Anticancer effects of rutin from Fagopyrum tataricum (tartary buckwheat) against osteosarcoma cell line.

BACKGROUND: The present study is analysisof the seeds of buckwheat (Fagopyrum sp.),member of the Polygonaceae family for isolation of rutin and its anticancer property againstOsteosarcoma celllines (SAOS2). The selected plant is traditionally used for diabetes and cancer. It has several biological properties such as antibacterial, antioxidant and anti-aging. PURPOSE: Thirty-five buckwheat cultivars were obtained from Nepal Agriculture Genetic Resources Centre (NAGRC) Khumaltar, Kathmandu, Nepal, and Kumrek Sikkim. These plant varieties are scientifically evaluated their biological properties. METHODS: Rutin wasfractionated from buckwheat seeds using methanol fraction and analysed for quality by HPLC method. The rutin fraction of the cultivar NGRC03731 a tartary buck wheat and standard rutin was used against Osteosarcoma cell lines (SAOS2) and human gingival fibroblast cells (hGFs) for anticancer activity. The cell viability using rutin fraction and standard rutin treated with SAOS2 cells were assessed by MTT assay. For further research, the best doses (IC-50: 20 g/ml) were applied. By using AO/EtBr dual staining, the effects of Rutin fraction on SAOS2 cell death were analysed. The scratch wound healing assay was used to analyse cell migration. Real-time PCR was used to analyse the pro-/anti-apoptotic gene expression. RESULTS: The seeds with the highest rutin content, NGRC03731 seeds, had 433 mg/100 g of rutin.The rutin fraction treatment and standard rutin significantly reduced cell viability in the MTT assay, and osteosarcoma cells were observed on sensitive to the IC-50 dose at a concentration of 20 g/ml after 24 h.The SAOS2 cells exposed to rutin fraction at 20 g/ml and standard rutin at 10 g/ml exhibited significant morphological alterations, cell shrinkage and decreased cell density, which indicate apoptotic cells.Rutin-fraction treated cells stained with acridine orange/ethidium bromide (AO/EtBr) dual staining cells turned yellow, orange, and red which indicatesto measure apoptosis.The anti-migration potential of rutin fraction, results prevented the migration of SAOS2 cancer cells.Rutin-fraction significantly increased the expression of pro-apoptotic proteinsBad, using real-time PCR analysis (mRNA for Bcl-2 family proteins) resulted Bcl-2's expression is negatively regulated. CONCLUSION: Osteosarcoma (SAOS2) cell lines' proliferation, migration, and ability to proliferate were reduced markedly by rutin fraction and it also causes apoptosis of Osteosarcoma cell lines (SAOS2).

Mosquitocidal effect of monoterpene ester and its acetyl derivative from Blumea mollis (D. Don) Merr against Culex quinquefasciatus (Diptera: Culicidae) and their insilico studies.

The present study was conducted to assess the mosquitocidal efficiency of compound isolated from Blumea mollis (D. Don) Merr against Culex quinquefasciatus. Eggs and larvae of Cx. uinquefasciatus were exposed to different concentrations 0.5, 1.0, 1.5 and 2.0 ppm of compounds prepared using DMSO. Compound 1 was identified as (4R, 5S)-4-hydroxy-7-tigloyloxy carvotanacetone, from which new derivative was synthesized and confirmed as (4R, 5S)-4-acetoxy-7-tigloyloxy carvotanacetone. Both the compounds presented larvicidal and ovicidal activities. Compounds 1 and 2 at 2-ppm concentration showed 64% and 78% larval mortality in 24 h, respectively. The LC50and LC90values of compounds 1 and 2 on Cx. quinquefasciatus larvae were 1.73, 1.27 and 4.59, 3.33 ppm, respectively. The eluted compound 1 and synthesized compound 2 presented 68% and 77% of ovicidal activity, respectively, against eggs of Cx. quinquefasciatus at 120 h post-treatment. Histopathological studies of the compound-treated larvae revealed serious damage on the larval midgut cells. Furthermore, compounds 1 and 2 was tested for toxicity study and the results showed both the compounds were found to be harmless to non-target organism Poecilia reticulata. Computational analysis of compound 2 showed strong binding interaction with the AChE1 of Cx. quinquefasciatus. These results clearly suggest that compounds from Blumea mollis could act as good mosquitocidal agents against Cx.quinquefasciatus and compound 2 was first time reported.

A New Strategy to Identify ceRNA-Based CCDC144NL-AS1/SERPINE1 Regulatory Axis as a Novel Prognostic Biomarker for Stomach Adenocarcinoma via High Throughput Transcriptome Data Mining and Computational Verification.

Stomach adenocarcinoma (STAD) is one of the most malignant cancers that endanger human health. There is growing evidence that competitive endogenous RNA (ceRNA) regulatory networks play an important role in various human tumors. However, the complexity and behavioral characteristics of the ceRNA network in STAD are still unclear. In this study, we constructed a ceRNA regulatory network to identify the potential prognostic biomarkers associated with STAD. The expression profile of lncRNA, miRNA, and mRNA was downloaded from The Cancer Genome Atlas (TCGA). After performing bioinformatics analysis, the CCDC144NL-AS1/hsa-miR-145-5p/SERPINE1 ceRNA network associated to STAD prognosis of STAD was obtained. The CCDC144NL-AS1/SERPINE1 axis in the ceRNA network was identified by correlation analysis and considered as a clinical prognosis model by Cox regression analysis. In addition, methylation analysis indicated that the abnormal upregulation of CCDC144NL-AS1/SERPINE1 axis might be related to the aberrant methylation of some sites, and immune infiltration analysis suggested that CCDC144NL-AS1/SERPINE1 axis probably influences the alteration of tumor immune microenvironment and the occurrence and development of STAD. In particular, the CCDC144NL-AS1/SERPINE1 axis based on the ceRNA network constructed in the present study might be an important novel factor correlating with the diagnosis and prognosis of STAD.

Effect of monoterpene ester from Blumea axillaris (Lam.) DC and its acetyl derivative against plant pathogenic fungi and their in silico molecular docking.

The present study was aimed to isolate active constituents from Blumea axillaris (Lam.) DC (Asteraceae) against phytopathogenic fungi. Bioactivity guided fractionation of the successive n-hexane, chloroform and methanol extract led to the isolation of the monoterpene ester (4 R,5S)-4-hydroxy-7-tigloyloxycarvotanacetone (1). The compound 1 was converted into acetyl derivative (2). The acetyl derivative (2) and the parent compound 1 were tested again phytopathogenic fungi by using mycelial inhibition and minimal inhibitory concentration values were found out by the broth microdilution method. The acetyl derivative (2) showed the highest antifungal activity against Rhizoctonia solani and Aspergillus niger. Based upon in vitro results, compound 1 was tested against Fusarium oxyporum (wilting disease) and compound 2 was tested against R. solani (leaf blight disease) in vivo using the foliar spray method. Both compounds had no phytotoxicity and also in silico docking study showed that both compounds were binding similarly as commercial fungicide carbendazim.

Effect of tiliamosine, a bis, benzylisoquinoline alkaloid isolated from Tiliacora acuminata (Lam.) Hook. f. & Thom on the immature stages of filarial mosquito Culex quinquefasciatus say (Diptera: Culicidae).

The present study was aimed to check the mosquitocidal activity of tiliamosine isolated from Tiliacora acuminata (Lam.) Hook. f. & Thom against immature stages of Culex quinquefasciatus. Eggs and larvae of Cx. quinquefasciatus were exposed to different concentrations of tiliamosine - 0.5, 1.0, 1.5 and 2.0 ppm - prepared using DMSO. The compound tiliamosine showed good larvicidal activity with LC50 and LC90 values of 1.13 and 2.85 ppm respectively, against third-instar larvae of Cx. quinquefasciatus at 24 h. In control, the larvae exhibited normal movement. Tiliamosine exhibited 91% ovicidal activity at 2.0 ppm concentration after 120 h post-treatment. Lowest concentration of tiliamosine (0.5 ppm) showed 19% egg mortality. Histopathology study of the compound-treated larvae showed serious damage on the larval midgut cells. The treated larvae showed restless movement which was different from that of the control larvae. The larvae exhibited malformation in development. The compound tiliamosine was harmless to non-target organisms P. reticulata and Dragon fly nymph at tested concentrations. The compound was highly active and inhibited AChE in a concentration-dependent manner. Computational analysis of the tiliamosine had strong interaction with AChE1 of Cx. quinquefasciatus. This report clearly suggests that the isolated compound can be used as an insecticide to control mosquito population and thus prevent the spread of vector-borne diseases.

Molecular docking analysis of phytoconstituent from Momordica charantia with Guanylate Cyclase catalytic domain.

Soluble guanylate cyclase (sGC) is a type of lyase enzyme with profoundly increasing importance in treatments of cardiovascular and neurodegenerative disorders. Modulation of sGC activity demonstrated beneficial effects against Parkinson's disease by reducing glutamate excitotoxicity. It is of interest to evaluate the pharmacological activity of Momordica charantia phytoconstituent (DGalacturonic acid) and ODQ with catalytic domain of sGC enzyme, using Autodock version 4.2 programs. Docking results revealed the binding ability of ODQ at the allosteric sites of sGC. D-galacturonic acid also shows binding interaction at the same allosteric sites in the catalytic domain of sGC like ODQ. Results show that both the ligands have efficient binding to THR 474 amino acid residue of beta 1 subunit of the enzyme. The drug likeliness score further implies the suitability of D-Galacturonic acid as a drug-like molecule. The binding property of ODQ and D-Galacturonic acid with the catalytic domain help to inhibit sGC activity having pharmacological effects. Moreover, ODQ interaction with heme site of sGC is already known while its interaction with the catalytic domain is shown in this report.

Antibacterial Activity study of Musizin isolated from Rhamnus wightii Wight and Arn.

The crude extracts and the compounds isolated from traditional medicinal plants are used to treat infectious diseases caused by bacteria, fungi, and viruses. An attempt has been made in the present investigation to evaluate the antibacterial activity of musizin isolated from Rhamnus wightii, (Family: Rhamnaceae) against Gram-positive (Bacillus cereus, Staphylococcus aureus, Streptococcus faecalis), and Gramnegative (Escherichia coli, Klebsiella pneumonia, and Pseudomonas aeruginosa) bacteria. The tested compound showed more pronounced antibacterial activity against the tested pathogens than the standard antibiotics like streptomycin and gentamycin with the lowest minimum inhibitory concentration (MIC). Molecular docking analysis was performed to study the effectiveness of musizin compared to the standard antibiotics; it showed a significant interaction with the target proteins such asalgR (P. arginosa), divIVA (E. faecalis), icaA (S. aureus), plcR(B. cereus), treC (K. pneumonia) and ftsl (E. coli) and found that musizin showed higher potential with least binding energy. It has also been found that musizin had better ADMET properties than the standard drugs. Thus,musizin acts as an inhibitor of bacterial growth for consideration as a drug to treat bacterial infections.

Protective effects of Ficus carica leaves on glucose and lipids levels, carbohydrate metabolism enzymes and ß-cells in type 2 diabetic rats.

CONTEXT: The decoctions of Ficus carica Linn. (Moraceae) leaves are used in the folklore treatment of diabetes. OBJECTIVE: To evaluate the effect of F. carica on glucose and lipids levels, carbohydrate metabolism enzymes and ß-cells protective effects in type 2 diabetes. MATERIAL AND METHODS: Diabetes was induced in 15 days high-fat diet (HFD)-fed Wistar rats by intraperitoneal injection of streptozotocin (STZ) (40 mg/kg). The ethyl acetate extract (250 and 500 mg/kg) of F. carica leaves was administered for 28 days. Oral glucose tolerance (OGTT) and intraperitoneal insulin tolerance tests (ITT) were evaluated on 15th and 25th days, respectively. RESULTS: The ethyl acetate extract (250 and 500 mg/kg) of n F. carica leaves showed significant effect (p < 0.005) in the levels of blood glucose, total cholesterol (TC), triglycerides (TG), body weight and hepatic glycogen. In OGTT, F. carica (250 and 500 mg/kg) significantly (p < 0.005) detained the increase in blood glucose levels at 60 and 120 min and in ITT, F. carica enhanced the glucose utilization significantly (p < 0.005) over 30 and 60 min compared to diabetic control. Further, the altered activities of key carbohydrate metabolizing enzymes such as glucose-6-phosphatase, fructose-1,6-bisphosphatase and hexokinase in the liver tissue of diabetic rats were significantly (p < 0.005) reverted to near normal levels upon treatment with F. carica. Immumohistochemical studies of islets substantiated the cytoprotective effect on pancreatic ß-cells. DISCUSSION AND CONCLUSIONS: F. carica leaves exerted significant effect on carbohydrate metabolism enzymes with promising hypoglycemic and hypolipidemic activities in type 2 diabetic rats.