Open access peer-reviewed chapter

Antidiabetic Potential of Plants Used in Bulgarian Folk Medicine and Traditional Diet

Written By

Milka Nashar, Yoana D. Kiselova-Kaneva and Diana G. Ivanova

Submitted: 06 February 2019 Reviewed: 25 February 2019 Published: 25 March 2019

DOI: 10.5772/intechopen.85445

From the Edited Volume

Nutrition in Health and Disease - Our Challenges Now and Forthcoming Time

Edited by Gyula Mózsik and Mária Figler

Chapter metrics overview

1,272 Chapter Downloads

View Full Metrics


The idea of this chapter is that currently available antidiabetic drugs specifically target several points of the T2D pathophysiology but they do not cover all aspects of the disease. In addition, many adverse effects of synthetic antidiabetic agents have been reported. The suggested manuscript is an overview of the available scientific literature focused on antiobesity and antidiabetic potential of selected 42 medicinal and edible plants of the Bulgarian flora. Most of the reports reveal the effect of extracts or their active components on specific biochemical mechanisms. Mechanistic data about hypoglycemic and hypolipidemic action are presented for some of the plants. An essential part of this review is dedicated to the target mechanisms behind the effects of the selected plant species. The authors hope that this review will serve as a starting point for future investigations with a contribution to the prevention and therapy of diabetes.


  • medicinal plants
  • diabetes
  • folk medicine
  • traditional diet

1. Introduction

Diabetes is an endocrine disease related to impaired glucose metabolism due to either impaired insulin secretion or decreased sensitivity to its function, classified, respectively, as type 1 diabetes (T1D) and type 2 diabetes (T2D). Over time, chronic hyperglycemia can cause secondary micro- and macrovascular complications affecting the functions of the eyes, kidneys, peripheral nerves, and arteries. According to recent alarming data, the number of adults living with diabetes has almost quadrupled since 1980 to 2014. This dramatic rise is largely due to the number of T2D sufferers [1].

Although some of the characteristics of the modern lifestyle (obesity, stress, low physical activity) are considered to be risk factors with regard to the occurrence of diabetes, it should be noted that cases of the disease are described in written sources dating back to 3500 years [2, 3, 4]. Also, records exist from ancient Egypt, India, and Persia, indicating a long history of medicinal use of plants for treatment of conditions associated with diabetes [5]. Historical and archeological sources indicate that Thracians, the most ancient tribes on the territory of Bulgaria, were familiar with the healing power of the plants [6]. Over the years, empirical data about healing properties of plants used in Bulgarian folk medicine and traditional nutrition have been collected in several reference books [7, 8, 9, 10]. Although plants have been used to treat diabetes for centuries, the number of species with completely clarified antidiabetic mechanisms of action is still limited.

Currently available antidiabetic drugs could specifically target several points of the T2D pathophysiology, but they do not cover all aspects of the disease [11, 12]. In addition, many adverse effects of synthetic antidiabetic agents have been reported [11].

Therefore, it is not surprising that in recent years, the scientific interest is focused on identifying naturally derived compounds and preparations with hope to address more aspects of the disease without undesirable side effects.

This chapter is an overview of the available scientific literature focused on antiobesity and antidiabetic potential of selected 42 medicinal and edible plants of the Bulgarian flora. Most of the reports reveal the effect of extracts or their active components on specific biochemical mechanisms. Mechanistic data for hypoglycemic and hypolipidemic action are presented for some of the plants (references summarized in Table 1). An essential part of this review is dedicated to the target mechanisms behind the effects of the selected plant species.

No. Plant Common name Used parts References
1 Achillea millefolium L. (Asteraceae) White yarrow Aerial parts [13, 14, 15, 16, 17, 18, 19, 20]
2 Agrimonia eupatoria L. (Rosaceae) Agrimony Aerial parts [21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31]
3 Alchemilla vulgaris L. (Rosaceae) Lady’s Mantle Stalk [21, 32, 33]
4 Arctium lappa L. (Asteraceae) Burdock Root [21, 34, 35, 36]
5 Arctostaphylos uva-ursi L. (Ericaceae) Bearberry Leaves [37, 38]
6 Asparagus officinalis L. (Liliaceae) Sparrow grass Stalk [39, 40, 41]
7 Berberis vulgaris L. (Berberidaceae) Barberry Fruits [42, 43, 44]
8 Betula sp. (Betulaceae) Birch Leaves [45, 46]
9 Cichorium intybus L. (Asteraceae) Blue daisy, blue dandelion Stalk, root [13, 14, 21, 47]
10 Cotinus coggygria Scop. (Anacardiaceae) Smoke tree, sumach Leaves [25, 48]
11 Cydonia vulgaris Pers. (Rosaceae) Quince Leaves [49, 50, 51]
12 Foeniculum vulgare Mill. (Apiaceae) Dill Fruits [52, 53, 54]
13 Fragaria vesca complex (Rosaceae) Wild strawberry Leaves [33, 55, 56]
14 Galega officinalis L. (Fabaceae) Goat’s rue Stalk [21, 57, 58, 59]
15 Hypericum perforatum L. (Hypericaceae) St. John’s wort Stalk [25, 60, 61]
16 Juglans regia L. (Juglandaceae) Walnut Leaves [62, 63, 64, 65, 66, 67, 68, 69]
17 Juniperus communis L. (Cupressaceae) Juniper Fruits [13, 14, 21, 31]
18 Lavandula angustifolia Mill. (Liliaceae) Lavender Flower [21, 25, 70, 71]
19 Melissa officinalis L. (Liliaceae) Melissa, lemon balm Stalk [25, 58, 71, 72]
20 Mentha piperita L. (Liliaceae) Mint Leaves [33, 71]
21 Morus nigra L. (Moraceae) Мulberry Leaves, fruits, root bark, heartwood [13, 14], 76, 77, 78, 79, 80, 81, 82
22 Ocimum basilicum L. (Liliaceae) Basil Leaves [73, 74, 75]
23 Ononis spinosa L. (Lamiaceae) Spiny restharrow Root [62]
24 Origanum vulgare L. (Liliaceae) Marjoram Stalk [25, 83, 84, 85]
25 Pelargonium sp. (Geraniaceae) Pelargonium Leaves [86, 87]
26 Phaseolus vulgaris L. (Fabaceae) Bean Pods [13, 14, 21, 88, 89, 90, 91]
27 Plantago major L. (Plantaginaceae) Broadleaf plantain Leaves [62]
28 Polygonum aviculare L. (Polygonaceae) Prostrate knotweed, birdweed, pigweed Stalk [26]
29 Rheum officinale Baill. (Polygonaceae) Rhubarb Root [92, 93]
30 Rosa canina L. (Rosaceae) Rose hip Fruits [55, 94, 95, 96]
31 Rosa damascenа auct. non-Mill. (Rosaceae) Oil rose Flower [97, 98]
32 Rubus sp. diversae Бlackberry Leaves [21, 25, 100, 101]
33 Salvia officinalis L. (Liliaceae) Garden sage Leaves [19, 47, 102, 103, 104, 105, 106]
34 Sambucus ebulus L. (Caprifoliaceae) Dwarf elderberry Fruits [33, 107, 108, 109, 110]
35 Sambucus nigra L. (Caprifoliaceae) European black elderberry Flower [34, 111, 112, 113]
36 Taraxacum officinale Wigg. (Asteraceae) Dandelion Root stalk [19, 21, 34, 81, 114]
37 Thymus sp. diversae (Liliaceae) Thyme Stalk [19, 77]
38 Tilia platyphyllos Scop. (Tiliaceae) Lime tree Flower [37, 115]
39 Urtica dioica L. (Urticaceae) Nettle Stalk [34, 67, 116, 117, 118, 119, 120]
40 Vaccinium myrtillus L. (Ericaceae) Blueberry Leaves and fruits [13, 14, 21, 81]
41 Veronica officinalis L. (Scrophulariaceae) Veronica, speedwell, Paul’s betony Stalk [121, 122]
42 Zea mays L. (Poaceae) Corn Silk [21, 123]

Table 1.

References in support of potentially antidiabetic properties of 42 selected plants.

Without claiming exhaustiveness, the authors hope that this review will serve as a starting point for future investigations with a contribution to the prevention and therapy of diabetes.


2. Effects of plants and plant-derived compounds on glucose homeostasis

2.1 Inhibition of digestive enzymes and glucose absorption in the intestine

Carbohydrates are an essential part of the human diet and are the main energy source of the body. Starch, sucrose, lactose, and glycogen are the main utilizable carbohydrates in human diet. After the action of salivary and pancreatic α-amylase, the digestion products of starch and glycogen along with disaccharides are further digested in the small intestine epithelium, where the membrane-bound enzyme α-glucosidase, as well as various disaccharidases (saccharase, maltase, lactase), catalyze the release of glucose, fructose, and galactose. Monosaccharides are absorbed through the walls of the small intestine and reach the liver by the portal vein.

Inhibition of digestive enzymes is one possible approach to control early-stage hyperglycemia. Inhibition of α-amylase and α-glucosidase can significantly delay the increase in glucose concentration in the postprandial phase [124, 125, 126, 127].

For a significant part of the plants presented in Table 1, data on the inhibitory effect of their extracts or active components on digestive enzymes in different experimental approaches were reported (Table 2). In vitro studies have found that aqueous extracts of basil and walnut leaves exert an inhibitory effect on α-amylase and α-glucosidase as well as on some disaccharidases without affecting insulin secretion and glucose transport proteins [63, 79]. Both studies suggest that polyphenols play a major role in the observed effects, as an extremely rich content of these active compounds in the two extracts is found. Another study [128] demonstrated a strong inhibitory activity of walnuts on the activity of α-amylase and disaccharidases.

Metabolic pathway/mechanism Effects on molecular targets Plant No. Type of studies
Carbohydrate digestion and absorption ↓ α-amylase 1, 3, 6, 8, 22, 26, 30, 31, 33, 36, 37, 39 Spectrophotometrical assessment of enzyme inhibition; STZ-induced diabetes; kinetics of enzyme inhibition
↓ α-glucosidase 1, 6, 8, 22, 26, 30, 31, 33, 36, 37 Spectrophotometrical assessment of enzyme inhibition; glucose oxidase-based method
↓ Disaccharidases 16, 22 Intestinal sucrase and maltase in rats with alloxan-induced diabetes
↓ Glucose absorption 1, 17, 33, 36, 37 Intestinal cell cultures; diabetic rodents
GNG PEPCK 16, 19, 21 Gene expression in hepatocytes of diabetic rodents
Fructose-1,6-bisphosphatase 14 Experimental and clinical studies with metformin
Glucose-6 phosphatase 14, 19 Gene expression in hepatocytes of diabetic rodents; experimental and clinical studies with metformin
Glycogen synthesis Glucokinase 16, 19 Gene expression in hepatocytes of diabetic rodents
Glycogen synthase 2, 6, 35 STZ-induced diabetes in rats; mice muscle cell cultures
Polyol pathway Aldose reductase 5, 24, 42 Diabetic rodents; in vitro enzyme activity in rats lences
Glucose uptake in IDTs GLUT-4 translocation 1, 16, 18, 19, 20,, 26, 33, 36, 37, 41 Glucose uptake in C2C12 myotubes; gene expression in 3T3-L1 cell culture
Insulin secretion SUR1 and Ca2+ channels 1, 2, 4, 6, 9, 16, 28 [Ca2+] and [insulin] in pancreatic beta cells
Lipid metabolism ↓ TAG 1, 2, 13, 16, 26, 30, 34 Rats with alloxan- or STZ-induced diabetes; human intervention studies 3T3-L1 cell cultures
↓ VLDL 1 Rats with alloxan- or STZ-induced diabetes
↓ HMG-CoA reductase 4, 9, 20, 22, 31, 39 Macrophage and 3T3-L1 cell cultures
↓ Total cholesterol 1, 2, 16, 33, 34 Rats with alloxan- or STZ-induced diabetes; human intervention studies
↓ LDL 1, 2, 34 Rats with alloxan- or STZ-induced diabetes; human intervention studies
↑ HDL 16, 34, 36 Rats with alloxan- or STZ-induced diabetes; human intervention studies; cholesterol fed rabbits
↑ HDL/LDL ratio 2, 34 Human intervention studies

Table 2.

Mechanisms of action of selected plants in respect of their antidiabetic potential; ↑-activation, ↓-inhibition.

Plant numbers are in the order as they are listed in Table 1.

Except aqueous extract of thyme, the extracted essential oil of the plant also exhibits an inhibitory effect on the amylase and glucosidase; Paddy et al. [19] and Pongpiriyadacha et al. [46] found that birch extract significantly reduced blood glucose levels after oral administration of sucrose to rats, a result demonstrating the inhibitory action of the extract on α-glucosidase. The same extract in an in vitro study had a concentration-dependent inhibitory effect on α-glucosidase, saccharase, and maltase.

2.2 Effects on glucose homeostasis in the liver

The liver has an essential role in maintenance of glucose homeostasis by controlling the utilization of excess glucose after meal for glycogen synthesis or secretion of free glucose into the circulation through glycogenolysis and gluconeogenesis (GNG) in fasting periods. Insulin and glucagon have a major regulatory role in the activity of these processes. In the periods when the nutrients do not enter the body, all the glucose coming into the circulation is delivered by the liver [129]. Upon food intake, increased glucose levels stimulate secretion of insulin, which has an inhibitory effect on hepatic mechanisms delivering free glucose.

In diabetic patients, this regulation is impaired, and even an increased activity of the key enzymes of gluconeogenesis and glycogenolysis is detected [130, 131].

Galega officinalis has been used from ancient times to alleviate polyuria in diabetic patients. Its active ingredients guanidine and gelagine have been shown to inhibit the enzyme fructose-1,6-bisphosphatase and glucose-6-phosphatase (Table 2).

Fructose-1,6-bisphosphatase is a rate-limiting enzyme in GNG, and its activity has been reported to be pathologically elevated in experimental models of insulin resistance (IR) and obesity [132]. Therefore, inhibition of the enzyme could be a promising target to overcome the chronic hyperglycemia and to maintain normoglycemic status during fasting periods. The search for new GNG inhibitors of natural origin may be of great importance in the control of diabetes, especially for patients intolerant to synthetic therapeutics [11].

Glucose-6-phosphatase is a key enzyme in GNG and glycogenolysis, catalyzing the last step—release of free glucose from the liver.

Several plants from our list are described to exert their hypoglycemic action by inhibiting enzymes from GNG (Table 2). According to folk medicine, Melissa sp. has pronounced spasmolytic and antibacterial action and a slight anxiolytic effect [7]. Scientific data from recent years reveal the antidiabetic potential of the plant ([72]. It was demonstrated that chronic administration of neral and geranial essential oils to db/db mice had significant hypoglycemic effect, due to their stimulatory and, respectively, inhibitory effects on the gene expression of glucokinase and glucose-6-phosphatase.

The enzyme glucokinase, also called the “glucose sensor,” has a key role in the pancreas and liver to maintain glucose homeostasis. Due to the fact that the enzyme has a high Km value for glucose, its role is to provide an excess of glucose (by phosphorylation to glucose-6-phosphate) to activate insulin secretion and glycogen synthesis. The search for active compounds that can stimulate the enzyme is a relatively new concept in the pharmacological approaches to diabetes treatment [11], and probably the role of medicinal plants as sources of such activators is yet to be explored.

The key enzyme for glycogen synthesis is glycogen synthase. Agrimonia eupatoria L., Asparagus officinalis L., and Sambucus nigra L. have shown a stimulating effect on the enzyme activity, but the mechanisms behind this effect remain unclear. Treatment with agrimony and sparrow grass extracts has resulted in increased amount of glycogen in the muscles and liver of rats with streptozotocin-induced diabetes [23, 39]. Elderberry aqueous extract applied to isolated mouse muscle cells stimulated both glucose transport and oxidation as well as glycogen synthesis [111]. Similarly, in cells and animal studies, it was found that preparations and active compounds from Morus sp. have inhibitory effects on gene expression of all regulatory GNG enzymes, including phosphoenolpyruvate carboxykinase (PEPCK) [133, 134].

2.3 Inhibition of polyol pathway of glucose metabolism

The most serious problems resulting from diabetes mellitus are the complications due to increased blood glucose levels.

The body has several options to metabolize the excess glucose. Among them, the polyol pathway is of utmost importance for the development of diabetic complications. Catalyzed by the aldose reductase enzyme, glucose is converted to sorbitol, an osmotically active metabolite which accumulates and damages the cells [135]. It has been shown that inhibition of aldose reductase is preventive against the development of micro- and macrovascular diabetic complications [136, 137].

For three of the selected medicinal plants, data exist about their inhibitory effect on aldose reductase (Table 2). Treatment of diabetic mice with ursolic acid isolated from the bearberry resulted in a reduction in fructose and sorbitol levels in the kidneys [38]. Active components of oregano (caffeic and rosmarinic acid) and of maize hair (hirsutrin) have proven in their in vitro inhibitory action on aldose reductase activity in rat lenses [83, 123].

Research on potential enzyme inhibitors has so far not led to the development of therapeutics of general usage [138]. Although scarce, data on such activity of medicinal plants is promising in future quests for such a therapeutic approach.

2.4 Effects of glucose transport in insulin-dependent tissues

Insulin modulates several metabolic pathways by activating the phosphatidylinositol-3-kinase (PI3K) cascade, including intracellular translocation of the GLUT-4 transport protein for glucose in skeletal and adipose tissues. In diabetes, the transfer of GLUT-4 towards plasma membrane cannot be accomplished.

The hypoglycemic properties of some medicinal plants are due to the ability of their active components to promote the translocation of GLUT-4 to the plasma membrane, resulting in a decrease in blood glucose concentration [20, 90, 106, 139].

Hypoglycemic potential based on this mechanism has been reported primarily for essential oils of lavender, lemon balm, and mint [71, 72]. Luteolin, the flavan derived from Veronica officinalis, was shown to activate both the expression and translocation of the glucose transport protein [140].

2.5 Hypoglycemic activity of plants: putative mechanisms

Much of the data with regards to the antidiabetic activity of the plants were obtained using models of pharmacologically induced diabetes in experimental animals. The most commonly used diabetes-inducing agents are streptozotocin (STZ) and alloxan [141]. Both compounds have destructive effects on pancreatic β cells by different mechanisms. STZ enters the β cells through the transport protein GLUT-2 and damages DNA, resulting in overexpression of DNA repair systems and thus leading to depletion of cell stores of ATP and oxidized nicotinamide dinucleotide (NAD+) [142, 143]; alloxan, transported by GLUT-2, depletes the thiol groups in the cells, establishing a permanent redox cycle with the dialuric acid (its reduced form). This process leads to the accumulation of ROS and hence to the destruction of β cells, which in general have very limited store of endogenous antioxidants [144].

The models of in vivo induced diabetes are informative in terms of the hypoglycemic and insulin-like effects of plant extracts. For example, such was the effect of the aqueous oregano extract applied over a period of several weeks to rats with STZ-induced diabetes. In this study, the established potential of the extract to lower blood sugar and glycated hemoglobin was comparable to that of the antidiabetic drug glibenclamide [84]. In another similar in vivo study, the plant extract exhibited an insulin-like effect normalizing blood glucose levels without affecting plasma basal insulin levels [145]. Similar data was also obtained about black mulberry leaf extract [74]. However, in addition to the hypoglycemic effect, an increase in the insulin levels was reported, which may be attributed to the protective and possibly stimulatory action of the plant on β cells’ function. Data on the antidiabetic properties of Phaseolus vulgaris exist in folk medicine of different ethnic groups [146]. At present, many scientific studies confirm the hypoglycemic and hypolipidemic potential of the plant (predominantly of the pod extract), both in experimentally induced diabetes and in human intervention studies [147, 148, 149]. Vaccinium myrtillus fruits had beneficial effect on obese subjects in a 6-week intervention study as measured by improved insulin sensitivity, inflammatory biomarker levels, and lipid profile [150]. Zea mays hair extracts, as recommended by folk medicine as an antidiabetic remedy, was shown to reduce blood sugar and glycated hemoglobin levels, to stimulate β cells’ function and increase serum insulin levels in an experimental model of diabetes [151, 152]. Hypoglycemic and insulin-like effects have also been reported for Taraxacum officinale roots, for fruits and flowers of Sambucus nigra, stalks of Alchemilla vulgaris and Achillea millefolium, roots from Arctium lappa and Urtica dioica, Cydonia vulgaris leaves, and other plants presented in Table 1.


3. Effects of plants on insulin secretion

There are two mechanisms by which medicinal plants or their active components possibly stimulate insulin secretion [153]:

  • Plant active compounds bind to sulfonylurea binding site 1 (SUR1) of К+-АТP channels resulting in channel closure and membrane depolarization.

  • Direct activation of Са2+ channels.

Sulfonylurea derivatives, such as glibenclamide, are applied for treatment of T2D to stimulate translocation of insulin-containing secretory granules to plasma membrane and exocytosis of insulin in the extracellular matrix [11].

Medicinal plants with an effect on insulin secretion are presented in Table 2.

It should be noted that according to most of the studies, the stimulatory activity of medicinal plants on insulin secretion is attributed to their antioxidative potential and ability to prevent SZT- and alloxan-induced beta cell injury in experimental models of diabetes.


4. Plants that affect lipid metabolism

Defined as abnormal accumulation of adipose tissue, obesity is a major health problem worldwide [154]. As a condition that accompanies obesity, dyslipidemia is believed to be a basic factor for the development of obesity-related diseases such as T2D, cardiovascular diseases (CVD), and atherosclerosis [155]. Dyslipidemia is characterized by increased triacylglycerol (TAG) and total cholesterol levels and unfavorable changes in HDL-/LDL-cholesterol ratio [156, 157].

Many plants that are considered to have antidiabetic potential have beneficial effects on the lipid profile in addition to their hypoglycemic activities [158, 159]. These properties are attributed to their naturally occurring secondary metabolites, such as bioflavonoides.

Anthocyanin extracts and anthocyanin-rich diet can improve the parameters of lipid profile and therefore are considered to have anti-obesity and anti-atherogenic effects in humans and in rodents [160, 161, 162, 163, 164].

Sambucus ebulus (dwarf elderberry) is a plant widely used in Bulgarian folk medicine in various pathological conditions. Its fruits are rich in anthocyanins. Studies report that anthocyanin extracts can reduce body mass and adipose tissue volume in rats fed with high-fat and high-fructose diet [160, 165, 166, 167]. There are reports describing the also hypoglycemic activity of the S. ebulus fruits in rats on high-fat and high-fructose diet [168, 169].

A 30-day human intervention study with S. ebulus fruit tea decreased significantly TAG, total cholesterol, and LDL-cholesterol levels. Slight increase of HDL and significant increase in HDL/LDL ratio were found ([110].

Low HDL levels are recognized as an independent risk factor for the development of cardiovascular diseases [170]. Inhibition of cholesteryl ester transfer protein (CETP) is a probable cause for the increased HDL-cholesterol levels, and LDL-cholesterol levels decrease upon anthocyanin treatment [171]. Anthocyanins can decrease quantity and the activity of CETP in plasma of dyslipidemic patients [161].

The scientific data cited above are in support to the folk medicine reports about the healing properties of S. ebulus fruit preparations.

Likewise, lipid profile improving properties have been reported for Agrimonia eupatoria (agrimony). Its effect on lipid profile was estimated in our study in a model of metabolic disturbances in rats on high-fructose diet. Intake of 40% aqueous-ethanol extract prevented fat accumulation in the liver and adipose tissue and normalized levels of serum lipids [167].

In addition, we performed a human intervention study with 30-day agrimony tea consumption. As a result, increased levels of HDL cholesterol were established, and LDL-cholesterol levels remained unchanged at the same time [29]. These results reveal good potential of agrimony to improve lipid profile, which is important in prophylaxis of CVD and diabetes.

It can be assumed that polyphenols play a role in the mechanisms by which the plant manifests its effects. It is known that diet rich in polyphenols may improve lipid profile in individuals with normal or compromised health status [172, 173]. Polyphenol preparations and polyphenol-rich extracts have also the potential to improve lipid profile [174, 175, 176, 177]. As it was already mentioned, S. ebulus fruits are a rich source of polyphenols and especially of anthocyanins [33, 108]. Also, it was found that the aqueous and aqueous alcoholic extracts of agrimony have a high polyphenol content [25, 178], although their exact polyphenol composition has not yet been identified. Polyphenols have limited bioavailability; however, many of the products of their intestinal metabolism overcome the intestinal barrier and reach the tissues where they exert their biological effects [179].

Some of the selected plants (Table 1) can exert their effects by inhibiting the activity of the rate-limiting enzyme in cholesterol synthesis—HMG-CoA reductase [99]. Cholesterol is the most abundant sterol in the human body and is essential for the normal functioning of the cells. Cholesterol homeostasis is of great importance for the health status. Apart from being a risk factor for atherosclerosis, increased plasma cholesterol levels are often an accompanying parameter of the metabolic disturbances, such as diabetes. Despite being applied for decades, HMG-CoA reductase inhibitors have adverse and unwanted effects, such as myopathy, liver insufficiency, etc. [99].

Even more, in a case of strictly controlled LDL-cholesterol levels by statins, not always TAG and HDL-cholesterol levels are sensitive to the therapy, and there is still a chance that CVD risk would remain high [180]. Interventions with S. ebulus and A. eupatoria tea resulted in significantly increased HDL/LDL ratio; beneficial effects of these plants on plasma TAG and total cholesterol levels were established, so it is likely that the plants improve all parameters of the lipid profile. This makes them promising sources of active compounds with a potential to prevent and supplement the therapy of T2D and CVD.

In addition to the above, scientific data about the beneficial effects of rosehip, strawberries, and raspberries on lipid metabolism and inflammation exist (Table 1). These plants are rich in the glycoside flavonoid tiliroside, which was shown to inhibit postprandial inflammation, to play a role in the prevention of obesity, hyperinsulinemia, and hyperlipidemia. Its action is associated with elevated levels of adiponectin and also facilitated fatty acids oxidation in the liver and skeletal muscles [181]. Strawberry anthocyanin pelargonidin sulfate and pelargonidin-3-O-glycoside reduced postprandial inflammation and increased insulin sensitivity in overweight individuals [56]. Polyphenols extracted from strawberry decreased postprandial LDL oxidation and enhanced lipid metabolism in a high-fat intervention with overweight individuals with hyperlipidemia [182]. Six of the plants listed in Table 1 (Arctium lappa, Cichorium intybus, Mentha piperita, Ocimum basilicum, Rosa damascenа, Urtica dioica) had also inhibitory effect of HMG-CoA reductase. Among them, the extract of R. damascena was found to be the most potent one [99].

The discovery of new effective and safe in long-term application therapeutics is essential for the control and prevention of obesity-related diseases. In this respect, the potential of medicinal and edible plants is still to be explored.


5. Conclusions

The summarized scientific data give а concept about the mechanisms behind the healing effects of plants traditionally used in Bulgarian folk medicine and traditional diet. The selected plants and their active compounds could exert their hypoglycemic and antiobese effects by affecting simultaneously several molecular markers in various processes from carbohydrate and lipid metabolism. Moreover, along with their insulin-like properties, many of the plants can stimulate the insulin secretion. This makes them invaluable in prevention and therapy of socially significant diseases such as diabetes and cardiovascular diseases. Despite the capacity of biotechnology methods to develop new therapeutics, it may be worth to turn a look at the natural resources which potential is still unrevealed.


  1. 1. WHO Report. Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia. 2006. ISBN: 9241594934
  2. 2. Ahmed AM. History of diabetes mellitus. Saudi Medical Journal. 2002;23:373-378
  3. 3. Eknoyan G, Nagy J. A history of diabetes mellitus or how a disease of the kidneys evolved into a kidney disease. Advances in Chronic Kidney Disease. 2005;12:223-229
  4. 4. Lasker SP, McLachlan CS, Wang L, Ali SMK, Jelinek HF. Discovery, treatment and management of diabetes. Journal of Diabetology. 2010;1:1
  5. 5. Eddouks M, Zeggwagh NA. Hypoglycemic Plants: Folklore to modern evidence review. In: Eddouks M, Chattopadhyay D, editors. Phytotherapy in the management of diabetes and hypertension. Bentham Science Publishers, Sharjah, U.A.E.; 2012:164-192. ISBN: 978-1-60805-567-8
  6. 6. Teodorov E. Ancient-Thracian Heritage in Bulgarian Folklore. Academic Publishing House of Bulgarian Academy of Sciences “Professor Marin Drinov”, Sofia, Bulgaria; 1999. ISBN: 9544304983
  7. 7. Dimkov P. Bulgarian Folk Medicine. Vol. 1. Sofia, Bulgaria; BASPRESS: Publishing House of Bulgarian Academy of Sciences; 1977
  8. 8. Dimkov P. Bulgarian Folk Medicine. Vol. 2. BASPRESS: Publishing House of Bulgarian Academy of Sciences, Sofia, Bulgaria; 1978
  9. 9. Dimkov P. Bulgarian Folk Medicine. Vol. 3. BASPRESS: Publishing House of Bulgarian Academy of Sciences, Sofia, Bulgaria; 1979
  10. 10. Nedelcheva A. Medicinal plants from an old Bulgarian medical book. Journal of Medicinal Plants Research. 2012;6(12):2324-2339
  11. 11. Verspohl EJ. Novel pharmacological approaches to the treatment of type 2 diabetes. Pharmacological Reviews. 2012;64:188-237
  12. 12. Tahrani A. Novel therapies in type 2 diabetes: Insulin resistance. Practical Diabetes. 2017;34(5):161-166
  13. 13. Petlevski R, Hadzija M, Slijepcevic M, Juretic D. Effect of ‘antidiabetis’ herbal preparation on serum glucose and fructosamine in NOD mice. Journal of Ethnopharmacology. 2001;75(2-3):181-184
  14. 14. Petlevski R, Hadžija M, Slijepčević M, Juretić D, Petrik J. Glutathione S-transferases and malondialdehyde in the liver of NOD mice on short-term treatment with plant mixture extract P-9801091. Phytotherapy Research. 2003;17(4):311-314
  15. 15. Yazdanparast R, Ardestani A, Jamshidi S. Experimental diabetes treated with Achillea santolina: Effect on pancreatic oxidative parameters. Journal of Ethnopharmacology. 2007;112(1):13-18
  16. 16. Saeidnia S, Gohari AR, Mokhber-Dezfuli N, Kiuchi F. A review on phytochemistry and medicinal properties of the genus Achillea. Daru. 2011;19(3):173-186
  17. 17. Mustafa KG, Ganai BA, Akbar S, Dar MY, Masood A. β-Cell protective efficacy, hypoglycemic and hypolipidemic effects of extracts of Achillea millifolium in diabetic rats. Chinese Journal of Natural Medicines. 2012;10(3):0185-0189
  18. 18. Zolghadri Y, Fazeli M, Kooshki M, Shomali T, Karimaghayee N, Dehghani M. Achillea millefolium L. hydro-alcoholic extract protects pancreatic cells by down regulating IL- 1β and iNOS gene expression in diabetic rats. International Journal of Molecular and Cellular Medicine. 2014;3(4):255-262
  19. 19. Paddy V, van Tonder JJ, Steenkamp V. In vitro antidiabetic activity of a polyherbal tea and its individual ingredients. British Journal of Pharmaceutical Research. 2015;6(6):389-401
  20. 20. Chávez-Silva F, Cerón-Romeroa L, Arias-Durána L, Navarrete-Vázqueza G,Almanza-Pérezb J, Román-Ramosb R, et al. Antidiabetic effect of Achillea millefollium through multitarget interactions: α-glucosidases inhibition, insulin sensitization and insulin secretagogue activities. Journal of Ethnopharmacology. 2018;212:1-7
  21. 21. Bailey CJ, Day C. Traditional plant medicines as treatments for diabetes. Diabetes Care. 1989;12(8):553-564
  22. 22. Kubinova R, Jankovska D, Bauerova V. Antioxidant and alpha-glucosidase inhibition activities and polyphenol content of five species of Agrimonia genus. Acta Fytotechnica et Zootechnica. 2012;2:38-41
  23. 23. Gray AM, Flatt PR. Actions of the traditional anti-diabetic plant, Agrimony eupatoria (agrimony): Effects on hyperglycaemia, cellular glucose metabolism and insulin secretion. The British Journal of Nutrition. 1998;80(1):109-114
  24. 24. Al-Snafi AE. The pharmacological and therapeutic importance of Agrimonia eupatoria—A review. Asian Journal of Pharmacy and Technology. 2015;5(2):112-117
  25. 25. Ivanova D, Gerova D, Chervenkov T, Yankova T. Polyphenols and antioxidant capacity of Bulgarian medicinal plants. Journal of Ethnopharmacology. 2005;96:45-150
  26. 26. Bnouham M, Abderrahim Z, Mekhfi H, Tahri A, Legssyer A. Medicinal plants with potential antidiabetic activity—A review of ten years of herbal medicine research (1990-2000). International Journal of Diabetes and Metabolism. 2006;14:1-25
  27. 27. Ivanova D, Tasinov O, Vankova D, Kiselova-Kaneva Y. Antioxidative potential of Agrimonia eupatoria L. Science and Technology. 2011;1(1):20-24
  28. 28. Patel DK, Prasad SK, Kumar R, Hemalatha S. An overview on antidiabetic medicinal plants having insulin mimetic property. Asian Pacific Journal of Tropical Biomedicine. 2012;2(4):320-330
  29. 29. Ivanova D, Vankova D, Nashar M. Agrimonia eupatoria tea consumption in relation to markers of inflammation, oxidative status and lipid metabolism in healthy subjects. Archives of Physiology and Biochemistry. 2013;119(1):32-37
  30. 30. Kuczmannová A, Balažová A, Racanská E, Kameníková M, Fialová S, Majerník J, et al. Agrimonia eupatoria L. and Cynara cardunculus L. water infusions: Comparison of anti-diabetic activities. Molecules. 2016;21:564
  31. 31. Alam F, Shafique Z, Amjad ST, Asad M. Enzymes inhibitors from natural sources with antidiabetic activity: A review: New targets for antidiabetic treatment. Phytotherapy Research. 2019;33(1):41-54
  32. 32. Neagua E, Pauna G, Albua C, Radu GL. Assessment of acetylcholinesterase and tyrosinase inhibitory and antioxidant activity of Alchemilla vulgaris and Filipendula ulmaria extracts. Journal of the Taiwan Institute of Chemical Engineers. 2015;52:1-6
  33. 33. Kiselova Y, Ivanova D, Chervenkov T, Gerova D, Galunska B, Yankova T. Correlation between the in vitro antioxidant activity and polyphenol content of aqueous extracts from Bulgarian herbs. Phytotherapy Research. 2006;20:961-965
  34. 34. Swanston-Flatt SK, Day C, Flatt PR, Gould BJ, Bailey CJ. Glycaemic effects of traditional European plant treatments for diabetes. Studies in normal and streptozotocin diabetic mice. Diabetes Research. 1989;10(2):69-73
  35. 35. Chan YS, Cheng LN, Wu JH, Chan E, Kwan YW, Lee SM, et al. A review of the pharmacological effects of Arctium lappa (burdock). Inflammopharmacology. 2011;19(5):245-254
  36. 36. Xu Z, Wang X, Zhou M, Ma L, Deng Y, Zhang H, et al. The antidiabetic activity of total lignan from Fructus Arctii against alloxan-induced diabetes in mice and rats. Phytotherapy Research. 2008;22(1):97-101
  37. 37. Slanc P, Doljak B, Kreft S, Lunder M, Janes D, Strukelj B. Screening of selected food and medicinal plant extracts for pancreatic lipase inhibition. Phytotherapy Research. 2009;23(6):874-877
  38. 38. Wang P, Mariman E, Renes J, Keijer J. The secretory function of adipocytes in the physiology of white adipose tissue. Journal of Cellular Physiology. 2008;216:3-13
  39. 39. Zhao J, Zhang W, Zhu X, Zhao D, Wang K, Wang R, et al. The aqueous extract of Asparagus officinalis L. by-product exerts hypoglycaemic activity in streptozotocin-induced diabetic rats. Journal of the Science of Food and Agriculture. 2011;91(11):2095-2099
  40. 40. Hafizur RM, Kabir N, Chishti S. Asparagus officinalis extract controls blood glucose by improving insulin secretion and β-cell function in streptozotocin-induced type 2 diabetic rats. The British Journal of Nutrition. 2012;108(9):1586-1595
  41. 41. Zhang W, Wu W, Wang Q , Chen Y, Yue G. The juice of asparagus by-product exerts hypoglycemic activity in streptozotocin-induced diabetic rats. Journal of Food Biochemistry. 2014;38(5):509-517
  42. 42. Meliani N, Amine Dib ME, Allali H, Tabti B. Hypoglycaemic effect of Berberis vulgaris L. in normal and streptozotocin-induced diabetic rats. Asian Pacific Journal of Tropical Biomedicine. 2011;1(6):468-471
  43. 43. Hajzadeh MAR, Rajaei Z, Shafiee S, Alavinejhad A, Samarghandian S, Ahmadi M. Effect of barberry fruit (Berberis vulgaris) on serum glucose and lipids in streptozotocin-diabetic rats. Pharmacology Online. 2011;1:809-817
  44. 44. Arumugama G, Manjulab P, Paari N. A review: Anti diabetic medicinal plants used for diabetes mellitus. Journal of Acute Disease. 2013;2(3):196-200
  45. 45. Ahmad R, Srivastava SP, Maurya R, Rajendran SM, Arya KR, Srivastava AK. Mild antihyperglycaemic activity in Eclipta alba, Berberis aristata, Betula utilis, Cedrus deodara, Myristica fragrans and Terminalia chebula. Indian Journal of Science and Technology. 2008;1(5):1-6. DOI: 10.17485/ijst/2008/v1i5/29348
  46. 46. Pongpiriyadacha Y, Nuansrithong P, Chantip D. Antidiabetic activity of the methanolic extract from Betula alnoides Buch-Ham. ex G. Don. Journal of Applied Sciences Research. 2013;9(12):6185-6188
  47. 47. Abd El-Ghany MA, Nagib RM, Mamdouh SM. Anti-diabetic effect of some herbs and fruit against streptozotocin induced diabetic rats. Global Veterinaria. 2014;12(4):541-549
  48. 48. Savikin K, Zdunic G, Jankovic T, Stanojkovic T, Juranic Z, Menkovic N. In vitro cytotoxic and antioxidative activity of Cornus mas and Cotinus coggygria. Natural Product Research. 2009;23(18):1731-1739
  49. 49. Aslan M, Orhan N, Orhan DD, Ergun F. Hypoglycemic activity and antioxidant potential of some medicinal plants traditionally used in Turkey for diabetes. Journal of Ethnopharmacology. 2010;128(2):384-389
  50. 50. Khoubnasabjafari M, Jouyban A. A review of phytochemistry and bioactivity of quince (Cydonia oblonga Mill.). Journal of Medicinal Plant Research: Planta Medica. 2011;5(16):3577-3594
  51. 51. Sajid SM, Zubair M, Waqas M, Nawaz M, Ahmad Z. A review on quince (Cydonia oblonga): A useful medicinal plant. Global Veterinaria. 2015;14(4):517-524
  52. 52. Abou El-Soud N, El-Laithy N, El-Saeed G, Wahby KM, Morsy F, Shaffie N. Antidiabetic activities of Foeniculum vulgare Mill. essential oil in streptozotocin-induced diabetic rats. Macedonian Journal of Medical Sciences. 2011;4(2):139-146
  53. 53. Rathera MA, Dara BA, Sofia SN, Bhata BA, Qurishi MA. Foeniculum vulgare: A comprehensive review of its traditional use, phytochemistry, pharmacology, and safety. Arabian Journal of Chemistry. 2016;9:S1574-S1583
  54. 54. Hilmi Y, Abushama MF, Abdalgadir H, Khalid A, Khalid H. A study of antioxidant activity, enzymatic inhibition and in vitro toxicity of selected traditional sudanese plants with anti-diabetic potential. BMC Complementary and Alternative Medicine. 2014;14:149
  55. 55. Marles RJ, Farnsworth NR. Antidiabetic plants and their active constituents. Phytomedicine. 1995;2(2):137-189. DOI: 10.1016/S0944-7113(11)80059-0
  56. 56. Edirisinghe I, Banaszewski K, Cappozzo J, Sandhya K, Ellis CL, Tadapaneni R, et al. Strawberry anthocyanin and its association with postprandial inflammation and insulin. The British Journal of Nutrition. 2011;106(6):913-922. DOI: 10.1017/S0007114511001176
  57. 57. Lemus I, García R, Delvillar E, Knop G. Hypoglycaemic activity of four plants used in Chilean popular medicine. Phytotherapy Research. 1999;13(2):91-94
  58. 58. Andrade-Cetto A. Effects of medicinal plant extracts on gluconeogenesis. Botanics: Targets and Therapy. 2012;2:1-6
  59. 59. Hunter RW, Hughey CC, Lantier L, Sundelin EI, Peggie M, Zeqiraj E, et al. Metformin reduces liver glucose production by inhibition of fructose-1-6-bisphosphatase. Nature Medicine. 2018;24:1395-1406
  60. 60. Husain GM, Chatterjee SS, Singh PN, Kumar V. Hypolipidemic and antiobesity-like activity of standardised extract of Hypericum perforatum L. in rats. ISRN Pharmacology. 2011;2011:505247. 7 p. DOI: 10.5402/2011/505247
  61. 61. Tian J, Tao R, Zhang X, Liu Q , He Y, Su Y, et al. Effect of Hypericum perforatum L. extract on insulin resistance and lipid metabolic disorder in high-fat-diet induced obese mice. Phytotherapy Research. 2015;29(1):86-92
  62. 62. Çoban T, Çitoglu GS, Sever B, Iscan M. Antioxidant activities of plants used in traditional medicine in Turkey. Pharmaceutical Biology. 2003;41(8):608-613
  63. 63. Teimori M, Montasser Kouhsari MS, Ghafarzadegan R, Hajiaghaee R. Study of hypoglycemic effect of Juglans regia leaves and its mechanism. Journal of Medicinal Plants. 2010;9(Suppl 6):57-65
  64. 64. Taha NA, Alwadaan MA. Utility and importance of walnut, Juglans regia Linn: A review. African Journal of Microbiology Research. 2011;5(32):5796-5805
  65. 65. Hosseini S, Huseini HF, Larijani B, Mohammad K, Najmizadeh A, Nourijelyani K, et al. The hypoglycemic effect of Juglans regia leaves aqueous extract in diabetic patients: A first human trial. Daru. 2014;22(1):19
  66. 66. Pitschmann A, Zehl M, Atanasov AG, Dirsch VM, Heiss E, Glasl S. Walnut leaf extract inhibits PTP1B and enhances glucose-uptake in vitro. Journal of Ethnopharmacology. 2014;152(3):599-602
  67. 67. Rahimzadeh M, Jahanshahi S, Moein S, Moein MR. Evaluation of alpha-amylase inhibition by Urtica dioica and Juglans regia extracts. Iranian Journal of Basic Medical Sciences. 2014;17(6):465-469
  68. 68. Khoramdelazad H, Pourrashidi A, Hasanshahi G, Vazirinejad R, Hajizadeh M, Mirzaei M, et al. Effect of the Iranian walnut (Juglans regia) leaves extract on gene expression of gluconeogenic and glycogenolytic enzymes in stz-induced diabetic rats. International Journal of Current Research in Biosciences and Plant Biology. 2015;2(5):47-55
  69. 69. Panth N, Paudel KR, Karki R. Phytochemical profile and biological activity of Juglans regia. Journal of Integrative Medicine. 2016;14(5):359-373
  70. 70. Issa A, Mohammad M, Hudaib M, Tawah K, Abu Rjai T, Oran S, et al. A potential role of Lavandula angustifolia in the management of diabetic dyslipidemia. Journal of Medicinal Plant Research: Planta Medica. 2011;5(16):3876-3882
  71. 71. Yen HF, Hsieh CT, Hsieh TJ, Chang FR, Wang CK. In vitro anti-diabetic effect and chemical component analysis of 29 essential oils products. Journal of Food and Drug Analysis. 2015;23:124-129
  72. 72. Chung MJ, Cho SY, Bhuiyan MJH, Kim KH, Lee SJ. Anti-diabetic effects of lemon balm (Melissa officinalis) essential oil on glucose- and lipid-regulating enzymes in type 2 diabetic mice. British Journal of Nutrition. 2010;104:180-188
  73. 73. Volpatoa GT, Calderona IMP, Sinzatoa S, Camposa KE, Rudgea MVC, Damascenoa DC. Effect of Morus nigra aqueous extract treatment on the maternal–Fetal outcome, oxidative stress status and lipid profile of streptozotocin-induced diabetic rats. Journal of Ethnopharmacology. 2011;138:691-696
  74. 74. Abd El-Mawla AMA, Mohamed KM, Mostafa AM. Induction of biologically active flavonoids in cell cultures of Morus nigra and testing their hypoglycemic efficacy. Scientia Pharmaceutica. 2011;79:951-961
  75. 75. Pasheva M, Nashar M, Tasinov O, Ivanova D. Effects of mulberry heartwood extract on genes related to lipid metabolism. Scripta Scientifica Pharmaceutica. 2015;2(1):34-39
  76. 76. Agrawal P, Rai V, Singh RB. Randomized placebo-controlled, single blind trial of holy basil leaves in patients with noninsulin-dependent diabetes mellitus. International Journal of Clinical Pharmacology and Therapeutics. 1996;34(9):406-409
  77. 77. Lee SJ, Umano K, Shibamoto T, Lee KG. Identification of volatile components in basil (Ocimum basilicum L.) and thyme leaves (Thymus vulgarisL.) and their antioxidant properties. Food Chemistry. 2005;91:131-137
  78. 78. Zeggwagh NA, Sulpice T, Eddouks M. Anti-hyperglycaemic and hypolipidemic effects of Ocimum basilicum aqueous extract in diabetic rats. American Journal of Pharmacology and Toxicology. 2007;2(3):123-129
  79. 79. El-Beshbishy H, Bahashwan S. Hypoglycemic effect of basil (Ocimum basilicum) aqueous extract is mediated through inhibition of α-glucosidase and α-amylase activities: An in vitro study. Toxicology and Industrial Health. 2012;28(1):42-50
  80. 80. Ugwu MN, Umar IA, Utu-Baku AB, Dasofunjo K, Ukpanukpong RU, Yakubu OE, et al. Antioxidant status and organ function in streptozotocin-induced diabetic rats treated with aqueous, methanolic and petroleum ether extracts of Ocimum basilicum leaf. Journal of Applied Pharmaceutical Science. 2013;3(4 Suppl 1):S75-S79
  81. 81. Rouhi-Boroujeni H, Rouhi-Boroujeni H, Heidarian E, Mohammadizadeh F, Rafieian-Kopaei M. Herbs with anti-lipid effects and their interactions with statins as a chemical anti- hyperlipidemia group drugs: A systematic review. ARYA Atherosclerosis. 2015;11(4):244-251
  82. 82. Choudhury H, Pandey M, Hua CK, Mun CS, Jing JK, Kong L, et al. An update on natural compounds in the remedy of diabetes mellitus: A systematic review. Journal of Traditional and Complementary Medicine. 2018;8(3):361-376
  83. 83. Veeresham C, Rao AR, Asres K. Aldose reductase inhibitors of plant origin. Phytotherapy Research. 2013;28:317-333. DOI: 10.1002/ptr.5000
  84. 84. Mohamed NA, Nassier OA. The antihyperglycaemic effect of the aqueous extract of Origanium vulgare leaves in streptozotocin-induced diabetic rats. Jordan Journal of Biological Sciences. 2013;6(1):31-38
  85. 85. Vujicic M, Nikolic I, Kontogianni VG, Saksida T, Charisiadis P, Orescanin-Dusic Z, et al. Methanolic extract of Origanum vulgare ameliorates type 1 diabetes through antioxidant, anti-inflammatory and anti-apoptotic activity. The British Journal of Nutrition. 2015;113(5):770-782
  86. 86. Boukhris M, Bouaziz M, Feki I, Jemai H, El Feki A, Sayadi S. Hypoglycemic and antioxidant effects of leaf essential oil of Pelargonium graveolens L. in alloxan induced diabetic rats. Lipids in Health and Disease. 2012;11:81
  87. 87. Saraswathi J, Venkatesh K, Baburao N, Hilal MH, Rani AR. Phytopharmacological importance of Pelargonium species. Journal of Medicinal Plants Research. 2011;5(13):2587-2598
  88. 88. Tormo MA, Gil-Exojo I, Romero de Tejada A, Campillo JE. Hypoglycaemic and anorexigenic activities of an alpha-amylase inhibitor from white kidney beans (Phaseolus vulgaris) in Wistar rats. The British Journal of Nutrition. 2004;92(5):785-790
  89. 89. Carai MAM, Fantini N, Loi B, Colombo G, Riva A, Morazzoni P. Potential efficacy of preparations derived from Phaseolus vulgaris in the control of appetite, energy intake, and carbohydrate metabolism. Diabetes, Metabolic Syndrome and Obesity. 2009;2:145-153
  90. 90. Fatima A, Agrawal P, Singh PP. Herbal option for diabetes: An overview. Asian Pacific Journal of Tropical Disease. 2012;2:S536-S544
  91. 91. Etxeberria U, de la Garza AL, Campión J, Martínez JA, Milagro FI. Antidiabetic effects of natural plant extracts via inhibition of carbohydrate hydrolysis enzymes with emphasis on pancreatic alpha amylase. Expert Opinion on Therapeutic Targets. 2012;16(3):269-297
  92. 92. Kemper KJ. Rhubarb root (Rheum officinale or R. palmatum). The Center for Holistic Pediatric Education and Research. Longwood Herbal Task Force. Available from:
  93. 93. Gao Q , Qin WS, Jia ZH, Zheng JM, Zeng CH, Li LS, et al. Rhein improves renal lesion and ameliorates dyslipidemia in db/db mice with diabetic nephropathy. Planta Medica. 2010;76(1):27-33
  94. 94. Cosima C, Roufogalis BD, Müller-Ladner U, Chrubasik S. A systematic review on the Rosa canina effect and efficacy profiles. Phytotherapy Research. 2008;22:725-733
  95. 95. Orhan N, Aslan M, Hosbas S, Deliorman OD. Antidiabetic effect and antioxidant potential of Rosa canina fruits. Pharmacognosy Magazine. 2009;5:309-315
  96. 96. Asghari B, Salehi P, Farimani MM, Ebrahimi SN. α-Glucosidase inhibitors from fruits of Rosa canina L. Rec. Journal of Natural Products. 2015;9:3276-3283
  97. 97. Boskabady MH, Shafei MN, Saberi Z, Amini S. Pharmacological effects of Rosa damascene. Iranian Journal of Basic Medical Sciences. 2011;14(4):295-307
  98. 98. Gholamhoseinian A, Fallah H, Sharifi far F. Inhibitory effect of methanol extract of Rosa damascena Mill. flowers on alpha-glucosidase activity and postprandial hyperglycemia in normal and diabetic rats. Phytomedicine. 2009;16(10):935-941
  99. 99. Gholamhoseinian A, Shahouzehi B, Sharifi-Far F. Inhibitory activity of some plant methanol extracts on 3-hydroxy-3-methylglutaryl coenzyme a reductase. International Journal of Pharmacology. 2010;6(5):705-711
  100. 100. Bispo K, Piovezan M, García-Seco D, Amusquivar E, Dudzik D, Ramos-Solano B, et al. Blackberry (Rubus sp. var. Loch Ness) extract reduces obesity induced by a cafeteria diet and affects the lipophilic metabolomic profile in rats. Journal of Food and Nutritional Disorders. 2014;3:4
  101. 101. Zia-Ul-Haq M, Riaz M, De Feo V, Jaafar HZE, Moga M. Rubus fruticosus L.: Constituents, biological activities and health related uses. Molecules. 2014;19:10998-11029
  102. 102. Eidi M, Eidi A, Zamanizadeh H. Effect of Salvia officinalis L. leaves on serum glucose and insulin in healthy and streptozotocin-induced diabetic rats. Journal of Ethnopharmacology. 2005;100(3):310-313
  103. 103. Lima CF, Andrade PB, Seabra RM, Fernandes-Ferreira M, Pereira-Wilson C. The drinking of a Salvia officinalis infusion improves liver antioxidant status in mice and rats. Journal of Ethnopharmacology. 2005;97:383-389
  104. 104. Alarcon-Aguilar FJ, Roman-Ramos R, Flores-Saenz JL, Aguirre-Garcia F. Investigation on the hypoglycaemic effects of extracts of four Mexican medicinal plants in normal and alloxan-diabetic mice. Phytotherapy Research. 2002;16:383-386
  105. 105. Lima CF, Azevedo MF, Araujo R, Fernandes-Ferreira M, Pereira-Wilson C. Metformin-like effect of Salvia officinalis (common sage): Is it useful in diabetes prevention? The British Journal of Nutrition. 2006;96:326-333
  106. 106. Moradabadi L, Montasser Kouhsari S, Fehresti Sani M. Hypoglycemic effects of three medicinal plants in experimental diabetes: Inhibition of rat intestinal α-glucosidase and enhanced pancreatic insulin and cardiac glut-4 mRNAs expression. Iranian Journal of Pharmaceutical Research. 2013;12(3):387-397
  107. 107. Shokrzadeh M, Saravi S. The chemistry, pharmacology and clinical properties of Sambucus ebulus: A review. Journal of Medicinal Plant Research: Planta Medica. 2010;4(2):095-103
  108. 108. Tasinov O, Kiselova–Kaneva Y, Ivanova D. Antioxidant activity, total polyphenol content and anthocyanins content of Sambucus ebulus L. aqueous and aqueous—Ethanolic extracts depend on the type and concentration of extragent. Science & Technologies. 2012;2(1):37-41
  109. 109. Tasinov O, Kiselova-Kaneva Y, Ivanova D. Sambucus ebulus L. fruit aqueous infusion modulates GCL and GPx4 gene expression. Bulgarian Journal of Agricultural Science. 2013;19(Supplement 2):143-146
  110. 110. Tasinov О. Investigation of antioxidant, antiobesity and antidiabetic action of Sambucus ebulus fruit extracts in vitro and in vivo [thesis]. 2015
  111. 111. Gray AM, Abdel-Wahab YH, Flatt PR. The traditional plant treatment, Sambucus nigra (elder), exhibits insulin-like and insulin-releasing actions in vitro. The Journal of Nutrition. 2000;130(1):15-20
  112. 112. Ciocoiu M, Miron A, Mares L, Tutunaru D, Pohaci C, Groza M, et al. The effects of Sambucus nigra polyphenols on oxidative stress and metabolic disorders in experimental diabetes mellitus. Journal of Physiology and Biochemistry. 2009;65(3):297-304
  113. 113. Badescu L, Badulescu O, Badescu M, Ciocoiu M. Mechanism by Sambucus nigra extract improves bone mineral density in experimental diabetes. Evidence-based Complementary and Alternative Medicine. 2012;2012:848269
  114. 114. Yarnell E, Abascal K. Dandelion (Taraxacum officinale and T. mongolicum). Journal of Integrative Medicine. 2009;8(2):35-38
  115. 115. European Medicines Agency of EU. Committee on Herbal Medicinal Products. Assessment report on Tilia cordata Mill., Tilia platyphyllos Scop., Tilia x vulgaris Heyne or their mixtures, flos. 2012. Document 337067/2011, Available from:
  116. 116. Das M, Sarma BP, Rokeya B, Parial R, Nahar N, Mosihuzzaman M. Antihyperglycemic and antihyperlipidemic activity of Urtica dioica on type 2 diabetic model rats. Journal of Diabetology. 2011;2:2
  117. 117. Mobaseri M, Aliasgarzadeh A, Bahrami A, Zargami N, Tabrizi A. Efficacy of the total extract of Urtica dioica on the glucose utilization by the human muscle cells. Journal of Clinical and Diagnostic Research. 2012;6:437-440
  118. 118. Ahangarpour A, Mohammadian M, Dianat M. Antidiabetic effect of hydroalcholic Urtica dioica leaf extract in male rats with fructose-induced insulin resistance. Iranian Journal of Medical Sciences. 2012;37(3):181-186
  119. 119. Qujeq D, Tatar M, Feizi F, Parsian H, Faraji AS, Halalkhor S. Effect of Urtica dioica leaf alcoholic and aqueous extracts on the number and the diameter of the islets in diabetic rats. International Journal of Molecular and Cellular Medicine. 2013;2(1):21-26
  120. 120. Kianbakht S, Khalighi-Sigaroodi F, Dabaghian FH. Improved glycemic control in patients with advanced type 2 diabetes mellitus taking Urtica dioica leaf extract: A randomized double-blind placebo-controlled clinical trial. Clinical Laboratory. 2013;59(9-10):1071-1076
  121. 121. Gründemann C, Garcia-Käufer M, Sauer B, Stangenberg E, Könczöl M, Merfort I, et al. Traditionally used Veronica officinalis inhibits proinflammatory mediators via the NF-κB signalling pathway in a human lung cell line. Journal of Ethnopharmacology. 2013;145(1):118-126
  122. 122. Crişan G, Tămaş M, Miclăuş V, Krausz T, Sandor V. A comparative study of some Veronica species. Revista Medico-Chirurgicală̆ a Societă̆ţ̜ii de Medici şṃi Naturalişṃti din Iaşṃi. 2007;111(1):280-284
  123. 123. Kim TH, Kim JK, Kang YH, Lee JY, Kang IJ, Lim SS. Aldose reductase inhibitory activity of compounds from Zea mays L. BioMed Research International. 2013;2013:727143. 8 pages. DOI: 10.1155/2013/727143
  124. 124. Layer P, Zinsmeister AR, DiMagno EP. Effects of decreasing intraluminal amylase activity on starch digestion and postprandial gastrointestinal function in humans. Gastroenterology. 1986;91(1):41-48
  125. 125. Bischoff H. Pharmacology of alpha-glucosidase inhibition. European Journal of Clinical Investigation. 1994;24(Suppl 3):3-10
  126. 126. Park MH, Ju JW, Park MJ, Han JS. Daidzein inhibits carbohydrate digestive enzymes in vitro and alleviates postprandial hyperglycemia in diabetic mice. European Journal of Pharmacology. 2013;712(1-3):48-52
  127. 127. Hamden K, Mnafgui K, Amri Z, Aloulou A, Elfeki A. Inhibition of key digestive enzymes related to diabetes and hyperlipidemia and protection of liver-kidney functions by trigonelline in diabetic rats. Scientia Pharmaceutica. 2013;81(1):233-246
  128. 128. Fukuda T, Ito H, Yoshida T. Effect of the walnut polyphenol fraction on oxidative stress in type 2 diabetes mice. BioFactors. 2004;2:251-253
  129. 129. Tan B, Ong K. Influence of dietary polyphenols on carbohydrate metabolism. In: Watson RR, Preedy VR, Zibadi S, editors. Polyphenols in Human Health and Disease. Vol. 2, Academic Press Elsevier Inc, London, UK; 2014. pp. 95-111. ISBN: 978-1239-8471-2
  130. 130. Firth RG, Bell PM, Marsh HM, Hansen I, Rizza RA. Postprandial hyperglycemia in patients with noninsulin-dependent diabetes mellitus. Role of hepatic and extrahepatic tissues. The Journal of Clinical Investigation. 1986;77(5):1525-1532
  131. 131. Guyton A, Hall J. Textbook of Medical Physiology. 11th ed. Philadelphia: Elsevier; 2006. pp. 836-839
  132. 132. Visinoni S, Fam BC, Blair A, Rantzau C, Lamont BJ, Bouwman R, et al. Increased glucose production in mice overexpressing human fructose-1,6-bisphosphatase in the liver. American Journal of Physiology. Endocrinology and Metabolism. 2008;295:E1132-E1141
  133. 133. Tiana S, Tanga M, Zhao B. Current anti-diabetes mechanisms and clinical trials using Morus alba L. Journal of Traditional Chinese Medical Sciences. 2016;3(1):3-8
  134. 134. Rodrigues EL, Marcelino G, Silva GT, Figueiredo PS, Garcez WS, Corsino J, et al. Nutraceutical and medicinal potential of the Morus species in Metabolic dysfunctions. International Journal of Molecular Sciences. 2019;20(2):301
  135. 135. Dvornik E, Simard-Duquesne N, Krami M, Sestanj K, Gabbay KH, Kinoshita JH, et al. Polyol accumulation in galactosemic and diabetic rats: Control by an aldose reductase inhibitor. Science. 1973;182:1146-1148
  136. 136. Suzen S, Buyukbingol E. Recent studies of aldose reductase enzyme inhibition for diabetic complications. Current Medicinal Chemistry. 2003;10:1329-1352
  137. 137. Vikramadithyan RK, Hu Y, Noh HL, Liang CP, Hallam K, Tall AR, et al. Human aldose reductase expression accelerates diabetic atherosclerosis in transgenic mice. The Journal of Clinical Investigation. 2005;115:2434-2443
  138. 138. Forbes JM, Cooper ME. Mechanisms of diabetic complications. Physiological Reviews. 2013;93:137-188
  139. 139. Ebrahimi E, Shirali S, Afrisham R. Effect and mechanism of herbal ingredients in improving diabetes mellitus complications. Jundishapur Journal of Natural Pharmaceutical Products. 2017;12(1):e31657
  140. 140. Ong KW, Hsu A, Song L, Huang D, Tan BK. Polyphenols rich Verinoca amygdalina shows anti-diabetic effects in streptozotocin-induced diabetic rats. Journal of Ethnopharmacology. 2011;133(2):598-607
  141. 141. Fröde TS, Medeiros YS. Animal models to test drugs with potential antidiabetic activity. Journal of Ethnopharmacology. 2008;115(2):173-183
  142. 142. Mythili MD, Vyas R, Akila G, Gunasekaran S. Effect of streptozotocin on the ultrastructure of rat pancreatic islets. Microscopy Research and Technique. 2004;63(5):274-281
  143. 143. Eleazu CO, Eleazu KC, Chukwuma S, Essien UN. Review of the mechanism of cell death resulting from streptozotocin challenge in experimental animals, its practical use and potential risk to humans. Journal of Diabetes and Metabolic Disorders. 2013;12:60
  144. 144. Szudelski T. The mechanism of alloxan and streptozotocin action in cells of the rat pancreas. Physiology Research. 2001;50:536-546
  145. 145. Lemhadri A, Zeggwagh NA, Maghrani M, Jouad H, Eddouks M. Anti-hyperglycaemic activity of the aqueous extract of Origanum vulgare growing wild in Tafilalet region. Journal of Ethnopharmacology. 2004;92(2-3):251-256
  146. 146. Helmstädter A. Beans and diabetes: Phaseolus vulgaris preparations as antihyperglycemic agents. Journal of Medicinal Food. 2010;13(2):251-254. DOI: 10.1089/jmf.2009.0002
  147. 147. Venkateswaran S, Pari L. Antioxidant effect of Phaseolus vulgaris in streptozotocin-induced diabetic rats. Asia Pacific Journal of Clinical Nutrition. 2002;11(3):206-209
  148. 148. Pari L, Venkateswaran S. Effect of an aqueous extract of Phaseolus vulgaris on the properties of tail tendon collagen of rats with streptozotocin-induced diabetes. Brazilian Journal of Medical and Biological Research. 2003;36:861-870
  149. 149. Celleno L, Tolaini MV, D’Amore A, Perricone NV, Preuss HG. A dietary supplement containing standardized Phaseolus vulgaris extract influences body composition of overweight men and women. International Journal of Medical Sciences. 2007;4(1):45-52
  150. 150. Stull AJ, Cash KC, Johnson WD, Champagne CM, Cefalu WT. Bioactives in blueberries improve insulin sensitivity in obese, insulin-resistant men and women. The Journal of Nutrition. 2010;140(10):1764-1768
  151. 151. Guo J, Liu T, Tan L, Liu Y. The effect of corn silk on glycemic metabolism. Nutrition and Metabolism. 2009;6:47
  152. 152. Zhao W, Yina Y, Yua Z, Liub J, Chenc F. Comparison of anti-diabetic effects of polysaccharides from corn silk on normal and hyperglycemia rats. International Journal of Biological Macromolecules. 2012;50(4):1133-1137
  153. 153. Prabhakar PK, Doble M. Mechanism of action of natural products used in the treatment of diabetes mellitus. Chinese Journal of Integrative Medicine. 2011;17(8):563-574
  154. 154. WHO Technical Report Series 894. Obesity: Preventing and Managing The Global Epidemic. Geneva: WHO; 2004. Available from:
  155. 155. Klop B, Elte JWF, Cabezas MC. Dyslipidemia in obesity: Mechanisms and potential targets. Nutrients. 2013;5(4):1218-1240
  156. 156. Peterson AL, McBride PE. A review of guidelines for dyslipidemia in children and adolescents. Wisconsin Medical Society. 2012;111(6):274-281
  157. 157. Miller M. Dyslipidemia and cardiovascular risk: The importance of early prevention. QJM: An International Journal of Medicine. 2009;102(9):657-667. DOI: 10.1093/qjmed/hcp065
  158. 158. Mopuri R, Islam MS. Medicinal plants and phytochemicals with anti-obesogenic potentials: A review. Biomedicine & Pharmacotherapy. 2017;89:1442-1452
  159. 159. de Freitas Junior LM, de Almeida EB Jr. Medicinal plants for the treatment of obesity: Ethnopharmacological approach and chemical and biological studies. American Journal of Translational Research. 2017;9(5):2050-2064
  160. 160. Titta L, Trinei M, Stendardo M, Berniakovich I, Petroni K, Tonelli C, et al. Blood orange juice inhibits fat accumulation in mice. International Journal of Obesity. 2010;34(3):578-588
  161. 161. Qin Y, Xia M, Ma J, Hao Y, Liu J, Mou H, et al. Anthocyanin supplementation improves serum LDL- and HDL-cholesterol concentrations associated with the inhibition of cholesteryl ester transfer protein in dyslipidemic subjects. The American Journal of Clinical Nutrition. 2009;90(3):485-492. DOI: 10.3945/ajcn.2009.27814
  162. 162. Basuny AMM, Arafat SM, El-Marzooq MA. Antioxidant and antihyperlipidemic activities of anthocyanins from eggplant peels. Journal of Pharma Research & Reviews. 2012;2(3):50-57
  163. 163. Hansen AS, Marckmann P, Dragsted LO, Finné Nielsen IL, Nielsen SE, Grønbaek M. Effect of red wine and red grape extract on blood lipids, haemostatic factors, and other risk factors for cardiovascular disease. European Journal of Clinical Nutrition. 2005;59(3):449-455
  164. 164. Broncel M, Kozirog M, Duchnowicz P, Koter-Michalak M, Sikora J, Chojnowska-Jezierska J. Aronia melanocarpa extract reduces blood pressure, serum endothelin, lipid, and oxidative stress marker levels in patients with metabolic syndrome. Medical Science Monitor. 2010;16(1):CR28-CR34
  165. 165. Tsuda T, Horio F, Uchida K, Aoki H, Osawa T. Dietary cyanidin 3-O-beta-D-glucoside-rich purple corn color prevents obesity and ameliorates hyperglycemia in mice. The Journal of Nutrition. 2003;133(7):2125-2130
  166. 166. Kwon SH, Ahn IS, Kim SO, Kong CS, Chung HY, Do MS, et al. Anti-obesity and hypolipidemic effects of black soybean anthocyanins. Journal of Medicinal Food. 2007;10(3):552-556
  167. 167. Bratoeva K, Bekyarova G, Kiselova Y, Ivanova D. Effect of Bulgarian herb extracts of polyphenols on metabolic disorders—Induced by high-fructose diet. Trakia Journal of Sciences. 2010;8(2):56-60
  168. 168. Grace MH, Ribnicky DM, Kuhn P, Poulev A, Logendra S, Yousef GG, et al. Hypoglycemic activity of a novel anthocyanin-rich formulation from lowbush blueberry, Vaccinium angustifolium aiton. Phytomedicine. 2009;16(5):406-415
  169. 169. Takikawa M, Inoue S, Horio F, Tsuda T. Dietary anthocyanin-rich bilberry extract ameliorates hyperglycemia and insulin sensitivity via activation of AMP-activated protein kinase in diabetic mice. The Journal of Nutrition. 2010;140(3):527-533
  170. 170. Watson RT, Kanzaki M, Pessin JE. Regulated membrane trafficking of the insulin-responsive glucose transporter 4 in adipocytes. Endocrine Reviews. 2004;25(2):177-204
  171. 171. Inazu A, Brown ML, Hesler CB, Agellon LB, Koizumi J, Takata K, et al. Increased high-density lipoprotein levels caused by a common cholesteryl-ester transfer protein gene mutation. The New England Journal of Medicine. 1990;323(18):1234-1238
  172. 172. Baba S, Osakabe N, Kato Y, Natsume M, Yasuda A, Kido T, et al. Continuous intake of polyphenolic compounds containing cocoa powder reduces LDL oxidative susceptibility and has beneficial effects on plasma HDL-cholesterol concentrations in humans. The American Journal of Clinical Nutrition. 2007;85(3):709-717
  173. 173. Marnewick JL, Rautenbach F, Venter I, Neethling H, Blackhurst DM, Wolmarans P, et al. Effects of rooibos (Aspalathus linearis) on oxidative stress and biochemical parameters in adults at risk for cardiovascular disease. Journal of Ethnopharmacology. 2011;133(1):46-52. DOI: 10.1016/j.jep.2010.08.061
  174. 174. Yugarani T, Tan BK, Das NP. The effects of tannic acid on serum and liver lipids of RAIF and RICO rats fed on high fat diet. Comparative Biochemistry and Physiology. Comparative Physiology. 1993;104(2):339-343
  175. 175. Al-Assafa S, Phillips GO, Williams PA. Studies on acacia exudate gums. Part I: The molecular weight of Acacia senegal gum exudate. Food Hydrocolloids. 2005;19(4):647-660
  176. 176. Bornhoeft J, Castaneda D, Nemoseck T, Wang P, Henning SM, Hong MY. The protective effects of green tea polyphenols: Lipid profile, inflammation, and antioxidant capacity in rats fed an atherogenic diet and dextran sodium sulfate. Journal of Medicinal Food. 2012;15(8):726-732. DOI: 10.1089/jmf.2011.0258
  177. 177. Basu A, Fu DX, Wilkinson M, Simmons B, Wu M, Betts NM, et al. Strawberries decrease atherosclerotic markers in subjects with metabolic syndrome. Nutrition Research 2010;30(7):462-469
  178. 178. Kiselova-Kaneva Y. Total antioxidant capacity and polyphenol content correlation in aqueous-alcoholic plant extracts used in phytotherapy. Scripta Scientifica Medica. 2004;3:11-13
  179. 179. Pandey KB, Rizvi SI. Plant polyphenols as dietary antioxidants in human health and disease. Oxidative Medicine and Cellular Longevity. 2009;2(5):270-278
  180. 180. Freitas WM, Quaglia LA, Santos SN, de Paula RC, Santos RD, Blaha M, et al. Low HDL cholesterol but not high LDL cholesterol is independently associated with subclinical coronary atherosclerosis in healthy octogenarians. Aging Clinical and Experimental Research. 2015;27(1):61-67. DOI: 10.1007/s40520-014-0249-4
  181. 181. Goto T, Teraminami A, Lee JY, Ohyama K, Funakoshi K, Kim YI, et al. Tiliroside, a glycosidic flavonoid, ameliorates obesity-induced metabolic disorders via activation of adiponectin signaling followed by enhancement of fatty acid oxidation in liver and skeletal muscle in obese-diabetic mice. The Journal of Nutritional Biochemistry. 2012;23(7):768e776
  182. 182. Burton-Freeman B, Linares A, Hyson D, Kappagoda T. Strawberry modulates LDL oxidation and postprandial lipemia in response to high-fat meal in overweight hyperlipidemic men and women. Journal of the American College of Nutrition. 2010;29(1):46-54

Written By

Milka Nashar, Yoana D. Kiselova-Kaneva and Diana G. Ivanova

Submitted: 06 February 2019 Reviewed: 25 February 2019 Published: 25 March 2019