Forty-One Plant Extracts Screened for Dual Antidiabetic and Antioxidant Functions: Evaluating the Types of Correlation between -Amylase Inhibition and Free Radical Scavenging.

Dysregulation of glucose homeostasis followed by chronic hyperglycemia is a hallmark of diabetes mellitus (DM), a disease spreading as a worldwide pandemic for which there is no satisfactory dietary treatment or cure. The development of glucose-controlling drugs that can prevent complications of DM, such as hyperglycemia and oxidative stress, which contribute to the impairment of the key physiological processes in the body, is of grave importance. In pursuit of this goal, this study screened 41 plant extracts for their antidiabetic and antioxidant activities by employing assays to test for α-amylase inhibition and free radical scavenging activity (FRSA) and by measuring glucose uptake in L6-GLUT4myc cells. While extracts of Rhus coriaria, Punica granatum, Olea europaea, Pelargonium spp., Stevia rebaudiana, and Petroselinum crispum demonstrated significant α-amylase inhibition, the extracts of Rhus coriaria and Pelargonium spp. also demonstrated increased FRSA, and the extract of Rhus coriaria stimulated glucose uptake. These natural extracts, which are believed to have fewer side effects because they are prepared from edible plants, interfere with the process in the small intestine that breaks down dietary carbohydrates into monosaccharide and disaccharide derivatives, and thereby suppress increases in diet-induced blood glucose; hence, they may have clinical value for type 2 diabetes management. The Pelargonium spp. and Rhus coriaria extracts demonstrated the highest antidiabetic and antioxidant activities. Both plants may offer valuable medical benefits, especially because they can be taken as dietary supplements by patients with diabetes and can serve as sources of new, natural-based antidiabetic drug candidates. The enhancement of cellular glucose uptake stimulated by Rhus coriaria extract could lead to the development of clinical applications that regulate blood glucose levels from within the circulatory system. Isolating bioactive substances from these plant extracts and testing them in diabetic mice will significantly advance the development of natural drugs that have both antidiabetic and free radical-scavenging properties, likely with lesser side effects.

Correlation between cytotoxicity in cancer cells and free radical-scavenging activity: In vitro evaluation of 57 medicinal and edible plant extracts.

Cancer is a complex interaction among multiple signaling pathways involving a variety of target molecules. Cancer causes morbidity and mortality in millions of people worldwide, and due to its prevalence, the discovery of novel anticancer drugs is urgently required. Nature is considered an important source of the discovery of anticancer treatments, and many of the cytotoxic medicines in clinics today are derived from plants and other natural sources. Reactive oxygen species (ROS) induce a variety of human cancers, and antioxidants or scavengers are used to counteract them. The current study reports on the screening of extracts from 57 plants that are used in the galilee district as a food and/or for traditional medicine. Investigating the free radical scavenging capacity and these plants, and their cytotoxicity, may prove helpful to high-throughput screening projects that use antioxidants and cytotoxic natural products. The current study assessed the correlation between free radical scavenging and cytotoxicity. Correlational analysis is important for increasing the efficiency of the screening process. In the present study, free radical scavenging was assessed using a DPPH assay, while cytotoxicity was measured using a XTT assay. A total of 9 extracts were indicated to exhibit EC50 values <250 µg/ml, and 4 others exhibited a high antioxidant content, with EC50 values, for free radical scavenging, of <0.5 µg/ml. An in-depth analysis of the results revealed that the extracts of plants that exhibit an EC50 of free radical scavenging ≤10 µg/ml show a degree of enrichment toward increased cytotoxicity. It is recommended that future studies test the validity of the conclusions of the current study on other cancer cell-lines, and isolate and identify the bioactive agents that are found in the most cytotoxic extracts of plants.

Phytochemical Composition and Biological Activities of Wild Scolymus maculatus L.

Background: The wild population of spotted golden thistle, Scolymus maculatus, which belongs to the Compositae family, is believed to be one of the multi-curative wild plants mentioned in Flora Palaestina. This study aims to disclose the phytochemical composition, antioxidant potential, and antimicrobial activity of wild S. maculatus collected from the farms of Kabul, a village in northwest Galilee, for the first time. Methods: The phytochemical components of crude S. maculatus extracts from methanol, ethyl acetate, and n-hexane solvents were separated and identified using gas chromatography-mass spectrometry (GC-MS) in the electron impact (EI) mode. The free radical scavenging of the plant extracts was measured by DPPH assay. The microdilution test was used to determine the minimum inhibitory concentrations (MICs) of different S. maculatus extracts and to evaluate their antimicrobial activities. Results: Thirty-two phytochemicals were found in S. maculatus extracts including stigmasterol, γ-sitosterol, lupeol, lupeol acetate, and ß-amyrin. Phytochemicals, such as 2-linoleoylglycerol, γ-sitosterol, ß-amyrin, lupeol, (3α)-12-oleanen-3-yl acetate, and lupenyl acetate, were found to dominate the methanol extract. Most of these compounds were also observed in ethyl acetate and n-hexane extracts, but at different levels, in addition to some other minor compounds. The various extracts were investigated for their antioxidant and antimicrobial activity. The ethanolic and the methanolic extracts were shown to exhibit the highest free radical scavenging by DPPH assay with a half-maximally effective concentration (EC50) of 0.37 and 0.65 mg/mL respectively, while the other three extracts (aqueous, ethyl acetate and n-hexane) were less active and their EC50 (effective concentration at which DPPH radical was scavenged by 50%) were above 1.0 mg/mL. Moreover, MICs were determined to be effective against Staphylococcus aureus, Salmonella typhimurium, and Candida albicans microorganisms. Ethyl acetate and the ethanolic extracts are active against the three types of microorganisms at a minimum inhibitory concentration (MIC) of 0.5 mg/mL, while aqueous and the n-hexane extracts are inactive against Salmonella typhimurium. Conclusions: The results show that S. maculatus extracts are a rich source of compounds that can play an important role in human health, and in a broader context, in the treatment of various diseases, such antimicrobial and antioxidant-related ailments.

Discovering highly selective and diverse PPAR-delta agonists by ligand based machine learning and structural modeling.

PPAR-δ agonists are known to enhance fatty acid metabolism, preserving glucose and physical endurance and are suggested as candidates for treating metabolic diseases. None have reached the clinic yet. Our Machine Learning algorithm called "Iterative Stochastic Elimination" (ISE) was applied to construct a ligand-based multi-filter ranking model to distinguish between confirmed PPAR-δ agonists and random molecules. Virtual screening of 1.56 million molecules by this model picked ~2500 top ranking molecules. Subsequent docking to PPAR-δ structures was mainly evaluated by geometric analysis of the docking poses rather than by energy criteria, leading to a set of 306 molecules that were sent for testing in vitro. Out of those, 13 molecules were found as potential PPAR-δ agonist leads with EC50 between 4-19 nM and 14 others with EC50 below 10 µM. Most of the nanomolar agonists were found to be highly selective for PPAR-δ and are structurally different than agonists used for model building.

Anticancer activity and phytochemical composition of wild Gundelia tournefortii.

Artichoke-like wild thistles are often used in Palestinian cuisine. One of the most commercially recognized species of these wild edible thistles is Gundelia tournefortii, a common plant in the Mediterranean region. G. tournefortii, or 'Akoob' in Arabic, remains uncultivated, harvested wild by local populations and considered highly valuable due to its reputed health benefits. The present study aimed to investigate the anticancer effects of G. tournefortii on the human colon carcinoma HCT-116 cell line. Methanol and hexane extracts were identified to exert considerable antitumor activity against the HCT-116 cancer cell line, while the aqueous extract was inactive. The phytochemical profiles of the methanol and hexane extracts were investigated using gas chromatography-mass spectrometry. A total of 6 of the 27 natural compounds identified, including sitosterol, stigmasterol, lupeol, gitoxigenin, α-amyrin and artemisinin, have been previously validated as being active against cancerous cells. Therefore, the presence of these phytochemicals in G. tournefortii is of importance in its role in preventing and treating cancer.

Sesamin from Cuscuta palaestina natural plant extracts: Directions for new prospective applications.

The aim of this study is to disclose the potential bioactive components of Cuscuta palaestina, a native parasitic natural plant of flora palaestina and to open direction towards new prospective application. GC-MS analysis identified 18 components in the methanolic extract of C. palaestina for the first time. The most appealing among them are Sesamin and two other phytosterols (Campesterol and Stigmasterol), all of which are documented in the scientific literature for their anticancer activity. Quantitation of Sesamin extracted from C. palaestina by HPLC-PDA with the use of three organic solvents showed that the Sesamin content in the methanolic extract was the highest. Following the disclosure of Sesamin presence in C. palaestina, we raised the question of whether it is produced naturally in C. palaestina or acquired from the host plant. The quantitation of Sesamin in C. palaestina was performed while being with five different host plants, and was compared with the amount of Sesamin in C. palaestina grown alone. The findings reveal that Sesamin is an endogenous secondary metabolite in C. palaestina. Thus, further studies are required to prove if C. palaestina can be used as an alternative source of anticancer phytochemicals, mainly Sesamin, and if proteins in the Sesamin production pathway could be valid biological targets for the development of novel and selective pesticides for control/ eradication of C. palaestina and maybe some other Cuscuta species. As well, the findings from this study raise a big question of whether inferring Sesamin production in C. palaestina could reduce its attack ability to host plants.

From medicinal plant extracts to defined chemical compounds targeting the histamine H4 receptor: Curcuma longa in the treatment of inflammation.

OBJECTIVES: The aim was to evaluate the activity of seven medicinal, anti-inflammatory plants at the hH4R with focus on defined chemical compounds from Curcuma longa. MATERIALS: Activities were analyzed with membrane preparations from Sf9 cells, transiently expressing the hH4R, Gαi2 and Gß1γ2 subunits. METHODS: From the methanolic extract of C. longa curcumin (1), demethoxycurcumin (2) and bis(4-hydroxy-cinnamoyl)methane (3) were isolated, purified with HPLC (elution-time 10.20, 9.66, 9.20 min, respectively) and together with six additional extracts, were characterized via radioligand binding studies at the hH4R. RESULTS: Compounds from C. longa were the most potent ligands at the hH4R. They exhibited estimated K i values of 4.26-6.26 µM (1.57-2.31 µg/mL) (1); 6.66--8.97 µM (2.26-3.04 µg/mL) (2) and 10.24-14.57 µM (3.16-4.49 µg/mL) (3) (95% CI). The estimated K i value of the crude extract of curcuma was 0.50-0.81 µg/mL. Fractionated curcumin and the crude extract surpassed the effect of pure curcumin with a K i value of 5.54 µM or 2.04 µg/mL [95% CI (4.47-6.86 µM), (1.65-2.53 µg/mL)]. CONCLUSION: Within this study, defined compounds of C. longa were recognized as potential ligands and reasonable lead structures at the hH4R. The mode of anti-inflammatory action of curcumin was further elucidated and the role of extracts in traditional phytomedicine was strengthened.

Inhibitory capacity of Rhus coriaria L. extract and its major component methyl gallate on Streptococcus mutans biofilm formation by optical profilometry: Potential applications for oral health.

Streptococcus mutans (S. mutans) bacterium is the most well recognized pathogen involved in pathogenesis of dental caries. Its virulence arises from its ability to produce a biofilm and acidogenicity, causing tooth decay. Discovery of natural products capable to inhibit biofilm formation is of high importance for developing health care products. To the best of our knowledge, in all previous scientific reports, a colorimetric assay was applied to test the effect of sumac and methyl gallate (MG) on S. mutans adherence. Quantitative assessment of the developed biofilm should be further performed by applying an optical profilometry assay, and by testing the effect on both surface roughness and thickness parameters of the biofilm. To the best of our knowledge, this is the first study to report the effect of sumac extract and its constituent MG on biofilm formation using an optical profilometry assay. Testing antibacterial activity of the sumac extract and its fractions revealed that MG is the most bioactive component against S. mutans bacteria. It reduced S. mutans biofilm biomass on the polystyrene surface by 68­93%, whereas 1 mg/ml MG was able to decrease the biofilm roughness and thickness on the glass surface by 99%. MG also prevented a decrease in pH level by 97%. These bioactivities of MG occurred in a dose­dependent manner and were significant vs. untreated bacteria. The findings are important for the development of novel pharmaceuticals and formulations of natural products and extracts that possess anti­biofilm activities with primary applications for oral health, and in a broader context, for the treatment of various bacterial infections.