Effect of two andrographolide derivatives on cellular and rodent models of non-alcoholic fatty liver disease.

The prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD) is increasing and there is an increasing interest in natural products to treat NAFLD. This study aimed to evaluate the hepatoprotective effect of andrographolide and two of its derivatives; in one the OH group at C-14 was removed and in the other OH groups at C-3 and C-19 were protected. Andrographolide (AN) was isolated from the aerial parts of Andrographis paniculata Wall. Isoandrographolide (IAN) and 3,19-acetonylidene andrographolide (ANA) were derivatized from AN. Drug likeness of the compounds was studied using DataWarrior. The effect of the compounds in ameliorating hepatic steatosis and lipotoxicity was assessed using palmitate-oleate induced steatotic HepG2 cell lines. In vivo efficacy of the compounds was assessed by using HFD fed rats. IAN showed comparatively high drug score and low irritability than AN. MTT assay indicated that the treatment with IAN had comparatively less toxicity than AN and ANA to HepG2 cells. The treatment with IAN significantly reduced the lipid accumulation and the leakage of LDH and transaminases, while the treatments with AN and ANA did not prohibit the leakage. In the in vivo experiment, the treatment with IAN showed comparatively better hepatoprotection by reducing the serum lipid, transaminases and ALP levels than with AN and ANA. Our results showed that IAN could be a promising lead to treat NAFLD with comparatively low toxicity and improved efficacy.

Antihyperlipidemic and hepatoprotective effects of Gardenin A in cellular and high fat diet fed rodent models.

The gum of Gardenia resinifera Roth., is one of the important drugs used in the Indian system of medicine and a source of unique polymethoxylated flavones. This study was aimed to evaluate the antihyperlipidemic and anti-NAFLD effects of Gardenin A (Gar-A) from G. resinifera gum using in vitro and in vivo models. Gar-A was isolated from G. resinifera gum and was identified on the basis of the physical and spectral data. Toxicity of Gar-A to HepG2 cells was evaluated using MTT assay. The ability of Gar-A to reduce steatosis was assessed using oleate-palmitate induced HepG2 cell lines by estimating the lipid levels by ORO staining and by estimating the intracellular triglyceride content. Effect of Gar-A on amelioration of lipotoxicity was measured by estimating the LDH levels. The doses for in vivo experiments were fixed by Irwin test, between 50 and 100 mg/kg concentrations, through oral route. The acute antihyperlipidemic effect of Gar-A was assessed in Triton WR-1339 induced hyperlipidemic animals. The chronic antihyperlipidemic and anti-NAFLD effects of Gar-A were evaluated in HFD fed rats. In vitro experiments with HepG2 cell line indicated that the cells treated with Gar-A did not show any significant reduction in the viability up to 70 µg/mL concentration. Steatotic HepG2 cells treated with Gar-A showed a significant reduction in lipid accumulation at 2.5-10 µg/mL concentrations. In triton induced hyperlipidemic rats, the treatment significantly reduced the lipid levels at the synthesis phase. The treatment with Gar-A to the HFD fed animals significantly lowered the steatosis and transaminase levels. The other biochemical parameters such as TC, TG, LDL-c, ALP and ACP were also decreased significantly. Treatment with Gar-A significantly lowered the hyperlipidemia and fat accumulation in the liver; detailed molecular investigations are necessary to establish the antihyperlipidemic and hepatoprotective potentials of Gar-A.

Larvicidal and Pupicidal Activities of Alizarin Isolated from Roots of Rubia cordifolia Against Culex quinquefasciatus Say and Aedes aegypti (L.) (Diptera: Culicidae).

The mosquitocidal activities of different fractions and a compound alizarin from the methanol extract of Rubia cordifolia roots were evaluated on larvae and pupae of Culex quinquefasciatus Say and Aedes aegypti (L.) (Diptera: Culicidae). Larvae and pupae were exposed to concentrations of 2.5, 5.0, 7.5 and 10 ppm for fractions and 0.5, 1.0, 1.5 and 2.0 ppm for compound. After 24 h, the mortality was assessed and the LC50 and LC90 values were estimated for larvae and pupae. Among the 23 fractions screened, fraction 2 from the methanol extract of R. cordifolia showed good mosquitocidal activity against C. quinquefasciatus and A. aegypti. LC50 and LC90 values of fraction 2 were 3.53 and 7.26 ppm for C. quinquefasciatus and 3.86 and 8.28 ppm for A. aegypti larvae, and 3.76 and 7.50 ppm for C. quinquefasciatus and 3.92 and 8.05 ppm for A. aegypti pupae, respectively. Further, the isolated compound alizarin presented good larvicidal and pupicidal activities. LC50 and LC90 values of alizarin for larvae were 0.81 and 3.86 ppm against C. quinquefasciatus and 1.31 and 6.04 ppm for A. aegypti larvae, respectively. Similarly, the LC50 and LC90 values of alizarin for pupae were 1.97 and 4.79 ppm for C. quinquefasciatus and 2.05 and 5.59 ppm for A. aegypti pupae, respectively. The structure of the isolated compound was identified on the basis of spectroscopic analysis and compared with reported spectral data. The results indicated that alizarin could be used as a potential larvicide and pupicide.

Symptomatic venous thromboembolism following circular frame treatment for tibial fractures.

INTRODUCTION: Venous thromboembolism (VTE) is a significant cause of morbidity and mortality following tibial fractures. The risk is as high as 77% without prophylaxis and around 10% with prophylaxis. Within the current literature there are no figures reported specifically for those individuals treated with circular frames. Our aim was to evaluate the VTE incidence within a single surgeon series and to evaluate potential risk factors. METHODS: We retrospectively reviewed our consecutive single surgeon series of 177 patients admitted to a major trauma unit with tibial fractures. All patients received standardised care, including chemical thromboprophylaxis within 24h of injury until independent mobility was achieved. We comprehensively reviewed our prospective database and medical records looking at demographics and potential risk factors. RESULTS: Seven patients (4.0% ± 2.87%) developed symptomatic VTE during the course of frame treatment; three deep vein thrombosis (DVTs) and four pulmonary embolisms (PEs). Those with a VTE event had significantly increased body mass index (BMI) (p = 0.01) when compared to those without symptomatic VTE. No differences (p > 0.05) were observed between the groups in age, gender, smoking status, fracture type (anatomical allocation or open/closed), delay to frame treatment, weight bearing status post-frame, inpatient stay or total duration of frame treatment. CONCLUSION: This study suggests that increased BMI is a statistically significant risk factor for VTE, as reported in current literature. In addition, we calculated the true risk of VTE following circular frame treatment for tibial fracture in our series is from 1.13% to 6.87%, which is at least comparable to other forms of treatment.

Comprehensive processing, display and analysis for in vivo MR spectroscopic imaging.

Image reconstruction for magnetic resonance spectroscopic imaging (MRSI) requires specialized spatial and spectral data processing methods and benefits from the use of several sources of prior information that are not commonly available, including MRI-derived tissue segmentation, morphological analysis and spectral characteristics of the observed metabolites. In addition, incorporating information obtained from MRI data can enhance the display of low-resolution metabolite images and multiparametric and regional statistical analysis methods can improve detection of altered metabolite distributions. As a result, full MRSI processing and analysis can involve multiple processing steps and several different data types. In this paper, a processing environment is described that integrates and automates these data processing and analysis functions for imaging of proton metabolite distributions in the normal human brain. The capabilities include normalization of metabolite signal intensities and transformation into a common spatial reference frame, thereby allowing the formation of a database of MR-measured human metabolite values as a function of acquisition, spatial and subject parameters. This development is carried out under the MIDAS project (Metabolite Imaging and Data Analysis System), which provides an integrated set of MRI and MRSI processing functions. It is anticipated that further development and distribution of these capabilities will facilitate more widespread use of MRSI for diagnostic imaging, encourage the development of standardized MRSI acquisition, processing and analysis methods and enable improved mapping of metabolite distributions in the human brain.