Mini Review

A quick overview on some aspects of endocrinological and therapeutic effects of Berberis vulgaris L.

Ali Zarei1, Saeed Changizi-Ashtiyani2*, Soheila Taheri3, Majid Ramezani4

1Young Researchers and Elite Club, Abadeh Branch, Islamic Azad University, Abadeh, Iran 2Department of Physiology, Arak University of Medical Sciences, Arak, Iran 3Education Development Center, Arak University of Medical Sciences, Arak, Iran 4Osteoporosis Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

Article history: Abstract Received: Sep 5, 2014 Many herbaceous plants contain compounds that have Received in revised form: Mar biological effects in addition to their medicinal properties. 18, 2015 They have compounds with numerous properties, including Accepted: Apr 21, 2015 hypo lipidemic, hypoglycemic, antioxidant, and hepato Vol. 5, No. 6, Nov-Dec 2015, protective ones, which have been analyzed at different levels. 485-497. One of these plants, with the scientific name of Berberis

* Corresponding Author: vulgaris, is barberry. The most important compounds identified Tel: 08634173526 in this plant are berberine, oxycontin, palmatine, bervulcine, Fax: 08634173638 berbamine, columbamine, jatrorrhizine, coptisine, and ‎[email protected] berbamine. In addition to alkaloids, organic acids such as chelidonic acid, citric acid, malic acid, resin, tannin, pectinic, Keywords: and mucilagic substances are among the ingredients of Liver barberry. Cholesterol In this paper, it was attempted to determine the role and effect Diabetes of the extract of barberry on various body organs. The results Thyroid, showed that berberine actually increases insulin sensitivity and Barberry Berberis Vulgaris is capable of inhibiting alpha glucosidase, adipogenesis, and thus acts as an anti-obesity and hypoglycemic agent. Berberine reduces the density of serum cholesterol and triglycerides and can improve the function of liver enzymes, therefore, it can be suggested as a hypo lipidemic and hepato protective plant extract. The hepato protective effects of this extract are probably due to its antioxidant properties. Studies showed that barberry have numerous health benefits, including anti-inflammatory ones. Moreover, it can be used as a medicinal herb to treat a variety of disorders, such as diabetes, liver disease, gallbladder pain, digestive, urinary tract diseases, and gallstones. However, more studies on this issue and doing more focused and intensive researches in this field are

recommended.

Please cite this paper as: Zarei A, Changizi-Ashtiyani S, Taheri S, Ramezani M. A quick overview on some aspects of endocrinological and therapeutic effects of Berberis vulgaris L. Avicenna J Phytomed, 2015; 5 (6): 485-497.

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Introduction in northern Europe to treat disorders of the Due to the multiple hazards of chemical bladder, liver, and gallbladder. In Russia compounds such as drug resistance, and Bulgaria, it is used to treat environmental problems, high production rheumatism, abnormal uterine bleedings costs, and side effects, the tendency (Fatehi et al.,2005 b, Ivanovska et toward using medicinal plants in all al.,1996), and in north America for malaria health-related sciences is increasing and general strengthening of the body (Rajaian et al., 2002). (Imanshahidi et al., 2008). American For centuries, medicinal plants have Indians have used it as a medicine to help been the only available source for treating improve appetite (Abd El-Wahab et al., pains and pacifying human sufferings. In 2013). New experimental and animal the present era, despite remarkable studies have indicated the beneficial progress in the production and use of effects of this plant on blood pressure and synthetic drugs, medicinal plants in all lipid profiles, as well as its anti- their pharmaceutical forms are still widely inflammatory properties (Ebrahimi- used. Iran, due to its climate variability, Mamaghani et al., 2009). has rich vegetation, especially medicinal Various parts of the plant including the plants and consequently has had a long bark, root, rhizomes, stem, leaf, and fruit history in traditional medicine, a fact are used in medicine (Arayne et al., 2007). which makes it so reasonable to pay Phyto chemical and pharmacological special attention to these invaluable studies have shown that all the various resources (Changizi-Ashtiyani et al., species of the genus Berberis have 2013a), (Figure 1). antimicrobial, antiemetic, antipyretic, In this regard, one of the medicinal antioxidant, anti-inflammatory, anti- plants is barberry, with the scientific name arrhythmic, sedative, anti-cholinergic, of Berberis vulgaris from the family of cholagogic, anti-leishmaniasis, and anti- Berberidaceae (Figure 1) which grows malaria properties (Table 1). abundantly in the mountainous north-east In this paper, while generally referring of Iran and Khorasan (Fatehi et al., 2005a). to substances and active ingredients in the The six known species of barberry include plant (Table 1) and reviewing the known Berberis crataegina, Berberis integerriam, effects of the extract of Berberis vulgaris Berberis khorasanica, Berberis (Table 2), we have paid especial attention orthobotrys, Berberis vulgaris, and to the impact of these compounds on some Berberis thunbergii var. atropurpurea tissues and organs. Berberine and (Fatehi et al., 2005b). berbamine are the most important Barberry is one of the plants that compounds found in all barberry species. contain berberine and has had a long Phytochemical analyses of different history in eastern and western medical species of this genus have detected tradition (Abd El-Wahab et al., 2013, alkaloids, tannins, phenolic compounds, Chevallier et al., 2001). In Iran and India, sterols, and triterpenes in them, too it goes back to at least 3,000 years (Souri (Arham et al., 2012, Mokhber-Dezfuli et et al., 2004, Timothy et al., 1997). al., 2014). Berberin is the main active According to traditional medicine, the fruit alkaloid with atetrabenzyl-hydroxy of this plant has a cold and dry nature. quinoline structure that can be found in all Ancient Egyptians used barberry and parts of the plant, especially in the roots. fennel seed to cure fever. Iranian Berberine value of the fruit is about 5.5– physicians used it as a sedative and it has 7.7%. Berberine is not toxic at the doses been used to treat diarrhea by Indian used in clinical studies and no cytotoxic or physicians (Chevallier et al., 2001, mutagenic effects or adverse reactions Kunwar et al., 2006).This plant is still used have been observed (Shidfaraet al., 2012).

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Table 1. Chemical compounds of Berberis vulgaris L. (Imanshahidi et al., 2008).

Compound Type Part of plant Acanthine Isoquinoline alkaloid Root Bark Root bark Stem bark Shoots Leaf

Aesculetin Coumarin Fruit Ascorbic acid Vitamin Fruit Leaf Bargustanine Isoquinoline alkaloid Root Berbamine Isoquinoline alkaloid Bark Root Steam bark

Berberrubine Isoquinoline alkaloid Root Berberine Isoquinoline alkaloid Root Root bark Bark Stem bark Root wood Flowers Stem Fruit Shoots

Berberrubine Isoquinoline alkaloid Bark Beriambine Isoquinoline alkaloid Root Bervulcine Isoquinoline alkaloid Fruit Caffeic acid Phenylpropanoid Fruit Carotene, beta: Carotenoid Fruit Chlorogenic acid Phenylpropanoid Fruit Chrysanthemin Flavonoid Root Columbamine Isoquinoline alkaloid Bark Stem bark Delphinidin-3-o-beta-d-glucosido Flavonoid Leaf Glucan, alpha: Carbohydrate Leaf Hyperoside Flavonol Fruit Leaf Jatrorrhizine Isoquinoline alkaloid Root Root bark Bark Stem bark Lambertine Isoquinoline alkaloid Root Magnoflorine Isoquinoline alkaloid Root bark Root Stem bark Malic acid Alkane to c4 Fruit Palmatine Isoquinoline alkaloid Root Bark Root bark Fruit

Pectin Carbohydrate Fruit Pelargonin Flavonoid Fruit Petunidin-3-o-beta-d-glucoside Flavonoid Fruit Polysaccharide Carbohydrate Fruit Quercetin Flavonol Leaf Sucrose Carbohydrate Leaf Tannin Tannin Fruit Thaliemidine Isoquinoline alkaloid Fruit Tocopherol, alpha: Oxygen heterocycle Leaf Urosolic acid Triterpene Leaf Fruit Vitamin K Vitamin Leaf

Vulvracine Alkaloid-misc Xylan, beta Carbohydrate Leaf

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The most important alkaloids identified Science Direct, Pub Med, Google Scholar, in the roots of the plant are magno florine, Persian Electronic Scientific Information berberine, oxycontin, berbamine, Database (SID), Iran medex, and Magiran palmatine, bervulcine, berlambine, as well as the available paper resources in berbamine, columbamine, jateorhizine, Persian scientific journals and coptisine. In addition to alkaloids, mainlybetween2008-2014. there are also organic acids such as chelidonic acid, citric acid, malic acid, resin, tannin, pectinic, and mucilagic substances in the roots (Fatehi et al., 2005a, Zarei et al., 2012). The fruit is sour and contains sugars such as dextrose and fructose, malic acid, pectin, gum, tartaric, and citric acids. The berberine found in barberry root has anticonvulsant, sedative, and diuretic effects. Recent studies have suggested that berberine has other beneficial biological effects including anti- inflammatory ones (Javadzadeh et al., Figure 1.The aerial parts of Berberis Vulgaris. 2012). The following keyword was used: Berberine is effective in the prevention “Berberis vulgaris”. To obtain additional of coronary artery diseases and may data, a manual search was performed using decrease the total cholesterol and the reference lists of included articles. triglyceride levels. The main effect of berbamine is blocking calcium channels. The effect of Berberis vulgaris extract on This alkaloid showed peroxidation lipid profiles activities in experiments on lipid Hyperlipidemia refers to a group of peroxidation of red blood cells and could heterogeneous disorders characterized by exert anti-myocardial ischemia and anti- high levels of blood lipid profiles. arrhythmia effects. Moreover, oxycanthine Hyperlipidemia, regardless of its cause, is acted as a sympatholytic agent and a a major, yet manageable risk factor for vasodilator (Kong et al., 2004, Fatehi et coronary heart diseases. The treatment al., 2005). goals can be designed on the basis of The aim of this study was to review the absolute levels of lipid and the presence or beneficial effects of Berberis vulgaris absence of risk factors. Studies show that extract on the liver, thyroid, immune the therapies leading to effective reduction system, adipose tissue, and the plasma of low-density lipoprotein (LDL) levels concentration of some biochemical factors. are clearly effective in decreasing mortality in patients with coronary artery disease. Studies show that the risk of recurring Materials and Methods cardiovascular attacks in high-risk patients In this review article the role of has a significant relationship with the barberry extract in different body tissues period of using statins, as a group of with respect to the literature and numerous common cholesterol-lowering drugs, empirical articles on this subject was which act by inhibiting the hydroxyl reviewed. To do so, using proper key methylglutaryl coenzyme A reductase words, a comprehensive electronic search (HMG-CoA reductase) (Mancini et al., was done in authentic data bases such as 2011).

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Evidence suggests that long-term through cholesterol release and consumption of high-dose statins involves consequently reduce its value. In addition, some less severe side effects such as alkaloids inhibit the synthesis of headache, nausea and vomiting, cholesterol (Matralis et al., 2013). Since constipation, muscle pain, and many barberry also contains powerful serious side effects such as liver damage, antioxidants (Mokhber-Dezfuli et al., rhabdomyolysis, renal failure, and loss or 2014, Motalleb et al., 2008), its effect on damage to memory as well as being fat loss is not unexpected. The inhibitory forbidden during pregnancy (Rubenfire et effects of barberry root extract on al., 2010).That is why the tendency toward oxidative stress have also been reported using herbs as a supplement or alternative (Eshraghi et al., 2011). Doggrell and medicine has recently increased. colleagues also showed that berberine Changizi-Ashtiyani et al. in a study significantly reduced cholesterol (Doggrell examined the effects of barberry root et al., 2005). Shidfar and colleagues extract on cholesterol, triglycerides, and indicated that the administration of high and low-density lipoproteins and aqueous extract of the grainy fruit of compared its effects with those of oral mountain barberry (Berberis harrisoniana) atorvastatin. They showed that the ethanol had an important role in reducing blood extract of barberry root reduced cholesterol and triglyceride (Shidfar et al., cholesterol and elevated the levels of 2012). triglyceride (TG), high-density lipoprotein Clinical trial studies suggest that the (HDL), and low-density lipoprotein LDL. aqueous extract of barberry is highly able Atorvastatin, too, reduced the amount of to efficiently increase cardiac contractility, cholesterol and triglycerides. Probably one and reduce blood pressure by reducing of the alkaloids found in this plant, i.e., peripheral resistance. Berberine increases berberine, through various mechanisms, mRNA activity and increases the affected the process of absorption, expression of LDL-C receptors, which in synthesis, and excretion of lipids. turn improve the plasma clearance through However, further studies are needed to receptor-mediated endocytosis, which understand the involved mechanisms consequently leads to the inhibition of (Changizi-Ashtiyani et al. 2013b, Arayne cholesterol biosynthesis of the cell. Hence, et al., 2007). Recently, studies have also among the organic medicinal herbs, reported that berberine reduces cholesterol berberine may be an ideal candidate for the with a mechanism different from statin treatment of hypercholesterolemia. drugs. If statin and berberine are taken Berberine has beneficial effects on together, they can inhibit cholesterol much inflammatory fever because of the better than when they are used alone. presence of citric acid, malic acid, and Berberine increases the production of a ascorbic acid in its aqueous extract. The receptor in the liver which bonds with aqueous extract of barberry has a great cholesterol and facilitates its excretion potential as future green medicine (Doggrell et al., 2005, Rajaian et al., (Pradhan et al., 2013). 2002). Berberine reduces lipid Studies have shown that berberine peroxidation effectively by its antioxidant reduces the density of serum cholesterol, property. Thus, it supports the antioxidant triglycerides, and LDL-C in patients and enzymes such as superoxide dismutase animal models with dyslipidemia. (SOD) against oxygen free radicals and Berberine can act as an AMPK hydrogen peroxide (Ziai et al., 2010, (5'adenosine monophosphate-activated Thirupurasundari et al., 2009). protein kinase) and increases AMP/ATP Antioxidants prevent high blood and is able to inhibit the biosynthesis of cholesterol and possibly increase excretion ATP in mitochondria. Berberine actually

AJP, Vol. 5, No. 6, Nov-Dec 2015 489 Zarei et al. increases insulin sensitivity and is capable showed that the aqueous extract of of inhibiting alpha glucosidase and mountain barberry fruit could activate liver adipogenesis and thus acts as an anti- function and was effective in lipid analysis obesity agent. Furthermore, berberine can and possibly in adjusting their levels in increase LDL receptor mRNA and as an blood (Rajaian et al., 2002). antioxidant can scavenge free radicals Berberine which is an organic cation (Shidfar et al., 2012). simply passes through cell membrane and forms a complex with DNA molecule, The effects of barberry extract on liver causing structural changes in DNA function tests resulting in the imposition of regulatory Taheri and colleagues evaluated the functions of the genes and disruption of effects of root extract of Berberis vulgaris the differentiation process (Yin J et al., and atorvastatin on the levels of liver 2008a, Yuan Heng et al., 1961). In enzymes in hyper cholesterolaemiac male addition, while fetal cells are dividing, the rats and showed that the enzymes alanine formation of proto berberine complexes aminotransferase (ALT) and alkaline with DNA can stop the growth of the fetus. phosphatase (ALP) increased in the control The reduction of maternal and fetal blood group receiving only fatty food. While lipids and blood glucose can also be these levels decreased in both the effective in reducing the growth of the experimental groups receiving the extract fetus. Berberine can improve liver function of barberry and in the group receiving and bile secretion and reduce LDL (Yin et atorvastatin, no significant changes were al., 2008b, Wu LY et al., 2009). Berberine observed in aspartate aminotransferase similar to metformin is effective in (AST). Therefore, due to the antioxidant lowering blood sugar and the mechanisms properties of the extract and its effects on in both involve inhibiting aldose reductase, the activity of liver enzymes, it could be inducing glycolysis, and preventing suggested that the plant extracts could resistance to insulin by increasing insulin improve the function of liver enzymes. receptor expression. (Yin et al., 2008b, Polyphenolic compounds are important Lou et al.,2011, JU et al.,1990). antioxidants. These compounds, especially Hermenean et al. studied the hepato flavonoids, also have a protective effect on protective properties of Berberis vulgaris the liver against damage caused by free extract on carbon tetrachloride-induced radicals and toxins in the liver. The hepato toxicity in rats. The results showed inhibitory effects of barberry root extract that carbon tetrachloride administered in on oxidative stress have been recently rats could alone increase liver enzyme reported (Taheri et al., 2012). Eshraqi also levels and in histological studies extensive investigated the antioxidant effects of necrosis and fibrosis were observed in Jujube plants, barberry, purslane and liver. However, following the acanthus on liver oxidative system, red administration of barberry extract with blood cells, and hemoglobin non- carbon tetrachloride, the ALT, AST, enzymatic glycosylation and showed that gamma glutamyl transferase, direct glycosylation of hemoglobin in the bilirubin, total protein, and presence of the studied plants was well malondialdehyde (MDA) reduced and the prohibited, most effectively by acanthus amount of glutathione (GSH), superoxide and barberry. Lipid peroxidation was well dismutase (SOD), catalase (CAT), and controlled in the presence of various glutathione peroxidase (GPx) increased. concentrations of purslane, barberry, and Thus, according to the results of the acanthus. These plants in some majority of the studies, this extract has concentrations showed antioxidant effects, hepato protective effects due to its too (Eshraghi et al., 2011). Studies also antioxidant properties (Hermenean et al.,

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2012).The study done by Abd El-Wahab et be used as a medicinal herb to treat a al. in 2013 showed the impact of the raw variety of injuries, such as diabetes, liver extract of barberry and its effective disease, gallbladder pain, digestive, alkaloid (barberine) on the suppression of urinary tract diseases, and gallstones. lipid peroxidation in liver cells which Several animal studies indicated that the suggested a promising compound in the aqueous and alcoholic extracts of the plant treatment of hepatic oxidative stress (Abd fruit had antihypertensive properties El-Wahab et al., 2103). (Saleem et al., 2005, and Meliani et al., The results of a study by Hanachi and 2011). colleagues on the effects of the aqueous extract of barberry with the concentrations The anti-inflammatory and antioxidant of 50, 100, and 250 mg/kg by gavage for 7 effects of barberry extract weeks on the process of apoptosis in rats In a series of studies, the barbamine with liver cancer showed that in a dose- present in barberry was mentioned as an dependent process it could promote anti-inflammatory and antioxidant agent apoptosis (Hanachi et al., 2008). (Eshraghi et al., 2011, JU et al., 1990). It is Falah-Huseini et al. in a study on the also shown that the antioxidant effect of intra peritoneal injection of hydro barberry on hepatocytes is similar to those alcoholic barberry root extract at a doses of silymarin which is a known hepato of 300, 600, and 900 mg/kg in rats with protective agent (Tsai et al., liver injury induced by CCL4 showed that 2004).According to a study, the activities the extract at doses 30 times more than the of antioxidant enzymes such as catalase usual dose improved liver damage (Falah- and superoxide dismutase in the livers of Huseini et al.,2010). The antioxidant, cyto the rats with barberry plant in their diets protective, and hepato protective were higher than in the control group, properties of barberry have been reported implying the barberry's inhibitory effect on in several experimental studies, too (Abd lipid peroxidation through increasing the El-Wahab et al., 2103, Eshraghi et al., antioxidant enzymes (Murugesh et al., 2011). 2005). In a study in 2009, it was shown According to most studies, the majority that the barberry plant had positive effects of the medicinal properties of the plant are on the liver of diabetic rats and might be due to the various alkaloids present in effective in preventing complications of different parts of it. The fruit contains diabetes as it regulated glucose dihydro palmitinium hydroxide which is homeostasis by decreasing glucose an anti-estrogen substance that causes production and oxidative stress (Singh J et endometrial atrophy and crumple of gastric al., 2009). In the study by Lee et al. (2006) glands. These changes result in nutrition it was shown that the berberine in barberry disorders in the fetus and its growth. could lower lipogenesis and had its Barberry root is a laxative which opens inhibitory effects on lipid peroxidation hepatic duct and cystic duct (Javadzadeh et (Lee et al., 2006). Therefore, we conclude al., 2012). that it is possible to use barberry as Several studies on the antimicrobial and antioxidant supplements in illnesses such antioxidant effects of the aqueous extract as diabetes, liver disease, and of barberry showed that the fruit could act atherosclerosis as prevention or treatment both as an antioxidant (Eshraghi et al., (Eshraghi et al., 2011). 2011) and a natural anti-bacterial agent In an in vitro experiment in which (Dashti et al., 2014). human cell lines were used, it was shown Studies showed that barberry had that berberine could inhibit activator numerous health benefits, including hepato protein1 (AP-1) as an important agent protective and hypoglycemic ones and can causing inflammation and cancer.

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Similarly, in a study using human on acute inflammation (caused by plantar peripheral lymphocytes, it was proved that injection of formalin, xylene to ear and berberine was able to inhibit lymphocyte acetic acid to peritoneum) and chronic one transformation which would justify its (caused by gauze implanted in the groin) anti-inflammatory properties as it could in rats, it was shown that the consumption inhibit DNA synthesis in active of alcoholic extract of the plant fruit was lymphocytes. According to another study, able to reduce acute and chronic in case of tissue injury, berberine had an inflammation (Kiasalari et al., 2011). influential direct role in many stages of Minaiyan et al. in a comparative study of platelet-dependent inflammatory process. the effects of fruit extract of barberry, Here, berberine showed dose-dependent berberine chloride, and corticosteroids on inhibition of arachidonic acid release from a rat model of ulcerative colitis concluded cell membrane phospholipids, inhibition of that the gavage of the extract that was thromboxane A2 from platelets, and inhibition of thrombus formation (Fukuda, virtually free from berberine was et al., 1999). significantly effective in preventing colitis Ebrahimi-Mameghani and colleagues in injuries which could be due to its their study on the effects of Berberis anthocyanin compounds (Minaiyan et al., vulgaris extract on blood pressure and 2011). inflammatory markers showed that black The phyto chemical analysis of barberry had no effects on serum barberry root and stem revealed the concentrations of interleukin-6 (IL-6) and presence of proto berberines and C-reactive protein (CRP). The results of bisenzyliso quinoline alkaloids this study showed no effects on systolic (berbamine, tetrandrine and chondocurine) and diastolic blood pressure and with anti-inflammatory and inflammatory markers by processed black immunosuppressive properties (Li et al., barberry and the positive effect of apple 1989). The results of a comparative study vinegar on interleukin-6 (Ebrahimi- done by Minaiyan et al. on the effects of Mamaghani et al., 2009). barberry fruit extract and chloride Shamsa and colleagues studied anti- berberine on the rats' acetic acid-induced inflammatory effects of barberry fruit on colitis showed that the oral administration guinea pigs and showed that the addition of the extract at a dose of 750-1500 mg/kg of black barberry fruit extract to the was useful against the colic. isolated terminal ileum of guinea pigs, similar to dexchlorpheniramine caused a They concluded that since fruit extract decrease in histamine dose-dependently is nearly devoid of berberine so this and like atropine it decreased acetylcholine protective effect may be attributed to the in a dose-dependent manner. Histamine anthocyanin compounds present in the causes the release of IL-6 stored in T-cells. plant (Minaiyan et al., 2011). Histamine also causes dilation of local The major sugars of fruit are glucose blood vessels and increases capillary 8.48 g/dl and fructose 6.12 g/dl and the permeability and leakage of large amounts organic acids are malic and citric. The of fluid into the interstitial spaces and main antioxidant capacity of barberry lies inflammation. Thus, it is likely that the use in its high levels of phenols and flavonoids of black barberry fruit extract can lower such as anthocyanins and other IL-6 concentration through decreasing polyphenolic compounds which account histamine and consequently can help for its unique place among all fruits reduce inflammation (Shamsa et al., 1999). (Ozgen et al.,2012). In a study by Kiasalari and colleagues on the effect of Berberis vulgaris extract

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The effects of barberry extract on blood scavenge free radicals (Tomosaka et al., sugar 2008; Shidfar et al., 2012). Diabetes mellitus is a complex Meliani and colleagues also studied the metabolic disorder caused by a deficiency effects of Berberis vulgaris extract on or lack of insulin secretion or reduced normal and diabetic rats, and showed that insulin sensitivity of tissues (Ahangarpour the administration of saponin and barberry et al., 2012). About 800 kinds of medicinal extract for a week reduced blood sugar in plants have been used in traditional normal rats. Furthermore, in addition to medicine to treat diabetes. The lowering blood glucose in diabetic rats, it hypoglycemic effects of many of these lowered cholesterol and triglycerides as plants in animal models and clinical well. Therefore, the plant can be effective studies have been studied and approved in the treatment of diabetes (Meliani et al., (Arumugam et al., 2013; Ahangarpour et 2011). al., 2012). In another study, Ashraf and colleagues Having given the history of barberry examined the effect of aqueous extract of plants used in traditional medicine for Zarafshan barberry root on testes and lowering blood sugar, Ahangpour et al. testosterone levels in streptozotocin- examined the effects of barberry extract on induced diabetic rats. In this study, insulin release from the isolated pancreatic diabetes caused a significant decrease in islets of male mouse. The findings of this testosterone levels, diameter of research indicated an increase in insulin seminiferous tubules, spermiogenesis secretion in the presence of the extract. index, and the thickness of the epithelium Thus, it may be suggested that one blood as well as a significant increase in the sugar lowering mechanism by barberry is thickness of the interstitial tissues and through its effect on pancreatic islets. It is blood glucose levels in diabetic group in noteworthy that the increasing effect of the comparison to the other groups. By using extract on insulin secretion is less than that barberry root, these changes were brought of glibenclamide (Ahangarpour et to normal levels (Ashraf et al., 2013). al.,2012). Abd El-Wahab and colleagues (2013) In a study conducted by Yin and in an in vitro study examined the colleagues it was found that berberine had antioxidant, anti-acetyl cholinesterase, a lowering effect on glucose in anti-cancerous, and anti diabetic properties hepatocytes (Yin et al.,2002).Moreover, in of Berberis vulgaris and its active another study, it was proved that the compound, i.e., berberine. The study berberine in barberry acted similar to showed that the plant compounds had the metformin in increasing insulin sensitivity biological potential of inhibiting lipid in rats receiving high fat diets (Gao et peroxidation (Abd El-Wahab et al., 2013). al.,1997).Berberine can act as an activated The results of the study done by protein kinase (AMPK) and can increase Shidfaret al. showed that a daily intake of the ratio of AMP to ATP and inhibit the 3 g fruit extract over a period of 3 months biosynthesis of ATP in mitochondria (Yin had beneficial effects on the lipoprotein et al., 2008b;Shidfar et al., 2012). In and apoprotein concentrations as well as addition to increasing insulin sensitivity, triglyceride and glycemic control in berberine acts as an alpha-glucosidase patients with type 2 diabetes (Shidfar et inhibitor (Tang et al., 2006; Leng et al., al., 2012). 2005) and inhibits adipogenesis, hence, Studies have shown that the activity of exhibits anti-obesity activity (Kim et al., berberine is comparable to sulfonylureas 2009). Berberine also increases LDL-C and metformin. The administration of receptors and as an antioxidant can berberine can reduce FBS (fasting blood sugar) and HbA1C in patients with newly

AJP, Vol. 5, No. 6, Nov-Dec 2015 493 Zarei et al. diagnosed type 2 diabetes. Berberine The groups treated with the extract of reduces weight, increases insulin barberry root did not show significant sensitivity, decreases insulin resistance, changes in TSH levels. The increased and thereby reduces blood sugar in genetic levels of thyroid hormone and decreased models of type 2 diabetes (Shidfaret al., TSH levels in the group receiving 2012). atorvastatin were possibly due to negative The administration of barberry root feedback effect of thyroid hormones on aqueous extract in streptozotocin-induced TSH. The increased levels of T3 andT4 diabetic rats showed a significant anti with no effects on TSH levels in the hyperglycaemic effects. This suggests that experimental groups receiving barberry the effects may be related to the presence root extract indicated euthyroid hyper of saponin in the extract with its thyroxinemia. stimulatory effects on residual beta-cell These changes might be caused by (Meliani et al., 2011). increased plasma proteins, including albumin, reduced fat and leptin levels, and The effects of barberry extract on increased neuropeptide Y as well as thyroid function stimulated hypothalamic para venericular The thyroid gland, secreting thyroxine nuclei which were possibly made by (T4) and triiodothyronine (T3) hormones, alkaloid compounds found in the plant. It has undeniably profound effects on seems that the extract at above-mentioned metabolism. Researchers found that blood doses caused pathological changes in the lipid levels were inversely correlated with pituitary-thyroid axis (Zarei et al., 2015). thyroid hormone levels and by increasing Due to multiple properties of the root hormones, the lipid profile levels dropped. and fruit of barberry on controlling the Even in patients with hypothyroidism, complications of diabetes, reducing and the level of LDL cholesterol increases controlling lipid profiles and liver while it is reduced in hyperthyroidism enzymes, and its obvious antioxidant and (Zarei et al., 2012a). Studies also show anti-inflammatory properties, as well as its that levels of blood fats such as cholesterol ability to influence the secretion of the and triglyceride (TG) increase in groups thyroid hormones, therefore this plant can with high fat diet. There is also a direct be considered as a drug candidate for the correlation between fat and leptin, while prevention and control of cardiovascular the correlation between T3 and leptin is an diseases, diabetes, thyroid disorders and inversely significant one. However, blood liver disease. lipid levels do not correlate with TSH levels. This actually represents an Acknowledgment association between fat, leptin, and thyroid This article was part of the research hormones (ShekarForosh et al., 2012; project of the research committee and Zarei et al., 2013b). Accordingly, Zarei et ethics committee No: 90-123-12 of Arak al. in a study surveyed the effects of the University of Medical Sciences, Arak, root extract of barberry and atorvastatin on Iran. The authors would like to thank the thyroid hormone levels in rats with moral and financial support provided by hypercholesterolemia. The results showed the vice-presidency of Research of Arak that in the groups receiving the extract of University of Medical Sciences. the barberry roots and atorvastatin the levels of thyroid hormones (T3 and T4) Conflict of interest increased while the level of thyroid- There is no conflict of interest in this stimulating hormone (TSH) decreased in study. the groups receiving atorvastatin.

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