Association of hypertriglyceridemic waist phenotype with metabolic syndrome traits and its diagnostic potential to predict metabolic syndrome in adults with excess body weight: A community-based cross-sectional study.

BACKGROUND: The hypertriglyceridemic waist (HTGW) phenotype is a simple measure to identify individuals at increased risk of metabolic syndrome (MetS) traits. The present study aimed to describe the HTGW prevalence, and its associations with MetS traits, and also determine the diagnostic potential of the mirror indices of HTGW phenotype to predict MetS and its components in community-dwelling adults with overweight or obesity in Southern, Sri Lanka. METHODS: In a cross-sectional study, 300 adults with excess body weight (body mass index >23 kg/m2) were enrolled and examined for the HTGW phenotype (fasting plasma triglyceride concentration ≥1.695 mmol/L and waist circumference >90 and >85 cm in males and females, respectively). RESULTS: One in five adults with excess body weight had the HTGW phenotype. Phenotype-positive adults had significantly higher fasting plasma glucose (FPG) (p = 0.010), low-density lipoprotein cholesterol (HDL-C) (p < 0.001), total cholesterol (p < 0.001), atherogenic index (p < 0.001), coronary risk index (p = 0.001), triglyceride glucose index (p = 0.040), bioimpedance visceral fat (p = 0.041) and significantly lower HDL-C (p = 0.001) and cardioprotective index (p = 0.009) than those without the HTGW phenotype. Adults with excess body weight and the HTGW phenotype had an increased risk of FPG (odds ratio [OR] = 1.294; 95% confidence interval [CI] 1.051-1.594), atherogenic index (OR = 3.138; 95% CI = 1.559-6.317) and triglyceride glucose index (OR = 3.027; 95% CI = 1.111-8.249). The HTGW phenotype was strongly associated with MetS traits (OR = 16.584; 95% CI = 6.230-44.147). The cut-off values for the product of waist circumference × triglyceride, to identify the risk of having MetS and dyslipidemia among adults with excess body weight were 158.66 and 160.15 cm × mmol/L, respectively. CONCLUSIONS: The readily available and inexpensive measures of the HTGW phenotype could serve as a clinically useful marker to identify MetS traits in adults with excess body weight.

Gelatine nanoparticles encapsulating three edible plant extracts as potential nanonutraceutical agents against type 2 diabetes mellitus.

AIM: To optimise, and characterise gelatine nanoparticles (GNPs) encapsulating plant extracts and evaluate the glucose-lowering potential. METHODS: GNPs encapsulating plant extracts were prepared by desolvation method followed by adsorption. The GNPs were characterised by loading efficiency, loading capacity, particle size, zeta potential, SEM and FTIR. The glucose-lowering activity of GNPs was determined using oral glucose tolerance test in high-fat diet fed streptozotocin-induced Wistar rats. RESULTS: Loading efficiency and capacity, particle mean diameter, and zeta potential of optimised GNPs 72.45 ± 13.03% w/w, 53.05 ± 26.16% w/w, 517 ± 48 nm and (-)23.43 ± 9.96 mV respectively. GNPs encapsulating aqueous extracts of C. grandis, S. auriculata, and ethanol 70% v/v extracts of M. koenigii showed glucose-lowering activity by 17.62%, 11.96% and 13.73% (p < 0.05) compared to the non-encapsulated extracts. FTIR analysis confirmed the encapsulation of phytoconstituents into GNPs. SEM imaging showed spherical GNPs (174 ± 46 nm). CONCLUSION: GNPs encapsulating plant extracts show promising potential to be developed as nanonutraceuticals against diabetes.

Synthesis and bioactivity assessment of Coccinia grandis L. extract encapsulated alginate nanoparticles as an antidiabetic drug lead.

AIM: This study aimed to prepare, characterise, and evaluate the antidiabetic activity of Coccinia grandis (L.) extracts encapsulated alginate nanoparticles. METHODS: Alginate nanoparticles were prepared using the ionic gelation method and characterised by encapsulation efficiency %w/w, loading capacity %w/w, particle size analysis, zeta potential, Fourier transform infra-red spectroscopy (FTIR), and scanning electron microscopy (SEM). In vitro antidiabetic activity was also evaluated. RESULTS: Encapsulation efficiency %w/w, loading capacity %w/w, mean diameter, zeta potential of C. grandis encapsulated alginate nanoparticles ranged from 10.51 ± 0.51 to 62.01 ± 1.28%w/w, 0.39 ± 0.04 to 3.12 ± 0.11%w/w, 191.9 ± 76.7 to 298.9 ± 89.6 nm, -21.3 ± 3.3 to -28.4 ± 3.4 mV, respectively. SEM and FTIR confirmed that particles were in nano range with spherical shape and successful encapsulation of plant extracts into an alginate matrix. The antidiabetic potential of aqueous extract of C. grandis encapsulated alginate nanoparticles (AqCG-ANP) exhibited inhibition in α-amylase, α-glucosidase and dipeptidyl peptidase IV enzymes of 60.8%c/c, 19.1%c/c, and 30.3%c/c, respectively, compared to the AqCG. CONCLUSION: The AqCG-ANP exerted promising antidiabetic potential as an antidiabetic drug lead.

Bael (Aegle marmelos L. Correa) fruit extracts encapsulated alginate nanoparticles as a potential dietary supplement with improved bioactivities.

Nanoencapsulated bael fruit (Aegle marmelos L. Correa (Family: Rutaceae)) extracts reveal novel prospects in the development of dietary supplements with improved biological activities in the field of the food industry. The main objectives of this study were to prepare and characterize aqueous, ethanol, 50% ethanol, and 50% acetone extracts of bael fruit encapsulated alginate nanoparticles and investigate the effect of encapsulation on in vitro release of polyphenols, antidiabetic, antioxidant, and anti-inflammatory activities, and their stability. Bael fruit extracts encapsulated alginate nanoparticles were prepared using the ionic gelation method. Characterization, in vitro release profiles of polyphenols, determination of antidiabetic, anti-inflammatory, antioxidant activity, and accelerated stability were conducted. The results of the characterization confirmed the successful encapsulation of extracts of bael fruit in the alginate matrix. The aqueous extract of bael fruit encapsulated alginate nanoparticles exhibited a more controlled slow-release profile, accounting for 21.82% ± 1.17% and 48.14% ± 0.52% of polyphenols at solutions of pH 1.2 and pH 6.8, respectively. In general, the results of the bioactivity assessment suggested that nanoencapsulation could facilitate the enhancement of its antidiabetic, antioxidant, and anti-inflammatory properties. The results of thermogravimetric analysis and thin layer chromatography fingerprint showed the stability of aqueous bael fruit extract encapsulated alginate nanoparticles at 27 and 4°C over a month. In summary, the results of this study revealed the potency of nanoencapsulated aqueous extract of bael fruit to develop a dietary supplement with improved antidiabetic, antioxidant, and anti-inflammatory activities. PRACTICAL APPLICATION: The encapsulation of bael fruit extracts into a nanocarrier enhances bioactivities and promotes the controlled release of bioactive compounds. This could be useful in the future food industry, based on scientifically proven data, and inspire the market by means of the development of dietary supplements. Overall, the results would facilitate the formulation of novel commercially elegant nanoencapsulated dietary supplements with improved potential to manage a healthy life.

Herbal Extracts Encapsulated Nanoliposomes as Potential Glucose-lowering Agents: An in Vitro and in Vivo Approach Using Three Herbal Extracts.

Encapsulation of polyphenol-rich herbal extracts into nanoliposomes is a promising strategy for the development of novel therapeutic agents against type 2 diabetes mellitus. An attempt was made to encapsulate aqueous, ethanol, and aqueous ethanol (70% v/v) extracts of Senna auriculata (L.) Roxb., Murraya koenigii (L.) Spreng,. and Coccinia grandis (L.) Voigt into nanoliposomes and to screen acute bioactivities in vitro and in vivo. A wide spectrum of bioactivity was observed of which aqueous extracts encapsulated nanoliposomes of all three plants showed high bioactivity in terms of in vivo glucose-lowering activity in high-fat diet-fed streptozotocin induced Wistar rats, compared to respective free extracts. The particle size, polydispersity index, and zeta potential of the aforementioned nanoliposomes ranged from 179-494 nm, 0.362-0.483, and (-22) to (-17) mV, respectively. The atomic force microscopy (AFM) imaging reflected that the nanoparticles have desired morphological characteristics and Fourier-transform infrared (FTIR) spectroscopy analysis revealed successful encapsulation of plant extracts into nanoparticles. However, only the S. auriculata aqueous extract encapsulated nanoliposome, despite the slow release (9% by 30 hours), showed significant (p < 0.05) in vitro α-glucosidase inhibitory activity and in vivo glucose-lowering activity compared to free extract, proving worthy for future investigations.

Association of dietary intake with body mass index and glycemic profile among newly diagnosed patients with type 2 diabetes mellitus.

INTRODUCTION: Dietary intake plays an important role in determining body mass index (BMI) and glycemic profile in patients with type 2 diabetes mellitus (T2DM). Our aim was to describe habitual dietary intake and its associations with BMI and glycemic profile in a cohort of patients with newly diagnosed T2DM in Sri Lanka. METHODS: A cross-sectional study was carried out among 158 patients with newly diagnosed T2DM in Galle, Sri Lanka. Data on demographic, lifestyle, and family history of diabetes mellitus, and clinical measures were collected. The dietary information was collected using a 24-h dietary recall. RESULTS: Among the total number of study subjects, only 12.0%, 5.7% and 1.3% met the recommended daily consumption value of protein, fat, and fiber, respectively, whereas 99.4% of subjects had taken carbohydrates that exceeded the recommended consumption. There was a positive association between carbohydrate intake and BMI (0.004, [0.002], p = .048) and carbohydrate intake and glycated hemoglobin (HbA1C ) (0.001, [0.000], p = .049). Fat intake showed positive associations with BMI (0.029, [0.011], p = .006) and HbA1C (0.005, [0.002], p = .050). Protein intake showed a positive association with HbA1C (0.006, [0.003], p = .023). The aforementioned associations were observed after adjusting for demographic, lifestyle, and history of diabetes among the first-degree family members. The carbohydrate intake was positively associated with BMI (0.010, [0.003], p = .003) and HbA1C (0.001, [0.000], p = .050) with further adjustment in nutrient intake (except when used as an independent variable). Furthermore, the fat intake was associated with BMI (0.031, [0.011], p = .004) and HbA1C (0.005 [0.002], p = .050) with additional adjustments. CONCLUSIONS: The diet of the majority of newly diagnosed T2DM patients in this cohort consisted of a higher carbohydrate intake than the recommended level. However, they did not meet the recommended daily intake of protein, fat, and fiber. Both carbohydrate and fat intake were significantly and positively associated with BMI and HbA1C in patients with newly diagnosed T2DM.

In vitro antioxidant activity of alginate nanoparticles encapsulating the aqueous extract of Coccinia grandis L.

Bioactive compounds in medicinal plants are more susceptible to preventing oxidative stress. Encapsulation of herbal extracts has empowered the properties and characteristics of bioactive compounds. Nanoencapsulation allows the enhancement of the stability of extracts and targeted drug delivery. The present study aims to determine the antioxidant activity of alginate nanoparticles encapsulating the aqueous extract of Coccinia grandis L. (Family: Cucurbitaceae). The aqueous extract of C. grandis (AqCG) was prepared by using ultrasonication (40 °C, 20 min, 40 kHz) followed by refluxing (2½ h). The prepared AqCG (1-5 mg/mL) encapsulated alginate nanoparticles were synthesized by ionic gelation with the addition of extracts and CaCl2. Characterization of nanoparticles was performed via encapsulation efficiency (EE%), loading capacity (LC%), particle size (PS), scanning electron microscopy (SEM), zeta potential and Fourier transform infrared (FTIR) spectroscopy analysis. The antioxidant activity of the nanoparticles was evaluated in vitro by the ferric reducing antioxidant (FRAP) assay, 2,2-di-phenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assay. One-way analysis of variance (ANOVA) followed by Tukey's posthoc test was used to analyze the data. Maximum LC% (3.07 ± 0.11) and average particle size (71 nm from SEM) were obtained for alginate nanoparticles encapsulated at 4 mg/mL extract concentration. The IC50 values for DPPH, ABTS, and FRAP were 6.49 ± 0.10 mg/mL, 0.24 ± 0.01 mg/mL, and 20.63 ± 0.28 mg Trolox equivalent/g of extract respectively for alginate nanoparticles encapsulating the AqCG. Nanoparticles have shown a significant difference in IC50 values compared to Trolox (p < 0.05). The successful encapsulation of the AqCG in the alginate matrix was evidenced by FTIR and SEM analysis. Encapsulation contributed to enhancing the antioxidant activity in terms of ABTS assay when compared to the AqCG. However, in vitro release and stability studies are warranted to facilitate the development of a commercially viable nanonutraceutical using alginate nanoparticles encapsulating the AqCG.

Nanoformulation of Plant-Based Natural Products for Type 2 Diabetes Mellitus: From Formulation Design to Therapeutic Applications.

Background: Herbal remedies are used to manage type 2 diabetes mellitus (type 2 DM) as the sole treatment or as a complementary therapy. Limitations of herbal remedies, such as poor stability and limited absorption, impede their development as therapeutic agents, which could be overcome by nanoformulations. Objectives: This review attempts to summarize the studies reported between 2009 and 2020 in the development of medicinal plant-based nanoformulations for the management of type 2 DM, discuss formulation methods, mechanisms of action, and identify gaps in the literature to conduct future research on nanoparticle-based herbal treatment options targeting type 2 DM. Methods: To retrieve articles published between January 2009 and December 2020, the electronic databases PubMed, Science Direct, and Google Scholar were searched with the keywords nanoparticle, plant, and diabetes in the entire text. Peer-reviewed research articles on herbal nanoformulations published in English-language based on in vitro and/or in vivo models of type 2 DM and/or its complications were included. The literature search and selection of titles/abstracts were carried out independently by 2 authors. The list of full-text articles was selected considering inclusion and exclusion criteria, with the agreement of all the authors. Results: Among the reported studies, 68% of the studies were on inorganic herbal nanoformulations, whereas 17% and 8% were of polymer-based and lipid-based herbal nanoformulations, respectively. Some of the important biological properties of nanoformulations included improvement in glycemic control and insulin levels, inhibition of the formation of advanced glycation end products, and regeneration of pancreatic ß cells. The aforementioned properties were observed by screening nanoformulations using in vitro cellular and noncellular models, as well as in vivo animal models of type 2 DM studied for acute or subacute durations. Only 2 clinical trials with patients with diabetes were reported, indicating the need for further research on medicinal plant-based nanoformulations as a therapeutic option for the management of type 2 DM. Conclusions: Medicinal plant extracts and isolated compounds have been nanoformulated using various methods. The properties of the nanoformulations were found superior to those of the corresponding herbal extracts and isolated compounds. At both the preclinical and clinical levels, there are a number of poorly explored research areas in the development and bioactivity assessment of herbal nanoformulations. (Curr Ther Res Clin Exp. 2022; 83:XXX-XXX) © 2022 Elsevier HS Journals, Inc.

Herbal Medicines Targeting the Improved ß-Cell Functions and ß-Cell Regeneration for the Management of Diabetes Mellitus.

There is an increasing trend of investigating natural bioactive compounds targeting pancreatic ß-cells for the prevention/treatment of diabetes mellitus (DM). With the exploration of multiple mechanisms by which ß-cells involve in the pathogenesis of DM, herbal medicines are gaining attention due to their multitasking ability as evidenced by traditional medicine practices. This review attempts to summarize herbal medicines with the potential for improvement of ß-cell functions and regeneration as scientifically proven by in vivo/in vitro investigations. Furthermore, attempts have been made to identify the mechanisms of improving the function and regeneration of ß-cells by herbal medicines. Relevant data published from January 2009 to March 2020 were collected by searching electronic databases "PubMed," "ScienceDirect," and "Google Scholar" and studied for this review. Single herbal extracts, polyherbal mixtures, and isolated compounds derived from approximately 110 medicinal plants belonging to 51 different plant families had been investigated in recent years and found to be targeting ß-cells. Many herbal medicines showed improvement of ß-cell function as observed through homeostatic model assessment-ß-cell function (HOMA-ß). Pancreatic ß-cell regeneration as observed in histopathological and immunohistochemical studies in terms of increase of size and number of functional ß-cells was also prominent. Increasing ß-cell mass via expression of genes/proteins related to antiapoptotic actions and ß-cell neogenesis/proliferation, increasing glucose-stimulated insulin secretion via activating glucose transporter-2 (GLUT-2) receptors, and/or increasing intracellular Ca2+ levels were observed upon treatment of some herbal medicines. Some herbal medicines acted on various insulin signaling pathways. Furthermore, many herbal medicines showed protective effects on ß-cells via reduction of oxidative stress and inflammation. However, there are many unexplored avenues. Thus, further investigations are warranted in elucidating mechanisms of improving ß-cell function and mass by herbal medicines, their structure-activity relationship (SAR), and toxicities of these herbal medicines.

Value of simple clinical parameters to predict insulin resistance among newly diagnosed patients with type 2 diabetes in limited resource settings.

BACKGROUND: Insulin resistance (IR) has been considered as a therapeutic target in the management of type 2 diabetes mellitus (T2DM). Readily available, simple and low cost measures to identify individuals with IR is of utmost importance for clinicians to plan optimal management strategies. Research on the associations between surrogate markers of IR and routine clinical and lipid parameters have not been carried out in Sri Lanka, a developing country with rising burden of T2DM with inadequate resources. Therefore, we aimed to study the utility of readily available clinical parameters such as age, body mass index (BMI), waist circumference (WC) and triglyceride to high density lipoprotein cholesterol ratio (TG/HDL-C) in the fasting lipid profile in predicting IR in a cohort of patients with newly diagnosed T2DM in Sri Lanka. METHODS AND FINDINGS: We conducted a community based cross sectional study involving of 147 patients (age 30-60 years) with newly diagnosed T2DM in a suburban locality in Galle district, Sri Lanka. Data on age, BMI, WC, fasting plasma glucose (FPG) concentration, fasting insulin concentration and serum lipid profile were collected from each subject. The indirect IR indices namely homeostasis model assessment (HOMA), quantitative insulin sensitivity check index (QUICKI) and McAuley index (MCA) were estimated. Both clinical and biochemical parameters across the lowest and the highest fasting insulin quartiles were compared using independent sample t-test. Linear correlation analysis was performed to assess the correlation between selected clinical parameters and indirect IR indices. The area under the receiver operating characteristic (ROC) curve was obtained to calculate optimal cut-off values for the clinical markers to differentiate IR. BMI (p<0.001) and WC (p = 0.01) were significantly increased whereas age (p = 0.06) was decreased and TG/HDL-C (p = 0.28) was increased across the insulin quartiles. BMI and WC were significantly correlated (p<0.05) with HOMA, QUICKI and MCA. Out of the clinical parameters, age showed a borderline significant correlation with QUICKI and TG/HDL-C showed a significant correlation only with MCA. The area under ROC of BMI was 0.728 (95% CI 0.648-0.809; p<0.001) and for WC, it was 0.646 (95% CI 0.559-0.734; p = 0.003). The optimized cut-off value for BMI and WC were 24.91 kg/m2 and 81.5 cm respectively to differentiate the patients with IR or ID. Study limitations include small sample size due to recruitment of patients only from a limited geographical locality of the country and not totally excluding of the possibility of inclusion of some patients with slowly progressive type 1 DM or Latent onset diabetes of adulthood from the study population. CONCLUSIONS: The results revealed that there was a significant positive correlation between BMI, WC and HOMA while a significant negative correlation with QUICKI and MCA among the cohort of patients with newly diagnosed T2DM. The cut-off values of BMI and WC as 24.91 kg/m2 and 81.5 cm respectively could be used as simple clinical parameters to identify IR in newly diagnosed patients with T2DM. Our results could be beneficial in rational decision making in the management of newly diagnosed patients with T2DM in limited resource settings.

Antidiabetic Activity of Widely Used Medicinal Plants in the Sri Lankan Traditional Healthcare System: New Insight to Medicinal Flora in Sri Lanka.

The use of medicinal plant extracts and their isolated bioactive compounds for the management of diabetes mellitus has been tremendously increased in recent decades. The present study aimed at providing in-depth information on medicinal flora that has been widely used in the Sri Lankan traditional healthcare system for the management of diabetes mellitus. The data of this review article were obtained from published articles from January 2000 to September 2020 in scientific databases of PubMed, Web of Science, and Google Scholar. In this review, a total number of 18 medicinal plants with the antidiabetic activity were expressed, and their isolated antidiabetic active compounds were highlighted as new drug leads. Results of the reported studies revealed that medicinal plants exert a potent antidiabetic activity via both in vitro and in vivo study settings. However, bioactive compounds and antidiabetic mechanism (s) of action of many of the reported medicinal plants have not been isolated/elucidated the structure in detail, to date. Reported antidiabetic medicinal plants with other properties such as antioxidant and antihyperlipidemic activities deliver new entities for the development of antidiabetic agents with multiple therapeutic targets. This is a comprehensive review on potential antidiabetic activities of the Sri Lankan medicinal plants that have been widely used in the traditional healthcare system. The information presented here would fill the gap between the use of them by traditional healers in the traditional medicine healthcare system in Sri Lanka and their potency for development of new drug entities in future.

Optimization of 25% Sulfosalicylic Acid Protein-to-Creatinine Ratio for Screening of Low-Grade Proteinuria.

Proteinuria is an important prognostic marker in the diagnosis and management of kidney diseases. Sulfosalicylic acid method (SSA) is a simple, low cost, qualitative test, widely used to assess proteinuria. The aim of this study was to optimize SSA test as a quantitative screening tool to assess proteinuria at lower excretory levels which would facilitate the screening and early diagnosis of renal impairment using protein-to-creatinine ratio (PCR). The study was conducted in two phases. In phase I, optimum SSA percentage to detect low-grade proteinuria was selected by comparing the performance of 3%, 6%, and 25% SSA methods in manual spectrophotometric analysis. In phase II, clinical applicability of the optimized method was evaluated using retained urine samples of patients with chronic kidney disease (CKD) assessed for urine protein by the pyrogallol red (PGR) method in a tertiary care hospital in Sri Lanka. Optimized 25% SSA protein-to-creatinine ratio (PCR) was compared with PGR PCR and albumin-to-creatinine ratio (ACR). Sensitivity, specificity, degree of agreement, correlation, and diagnostic accuracy were evaluated. Turbidimetric analysis using 25% SSA was linear in the range 3-50 mg/dL giving the highest analytical sensitivity. The test yielded a sensitivity of 86.5% and specificity of 96.5% and a degree of agreement of 5 mg/dL with the PGR method. Optimal cut-off for 25% SSA PCR in receiver operating characteristic analysis was 166 mg/g. Spearman's correlation coefficient for 25% SSA PCR versus ACR was r = 0.823, p < 0.0001, and for 25% SSA PCR versus PGR PCR was r = 0.913, p < 0.0001. The 25% SSA PCR has a sensitivity of 92% against ACR, the current prognostic marker for proteinuria in patients with CKD. The 25% SSA test is a simple method, and it performs satisfactorily as a screening test with a cut-off for PCR optimized at 166 mg/g. The test merits further evaluation due to its low cost.

Effect of Sample Volume Variation and Delay in Analysis on Plasma Glucose Concentration in Sri Lankan Healthy Adults.

The correct volume of sample and time of storing prior to the analysis are important considerations in the estimation of plasma glucose concentration of patients. The present study was to determine the effect of sample volume variation and time delay in the analysis of plasma glucose results in healthy adults. A total of 30 individuals aged between 20 and 30 years were selected for the study. Blood samples were collected into three fluoride-oxalate collection tubes separately. The results revealed that the sample volume variation from 2.0 mL fluoride-oxalate tube to 1.0 mL and 3.0 mL did not significantly affect the plasma glucose concentration (p > 0.05). However, the plasma glucose concentration in the sample significantly decreased upon delaying the analysis. The mean fasting plasma glucose concentration of analysis after one hour of collection and analysis after three hours of collection was not significantly different (p > 0.05). The mean fasting plasma glucose concentrations between one hour and five hours timepoints after collection (p < 0.001) and between three hours and five hours after collection (p = 0.014) were significantly different. In conclusion, overfilling and underfilling (2.0 ± 1.0 mL) of fluoride-oxalate tubes did not affect the plasma glucose results significantly. If the samples are analyzed within three hours of collection, the time dependent change too is not statistically significant.

Efficacy and safety of a herbal drug of Coccinia grandis (Linn.) Voigt in patients with type 2 diabetes mellitus: A double blind randomized placebo controlled clinical trial.

BACKGROUND: Several lines of preclinical studies have shown promising antidiabetic effects of the aqueous leaves extract of Coccinia grandis (Linn.) Voigt (Cucurbitaceae) in vivo and in vitro. PURPOSE: The present study was conducted to evaluate the efficacy and safety of a newly developed herbal formulation of C. grandis in newly diagnosed patients with type 2 diabetes mellitus (T2DM). STUDY DESIGN: A three months long, randomized, double blind, placebo controlled clinical trial in patients with newly diagnosed T2DM. METHOD: Based on fasting plasma glucose (FPG) concentration, a total number of 158 newly diagnosed patients with T2DM (45 ± 15 years age) were recruited for the present trial from the University Medical Clinic, Teaching Hospital, Karapitiya, Galle, Sri Lanka. They were randomly assigned to the test or placebo group to receive 500 mg of herbal drug (n = 79) or placebo drug (n = 79) once daily for three months. Patients and investigators were blinded for the treatment. Percentage of glycated hemoglobin (HbA1C %), insulin and lipid profile parameters were estimated at the base line and at the end of the intervention. Serum concentration of fructosamine was assessed at every other visit of the trial. The homeostatic model assessment for insulin resistance (HOMA-IR), atherogenic index (AI), cardio-protective index (CPI) and coronary risk index (CRI) were calculated. Furthermore, fasting plasma glucose concentration, renal and liver toxicity parameters, hematological parameters, blood pressure (BP) were assessed throughout the study in two weekly intervals till the end of three months. RESULTS: Out of 158, a total number of 145 patients completed the entire clinical trial period successfully. Mean (SD) changes of variables from the baseline to the end of the intervention in test and placebo groups were 0.65 (0.54) and 0.08 (0.66) for HbA1C % (p < 0.001), 1.91 (3.07) and -1.28 (9.77) for insulin (p < 0.001), 0.02 (0.03) and -0.01 (0.04) for frucosamine (p < 0.001), 1.51 (0.49) and 0.05 (0.50) for FPG (p < 0.001), 1.73 (1.36) and -0.37 (3.38) for HOMA-IR (p < 0.001), 0.16 (0.18) and -0.04 (0.42) for TG (p < 0.001), 0.07 (0.08) and -0.02 (0.19) for VLDL-C (p < 0.001), respectively. However, the herbal drug of C. grandis was unable to change other outcome variables significantly when compared to the placebo (p > 0.05). All the renal, liver and toxicity parameters, hematological parameters and BP were within the normal physiological reference ranges at each visit. CONCLUSION: Treatment with herbal drug of C. grandis (500 mg per day) for three months for patients with newly diagnosed T2DM significantly improved their glycemic and selected lipid profile parameters with well tolerated safety.

Dual mechanisms of a Sri Lankan traditional polyherbal mixture in the improvement of pancreatic beta cell functions and restoration of lipoprotein alterations in streptozotocin induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional polyherbal preparations have been utilized in Sri Lanka since ancient times and have gained a wide acceptance throughout the country. Although an extensive body of evidence supports the use of traditional herbal mixtures in the treatment of diabetes mellitus, only a few polyherbal mixtures have been subjected to systematic scientific investigations and their mechanisms for long-term glucose control remain unclear. In general, scientific evaluations of the effectiveness of antidiabetic formulations which are prescribed by traditional practitioners have received great attention, and therefore uncovering their mechanism of action would be beneficial. AIM: The aim of the present study was to investigate the therapeutic efficacy, in terms of antidiabetic and antihyperlipidaemic activities, of a well-known traditional polyherbal mixture composed of leaves of Murraya koenigii L., -cloves of Allium sativum L., - fruits of Garcinia quaesita Pierre and seeds of Piper nigrum L. in streptozotocin induced diabetic rats. MATERIALS AND METHODS: Equal amounts from each of the above plant parts (100 g) were mixed together and extracted into cold water, hot water (3 h, refluxed) and water-acetone (1:1) separately. Dose response study of cold water, hot water, and water-acetone extracts of the polyherbal mixture at three selected doses of 0.5 g/kg, 1.0 g/kg and 1.5 g/kg was conducted in streptozotocin (STZ) induced diabetic rats. Based on the dose response data, hot water and water-acetone extracts at the therapeutic dose of 1.0 g/kg were administered to STZ induced diabetic rats (n = 6/group) daily for 30 days in the long-term study. Glibenclamide (0.5 mg/kg) was used as the positive control. Glycaemic parameters, pancreatic ß cell restoration, and lipid profile were evaluated in diabetic rats treated with the plant extract mixture. HPLC fingerprints of hot water and water-acetone extracts of the polyherbal mixture were compared with those of extracts of individual plants with the respective solvents, in the standardisation protocol. RESULTS: The hot water and water-acetone extracts were shown to be active in the dose response study and 1.0 g/kg was selected for the long term study. Treatment with the hot water and water-acetone extracts of the polyherbal mixture and glibenclamide significantly lowered the glycated haemoglobin by 19%, 26%, and 43%, respectively, at the end of the intervention (p < 0.05). The serum insulin concentration was significantly increased (p < 0.05) upon the plant treatment, corroborating the evidence of ß-cell restoration in the pancreas of H and E stained sections. Moreover, the above extracts reported an impressive restoration of lipoproteins in diabetic rats compared to the diabetic control rats. The homeostatic assessment of ß-cell functions (HOMA-ß) was also improved in rats treated with the hot water and water-acetone extracts of the polyherbal mixture. The HPLC fingerprints of the polyherbal mixture and the individual plants showed shifts in some peaks and formation of new peaks. CONCLUSION: The results revealed that the aforementioned polyherbal mixture possesses potent antihyperglycaemic and antihyperlipidaemic effects with considerable restoration of pancreatic ß-cells, justifying the traditional use of the mixture in diabetes associated dyslipidaemia.

Acute and Subchronic Toxicity Profile of a Polyherbal Drug Used in Sri Lankan Traditional Medicine.

A polyherbal drug composed of leaves of Murraya koenigii L. Spreng, cloves of Allium sativum L., fruits of Garcinia quaesita Pierre, and seeds of Piper nigrum L. is a popular drug which has been used by indigenous practitioners in Sri Lanka for the treatment of diabetes mellitus and dyslipidemia. The acute toxicity assessment was conducted, following a single oral dose of 0.25-2.0 g/kg in healthy rats, and rats were observed up to 14 days. The hot water extract (1.0 g/kg) and the water : acetone extract (0.5, 1.0, and 1.5 g/kg) were administered to Wistar rats for 28 days in the subchronic study. Hypoglycemic and antihyperglycemic activities (dose response studies) of cold water, hot water, and water : acetone extracts of the polyherbal mixture were evaluated at the doses of 0.5, 1.0, and 1.5 g/kg in healthy and streptozotocin-induced diabetic rats (70 mg/kg, ip), respectively. Acute toxicity study showed that the polyherbal drug did not cause any change in animals throughout the experimental period of 14 days. The administration of the hot water extract and the water : acetone extract of the polyherbal drug for 28 days did not produce changes in the selected biochemical and hematological parameters in Wistar rats (p > 0.05). The histological assessment corroborated the biochemical findings with no significant treatment-related changes in the kidney and liver. The treatment of polyherbal drug significantly lowered the serum glucose concentration compared to the diabetic control rats (p < 0.05) while it did not lead to a severe reduction of glucose concentration in healthy rats. The hot water and water : acetone extracts of the polyherbal drug showed a statistically significant improvement on total area under the glucose tolerance curve in diabetic rats (p < 0.05), reflecting dose-dependent antihyperglycemic effects of the drug. Based on the results, we conclude that the aforementioned antidiabetic polyherbal remedy is free of toxic/adverse effects at the equivalent human therapeutic dose in healthy Wistar rats and would be a safe therapeutic agent for long-term treatments.

Demographic Associations of Diabetes Status by Both Fasting Plasma Glucose Concentration and Glycated Hemoglobin in a Community Survey in Galle District, Sri Lanka.

Diagnostic tools used in detecting individuals with diabetes mellitus (DM) include fasting plasma glucose (FPG), glycated hemoglobin (HbA1C), and oral glucose tolerance test (OGTT). The present study was aimed to determine the demographic associations of diabetes status by both tests (FPG and HbA1C) in Galle district, Sri Lanka. 147 adults (30-60 years) who are having FPG ≥ 126 mg/dL underwent demographic evaluations and testing for HbA1C. Group 01 (diabetes status diagnosed by both tests) and group 2 (diabetes status diagnosed only by FPG) were compared using independant sample t-test and chi-square test. Logistic regression was used to study the association between the demographic factors and the diabetes status by both tests. Of the 147 study subjects, 38.1% were males, 61.9% were females, and 63.3% had a family history of diabetes among first-degree relatives (FDR). Mean age, body mass index (BMI), waist circumference (WC), FPG, and HbA1C of the participants were 48.4 ± 7.2 years, 25.1 ± 4.0 kg/m2, 88.8 ± 9.0 cm, 139.4 ± 30.1 mg/dL, and 6.4 ± 0.7%, respectively. The prevalence of diabetes based on both tests was 55.1%. There is a significant difference in mean BMI and WC while no significant differences in mean age between groups 01 and 02. No association was seen between gender and diabetes status (X 2(1) = 0.086, p=0.770), while a significant difference was observed between DM among FDR and diabetes status (X 2(1) = 33.215, p < 0.001). Significance of odds of having diabetes by both tests with rising BMI (OR = 1.97, CI 1.15-3.36, p=0.013) and DM among FDR (OR = 7.95, CI 3.54-17.88, p=0.000) was seen. We conclude rising BMI and having DM among FDR are strongly associated with diabetes status diagnosed by both tests of FPG and HbA1C in community screening.

ß-cell Regenerative Potential of Selected Herbal Extracts in Alloxan Induced Diabetic Rats.

BACKGROUND: Effective ß-cell regeneration is a recognized therapeutic strategy in the treatment of type 1 diabetes mellitus. Regeneration of ß-cells could be achieved via exogenous natural sources as medicinal plant extracts. Medicinal plants selected for the investigation were Spondias pinnata (Linn. f.) Kurz, Coccinia grandis (L.) Voigt and Gmelina arborea Roxb. The objective was to determine the ß-cell regenerative potential of these plant extracts in alloxan-induced diabetic rats. Alloxan monohydrate was used to induce diabetes (150 mg/kg, ip). METHODS: Wistar albino rats were divided into six groups (n=6); healthy untreated rats (healthy control), alloxan-induced diabetic untreated rats (diabetic control), diabetic rats received the extracts (treatment groups) of S. pinnata (1.0 g/kg), C. grandis (0.75 g/kg), G. arobrea (1.00 g/kg) and diabetic rats received glibenclamide (0.5 mg/kg; positive control). The above treatment was continued for 30 days. On the 30th day, the rats were sacrificed and biochemical parameters were determined. In addition, histopathology and immunohistochemistry on the pancreatic tissue were done on the 30th day. RESULTS: According to the results obtained for biochemical parameters, there was a significant increase in the concentrations of serum insulin and C-peptide in plant extracts treated diabetic rats (p < 0.05). The extract of C. grandis produced the highest degree of ß-cell regeneration demonstrated through an increase in the number of islets and percentage of the insulin-secreting ß-cells (75%) in the pancreas of diabetic rats (p < 0.05) based on the histopathology and immunohistochemistry findings. CONCLUSION: The results revealed that the selected extracts of C. grandis (0.75 g/kg), G. arborea (1.00 g/kg) and S. pinnata (1.00 g/kg) exerted ß-cell regenerative potential in diabetic rats. The three plant extracts would be valued as natural agents of prompting the ß-cell regeneration in vivo.

Corrigendum to "Gmelina arborea Roxb. (Family: Verbenaceae) Extract Upregulates the ß-Cell Regeneration in STZ Induced Diabetic Rats".

[This corrects the article DOI: 10.1155/2016/4513871.].

Gmelina arborea Roxb. (Family: Verbenaceae) Extract Upregulates the ß-Cell Regeneration in STZ Induced Diabetic Rats.

Gmelina arborea Roxb. (common name: Et-demata, Family: Verbenaceae) has been used traditionally in Sri Lanka as a remedy against diabetes mellitus. The objective of the present study was to evaluate antidiabetic mechanisms of the aqueous bark extract of G. arborea in streptozotocin induced (STZ) diabetic male Wistar rats. Aqueous bark extract of G. arborea (1.00 g/kg) and glibenclamide as the standard drug (0.50 mg/kg) were administered orally using a gavage to STZ diabetic rats (65 mg/kg, ip) for 30 days. The antidiabetic mechanisms of aqueous extract of G. arborea (1.00 g/kg) were determined at the end of the experiment. The fasting blood glucose concentration was significantly lowered and the serum insulin and C-peptide concentrations were increased by 57% and 39% in plant extract treated rats on day 30, respectively (p < 0.05). The histopathology and immunohistochemistry results of the plant extract treated group showed a regenerative effect on ß-cells of the pancreas in diabetic rats. In addition, serum lipid parameters were improved in G. arborea extract treated diabetic rats. The results revealed that the aqueous stem bark extract of G. arborea (1.00 g/kg) showed beneficial effects against diabetes mellitus through upregulating the ß-cell regeneration and biosynthesis of insulin in diabetic rats.