Methanolic extract of Teucrium persicum up-regulates and induces the membrane restoration of E-cadherin protein in PC-3 cells.

Teucrium persicum Boiss. an Iranian endemic plant is used in Iranian traditional medicine. E-cadherin transmembrane protein participates in adherens junctions and is the main partner for ß-catenin protein. The GC-MS analysis was used to detect the chemical constituents of the methanolic extract. Its effects on the transcription of the E-cadherin encoding gene, cellular levels, and localization of E-cadherin protein in PC-3 cells were investigated. About 70 chemical constituents were identified. Indirect immunofluorescence microscopy and western blotting results revealed the restoration of E-cadherin protein at cell adhesion contact sites in cells treated with T. persicum extract. Gene expression studies revealed that the extract increased the transcription of the E-cadherin encoding gene in PC-3 cells. These results suggest that T. persicum extract may contain potent compounds that provide further support for the anticancer properties of T. persicum. Surely, detailed molecular investigations are needed to find the mechanism(s) behind these effects.

Sublingual Administration of Teucrium Polium-Loaded Nanofibers with Ultra-Fast Release in the Treatment of Diabetes Mellitus: In Vitro and In Vivo Evaluation.

In this study, Teucrium polium (TP) methanolic extract, which has antidiabetic activity and protects the ß-cells of the pancreas, was loaded in polyethylene oxide/sodium alginate nanofibers by electrospinning and administered sublingually to evaluate their effectiveness in type-2 diabetes mellitus (T2DM) by cell culture and in vivo studies. The gene expressions of insulin, glucokinase, GLUT-1, and GLUT-2 improved in TP-loaded nanofibers (TPF) on human beta cells 1.1B4 and rat beta cells BRIN-BD11. Fast-dissolving (<120 s) sublingual TPF exhibited better sustainable anti-diabetic activity than the suspension form, even in the twenty times lower dosage in streptozotocin/nicotinamide-induced T2DM rats. The levels of GLP-1, GLUT-2, SGLT-2, PPAR-γ, insulin, and tumor necrosis factor-alpha were improved. TP and TPF treatments ameliorated morphological changes in the liver, pancreas, and kidney. The fiber diameter increased, tensile strength decreased, and the working temperature range enlarged by loading TP in fibers. Thus, TPF has proven to be a novel supportive treatment approach for T2DM with the features of being non-toxic, easy to use, and effective.

Novel zinc oxide nanoparticles of Teucrium polium suppress the malignant progression of gastric cancer cells through modulating apoptotic signaling pathways and epithelial to mesenchymal transition.

Management of gastric cancer is still challenging due to resistance to current chemotherapeutics and recurrent disease. Moreover, green- synthesized zinc oxide nanoparticles (ZnO-NPs) using natural resources are one of the most promising therapeutic agents for anticancer therapy. Here we report the facile green synthesis and characterization of ZnO-NPs from Teucrium polium (TP-ZnO-NP) herb extract and the anticancer activities of these nanoparticles on gastric cancer cells. Facile green synthesis of TP-ZnO-NP was achieved using zinc acetate dihydrate. For the characterization of TP-ZnO-NP, UV-vis spectroscopy, FTIR, SEM, XRD and EDX analyses were performed. Antiproliferative and anticancer activities of TP-ZnO-NP were explored using the HGC-27 gastric cancer cell line model. MTT cell viability and colony formation assays were used for the analysis of cell proliferation and migration. Wound healing assay was used to analyze the migration capacities of cells. Annexin V/PI double staining, DNA ladder assay, and Acridine orange/Ethidium bromide staining were performed to analyze the induction of apoptosis. qPCR was used to determine gene expression levels of apoptotic and epithelial to mesenchymal transition marker genes. The aqueous extract of TP served as both a reducing and capping agent for the successful biosynthesis of zinc oxide nanoparticles. Remarkably, synthesized TP-ZnO-NPs were found to have significant antiproliferative and anticancer activities on HGC-27 gastric cancer cells. Collectively, current data suggest that TP-ZnO-NP is a novel and promising anticancer agent for future therapeutic interventions in gastric cancer.

Oxaliplatin-loaded nanoemulsion containing Teucrium polium L. essential oil induces apoptosis in Colon cancer cell lines through ROS-mediated pathway.

Oxaliplatin (Oxa)-associated adverse side effects have considerably limited the clinical use of the drug in colon cancer therapy. Mutant p53 has diverse mutational profiles in colon cancer, and it influences the potencies of various chemotherapeutic drugs, including Oxa. Thus, it would be highly beneficial to identify an alternative therapeutic strategy that not only reduces the toxicity of Oxa, but also exerts a synergistic effect against colon cancers, regardless of their p53 profiles. The present study was aimed at preparing and optimizing Teucrium polium L. essential oil nanoemulsion (TPO-NANO) and investigating its effect on the sensitivity of colon cancer cells with differences in p53 status (HCT116 wild-type and HT-29 mutant-type) to Oxa. The viability of treated cells was determined and the combination index (CI) was calculated. Morphological changes were determined under inverted microscopy, while percentage apoptosis was assayed using flow cytometry. Intracellular ROS and the protein levels of p53 and Bax were measured. The colony-forming potential of treated cells was determined using colony assay. The size of TPO-NANO was markedly increased from 12.90 ± 0.04 nm to 14.47 ± 0.53 nm after loading Oxa (p ≤ 0.05). The combination (Oxa + TPO-NANO) produced a synergetic effect in HCT116 and HT-29, with CI of 0.94 and 0.88, respectively. Microscopic examination and flow cytometric analysis revealed that cells treated with Oxa + TPO-NANO had a higher percentage of apoptosis than cells exposed to monotherapy. Cumulatively, Oxa exerted an apoptotic effect on wild or mutant p53 colon cancer cells when combined with TPO-NANO, through a mechanism involving ROS-mediated mitochondrial apoptosis.

Effects of calcareous and serpentinite parent material on the mineral characteristics of soils and plant material of Teucrium montanum L. (Lamiaceae).

The objective of this study was to determine eco-edaphic characteristics and influence of different substrates on mineral characteristics of facultative serpentinophyte. The total concentration of 20 elements Al, As, B, Ca, Cd, Co, Cr, Cu, Fe, K, Li, Mg, Mn, Na, Ni, P, Pb, S, Se, and Zn in soil samples and aboveground parts of medicinal plant species Teucrium montanum from various calcareous and serpentinite habitats in the territory of Serbia was determined. The concentration of the elements was established by inductively coupled plasma optical emission spectrometry-ICP-OES. The obtained results showed that the quantities of certain elements Al, As, B, Ca, Cd, Cu, K, Li, P, Se, and Zn were detected more in the soil samples from calcareous habitats in comparison to the quantities of other metals Co, Cr, Fe, Mg, Mn, Na, Ni, which were more frequently found in the soil samples from the serpentinite habitats. Analyzed plant samples from calcareous habitats contained higher concentrations of Al, Ca, Li, and Zn as opposed to serpentinite containing higher concentrations of Co, Cr, Fe, Mg, Mn, Na, Ni, and Se. Examined species can accumulate macro- and microelements in different quantities, depending on the substrate type. Differences in the concentration of certain elements in the soil samples and aboveground parts of the T. montanum from calcareous and serpentinite habitats indicate significant phenotypic plasticity of the investigated species as well as the existence of specific serpentinite ecotypes developed by the activity of various edaphic factors.

Secondary metabolites and metal content dynamics in Teucrium montanum L. and Teucrium chamaedrys L. from habitats with serpentine and calcareous substrate.

The purpose of this comparative analysis is the determination of the total quantity of metals (Mg, Ca, K, Ni, Fe, Mn, Zn, Cu, Cr and Pb) in soil samples, above ground plant parts and tea made of plants Teucrium montanum and T. chamaedrys from different serpentine and calcareous habitats as well as of the total quantity of phenolic compounds and antioxidant activity. The obtained results showed that the quantities of certain metals (Mg, Fe, Ni and Mn) in the soil from the serpentine habitats were greater in comparison with other metals (Ca, Zn and Pb) which were more frequently found in the soil from the calcareous habitats. The results demonstrated that the analysed plant samples from the serpentine habitats contained higher quantity of Fe, Ni and Cr as opposed to the plant samples from the calcareous habitats which contained greater quantity of Ca and Zn. Although the studied species accumulate analysed metals in different quantities, depending on the substrate type, they are not hyperaccumulators of these metals. The use of these species from serpentine habitats for tea preparation is safe to a great extent, because in spite of the determined metal absorption by plant organs, the tea does not contain dangerous quantity of heavy metals. The results showed greater total quantity of phenolic compounds and the higher level of antioxidant activity in the plant samples from serpentine habitats in comparison with the samples from calcareous habitats, which is an indicator of one of the mechanisms of adaptation to the serpentine habitat conditions.

Guaiasistanol: A new guaiane sesquiterpenoid from Teucrium persicum Boiss.

In this study, a new guaiane type skeleton sesquiterpenoid named guaiasistanol (6α, 10α-epoxy-4α-hydroxyguaiane) was isolated from chloroform part of the Teucrium persicum extract, also chrysothol. Spectroscopic means explained the structures. This compound was evaluated for inhibitory activity against acetylcholinesterase and it showed a moderate activity with 28% inhibition.

NMR-based metabolic profiling and in vitro antioxidant and hepatotoxic assessment of partially purified fractions from Golden germander (Teucrium polium L.) methanolic extract.

Golden germander (Teucrium polium L.) is a Mediterranean shrub of the Labiatae family, used in traditional medicine for its diuretic, antipyretic, diaphoretic, antispasmodic, tonic, anti-inflammatory, antihypertensive, anorexic, analgesic, antibacterial and antidiabetic effects. Like other plants of the Teucrium genus, it was widely popular because of its hypoglycemic and hypolipidemic properties but various cases of T. polium-induced hepatitis have been reported. neo-Clerodane diterpenoids, considered chemotaxonomic markers for the Teucrium genus, are believed to be responsible for the observed hepatotoxicity. The plant also produces flavonoids and phenylethanoid glycosides to which the antioxidant and cytoprotective therapeutic properties of its preparations can be traced back. In order to establish a herbal formula that preserves the plant beneficial properties, T. polium leaf drug has been subjected to a bio-guided fractionation. The different phytocomplexes obtained were analyzed by means of an extensive antioxidant screening and hepatotoxicity evaluation against HepG2, a human hepatoblastoma cell line. The cytotoxicity of the fractions was also evaluated against HeLa and A549 cell lines. In order to identify the substances responsible for the bioactivities, NMR-based metabolic profiling techniques of all the phytocomplexes were performed. Data obtained highlighted the possibility of preparing strong antioxidant extracts, useful as food additives, such as MeOH-2, and MeOH-3, completely devoid of hepatotoxic components.

Teucrium plant species as natural sources of novel anticancer compounds: antiproliferative, proapoptotic and antioxidant properties.

This study deals with total phenolic content, antiproliferative and proapoptotic activity of methanolic extracts from different Teucrium species and the effect on the prooxidant/antioxidant status in HCT-116 cells. The total phenolic content of the extracts was measured spectrophotometricaly and the obtained results ranged from 56.62 mg/g to 172.50 mg GA/g. The antiproliferative activity of methanolic extracts from different Teucrium species was determined using MTT cell viability assay, where IC(50) value was used as a parameter for cytotoxicity. The type of cell death was explored by fluorescence microscopy using the acridin orange/ethidium bromide method. MTT assay showed that all extracts significantly reduced cell viability in a dose-dependent manner, with very low IC(50) values. The highest content of phenolic compounds and the best cytotoxic activity on HCT-116 cells after 24 h of exposure was in T. chamaedrys extract, with IC(50) values of 5.48 × 10(-9) µg/mL. After 72 h, methanolic extract of T. arduini appeared to have the best cytotoxic activity on HCT-116, with IC(50) values of 0.37 µg/mL. Treatments caused typical apoptotic morphological changes in HCT-116 cells and showed a high percentage of apoptotic cells. The results of the presented research indicate that some Teucrium extracts are a very rich source of phenols, which may directly contribute to high antiproliferative and proapoptotic activity.

Extraction of Teucrium manghuaense and evaluation of the bioactivity of its extract.

The ethanol extract of Teucrium manghuaense grown in Hainan province (China) was analysed by GC and GC/MS. Of the constituents 84-96% were identified on the basis of their GC retention times and their mass spectra in regard to authentic compounds. The results revealed that it contained 9-methyl-9-azabicyclo[4.2.1]nonane (7.43%), 2-methylpyrrolidine (19.42%), 3,7,11,15-tetramethyl-2-hexadecen-1-ol (10.84%), and squalene (28.55%), as major components, constituting 66.24% of the extract. The chemical characterization of the ethanol extract by GC/MS also allowed identification of 1-octen-3-one (3.41%), 2-pentyl-piperidine (2.25%), 1-(2-methyl-1-propenyl)-piperidine (4.63%), 2,2'-diethoxy-5,5'-bi-1-pyrroline (0.41%), (Z,Z,Z)-9,12,15-octadecatrieniic acid, 2,3-dihydroxypropyl ester (1.56%), vitamin E (2.95%) and stigmasterol (1.39%). Finally, the antioxidant and anti-tumor activities of the ethanol extract have been evaluated. Results show that the extract of Teucrium manghuaense leaf possesses strong DPPH(-), hydroxyl radical scavenging activity and anti-tumor activity.

Methanolic extract of Teucrium polium L. potentiates the cytotoxic and apoptotic effects of anticancer drugs of vincristine, vinblastine and doxorubicin against a panel of cancerous cell lines.

UNLABELLED: A growing body of evidence indicates that specific phytochemicals can increase an efficacy of cancer chemotherapy. AIM: To evaluate promoting effect of the methanolic extract of Teucrium Polium (Me-TP) on cytotoxic and apoptotic activity of anticancer drugs of vinblastine, vincristine and doxorubicin in vitro. METHODS: Skmel-3, Saos-2, SW480, MCF-7, KB, EJ and A431 cell lines were used. Cytotoxicity was determined by MTT assay and colony formation assay. The nature of interactions was analyzed by combination index (CI) method. Apoptotic cells were assessed by DAPI staining. RESULTS: The vincristine/Me-TP, vinblastine/Me-TP and doxorubicin/Me-TP combinations showed a strong synergistic effect in the cell growth inhibition (0.1380%) compared to effect of individual drugs (0-3%). At the additional experiments, Me-TP reduced marginally to significantly the cytotoxic effects of vincristine and vinblastine toward the human fibroblasts (p<0.05 to 0.001). CONCLUSIONS: The present study suggests that Me-TP has the potential to be an effective and safe chemosensitizer agent for cancer therapy.