multi-factorial disease, the available pharmaceuticals, despite their sensible treatment, target mostly one pathway to control hyperglycemia and encounter several side effects. Therefore, new therapeutic paradigms aim to hit several pathways using only one agent. Traditionally, antidiabetic plants and/or their active constituents may fulfill this need. More than 200 species of plants possess antidiabetic properties which were evaluated mostly by screening tests without digging far for the exact mode of action. Searching among the different literature resources and various database and in view of the above aspects, the present article provides a comprehensive review on the available antidiabetic plants that have been approved by pharmacological and clinical evaluations, and which their mechanism(s) of action is assured. These plants are categorized according to their proved mode of action and are classified into those that act by inhibiting glucose absorption from intestine, increasing insulin secretion from the pancreas, inhibiting glucose production from hepatocytes, or enhancing glucose uptake by adipose and muscle tissues. The current review also highlights those that mimic in their action the new peptide analogs, such as exenatide, liraglutide and dipeptidylpeptidase-4 inhibitors that increase glucagon-like peptide-1 serum concentration and slow down the gastric emptying.
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