Phytochemical, Antioxidant Activity, and Toxicity of Wild Medicinal Plant of Melitotus albus Extracts, In Vitro and In Silico Approaches.

Morocco is known for its high plant biodiversity, but many plants are poorly valorized. For this reason, this study aims to valorize the methanolic and aqueous extracts of Melitotus albus leaves by studying their antioxidant activity and toxicity. The extracts' antioxidant activity is assessed using the FRAP, DPPH, CAT, and ABTS methods. The chemical composition was determined using LC-MS analysis and evaluated using in silico studies. The results revealed that the total polyphenol content of the aqueous extract, 259.26 ± 7.79 (mg GAE/g), is higher than that of the methanolic extract, 131.41 ± 12.64 (mg GAE/g). The antioxidant activity by the methods of DPPH, ABTS, and phosphor molybdenum of aqueous extracts (0.087 ± 0.015, 0.014 ± 0.001 and 6.157 ± 1.050 mg eq vit C/g, respectively) is greater than that of methanolic extracts (0.107 ± 0.02, 0.167 ± 0.03, and 0.453 ± 0.014 mg eq vit C/g, respectively). The reducing power of iron (FRAP) shows that the methanolic extract has a greater reducing power than that of the aqueous extract with a low IC50 (0.011 ± 0.003 and 0.199 ± 0.016 mg/mL, respectively). The study of acute and subacute toxicity shows that the administration of the aqueous extract of M. albus at different doses increases the body weight of rats without modifying their general behavior. The M. albus extract had a 99.99% total phenolic content, as determined by LC-MS, consisting of 12 different components. The primary constituents of the extract are chlorogenic acid (43.68%), catechin/epicatechin (24.82%), quercetin-3-O-glucuronic acid (9.91%), naringin (7.64%), and p-hydroxybenzoic/salicylic acid (2.95%). The in-silico study showed that these compounds can passively permeate through the blood and have a beneficial effect on various organs of the body. Based on these results, M. albus can be used as a medicinal plant in phytotherapy, cosmetics, or as a dietary supplement. The bioactive compounds of these plants will require a lot of further effort in terms of isolation and characterization.

Phenolic Composition, Wound Healing, Antinociceptive, and Anticancer Effects of Caralluma europaea Extracts.

Caralluma europaea (Guss.) is an important medicinal plant widely used in Morocco for various traditional purposes. Our work aimed to evaluate the phenolic composition, wound healing, antinociceptive, and anticancer activities of C. europaea extracts. Moreover, this study assessed the beneficial effect of C. europaea phytocompounds on the TRADD, cyclooxegenase-2, Wnt/ß-catenin, and tyrosine kinase signaling pathways. The wound healing effect of C. europaea formulations against skin burn was evaluated for 21 days. The cytotoxic effect of the C. europaea extracts was evaluated against human leukemic (K562 and HL60) and liver cancer cell lines (Huh-7) using the MTT test. All the phytoconstituents identified by UHPLC in the polyphenols were docked for their inhibitory power on protein casein kinase-1, glycogen synthase kinase-3-ß, cyclooxegenase-2, tyrosine kinase, and TRADD. Luteolin and kaempferol are the main compounds identified in C. europaea polyphenols. The group treated with polyphenols showed the greatest wound contractions and all tested extracts presented a significant antinociceptive effect. Polyphenols showed a remarkable antitumoral activity against the K562, HL60 and Huh-7 cell lines. Saponins exerted an important cytotoxic effect against the Huh-7 cell line, whereas no cytotoxicity was observed for the hydroethanolic and flavonoids extracts. Hesperetin and trimethoxyflavone presented the highest docking G-score on tyrosine kinase and cyclooxygenase, respectively.

Antileukemic, Antioxidant, Anti-Inflammatory and Healing Activities Induced by a Polyphenol-Enriched Fraction Extracted from Leaves of Myrtus communis L.

Natural products have offered a number of exciting approaches in cancer treatment over the years. In this study, we investigated the prophylactic and therapeutic effects of the polyphenol-enriched fraction extracted from Myrtus communis (PEMC) on acute and chronic leukemia. According to the UHPLC-MSn, the fraction is rich in flavonoids. Protective activity of the PEMC was assessed by evaluating the antioxidant, anti-inflammatory, wound healing, and hemolysis potential in a series of in vivo and in vitro assays, while the therapeutic approach consisted of the evaluation of cytotoxic activity of the PEMC against HL60 and K562 leukemia cell lines. Safety of the fraction was also evaluated on a non-cancerous Vero cell line and by an acute toxicity test performed in mice. The PEMC demonstrated a significant anti-inflammatory and healing potential. The activities found at the dose of 100 mg/kg were better than those observed using a reference drug. The PEMC demonstrated a significant antioxidant effect and a specific cytotoxicity towards HL60 (IC50 = 19.87 µM) and K562 (IC50 = 29.64 µM) cell lines being non-toxic to the Vero cell line. No hemolytic activity was observed in vitro and no toxicity effect was found in mice. Thus, the PEMC has a pharmacological potential as both preventive and therapeutic agent. However, further research is necessary to propose its mechanism of action.

Evaluation of Acute and Subacute Toxicity and LC-MS/MS Compositional Alkaloid Determination of the Hydroethanolic Extract of Dysphania ambrosioides (L.) Mosyakin and Clemants Flowers.

Dysphania ambrosioides (L.) Mosyakin and Clemants is a medicinal plant that has traditionally been used to cure a range of diseases. There has been no thorough investigation of the potential toxicity of this plant. The objective of this study is to assess the acute and subacute toxicity of D. ambrosioides hydroethanolic extract (DAHE), as well as it alkaloids composition, utilizing LC-MS/MS analysis. An in silico approach was applied to determine pharmacokinetic parameters and to predict the toxicity of D. ambrosioides identified alkaloids. A 14-day treatment with a single oral dose of 1-7 g/kg was carried out to investigate acute toxicity. DAHE was given orally at dosages of 5, 50, and 500 mg/kg for 15 days in the subacute toxicity investigation, and body weight and biochemical parameters were evaluated. Livers, kidneys, lungs, and heart were examined histologically. Chromatographic investigation revealed the existence of nine alkaloids, with N-formylnorgalanthamine being the most prevalent. The oral LD50 value of DAHE was found to be 5000 mg/kg in an acute toxicity study. No variations were observed with respect to food intake, water consumption, mortality, or body and organ weight in the subacute toxicity study. On the other hand, DAHE (500 mg/kg) significantly enhanced alanineaminotransferase, aspartate aminotransferase, and urea. Liver and kidney histological examinations revealed modest infiltration of hepatocyte trabeculae by inflammatory cells in the liver and slight alteration in the kidney histoarchitecture. According to our findings, DAHE exhibits low to moderate toxicity.

Phytochemical Analysis, Antispasmodic, Myorelaxant, and Antioxidant Effect of Dysphania ambrosioides (L.) Mosyakin and Clemants Flower Hydroethanolic Extracts and Its Chloroform and Ethyl Acetate Fractions.

Dysphania ambrosioides (L.) Mosyakin and Clemants is an annual or ephemeral perennial herb used traditionally in the Mediterranean region in folk medicine to treat various illnesses, including those related to the digestive system. This study aims to assess the antispasmodic, myorelaxant, and antioxidant effects of D. ambrosioides flower hydroethanolic extract and its chloroform and ethyl acetate fractions in a comparative study to evaluate the result of the extraction type on the potential activity of the extract. Both rat and rabbit jejunum were used to evaluate the antispasmodic and myorelaxant effect, while the antioxidant effect was evaluated using DPPH, a ferric reducing power assay, and a beta-carotene bleaching test. LC/MS-MS analysis was carried out to reveal the composition of the different types of extract. Following the results, the hydroethanolic extract showed a significant myorelaxant effect (IC50 = 0.39 ± 0.01 mg/mL). Moreover, it was shown that the hydroethanolic extract demonstrated the best antispasmodic activity (IC50 = 0.51 ± 0.05 mg/mL), followed by the ethyl acetate (IC50 = 4.05 ± 0.32 mg/mL) and chloroform (IC50 = 4.34 ± 0.45 mg/mL) fractions. The antioxidant tests showed that the hydroethanolic extract demonstrated high antioxidant activity, followed by the ethyl acetate and chloroform fractions. The LC/MS-MS analysis indicates that the plant extract was rich in flavonoids, to which the extract activity has been attributed. This study supports the traditional use of this plant to treat digestive problems, especially those with spasms.

In Vivo and In Vitro Antidiabetic and Anti-Inflammatory Properties of Flax (Linum usitatissimum L.) Seed Polyphenols.

Flaxseed is an oilseed (45-50% oil on a dry-weight basis) crop. Its oil has demonstrated multiple health benefits and industrial applications. The goal of this research was to evaluate the antidiabetic and anti-inflammatory potential of the free polyphenol fraction of flax (Linum usitatissimum L.) seeds (PLU), based on their use in traditional medicine. Mice with alloxan-induced diabetes were used to study the antidiabetic activity of PLU in vivo, with an oral administration of 25 and 50 mg/kg over 28 days. Measurements of body weight and fasting blood glucose (FBG) were carried out weekly, and biochemical parameters were evaluated. An oral glucose tolerance test was also performed. Inhibitory activities of PLU on α-amylase and α-glucosidase activities were evaluated in vitro. The anti-inflammatory was evaluated in vivo in Wistar rats using the paw edema induction Test by carrageenan, and in vitro using the hemolysis ratio test. PLU administration to diabetic mice during the study period improved their body weight and FBG levels remarkably. In vitro inhibitory activity of digestive enzymes indicated that they may be involved in the proposed mode of action of PLU extract. Qualitative results of PLU revealed the presence of 18 polyphenols. These findings support daily consumption of flaxseed for people with diabetes, and suggest that polyphenols in flaxseed may serve as dietary supplements or novel phytomedicines to treat diabetes and its complications.

Antioxidant, Anti-Inflammatory and Antidiabetic Proprieties of LC-MS/MS Identified Polyphenols from Coriander Seeds.

Coriandrum sativum L. seeds are traditionally used to treat diabetes and its complications (inflammation and formation of reactive oxygen species) around the world. The present study investigates the antidiabetic, anti-inflammatory, and antioxidant effects of the polyphenol fraction of Coriandrum sativum seeds (PCS). Diabetic mice were orally administered with PCS (25 and 50 mg/kg b.w.) for 28 days. Oral glucose tolerance (OGTT) was also evaluated along with the anti-inflammatory effect, assessed by measuring paw edema development induced with carrageenan in Wistar rat and the antioxidant activity assessed using two tests (ß-carotene discoloration and DPPH). Treatment of diabetic mice with PCS for four weeks managed their high fasting blood glucose levels, improved their overall health, also revealed an excellent antihyperlipidemic activity. The OGTT result showed a potent antihyperglycemic activity, and following the anti-inflammatory and antioxidant effects, the PCS exhibited a perfect activity. LC-MS/MS result revealed the presence of 9 polyphenols. This modest work indicates that the PCS have an important antidiabetic, antihyperglycemic, antihyperlipidemic, anti-inflammatory, and antioxidant effect that can be well established treatment of diabetes and its complications.

Subacute Assessment of the Toxicity and Antidepressant-Like Effects of Origanum Majorana L. Polyphenols in Swiss Albino Mice.

Origanum majorana L. is a plant commonly used in folk medicine to treat depression and several neurological disorders. This study aims to evaluate the antidepressant-like effect of the Origanum majorana L. polyphenols (OMP) obtained from the aerial parts using two different depression model tests: The forced swimming test (FST) and the tail suspension test (TST) in Swiss albino mice. The experiments were performed on days 1, 7, 14, and 21 with daily administration of different treatments. Two different doses were chosen for this study (50 and 100 mg/kg), and paroxetine was used as a positive control. Immobility as a consequence of the depression state was significantly reduced following the treatment with OMP, indicating an antidepressant effect. A subacute toxicity study was also performed following the Organization for Economic Co-operation and Development (OECD) Guidelines (407), showing no sign of toxicity for the studied doses. The phytochemical screening revealed the presence of 12 components, all belonging to polyphenols: Arbutin, rosmarinic acid, ursolic acid, quercetin-3-O-glucoside, quercetin-7-O-glucuronic acid, luteolin-7-O-glucoside, kaempferol-3-0-glucuronic acid, Kaempferol-3-0-pentose, caffeic acid, catechin, quercetin, and rutin. These findings suggest that O. majorana has interesting antidepressant-like properties, which deserve further investigation.