Anti-inflammatory potential of spectroscopically analyzed trans-13-octadecenoic acid of Yucca elephantipes Regel roots: in-vitro and in-vivo analysis.

Plants are always better choice for treatment of disease in contrast to synthetic agents due to their less toxicity, and free availability with minor limitations of identifications, purity and potency which should be addressed. The objective of current study was to explore the anti-inflammatory effect of methanol extract of Yucca elephantipes roots by using oxidative burst assay and carrageen an induced rat paw edema. GC-MS analysis was carried for the determination of ani-inflammatory potential of fatty acids and other phytochemicals present in Yucca elephantipes roots. Among fifteen detected compounds trans-13-octadecenoic acid, n-hexadecanoic acid and 4-hydroxy benzoic acid were found as 84.21%, 5.21% and 2.17% respectively. Oxidative burst assay showed anti-inflammatory potential of Yucca elephantipes roots 74.58±0.32% with IC50 of 15.3±2.2µg/mL as compared to Ibuprofen with percentage of inhibition 73.20±0.17% and IC50 was 11.2±0.98µg/mL. Fortunately, less than 8g/kg dose of the Yucca elephantipes roots found safe in albino rats. Interestingly, in-vivo carrageen an induced paw edema method proved its anti-inflammatory potential at dose 100 and 200mg/kg in albino rats. Conclusively, 200mg/kg dose of Yucca elephantipes roots extract was optimized for 88.89±0.015% anti-inflammatory effect which can be considered most potent, safe and better alternative of synthetic drugs.

Synthesis of Ligand Functionalized ErbB-3 Targeted Novel DNA Nano-Threads Loaded with the Low Dose of Doxorubicin for Efficient In Vitro Evaluation of the Resistant Anti-Cancer Activity.

PURPOSE: Doxorubicin (Dox) being a hydrophobic drug needs a unique carrier for the effective encapsulation with uniformity in the aqueous dispersion, cell culture media and the biological-fluids that may efficiently target its release at the tumor site. METHODS: Circular DNA-nanotechnology was employed to synthesize DNA Nano-threads (DNA-NTs) by polymerization of triangular DNA-tiles. It involved circularizing a linear single-stranded scaffold strand to make sturdier and rigid triangles. DNA-NTs were characterized by the AFM and Native-PAGE tests. Dox binding and loading to the Neuregulin1 (NRG1) functionalized DNA based nano-threads (NF-DBNs) was estimated by the UV-shift analysis. The biocompatibility of the blank NRG-1/DNA-NTs and enhanced cytotoxicity of the NF-DBNs was assessed by the MTT assay. Cell proliferation/apoptosis was analyzed through the Flow-cytometry experiment. Cell-surface binding and the cell-internalization of the NF-DBNs was captured by the double-photon confocal microscopy (DPCM). RESULTS: The AFM images revealed uniform DNA-NTs with the diameter 30 to 80 nm and length 400 to 800 nm. PAGE native gel was used for the further confirmation of the successful assembly of the strands to synthesize DNA-NTs that gave one sharp band with the decreased electrophoretic mobility down the gel. MTT assay showed that blank DNA-NTs were biocompatible to the cells with less cytotoxicity even at elevated concentrations with most of the cells (94%) remaining alive compared to the dose-dependent enhanced cytotoxicity of NF-DBNs further evidenced by the Flow-cytometry analysis. CONCLUSION: Uniform and stiffer DNA-NTs for the potential applications in targeted drug delivery was achieved through circular DNA scaffolding.

Synthesis, characterization, computational assay and anti-inflammatory activity of thiosemicarbazone derivatives: Highly potent and efficacious for COX inhibitors.

Multiple studies in the literature have demonstrated that synthetic compounds containing heterocyclic rings possess a reparative potential against acute and chronic inflammation. In the present study, two novel thiosemicarbazone derivatives based on l-ethyl-6-(thiophen-2-yl)indoline-2,3-dione with different phenyl substituted thiosemicarbazides were synthesized by condensation reaction and the structures of proposed target compounds (KP-2 and KP-5) were confirmed by UV-VIS, FTIR, 1H-NMR and 13C-NMR. In-vitro anti-inflammatory behavior of KP-2 and KP-5 was confirmed by bovine serum albumin (BSA) and ovine serum albumin (OSA) analysis. Acute and chronic anti-inflammatory potential of synthesized compounds were evaluated by using carrageenan and complete Freund's adjuvant (CFA) as inflammation-inducing agents, respectively. Inhibition of pro-inflammatory mediators and prevention of protein denaturation owing to synchronization of more electronegative flouro-groups substituted on phenyl rings along with heterocyclic indoline ring provides anti-inflammatory effects and are corroborated by radiological, histopathological analysis. Additional support was provided through density functional theory (DFT) and molecular docking. KP-5 exhibited excellent lead-likeness based on its physicochemical parameters, making it a viable drug candidate. The synthesized compounds also showed promising ADMET properties, enhancing their potential as therapeutic agents. These findings emphasize the pivotal role of new compounds for drug design and development.

Synthetic NRG-1 functionalized DNA nanospindels towards HER2/neu targets for in vitro anti-cancer activity assessment against breast cancer MCF-7 cells.

DNA based nano-carriers synthesized from short circular scaffolds (circular DNA nanotechnology) attains stiffer topology for ligand functionalization (neuregulin-1/NRG-1 ligand) and biological applications (targeted drug delivery). Daunorubicin (DR) is a hydrophobic chemical that requires robust vectors to efficiently encapsulate and avoid its free dispersion in water, biological media and cell culture. Here we design DNA nanospindels (DNA-NS) to efficiently load DR and target the (highly expressed) HER2/neu receptors on the plasma membrane of drug-resistant MCF-7 (breast cancer) cells. DNA-NS were synthesized by polymerizing the DNA-triangles (utilizing 84-nt short circular scaffold strand) into larger DNA nano-ribbons characterized by the native-PAGE testing. AFM results revealed the spinning of DNA nanoribbons on its (own) axis because of the intrinsic curvature of the DNA double helix resulting in the formation of the firm and twisted DNA-NS with the diameter (50-70 nm) and length (0.5-4 µm). DA loading onto DNA-NS was confirmed by the UV shift analysis. The MTT results with the blank DNA-NS evidenced its biocompatibility (remained value of 93%) compared to the decreased viability of the MCF-7 cells after treatment with DNA-NS (DR loaded). These findings were further supported by the analysis of cell proliferation/apoptosis through flow cytometry showing 64% apoptosis after treating with the DR loaded DNA-NS. Hence, through the short circular DNA nanotechnology, we have achieved a stiffer, uniform, and biocompatible DNA-NS for applications in the targeted therapy.