Pancreatic lipase inhibitory activity of selected pharmaceutical agents

Twenty-five structurally diverse compounds have been tested in vitro for their pancreatic lipase (PL) inhibitory activity. Despite the diversity of tested compounds, the relationship comprising structural attributes of the compounds could be established to correlate with the observed inhibitory activity. Compounds that exerted inhibitory action through surface activity were of different profile from the rest of compounds. When co-incubated with orlistat (OsT), important synergistic effects for some compounds (orphenadrine, gliclazide, cefuroxime and sulfacetamide) were revealed, while antagonistic effects were demonstrated for others (camphor sulfonic acid and dinitro salicylic acid). Docking studies for the most active molecules were performed and molecular interaction forces with the PL active site were identified. The results suggested co-binding of OsT along with the other inhibitor in the binding site in cases of synergistic effect but not in the case of antagonistic effect. These results were additionally supported by affinity capillary electrophoresis. In conclusion, synergistic lipase inhibitory activity between OsT and some other pharmaceutical compounds was demonstrated for the first time, which might help improve the pharmacological effect of OsT

Evaluation of Antiproliferative Activity of Some Traditional Anticancer Herbal Remedies from Jordan

Purpose: To evaluate the in vitro antiproliferative activity of the extracts of the three plants against a panel of human tumor cell lines representing the most common types of cancer in Jordan, viz, breast and colorectal and skin cancers.Methods: The methanol extracts of the aerial parts of the three plants (Arbutus andrachne L., Chrysanthemum coronarium L., and Teucrium polium L.) were prepared and assessed for antiproliferative activity against six human tumor cell lines (A375.S2, WM1361A, CACO-2, HRT18, MCF-7, T47D) using 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide MTT cell proliferation assay.Results: C. coronarium extract, at the concentration range of 25 to 400 μg/mL, significantly inhibited (10 – 50 %) the proliferation of the 6 cell lines in a dose-dependent manner, whilst the extracts of the other two plants exhibited weak antiproliferative activity (2 – 10 % inhibition). The half-maximal inhibitory concentration (IC50) values of C. coronarium extract against the six cell lines were in the range of 75.8 to 138.5 μg/mL.Conclusion: The methanol extract of the aerial parts C. coronarium possesses a relatively potent antiproliferative activity and therefore might be a potential source of natural compounds that can be developed into new antineoplastic agents.Keywords: Antiproliferative, Arbutus andrachne L., Chrysanthemum coronarium L., Teucrium polium L. Jordan flora, Medicinal plants, Cancer, Antineoplasti

Evaluation of the efficacy and mechanisms of action of traditional plant treatments of diabetes

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

The Antiglycation Effect of Monomethyl Branched Chained Fatty Acid and Phytochemical Compounds and their Synergistic Effect on Obesity Related Colorectal Cancer Cell Panel

Background and aims: monomethyl branched chain fatty acids (mmBCFA) and phytochemicals including: Hydroxycitric Acid, Chlorogenic Acid and Piperine have been considered as an interesting agent for researches due to their role in diabetes and cancer. The present study examines the antiglycation effect of mmBCFA and phytochemicals and investigate their Synergistic effect on different colorectal cancer cell lines

Pharmacological and Phytochemical Appraisal of Selected Medicinal Plants from Jordan with Claimed Antidiabetic Activities

Plant species have long been regarded as possessing the principal ingredients used in widely disseminated ethnomedical practices. Different surveys showed that medicinal plant species used by the inhabitants of Jordan for the traditional treatment of diabetes are inadequately screened for their therapeutic/preventive potential and phytochemical findings. In this review, traditional herbal medicine pursued indigenously with its methods of preparation and its active constituents are listed. Studies of random screening for selective antidiabetic bioactivity and plausible mechanisms of action of local species, domesticated greens, or wild plants are briefly discussed. Recommended future directives incurring the design and conduct of comprehensive trials are pointed out to validate the usefulness of these active plants or bioactive secondary metabolites either alone or in combination with existing conventional therapies

Glycated LDL-C and glycated HDL-C in association with adiposity, blood and atherogenicity indices in metabolic syndrome patients with and without prediabetes

Background: The aim of the study was to compare and correlate glycated high-density lipoprotein (GHDL-C) and glycated low-density lipoprotein (GLDL-C) plasma levels with adiposity indices [weight/hip ratio (WHR) and body adiposity index (BAI)], lipid ratios and hematological indices [platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR)]. Methods: This was a cross-sectional study of 30 nondiabetic metabolic syndrome (MetS) patients, 30 prediabetic or type 2 diabetes mellitus (T2DM) patients and 30 normoglycemic controls. Results: Remarkably both GHDL-C and GLDL-C levels lacked any intergroup statistically significant discrepancy in either MetS or MetS-pre/T2DM versus control ( p > 0.05). Unlike GLDL-C/LDL-C ratios for either MetS groups; there were highly significant intergroup differences in the means of GHDL-C/HDL-C ratios when comparing both nondiabetic MetS and MetS-pre/T2DM groups versus controls ( p = 0.001). In MetS patients; GHDL-C and GLDL-C proportionally correlated with WHR ( p < 0.05). Also, MetS GHDL-C correlated inversely with MLR and monocytes ( p < 0.05). In MetS-pre/T2DM; GLDL-C directly correlated with BAI, platelet count and PLR ( p < 0.05). Conclusion: GLDL-C and GHDL-C are dysfunctional glucolipotoxicity lipoproteins and may present putatively surrogate biomarkers for prediction/prevention of metabolic disturbances

Evaluation of Pancreatic and Extra Pancreatic Effects of Branched Amino Acids

Background and aims: Leucine, Isoleucine, and Valine collectively known as Branched-chain amino acids (BCAAs), can be closely associated with metabolic dysregulates and with insulin resistance. We aimed to explore the role of BCAAs as potential treatment option for diabetes

Cross-sectional correlates of paraoxonase 1 and soluble intercellular adhesion molecule-1 in metabolic syndrome patients with and without diabetes

Background: Paraoxonase 1 (PON1) and soluble intercellular adhesion molecule-1(sICAM-1) are intricately involved in metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) pathophysiology. This study aimed to investigate PON1 and sICAM-1 plasma levels in addition to correlating them with adiposity, atherogenicity and hematological indices in T2DM and MetS. Methods: This cross-sectional study composed of 28 healthy lean subjects (control), 29 normoglycemic MetS subjects and 30 MetS-Pre/T2DM. Results: The sICAM-1 levels (ng/ml) were markedly higher in the pre/diabetic MetS group (828 ± 250.37 versus controls’ 608.62 ± 184; p < 0.05). Conversely, PON1 levels (mlU/ml) were markedly lower in the pre/diabetic MetS group [252,700 (163,950, 362,800) versus controls’ 394,900 (212,550, 469,350); p < 0.05]. sICAM-1 correlated directly with all adiposity indices [conicity index (CI), waist circumference (WC), waist–hip ratio (WHR) waist-to-height (WHtR) ratio, hip circumference (HC) and body adiposity index (BAI)] in addition to the atherogenicity index of plasma (AIP). PON1 correlated negatively and significantly with CI, WC, WHR, WHtR and HC but directly with lymphocyte. Significantly, a reciprocal sICAM-1–PON1 relationship was observed in the total population ( r = −0.262, p = 0.015). Conclusion: Utility of sICAM-1 and PON1 as surrogate prognostic biomarkers and putative therapeutic targets in the management of diabetes and MetS is strongly suggested

Cross-sectional correlates of increased IL-18 but reduced fetuin-A and oxytocin with adiposity and blood indices in metabolic syndrome patients with and without prediabetes

Background: Oxytocin (OXT), fetuin-A and interleukin-18 (IL-18) are involved in the development and progression of metabolic syndrome (MetS) and prediabetes (pre/T2DM). Aims, participants and methods: This study aimed to compare and correlate the plasma levels of OXT, fetuin-A and IL-18 with clinical parameters, haematological indices and adiposity indices in Jordanian MetS subjects. In a cross-sectional study, 30 normoglycaemic lean study participants (control), 30 MetS study participants, and 29 MetS pre/T2DM study participants were recruited. Results: Median circulating levels of both OXT and fetuin-A were lower in MetS and MetS pre/T2DM versus control group. OXT (pg/ml; median interquartile range): MetS 1975.4 and MetS pre/T2DM 1403 versus control 4176.6 ( p = 0.009 and p = 0.001, respectively). For fetuin-A (ng/ml), MetS (5784) and MetS pre/T2DM (2154) were lower versus control (6756.3) ( p = 0.040 and p = 0.007, respectively). Neither biomarker was described as substantially different in MetS versus MetS pre/T2DM ( p = 0.071 and p = 0.155, respectively). Conversely, a non-significant increase in IL-18 was observed in the MetS and MetS pre/T2DM groups compared to normoglycaemic lean controls (232 and 287.5, p > 0.05 versus 108 for both). In addition, conicity index (C-index), atherogenicity index (TG-HDL-C), waist to hip ratio, mean platelet volume (MPV; fl) and red cell distribution width (RDW-CV%) in both MetS and MetS pre/T2DM were significantly higher ( p < 0.001) versus controls. However all above MetS-related indices were not ascribed any statistically marked variation in the MetS group when compared to the MetS pre/T2DM group. Both total study pool of recruits’ fetuin-A (Spearman r = – 2.66, p = 0.049) as well as MetS pre/T2DM group IL-18 (Spearman r = 0.380, p = 0.046) were inversely correlated with RDW-CV%. OXT in MetS inversely correlated with waist circumference/hip circumference ratio (Spearman r = −0.387, p = 0.038). No other pronounced associations between biomarkers could be detected in any study arm. Conclusion: These findings substantiate the clinical relevance and significance of OXT, fetuin-A and IL-18 as surrogate screening/prognostic tools and therapeutic targets to predict/prevent metabolic dysregularities and anomalies