Ethnomedicinal documentation and anti-inflammatory effects of n-butanol extract and of four compounds isolated from the stems of Pituranthos scoparius: An in vitro and in vivo investigation.

ETHNOPHARMACOLOGICAL RELEVANCE: Pituranthos scoparius is a medicinal plant belonging to the Apiaceae family. It thrives in North Africa, and is widely distributed in the high plateau of most parts of the Sahara in Algeria. This plant is widely used in the Algerian traditional medicine to treat numerous infectious diseases, dermatoses, nervous breakdowns, digestive disorders, and calm abdominal pain. AIM OF THE STUDY: The aim of the present work was to examine the ethnomedicinal uses of Pituranthos scoparius in Setif region, Algeria, isolate and identify the chemical constituents of the n-butanol stem extract of P. scoparius (BEPS), and to determine the toxicity and anti-inflammatory effects of these compounds in addition to the extract. MATERIALS AND METHODS: The anti-inflammatory effects of BEPS and the four compounds isolated from the extract were evaluated using the in vitro protein denaturation assay, whereas the topical anti-inflammatory activity was assessed using the croton oil-induced ear edema in mice. Toxicity was determined based on assessment of in vitro cytotoxicity using hemolytic activity against human red blood cells (RBCs). RESULTS: Four compounds, identified as the rare isorhamnetin-3-O-ß-apiofuranosyl (1 â†’ 2)-ß glucopyranoside (2), in addition to three known compounds, namely isorhamnetin-3-O-ß-glucoside (1), D-mannitol (3), and isorhamnetin-3-O-ß-glucopyranosyl-(1 â†’ 6)-ß-glucopyranoside (4) were isolated from BEPS. These compounds were characterized by means of NMR and high-resolution mass spectral (HRMS) data. These four compounds were isolated for the first time from this traditional Algerian medicinal plant. Screening of the extract indicated the presence of alkaloids, polyphenols, flavonoids, free quinones, coumarins and tannins. Topical anti-inflammatory effect showed that the four isolated compounds, as well as BEPS, exhibit a significant (p < 0.05) dose-dependent (0.5 and 1 mg/ear) anti-inflammatory effect. At a dose of 1 mg/ear, compounds 1, 2, and 4, exhibited remarkable anti-inflammatory effect with a percentage inhibition of 85.50 ± 2.78, 79.78 ± 4.68, and 75.78 ± 2.98%, respectively. Results from in vitro cytotoxicity showed that the % lysis of the extract, along with isolated compounds was found to be virtually nontoxic. CONCLUSIONS: These results suggest that BEPS and isolated compounds are safe, nontoxic, and exert remarkable anti-inflammatory effects, and can be new sources of natural anti-inflammatory agents.

Grafting of anti-nucleolin aptamer into preformed and remotely loaded liposomes through aptamer-cholesterol post-insertion.

A new combination strategy of an active loading and active targeting approach was applied in this work. The liposomes actively loaded with Curcumin (CRM) (LipCRM) were decorated with cholesterol tagged-anti-nucleolin AS1411 aptamer (NCL) via a new post-insertion approach, utilizing the cholesterol as a wedge to incorporate aptamer into the surface of the liposome bilayer. A successful NCL post-insertion was verified by agarose gel electrophoresis and dynamic light scattering (DLS). The cellular uptake of AptNCL-Lip was investigated using flow cytometry and Confocal Laser Scanning Microscopy (CLSM) on two different human breast cancer cell lines (MCF-7 and MDA-MB-231). The uptake and cytotoxicity of loaded CRM were investigated using flow cytometry and MTT assay. Our results showed successful post insertion of NCL aptamer to the surface of Lip. Also, higher cellular uptake was noted for AptNCL-Alexa-LipRhod compared to blank LipRhod in both cell lines. Moreover, CLSM showed prominent endocytosis and uptake of AptNCL-Alexa-LipRhod into the cytoplasm of breast cancer cells. Furthermore, the results showed a significant increase in the uptake and cytotoxicity of AptNCL-LipCRM compared to LipCRM in both cell lines. Overall, our results demonstrate a successful post-insertion of cholesterol-tagged aptamer into liposomes and the possible combination between active loading and active targeting.