Haemodynamic Effects Of Adiponectin On PPAR–γ Receptors In Diabetic And Nondiabetic Wistar Kyoto And Spontaneously Hypertensive Rats

Prevalens hipertensi dan diabetes semakin meningkat dengan kadar yang belum pernah berlaku sebelum ini di kedua-dua negara sedang membangun dan juga di negara maju The prevalence of hypertension and diabetes is mounting with unprecedented degree in both developing and advanced countrie

Trinity of inflammation, innate immune cells and cross-talk of signalling pathways in tumour microenvironment

Unresolved inflammation is a pathological consequence of persistent inflammatory stimulus and perturbation in regulatory mechanisms. It increases the risk of tumour development and orchestrates all stages of tumorigenesis in selected organs. In certain cancers, inflammatory processes create the appropriate conditions for neoplastic transformation. While in other types, oncogenic changes pave the way for an inflammatory microenvironment that leads to tumour development. Of interest, hallmarks of tumour-promoting and cancer-associated inflammation are striking similar, sharing a complex network of stromal (fibroblasts and vascular cells) and inflammatory immune cells that collectively form the tumour microenvironment (TME). The cross-talks of signalling pathways initially developed to support homeostasis, change their role, and promote atypical proliferation, survival, angiogenesis, and subversion of adaptive immunity in TME. These transcriptional and regulatory pathways invariably contribute to cancer-promoting inflammation in chronic inflammatory disorders and foster “smouldering” inflammation in the microenvironment of various tumour types. Besides identifying common target sites of numerous cancer types, signalling programs and their cross-talks governing immune cells’ plasticity and functional diversity can be used to develop new fate-mapping and lineage-tracing mechanisms. Here, we review the vital molecular mechanisms and pathways that establish the connection between inflammation and tumour development, progression, and metastasis. We also discussed the cross-talks between signalling pathways and devised strategies focusing on these interaction mechanisms to harness synthetic lethal drug combinations for targeted cancer therapy

Synthesis and in vitro antidiabetic activity of some alkyl carbazole compounds

Purpose: To synthesize some alkyl derivatives of carbazole and evaluate their in vitro inhibitory effect on alpha amylase and alpha glucosidase.Methods: Synthesis of methylcarbazole, ethylcarbazole, propylcarbazole and butylcarbazole was carried out using acid-catalysed alkylation method while in vitro inhibitory assay on alpha amylase and alpha glucosidase enzymes on the  synthesized compounds was evaluated using standard procedures. Acarbose was used as the reference compound.Results: For carbazole, methylcarbazole, ethylcarbazole, propylcarbazole and butylcarbazole, the IC50 values of alpha amylase inhibitory assay were 87.47,  50.23, 47.20, 42.36 and 42.11 μg/mL respectively. IC50 values of alpha  glucosidase inhibitory assay for ethylcarbazole, propylcarbazole and butylcarbazole were 205.30, 153.93 and 152.90 μg/mL, respectively. Carbazole and  methylcarbazole had no inhibitory effect on this enzyme but the reference drug  (acarbose) had a better inhibitory effect towards the two enzymes than the synthesized products.Conclusion: Some alkyl-carbazoles with anti-diabetic effect have been successfully synthesised. Alkylation of carbazole increased the alpha amylase inhibitory effect of carbazole. The inhibitory effect is directly proportional to the chain length of the alkyl group.Keywords: Alkyl carbazole, alpha amylase, alpha glucosidase, synthesi

Evaluation of the antimicrobial and anticancer properties of the fruits of Synsepalum dulcificum (Sapotaceae)

Purpose: To evaluate the antimicrobial and anticancer activities of the fruit of Synsepalum dulcificum (Sapotaceae) against six bacterial strains and on two different colorectal cancer cell lines, respectively.Methods: The dried fruit of the plant was extracted in a Soxhlet apparatus successively with petroleum ether and ethanol, and concentrated in a rotary evaporator to obtain petroleum ether and ethanol extract, respectively. Phytochemical screening was done on the two extracts. The antimicrobial effects of the extracts against Bacillus subtilis, Staphylococcus aureus, Streptococcus pyogene, Pseudomonas aeruginosa, Klebsiella pneumoniae and Proteus vulgaris were evaluated using agar well diffusiontechnique while the anticancer effect of the ethanol extract was assessed on HCT-116 and primary colon epithelial (PCE) cell lines by MTT assay.Results: The results indicate that the petroleum ether extract of Synsepalum dulcificum fruits exerted stronger antimicrobial activity than the ethanol extract. The ethanol extract also showed significant anticancer activity (p < 0.05). The calculated half-maximal concentration (IC50) of the extract on HCT- 116 cells at 24, 48, and 72 h are 14.99, 8.97, and 8.54 μg/mL, respectively, while the IC50 of the extract on PCE cell lines at 24, 48, and 72 h are 236.25, 206.09, and 196.72 μg/mL, respectively. The extract was more toxic to cancer cells than to normal cells.Conclusion: The results of this study lend some justification for the use of the fruits of Synsepalum dulcificum as an antibacterial and anticancer agent

Evaluation for antiviral potential of ficus deltoidea against dengue virus type-2

Dengue is one of the most widespread arthropod-borne viral diseases that cause negative impact globally. Presently, no effective drug is available to safeguard people against dengue. Ficus deltoidea is Malaysia›s famous traditional herb belonging to Moraceae family due to its pharmacological potential. F. deltoidea leaves (FDL) were extracted with n-hexane, ethyl acetate and methanol. Cell cytotoxicity study using MTT assay measuring the formazan absorbance was conducted to determine maximum non-toxic concentration on Vero cells. The antiviral activities of various concentrations of FDL extracts were assessed using virus reduction neutralisation tests against dengue virus type 2. The CC20 value of n-hexane, ethyl acetate and methanol FDL extracts were 2.99 ± 0.31, 22.15 ± 2.39, and 25.22 ± 0.42 µg/mL, respectively. Methanol FDL extract at maximum non-toxic concentration exerted strongest direct extracellular virucidal effect against DENV-2. In cell protection assay, ethyl acetate FDL extract achieved highest reduction in viral infectivity (98.17%), whereas n-hexane FDL extract showed strongest inhibition in DENV-2 viral replication in post-infection assay. Methanol FDL extract showed highest selectivity index value in direct virus inhibition, cell protection and post-infection assay. Conclusively, FDL extracts, especially methanol FDL showed potential antiviral activity against DENV-2, thus considered as promising anti-dengue agent

Isolation and characterization of antioxidant constituents of the fruit of Telfairia occidentalis Hook F (Cucurbitaceae)

Purpose: To evaluate the antioxidant property of the fruit of Telfairia occidentalis and isolate the components responsible for the antioxidant activity.Methods: The fruit pericarp was macerated with methanol and the extract obtained successively partitioned with n-hexane, dichloromethane and ethyl acetate. The in vitro antioxidant activity of the extract and fractions was evaluated using 2,2-diphenyl-1-picryl hydrazyl (DPPH) radical scavenging, reducing power, nitric oxide scavenging, total antioxidant and hydrogen peroxide scavenging assays. The n-hexane fraction, which had the highest DPPH scavenging and total antioxidant activities, was subjected to column and thin layer chromatography to isolate the components. The isolated compounds were identified by ultraviolet-visible (UV), nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR) spectroscopy and mass spectrometry.Results: Among the fractions tested, n-hexane had the best total antioxidant activity of 99.44 % at 20 mg/ml (p < 0.05) compared to ascorbic acid at 99.71 % of 20 mg/ml. This fraction also had the highest DPPH radical scavenging activity of all the fractions (p < 0.05) at all test concentrations. For nitric oxide scavenging activity, the whole extract, and the chloroform and aqueous fractions exhibited activity ranging from 92.29 to 97.66 % compared to 98.93 % for ascorbic acid. The hydrogen peroxide scavenging activity of the extract and fractions ranged from 92.60 to 96.23 % compared with of the standard, ascorbic acid (101.68 %). The major components of the n-hexane fractions were α- amyrin and β-amyrin.Conclusion: The fruit pericarp of Telfairia occidentalis possesses good DPPH radical scavenging activity. This is the first time the antioxidant activity of the fruit (pericarp) and the presence of α- and β- amyrins in Telfairia occidentalis have been reported.Keywords: Telfairia occidentalis, Fluted pumpkin, Amyrin, Antioxidant

Renoprotective and haemodynamic effects of adiponectin and peroxisome proliferator-activated receptor agonist, pioglitazone, in renal vasculature of diabetic Spontaneously hypertensive rats.

Pioglitazone, a therapeutic drug for diabetes, possesses full PPAR-γ agonist activity and increase circulating adiponectin plasma concentration. Plasma adiponectin concentration decreases in hypertensive patients with renal dysfunctions. Present study investigated the reno-protective, altered excretory functions and renal haemodynamic responses to adrenergic agonists and ANG II following separate and combined therapy with pioglitazone in diabetic model of hypertensive rats. Pioglitazone was given orally [10mg/kg/day] for 28 days and adiponectin intraperitoneally [2.5μg/kg/day] for last 7 days. Groups of SHR received either pioglitazone or adiponectin in combination. A group of Wistar Kyoto rats [WKY] served as normotensive controls, whereas streptozotocin administered SHRs served as diabetic hypertensive rats. Metabolic data and plasma samples were taken on day 0, 8, 21 and 28. In acute studies, the renal vasoconstrictor actions of Angiotensin II [ANGII], noradrenaline [NA], phenylephrine [PE] and methoxamine [ME] were determined. Diabetic SHRs control had a higher basal mean arterial blood pressure than the WKY, lower RCBP and plasma adiponectin, higher creatinine clearance and urinary sodium excretion compared to WKY [all P<0.05] which were normalized by the individual drug treatments and to greater degree following combined treatment. Responses to intra-renal administration of NA, PE, ME and ANGII were larger in diabetic SHR than WKY and SHRs [P<0.05]. Adiponectin significantly blunted responses to NA, PE, ME and ANG II in diabetic treated SHRs by 40%, whereas the pioglitazone combined therapy with adiponectin further attenuated the responses to adrenergic agonists by 65%. [all P <0.05]. These findings suggest that adiponectin possesses renoprotective effects and improves renal haemodynamics through adiponectin receptors and PPAR-γ in diabetic SHRs, suggesting that synergism exists between adiponectin and pioglitazone. A cross-talk relationship also supposed to exists between adiponectin receptors, PPAR-γ and alpha adrenoceptors in renal vasculature of diabetic SHRs

Effect of pioglitazone on vasopressor responses to adrenergic agonists and angiotensin II in diabetic and non-diabetic spontaneously hypertensive rats

Pioglitazone, peroxisome proliferator-activated receptor (PPAR-γ) agonist, is a therapeutic drug for diabetes. Present study investigated the interaction between PPAR-γ and alpha adrenoceptors in modulating vasopressor responses to Angiotensin II (Ang II) and adrenergic agonists, in diabetic & non-diabetic Spontaneously Hypertensive Rats (SHRs). Diabetes was induced with an i.p injection of streptozotocin (40 mg/kg) in two groups (STZ-CON, STZ-PIO), whereas two groups remained non diabetic (ND-CO, ND-PIO). One diabetic and non-diabetic group received Pioglitazone (10mg/kg) orally for 21 days. On day 28, the animals were anaesthetized with sodium pentobarbitone (60mg/kg) and prepared for measurement of systemic haemodynamics. Basal mean arterial pressure of STZ-CON was higher than ND-CON, whereas following pioglitazone treatment, MAP was lower compared to respective controls. MAP responses to i.v administration of NA, PE, ME and ANG II were significantly lower in diabetic SHRs: STZ-CON vs ND-CON (35%). Pioglitazone significantly decreased responses to NA, PE, ME and ANG II in ND-PIO versus ND-CON by 63%. Responses to NA and ANG II were significantly attenuated in STZ-PIO vs. ND-PIO (40%). PPAR-γ regulates systemic hemodynamic in diabetic model and cross-talk relationship exists between PPAR-γ and α1-adrenoceptors, ANG II in systemic vasculature of SHRs

Phytochemical analysis and antioxidant activity of the seed of <i>Telfairia occidentalis</i> Hook (Cucurbitaceae)

<p>The 2,2-diphenyl-1-picryl hydrazyl (DPPH) radical, nitric oxide, reducing power, hydrogen peroxide scavenging, and total antioxidant activities of the methanol extract, <i>n</i>-hexane, dichloromethane, ethyl acetate, butanol and aqueous fractions of the seed of <i>Telfairia occidentalis</i> were evaluated. Total phenolic content was determined using the Folin–Ciocalteu method. The dichloromethane fraction exhibited the highest DPPH radical scavenging, reducing power and total antioxidant activities. Two pure compounds which were identified by FTIR, H-and 2D NMR and Mass spectroscopy as 9-octadecenoic acid (TOS B) and 10-hydroxyoctadecanoic acid (TOS C) and four oily isolates, TOS A, TOS D, TOS E and TOS F were obtained from the dichloromethane fraction. TOS E had the highest DPPH radical scavening activity comparable to that of ascorbic acid. GC-MS analysis revealed the major compounds in TOS E as 4-(2,2-Dimethyl-6-methylene cyclohexylidene)-2-butanol; 3-(3-hydroxybutyl)-2,4,4-trimethyl-2-cyclohexene-1-one and 1,2-Benzenedicarboxylic acid disooctyl ester. Thus, the seed of <i>T. occidentalis</i> can be consumed for its antioxidant property.</p