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.     

Effects of Aphloia theiformis on key enzymes related to diabetes mellitus

Context: Aphloia theiformis (Vahl.) Benn. (Flacourtiaceae) (AT) is traditionally used for the management of diabetes mellitus (DM), but there is no scientific data regarding activity against enzymes linked to this condition.

Objective: To evaluate the kinetics of AT on key enzymes inhibition related to DM, and establish the antioxidant profile of AT.

Materials and methods: Dried powdered AT leaves were used to prepare crude methanol extract (70% v/v) (CME). Kinetics of CME (5000 to 156.25?μg/mL) on α-amylase, α-glucosidase, and lipase inhibition were studied. CME was partitioned using solvents of increasing polarity and kinetics of enzyme inhibition of each fraction (1000–31.25?μg/mL) was evaluated. Potent fractions were combined to assess any synergistic effect. Total phenol, flavonoid, tannin, anthocyanin contents, and antioxidant capacity of AT was evaluated using standard spectrophotometric methods.

Results: CME, ethyl acetate, and n-butanol fractions showed potent inhibitory activities against the enzymes with IC₅₀ ranging from 22.94–939.97?μg/mL. Significant (p?50 (15.72 and 157.03?μg/mL against α-amylase and lipase, respectively) was observed when ethyl acetate and n-butanol fractions were combined; showing synergism. The extracts showed noncompetitive inhibition against α-amylase and α-glucosidase. Ethyl acetate, n-butanol fractions, and CME showed highest antioxidant capacities (0.44–1.41?μg GAE/mg sample), and phenol content (211.74-675.53?μg GAE/mg sample).

Conclusion: This study supports the use of AT in the management of DM and provides the rationale for bioactivity guided isolation and characterization of compounds from the ethyl acetate and n-butanol fractions.     

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.     

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.     

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.     

In vitro studies to assess the antidiabetic,antiperoxidative, and radical scavenging potential of Stereospermum colais

Context: Stereospermum colais (Buch.-Ham. ex Dillw.) Mabberley (Bignoniaceae), which has traditional medicinal properties, is distributed all over deciduous forests. In spite of its many uses, the antidiabetic, antiperoxidative and radical scavenging activities of this species have not been assessed, and its chemical composition is scarcely known.

Objective: Antidiabetic, antiperoxidation, xanthine oxidase (XO) inhibition, and radical scavenging activities of acetone and methanol extracts of Stereospermum colais roots were investigated. Protective effects of Stereospermum colais root extract in stabilizing sunflower oil was also examined.

Materials and methods: The protective effect of acetone (ASC) and methanol (MSC) extracts of Stereospermum colais root for the potential inhibition of α-glucosidase and α-amylase enzymes were studied by in vitro method. Glycation inhibitory activity was also studied to inhibit the production of glycated end products.

Results: Compared with acarbose, ASC showed a strong inhibitory activity against α-glucosidase (IC₅₀ 61.21 µg/mL) and a moderate inhibitory activity against α-amylase (IC₅₀ 681.08 µg/mL). Glycation inhibitory activity of Stereospermum colais root extracts by using an in vitro glucose-bovine serum albumin (BSA) assay was also done and compared with standard gallic acid. ASC also shows high XO inhibition potential, free radical scavenging activities, and low p-anisidine value indicates the high medicinal potency of Stereospermum colais root.

Discussion and conclusion: These results suggest that the extract of Stereospermum colais may be interesting for incorporation in pharmaceutical preparations for human health, since it can suppress hyperglycaemia, and or as food additives due to its antiradical efficiency.     

Inhibition of p-chlorophenoxyisobutyrate by 1-methyl-2-mercaptoimidazole and related compounds

The induction of both rat liver mitochondrial α-glycerophosphate dehydrogenase (GPD) and the soluble malic enzyme by thyroid hormone is enhanced by p-chlorophenoxyisobutyrate (CPIB). CPIB also affects lipid metabolism by a mechanism which is unrelated to the thyroid hormone.The intensification of the T₄ response by CPIB was blocked by the simultaneous administration of the goitrogen, l-methyl-2-mercaptoimidazole (methimazole, MI), and this particular inhibition of CPIB by MI was shared by a number of other compounds containing the ureido or substituted ureido grouping: 1-methylimidazole, imidazole, thiourea, 2-thiouracil, 2-mercaptobenzimidazole, 2-hydroxybenzimidazole and 2- mercaptopyrimidine. However, the effect of CPIB in (a) preventing an orotic acid fatty liver, or (b) intensifying the β-lipoprotein band in serum gel electrophoresis was not inhibited by imidazole.Rat liver malic enzyme activity was increased somewhat by MI and other ureido compounds per se.     

5种口服用药方案治疗2型糖尿病的成本-效果分析

目的:评价5种口服用药方案治疗2型糖尿病患者成本-效果。方法:运用药物经济学原理对5组治疗方案,A组二甲双胍 格列吡嗪缓释片,B组二甲双胍 瑞格列奈片,C组二甲双胍 罗格列酮片,D组二甲双胍 阿卡波糖片,E组二甲双胍 格列喹酮片,进行成本-效果分析。结果:5种用药方案在疗效上差异无统计学意义(P>0.05),5组成本分别为81.24、129.59、438.85、292.49和175.79元。成本-效果比分别为0.94、1.59、4.89、3.15和1.98。B、C、D、E组相对A组的增量成本-效果比例为-10.07、51.87、31.07和33.76。结论:5种口服用药方案中,A方案从药物经济学角度分析,为治疗2型糖尿病患者较优选择。     

Impact of weight gain on outcomes in type 2 diabetes

Abstract

Background:

The majority of patients with type 2 diabetes mellitus (T2DM) are overweight or obese. Obesity is a significant risk factor for increased morbidity and mortality in people with T2DM, and increased weight has been shown to worsen glycemic control and increase the risk of diabetes progression.     

In vitro antioxidant and inhibitory potential of Terminalia bellerica and Emblica officinalis fruits against LDL oxidation and key enzymes linked to type 2 diabetes

The present study evaluated the free radical scavenging capacity and antioxidant potential of different solvent extracts (Hexane (HE), ethyl acetate (EA), methanol (ME), 70% methanol (MW) and Water (WA)) of Terminalia bellerica (TB) and Emblica officinalis (EB) fruits. Methanol extract (ME) of TB and EB fruits exhibited maximum scavenging activity against DPPH, superoxide, hydroxyl and nitric oxide radicals. Cell based antioxidant activity was assayed by flow cytometry using DCFH-DA as probe. Methanol extracts were also screened for their antidiabetic activity via inhibition of α-amylase, α-glucosidase and antiglycation assays. Results showed that ME of TB and EB can act as potent α-amylase and α-glucosidase inhibitor. Significant antiglycation activity also confirms the therapeutic potential of these extracts against diabetes. Both the extracts significantly inhibited the oxidation of LDL under in vitro conditions. Liquid chromatography-mass spectroscopy (LC-MS) analysis revealed that methanol extract of TB and EB contains ellagic acid and ascorbic acid as the major compound respectively.     

Antidiabetic activity of Diospyros peregrina fruit: Effect on hyperglycemia, hyperlipidemia and augmented oxidative stress in experimental type 2 diabetes

Diospyros peregrina is an edible fruit of costal West-Bengal. The present investigation was undertaken to evaluate the role of aqueous extract of D. peregrina fruit in streptozotocin–nicotinamide induced type 2 diabetic rats. Oral administration of extract at the doses of 50 and 100 mg/kg body weight per day for 28 days to diabetic rats was found to possess significant dose dependant hypoglycemic and hypolipidemic activity. An increased reactive oxygen species and insufficient antioxidant activity is associated with diabetes mellitus, which is mainly responsible for diabetic pathogenesis. The role of extract on antioxidant markers of liver and kidney were estimated. The diabetic rats exhibited lower activities of superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) content in hepatic and renal tissues as compared with normal rats. The activities of SOD, CAT, and GSH were found to be increased in extract treated diabetic rats in selected tissues. The increased level of lipid peroxidation (thiobarbituric acid reactive substances and hydroperoxide) in diabetic rats was also found to be reverted back to near normal status in extract treated groups.     

Understanding adherence to medications in type 2 diabetes care and clinical trials to overcome barriers: a narrative review

Aim:

To identify factors affecting adherence to medications in type 2 diabetes (T2D) care and clinical trials.

Background:

Adherence to medication is associated with better patient outcomes, lower healthcare costs, and improved quality and robustness of trial data. In T2D, non-adherence to regimens may compromise glycemic, blood pressure and lipid control, which can, in turn, increase morbidity and mortality rates.

Design:

A literature search was performed to identify studies reporting adherence to medications and highlighting specific adherence challenges/approaches in T2D. The search was limited to clinical trials, comparative studies or meta-analyses, reported in English with a freely available abstract.

Data source:

MEDLINE (31 December 2008 to 31 December 2013).

Review methods:

Studies not reporting adherence to medications or highlighting adherence challenges/approaches in T2D, presenting only self-reported adherence or including fewer than 100 patients were excluded. Eligible reports are discussed narratively.

Results:

Factors identified as having a detrimental impact on adherence were smoking, depression and polypharmacy. Conversely, increased convenience (e.g. pen compared with vial and syringe; medication supplied by mail order vs. retail pharmacy) was associated with better patient adherence, as were interventions that increased patient motivation (e.g. individualized, nurse-led consultation) and education.

Conclusions:

Medication adherence is influenced by complex and multifactorial issues, which can include smoking, depression, polypharmacy, convenience of obtaining and administering the medication, patient motivation and education. We recommend simplifying treatment regimens, where possible, improving provider–patient communication, and providing support and education to increase medication adherence, with a view to improving patient outcomes and clinical trial data quality.     

抗2型糖尿病药西他列汀关键手性中间体的合成研究

目的合成2型糖尿病治疗药西他列汀的关键手性中间体。方法以2,4,5-三氟苯乙酸为原料,与2,2-二甲基-1,3-二烷-4,6-二酮缩合、脱羧得到3-氧代-4-(2,4,5-三氟苯基)丁酸甲酯,然后与R-α-苯乙胺缩合、不对称还原、脱除苄基保护基,再经Boc保护、水解得到西他列汀关键手性中间体(R)-3-(叔丁氧羰基氨基)-4-(2,4,5-三氟苯基)丁酸。结果与结论以总收率59.5%合成了西他列汀关键手性中间体,该合成路线具有步骤少、操作简便、收率高、立体选择性好、反应条件温和的特点。     

蒺藜皂苷对正常和2型糖尿病大鼠餐后血糖水平的影响

目的研究蒺藜皂苷（STT）对正常和2型糖尿病大鼠餐后血糖水平的影响及可能机理。方法正常和2型糖尿病大鼠灌胃蔗糖或葡萄糖,同时灌胃STT,60 min后,尾静脉采血,测定血糖浓度;提取大鼠小肠α-葡萄糖苷酶,体外测定STT对酶活性的抑制作用。结果正常和2型糖尿病大鼠灌胃蔗糖同时灌胃STT 60min后,血糖水平显著低于对照,分别为对照的70.19%（P〈0.001）和68.05%（P〈0.001）,但STT对灌胃葡萄糖后血糖水平的变化无显著性影响;0.1、1、10 mg/mL的STT能够显著抑制α-葡萄糖苷酶的体外活性（P〈0.001）,抑制率分别为20.83%、43.73%和52.62%。结论STT能够显著降低正常和2型糖尿病大鼠餐后血糖水平的升高,其可能机理为对小肠α-葡萄糖苷酶的抑制作用。     

Inhibition of Staphylococcus Aureus Mediated by Extracts from Iranian Plants

In order to find new antibacterial agents effective against Staphylococcus aureus, ethanolic extracts of 10 plants were tested. S. aureus (489 samples) were isolated either from healthy carriers (nose and throat) or clinical samples. Out of 489 isolates tested, 98.6% were sensitive to trimethoprim-sulfamethoxazole which was used as the reference antibiotic. From the plant extracts screened for antibacterial activity, Myrtus communis L. (leaves) had the greatest activity, inhibiting the growth of 99% of the isolates. Glycyrrhiza glabra L., Eucalyptus globolus Labill and Menta viridis L., were also active against the isolates inhibiting the growth of 90, 59.5 and 48.7% of the isolates, respectively. All of these extracts were active against the reference strains of S. aureus tested. Saturia hortensis L., Teucrium polium L., and Achillea santolina L., had very little antibacterial activity, while Trigonella foenum graecum L., Echium amoenum Fisch & Mey (flowers) and Juglans regia L. (leaves), had no antibacterial activity against the bacterial isolates.     

GFT505 for the treatment of nonalcoholic steatohepatitis and type 2 diabetes

Introduction: PPARs are nuclear receptors that play key roles in the regulation of metabolism and inflammation. GFT505 is a new dual agonist of the PPARα and PPARδ isoforms, which improves lipid and glucose metabolism in type 2 diabetes mellitus (T2DM) and exerts hepatoprotective effects in mouse models of nonalcoholic fatty liver disease (NAFLD).

Areas covered: This evaluation focuses on the pharmacology and clinical activity of GFT505 in metabolic diseases, including T2DM, dyslipidemia and NAFLD, as well as its promise as a therapeutic option for the treatment of nonalcoholic steatohepatitis. Original publications in English were selected, as well as abstracts of presentations in international congresses. Ongoing clinical trials were identified using the Clinicaltrial.gov database.

Expert opinion: Results from the completed short-term (4 – 8 weeks) Phase IIa studies indicate that GFT505 decreases plasma triglyceride levels and increases high-density lipoprotein-cholesterol, while lowering low-density lipoprotein-cholesterol in prediabetic patients. Hyperinsulinemic–euglycemic clamp studies have also demonstrated an insulin-sensitizing effect of GFT505, with a strong effect on the liver, with a significant lowering effect on plasma liver enzymes. The current safety profile is reassuring, without any signs of PPARγ-related side effects. The combination of its insulin sensitizing and hepatoprotective effects makes GFT505 an excellent drug candidate for NAFLD.