Effects of Isorhamnetin on Diabetes and Its Associated Complications: A Review of In Vitro and In Vivo Studies and a Post Hoc Transcriptome Analysis of Involved Molecular Pathways.

Diabetes mellitus, especially type 2 (T2DM), is a major public health problem globally. DM is characterized by high levels of glycemia and insulinemia due to impaired insulin secretion and insulin sensitivity of the cells, known as insulin resistance. T2DM causes multiple and severe complications such as nephropathy, neuropathy, and retinopathy causing cell oxidative damages in different internal tissues, particularly the pancreas, heart, adipose tissue, liver, and kidneys. Plant extracts and their bioactive phytochemicals are gaining interest as new therapeutic and preventive alternatives for T2DM and its associated complications. In this regard, isorhamnetin, a plant flavonoid, has long been studied for its potential anti-diabetic effects. This review describes its impact on reducing diabetes-related disorders by decreasing glucose levels, ameliorating the oxidative status, alleviating inflammation, and modulating lipid metabolism and adipocyte differentiation by regulating involved signaling pathways reported in the in vitro and in vivo studies. Additionally, we include a post hoc whole-genome transcriptome analysis of biological activities of isorhamnetin using a stem cell-based tool.

Effects of Allium roseum L. extracts on the proliferation and the differentiation of the acute myeloid leukemia cell line U937.

Epidemiologic studies keep up the proposition that Allium vegetables can lower the risk of cancers. Acute myeloid leukemia (AML) cells exhibit high proliferative potency and have a reduced capacity of undergoing apoptosis and maturation. The beneficial effects of Allium seem related to the organosulfur products generated upon processing of these species. For this purpose, the aim of this study was to test Allium roseum fresh (FAE), crude (CAE) and dried (DAE) aqueous extracts for activity against the human acute leukemia cell line (U937). As assessed by flow cytometry, inhibited cell proliferation was in a dose-dependent manner. Firstly, study showed that cell growth was inhibited with 20 mg/mL using FAE and CAE (60% and 73% respectively). Secondly, our experiments clearly indicate that all A. roseum extracts do not induce cell apoptosis. This was confirmed by the soft binding of Annexin V to phosphatidylserine. Finally, the high expression of macrophage's marker CD11 associated with adequate morphological changes proves clearly the differentiation aspect produced by A. roseum extract. Taken together, these data suggest that A. roseum could be a promising candidate for the alternative medicine in the field of cancer therapy.

Phenolic composition of Cynara cardunculus L. organs, and their biological activities.

Polyphenols are bioactive molecules exhibiting a lot of scientific attention due to their multiple biological activities. This study compared phenolic contents and antioxidant activity in Cynara cardunculus L. organs and focus on leaf phenolic compounds identification by RP-HPLC and their antibacterial activity. The analyzed organs exhibited different total polyphenol contents (7-14.8 mg GAE g(-1) DW). Leaf and seed phenolic contents were similar and two times higher than those in flowers. The same tendency was observed for the amount of flavonoids and tannins. However, seed extracts displayed the highest DPPH. scavenging ability with the lowest IC50 value (23 microg ml(-1)), followed by leaves and flowers (over 50 microg ml(-1)). In contrast, leaves showed the highest capacity to quench superoxide (IC50: 1 microg ml(-1)) as compared to seeds (6 microg ml(-1)). In addition, cardoon leaves were efficient to inhibit growth of pathogenic bacteria mainly against Staphylococcus aureus and Escherichia coli. The identification of phenolic compounds from leaves revealed that syringic and trans-cinnamic acids were the major molecules.

Influence of biological, environmental and technical factors on phenolic content and antioxidant activities of Tunisian halophytes.

Halophyte ability to withstand salt-triggered oxidative stress is governed by multiple biochemical mechanisms that facilitate retention and/or acquisition of water, protect chloroplast functioning, and maintain ion homeostasis. Most essential traits include the synthesis of osmolytes, specific proteins, and antioxidant molecules. This might explain the utilization of some halophytes as traditional medicinal and dietary plants. The present study aimed at assessing the phenolic content and antioxidant activities of some Tunisian halophytes (Cakile maritima, Limoniastrum monopetalum, Mesembryanthemum crystallinum, M. edule, Salsola kali, and Tamarix gallica), depending on biological (species, organ and developmental stage), environmental, and technical (extraction solvent) factors. The total polyphenol contents and antioxidant activities (DPPH and superoxide radicals scavenging activities, and iron chelating and reducing powers) were strongly affected by the above-cited factors. Such variability might be of great importance in terms of valorising these halophytes as a source of naturally secondary metabolites, and the methods for phenolic and antioxidant production.

Tamarix gallica phenolics protect IEC-6 cells against H2O2 induced stress by restricting oxidative injuries and MAPKs signaling pathways.

Polyphenolic compounds gained interest in the pharmaceutical research area due to their beneficial properties. Herein, antioxidant and cytoprotective capacities of T. gallica extract on H2O2-challenged rat small intestine epithelial cells were investigated. To set stress conditions, IEC-6 cultures were challenged with numerous H2O2 doses and durations. Then, 40µM H2O2 during 4h were selected to assess the cytoprotective effect of different T. gallica extract concentrations. Oxidative parameters, measured through CAT and SOD activities as well as MDA quantification were assessed. In addition, the expression of possibly involved MAPKs was also valued. Main results reported that T. gallica was rich in polyphenols and exhibited an important antioxidant activity (DPPH Assay, IC50=6µgmL-1; ABTS+ test, IC50=50µgmL-1; Fe-reducing power, EC50=100µgmL-1). The exposure of IEC-6 cultures to 40µM H2O2 during 4h caused oxidative stress manifested by (i) over 70% cell mortality, (ii) over-activity of CAT (246%), (iii) excess in MDA content (18.4nmolmg-1) and (iiii) a trigger of JNK phosphorylation. Pretreatment with T. gallica extract, especially when used at 0.25µgmL-1, restored cell viability to 122%, and normal cell morphology in H2O2-chalenged cells. In addition, this extract normalized CAT activity and MDA content (100% and 14.7nmolmg-1, respectively) to their basal levels as compared to control cells. Furthermore, stopping cell death seems to be due to dephosphorylated JNK MAPK exerted by T. gallica bioactive compounds. In all, T. gallica components provided a cross-talk between regulatory pathways leading to an efficient cytoprotection against harmful oxidative stimulus.

Anticancer effect of Tamarix gallica extracts on human colon cancer cells involves Erk1/2 and p38 action on G2/M cell cycle arrest.

Taking into account that oxidative stress is among the factors causing cancer-related death; chemoprevention which consists in using antioxidant substances such as phenolics could prevent cancer formation and progression. In the present study, phenolic contents and antioxidant activities of methanolic extracts from the halophyte Tamarix gallica shoots were determined. Moreover, the anticancer effect of this species on human colon cancer cells and the likely underlying mechanisms were also investigated. Shoot extracts showed an appreciable total phenolic content (85 mg GAE/g DW) and a high antioxidant activity (IC50 = 3.3 µg/ml for DPPH test). At 50 and 100 µg/ml, shoot, leaf, and flower extracts significantly inhibited Caco-2 cell growth. For instance, almost all plant part extracts inhibited cell growth by 62 % at the concentration 100 µg/ml. DAPI staining results revealed that these extracts decrease DNA synthesis and confirm their effect on Caco-2 cells proliferation, principally at 100 µg/ml. More importantly, cell mitosis was arrested at G2/M phase. The changes in the cell-cycle-associated proteins (cyclin B1, p38, Erk1/2, Chk1, and Chk2) are correlated with the changes in cell cycle distribution. Taken together, our data suggest that T. gallica is a promising candidate species to be used as a source of anticancer biomolecules.

In Vitro Antiproliferative Effect of Arthrocnemum indicum Extracts on Caco-2 Cancer Cells through Cell Cycle Control and Related Phenol LC-TOF-MS Identification.

This study aimed to determinate phenolic contents and antioxidant activities of the halophyte Arthrocnemum indicum shoot extracts. Moreover, the anticancer effect of this plant on human colon cancer cells and the likely underlying mechanisms were also investigated, and the major phenols were identified by LC-ESI-TOF-MS. Results showed that shoot extracts had an antiproliferative effect of about 55% as compared to the control and were characterised by substantial total polyphenol content (19 mg GAE/g DW) and high antioxidant activity (IC50 = 40 µ g/mL for DPPH test). DAPI staining revealed that these extracts decrease DNA synthesis and reduce the proliferation of Caco-2 cells which were stopped at the G2/M phase. The changes in the cell-cycle-associated proteins (cyclin B1, p38, Erk1/2, Chk1, and Chk2) correlate with the changes in cell cycle distribution. Eight phenolic compounds were also identified. In conclusion, A. indicum showed interesting antioxidant capacities associated with a significant antiproliferative effect explained by a cell cycle blocking at the G2/M phase. Taken together, these data suggest that A. indicum could be a promising candidate species as a source of anticancer molecules.

Effect of salt treatment on phenolic compounds and antioxidant activity of two Mesembryanthemum edule provenances.

Mesembryanthemum edule L. is an edible and medicinal halophyte widespread in Tunisia seashore. In this study, parameters of oxidative stress, phenolic compounds and antioxidant activities were comparatively investigated in two M. edule provenances (Jerba and Bizerte, respectively sampled from arid and humid bioclimatic stages). Plants were subjected to 0, 300 and 600mM NaCl treatment under glasshouse conditions. Results showed that M. edule response to salinity depends on provenance (P), salt treatment (T) and their interaction (P×T). (T) affected more significantly the oxidative stress parameters and antioxidant activities than (P) and (P×T). Conversely, (P) was much affluent for tannin polymerization degree and interaction between the two factors (P×T) was more determinants for analyzed antioxidant parameters. The higher salt tolerance of Jerba plants was associated with low levels of malondialdehyde and of electrolyte leakage mainly at 600mM NaCl. Besides, antioxidant activities of Jerba provenance, were more efficient than Bizerte. In addition, avicularin was the major phenolic in both provenances. This compound concentration increased with salinity in Jerba shoots, while it was reduced in Bizerte especially at 600mM NaCl. Overall, the higher salt tolerance of plants from Jerba provenance, and to a lower extent of those from Bizerte, may be partly related to their better capacity to limit oxidative damage when salt-challenged, and this is likely the result of redistribution in phenolic composition. Besides, abiotic factors such as salinity could be determinant in antioxidant potentiality of this medicinal plant.