Correlation between Body Mass Index and Lipid Profile in patients with Type 2 Diabetes attending a tertiary care hospital in Peshawar.

OBJECTIVE: To determine the correlation between body mass index (BMI) and lipid profile in patients with Type 2 Diabetes (T2DM) attending a tertiary care hospital in Peshawar. METHODS: A total of 305 patients (men, 132; women, 173) with T2DM visiting an Outpatient department in Northwest General Hospital and Research Centre, Peshawar from January 2016 to July 2016 were included in this study. The whole blood and sera were analyzed for Glycated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TGs), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C). The correlation of BMI with lipid ratios and individual lipid indices were analysed. RESULTS: Mean of BMI was 29.29±5.23. Dyslipidemia; increased TC, increased LDL-C, increased triglyceride and decreased HDL-C were noted in 40.7%, 54.1%, 69.5% and 41% respectively. The mean difference of LDL-C (p=0.006) was significant between male and female. BMI, TC, TGs, and LDL-C showed no significant correlation where as a significant negative correlation between BMI and HDL-C was observed (r=-0.125, p=0.029, R2=0.016). The mean values of TC, TG, LDL-C, TC/ HDL-C and LDL/HDL were greater in patients with normal BMI compared to overweight and obese; however, the differences were not significant. HDL-C differed significantly in BMI groups (p=0.040). CONCLUSION: A significant negative correlation between BMI and HDL-C was observed, while the correlation between BMI and LDL-C was observed to be insignificant. HDL-C was found significantly higher in patients with normal BMI. These results are important to indicate that there is modest impact of BMI on lipid profile. Therefore, assessment and management for altered blood lipids should not be based on a patient's body weight or BMI.

In-vitro and in-silico anticancer potential of taxoids from Taxus wallichiana Zucc.

INTRODUCTION: Natural products derived from medicinal plants provide beneficial cancer chemotherapeutic drugs. Bioactive constituents from plants are explored for their anticancer properties. METHODS: Three known compounds (deacetylbaccatin III, tasumatrol B, and taxawallin J) were isolated from Taxus wallichiana. Compounds were screened against four cancer cell lines, such as eA498, HepG2, NCI-H226, and MDR 2780AD. Cytotoxic activity was evaluated using MTT assay against cancer cell lines. RESULTS: Tasumatrol B showed good cytotoxic activity conducted for the improvement of inhibiting potential of these compounds against the cancer drug target protein (EGFR tyrosine kinase enzyme). The docking study showed that all compounds have binding affinities and interaction profile with the receptor tyrosine kinase. DISCUSSION: The study suggests that these compounds could be used for the discovery of novel inhibitors against the target receptors for the treatment of cancer.

Antinociceptive activity of cyclopeptide alkaloids isolated from Ziziphus oxyphylla Edgew (Rhamnaceae).

The current study was designed to evaluate the antinociceptive profile of five cyclopeptide alkaloids isolated from Ziziphus oxyphylla, including Oxyphylline-B 1, Oxyphylline C 2 Oxyphylline-D 3, Nummularin-C 4, and Nummularin-R 5. The effect was studied in acetic acid induced writhing and formalin induced flinching behavior tests, at 2.5 and 5mg/kg i.p. In the post-acetic acid induced writhing test, the compounds significantly ameliorated abdominal constrictions in a dose dependent manner, with compounds 1 and 5 showing 80.98% and 77.87% protection, respectively. When challenged in the formalin induced test, pretreatment of compounds significantly attenuated painful sensation in both phases. Moreover, compounds 1 and 5 were more effective with 45.32% and 75.32% for 1 and 36.77% and 71.10% protection for 5, in the 1st and 2nd phases respectively. The peripheral analgesia was strongly augmented by the central effects of these compounds. The current finding strongly supports the ethnomedicinal use of this valuable medicinal plant in various painful conditions.

In vivo screening of essential oils of Skimmia laureola leaves for antinociceptive and antipyretic activity.

OBJECTIVE: To study the screening of essential oils of Skimmia laureola leaves (SLO) for acute toxicity, antinociceptive, antipyretic and anticonvulsant activities in various animal models. METHODS: SLO were extracted using modified Clevenger type apparatus. Acute toxicity test was used in mice to observe its safety level. Antinociceptive activity of SLO was evaluated in acetic acid induced writhing and hot plate tests. Yeast induced hyperthermic mice and pentylenetetrazole induced convulsive mice were used for the assessment of its antipyretic and anticonvulsant profile respectively. RESULTS: Substantial safety was observed for SLO in acute toxicity test. SLO showed a high significant activity in acetic acid induced writhing test in a dose dependent manner with maximum pain attenuation of 68.48% at 200 mg/kg i.p. However, it did not produce any relief in thermal induced pain at test doses. When challenged against pyrexia evoked by yeast, SLO manifested marked amelioration in hyperthermic mice, dose dependently. Maximum anti-hyperthermic activity (75%) was observed at 200 mg/kg i.p. after 4 h of drug administration. Nevertheless, SLO had no effect on seizures control and mortality caused by pentylenetetrazole. CONCLUSIONS: In vivo studies of SLO showed prominent antinociceptive and antipyretic activities with ample safety profile and thus provided pharmacological base for the traditional uses of the plant in various painful conditions and pyrexia. Additional detail studies are required to ascertain its clinical application.

New 14-membered cyclopeptide alkaloids from Zizyphus oxyphylla Edgew.

Two new 14-membered cyclopeptide alkaloids, Oxyphylline B (4) and Oxyphylline C (5), along with three known 13-membered cyclopeptide alkaloids, were isolated from stem and roots of Zizyphus oxyphylla Edgew. The compounds were tested for antibacterial activity. Oxyphylline B (4) showed comparatively better antibacterial activities against Escherichia coli (MIC, 5 µg/mL) than other compounds. This compound also exhibited weak antimicrobial activities against Staphylococcus aureus (MIC, 25 µg/mL), Pseudomonas aeruginosa (MIC, 50 µg/mL) and Salmonella typhi (MIC, 50 µg/mL).

Analgesic and antiinflammatory activities of taxoids from Taxus wallichiana Zucc.

A study was conducted to identify constituents that might be responsible for analgesic and antiinflammatory conditions. Tasumatrol B, 1,13-diacetyl-10-deacetylbaccatin III (10-DAD) and 4-deacetylbaccatin III (4-DAB) were isolated from the bark extract of Taxus wallichiana Zucc. All the compounds were assessed for analgesic and antiinflammatory activities using an acetic acid-induced writhing model, a hot-plate test, a carrageenan-induced paw oedema model, a cotton-pellet oedema model and in vitro lipoxygenase inhibitory assay. All the compounds, especially tasumatrol B, revealed significant analgesic activity in comparison to a saline group based on an acetic acid-induced model. Similarly all of the test compounds, particularly tasumatrol B, showed significant antiinflammatory activity. However, all the compounds failed to exhibit any considerable activity in of the hot-plate test and the in vitro lipoxygenase inhibitory assay. This study has highlighted the potential of tasumatrol B to be further explored as a new lead compound for the management of pain and inflammation, one that has been discovered by scientific validation of the traditional medicinal use of T. wallichiana Zucc.

Anti-inflammatory activities of Taxusabietane A isolated from Taxus wallichiana Zucc.

Current study was conducted to identify constituents of Taxus wallichiana Zucc. that might be responsible for its folk use in anti-inflammatory conditions. Taxusabietane A was isolated from the bark extract of Taxus wallichiana Zucc. Taxusabietane A was analyzed for in-vitro and in-vivo anti-inflammatory activities using Lipoxygenase (LOX) inhibition assay and carrageenan-induced paw edema model. Taxusabietane A revealed considerable LOX inhibitory activity with the IC(50) value being 57 ± 0.31. Standard compound Baicalein showed the IC(50) value being 22.1 ± 0.03 µM. Taxusabietane A also showed significant (5 and 10 mg/kg) anti-inflammatory activity induced by carrageenan. However, this study highlighted the potential of Taxusabietane A to be further explored as a new lead compound for management of conditions associated with inflammation.

Molecular simulations probing Kushecarpin A as a new lipoxygenase inhibitor.

Zizyphus oxyphylla Edgew is used in Pakistan as a folk medicinal remedy for inflammatory conditions, pains especially rheumatic pain, fevers, allergy and diabetes. The aim of the current study was to scientifically validate the folk use of Z. oxyphylla Edgew by using the isolated compound in vitro and in vivo levels. Kushecarpin A was isolated from ethyl acetate fraction of the plant crude extract. Molecular docking simulations predicted Kushecarpin A as a potential new lipoxygenase (LOX) inhibitor. Kushecarpin A showed significant lipoxygenase inhibition (IC(50): 7.2 ± 0.02 µM) thus validated computational prediction. It also exhibited significant and highly significant inhibition (p < 0.05 and p < 0.01) of carrageenan-induced hind paw oedema at the doses of 5, 10 and 20 mg/kg. Kushecarpin A seems to be a potentially new anti-inflammatory compound responsible for anti-inflammatory activities of Z. oxyphylla Edgew. In vitro and in vivo anti-inflammatory inflammatory activities were found in good agreement with the folk medicinal use of Z. oxyphylla Edgew in inflammatory disorders.

Molecular simulations of Taxawallin I inside classical taxol binding site of ß-tubulin.

A new taxoid Taxawallin I (1) along with two known taxoids (2-3) were isolated from methanolic bark extract of Taxus wallichiana Zucc. Structural characterization was confirmed by mass and NMR spectral techniques. Taxawallin I exhibited significant in-vitro anticancer activity against HepG2, A498, NCI-H226 and MDR 2780AD cancer lines. Tubulin binding assay was performed to assess its tubulin binding activity. Molecular docking analysis was performed to study the potential binding mode inside the taxol binding site of ß-tubulin.

Stereochemistry and NMR data assignment of cyclopeptide alkaloids from Zizyphus oxyphylla.

The structures of (3S,7R,13S)-6-[2-(dimethylamino)-3-phenylpropanoyl]-19-methoxy-2-oxa-6,9,15-triazatetracyclo[16.3.1.0(3,7). 0(9,13)]docosa-1-(22),16,18,20-tetraene-8,14-dione (1), nummularin-C (2) and nummularin-R (3) have been previously determined mainly based on mass spectrometric data. Stereochemistry and complete 1H and 13C NMR spectroscopic data assignments of these compounds are now described. Compounds 1 and 2 are reported for the first time from Zizyphus oxyphylla.

Structural insights to investigate Conypododiol as a dual cholinesterase inhibitor from Asparagus adscendens.

The main aim of the current study was to explore molecular insights for potentially new dual cholinesterase inhibitor(s) from Asparagus adscendens via molecular docking. This medicinal plant is traditionally used as a nerve tonic and remedy for memory impairments. Conypododiol was isolated from the chloroform fraction of methanolic extract of A. adscendens, based on bioactivity guided isolation. Conypododiol exhibited significant inhibition of both acetylcholinesterase and butyrylcholinesterase, having the IC(50) values 2.17 ± 0.1 µM and 11.21 ± 0.1 µM, respectively. IC(50) values of the standard compound Galanthamine for both the enzymes were 0.537 ± 0.018 µM and 8.6 ± 0.27 µM, respectively. Based on MTT cytotoxicity assay, Conypododiol was found safe against LCMK-2 monkey kidney epithelial cells and mice hepatocytes. Molecular docking studies revealed the hydrogen bonding interactions of Conypododiol with His440 and Ser200 at esteratic site (ES), and also with Tyr334 at peripheral anionic site (PAS) of the aromatic gorge of acetylcholinesterase. Simultaneous contacts of Conypododiol with PAS and ES shows its significance as a bivalent ligand. This preliminary study highlighted the potential of Conypododiol to be further developed and modified as new lead compound identified by its folk use.