The effects of Ficus carica on the activity of enzymes related to metabolic syndrome

The present study aimed to investigate the effects of the various parts of Ficus carica L. (figs) on antioxidant, antidiabetic, and antiobesogenic effects in vitro. Fruit, leaves, and stembark of the F. carica plant were sequentially extracted using organic and inorganic solvents and their total polyphenol and flavonoid contents were estimated. The effects of the extracts on antioxidative, antidiabetic (inhibition of α-amylase and α-glucosidase enzymes), and antiobesogenic (antilipase) activities were measured using several experimental models. The fruit ethanolic extract contained a high quantity of polyphenols and flavonoids (104.67 ± 5.51 μg/mL and 81.67 ± 4.00 μg/mL) compared with all other extracts. The activity of the ethanolic extract of F. carica fruit was significantly (p < 0.05) higher than all other extracts and parts of the plant in terms of antioxidative, antidiabetic, and antiobesogenic effects. The IC₅₀ values of the fruit ethanolic extract in terms of antioxidative (134.44 ± 18.43 μg/mL), and inhibition of α-glucosidase (255.57 ± 36.46 μg/mL), α-amylase (315.89 ± 3.83 μg/mL), and pancreatic lipase (230.475 ± 9.65 μg/mL) activity indicate that the activity of fruit ethanolic extract is better than all other extracts of the plant. The gas chromatography–mass spectroscopy analysis of the fruit ethanolic extract showed the presence of a number of bioactive compounds such as butyl butyrate, 5-hydroxymethyl furfural, 1-butoxy-1-isobutoxy butane, malic acid, tetradecanoic acid, phytol acetate, trans phytol, n-hexadecanoic acid, 9Z,12Z-octadecadienoic acid, stearic acid, sitosterol, 3,5-dihydroxy-6-methyl-2,3-dihydro-4H-pyran-4-one, and 2,4,5-trimethyl-2,4-dihydro-3H-pyrazol-3-one. The results of this study suggest that the ethanolic extract of the fruit of F. carica may have potential antidiabetic and antiobesogenic agents.     

Inhibition of key enzymes linked to type 2 diabetes and sodium nitroprusside-induced lipid peroxidation in rat pancreas by water extractable phytochemicals from some tropical spices

Context: Spices have been used as food adjuncts and in folklore for ages. Inhibition of key enzymes (α-amylase and α-glucosidase) involved in the digestion of starch and protection against free radicals and lipid peroxidation in pancreas could be part of the therapeutic approach towards the management of hyperglycemia and dietary phenolics have shown promising potentials.

Objective: This study investigated and compared the inhibitory properties of aqueous extracts of some tropical spices: Xylopia aethiopica [Dun.] A. Rich (Annonaceae), Monodora myristica (Gaertn.) Dunal (Annonaceae), Syzygium aromaticum [L.] Merr. et Perry (Myrtaceae), Piper guineense Schumach. et Thonn (Piperaceae), Aframomum danielli K. Schum (Zingiberaceae) and Aframomum melegueta (Rosc.) K. Schum (Zingiberaceae) against α-amylase, α-glucosidase, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and sodium nitroprusside (SNP)-induced lipid peroxidation in rat pancreas - in vitro using different spectrophotometric method.

Materials and methods: Aqueous extract of the spices was prepared and the ability of the spice extracts to inhibit α-amylase, α-glucosidase, DPPH radicals and SNP-induced lipid peroxidation in rat pancreas - in vitro was investigated using various spectrophotometric methods.

Result: All the spice extracts inhibited α-amylase (IC₅₀?=?2.81–4.83?mg/mL), α-glucosidase (IC₅₀?=?2.02–3.52?mg/mL), DPPH radicals (EC₅₀?=?15.47–17.38?mg/mL) and SNP-induced lipid peroxidation (14.17–94.38%), with the highest α-amylase & α-glucosidase inhibitory actions and DPPH radical scavenging ability exhibited by X. aethiopica, A. danielli and S. aromaticum, respectively. Also, the spices possess high total phenol (0.88–1.3?mg/mL) and flavonoid (0.24–0.52?mg/mL) contents with A. melegueta having the highest total phenolic and flavonoid contents.

Discussion and conclusion: The inhibitory effects of the spice extracts on α-amylase, α-glucosidase, DPPH radicals and SNP-induced lipid peroxidation in pancreas (in vitro) could be attributed to the presence of biologically active phytochemicals such as phenolics and some non-phenolic constituents of the spices. Furthermore, these spices may exert their anti-diabetic properties through the mechanism of enzyme inhibition, free radicals scavenging ability and prevention of lipid peroxidation.     

Inhibition of key enzymes linked to type 2 diabetes by compounds isolated from Aframomum melegueta fruit

Context: The use of Aframomum melegueta K. Schum. (Zingiberaceae) fruit for treatment of diabetes has recently been established in Nigeria. However, compounds responsible for the antidiabetic action have not been identified.

Objective: The present study carried out the bioassay-guided isolation of possible bioactive compounds responsible for the antidiabetic action of A. melegueta fruit.

Materials and methods: The A. melegueta fruit was sequentially extracted using ethyl acetate (EtOAc), ethanol and water, and the most active extract (EtOAc) was subjected to column chromatography on a silica gel column using solvent gradient systems of hexane (HEX):EtOAc and EtOAc:MeOH and the isolation of compounds was guided by α-glycosidase and α-amylase inhibitory activities at various concentrations (30–240?μg/mL).

Results: According to the results, 3 arylalkanes, 6-paradol (1), 6-shogaol (2) and 6-gingerol (3) and a pentacyclic triterpene, oleanolic acid (4) were isolated from A. melegueta fruit. All the compounds exhibited inhibitory effects against α-amylase and α-glucosidase. 6-Gingerol (3) and oleanolic acid (4) showed higher inhibitory activity against α-amylase (IC₅₀: 6-gingerol: 81.78?±?7.79?μM; oleanolic acid: 91.72?±?1.63?μM) and α-glucosidase (IC₅₀: 6-gingerol: 21.55?±?0.45?μM; oleanolic acid: 17.35?±?0.88?μM) compared to the standard drug, acarbose and other isolated compounds. The kinetics of the enzyme action of the compounds showed a noncompetitive mode of inhibition.

Conclusion: The data of this study suggest that the 6-gingerol (3) and oleanolic acid (4) showed higher α-amylase and α-glucosidase inhibitory action and therefore could be responsible for the antidiabetic activity of A. melegueta fruit.     

Screening of antidiabetic and antihyperlipidemic potential of oil from Piper longum and piperine with their possible mechanism

Background: Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycaemia and other symptoms like polyuria (frequent urination), polydipsia (increased thirst) and polyphagia (increased hunger) which ultimately causes various other complications like retinopathy, neuropathy, nephropathy and microangiopathy.

Objectives: The antidiabetic and antihyperlipidemic potential of oil from Piper longum (PLO) and piperine was investigated with their possible mechanism using α-glucosidase, aldose reductase (AR), and pancreatic lipase inhibitory activity.

Methods: The biochemical parameters, viz. glucose level, insulin level, liver glycogen content, glycosylated hemoglobin, total plasma cholesterol, triglyceride, and antioxidant parameters, were estimated for all treated groups in acute and chronic antihyperglycemic animal models.

Results: PLO (100 and 200 mg/kg), piperine (25 and 50 mg/kg), and glibenclamide (0.6 mg/kg) in respective groups of diabetic animals administered for 28 days reduced the blood glucose level in streptozotocin-induced diabetic rats. There was significant increase in body weight, liver glycogen content, plasma insulin, and high-density lipoprotein and decrease in glycosylated hemoglobin, triglyceride, and total plasma cholesterol in PLO-administered groups as compared to control group. The IC₅₀ value of PLO for α-glucosidase, AR, and pancreatic lipase was found to be 150 ± 2.5, 120 ± 1.2, and 175 ± 1.2 μg/ml, respectively, which was found comparable with the standard drugs acarbose (90 ± 2.3 μg/ml), quercetin (80 ± 2.3 μg/ml), and orlistat (25 ± 0.5 μg/ml), respectively.

Conclusion: The investigation done reveals that PLO has significant antidiabetic and antihyperlipidemic activity.     

Evaluation of six plant species used traditionally in the treatment and control of diabetes mellitus in South Africa using in vitro methods

Context: Numerous plants are used by the local communities of South Africa for the treatment and management of type II diabetes.

Objectives: For this study, we undertook a survey of the plants sold for the management of diabetes in the town of Newcastle, South Africa. Identified plants were subsequently evaluated for their in vitro antidiabetic activity.

Materials and methods: Plants were identified through an interview with a herbalist at the market. Antidiabetic activity of extracts of purchased plants was evaluated using in vitro α-amylase and α-glucosidase activity, as well as islets of Langerhans excretory activity.

Results: Senna alexandrina Mill. (Fabaceae), Cymbopogon citrates Stapf. (Poaceae), Cucurbita pepo L. (Cucuribitaceae), Nuxia floribunda Benth. (Stilbaceae), Hypoxis hemerocallidea Fisch. and Mey (Hypoxidaceae), and Cinnamomum cassia Blume (Lauraceae) were identified. The hexane extract of S. alexandrina (EC₅₀?=?0.083?mg/ml), ethyl acetate extract of H. hemerocallidea (EC₅₀?=?0.29?mg/ml), and methanol extracts of Cymbopogon citratus (EC₅₀?=?0.31?mg/ml) and Cinnamomum cassia (EC₅₀?=?0.12?mg/ml) had the highest α-amylase inhibitory activity, albeit lower than acarbose (EC₅₀?=?0.50?mg/ml). All the plants had good α-glucosidase inhibitory activity (>50%) with the exception of some methanol (Cinnamomum cassia, N. floribunda, and Cymbopogon citratus) and acetone extracts (Cucurbita pepo and N. floribunda). Only the H. hemerocallidea acetone extract had an insulin stimulatory effect (2.5?U/ml at 8?μg/ml).

Conclusion: All the evaluated plants demonstrated inhibitory activity against the specific GIT enzyme systems evaluated. Only H. hemerocallidea had insulin secretory activity, adding evidence to the traditional use of these purchased plants in the management of the type II diabetic post-prandial hyperglycemia.     

The treatment of type 1 diabetes mellitus with agents approved for type 2 diabetes mellitus

Introduction: The management of type 1 diabetes remains a challenge for clinicians. Current practice is to administer insulin analogues to best mimic normal physiological insulin profiles. However, despite our best efforts the majority of individuals with type 1 diabetes continue to suffer from suboptimal glucose control, significant hypoglycemia and microvascular tissue complications of the disease. There is thus a significant unmet need in the treatment of T1DM to obtain better glycemic control.

Areas covered: We discuss the use of α-glucosidase inhibitors, dipeptidyl-peptidase inhibitors, glucagon-like peptide 1 agonists, biguanides, thiazolidinediones and sodium glucose co-transporter 2 inhibitors in individuals with T1DM.

Expert opinion: Non-insulin therapies present a unique and exciting adjunctive treatment for individuals with type 1 diabetes. Although data are scarce, the classes of medications discussed help to lower glucose, decrease glycemic excursions and in some cases improve body weight, along with allowing dose reductions in total daily insulin. Glucagon-like peptide 1 agonists and sodium glucose co-transporter 2 inhibitors, in particular, have been demonstrated to provide clinical improvements in individuals with T1DM and we feel their use can be explored in obese, insulin-resistant patients with T1DM, those with frequent and significant glycemic excursions or individuals with persistently elevated hemoglobin A1c.     

Effect of Ficus racemosa stem bark on the activities of carbohydrate hydrolyzing enzymes: An in vitro study

Herbal medicines have been used since prehistoric times by different cultures worldwide for the treatment of diabetes. The present investigation evaluated the effect of Ficus racemosa Linn. (Moraceae) stem bark on carbohydrate hydrolyzing enzymes, viz., porcine pancreatic α-amylase, rat intestinal α-glucosidase, sucrase, and almond β-glucosidase, using in vitro model systems. In addition, the effect of heat treatment was also studied. Untreated F. racemosa bark (FRB) significantly inhibited (p?≤?0.05) α-amylase, α-glucosidase, β-glucosidase, and sucrase in a dose-dependent manner. Heat treatment of the sample comparably increased α-amylase, α-glucosidase, and sucrase inhibitory activities, while a marginal decrease in β-glucosidase inhibitory activity was observed; however, no statistical differences were noted. Untreated FRB showed IC₅₀ values of 0.94% and 280, 212, and 367 μg/mL for α-amylase, α-glucosidase, β-glucosidase, and sucrase, respectively, while the IC₅₀ values for heat treated FRB were 0.58% and 259, 223, and 239 μg/mL, respectively. Further, a significant correlation (p?≤?0.01; r?=?0.791) was observed between α-amylase, α-glucosidase, β-glucosidase, and sucrase inhibitory activities of both untreated and heat treated FRB. The results clearly demonstrate that inhibition of carbohydrate hydrolyzing enzymes is one mechanism through which F. racemosa stem bark exerts its hypoglycemic effect in vivo. Therefore, the potential exists to explore the utilization of F. racemosa stem bark in the development of nutraceuticals and functional foods for the management of diabetes and related symptoms/disorders.     

Essential oil of Zygophyllum album inhibits key-digestive enzymes related to diabetes and hypertension and attenuates symptoms of diarrhea in alloxan-induced diabetic rats

Context: Zygophyllum album L. (Zygophyllaceae), commonly known as Bougriba, is widely used to treat diabetes, digestive tract spasm, and hypertension in folk medicine, in Tunisia.

Objective: This study investigates the antidiabetic, antidiarrheal, and antihypertensive activities of the leaves of the essential oil from Zygophyllum album (OZA) in alloxan-induced diabetic rats.

Materials and methods: The oil was obtained by hydrodistillation and analyzed by GC-MS. Males rats were divided into four groups: control, diabetic-untreated group, diabetic-treated group with acarbose (10?mg/kg), and diabetic-treated rats with OZA (200?mg/kg) for 30 d.

Results: At the end of the experimental period, the OZA significantly decreased the activity of α-amylase in pancreas and serum of the diabetic rats by 43% and 38%, respectively, which led to reduce the serum glucose level by 60% and lower of glycated hemoglobin (HbA1c) rate by 17% as compared with untreated diabetic animals. Moreover, the OZA treatment attenuated symptoms of diarrhea, improved lipid disorders, and hypertension through inhibiting the pancreatic lipase and angiotensin-converting enzyme (ACE) activities by 47% and 25%, respectively, in serum of diabetic rats.

Conclusion: OZA showed a good effect in the management of diabetes mellitus and exerted preventive action from related hypertension.     

New insights into seaweed polyphenols on glucose homeostasis

Abstract

Context: Polyphenol-rich marine macroalgae are gaining dietary importance due to their influence over diabetes mellitus and the role as a vital source of high-value nutraceuticals. Their assorted beneficial effects on human health include competitive inhibition of digestive enzymes, varying the activity of hepatic glucose-metabolizing enzymes, lowering the plasma glucose levels, and lipid peroxidation, delaying the aging process.

Objective: In this paper, we review the health beneficial effects of polyphenols and phlorotannins from brown seaweeds with special emphasis on their inhibitory effects on carbohydrate-metabolizing enzymes.

Methods: A survey of literature from databases such as Sciencedirect, Scopus, Pubmed, Springerlink, and Google Scholar from the year 1973 to 2013 was done to bring together the information relating to drug discovery from brown seaweeds as a source for diabetes treatment.

Results: Over the past two decades, 20 different bioactive polyphenols/phlorotannins have been isolated and studied from 10 different brown algae. Discussion of the positive effect on the inhibition of enzymes metabolizing carbohydrates in both in vitro and in vivo experiments are included.

Conclusion: Despite the recent advancements in isolating bioactive compounds from seaweeds with potential health benefit or pharmaceutical behavior, studies on the polyphenol effectiveness on glucose homeostasis in human beings are very few in response to their functional characterization. Added research in this area is required to confirm the close connection of polyphenol rich seaweed-based diet consumption with glucose homeostasis and the exciting possibility of prescribing polyphenols to treat the diabetes pandemic.     

The anti-obesity potential of sigmoidin A

Context: During the last few decades, the prevalence of obesity in the western world has dramatically increased with epidemic proportions. Hand in hand with this statistic, the incidences of obesity-linked diseases such as diabetes are increasing with pandemic rate. The search for novel drugs and nutritional intervention approaches for obesity is now of significant importance.

Objective: The anti-obesity potential of eriodictyol (ERD) and its close structural analogue, sigmoidin A (SGN), were evaluated. SGN was isolated from Erythrina abyssinica Lam. ex DC. (Fabaceae).

Materials and methods: Concentrations between 300 and 0.1 µM of test samples and reference drugs made in three-fold dilutions were tested for enzyme inhibitory effects. The major obesity target, pancreatic lipase, was used to test the anti-obesity potential while the selective effects of the compounds were determined through assessments of effects on α-glucosidase.

Results: The inhibitory effect of SGN on pancreatic lipase (IC₅₀, 4.5 ± 0.87 µM) was 30-times greater than that of ERD (IC₅₀, 134 ± 19.39 µM) while their effect on α-glucosidase enzyme was comparable (IC₅₀ value of 62.5 ± 9.47 and 57.5 ± 13.15 µM). The anti-obesity drug, orlistat, inhibited pancreatic lipase with an IC₅₀ value of 0.3 ± 0.04 µM, while the anti-diabetic drug, acarbose, inhibited α-glucosidase with an IC₅₀ value of 190.6 ± 16.05 µM.

Discussion: Although less active than the standard anti-obesity drug, orlistat, the observed activity indicated that prenylation of the flavonoid skeleton potently enhances anti-lipase activity.

Conclusion: Such groups of flavonoids need to be further investigated for their therapeutic and nutritional benefit in combating obesity problems.     

Effects of Sambucus nigra and Aronia melanocarpa extracts on immune system disorders within diabetes mellitus

Abstract

Context: The fruits of Aronia melanocarpa Elliot (Rosaceae), (black chokeberry), and Sambucus nigra L. (Caprifoliaceae), elderberries are rich in anthocyanins. Many studies have reported that anthocyanins are beneficial in diabetes due to their capacity to stimulate insulin secretion and reduce oxidative stress.

Objective: The purpose of this study is to prove the biologically active properties of polyphenols extracted from S. nigra and A. melanocarpa fruit. The study also details the influence of plant polyphenols on immune system imbalances within diabetes mellitus.

Materials and methods: Polyphenolic extract was administered to Wistar rats 0.040?g/kg body every 2?d for 16 weeks. The absorbencies of all the solutions were determined using a V-550 Able Jasco UV–VIS spectrophotometer. The immunomodulatory capacity of vegetal extracts was assessed by studying cytokines TNF-α and IFN-γ through the ELISA method and fibrinogen values.

Results and discussion: At 48?h, the anti-inflammatory effects of S. nigra and A. melanocarpa substances have been revealed by an increase of the TNF-α and IFN-γ levels in the diabetic group protected by these extracts. Seventy-two hours post-administration of both substances in the diabetic groups, the TNF-α level returns to the values read 24?h after substance administration. The vegetal extracts limit the production of fibrinogen in the diabetic rats under polyphenolic protection, the values being highly significant compared with the diabetic group.

Conclusions: Natural polyphenols extracted from S. nigra and A. melanocarpa modulate specific and non-specific immune defenses in insulin-deficiency diabetes and reduce the inflammatory status and self-sustained pancreatic insulitis.     

甲壳低聚糖对α-葡萄糖苷酶活性的影响及降血糖作用

目的探讨甲壳低聚糖对α-葡萄糖苷酶活性的影响及降糖效果。方法在体外建立标准酶反应体系,分别加入6%甲壳低聚糖50,100,150,200,250,300μl,用4-硝基酚-α-D呋喃葡萄糖苷法测定酶活性;再建立加有6%阿卡波糖200μl的酶反应体系,测定酶活性;以250 mg/(kg.d)剂量灌胃,观察其对实验性糖尿病大鼠空腹及餐后血糖的影响。结果甲壳低聚糖对α-葡萄糖苷酶具有明显抑制作用,抑制效果接近于阿卡波糖;甲壳低聚糖能显著降低糖尿病大鼠空腹及餐后血糖。结论甲壳低聚糖可能具有阿卡波糖样的降血糖作用。     

海参磷脂型二十碳五烯酸对糖尿病大鼠血葡萄糖耐量的影响

目的研究海参磷脂型二十碳五烯酸(eicosapentaeno-ic acid phosphatidylcholine,EPA-PC)对链脲佐菌素(streptozo-cin,STZ)诱导的糖尿病大鼠血葡萄糖耐量的影响。方法两次腹腔注射STZ建立糖尿病大鼠模型,经不同剂量的海参EPA-PC(25和75 mg.kg-1,以EPA含量计)灌胃60 d。实验结束后,分别检测大鼠空腹血糖(fasting blood-glucose,FBG)、口服葡萄糖耐量(oral glucose tolerance test,OGTT)、糖化血红蛋白(glycated hemoglobin,HbAlc)、糖化血清蛋白(glycated serum protein,GSP)、空腹血清胰岛素(fasting insu-lin,FIN)含量,并分别采用光镜和电镜观察胰腺组织的显微结构和胰岛β细胞的亚显微结构。结果海参EPA-PC可明显改善糖尿病大鼠OGTT(P<0.05),降低HbAlc和GSP的含量(P<0.01),促进FIN的分泌(P<0.01);明显改善胰腺组织的显微结构,修复受损胰岛β细胞的亚显微结构。结论海参EPA-PC对糖尿病大鼠具有明显改善血葡萄糖耐量的作用,其与恢复糖尿病大鼠受损的胰岛外周组织以及胰岛β细胞有关。     

Glycemic control after addition of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes showing inadequate response to thrice-a-day treatment with α-glucosidase inhibitors

Objective: We investigated the effect of addition of alogliptin, while continuing the α-glucosidase inhibitor (αGI) administration at the same or reduced dose, or discontinuing the drug, on the glycemic control in type 2 diabetic patients showing inadequate response to αGI treatment.

Research design and methods: A prospective, randomized, controlled, multicenter interventional study trial. Subjects were randomly assigned to treatment with alogliptin alone (Intake 0 group), or alogliptin in addition to an αGI administered once-/twice-/thrice-daily (Intake 1, 2 and 3 groups).

Main outcome measures: Changes in glycemic control were measured.

Results: The HbA1c and glycoalbumin levels at 1 and 3 months were significantly lower than the values at the baseline in the Intake 1, 2 and 3 groups, but not the Intake 0 group. The body weight at 3 months was significantly lower than that at the baseline in the Intake 3 group. There were no significant differences in the degree of satisfaction or participating volition recorded, before and after the start of the study treatments.

Conclusions: Addition of alogliptin to once-/twice-daily administration of an αGI may be effective for obtaining improved glycemic control, without lowering the treatment satisfaction level, in type 2 diabetic patients.     

五味子中提取α-葡萄糖苷酶抑制剂的研究

目的从中药五味子中提取分离α 葡萄糖苷酶抑制剂。方法利用浸提、超滤、柱层析、醋酸铅沉淀等方法进行纯化。结果初步分离得到α 葡萄糖苷酶抑制剂。结论该抑制剂成分为大分子糖苷类物质 ,相对分子量在 5万以上 ,抑制类型为非竞争性抑制。     

糖尿病对肌松药肌松效应的影响探讨

糖尿病周围神经病变在围术期影响肌松药的肌松效应,导致糖尿病患者术中应用肌松药后术后呼吸功能不全的发生率显著增加,加之糖尿病本身就可损伤呼吸系统,严重影响糖尿病患者的预后。本文探讨糖尿病对肌松药肌松效应的影响机制,并就糖尿病对临床常用肌松药(维库溴铵、罗库溴铵、阿曲库铵及顺式阿曲库铵)的影响进行综述。     

Contribution of momilactones A and B to diabetes inhibitory potential of rice bran: Evidence from in vitro assays

This study was the first to detect the presence of the two compounds momilactone A (MA) and momilactone B (MB) in rice bran using liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS). By in vitro assays, both MA and MB exhibited potent inhibitory activities on pancreatic α-amylase and α-glucosidase which were significantly higher than γ-oryzanol, a well-known diabetes inhibitor. Remarkably, MA and MB indicated an effective inhibition on trypsin with the IC₅₀ values of 921.55 and 884.03 µg/mL, respectively. By high-performance liquid chromatography (HPLC), quantities of MA (6.65 µg/g dry weight) and MB (6.24 µg/g dry weight) in rice bran were determined. Findings of this study revealed the α-amylase, α-glucosidase and trypsin inhibitors MA and MB contributed an active role to the diabetes inhibitory potential of rice bran.     

Arsenic-induced alteration in the expression of genes related to type 2 diabetes mellitus

Chronic exposure to high concentrations of arsenic in drinking water is associated with an increased risk for developing type 2 diabetes. The present revision focuses on the effect of arsenic on tissues that participate directly in glucose homeostasis, integrating the most important published information about the impairment of the expression of genes related to type 2 diabetes by arsenic as one of the possible mechanisms by which it leads to the disease. Many factors are involved in the manner in which arsenic contributes to the occurrence of diabetes. The reviewed studies suggest that arsenic might increase the risk for type 2 diabetes via multiple mechanisms, affecting a cluster of regulated events, which in conjunction trigger the disease. Arsenic affects insulin sensitivity in peripheral tissue by modifying the expression of genes involved in insulin resistance and shifting away cells from differentiation to the proliferation pathway. In the liver arsenic disturbs glucose production, whereas in pancreatic beta-cells arsenic decreases insulin synthesis and secretion and reduces the expression of antioxidant enzymes. The consequences of these changes in gene expression include the reduction of insulin secretion, induction of oxidative stress in the pancreas, alteration of gluconeogenesis, abnormal proliferation and differentiation pattern of muscle and adipocytes as well as peripheral insulin resistance.     

Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes

BACKGROUND AND PURPOSE

Cannabidiol (CBD) and Δ⁹-tetrahydrocannabinol (THC) interact with transient receptor potential (TRP) channels and enzymes of the endocannabinoid system.

EXPERIMENTAL APPROACH

The effects of 11 pure cannabinoids and botanical extracts [botanical drug substance (BDS)] from Cannabis varieties selected to contain a more abundant cannabinoid, on TRPV1, TRPV2, TRPM8, TRPA1, human recombinant diacylglycerol lipase α (DAGLα), rat brain fatty acid amide hydrolase (FAAH), COS cell monoacylglycerol lipase (MAGL), human recombinant N-acylethanolamine acid amide hydrolase (NAAA) and anandamide cellular uptake (ACU) by RBL-2H3 cells, were studied using fluorescence-based calcium assays in transfected cells and radiolabelled substrate-based enzymatic assays. Cannabinol (CBN), cannabichromene (CBC), the acids (CBDA, CBGA, THCA) and propyl homologues (CBDV, CBGV, THCV) of CBD, cannabigerol (CBG) and THC, and tetrahydrocannabivarin acid (THCVA) were also tested.

KEY RESULTS

CBD, CBG, CBGV and THCV stimulated and desensitized human TRPV1. CBC, CBD and CBN were potent rat TRPA1 agonists and desensitizers, but THCV-BDS was the most potent compound at this target. CBG-BDS and THCV-BDS were the most potent rat TRPM8 antagonists. All non-acid cannabinoids, except CBC and CBN, potently activated and desensitized rat TRPV2. CBDV and all the acids inhibited DAGLα. Some BDS, but not the pure compounds, inhibited MAGL. CBD was the only compound to inhibit FAAH, whereas the BDS of CBC > CBG > CBGV inhibited NAAA. CBC = CBG > CBD inhibited ACU, as did the BDS of THCVA, CBGV, CBDA and THCA, but the latter extracts were more potent inhibitors.

CONCLUSIONS AND IMPLICATIONS

These results are relevant to the analgesic, anti-inflammatory and anti-cancer effects of cannabinoids and Cannabis extracts.

LINKED ARTICLES

This article is part of a themed issue on Cannabinoids in Biology and Medicine. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue-7