An update on natural compounds in the remedy of diabetes mellitus: A systematic review.

Glycemic homeostasis refers to glucose balance or control within circulation in living organisms. It is normally and largely compromised in diabetes. The compromise when exacerbated, leads to several complications including retinopathy, nephropathy and neuropathy which are collectively known as diabetic complications and are the principal actors in co-morbidity and eventual mortality often associated with diabetes. The ability of therapeutic compounds including medicinal plants to restore glycemic balance or homeostasis in hyperglycemic condition is an index of their antidiabetic function and relevance. Alloxan and streptozotocin are the most popular diabetogenic agents used for assessing the antidiabetic or hypoglycemic capacity of test compounds. Notably, alloxan is far less expensive and more readily available than streptozotocin. On this ground, one will logically expect a preference for use of alloxan in experimental diabetes studies. Surprisingly, a sub meta-analysis of randomly selected studies conducted within the last one and half decade revealed otherwise. This observation necessitated the review of alloxan as a diabetogenic agent in animal studies.

https://www.mdpi.com/1648-9144/53/6/365/pdf

Alloxan-induced diabetes, a common model for evaluating the glycemic-control potential of therapeutic compounds and plants extracts in experimental studies.

Mentha longifolia (wild mint) is a popular folk remedy. Some parts of this plant have been used in traditional medicine of Iran and other countries. Many studies have shown various pharmacological and therapeutic effects of the plant. Our aim in preparing this study was to review the traditional uses of M. longifolia together with the pharmacological and therapeutic effects of its entire extract and major compounds. Mentha longifolia is an herb with a wide range of pharmacological properties such as antimicrobial, gastrointestinal, and nervous system effects. Pulegone is the main compound of the plant responsible for most of its pharmacological effects followed by menthone, isomenthone, menthol, 1, 8-cineole, borneol, and piperitenone. Moreover, the plant may dose-dependently exert toxic effects in different systems of the body. Based on the review of various studies, it can be concluded that M. longifolia is a potential natural source for the development of new drugs. However, further studies are required to determine the precise quality and safety of the plant to be used by clinicians.

Pharmacological and therapeutic effects of Mentha Longifolia L. and its main constituent, menthol.

The present review focused on plant extracts or phytochemicals role in diabetes management has been tried by many researchers. I have attempted to compile a list of total 419 plant species belongs to 133 families have been used for in-vitro and in-vivo studies. The plant extract or phytochemicals have involved in decreasing or increasing or stimulating different mechanisms in reducing diabetes and they have been listed in tabular form. By this review, few molecules are used in diabetes management and they possess molecular mechanisms or involved in signal transduction to initiate the insulin production or utilization of blood glucose level bring down to normal stage. The researchers have used different parts of the plant extracts or individual phytochemicalsfor antidiabetic activities. This review brings the researcher data on antidiabetic activities of different plant extracts role in reducing of diabetic problems.

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A Review on Role of Plant(s) Extracts and its Phytochemicals for the Management of Diabetes

Diabetes mellitus is a common form of metabolic disorder where level of blood glucose in the bloodstream raises high, because of deficiency of insulin and development of insulin resistance in diabetic individuals. It is categorize under modern age life style disorder, commonly affected by middle-aged people and the children in adolescents in most developed countries. Diabetic patients develop serious complication with the development of disease, such as obesity, risk of stroke and heart failure. The worldwide prevalence of diabetes is likely to increase from 382 million people in 2013 to 592 million by 2035. Globally antidiabetic drugs formulate the second-largest market by sales in the pharmaceuticals industry after cancer. Various novel targets have identified and recently various therapeutic leads successfully completed their different phases of clinical trials such as GLP-1 agonist, DPP-IV inhibitors, SGLT2 inhibitors, and are going to be the next generation therapy for management of diabetes. Presently the information was collects from PubMed, Science Direct, SciFinder and Google Scholar. In this review, we spotlighted on some common therapeutic targets involved in type 2 diabetes, offering a new concept for developing new drug candidates to produce newer generation antidiabetic drugs against type 2 diabetes.

Therapeutic Targets for Diabetes Mellitus: An Update

Background: Urtica dioica has been used as antihypertensive, antihyperlipidemic and antidiabetic herbal medicine. The purpose of this study was to study the effect of hydroalcoholic extract of Urtica dioica on fructose-induced insulin resistance rats. Methods: Forty male Wistar rats were randomly divided into five groups including control, fructose, extract 50, extract 100 and extract 200. The control rat received vehicle, the fructose and extract groups received fructose 10% for eight weeks. The extract groups received single daily injection of vehicle, 50, 100 or 200 mg/kg/day for the two weeks. Blood glucose, insulin, last fasting insulin resistance index (FIRI), serum triglyceride (TG), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), high-density lipoprotein (HDL), alanin trasaminase (AST) and alkaline phosphatase (ALP), leptin and LDL/HDL ratio were determined. Results: Compared to control group, daily administration of fructose was associated with significant increase in FIRI, blood glucose and insulin, significant decrease in lepin, and no significant change in TG, HDL, LDL, LDL/HDL ratio, VLDL, ALT, and ALP. The extract significantly decreased serum glucose, insulin, LDL and leptin, and LDL/HDL ratio and FIRI. It also significantly increased serum TG, VLDL, and AST, but did not change serum ALP. Conclusion: We suggest that Urtica dioica extract, by decreasing serum glucose, and FIRI, may be useful to improve type 2 diabetes mellitus. Also, by positive effect on lipid profile and by decreasing effect on leptin, it may improve metabolic syndrome.

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Antidiabetic effect of hydroalcholic urticadioica leaf extract in male rats with fructose-induced insulin resistance.

Background: Studies have shown that Physalis alkekengi reduces implantation and induces antifertility in rat. In Iranian traditional medicine it is believed that this plant has abortifacient and antifertility activities. Objective: The goal of this study was to evaluate the effect of Physalis alkekengi ripe fruit hydroalcoholic extract (PFE) on uterine contractility and its possible mechanism(s). Materials and Methods: Extraction of Physalis alkekengi fruit was carried out by maceration method (70% alcohol). Uterus was dissected out from adult non-pregnant rat (Wistar) and contracted by KCl (60mM) or oxytocin (10mU/ml) in an organ bath containing De Jalon solution and the effect of PFE on the uterine contractions was investigated. Furthermore, the role of α- and β-adrenoceptors, opioid receptors, nitric oxide and cyclic guanosine monophosphate synthesis inhibitors on the extract effects were evaluated. Results: KCl- and oxytocin-induced uterine contractions were inhibited (p<0.001) by the cumulative concentrations of the extract in a concentration dependent manner. Incubation of uterus with propranolol (1μM) and L-NAME (100μM) attenuated the PFE antispasmodic effect (p<0.05). But the PFE effect was unaffected by phentolamine (1μM), naloxone (1μM) or methylene blue (10μM). In Ca 2+ -free with high potassium (60mM) De Jalon solution, cumulative concentrations of CaCl2 (0.1-0.5mM) induced uterine contraction concentration-dependently (p<0.001). Uterus incubation (5min) with PFE (0.25-1.75mg/ml) attenuated the CaCl2–induced contractions (p<0.05). Conclusion: It seems that the extract induced antispasmodic effect mainly via calcium influx blockade and partially through blocking β-adrenoceptors and nitric oxide (NO) synthesis. However, neither α-adrenoceptors nor opioid receptors or cGMP synthesis were involved.

Antispasmodic effect of Physalis alkekengi fruit extract on rat uterus

The effect of Mentha longifolia (L.) leaf hydroalcoholic extract (MLE) was examined on rat ileal smooth muscle contractions. Last portion of ileum from male adult Wistar rat was mounted in an organ bath containing Tyrode solution. The tissue was contracted by carbachol (CCh, 10 microM), KCl (60 mM) and BaC12 (4 mM) and then MLE (0.0625-1 mg mL(-1)) was added to the bath cumulatively. The effect of MLE on KCl-induced contraction was examined after tissue incubation with propranolol (1 microM), naloxone (1 microM) and N omega-nitro-L-arginine methyl ester (L-NAME, 100 microM). The effect of MLE on CaCl2-induced ileal contraction in Ca(2+)-free with high potassium Tyrode solution was also evaluated. The role of potassium channels was examined by ileum incubation (5 mim) with tetraethylammonium (TEA, 1 mM). The results showed that KCl-, CCh and BaCl2-induced ileal contractions were inhibited (p < 0.001) by cumulative concentrations of MLE with the same potency. In addition, MLE (0.25-1 mg mL(-1)) inhibited (p < 0.01) ileal contractions induced by CaCl2 (0.45-2.7 mM) in a concentration-related manner. The antispasmodic effect of MLE was affected neither by propranolol, L-NAME nor by naloxone. The MLE concentration-response curve was shifted to the right (p < 0.05) by tissue incubation with TEA. From results it may be suggested that Mentha longifolia hydroalcoholic leaf extract induces its spasmolytic activity mainly through disturbance in calcium mobilization and partly by potassium channels activation. Present results show that Mentha longifolia leaf extract exerts relaxant effects on intestinal smooth muscle, consistent with the traditional use of the plant to treat gastrointestinal disorders such as diarrhea and colic.

Maryam Mohammadian

Papers

Antidiabetic effect of hydroalcholic urticadioica leaf extract in male rats with fructose-induced insulin resistance.

Antispasmodic effect of Physalis alkekengi fruit extract on rat uterus

Ileal relaxation induced by Mentha longifolia (L.) leaf extract in rat.