In vitro Analysis of the Anticancer and Antidiabetic Effects of Teucrium orientale Leaf Hydrophilic Extract Grown in Two Palestinian Geographic Areas
DOI:
https://doi.org/10.35516/jjps.v18i1.2492Keywords:
Teucrium orientale, α-Amylase, Lewis Lung Carcinoma, Cell proliferation, ApoptosisAbstract
Several studies have demonstrated that Teucrium orientale (T. orientale) species have therapeutic advantages, such as antioxidant, bacteriostatic, spasmolytic, and anti-inflammatory activity. This study aimed to assess the possible antidiabetic and anticancer activities of T. orientale leaf hydrophilic extracts collected from two distinct geographic regions in Palestine: Jerusalem and Ramallah. T. orientale hydrophilic extract was tested for its antidiabetic and anticancer properties on α-amylase activity and Lewis Lung Carcinoma (LLC) cells, respectively. The anticancer effect on LLC was evaluated by flow cytometry for cell proliferation and Annexin-V/propidium iodide (PI) staining for cell apoptosis. The T. orientale extract from Jerusalem had an IC50 of 7.43±0.84 μg/ml for inhibiting α-amylase enzyme activity, whereas the Ramallah extract had an IC50 value of 23.2±0.29 μg/ml. These values were compared to the positive control, Acarbose, which had an IC50 of 43.91±1.08 μg/ml. LLC cells were treated with one of the two extracts of T. orientale at different concentrations (0, 50, 100, 200, and 400 µg/ml) for 24 hours, and cell proliferation was assessed using an XTT assay. Total inhibition of LLC proliferation was achieved at 400 μg/ml in both extracts. The T. orientale extract from Jerusalem demonstrated a more efficient inhibitory effect at lower concentrations. Increasing concentrations of T. orientale (50, 100, 200, and 400 mg/ml) from the two geographic areas, Ramallah and Jerusalem, had no effect on the apoptosis rate in the control group. In contrast, elevated rates of apoptosis were observed following treatment with T. orientale extract in LLC cells at all tested concentrations, and this was positively associated with the late apoptosis marker Annexin-V+/PI+. Moreover, the T. orientale extract from Jerusalem exhibited an apoptotic rate of 90±3.4% at the highest concentration of 400 mg/ml, compared to 62.6±3.4% following treatment with the Ramallah extract. This suggests that the T. orientale extract from Jerusalem induced apoptosis in LLC cells more efficiently than the extract from Ramallah. The extracts derived from T. orientale show promising potential as a natural antidiabetic and anticancer agent, as evidenced by their ability to inhibit the α-amylase enzyme, impede the growth of LLC cells, and enhance apoptosis. Further in vivo and preclinical investigations are required to validate these effects.
References
Candela RG, Rosselli S, Bruno M, and Fontana G. A review of the phytochemistry, traditional uses and biological activities of the essential oils of genus Teucrium. Planta Medica. 2020; 87(06): 432-79. DOI: https://doi.org/10.1055/a-1293-5768
Alviri M, Bahadori MB, and Bahadori S. Flavonoid and Diterpenoid Components from Teucrium orientale subsp. orientale and their Radical Scavenging Activity. Biointerface Research in Applied Chemistry. 2022; 12(1): 682-9. DOI: https://doi.org/10.33263/BRIAC121.682689
Abdullah FO, Hussain FH, Sardar AS, Gilardoni G, Thu ZM, and Vidari G. Bio-Active compounds from Teucrium plants used in the traditional medicine of Kurdistan Region, Iraq. Molecules. 2022; 27(10): 3116. DOI: https://doi.org/10.3390/molecules27103116
Jaradat NA. Review of the taxonomy, ethnobotany, phytochemistry, phytotherapy and phytotoxicity of germander plant (Teucrium polium L.). Asian Journal of Pharmaceutical and Clinical Research. 2015; 8(2): 13 - 9.
Çakir A, Mavi A, Kazaz C, Yildirim A, and KÜFREVİOĞLU Öİ. Antioxidant activities of the extracts and components of Teucrium orientale L. var. orientale. Turkish Journal of Chemistry. 2006; 30(4): 483-94.
Reaisi Z, Yadegari M, and Shirmardia HA. Effects of Phenological Stage and Elevation on Phytochemical Characteristics of Essential Oil of Teucrium polium L. and Teucrium orientale L. International Journal of Horticultural Science and Technology. 2019; 6(1): 89-99.
Wang M, Yang Y, and Liao Z. Diabetes and cancer: epidemiological and biological links. World journal of diabetes. 2020; 11(6): 227. doi: 10.4239/wjd.v11.i6.227. DOI: https://doi.org/10.4239/wjd.v11.i6.227
Hu J, Fan H-D, Gong J-P, and Mao Q-S. The relationship between the use of metformin and the risk of pancreatic cancer in patients with diabetes: a systematic review and meta-analysis. BMC gastroenterology. 2023; 23(1): 1-21. DOI: https://doi.org/10.1186/s12876-023-02671-0
Dąbrowski M. Diabetes, antidiabetic medications and cancer risk in type 2 diabetes: focus on SGLT-2 inhibitors. International Journal of Molecular Sciences. 2021; 22(4): 1680. DOI: https://doi.org/10.3390/ijms22041680
Abdalla B, Mansour M, Ghanim M, Aia B, and Yassin M. The growing burden of cancer in the Gaza Strip. The Lancet Oncology. 2019; 20(8): 1054-6. DOI: https://doi.org/10.1016/S1470-2045(19)30460-7
Ballotari P, Vicentini M, Manicardi V, Gallo M, Ranieri SC, and Greci M, et al. Diabetes and risk of cancer incidence: results from a population-based cohort study in northern Italy. BMC cancer. 2017; 17(1): 1-8. DOI: https://doi.org/10.1186/s12885-017-3696-4
Zhu B. and Qu S. The relationship between diabetes mellitus and cancers and its underlying mechanisms. Frontiers in Endocrinology. 2022; 13: 800995. DOI: https://doi.org/10.3389/fendo.2022.800995
Yuliana ND, Khatib A, Choi YH, and Verpoorte R. Metabolomics for bioactivity assessment of natural products. Phytotherapy research: PTR. 2011; 25(2): 157-69. DOI: https://doi.org/10.1002/ptr.3258
James Hamuel D. Phytochemicals: Extraction Methods, Basic Structures and Mode of Action as Potential Chemotherapeutic Agents. In: Venketeshwer R, editor. Phytochemicals. Rijeka: IntechOpen; 2012. p. Ch. 1. In: Benzie IFF, Wachtel-Galor S, editors. Herbal Medicine: Biomolecular and Clinical Aspects. Boca Raton (FL): CRC Press/Taylor & Francis Copyright © 2011 by Taylor and Francis Group, LLC.; 2011. DOI: https://doi.org/10.5772/26052
Xu W, Cheng Y, Guo Y, Yao W, and Qian H. Effects of geographical location and environmental factors on metabolite content and immune activity of Echinacea purpurea in China based on metabolomics analysis. Industrial Crops and Products. 2022; 189: 115782. DOI: https://doi.org/10.1016/j.indcrop.2022.115782
Liu Y, Chen P, Zhou M, Wang T, Fang S, and Shang X, et al. Geographic variation in the chemical composition and antioxidant properties of phenolic compounds from Cyclocarya paliurus (Batal) Iljinskaja leaves. Molecules. 2018; 23(10): 2440. DOI: https://doi.org/10.3390/molecules23102440
Jaradat N, Qneibi M, Hawash M, Al-Maharik N, Qadi M, and Abualhasan MN, et al. Assessing Artemisia arborescens essential oil compositions, antimicrobial, cytotoxic, anti-inflammatory, and neuroprotective effects gathered from two geographic locations in Palestine. Industrial Crops and Products. 2022; 176: 114360. DOI: https://doi.org/10.1016/j.indcrop.2021.114360
Ghenabzia I, Hemmami H, Ilham B, Zeghoud S, Seghir BB, and Hammoudi R. Different methods of extraction of bioactive compounds and their effect on biological activity: A review. International Journal of Secondary Metabolite. 2023; 10(4): 469-94. DOI: https://doi.org/10.21448/ijsm.1225936
Townsend CC. Kew Bulletin. 1980; 35(3): 705-7. DOI: https://doi.org/10.2307/4110027
Nishiyama J, Kuninori T, and Matsumoto H. The use of 1, 1‐diphenyl‐2‐picrylhydrazyl for detecting free radicals in wheat flour dough. Journal of the Science of Food and Agriculture. 1978; 29(3): 267-73. DOI: https://doi.org/10.1002/jsfa.2740290312
Bertram JS. and Janik P. Establishment of a cloned line of Lewis Lung Carcinoma cells adapted to cell culture. Cancer letters. 1980; 11(1): 63-73. DOI: https://doi.org/10.1016/0304-3835(80)90130-5
Assali M, Kittana N, Alhaj-Qasem S, Hajjyahya M, Abu-Rass H, and Alshaer W, et al. Noncovalent functionalization of carbon nanotubes as a scaffold for tissue engineering. Scientific Reports. 2022; 12(1): 12062. DOI: https://doi.org/10.1038/s41598-022-16247-7
Jaradat N, Khasati A, Hawi M, Hawash M, Shekfeh S, and Qneibi M, et al. Antidiabetic, antioxidant, and anti-obesity effects of phenylthio-ethyl benzoate derivatives, and molecular docking study regarding α-amylase enzyme. Scientific Reports. 2022; 12(1): 3108. DOI: https://doi.org/10.1038/s41598-022-07188-2
Jaradat N, Qneibi M, Hawash M, Sawalha A, Qtaishat S, and Hussein F, et al. Chemical Composition, Antioxidant, Antiobesity, and Antidiabetic Effects of Helichrysum sanguineum (L.) Kostel. from Palestine. Arabian Journal for Science and Engineering. 2021; 46(1): 41-51. DOI: https://doi.org/10.1007/s13369-020-04707-z
Rates SMK. Plants as source of drugs. Toxicon. 2001; 39(5): 603-13. DOI: https://doi.org/10.1016/S0041-0101(00)00154-9
Karimi A, Majlesi M, and Rafieian-Kopaei M. Herbal versus synthetic drugs; beliefs and facts. Journal of nephropharmacology. 2015; 4(1): 27.
Jaradat N, Al-Lahham S, Abualhasan MN, Bakri A, Zaide H, and Hammad J, et al. Chemical constituents, antioxidant, cyclooxygenase inhibitor, and cytotoxic activities of Teucrium pruinosum boiss. Essential oil. BioMed Research International. 2018; 2018. DOI: https://doi.org/10.1155/2018/4034689
Eskandani M, Babak Bahadori M, Zengin G, Dinparast L, and Bahadori S. Novel natural agents from Lamiaceae family: An evaluation on toxicity and enzyme inhibitory potential linked to diabetes mellitus. Current Bioactive Compounds. 2016; 12(1): 34-8. DOI: https://doi.org/10.2174/1573407212666151231183118
Dastjerdi ZM, Namjoyan F. and Azemi ME. Alpha amylase inhibition activity of some plants extract of Teucrium species. European Journal of Biological Sciences. 2015; 7(1): 26-31.
Tahmasebpour N, Dehghan G, Feizi MAH, and Esmaeili HA. Variation in body weight and some hematological parameters in streptozotocin-induced diabetic rats, treated with Teucrium orientale. Pharmacology online. 2013; 3: 32-6.
Dehghan G, Tahmasebpour N, Hosseinpourfeizii M, Sheikhzadeh F, and Banan Khojasteh S. Hypoglycemic, antioxidant and hepato-and nephroprotective effects of Teucrium orientale in streptozotocin diabetic rats. Pharmacol online. 2013; 1: 182-9.
Smith DL, Orlandella RM, Allison DB, and Norian LA. Diabetes medications as potential calorie restriction mimetics—a focus on the alpha-glucosidase inhibitor acarbose. GeroScience. 2021; 43: 1123-33. DOI: https://doi.org/10.1007/s11357-020-00278-x
Kasabri V, Afifi FU, and Hamdan I. In vitro and in vivo acute antihyperglycemic effects of five selected indigenous plants from Jordan used in traditional medicine. Journal of ethnopharmacology. 2011; 133(2): 888-96. DOI: https://doi.org/10.1016/j.jep.2010.11.025
Asghari AA, Mokhtari-Zaer A, Niazmand S, Mc Entee K, and Mahmoudabady M. Anti-diabetic properties and bioactive compounds of Teucrium polium L. Asian Pacific Journal of Tropical Biomedicine. 2020; 10(10): 433. DOI: https://doi.org/10.4103/2221-1691.290868
Eid A, Jaradat N, Issa L, Khraiwesh E, and Yaish Z. Qualitative analysis of the antioxidant, carbohydrates, and lipids enzymes inhibitory effects of Coriandrum sativum seeds; a member of Palestinian flora. Palestinian Medical and Pharmaceutical Journal. 2023; 8(2): 11. DOI: https://doi.org/10.59049/2790-0231.1164
Tamil IG, Dineshkumar B, Nandhakumar M, Senthilkumar M, and Mitra A. In vitro study on α-amylase inhibitory activity of an Indian medicinal plant, Phyllanthus amarus. Indian journal of pharmacology. 2010; 42(5): 280. DOI: https://doi.org/10.4103/0253-7613.70107
Safamansouri H, Nikan M, Amin G, Sarkhail P, Gohari AR, and Kurepaz-Mahmoodabadi M. et al. α-Amylase inhibitory activity of some traditionally used medicinal species of Labiatae. Journal of Diabetes & Metabolic Disorders. 2014; 13(1): 1-5. DOI: https://doi.org/10.1186/s40200-014-0114-1
Hussain SA, Hameed A, Fu J, Xiao H, Liu Q, and Song Y. Comparative in vitro analysis of anti-diabetic activity of Indo-Pak black cardamom (Amomum subulatum Roxb.) and Chinese black cardamom (Amomum tsao-ko Crevost et Lemaire). Prog Nutri. 2018; 20: 403-14.
Nikavar B. and Yousefian N. Inhibitory effects of six Allium species on α-amylase enzyme activity. 2009.
Yuniarto A, Sukandar EY, Fidrianny I, Setiawan F, and Ketut I. Antiobesity, Antidiabetic and Antioxidant Activities of Senna (Senna alexandrina Mill.) and Pomegranate (Punica granatum L.) Leaves Extracts and Its Fractions. International Journal of Pharmaceutical and Phytopharmacological Research (eIJPPR). 2018; 8(3): 18-24.
Subramanian R, Asmawi MZ, and Sadikun A. In vitro alpha-glucosidase and alpha-amylase enzyme inhibitory effects of Andrographis paniculata extract and andrographolide. Acta Biochimica Polonica. 2008; 55(2): 391-8. DOI: https://doi.org/10.18388/abp.2008_3087
Nakajima K. Low serum amylase and obesity, diabetes and metabolic syndrome: A novel interpretation. World journal of diabetes. 2016; 7(6): 112. DOI: https://doi.org/10.4239/wjd.v7.i6.112
Kaur N, Kumar V, Nayak SK, Wadhwa P, Kaur P, and Sahu SK. Alpha‐amylase as molecular target for treatment of diabetes mellitus: A comprehensive review. Chemical Biology & Drug Design. 2021; 98(4): 539-60. DOI: https://doi.org/10.1111/cbdd.13909
Mukattash HK, Issa R, Abu Hajleh MN, and Al-Daghistani H. Inhibitory Effects of Polyphenols from Equisetum ramosissimum and Moringa peregrina Extracts on Staphylococcus aureus, Collagenase, and Tyrosinase Enzymes: In vitro Studies. Jordan Journal of Pharmaceutical Sciences. 2024; 17(3): 530-48. DOI: https://doi.org/10.35516/jjps.v17i3.2164
Jaradat N, Al-Maharik N, Abdallah S, Shawahna R, Mousa A, and Qtishat A. Nepeta curviflora essential oil: phytochemical composition, antioxidant, anti-proliferative and anti-migratory efficacy against cervical cancer cells, and α-glucosidase, α-amylase and porcine pancreatic lipase inhibitory activities. Industrial Crops and Products. 2020; 158: 112946. DOI: https://doi.org/10.1016/j.indcrop.2020.112946
Jaradat NA, Al-lahham S, Zaid AN, Hussein F, Issa L, and Abualhasan MN, et al. Carlina curetum plant phytoconstituents, enzymes inhibitory and cytotoxic activity on cervical epithelial carcinoma and colon cancer cell lines. European Journal of Integrative Medicine. 2019; 30: 100933. DOI: https://doi.org/10.1016/j.eujim.2019.100933
Tan G, Gyllenhaal C, and Soejarto D. Biodiversity as a source of anticancer drugs. Current drug targets. 2006; 7(3): 265-77. DOI: https://doi.org/10.2174/138945006776054942
Stankovic MS, Curcic MG, Zizic JB, Topuzovic MD, Solujic SR, and Markovic SD. Teucrium plant species as natural sources of novel anticancer compounds: antiproliferative, proapoptotic and antioxidant properties. International journal of molecular sciences. 2011; 12(7): 4190-205. DOI: https://doi.org/10.3390/ijms12074190
Tafrihi M, Toosi S, Minaei T, Gohari AR, Niknam V, and Arab Najafi SM. Anticancer properties of Teucrium persicum in PC-3 prostate cancer cells. Asian Pacific Journal of Cancer Prevention. 2014; 15(2): 785-91. DOI: https://doi.org/10.7314/APJCP.2014.15.2.785
Milutinović MG, Maksimović VM, Cvetković DM, Nikodijević DD, Stanković MS, and Pešić M, et al. Potential of Teucrium chamaedrys L. to modulate apoptosis and biotransformation in colorectal carcinoma cells. Journal of ethnopharmacology. 2019; 240: 111951. DOI: https://doi.org/10.1016/j.jep.2019.111951
Yildirmiş S, Aliyazicioglu R, Emre Eyupoglu O, Ozgen U, and Alpay Karaoglu S. Biological Activity and Characterization of Volatile Compounds of Teucrium orientale Var. glabrescens by SPME and GC‐FID/MS. Journal of Food Biochemistry. 2017; 41(1): e12284. DOI: https://doi.org/10.1111/jfbc.12284
DÖNMEZ İ. VOLATILE OIL COMPOSITION OF TEUCRIUM SPECIES OF NATURAL AND CULTIVATED ORIGIN IN THE LAKE DISTRICT OF TURKEY. Applied Ecology & Environmental Research. 2022; 20(3). DOI: https://doi.org/10.15666/aeer/2003_22352245
Zlatić NM, Stanković MS, and Simić ZS. Secondary metabolites and metal content dynamics in Teucrium montanum L. and Teucrium chamaedrys L. from habitats with serpentine and calcareous substrate. Environmental monitoring and assessment. 2017; 189: 1-15. DOI: https://doi.org/10.1007/s10661-017-5831-8
Afifi F, Abu–Irmaileh B, and Al-Noubani R. Comparative analysis of the essential oils of Teucrium polium L. grown in different arid & semi arid habitats in Jordan. Jordan Journal of Pharmaceutical Sciences. 2009; 2(1).
Lakušić B, Stevanović B, Jančić R, and Lakušić D. Habitat-related adaptations in morphology and anatomy of Teucrium (Lamiaceae) species from the Balkan peninsula (Serbia and Montenegro). Flora-Morphology, Distribution, Functional Ecology of Plants. 2010; 205(10): 633-46. DOI: https://doi.org/10.1016/j.flora.2010.04.018
Alhalaseh L, Issa R, Said R, and Al-suhaimat R. Antioxidant Activity, Phytochemical Screening published. Jordan Journal of Pharmaceutical Sciences. 2024; 17. DOI: https://doi.org/10.35516/jjps.v17i4.2442
Al-Gharaibeh MM, Maslat AO, Kanakr NAA, and Jarra YB. In Vivo Evaluation of Genotoxicity and Antioxidant Capacity of Ajuga Orientalis L. (Lamiaceae) Leaf Extracts. Jordan Journal of Pharmaceutical Sciences. 2024; 17(4): 755-66. DOI: https://doi.org/10.35516/jjps.v17i4.2466
Richard M. and Issac J. Analysis of climatic variability and its environmental impacts across the occupied Palestinian territory. Water and Environment Research Department, Applied Research Institute–Jerusalem Bethlehem, Palestine. 2012.