Compatibility analysis of bergapten with different pharmaceutical excipients used in nanostructured lipid carriers.

In pharmaceuticals sciences, Fourier-transform infrared spectroscopy (FTIR) is a very useful technique to measure the compatibility and interaction between ingredients, therefore in the current study, compatibility of bergapten with different excipients was analyzed via FTIR. Nanostructured lipid carriers (NLCs) are the second generation of lipid nanocarriers and very useful for the drug delivery systems. Nanoparticles (NPs) were prepared by a nanotemplate engineering technique and scanning of pure drug, individual ingredients and, physical mixtures of different ingredients was carried out. The characteristic peak of the carboxylic groups of bergapten is shifted from 3088.1 cm-1 to 3399.3 cm-1 due to formulation development and it confirmed that it was properly incorporated into the formulation. Other peaks of the drug were also present in formulation with minor shortening/broadening of peaks. The resulted peaks of IR spectra depicted that the ingredients used in the formulation had no considerable interaction and were found compatible with each other.

Isolation and in silico prediction of potential drug-like compounds from Anethum sowa L. root extracts targeted towards cancer therapy.

Anethum sowa L. has been used as a spice herb in the Asian and European culinary systems to add flavour and taste. The studied plant has diverse folkloric medicinal value. Present study was designed to isolate phytochemicals from the hexane, chloroform and ethyl acetate extracts of the roots by various chromatographic techniques. Based on spectral analysis (IR, LC-MS, NMR) the isolated compounds were identified as physcione (1), ß-sitosterol (2), stigmasterol (3), 2-oxo-3-propyl-2H-chromene-7-carboxylic acid (4), bergapten (5), 3-ethyl-7-hydroxy-2H-chromen-2-one (6) and graveolone (7). The mentioned compounds have been isolated for the first time from the roots part of the plant. Based on extensive literature review, physcione and bergapten were inferred to exhibit crucial bioactivities including inhibitory efficacy against various forms of cancer. Accordingly, in the present research approach molecular docking investigations of the isolated phytochemicals have been robustly executed with different oncogenes that have been reported to be actively involved in various forms of carcinoma. In silico investigations encompassing molecular docking analysis and drug-likeness profiling was executed to estimate the potential therapeutic tendencies of the phytochemicals targeted towards effective cancer therapy. Current investigation offers meaningful know-how pertaining to potential anticancer activities of the phytochemicals extracted from the roots of Anethum sowa L. and might open up new revenues towards effective drug development against cancer.

Accelerated Development and Toxin Tolerance of the Navel Orangeworm Amyelois transitella (Lepidoptera: Pyralidae) in the Presence of Aspergillus flavus.

The navel orangeworm (Amyelois transitella) and the fungus Aspergillus flavus constitute a facultative mutualism and pest complex in tree nut and fruit orchards in California. The possibility exists that the broad detoxification capabilities of A. flavus benefit its insect associate by metabolizing toxicants, including hostplant phytochemicals and pesticides. We examined this hypothesis by conducting laboratory bioassays to assess growth rates and survivorship of pyrethroid-resistant (R347) and susceptible (CPQ) larval strains on potato dextrose agar diet containing almond meal with and without two furanocoumarins, xanthotoxin and bergapten, found in several hostplants, and with and without two insecticides, bifenthrin and spinetoram, used in almond and pistachio orchards. Additionally, fungi were incubated in liquid diets containing the test chemicals, and extracts of these diets were added to almond potato dextrose agar (PDA) diets and fed to larvae to evaluate the ability of the fungus to metabolize these chemicals. Larvae consuming furanocoumarin-containing diet experienced higher mortality than individuals on unamended diets, but adding A. flavus resulted in up to 61.7% greater survival. Aspergillus flavus in the diet increased development rate > two-fold when furanocoumarins were present, demonstrating fungal enhancement of diet quality. Adding extracts of liquid diets containing xanthotoxin and fungus decreased mortality compared to xanthotoxin alone. On diets containing bifenthrin and spinetoram, however, mortality increased. These results support the hypothesis that A. flavus enhances navel orangeworm performance and contributes to detoxification of xenobiotics. Among practical implications of our findings, this mutualistic association should be considered in designing chemical management strategies for these pests.

Bergapten inhibits liver carcinogenesis by modulating LXR/PI3K/Akt and IDOL/LDLR pathways.

Oxysterol receptors LXRs (α and ß) are recently reported to be one of the novel and potential therapeutic targets in reducing cell proliferation and tumor growth in different system model. Activation of LXRs is correlated with modification of PI3K/Akt pathway. LXRs are also found to play a critical role in maintaining lipid homeostatais by regulating ABCA1, IDOL, SREBP1, LDLR and also certain lipogenic genes such as FASN and SCD1. In the present study a potential furanocoumarin, Bergapten (BeG) has been evaluated for its anticancer property on Hepatocellular Carcinoma (HCC) on LXR axis. The molecular docking analysis was carried out for BeG on LXR (α & ß) using Maestro tool and compared with reference ligands. This was followed by in vitro (HepG2 cell lines) and in vivo (on NDEA induced HCC in Wistar albino rats) anticancer evaluation of BeG. The docking results revealed polar and hydrophobic interactions of BeG with LXR (α,ß). The in vitro studies revealed the potential of BeG in lowering the accumulation of lipid droplets in HepG2 cells which was correlated with increase in LXR (α,ß) protein expressions. Furthermore, the in vivo studies demonstrated the potential of BeG in ameliorating the cancer induced alterations in body weight, liver weight and significant restoration of the changes in mRNA and protein expressions of LXR(α,ß), ABCA1, IDOL, SREBP1 and LDLR. BeG also modulated the expressions of PI3K, Akt and certain lipogenic genes like FASN and SCD1 and reduced the lipid droplets level in liver cancer cells. These results provide evidence and validates the critical role of BeG in maintaining the lipid homeostasis and justifies its anticancer potential against NDEA-induced HCC.