Herbal Therapies for Type 2 Diabetes Mellitus: Chemistry, Biology, and Potential Application of Selected Plants and Compounds
04 Apr 2013-Evidence-based Complementary and Alternative Medicine (Hindawi Publishing Corporation)-Vol. 2013, Iss: 2013, pp 378657-378657
TL;DR: Blood glucose-lowering medicinal herbs that have the ability to modulate one or more of the pathways that regulate insulin resistance, β-cell function, GLP-1 homeostasis, and glucose (re)absorption are selected and discussed.
Abstract: Diabetes mellitus has been recognized since antiquity. It currently affects as many as 285 million people worldwide and results in heavy personal and national economic burdens. Considerable progress has been made in orthodox antidiabetic drugs. However, new remedies are still in great demand because of the limited efficacy and undesirable side effects of current orthodox drugs. Nature is an extraordinary source of antidiabetic medicines. To date, more than 1200 flowering plants have been claimed to have antidiabetic properties. Among them, one-third have been scientifically studied and documented in around 460 publications. In this review, we select and discuss blood glucose-lowering medicinal herbs that have the ability to modulate one or more of the pathways that regulate insulin resistance, β-cell function, GLP-1 homeostasis, and glucose (re)absorption. Emphasis is placed on phytochemistry, anti-diabetic bioactivities, and likely mechanism(s). Recent progress in the understanding of the biological actions, mechanisms, and therapeutic potential of compounds and extracts of plant origin in type 2 diabetes is summarized. This review provides a source of up-to-date information for further basic and clinical research into herbal therapy for type 2 diabetes. Emerging views on therapeutic strategies for type 2 diabetes are also discussed.
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TL;DR: This review compiles the principal articles on medicinal plants used for treating diabetes and its comorbidities, as well as mechanisms of natural products as antidiabetic agents, and considers compounds of high interest as potential antidiabetics.
Abstract: Type 2 diabetes mellitus is a metabolic disease characterized by persistent hyperglycemia. High blood sugar can produce long-term complications such as cardiovascular and renal disorders, retinopathy, and poor blood flow. Its development can be prevented or delayed in people with impaired glucose tolerance by implementing lifestyle changes or the use of therapeutic agents. Some of these drugs have been obtained from plants or have a microbial origin, such as galegine isolated from Galega officinalis, which has a great similarity to the antidiabetic drug metformin. Picnogenol, acarbose, miglitol, and voglibose are other antidiabetic products of natural origin. This review compiles the principal articles on medicinal plants used for treating diabetes and its comorbidities, as well as mechanisms of natural products as antidiabetic agents. Inhibition of α-glucosidase and α-amylase, effects on glucose uptake and glucose transporters, modification of mechanisms mediated by the peroxisome proliferator-activated receptor, inhibition of protein tyrosine phosphatase 1B activity, modification of gene expression, and activities of hormones involved in glucose homeostasis such as adiponectin, resistin, and incretin, and reduction of oxidative stress are some of the mechanisms in which natural products are involved. We also review the most relevant clinical trials performed with medicinal plants and natural products such as aloe, banaba, bitter melon, caper, cinnamon, cocoa, coffee, fenugreek, garlic, guava, gymnema, nettle, sage, soybean, green and black tea, turmeric, walnut, and yerba mate. Compounds of high interest as potential antidiabetics are: fukugetin, palmatine, berberine, honokiol, amorfrutins, trigonelline, gymnemic acids, gurmarin, and phlorizin.
323 citations
14 Sep 2017
TL;DR: The role of endophytic bacteria in synthesis and modulation of bioactive compounds is summarized, which helps the plants to establish systemic resistance against pathogens invasion.
Abstract: In recent years, bioactive compounds are in high demand in the pharmaceuticals and naturopathy, due to their health benefits to human and plants. Microorganisms synthesize these compounds and some enzymes either alone or in association with plants. Microbes residing inside the plant tissues, known as endophytes, also produce an array of these compounds. Endophytic actinomycetes act as a promising resource of biotechnologically valuable bioactive compounds and secondary metabolites. Endophytic Streptomyces sp. produced some novel antibiotics which are effective against multi-drug-resistant bacteria Antimicrobial agents produced by endophytes are eco-friendly, toxic to pathogens and do not harm the human. Endophytic inoculation of the plants modulates the synthesis of bioactive compounds with high pharmaceutical properties besides promoting growth of the plants. Hydrolases, the extracellular enzymes, produced by endophytic bacteria, help the plants to establish systemic resistance against pathogens invasion. Phytohormones produced by endophytes play an essential role in plant development and drought resistance management. The high diversity of endophytes and their adaptation to various environmental stresses seem to be an untapped source of new secondary metabolites. The present review summarizes the role of endophytic bacteria in synthesis and modulation of bioactive compounds.
190 citations
Cites background from "Herbal Therapies for Type 2 Diabete..."
...Nowadays, bioactive compounds are used as preferred synthetic medicines for various diseases with very few side effects (Chang et al. 2013)....
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...microbes, and have broad pharmaceutical properties including anti-cancer, cardiovascular, anti-lipidemic, antihypertensive, anti-glycaemic, antithrombotic, anti-atherogenic and anti-diabetic (Puri et al. 2005; Chang et al. 2013; Atanasov et al. 2015; Villaescusa et al. 2015)....
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...…produced by plants and microbes, and have broad pharmaceutical properties including anti-cancer, cardiovascular, anti-lipidemic, antihypertensive, anti-glycaemic, antithrombotic, anti-atherogenic and anti-diabetic (Puri et al. 2005; Chang et al. 2013; Atanasov et al. 2015; Villaescusa et al. 2015)....
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TL;DR: The extraction, isolation and identification of bioactive compounds and its molecular mechanisms in the prevention of diabetes associated complications are described.
Abstract: Diabetes is a metabolic, endocrine disorder which is characterized by hyperglycemia and glucose intolerance due to insulin resistance. Extensive research has confirmed that inflammation is closely involved in the pathogenesis of diabetes and its complications. Patients with diabetes display typical features of an inflammatory process characterized by the presence of cytokines, immune cell infiltration, impaired function and tissue destruction. Numerous anti-diabetic drugs are often prescribed to diabetic patients, to reduce the risk of diabetes through modulation of inflammation. However, those anti-diabetic drugs are often not successful as a result of side effects; therefore, researchers are searching for efficient natural therapeutic targets with less or no side effects. Natural products’ derived bioactive molecules have been proven to improve insulin resistance and associated complications through suppression of inflammatory signaling pathways. In this review article, we described the extraction, isolation and identification of bioactive compounds and its molecular mechanisms in the prevention of diabetes associated complications.
144 citations
Cites background from "Herbal Therapies for Type 2 Diabete..."
...Natural phyto bioactive compounds are currently more in demand than the synthetic medicines for the treatment of diabetes owing to the rich availability, efficacy and fewer side effects [33,34]....
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TL;DR: An update of the findings from clinical research into medicinal plant therapy for T2DM is presented, finding bioactive molecules isolated from natural sources have been proven to lower blood glucose levels via regulating one or more of the following mechanisms.
Abstract: Diabetes mellitus is a metabolic disorder that majorly affects the endocrine gland, and it is symbolized by hyperglycemia and glucose intolerance owing to deficient insulin secretory responses and beta cell dysfunction. This ailment affects as many as 451 million people worldwide, and it is also one of the leading causes of death. In spite of the immense advances made in the development of orthodox antidiabetic drugs, these drugs are often considered not successful for the management and treatment of T2DM due to the myriad side effects associated with them. Thus, the exploration of medicinal herbs and natural products as therapeutic sources for the treatment of T2DM is promoted because they have little or no side effects. Bioactive molecules isolated from natural sources have been proven to lower blood glucose levels via regulating one or more of the following mechanisms: improvement of beta cell function, insulin resistance, glucose (re)absorption, and glucagon-like peptide-1 homeostasis. In recent times, the mechanisms of action of different bioactive molecules with antidiabetic properties and phytochemistry are gaining a lot of attention in the area of drug discovery. This review article presents an update of the findings from clinical research into medicinal plant therapy for T2DM.
127 citations
Cites background from "Herbal Therapies for Type 2 Diabete..."
...The ethanolic extract of Glycyrrhiza uralensis was able to reduce blood sugar, body fats, and blood pressure in a rat model [244, 249]....
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...Oxidative stress in a diabetic subject causes insulin resistance, beta cell dysfunction, and insulin secretion which could be modulated by phytocompounds with strong antioxidant potential via either regulating blood sugar levels or attenuating no less than one of the following mechanisms linked with insulin resistance: beta cell function, glucose (re)absorption, and incretin-related pathways [244]....
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TL;DR: This review evaluates the clinical and experimental literature on herb–drug interactions in the treatment of diabetes and some commonly used herbs which can interact with antidiabetic drugs summarised.
Abstract: Diabetes is a complex condition with a variety of causes and pathophysiologies. The current single target approach has not provided ideal clinical outcomes for the treatment of the disease and its complications. Herbal medicine has been used for the management of various diseases such as diabetes over centuries. Many diabetic patients are known to use herbal medicines with antidiabetic properties in addition to their mainstream treatments, which may present both a benefit as well as potential risk to effective management of their disease. In this review we evaluate the clinical and experimental literature on herb–drug interactions in the treatment of diabetes. Pharmacokinetic and pharmacodynamic interactions between drugs and herbs are discussed, and some commonly used herbs which can interact with antidiabetic drugs summarised. Herb–drug interactions can be a double-edged sword presenting both risks (adverse drug events) and benefits (through enhancement). There is a general lack of data on herb–drug interactions. As such, more rigorous scientific research is urgently needed to guide clinical practice as well as to safeguard the wellbeing of diabetes patients.
115 citations
Cites background from "Herbal Therapies for Type 2 Diabete..."
...Although the vast majority of available evidence suggests that herbal medicines are relatively safe one case report showed that a patient with T2DM who was treated with the combination of Metformin and Repaglinide experienced hypoglycaemia [93], suggesting that patients and clinicians should indeed be alert to this possibility....
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...One study showed a positive interaction between the combined effect of prickly pear cactus pad and glipizide and metformin in T2DM patients....
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...Nevertheless, a large number of potentially bio-active molecules have been isolated and identified, among which include complex carbohydrates, alkaloids, glycopeptides, terpenoids, peptides, amines, steroids, flavonoids, lipids, coumarins, sulphur compounds and inorganic ions [32]....
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...Approximately 90% of participants were treated by oral therapy for T2DM although the authors did not compare the effects of olive leaf extract between the two groups, and thus further research is required to determine whether there was an interaction between the olive leaf extract and oral hypoglycaemic medication....
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...Abbreviations T1DM: type 1 diabetes mellitus; T2DM: type 2 diabetes mellitus; HDI: herb– drug interaction; STZ: streptozotocin; V/F: final velocity; CYP450: cytochrome P450....
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References
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TL;DR: These predictions, based on a larger number of studies than previous estimates, indicate a growing burden of diabetes, particularly in developing countries.
6,868 citations
"Herbal Therapies for Type 2 Diabete..." refers background in this paper
...7% of the world population by 2030 [1]....
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TL;DR: The prevention of diabetes and control of its micro- and macrovascular complications will require an integrated, international approach if the authors are to see significant reduction in the huge premature morbidity and mortality it causes.
Abstract: Changes in human behaviour and lifestyle over the last century have resulted in a dramatic increase in the incidence of diabetes worldwide. The epidemic is chiefly of type 2 diabetes and also the associated conditions known as 'diabesity' and 'metabolic syndrome'. In conjunction with genetic susceptibility, particularly in certain ethnic groups, type 2 diabetes is brought on by environmental and behavioural factors such as a sedentary lifestyle, overly rich nutrition and obesity. The prevention of diabetes and control of its micro- and macrovascular complications will require an integrated, international approach if we are to see significant reduction in the huge premature morbidity and mortality it causes.
5,733 citations
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...usually accompanies obesity and T2D [148, 149]....
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TL;DR: Eight players comprise the ominous octet and dictate that treatment should be based upon reversal of known pathogenic abnormalities and not simply on reducing the A1C, and therapy must be started early to prevent/slow the progressive β-cell failure that already is well established in IGT subjects.
Abstract: Insulin resistance in muscle and liver and β-cell failure represent the core pathophysiologic defects in type 2 diabetes. It now is recognized that the β-cell failure occurs much earlier and is more severe than previously thought. Subjects in the upper tertile of impaired glucose tolerance (IGT) are maximally/near-maximally insulin resistant and have lost over 80% of their β-cell function. In addition to the muscle, liver, and β-cell (triumvirate), the fat cell (accelerated lipolysis), gastrointestinal tract (incretin deficiency/resistance), α-cell (hyperglucagonemia), kidney (increased glucose reabsorption), and brain (insulin resistance) all play important roles in the development of glucose intolerance in type 2 diabetic individuals. Collectively, these eight players comprise the ominous octet and dictate that: 1 ) multiple drugs used in combination will be required to correct the multiple pathophysiological defects, 2 ) treatment should be based upon reversal of known pathogenic abnormalities and not simply on reducing the A1C, and 3 ) therapy must be started early to prevent/slow the progressive β-cell failure that already is well established in IGT subjects. A treatment paradigm shift is recommended in which combination therapy is initiated with diet/exercise, metformin (which improves insulin sensitivity and has antiatherogenic effects), a thiazolidinedione (TZD) (which improves insulin sensitivity, preserves β-cell function, and exerts antiatherogenic effects), and exenatide (which preserves β-cell function and promotes weight loss). Sulfonylureas are not recommended because, after an initial improvement in glycemic control, they are associated with a progressive rise in A1C and progressive loss of β-cell function.
The natural history of type 2 diabetes has been well described in multiple populations (1–16) (rev. in (17,18). Individuals destined to develop type 2 diabetes inherit a set of genes from their parents that make their tissues resistant to insulin (1,16,19–24). In liver, the insulin resistance is manifested by …
2,184 citations
"Herbal Therapies for Type 2 Diabete..." refers background in this paper
...Targeting β-cell failure early in disease progression has evolved as a new approach to treat T2D [9]....
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TL;DR: There have been major advances in the understanding of the enzymology of sirtuins, their regulation, and their ability to broadly improve mammalian physiology and health span, and the challenges that will confront the field in the coming years are discussed.
Abstract: Aging is accompanied by a decline in the healthy function of multiple organ systems, leading to increased incidence and mortality from diseases such as type II diabetes mellitus, neurodegenerative diseases, cancer, and cardiovascular disease. Historically, researchers have focused on investigating individual pathways in isolated organs as a strategy to identify the root cause of a disease, with hopes of designing better drugs. Studies of aging in yeast led to the discovery of a family of conserved enzymes known as the sirtuins, which affect multiple pathways that increase the life span and the overall health of organisms. Since the discovery of the first known mammalian sirtuin, SIRT1, 10 years ago, there have been major advances in our understanding of the enzymology of sirtuins, their regulation, and their ability to broadly improve mammalian physiology and health span. This review summarizes and discusses the advances of the past decade and the challenges that will confront the field in the coming years.
1,765 citations
"Herbal Therapies for Type 2 Diabete..." refers background in this paper
...In addition, resveratrol enhanced glucose-mediated insulin secretion in β cells via the activation of SIRT1 [124], one of the cellular targets of resveratrol [222, 223]....
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TL;DR: Integrated incremental immunoreactive insulin and connecting peptide responses to an oral glucose load and an “isoglycaemic” intravenous glucose infusion, respectively, were measured in 14 Type 2 diabetic patients and 8 age- and weight-matched metabolically healthy control subjects.
Abstract: Integrated incremental immunoreactive insulin and connecting peptide responses to an oral glucose load of 50 g and an "isoglycaemic" intravenous glucose infusion, respectively, were measured in 14 Type 2 (non-insulin-dependent) diabetic patients and 8 age- and weight-matched metabolically healthy control subjects. Differences between responses to oral and intravenous glucose administration are attributed to factors other than glucose itself (incretin effect). Despite higher glucose increases, immunoreactive insulin and connecting peptide responses after oral glucose were delayed in diabetic patients. Integrated responses were not significantly different between both groups. However, during "isoglycaemic" intravenous infusion, insulin and connecting peptide responses were greater in diabetic patients than in control subjects as a consequence of the higher glycaemic stimulus. The contribution of incretin factors to total insulin responses was 72.8 +/- 6.9% (100% = response to oral load) in control subjects and 36.0 +/- 8.8% in diabetic patients (p less than or equal to 0.05). The contribution to connecting peptide responses was 58.4 +/- 7.6% in control subjects and 7.6 +/- 14.5% (p less than or equal to 0.05) in diabetic patients. Ratios of integrated insulin to connecting peptide responses suggest a reduced (hepatic) insulin extraction in control subjects after oral as compared to intravenous glucose. This was not the case in diabetic patients. Immunoreactive gastric inhibitory polypeptide responses were not different between control subjects and diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)
1,286 citations