Host-Guest Interaction Study of Olmesartan Medoxomil with ß-Cyclodextrin Derivatives.

Olmesartan medoxomil (OLM) is a selective angiotensin II receptor antagonist used in the treatment of hypertension. Its therapeutic potential is limited by its poor water solubility, leading to poor bioavailability. Encapsulation of the drug substance by two methylated cyclodextrins, namely randomly methylated ß-cyclodextrin (RM-ß-CD) and heptakis(2,3,6-tri-O-methyl)-ß-cyclodextrin (TM-ß-CD), was carried out to overcome the limitation related to OLM solubility, which, in turn, is expected to result in an improved biopharmaceutical profile. Supramolecular entities were evaluated by means of thermoanalytical techniques (TG-thermogravimetry; DTG-derivative thermogravimetry), spectroscopic methods including powder X-ray diffractometry (PXRD), universal-attenuated total reflectance Fourier-transform infrared (UATR-FTIR) and UV spectroscopy, saturation solubility studies, and by a theoretical approach using molecular modeling. The phase solubility method reveals an AL-type diagram for both inclusion complexes, indicating a stoichiometry ratio of 1:1. The values of the apparent stability constant indicate the higher stability of the host-guest system OLM/RM-ß-CD. The physicochemical properties of the binary systems are different from those of the parent compounds, emphasizing the formation of inclusion complexes between the drug and CDs when the kneading method was used. The molecular encapsulation of OLM in RM-ß-CD led to an increase in drug solubility, thus the supramolecular adduct can be the subject of further research to design a new pharmaceutical formulation containing OLM, with improved bioavailability.

Oridonin from Rabdosia rubescens: An emerging potential in cancer therapy - A comprehensive review.

Cancer incidences are rising each year. In 2020, approximately 20 million new cancer cases and 10 million cancer-related deaths were recorded. The World Health Organization (WHO) predicts that by 2024 the incidence of cancer will increase to 30.2 million individuals annually. Considering the invasive characteristics of its diagnostic procedures and therapeutic methods side effects, scientists are searching for different solutions, including using plant-derived bioactive compounds, that could reduce the probability of cancer occurrence and make its treatment more comfortable. In this regard, oridonin (ORI), an ent-kaurane diterpenoid, naturally found in the leaves of Rabdosia rubescens species, has been found to have antitumor, antiangiogenesis, antiasthmatic, antiinflammatory, and apoptosis induction properties. Extensive research has been performed on ORI to find various mechanisms involved in its anticancer activities. This review article provides an overview of ORI's effectiveness on murine and human cancer populations from 1976 to 2022 and provides insight into the future application of ORI in different cancer therapies.

Selective in vitro anti-melanoma activity of ursolic and oleanolic acids.

Products of natural origin have become important agents in the treatment of cancer, and the active principles of natural sources could be used in combination with chemotherapeutic agents to increase their effects and to minimize their toxicity. Oleanolic (OA) and ursolic (UA) acids are intensely studied for their promising anticancer potential. The aim of this study was focused on the in vitro toxicological effects induced by UA and OA human mesenchymal stem cells and on melanoma, one of the most frequent cancers whose incidence is increasing every year. The two compounds were tested for their cytotoxic, cell cycle arrest and pro-apoptotic effects on melanoma cells (A375 and B164A5) and mesenchymal stem cells. UA exerted a cytotoxic effect in a dose-dependent manner on melanoma cells, while OA's activity has been shown to be low or moderate. Both compounds produced alterations of the cell cycle, arresting cells in the G0/G1 phase. Furthermore, UA induced significant apoptosis through the bcl-2 genes family pathway, with the decrease of the bcl-2 gene expression. The two compounds exerted selective effects on melanoma cells with no effects on human mesenchymal stem cells. The presented results reveal the anticancer potential of UA on melanoma cells, with no detectable toxicity on the mesenchymal stem cells.

Effects of ursolic and oleanolic on SK­MEL­2 melanoma cells: In vitro and in vivo assays.

Among the triterpenoids, oleanolic acid (OA) and its isomer, ursolic acid (UA) are promising therapeutic candidates, with potential benefits in the management of melanoma. In this study, we aimed to examine the in vitro and in vivo anti­invasive and anti­metastatic activity of OA and UA to determine their possible usefulness as chemopreventive or chemotherapeutic agents in melanoma. For the in vitro experiments, the anti­proliferative activity of the triterpenic compounds on SK­MEL­2 melanoma cells was examined. The anti­invasive potential was assessed by testing the effects of the active compound on vascular cell adhesion molecule (VCAM) and intercellular adhesion molecule (ICAM) adhesion to melanoma cells. Normal and tumor angiogenesis were evaluated in vivo by chicken embryo chorioallantoic membrane (CAM) assay. The two test triterpenoid acids, UA and OA, exerted differential effects in vitro and in vivo on the SK­MEL­2 melanoma cells. UA exerted a significant and dose­dependent anti­proliferative effect in vitro, compared to OA. The cytotoxic effects in vitro on the melanoma cells were determined by the examining alterations in the cell cycle phases induced by UA that lead to cell arrest in the S phase. Moreover, UA was found to affect SK­MEL­2 melanoma cell invasiveness by limiting the cell adhesion capacity to ICAM molecules, but not influencing their adhesion to VCAM molecules. On the whole, in this study, by assessing the effects of the two triterpenoids in vivo, our results revealed that OA had a greater potential to impair the invasive capacity and tumor angiogenesis compared with UA.

Design management of functional foods for quality of life improvement.

The paper examines the benefit of bread enriched with antioxidants on oxidative stress, and on the quantities of hydrosoluble antioxidants in a group of human subjects. The home-management of functional foods strategy seeks to improve prompt and effective basic nutrition using additional attributes that are directly positively beneficial for health and well-being. The purpose of this clinical study was to test the tolerance and benefits of multicomponent functional foods enriched with antioxidant compounds obtained from plant extracts on healthy adult volunteers. A detailed protocol was created to formalize and standardize the procedures for data collection, e.g. filling out standardized forms and functional diet questionnaires. For the research method, Group A was given the special diet enriched with multicomponent antioxidant foods and Group B (control). The data were analysed using the quantitative methods. They showed significant increase of hydrosoluble antioxidants in group A compared to control, from 220.61+/-27.92 - 313.56+/-37.09 micrograms/mL (p=0.05), compared to 280.47+/-32.1 - 238.27+/-44.93 micrograms/mL (p=0.45). Also, oxidative stress values showed a decrease in the diet group compared to control that reached statistical significance. Oxidative stress decreased in the diet group to 244 +/- 89 compared to 308+/-108 UFORT in the control group. The responses of the prevention of chronic diseases to a functional foods strategy depend on how they are absorbed and utilized in the body. An anti-oxidant diet with natural bioactive components could become an interesting solution for degenerative disorders in which oxidative stress is increased.

Study on the stability and antioxidant effect of the Allium ursinum watery extract.

BACKGROUND: Organosulfur compounds usually present a reduced stability especially in the presence of oxygen. This research aimed to study the stability and antioxidant potential of the Allium ursinum watery extract. RESULTS: The decrease of the antioxidant capacity verifies an exponential relation which may be formally associated to a kinetically pseudomonomolecular process. The exponential regression equation allows the half-life of the degradation process to be determined, this being 14 hours and 49 minutes in a watery environment at room temperature. CONCLUSIONS: The watery extract of Allium ursinum changes its proprieties in time. This might be explained by the network of hydrogen bonds in a watery environment which has a protective effect on the dissolved allicin molecule.

Reverse phase chromatographic behaviour of major components in Capsicum Annuum extract.

BACKGROUND: The purpose of the study is to develop a suitable analytical method in order to establish appropriate conditions for isolation and assay of the dominant compounds in extracts of Capsicum annuum. RESULTS: The studies are performed with standard substances to establish the HPLC conditions for complete separation of capsaicin and dihydrocapsaicin, the two major components of interest. Because of their prevalent apolar features, reverse phase chromatographic version was approached. Systematic studies on different eluents revealed the 65% methanol-35% water mixture as a proper mobile phase providing a complete separation of the components according to analytical claims. CONCLUSIONS: The results may be of interest to develop a specific analytical procedure with advanced specificity for quantitative assay of capsaicin and dihydrocapsaicin in pharmaceutical products and in foods.

Design of optimal solvent for extraction of bio-active ingredients from six varieties of Medicago sativa.

BACKGROUND: Extensive research has been performed worldwide and important evidences were collected to show the immense potential of plants used in various traditional therapeutic systems. The aim of this work is to investigate the different extracting solvents in terms of the influence of their polarity on the extracting ability of bioactive molecules (phenolic compounds) from the M. sativa flowers. RESULTS: The total phenolic content of samples was determined using the Folin Ciocalteu (FC) procedure and their antioxidant activity was assayed through in vitro radical decomposing activity using the radical DPPH° assay (IUPAC name for DPPH is (phenyl)-(2,4,6-trinitrophenyl) iminoazanium). The results showed that water was better than methanol and acetic acid for extracting bioactive compounds, in particular for total phenolic compounds from the flowers of alfalfa. The average content of bioactive molecules in methanol extract was 263.5±1.02 mg GAE/100g of dry weight lyophilized extract. The total phenolic content of the tested plant extracts was highly correlated with the radical decomposing activity. However, all extracts were free-radical inhibitors, but the water extract was more potent than the acetic and the methanol ones. The order of inhibitor effectiveness (expressed by IC50) proved to be: water extract (0.924mg/mL) > acetic acid extract (0.154mg/mL) > methanol (0.079mg/mL). The profiles of each extract (fingerprint) were characterized by FT-MIR spectroscopy. CONCLUSIONS: The present study compares the fingerprint of different extracts of the M. sativa flowers, collected from the wild flora of Romania. The total phenolic content of the tested plant extracts was highly correlated with the radical decomposing activity. The dependence of the extract composition on the solvent polarity (acetic acid vs. methanol vs. water) was revealed by UV-VIS spectrometry and Infrared fingerprint.