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Laurel Zuev
Laurel Zuev

Phytotherapy In The Management Of Diabetes And ...



Medicinal plants are a source of potential therapeutic compounds. Phytotherapy can give patients long term benefits with less or no side effects. Phytotherapy in the Management of Diabetes and Hypertension is a book series which emphasizes the biochemistry behind diabetes mellitus and hypertension, along with the control or remediation of these conditions through cost effective, safe and easily-adaptable methods validated by scientific research. This is the fourth volume of the series which features reviews on selected natural products used to treat diabetes and hypertension. This volume brings 6 chapters contributed by 14 researchers that cover general updates on diabetic phytotherapy, circumin, and the medicinal use of olive leaves, passion fruit and spiral gingers in the treatment of diabetes and hypertension.




Phytotherapy in the management of diabetes and ...



Phytotherapy has long been a source of medicinal products and over the years there have been many attempts to use herbal medicines for the treatment of diabetes. Several medicinal plants and their preparations have been demonstrated to act at key points of glucidic metabolism. The most common mechanisms of action found include the inhibition of α-glucosidase and of AGE formation, the increase of GLUT-4 and PPARs expression and antioxidant activity. Despite the large amount of literature available, the actual clinical effectiveness of medicinal plants in controlling diabetes-related symptoms remains controversial and there is a crucial need for stronger evidence-based data. In this review, an overview of the medicinal plants, which use in the management of diabetes is supported by authoritative monographs, is provided. References to some species which are currently under increasing clinical investigation are also reported.


Methods: A cross sectional study was conducted on diabetic patients attending the outpatient clinics in 4 major hospitals in Riyadh, Kingdom of Saudi Arabia. These were: King Khalid University Hospital, King Abdul-Aziz University Hospital, Prince Salman Hospital and Riyadh Medical Complex over a 3-month period which started in September 1999. Patients were interviewed by trained medical students through a predesigned questionnaire that contains items that are related to diabetes and the use of herbs by diabetics.


Conclusion: The use of herbs is not rare among diabetic patients. Doctors caring for diabetic patients should encourage them to talk regarding the use of herbs as it may effect the outcome and the management of their disease.


Phytotherapy has long been a source of medicinal products and there have been many attempts to use herbal medicines for the treatment of diabetes over the years [12,13]. Furthermore, the number of scientific publications regarding herbal medicine and type 2 diabetes is continuously increasing [14].


Among the possible mechanisms of action of natural products in diabetes, such as the inhibition of α-glucosidase and α-amylase, the effects on glucose uptake and glucose transporters, the enhancement of insulin secretion and of pancreatic β-cell proliferation, the inhibition of protein tyrosine phosphatase 1B activity and the antioxidant activity have been studied in depth [15].


Despite the large amount of available literature, the real clinical effectiveness of medicinal plants in the management of diabetes is still controversial and there is a crucial need for stronger evidence-based data [16]. Indeed, despite a long folk medicine history, most of the popular species used suffer from clinical inconsistency, mainly due to the poor quality of the clinical studies [17]. Another aspect to be considered is the variability of the raw herbal materials and preparations used, which may lead to the non-reproducibility of results among different trials [18].


A preliminary study evaluated the hypoglycemic effects of the oral administration of small slices of A. cepa (100 g/day) in type 1 and type 2 diabetic patients. Onion exhibited significant antidiabetic effects, reducing fasting blood glucose by about 89 mg/dL in type 1 diabetes patients and by 40 mg/dL in type 2 diabetes patients. A reduction of the induced hyperglycemia by 120 mg/dL in the diabetes 1 group and by 159 mg/dL in the type 2 diabetes was also observed [29].


The activation of the AMP-activated protein kinase (AMPK) system and a role of the α- and γ-peroxisome proliferator-activated receptors (PPARα and PPARγ) have been hypothesized as possible mechanisms of action for M. charantia in diabetes treatment [54,55,56].


In 1996, a randomized, placebo-controlled, crossover single blind trial analyzed the effects of O. tenuiflorum and O. album leaves on fasting and postprandial blood glucose and serum cholesterol levels in patients with noninsulin-dependent diabetes mellitus. A significant decrease in fasting and postprandial blood glucose levels, a similar trend in urine glucose, and a mild reduction of mean total cholesterol levels during treatment period were observed [67].


Gymnema sylvestre (Retz.) R.Br. ex Sm., commonly known as gurmar, has been used since ancient times, particularly in Ayurvedic medicine, and its anti-obesity and anti-diabetic efficacy has been clinically demonstrated [139] and confirmed in animal models [140]. The anti-diabetic activity of gurmar has been attributed mainly to gymnemic acids, gymnemasaponins and gurmarin contained in the leaves [141]. A dihydroxygymnemic acetate (20 mg/kg), isolated from G. sylvestre leaves, has been administered in streptozocin-induced diabetic rats for 45 days, causing a significative reduction of plasma glucose and glycated hemoglobin level, and an increase of plasma insulin and muscle and liver glycogen [142]. The proposed mechanisms of action include the increase of insulin secretion and the promotion of islet cell regeneration, together with the reduction of intestinal and blood glucose adsorption [13]. Some products derived from G. sylvestre have been patented in different European countries. In 2010, a high molecular weight leaves extract (1 g/day for 60 days) was found to significantly increase the circulating insulin and C-peptide levels and reduced fasting and post-prandial blood glucose in a small cohort of patients with type 2 diabetes [143]. In the same year, a different G. sylvestre leaves extract (500 mg/day for 3 months) was similarly able to reduce fasting and post prandial blood glucose and glycated hemoglobin, causing a favourable shift in lipid profile, in type 2 diabetic patieints [144]. Nevertheless, more studies are needed in order to support the use of gurmar in the treatment of diabetic patients [145].


According to a recent systematic review, Curcuma longa L. can be considered a promising species for the management of impaired glucose tolerance, as curcumin is able to significantly reduce fasting blood glucose, glycosylated hemoglobin and insulin resistance after 3, 6 and 9 months of treatment [146]. Moreover, when administered together with an absorption enhancer (i.e., piperine 10 mg/day), curcuminoids (1000 mg/day) were able to reduce serum levels of atherogenic lipid indices, which are risk factors for cardiovascular events in type 2 diabetes patients [146].


The potential of ω-3 fatty acids on glycemic control is widely discussed [149]. Linum usitatissimum L. seed oil, also referred to as flaxseed oil, is contains over than 50% ω-3 fatty acids, mainly represented by α-linolenic acid [150]. A recent randomized controlled interventional trial demonstrated the ability of L. usitatissimum seed oil (25 mg/day) to ameliorate some symptoms of metabolic syndrome, including blood pressure and lipid peroxidation [151]. In type 2 diabetic patients with coronary heart disease, the supplementation with L. usitatissimum oil (1000 mg/day for 12 weeks) increased gene expression levels of PPAR-γ and downregulated gene expression of lipoprotein(a), IL-1 and TNF-α [152]. Moreover, L. usitatissimum seed powder (10 g/day for 1 month), containing not quantified ω-3 fatty acids and lignans, reduced fasting blood glucose, glycated hemoglobin, triglycerides, total and LDL cholesterol and apolipoprotein B, and increase HDL cholesterol levels in type 2 diabetes patients [153]. Similar results were obtained by the supplementation with L. usitatissimum gum (5 g/day for 3 months) [154].


Insulin-like proteins from Moringa oleifera Lam. leaves have been addressed for their potential role in the management of diabetes [157]. In alloxan-induced diabetic mice, a leaf protein isolate from M. oleifera (500 mg/kg) reduced blood glucose level and oxidative stress, but did not stimulate insulin secretion [158]. A reduction of blood glucose and a high antioxidant activity was also observed in streptozocin-induced diabetic rats treated with a M. oleifera leaves methanol extract (250 mg/kg) [159]. However, clinical validation has to be carried out, since very little information is currently available, with only one preliminary clinical trial been conducted by administering M. oleifera leaf powder to healthy subject and evaluating outcome related to diabetes [160].


The anti-diabetic potential of several Morinda citrifolia L. preparations has been reviewed recently: although there is a wide number of products on the market, there is still the need for well-conducted clinical trials in order to better investigate the role of this herbal product in diabetes [163].


The consumption of tea (Camellia sinensis (L.) Kuntze) and coffee (Coffea Arabica L.) has been related to a lowered risk of type 2 diabetes onset [164] and these beverage were also found to be effective in impaired glucose tolerance. Some of the effects of coffee involved in the prevention of type 2 diabetes includes: improvement of glucose tolerance, insulin sensitivity and insulin secretion, reduction of glucose intestinal uptake and regulation of glucose metabolism [165]. Moreover, a randomized acute crossover intervention study conducted in healthy volunteers showed the ability of coffee polyphenols to improve postprandial hyperglycemia, increasing glucagon-like peptide 1 secretion and decreasing oxidative stress [166]. Type 2 diabetic patients drinking three cups (600 mL) of black tea per day for 12 weeks reported a significant reduction in glycated hemoglobin level, together with an amelioration of the immune function relevant to prevention and management of type 2 diabetes [167]. The effect of tea seems to be related to its polyphenol contents, and in particular to epigallocatechin-3-gallate, which may act on glucose intestinal and cellular uptake and on oxidative stress [168]. 041b061a72


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