Antioxidant Properties of Teucrium polium Extract Contribute to Neurochemical and Brain Structural Modulations in Nicotine-Induced Mice.

INTRODUCTION: Tobacco use is a major global health issue linked to psychiatric illnesses and high mortality rates. Nicotine, the primary compound absorbed during smoking, causes harm to various organs, particularly the brain. The current study examined the modulatory effect of Teucrium polium extract (TPE) on nicotine-induced biochemical and histological changes in the brains of mice. METHODS: Twenty-four mice were divided into four groups and were treated for three weeks. Group one was the control; Group two received 100 mg/kg TPE orally; Group three was subcutaneously injected with 2.5 mg/kg nicotine, and Group four received both nicotine and TPE. RESULTS: The brain tissue of the nicotine-induced group showed histopathological alterations and oxidative stress as indicated by increased lipid peroxidation and nitric oxide levels concomitant with decreased glutathione content and superoxide dismutase activity. DNA fragmentation was also detected by comet assay. Treatment with TPE significantly decreased oxidative stress and DNA fragmentation while increasing antioxidant biomarkers. Histopathological changes were also diminished. CONCLUSION: Through the antioxidant activity of TPE, it protected against nicotine-induced neurotoxicity in mice by impacting oxidative stress, DNA fragmentation, and brain histopathological changes.

Exploring the Antioxidant and Anti-Inflammatory Effects of Rhoifolin Isolated from Teucrium Polium on Rats' Lungs Exposed to Tobacco Smoke.

Cigarette smoking exacerbates respiratory diseases, while plant-derived polyphenols offer antioxidant and anti-inflammatory benefits. This study exploresd the effects of Rhoifolin (ROF), a polyphenol from Jordanian Teucrium polium, on lung health in rats exposed to tobacco smoke. Male rats were divided into two groups: one exposed to cigarette smoke (CS), and the other to ROF treatment alongside smoke exposure (CS/ROF). ROF was administered orally for 21 days before smoke exposure. Results showed smoke-induced lung inflammation and oxidative stress, mitigated by ROF treatment. Histological examination revealed smoke-related morphological changes in lung tissue. ROF treatment reduced oxidative stress and inflammation, as evidenced by decreased proinflammatory cytokines. In silico docking demonstrated ROF's potential as an inhibitor of proinflammatory cytokines. This study demonstrates the therapeutic potential of ROF and similar polyphenols in mitigating the harmful effects of cigarette smoke on lung health.

Anticoccidial and Antioxidant Activities of an Ethanolic Extract of Teucrium polium Leaves on Eimeria papillate-Infected Mice.

Eimeria spp. are responsible for the economic loss of both domestic and wild animals due to coccidiosis, the most common parasitic disease. The resistance to currently available drugs used to treat coccidiosis has been proven. Medicinal plants that contain physiologically active phytochemicals have been widely used in traditional medicine. Teucrium polium leaf extract (TPLE) has been shown to exhibit pharmacological, antioxidant, and anticoccidial properties in different experiments. Here, our investigation focused on how T. polium leaf extract affected the way that Eimeria papillate caused intestinal injury in mice. Thirty-five male Swiss albino mice were divided into seven groups, as follows: group I: untreated and uninfected (negative control); group II: uninfected, treated group with TPLE (150 mg/kg b.w); and group III: infected untreated (positive control). Groups III-VII were orally administered 103 sporulated E. papillata oocysts. A total of 60 min after infection, groups IV-VI were treated for five successive days with 50, 150, and 250 mg/kg b.w TPLE, respectively, while group VII was treated with amprolium (120 mg/kg b.w.). The mice had been euthanized on the fifth day post-infection, and the jejunum tissues were prepared for histology and oxidative stress studies. A total of 150 mg/kg of TPLE was the most effective dosage, significantly decreasing oocyst output by about 80.5%, accompanied by a significant reduction in the number of developmental parasitic phases in jejunal sections. In addition, the decrease in the number of goblet cells in the jejuna of mice raised after treatment. Also, TPLE greatly diminished the body weight loss of infected mice. Moreover, our research proved that TPLE reduced oxidative damage due to E. papillata infection via decreasing intestinal malondialdehyde (MDA) and nitric oxide (NO) levels and increasing reduced superoxide dismutase (SOD) and glutathione (GSH) levels. These results demonstrated that TPLE had potent anticoccidial properties. TPE's efficacy as a natural antioxidant has also been demonstrated in reducing oxidative stress and enhancing antioxidant systems to mitigate biochemical and histological changes in the jejunum caused by E. papillata.

Teucrium polium: new toxic effects added to the literature: a case report.

Introduction and importance: Teucrium polium is one of the aromatic plants that grows in the Mediterranean region, and had been used as an herbal treatment for diabetes due to its hypoglycaemia effect. Although this plant is being studied now for its therapeutic role, its side effects are not taken enough into consideration, so this unique case can shed the light on serious toxic effects of this plant. Case presentation: A 68-year-old woman presented to the hospital with generalized fatigue, malaise, nausea, vomiting, abdominal pain, polydipsia, polyuria, breathlessness, and no defecation for 2 days after drinking big amounts of teucrium polium. The diagnosis was diabetic ketoacidosis (DKA), complete heart block, acute liver and kidney damage, and urinary tract infection (UTI). The patient was admitted to the ICU and treated for the DKA with an insulin pump, an antibiotic treatment for UTI, in addition to a dopamine pump and atropine, and then a temporary pacemaker was placed. The patient's DKA, liver and kidney damage were improved on day 9, heart rate returned normal and she was discharged to insert a permanent pacemaker. However, the patient passed away at the end. Clinical discussion: Most studies made on this plant focused on the hypoglycaemia effect, with no attention to its toxic effects, so only few studies showed that teucrium polium can cause hepatic, renal toxicity and hyperglycaemia and most of them were studied in animals. While cardiac toxicity has never been noticed before. Conclusion: For this reason, herbal treatment should be used with caution to avoid catastrophic side 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.

Protective potential effects of hydroalcoholic extract of Teucrium polium L. (Lamiaceae) against paraquat-induced lung fibrosis: An experimental study in rats.

Objective: Paraquat (PQ) is a highly toxic herbicide that causes pulmonary fibrosis (PF), and no specific antidote is available against it. Teucrium polium L. is a plant that exhibits antioxidant and anti-inflammatory activities. The present study evaluates the preventive and therapeutic effects of T. polium extract (TPE) against PQ-induced lung fibrosis in rats. Materials and Methods: We divided rats into five groups of eight. Groups one and two received saline and PQ (20 mg/kg, i.p.), respectively. Groups three to five were treated with TPE (50, 100, and 200 mg/kg, by gavage) started one week before PQ administration and lasted three weeks after PQ administration. Results: Our findings showed that PQ significantly increased lung malondialdehyde, nitric oxide, hydroxyproline, lung index, Ashcroft score, red blood cells accumulation, and inflammatory cell infiltration. Moreover, PQ decreased catalase and glutathione peroxidase activities and glutathione content. The results of hematoxylin-eosin and Masson's trichrome staining indicated that PQ destroyed lung parenchyma and developed PF (p<0.05 to p<0.001). Gavage with TPE significantly improved biochemical and histological abnormalities induced by PQ in rats (p<0.05 to p<0.001). Conclusion: The current survey indicated that treatment with TPE could reduce and reverse PQ-induced PF, which may be due to the phenolic compounds present in TPE.

LC-MS based metabolic profiling and wound healing activity of a chitosan nanoparticle-loaded formula of Teucrium polium in diabetic rats.

Healing of wounds is the most deteriorating diabetic experience. Felty germander (Teucrium polium) possesses antioxidant, anti-inflammatory and antimicrobial activities that could accelerate wound healing. Further, nanohydrogels help quicken healing and are ideal biomaterials for drug delivery. In the current study, the chemical profiling, and standardization of T. polium methanolic extract by LC-ESI/TOF/MS/MS and quantitative HPLC-DAD analyses were achieved. The wound healing enhancement in diabetic rats by T. polium nanopreparation (TP-NP) as chitosan nanogel (CS-NG) and investigating the potential mechanisms were investigated. The prepared hydrogel-based TP-NP were characterized with respect to particle size, zeta potential, pH, viscosity, and release of major components. LC-ESI/TOF/MS/MS metabolomic profiling of T. polium revealed the richness of the plant with phenolic compounds, particularly flavonoids. In addition, several terpenoids were detected. Kaempferol content of T. polium was estimated to be 7.85 ± 0.022 mg/ g of dry extract. The wound healing activity of TP-NP was explored in streptozotocin-induced diabetic rats. Diabetic animals were subjected to surgical wounding (1 cm diameter). Then they were divided in 5 groups (10 each). These included Group 1 (untreated control rats), Group 2 received the vehicle of CS-NG; Group 3 (0.5 g of TP prepared in hydrogel), Group 4 (0.5 g of TP-NP), Group 5 represented a positive control treated with 0.5 g of a commercial product. All treatments were applied topically for 21 days. Application of TP-NP on skin wounds of diabetic animals accelerated the healing process as evidenced by epithelium regeneration, formation of granulation tissue followed by epidermal proliferation, along with keratinization as verified by H&E. This was confirmed through enhanced collagen synthesis, as shown by raised hydroxyproline content and Col1A1 gene expression. Moreover, TP-NP significantly alleviated wound oxidative burst and diminished the expressions of inflammatory biomarkers. Meanwhile, TP-NP could enhance the expressions of transforming growth factor beta1 (TGF-ß1), in addition to the angiogenic markers; vascular endothelia growth factor A (VEGFA) and platelet-derived growth factor receptor alpha (PDGFRα). Collectively, chitosan nanogel of T. polium accelerates wound healing in diabetic rats, which could be explained - at least partly - through alleviating oxidative stress and inflammation coupled with pro-angiogenic capabilities.

Teucrium polium Extract Alleviates Pathological Features of Asthma via lL-12 and IFN-γ Modulation in Murine OVA-induced Allergic Asthma.

Asthma is a chronic disorder characterized by airway overreaction and remodeling, eosinophilia, and neutrophilic inflammation, accompanied by thickening of the airways and breathlessness. Teucrium polium (TP) is a plant with anti-inflammatory properties and is considered for the treatment of allergic disorders. In this study, we examined the effects of TP extract on ovalbumin (OVA)-induced asthma. Thirty female mice (5-6 weeks old) were divided into 5 groups of 6 each, including a control group and 4 groups treated with OVA, OVA + TP extract (50 mg/kg), OVA + TP extract (150 mg/kg), OVA + TP extract (300 mg/kg). Twenty-four hours after the last treatment, lung, serum, and spleen samples were collected and used for the evaluation of leukocyte infiltration, serum cytokine Interferon-gamma (IFN-γ) levels, and the expression of the Interleukin-12A (IL12A) gene, respectively. Hematoxylin-eosin staining was used to evaluate pathological changes in the lung tissue sections. Treatment with TP extract reduced inflammatory cells such as eosinophils and neutrophils in the airways. Furthermore, it increased serum levels of IFN-γ and IL-12A at a dose of 50, 150, and 300 mg/kg compared to the OVA group. This study showed that the administration of TP extract could improve pathological features, such as airway inflammation, and reduce systemic inflammation.

Screening of the phytochemical constituents of Teucrium polium extract and evaluation of their prophylactic role against the oxidative damage and cytotoxicity of Aflatoxin B1 in rats.

Aflatoxin B1 (AFB1) is common carcinogen causing acute and chronic hepatocyte injuries. This study aimed to determine the bioactive components of Teucrium polium methanolic extract (TPE) and to evaluate their protective role against AFB1-induced oxidative damage, cytotoxicity, and genotoxicity in rats. Six groups of male albino rats were treated orally for 4 weeks including the control group, the ِAFB1-treated group (80 µg/kg b.w.), the groups treated with low (LD) or high (HD) dose TPE (50 or 100 mg/kg b.w.), and the groups treated with AFB1 plus TEP (LD) or TPE (HD). Blood and serum samples were collected for different assays. The GC-MS identified 34 compounds, the major compounds were pinene, germacrene D, α-cadinol, α-thujene, epi-bicyclosesquiphellandrene, and limonene. Animals that received AFB1 showed significant changes in all indicators of oxidative stress, biochemistry, cytokines, MNPCEs, comet tail formation in bone marrow, mRNA expression of inflammatory-related genes, Nrf2, and iNOS beside histological changes in the liver. TPE at the two doses tested showed insignificant changes in all tested parameters. The extract could normalize most of these parameters and the hepatic structure in AFB1-treated animals in a dose-dependent fashion. therefore, we concluded that TPE supplementation is effective for protection against AFB1 in endemic areas.

Teucrium polium Extract Attenuates Inflammation in Asthma by Reducing RORγt Transcription and Increasing IL-10 Secretion in an Ovalbumin-induced Murine Asthma Model.

Background: One of the inflammatory diseases of the respiratory system is asthma. Teucrium polium (TP) has anti-inflammatory and anti-allergic properties and its anti-asthmatic effects have not been investigated yet. RORγt is an inflammatory transcription factor for Th17 differentiation. By secreting IL-17, Th17 leads to neutrophilic inflammation in the lungs. As an anti-inflammatory cytokine, IL-10 reduces the dissemination of inflammatory elements in the airways. Objective: To evaluate the effect of TP extract in asthma treatment. Methods: Thirty female Balb/c mice were distributed into 5 groups (n=6) including the control, treated with ovalbumin (OVA), and OVA+ various doses of TP (50, 150, and 300 mg/kg). All groups except the control group were sensitized to OVA solution on days 0, 7, and 14 by subcutaneous injection. The challenge was performed on days 18 to 21 by the inhalation of 1% OVA and the treatment was done with TP extract in the treatment groups, half an hour before the challenge. On day 22, the serum and spleen samples were collected to determine IL-10 serum levels and RORγt gene expression, respectively. Results: In the treatment groups, the expression of RORγt significantly decreased when using OVA+ Tp extract (150 mg/kg and 300 mg/kg), and IL-10 serum levels significantly increased when using OVA+ TP extract (150 mg/kg) compared with the OVA group. Conclusion: It is possible that TP extract can be effective in improving asthma by reducing inflammation.

Beneficial effects of Teucrium polium hydroalcoholic extract on letrozole-induced polycystic ovary syndrome in rat model.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is an endocrine disorder that disrupts the menstrual cycle and causes infertility. Considering the increasing use of medicinal plants, the present study aimed to evaluate the effects of Teucrium polium L. on letrozole-induced PCOS in female rats. METHODS: Six groups of rats (n=7 each) were evaluated. The control group received 1% carboxy methyl cellulose as vehicle, while the five other groups received letrozole 1 mg/kg orally for 21 days. After PCOS induction, the rats were orally administered T. polium extract (50, 100, and 200 mg/kg) or metformin (200 mg/kg) for 28 days. Subsequently, body and ovarian weights and serum levels of follicle stimulating hormone, luteinizing hormone (LH), estradiol, progesterone, and testosterone were measured. Finally, the ovarian tissues were isolated for histological examination. RESULTS: There were no significant changes in weekly body weight in any group. After 21 days of letrozole administration, PCOS induction was confirmed by estrous cycle irregularities and increased LH and testosterone levels. After treatment with the hydroalcoholic extract of T. polium, testosterone and LH levels were significantly reduced in all groups (P<0.05). Histological studies of ovaries in the metformin and T. polium groups exhibited normal follicular development with fewer and smaller cystic follicles than those in the PCOS group. CONCLUSION: The hydroalcoholic extract of T. polium improves serum levels of sex hormones, restores ovarian morphology in PCOS-induced rats, and is a good candidate for further clinical trials.

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.

Vasorelaxant Mechanism of Herbal Extracts from Mentha suaveolens, Conyza canadensis, Teucrium polium and Salvia verbenaca in the Aorta of Wistar Rats.

Mentha suaveolens (MS), Conyza canadensis (CC), Teucrium polium (TP) and Salvia verbenaca (SV) are used in Morocco to treat hypertension. Our aim was to characterize the composition and vasoreactivity of extracts of MS, CC, TP and SV. The chemical compositions of aqueous extracts of MS, SV and TP, and of a hydromethanolic extract of CC, were identified by HPLC-DAD. The vasoreactive effect was tested in rings of the thoracic aorta of female Wistar rats (8-14 weeks-old) pre-contracted with 10 µM noradrenaline, in the absence or presence of L-NAME 100 µM, indomethacin 10 µM or atropine 6 µM, to inhibit nitric oxide synthase, cyclooxygenase or muscarinic receptors, respectively. L-NAME and atropine decreased the vasorelaxant effect caused by low concentrations of MS. Atropine and indomethacin decreased the vasorelaxant effect of low concentrations of SV. High concentrations of MS or SV and the effect of SV and TP were not altered by any antagonist. The activation of muscarinic receptors and NO or the cyclooxygenase pathway underlie the vasorelaxant effect of MS and SV, respectively. Neither of those mechanisms underlines the vasorelaxant effect of CC and TP. These vasorelaxant effect might support the use of herbal teas from these plants as anti-hypertensives in folk medicine.

Aqueous extract of Teucrium polium ameliorates diabetes and induced-prostatic complication.

Purpose: Prostatic complications are common among diabetic patients. Previous research demonstrates that Teucrium polium (T. polium) has beneficial effects in diabetic cases. This study, therefore, aimed to evaluate the impacts of T. polium aqueous extract on the prostate of diabetic rats. Methods: Diabetes was induced in male Wistar rats by intraperitoneal injection of streptozotocin (50 mg/kg). a total of 40 Rats were randomly divided into the following groups: Control, Control + TP100 (TP100), Diabetic, Diabetic + TP100 (DTP100) and Diabetic + TP200 (DTP200). The intervention was done orally once per day for 56 days (8 weeks). An oral glucose tolerance test was conducted, glucose and insulin levels were assessed. Microscopic features of the ventral prostatic lobe were evaluated pathologically. Results: T. polium at both doses significantly reduced glucose levels in an insulin-independent pathway. T. polium at both doses significantly improved prostate weight, prostate epithelium height, and prostate secretory activity in comparison with the diabetic group. Interestingly, treatment of T. polium to healthy rats led to decreased epithelial height. Conclusion: It could be deduced that T. polium has useful impacts on glucose control and may prevent prostatic complications. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-00979-4.

Evaluation of Possible Antioxidant, Anti-Hyperglycaemic, Anti-Alzheimer and Anti-Inflammatory Effects of Teucrium polium Aerial Parts (Lamiaceae).

Teucrium polium L. is commonly used in folk medicine to treat hypertension and diabetes and to heal wounds. The present work aimed to evaluate the different biological activities of T. polium hydroalcoholic extract, its total phenol and flavonoid content, and its mineral elements. Results showed that T. polium extract showed significant antioxidant potential in 2-diphenyl-1-picrylhydrazyl (DPPH) assay with IC50 equal to 8.68 µg/mL but with moderate activity in galvinoxyl assay with IC50 of 21.82 µg/mL and mild activity in the ß-carotene assay. It also showed a pronounced anti-hyperglycemic activity using α-amylase inhibitory assay (IC50 = 111.68 µg/mL) and exceeds that of acarbose. T. polium showed excellent activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50 values of 28.69 and 4.93 µg/mL, respectively, postulating its promising anti-Alzheimer potential. The plant extract exhibited a strong anti-inflammatory effect with Bovine Serum Albumin (BSA) denaturation inhibitory potential estimated by 97.53% at 2 mg/mL, which was further confirmed by the in vivo carrageen-induced edema model. The extract revealed its richness in flavonoids and phenols, evidenced by its polyphenols content (36.35 ± 0.294 µg GAE/mg) and flavonoids (24.30 ± 0.44 µg QE/mg). It is rich in minerals necessary for human health, such as calcium, potassium, iron, sodium, magnesium, manganese and zinc. Molecular docking performed for previously identified compounds on human α-amylase, 5-lipoxygenase (5-LOX) and acetylcholine esterase confirmed the results. Thus, it can be concluded that T. polium can be a good candidate for alleviating many health-debilitating problems and can be highly beneficial in the pharmaceutical industry and medical research.

Teucrium polium L: An updated review of phytochemicals and biological activities.

Objective: Medicinal plants and their components are potential novel sources for developing drugs against various diseases. Teucrium polium L. (syn Teucrium capitatum L. or felty germander) from the Lamiaceae family, is widely distributed in the dry and stony places of the hills and deserts of almost all Mediterranean countries, southwestern Asia, Europe, and North Africa. Based on traditional Iranian medicine (TIM), T. polium is used for treating many diseases, including abdominal pain, indigestion, and type 2 diabetes. Materials and Methods: In our previous review article published in 2012 and based on 100 articles published from 1970 to 2010, the main compounds purified from T. polium were terpenes, terpenoids, and flavonoids with antioxidant, anticancer, anti-inflammatory, hypoglycemic, hepatoprotective, hypolipidemic, antibacterial, and antifungal activities. Results: In this article, the phytochemistry and pharmacological activities of the plant reported from 2011 to 2020 have been evaluated. Therefore, a search was done in the databases PubMed, Science Direct and Google Scholar, Scopus, and Web of Science with the terms "T. polium," "T. capitatum." and felty germander', which included about 100 articles published since 2011 about T. polium pharmacological activities and isolated compounds. Most studies of this review focused on the antioxidant and antidiabetic effects of the plant. Conclusion: Considering the position of T. polium in folk medicine, mainly as an antidiabetic agent, purification, structural and biological characterization of the active components appears essential for effective use of the plant.

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.

Pharmacokinetics and Therapeutic Potential of Teucrium polium against Liver Damage Associated Hepatotoxicity and Oxidative Injury in Rats: Computational, Biochemical and Histological Studies.

This study investigated the druggability, pharmacokinetics and ethyl acetate extract of Teucrium polium (EA T. polium) and the protective effect against carbon tetrachloride (CCl4) induced liver cirrhosis in rats. The total antioxidant capacity (TAC) and scavenging activity of the extract were examined. The in vivo protective study was based on the use of an animal model of CCl4-induced liver cirrhosis. Four groups of rats have been used: Group I: control rats; Group II: received CCl4 in olive oil (0.5 mL/kg); Group III: received the EA T. polium (25 mg/kg) of pretreatment for seven days by gavage then CCl4 in olive oil by gavage for 15 days. Group IV: received the EA of T. polium for seven days (25 mg/kg). EA T. polium was found to possess significant antioxidant capacity. CCl4 caused a hepatotoxicity associated increase in both levels of AST and ALT, which were reduced back to normal values following EA T. polium pretreatment. Hepatotoxicity associated structural modifications of liver tissues and increase in thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and carbonyl proteins (CP), associated decreases in several assessed antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT). The in vivo findings on the protective effect of T. polium were supported by its druggability, its pharmacokinetic properties and molecular docking assays. These results confirm the modulatory antioxidant and hepatoprotective potential of T. polium in this experimental liver cirrhosis model. T. polium phytochemicals are good candidates for further pharmaceutical explorations and drug design.

Teucrium polium (L.): Phytochemical Screening and Biological Activities at Different Phenological Stages.

The aim of the present study was to investigate the changes in the content of phytochemical compounds and in vitro antioxidant, antibacterial, and anti-inflammatory activities of Teucrium polium L. aerial parts and root methanolic extracts at different phenological stages (vegetative, flowering, and seeding). The T. polium extracts were analyzed using gas chromatography−mass spectrometry (GC-MS), and their antioxidant properties were tested with the 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO), ferrous ions (Fe2+), and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) methods. Forty-nine compounds were identified with the majority of germacrene D, t-cadinol, ß-pinene, carvacrol, bicyclogermacrene, α-pinene, and limonene. The results show that the extracts significantly differ between different phenological stages of the plant material used in terms of the phytochemical composition (total phenolic compounds, total flavonoids, total alkaloids, and total saponin contents) and bioactivities (antioxidant, antibacterial, and anti-inflammatory) (p < 0.05). The highest total contents of phenolics (72.4 ± 2.5 mg gallic acid equivalent (GAE)/g dry weight), flavonoids (36.2 ± 3.1 mg quercetin equivalent (QE)/g dry weight), alkaloids (105.7 ± 2.8 mg atropine equivalent (AE)/g dry weight), and saponins (653 ± 6.2 mg escin equivalent (EE)/g dry weight), as well as antioxidant, antibacterial, and anti-inflammatory activities, were measured for the extract of the aerial parts obtained at the flowering stage. The minimum inhibitory concentration (MIC) values for the extracts were varied within 9.4−300 µg/mL, while the minimum bactericidal concentration (MBC) values were varied within 18.75−600 µg/mL. In addition, they were more active on Gram-positive bacteria than Gram-negative bacteria. The data of this work confirm that the T. polium extracts have significant biological activity and hence can be used in the pharmaceutical industry, clinical applications, and medical research, as well as cosmetic and food industries.

Phytochemical Composition and Bioassay on Iranian Teucrium Polium Extracts against Anopheles Stephensi (Diptera: Culicidae).

Background: Anopheles stephensi is an important malaria vector mosquito in Iran and other western Asian countries. In many human communities, plant products have been used traditionally instead of synthetic pesticides for mosquito control due to their minimal hazardous effects. Teucrium polium, known popularly as felty germander, has been introduced in Persian Medicine (PM) as an insect repellent from a long time ago. Methods: The present study was undertaken to evaluate repellent and larvicidal activity of dichloromethane (DCMETP) and ethanolic extracts (EE-TP) of T. polium against An. stephensi under laboratory conditions. The possible chemical components of the extracts were also investigated through gas chromatography/mass spectrometry (GC-MS) technique. Results: Based on the results, DCME-TP showed better repellent activity than EE-TP with 56.67 and 28.33 % protection, respectively. Larvicidal activity of DCME-TP with 49.41% mortality was also higher than EE-TP (20.24%). The main identified constituents of DCME-TP were long chain alkanes, phenol, aromatic ester, oxaspiro and triterpenoid. While phenolic and aliphatic acid were only the identified components in EE-TP. It is notable that lupeol was detected in DCME of T. polium for the first time. Conclusion: DCME-TP can be considered as a new herbal candidate to control An. stephensi mosquitoes. Further studies are required on this extract for the fractionation and identification of the active compounds, and the evaluation of their bioactivity in the laboratory and field.