|Year : 2020 | Volume
| Issue : 10 | Page : 433-441
Anti-diabetic properties and bioactive compounds of Teucrium polium L.
Ali Akbar Asghari1, Amin Mokhtari-Zaer1, Saeed Niazmand1, Kathleen Mc Entee2, Maryam Mahmoudabady3
1 Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
2 Laboratory of Physiology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium
3 Department of Physiology, Faculty of Medicine; Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
|Date of Submission||15-Jan-2020|
|Date of Decision||06-Feb-2020|
|Date of Acceptance||19-May-2020|
|Date of Web Publication||03-Aug-2020|
Department of Physiology, Faculty of Medicine; Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad
Source of Support: None, Conflict of Interest: None
Diabetes mellitus is a common metabolic disease with considerable morbidity and mortality. Untreated or improperly-treated diabetes can be associated with several long-term complications that necessitate an effective way to manage diabetes. Due to the side effects of synthetic glucose-lowering agents, alternative therapeutic modalities such as medicinal plants have attracted notable attention. Teucrium polium L. is a medicinal herb with antioxidant, antinociceptive, anti-inflammatory, hypolipidemic, hepatoprotective, and hypoglycemic properties. In vitro and in vivo studies have been conducted to characterize the anti-diabetic properties of Teucrium polium L. and its bioactive compounds. We conducted a literature study using Scopus, PubMed, and Google Scholar including the keywords “diabetes” and “Teucrium polium”. We also scanned all the references cited by the retrieved articles. According to this review, Teucrium polium administration displayed anti-diabetic effects by targeting different mechanisms and pathways, such as enhancement of insulin secretion and insulin level, improvement of oxidative damage, regeneration of pancreatic β-cells, and promotion of glucose uptake in muscle tissues by increasing GLUT-4 translocation as well as inhibiting α-amylase activity. Although Teucrium polium has been widely regarded as a traditional method, the pharmacological studies on anti-diabetic effects are not sufficient, most studies are either in-vivo or in-vitro. The preclinical and clinical studies are further required to confirm the efficacy of Teucrium polium.
Keywords: Teucrium polium L.; Diabetes mellitus; Oxidative stress; Inflammation
|How to cite this article:|
Asghari AA, Mokhtari-Zaer A, Niazmand S, Mc Entee K, Mahmoudabady M. Anti-diabetic properties and bioactive compounds of Teucrium polium L. Asian Pac J Trop Biomed 2020;10:433-41
|How to cite this URL:|
Asghari AA, Mokhtari-Zaer A, Niazmand S, Mc Entee K, Mahmoudabady M. Anti-diabetic properties and bioactive compounds of Teucrium polium L. Asian Pac J Trop Biomed [serial online] 2020 [cited 2021 Jan 18];10:433-41. Available from: https://www.apjtb.org/text.asp?2020/10/10/433/290868
| 1. Introduction|| |
Diabetes mellitus (DM) is a typical metabolic disease with conspicuous human morbidity and mortality. Affecting 451 million people globally in 2017, DM is predicted to increase to 693 million by 2045. Untreated or improperly-treated DM can be associated with several acute and chronic problems, including cardiovascular disease, kidney damage, eye problems, foot ulcer, impotence, and even death.
DM is characterized by a disturbance of glucose homeostasis and hyperglycemia. Tight control of blood glucose levels is achieved in a relatively small range (80–100 mg/dL) via coordinating various peripheral organs, such as the pancreas, adipose tissue, skeletal muscle, liver, and central nervous system in healthy animals and humans. Normal fasting blood glucose levels should be maintained within 80-100 mg/dL. When one or several organs cannot help maintain glucose homeostasis, it will lead to prediabetes (glucose intolerance) and then DM. Common reasons for DM include the malfunctioned insulin secretion from pancreatic β-cells and the resistance to insulin-mediated glucose disposal in peripheral tissues (e.g. the muscle, adipose tissue, and liver). The improper treatment of diabetes can lead to long-term complications, such as cardiomyopathy, retinopathy, and nephropathy. Thus, effective management of diabetes is important. Given the side effects of many synthetic glucose-lowering agents, natural resources such as medicinal herbs can be more helpful and cost-effective alternative treatments for DM.
Used for hundreds of years for human diseases, medicinal herbs are great sources of various pharmacologically-active compounds. Today, many drugs that are available on the market may originate directly or indirectly from natural products. For instance, galegine is an alkaloid isolated from Galega officinalis, which is structurally related to metformin and used as an anti-diabetic before metformin synthesis,.
Teucrium polium L. (T. polium) is a member of the Lamiaceae family and one of the most promising nutraceuticals that exerts a wide range of anti-inflammatory, antioxidant,,, vasorelaxant, memory enhancer, anti-diabetic,, and hypolipidemic effects. Also, T. polium has anti-carcinogenic, anti-hypertensive, antinociceptive, and cardioprotective properties. Moreover, it has anti-diabetic effect via several distinct molecular mechanisms, such as enhancing insulin secretion and insulin level, reducing oxidative damage, stimulating regeneration of pancreatic β-cells, promoting glucose uptake in muscle tissues by increasing GLUT-4 translocation and inhibiting α-amylase activity. T. polium can be found in Europe, North Africa, and Southwestern Asia. In Iran, it has been used to treat diabetes, heart failure, and gastrointestinal disorders. Previous phytochemical studies of T. polium revealed the presence of various compounds in the plant, such as flavonoids, terpenoids, and iridoids. In this study, we discussed the hypoglycemic and anti-diabetic effects of T. polium with a specific emphasis on the mechanisms of action.
| 2. Antihyperglycemic and hypolipidemic effects of T. polium|| |
The antihyperglycemic and hypolipidemic properties of T. polium have been shown in several studies and the glucose-lowering properties of T. polium have been demonstrated by a variety of in vitro and in vivo studies,,. In streptozotocin (STZ)-induced diabetic rats, an aqueous decoction prepared from the aerial parts of T. polium displayed a significant reduction in blood glucose level 4 h after intravenous administration and 24 h after intraperitoneal administration. This effect could be attributed to that of T. polium in peripheral metabolism of glucose rather than an increase in insulin release; however, no additional information was provided (e.g. insulin concentration level and/or histological findings) to support their assumption. In another study, oral administration of T. polium aqueous extract in STZ-induced diabetic rats exerted a significant decrease in serum glucose level after 24 h, reaching the level of the normoglycemic animals in 8 days. One study reported that the administration of T. polium (0.5 mg/kg) oral powder for 6 weeks significantly reduced the blood glucose levels in STZ-induced diabetic rats. However, in the alloxan-induced diabetic rabbits, intranasal administration of 10% aqueous T. polium extract (0.1 mL/kg) did not affect the blood sugar concentration. In another study, the treatment of diabetic rats with T. polium aqueous extract (50 mg/kg) for a month could decrease hyperglycemia. However, T. polium increased the levels of cholesterol, triglycerides, low-density lipoproteins, alanine transaminase, and aspartate transaminase. These inconsistent results may have been due to the difference in the method of T. polium administration. Another study showed the consistently-reduced blood glucose, total cholesterol, very low-density lipoprotein, and triglycerides in diabetic rats treated by hydroalcoholic extract of T. polium (300 mg/kg) orally for 14 days.
Several studies indicated that the serum levels of cholesterol and triglycerides were typically high in diabetic patients. The hyperlipidemia in DM mainly occurs as a consequence of a deficiency in insulin and dysregulation of metabolic processes such as lipolysis and lipogenesis. The hypolipidemic and hepatoprotective action of T. polium has been proposed as one of the major possible mechanisms for the protective actions of the plant against DM. In an experimental study, diabetic animals displayed hypertriglyceridemia, and the treatment with T. polium significantly decreased the hyperlipidemia,. Another study showed that administration of T. polium hydroalcoholic extract at 170 mg/ kg for 8 weeks effectively reduced the levels of inflammatory serum indices and lipid profile. Therefore, T. polium can help prevent the dyslipidemia-related complications of diabetic patients by suppressing hyperlipidemia. However, an overall ranking of antihyperglycemic and hypolipidemic effects of T. polium cannot be determined due to the difference in the methods of T. polium administration and experimental procedures used in various studies. Further studies are needed to define possible mechanisms and assess the beneficial value of T. polium to manage hyperlipidemic conditions.
| 3. Anti-diabetic mechanisms of T. polium|| |
3.1. Stimulation of pancreatic insulin secretion
Loss of β-cells in the pancreas is a pathologic feature observed in diabetic patients. Oxidative stress has been implicated in β-cell destruction. Compounds with anti-oxidative effects may contribute to the regeneration of β-cells and the restoration of insulin levels. The published data suggest that T. polium may lower blood glucose by increasing insulin secretion and regenerating the β-cells,. The antihyperglycemic and anti-diabetic actions of T. polium extract have been shown in in vitro studies. In a rat insulinoma cell line, freeze-dried extract of T. polium containing flavonoids showed insulinotropic effects at a dose of 500 μg/mL. However, no difference has been found in the cholesterol and triglyceride levels following the administration of T. polium extract in diabetic animals. Monfared and Pournourmohammadi reported that T. polium (0.01 mg/mL), sodium molybdate and sodium orthovanadate, alone or in combination with each other, improved insulin-secretory function of the cultured islet cells, which compared to the matched control, increased the insulin secretion significantly at high glucose concentration (16.7 mM). Furthermore, the results from other studies showed that in STZ-induced diabetic rats, the administration of ethanol extract of aerial parts of T. polium at a dose of 0.5 g/ kg body weight for 6 weeks decreased the blood glucose levels significantly. Also, the treatment at a concentration of 0.1 mg/mL increased the rate of insulin release. The stimulation of insulin secretion by rutin and apigenin (major flavonoids from T. polium) has been reported, in which the administration of rutin and apigenin increased insulin release due to their antioxidant activity. Furthermore, these flavonoids had free radical scavenging and antiglycation activity, as well as inhibitory effects on the advanced glycation end product production. In another study, rutin and apigenin (0.5 mM to 8 mM) had no effects on insulin secretion in rat-isolated pancreatic islets in the presence of either 5 or 11.1 mM of the glucose. However, in pancreatic islets treated with STZ, insulin secretion was increased in the presence of the same amounts of glucose.
Pancreas regeneration is facilitated by T. polium. Given the effects of T. polium on pancreatic regeneration, the administration of T. polium aerial parts extract twice a day during 14 days could enhance the regeneration of the STZ-destructed islets. To evaluate this capacity and histopathologic examination, the pancreatic tissue was stained with hematoxylin and eosin. This effect is probably due to the fact that the pancreas contains stable cells, which are capable of regeneration. Yazdanparast et al. conducted a series of studies on the hypoglycemic effects of T. polium on isolated rat islets. Accordingly, the regeneration of the β-cells and insulin release is increased by T. polium extract (0.1 mg/mL). This study could provide evidence for the effectiveness of T. polium on the pancreatic islets regeneration in diabetic rats. Also, oral administration of aqueous extract of T. polium to healthy and STZ-induced diabetic rats for several days showed that the aqueous extract reduced the level of serum glucose during oral glucose tolerance tests in diabetic animals. As a result, the number of pancreatic islets per unit area was increased, while the glucokinase activity was elevated in diabetic animals treated with the T. polium extract. A former study by Tabatabaie et al. showed that the treatment of the STZ-induced DM rats with T. polium extract (0.5 g/kg) for six consecutive weeks relieved dyslipidemia and oxidative stress-associated diabetes. Here, glucose tolerance showed a remarkable improvement among the treatment groups, suggesting the presence of elevated insulin levels in blood.
Glucokinase, an insulin sensor in the pancreatic beta cells, is a novel target for anti-diabetic therapy. In this regard, the beneficial effect of T. polium on the regeneration of pancreatic islets and glucokinase activity was previously reported. Taken together, these results suggest that T. polium can potentiate the rate of insulin secretion from islets and regeneration of the pancreas, implying that T. polium may be useful for the development of novel insulin secretagogues (insulin secretion) agent for DM treatment. Although the results of these studies have shown that T. polium extracts have protective effects in all doses, more significant protection was observed in special doses. These findings needed to be confirmed by additional studies.
3.2. Enhancement of glucose uptake in the skeletal muscle
As a prominent feature of DM, any defect in GLUT4 transport or trafficking pathway may lead to insulin resistance. Thus, special attention is being paid to compounds that can enhance this translocation process in the absence of insulin. Insulin stimulates the transport of glucose in target tissues by recruiting intracellular membrane vesicles and containing the glucose transporter GLUT4 to the plasma membrane, which results in increased glucose uptake.
The study performed by Kadan et al. indicated that both hexane and methanol extract of T. polium showed in vitro insulin-independent, as well as the insulin-dependent translocation of GLUT4 to the plasma membrane of skeletal muscle, leading to in vivo improvement of glycemia. These results indicate the synergistic effects between insulin and extract on the active GLUT4 translocation through insulin-independent signaling cascades. Furthermore, gas-chromatography mass spectrometry was used for phytochemical screening of the active ingredients of T. polium. A mixture of a wide range of phytochemicals was extracted. Methanolic extracts contained (5E,8E,11E)-methyl heptadeca-5, 8 ,11-trienoate (5.6%); (9Z,12Z)-octadeca-9,12-dienoic acid (4.5%); 3, 7, 11- trimethyldodeca-1, 6, 10-trien-3-ol (4.4%), and palmitic acid (4.2%) as the major compound. Cisvaccenic acid (20%), butyl (2-ethylhexyl) phthalate (12.2%), and palmitic acid (7.2%) are the main components in the hexane extract. Alternately, the active components of T. polium facilitated GLUT4 translocation in insulin-independent mechanisms. It is possible that active components of T. polium possess insulin-sensitizing activity. It is needful to separate these compounds to show its cellular molecular pathways and to identify its specific anti-diabetic mechanisms.
3.3. Inhibition of glucose absorption
The inhibition of the digestion and absorption of dietary carbohydrates represents an important target in the management of diabetes. Thus, finding α-glucosidase and α-amylase inhibitors from natural resources can be a milestone in drug discovery research associated with DM.
One of the possible mechanisms in the anti-diabetic effect of T. polium is the inhibition of carbohydrate-hydrolyzing enzymes, pancreatic α-amylase, and intestinal α-glucosidase. According to Salehi et al., T. polium methanolic extract [(10.2 ± 0.4) μg/mL] exhibited α-glucosidase inhibitory properties that can be considered as the first-line treatment for type 2 diabetes. In starch-fed animals, oral administration of aqueous liquid extract in the aerial parts of T. polium at a dose of 125 mg/kg diminished peak hyperglycemia at 45 minutes from about 6.5 to 5 mM. In an oral glucose tolerance test, the extract at a dosage of 500 mg/kg effectively reduced glycemia.
Furthermore, the extract at 125 mg/kg had no effects on improving glucose tolerance in an oral glucose tolerance test. However, at 500 mg/kg, it decreased glycemia from about 6.5 to 5.5 mM. The extract at 10 g/100 mL demonstrated no appreciable anti-α-amylase or anti- glucosidase efficacy in vitro. In another study, weak α-amylase inhibitory activity (5%) was observed with the 50% methanolic extract of T. polium. Despite several studies have shown T. polium extracts possess anti-α-glucosidase and anti-α-amylase effectiveness, some indicated weak inhibition effect on α-glucosidase and α-amylase. This fact may arise from the difference in administration methods and polarities of the solvents.
3.4. Inhibition of oxidative damage
Oxidative stress occurs as a result of an imbalance between the production and scavenging of free radical species,,. The increased oxidative stress plays an important role in the initiation and progression of numerous chronic disorders,. Several studies have shown that the development of DM complications is attributed to the uncontrolled production of reactive oxygen species,. Thus, effective antioxidant therapy is required to prevent or ameliorate the complications of diabetes caused by oxidative damage. Medicinal plants contain bioactive antioxidant compounds.
A number of in vitro and in vivo studies have shown that the extract of the T. polium has potent antioxidant properties,,,,. Antioxidant activity of T. polium can be attributed to its constituents, especially phenolic compounds. Phenolic compounds include such compounds as flavonoids, tannins, and phenolic acids,,. In an in vitro study, Kadifkova et al. investigated the effect of the chemical composition and antioxidant activity of various extracts obtained from Teucrium species. The obtained results showed that Teucrium species possess free radical and hydroxyl radical scavenging as well as antioxidant activity. In the same study, the results indicated that ethyl acetate fraction of T. polium possessed the highest antioxidant capacity, which was similar to Trolox (water-soluble vitamin E analogue). In another study, it was reported that T. polium extracts could attenuate oxidative damage leading to β-cell dysfunction, significantly enhance insulin release and peripheral metabolism of glucose, and ameliorate glycemic control,,. In STZ-induced diabetic rats, oral administration of hydroethanolic extract of aerial parts of T. polium at a dose equivalent to 0.5 g plant powder/kg/day for 30 days decreased blood glucose level from 294 to 98 mg/dL. Also, this regimen lowered the lipid peroxidation of the pancreas by 64%, elevated activities of superoxide dismutase, catalase, and increased contents of glutathione by 45%, 52%, and 105%, respectively. In addition, nitric oxide levels were also restored to the level of the nondiabetic group by treatment with the extract.
T. polium is known to contain the flavones eupatorin, cirsimaritin, apigenin-4’,7-dimethylether, cirsiliol as well as rutin, apigenin, and 3,6-dimethoxy-apigenin, 4,7-dimethoxy apigenin, which are antioxidant in vitro. Rutin (quercetin-3-O-rutinoside) along with flavone apigenin was isolated from T. polium and identified as in vitro free radical scavenging and antiglycation agents. Moreover, these two flavonoids showed inhibitory effects on the formation of advanced glycation end products from bovine serum albumin in the presence of glucose. These two flavonoids also prevented oxidative stress conditions produced by STZ, which could increase insulin secretion. These findings suggest the existence of sterols and flavonoids in T. polium extract and its antioxidant effect is a possible mechanism of action underlying the anti-diabetic effects of T. polium.
3.5. Increased activation of adenosine monophosphate–activated protein kinase (AMPK)
AMPK has been considered to be a potential therapeutic target to treat numerous diseases such as DM,. It is a central metabolic sensor and senses the ratio of ATP to AMP, which helps maintain cellular energy homeostasis. AMPK becomes activated when the ATP/AMP ratio is decreased. Moreover, AMPK activity is reduced in response to chronic low-grade inflammation associated with diabetes and insulin resistance. T. polium activates the energy metabolism and insulin secretion by stimulating AMPK. Qujeq et al. demonstrated that the T. polium leaf extract enhanced the insulin content and AMPK level compared to the untreated group in isolated pancreases. These results suggest that T. polium leaf extract stimulates AMPK level that could play an important role in insulin release, but the biochemical relevance of these findings is unclear. Therefore, further studies are necessary to confirm this potential.
The anti-diabetic activities of T. polium in both in vivo and in vitro reports are summarized in [Table 1]. Our review of literature data indicated that T. polium treatment affects DM via several mechanisms, including antioxidant activity, increasing insulin secretion and insulin level, regeneration of pancreatic β-cells, promotion of glucose uptake through stimulation of GLUT-4 translocation, and inhibiting α-amylase activity [Figure 1].
|Table 1: Summary of experimental studies on antidiabetic activities of Teucrium polium (T. polium).|
Click here to view
|Figure 1: Antidiabetic properties of Teucrium polium extract which seems to mediate, at least partially, through improving insulin secretion, promoting AMPK activity, increasing antioxidant parameters, decreasing α-amylase and α-glucosidase activity, and stimulating GLUT4 translocation.|
Click here to view
| 4. Toxicity and adverse effects|| |
Despite anti-diabetic properties of T. polium extract (e.g. stimulation of pancreatic insulin secretion, enhanced glucose uptake in the skeletal muscle, and B cells) in diabetic rats, there are a few reports about toxic effects. For instance, intra-esophageal administration of 1 g/mL T. polium extract in diabetic rats twice daily or 10 days resulted in hepatic necrosis that was widespread in periventricular and midzonal areas of the liver lobules. A similar study showed an increase in enzyme activities of alanine aminotransferase and aspartate aminotransferase in female rats receiving 300 mg/kg T. polium. On the other hand, a significant increase was observed in the liver weight of diabetic male rats receiving 600 mg/kg. A recent report also indicated at 200 mg/kg, T. polium extract provoked liver and kidney tissue damages with a significant rise in biochemical markers of tissue injury. Moreover, T. polium has shown toxic effects on embryogenesis at the early stage in a dose-dependent manner, in which the liver could be as a target organ. This may be due to the presence of several neoclerodane diterpenoids in T. polium extract. So, despite the great effects of T. polium extracts in ameliorating diabetes, high dose usage should be limited due to hepatic effects in subchronic cases.
| 5. Conclusion|| |
T. polium treatment displayed anti-diabetic effects by targeting different mechanisms and pathways, such as enhancing insulin secretion and insulin level, improving oxidative damage, regenerating the pancreatic β-cells, and promoting the glucose uptake in muscle tissues by increasing of GLUT-4 translocation, as well as inhibiting α-amylase activity. T. polium extracts suppress pathophysiologic pathways associated with insulin resistance and improve glycemic control. It is to a great safe in low doses and might serve as an effective adjunct with other anti-diabetic medications to lower the side effects and increase the efficacy. Moreover, it could be used to palliate insulin resistance as a nutritional supplement in prediabetes. Therefore, T. polium and its bioactive compounds have great potential for managing diabetes. There have been no studies regarding the effects of T. polium on long-term microvascular implications of diabetes, such as retinopathy, cardiomyopathy, nephropathy, and endothelial dysfunction. Thus, to evaluate the effects of T. polium on these complications, the following assessments are recommended: evaluating the biomarkers and mediators of diabetic retinopathy such as those related to inflammation and angiogenesis (e.g. vascular endothelial growth factor), cardiac enzymes, pathways involved in apoptosis and fibrosis of the heart and kidney, cardiac and kidney function, factors involved in vascular dysfunction, such as endothelial adhesion molecules and nitric oxide level.
Despite all the endeavors, some studies in the future should focus on the fine molecular targets and its bioactive compounds. Also, extended clinical studies with T. polium should also be designed, conducted, and evaluated critically to explore the detailed health benefits of this medicinal herb. All the above-collected data show that T. polium extracts have a broad range of pharmacological attributes, such as antioxidant, antinociceptive, anti-inflammatory, hypolipidemic, hepatoprotective, and hypoglycemic effects. Results of studies on the chemical, toxicity, and pharmacological properties of T. polium support the opinion that this plant possesses useful therapeutic characteristics. On the other hand, further studies should be conducted to categorize the active constituents and confirm their related pharmacological components.
Conflict of interest statement
We declare that there is no conflict of interest.
AAA and MM conceived and organized the review; AMZ, SN and KME contributed to the writing and editing of the manuscript.
| References|| |
Cho NH, Shaw JE, Karuranga S, Huang Y, da Rocha Fernandes JD, Ohlrogge AW, et al. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract
Fowler MJ. Microvascular and macrovascular complications of diabetes. Clin Diabetes
Aronoff SL, Berkowitz K, Shreiner B, Want L. Glucose metabolism and regulation: Beyond insulin and glucagon. Diabetes Spectr
UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet
Vuorela P, Leinonen M, Saikku P, Tammela P, Rauha JP, Wennberg T, et al. Natural products in the process of finding new drug candidates. Curr Med Chem
Campbell IW. Metformin-life begins at 50: A symposium held on the occasion of the 43rd Annual Meeting of the European Association for the Study of Diabetes, Amsterdam, The Netherlands, September 2007. Br J Diabetes Vasc Dis
Bailey CJ, Day C. Metformin: Its botanical background. Pract Diabetes Int
Tariq M, Ageel AM, Al-Yahya MA, Mossa JS, Al-Said MS. Antiinflammatory activity of Teucrium polium. Int J Tissue React
Ardestani A, Yazdanparast R, Jamshidi S. Therapeutic effects of Teucrium polium
extract on oxidative stress in pancreas of streptozotocin-induced diabetic rats. Food Chem Toxicol
Šamec D, Gruz J, Strnad M, Kremer D, Kosalec I, Grubešić RJ, et al. Antioxidant and antimicrobial properties of Teucrium arduini
L.(Lamiaceae) flower and leaf infusions (Teucrium arduini
L. antioxidant capacity). Food Chem Toxicol
Zabihi NA, Mousavi SM, Mahmoudabady M, Soukhtanloo M, Sohrabi F, Niazmand S. Teucrium polium
L. improves blood glucose and lipids and ameliorates oxidative stress in heart and aorta of diabetic rats. Int J Prev Med
Niazmand S, Fereidouni E, Mahmoudabady M, Hosseini M. Teucrium polium
-induced vasorelaxation mediated by endothelium-dependent and endothelium-independent mechanisms in isolated rat thoracic aorta. Pharmacogn Res
Mousavi SM, Niazmand S, Hosseini M, Hassanzadeh Z, Sadeghnia HR, Vafaee F, et al. Beneficial effects of Teucrium polium
and metformin on diabetes-induced memory impairments and brain tissue oxidative damage in rats. Int J Alzheimers Dis
Esmaeili MA, Sadeghi H. Pancreatic β-cell protective effect of rutin and apigenin isolated from Teucrium polium. Pharmacologyonline
Esmaeili MA, Yazdanparast R. Hypoglycaemic effect of Teucrium polium:
Studies with rat pancreatic islets. J Ethnopharmacol
Solati M, Farshidfar G, Vakil MK, Saberi P, Kamalinejad M, Soltani N. Effect of administration of Teucrium polium
on blood glucose and lipid levels in streptozotocin-induced diabetic rats. J Physiol Pharmacol
Movahedi A, Basir R, Rahmat A, Charaffedine M, Othman F. Remarkable anticancer activity of Teucrium polium
on hepatocellular carcinogenic rats. Evid Based Complement Alternat Med
Mahmoudabady M, Shafei MN, Niazmand S, Khodaee E. The effects of hydroalchoholic extract of Teucrium polium
L. on hypertension induced by angiotensin II in rats. Int J Prev Med
Baluchnejadmojarad T, Roghani M, Roghani-Dehkordi F. Antinociceptive effect of Teucrium polium
leaf extract in the diabetic rat formalin test. J Ethnopharmacol
Mahmoudabady M, Haghshenas M, Niazmand S. Extract from Teucrium polium
L. protects rat heart against oxidative stress induced by ischemic–reperfusion injury. Adv Biomed Res
Bahramikia S, Yazdanparast R. Phytochemistry and medicinal properties of Teucrium polium
L. (Lamiaceae). Phytother Res
Mir H. Encyclopedia of medicinal plant of Iran
. 5th ed. Tehran: Islamic Culture Press; 2004.
Piozzi F, Bruno M, Rosselli S. Advances on the chemistry of furano-diterpenoids from Teucrium
Ardestani A, Yazdanparast R, Jamshidi SH. Therapeutic effects of Teucrium polium
extract on oxidative stress in pancreas of streptozotocin-induced diabetic rats. J Med Food
Gharaibeh MN, Elayan HH, Salhab AS. Hypoglycemic effects of Teucrium polium. J Ethnopharmacol
Zal F, Rasti M, Vesal M, Vaseei M. Hepatotoxicity associated with hypoglycemic effects of Teucrium polium
in diabetic rats. Arch Irn Med
Afifi FU, Al-Khalidi B, Khalil E. Studies on the in vivo
hypoglycemic activities of two medicinal plants used in the treatment of diabetes in Jordanian traditional medicine following intranasal administration. J Ethnopharmacol
Shahraki MR, Arab MR, Mirimokaddam E, Palan MJ. The effect of Teucrium polium
(Calpoureh) on liver function, serum lipids and glucose in diabetic male rats. Iran Biomed J
Ayoubi A. Effect of hydroalcoholic extract of Aloe vera
on serum glucose and lipid profile in streptozotocin diabetic male rats. J Birjand Univ Med Sci
Patel J. Diabetes: Managing dyslipidaemia. BMJ Clin Evid
Arner P. Human fat cell lipolysis: Biochemistry, regulation and clinical role. Best Pract Res Clin Endocrinol Meta
Sarkarizi HK, Sazegar G, Rajabzadeh A. Effect of hydro-alcoholic Teucrium polium
L. extract and glibenclamide administration on blood glucose and lipid profile levels in streptozotocin-induced diabetic rats. Clin Res
Tabatabaie PS, Yazdanparast R. Teucrium polium
extract reverses symptoms of streptozotocin-induced diabetes in rats via
rebalancing the Pdx1 and FoxO1 expressions. Biomed Pharmacother
Amraei M, Ghorbani A, Seifinejad Y, Mousavi SF, Mohamadpour M, Shirzadpour E. The effect of hydroalcoholic extract of Teucrium polium
L. on the inflammatory markers and lipid profile in hypercholesterolemic rats. J Inflamm Res
Cnop M, Welsh N, Jonas JC, Jörns A, Lenzen S, Eizirik DL. Mechanisms of pancreatic β-cell death in type 1 and type 2 diabetes: Many differences, few similarities. Diabetes
(suppl 2): S97-S107.
Mirghazanfari SM, Keshavarz M, Nabavizadeh F, Soltani N, Kamalinejad M. The effect of “Teucrium polium
L.” extracts on insulin release from in situ
isolated perfused rat pancreas in a newly modified isolation method: The role of Ca2
+ and K+
channels. Iran Biomed J
Tatar M, Qujeq D, Feizi F, Parsian H, Faraji AS, Halalkhor S, et al. Effects of Teucrium polium
aerial parts extract on oral glucose tolerance tests and pancreas histopathology in streptozocin-induced diabetic rats. Int J Mol Cell Med
Stefkov G, Kulevanova S, Miova B, Dinevska-Kjovkarovska S, Molgaard P, Jager AK, et al. Effects of Teucrium polium
spp. capitatum flavonoids on the lipid and carbohydrate metabolism in rats. Pharm Biol
Monfared SSMS, Pournourmohammadi S. Teucrium polium
complex with molybdate enhance cultured islets secretory function. Biol Trace Elem Res
Esmaeili MA, Zohari F, Sadeghi H. Antioxidant and protective effects of major flavonoids from Teucrium polium
on beta-cell destruction in a model of streptozotocin-induced diabetes. Planta Med
Yazdanparast R, Esmaeili MA, Ashrafi Helan J. Teucrium polium
extract effects pancreatic function of streptozotocin diabetic rats: A histopathological examination. Iran Biomed J
Vesal M, Zal F, Vaseei M. Effects of Teucrium polium
on oral glucose tolerance test, regeneration of pancreatic islets and activity of hepatic glucokinase in diabetic rats. Arch Iranian Med
Sarabu R, Grimsby J. Targeting glucokinase activation for the treatment of type 2 diabetes--a status review. Curr Opin Drug Discov Dev
Cheatham B. GLUT4 and company: SNAREing roles in insulin-regulated glucose uptake. Trends Endocrinol Metab
Kadan S, Sasson Y, Abu-Reziq R, Saad B, Benvalid S, Linn T, et al. Teucrium polium
extracts stimulate GLUT4 translocation to the plasma membrane in L6 muscle cells. Adv Med Plant Res
Akkarachiyasit S, Charoenlertkul P, Yibchok-anun S, Adisakwattana S. Inhibitory activities of cyanidin and its glycosides and synergistic effect with acarbose against intestinal a-glucosidase and pancreatic a-amylase. Int J Mol Sci
Salehi P, Asghari B, Esmaeili MA, Dehghan H, Ghazi I. a-Glucosidase and a-amylase inhibitory effect and antioxidant activity of ten plant extracts traditionally used in Iran for diabetes. J Med Plants Res
Kasabri V, Afifi FU, Hamdan I. In vitro
and in vivo
acute antihyperglycemic effects of five selected indigenous plants from Jordan used in traditional medicine. J Ethnopharmacol
Soud A, Rawand S, Afifi FU. Alpha amylase inhibitory activitv of some plant extracts with hyporrlycemic activity. Sci Pharm
Ceriello A, Motz E. Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited. Arterioscler Thromb Vasc Biol
Henriksen EJ. Exercise training and the antioxidant a-lipoic acid in the treatment of insulin resistance and type 2 diabetes. Free Radical Biol Med
Di Domenico F, Barone E, Perluigi M, Butterfield DA. The triangle of death in Alzheimer’s disease brain: The aberrant cross-talk among energy metabolism, mammalian target of rapamycin signaling, and protein homeostasis revealed by redox proteomics. Antioxid Redox Signal
Seet RCS, Lee CYJ, Lim ECH, Tan JJH, Quek AML, Chong WL, et al. Oxidative damage in Parkinson disease: Measurement using accurate biomarkers. Free Radical Biol Med
Baynes JW. Role of oxidative stress in development of complications in diabetes. Diabetes
Wolff SP. Diabetes mellitus and free radicals: Free radicals, transition metals and oxidative stress in the aetiology of diabetes mellitus and complications. Br Med Bull
Gülçin I, Uguz MT, Oktay M, Beydemir S, Küfrevioglu Ö. Antioxidant and antimicrobial activities of Teucrium polium
L. J Food Technol
Khodadadi S, Zabihi NA, Niazmand S, Abbasnezhad A, Mahmoudabady M, Rezaee SA. Teucrium polium
improves endothelial dysfunction by regulating eNOS
genes expression and vasoreactivity in diabetic rat aorta. Biomed Pharmacother
Macedonia R. In vitro
antioxidant activity of some Teucrium
species (Lamiaceae). Acta Pharm
Alali RG, Khazem MR. Total phenolic content and antioxidant activity of two Teucrium
species from Syria. J Pharm Nutr Sci
Rahmouni F, Saoudi M, Amri N, El-Feki A, Rebai T, Badraoui R. Protective effect of Teucrium polium
on carbon tetrachloride induced genotoxicity and oxidative stress in rats. Arch Physiol Biochem
Tawaha K, Alali FQ, Gharaibeh M, Mohammad M, El-Elimat T. Antioxidant activity and total phenolic content of selected Jordanian plant species. Food Chem
Yassine EL, Aouam I, El Kamari F, Taroq A, Zejli H, Taleb M, et al. Antioxidant activities, total phenol an flavonoid contents of two Teucrium polium
subspecies extracts. Moroccan J Chem
Malki S, Abidi L, Hioun S, Yahia A. Variability of phenolic contents in ethanolic extracts of Teucrium polium
L. populations and effect on antioxidant and antimicrobial activities. J Microbiol Biotechnol Res
Kadifkova Panovska T, Kulevanova S, Stefova M. In vitro
antioxidant activity of some Teucrium
species (Lamiaceae). Acta Pharm
Ardestani A, Yazdanparast R. Inhibitory effects of ethyl acetate extract of Teucrium polium
on in vitro
protein glycoxidation. Food Chem Toxicol
Esmaeili MA, Zohari F, Sadeghi H. Antioxidant and protective effects of major flavonoids from Teucrium polium
on beta-cell destruction in a model of streptozotocin-induced diabetes. Planta Med
Verykokidou-Vitsaropoulou E, Vajias C. Methylated flavones from Teucrium polium. Planta Med
Sharififar F, Dehghn-Nudeh G, Mirtajaldini M. Major flavonoids with antioxidant activity from Teucrium polium
L. Food Chem
Rourke JL, Hu Q, Screaton RA. AMPK and friends: Central regulators of β cell biology. Trends Endocrinol Metab
Hardie DG. Adenosine monophosphate-activated protein kinase: A central regulator of metabolism with roles in diabetes, cancer, and viral infection. Cold Spring Harb Symp Quant Biol
Coughlan KA, Valentine RJ, Ruderman NB, Saha AK. AMPK activation: A therapeutic target for type 2 diabetes? Diabetes Metab Syndr Obes
Gauthier MS, O’Brien EL, Bigornia S, Mott M, Cacicedo JM, Xu XJ, et al. Decreased AMP-activated protein kinase activity is associated with increased inflammation in visceral adipose tissue and with whole-body insulin resistance in morbidly obese humans. Biochem Biophys Res Commu
Qujeq D, Tatar M, Feizi F, Parsian H, Halalkhor S. Effect of Teucrium polium
leaf extracts on AMPK level in isolated rat pancreases. Res Mol Med
Rasekh HR, Yazdanpanah H, Hosseinzadeh L, Bazmohammadi N, Kamalinejad M. Acute and subchronic toxicity of Teucrium polium
total extract in rats. Iran J Pharm Res
Ghasemi T, Keshavarz M, Parviz M. Acute hepatorenal dose dependent toxicity of Teucrium polium
hydro alcoholic extract in rat. Int J Pediatr
Al-Qahdi SS, Alzohari N, Alsaid AY, Ashour AA, Aboulkassim T, Vranic S, et al. Teucrium polium
plant extract provokes substantial cytotoxicity at the early stage of embryonic development. Bosn J Basic Med Sci