Antiinflammatory and antidiabetic activity of Ballota L. species grown in Turkey

Abstract

Background and Aims: Ballota is represented by 12 species and 16 taxa in Turkey. Eleven of the 16 taxa are endemic to Turkey. Ballota have been used in different treatments in folk medicine. Antiinflammatory drugs act by protecting lysosomal membrane integrity or inhibiting enzymes of prostaglandins and thromboxane inflammatory mediators synthesized by deactivating of cyclooxygenase (COX), COX-1 and COX-2 enzymes. Besides, degradation of lysosomal membrane brings on the release inflammatory mediators so human red blood cells (HRBC) can be used for evaluating of antiinflammatory activity. One of the treatment approaches of diabetes mellitus is α-glucosidase enzyme inhibition. These enzymes play an important role in glucose releasing from carbohydrates. Due to the adverse effects of synthetic drugs, natural α-glucosidase inhibitors have been discussed as therapeutic agents to manage diabetes mellitus. In the light of the traditional use of Ballota species, we aimed to investigate the antiinflammatory and antidiabetic activities of the ethanol and aqueous extracts from the aerial parts of 14 Ballota taxa. Methods: HRBC membrane stabilizing and α-glucosidase inhibitory methods are used for determining antiinflammatory and antidiabetic activities of 14 Ballota taxa, respectively. Results: According to our results, the ethanolic extracts showed higher membrane stabilization profile than aqueous extracts generally. And for antidiabetic activity, it is concluded that aqueous and ethanol extracts of Ballota glandulosissima exhibited the maximum α-glucosidase inhibitory activity. Conclusion: According to our results, IC50 values of antiinflammatory effect of ethanolic and aqueous extracts of 14 Ballota samples ranged from 4,30-12,88 and 3,18-20,25 mg/ml, respectively. It is observed that aqueous extracts of Ballota nigra subsp. anatolica exhibited the maximum antiinflammatory effect. Both aqueous and ethanol extracts of Ballota glandulosissima are found to exhibit the maximum α-glucosidase inhibitory activity with IC50 values of 2,18 and 2,30 μg/ml, respectively. Among the ethanolic extracts of Ballota species, the strongest α-glucosidase inhibitory activities are found as B. glandulosissima>B. cristata>B. saxatilis subsp. brachyodonta in descending order.

Keywords

• α-glucosidase
• antiinflammatory activity
• antidiabetic activity
• Ballota species

References

1. • Baytop, T. (1999). Türkiye’de Bitkilerle Tedavi- Geçmişte ve Bugün- Nobel Tıp Kitapevleri.
2. • Bhalodia, N.R. & Shukla, V. (2011). Antibacterial and antifungal activities from leaf extracts of Cassia fistula l.: An ethnomedicinal plant. Journal of Advanced Pharmaceutical Technology & Research, 2, 104-109. https://www.japtr.org/temp/JAdvPharmTechRes22104- 7012802_192848.pdf
3. • Chowdhury, A., Azam, S., Jainul, M. A., Faruq, K. O., & Islam, A. (2014). Antibacterial Activities and In-vitro antiinflammatory (Membrane Stability) Properties of Methanolic Extracts of Gardenia coronaria Leaves. International Journal of Microbiology 2014,1-5. https:// www.hindawi.com/journals/ijmicro/2014/410935/
4. • Çitoğlu, G., Tanker, M., Sever, B., Englert, J., Anton, R., & Altanlar, N. (1998). Antibacterial activities of diterpenoids isolated from Ballota saxatilis subsp. saxatilis. Planta Medica, 64, 484-485. https:// doi.org/10.1055/s-2006-957494.
5. • Çitoğlu, G., Sever B., Antus, S., Baitz-Gacs, E., & Altanlar, N. (2003). Antifungal Flavonoids from Ballota glandulosissima. Pharmaceutical Biology, 41(7), 483-486. https://doi. org/10.1080/13880200308951339.
6. • Davis, P. H. (1982). Flora of Turkey and the East Aegean Islands, Vol. 7, Edinburgh University Press.
7. • Dinarello, C. A. (2010). Antiinflammatory agents: present and future. Cell, 140(6), 935-950. https://www.ncbi.nlm.nih.gov/pmc/ articles/PMC3752337/pdf/nihms-186840.pdf
8. • Dulger, B., & Sener, A. (2010). Evaluation of antimicrobial activity of Ballota acetabulosa. African Journal of Microbiology Research, 4(12), 1235-1238. https://academicjournals.org/journal/AJMR/ edition/18_June,_2010

9. • Erdoğan Orhan, I., Sever Yılmaz, B., Altun, L. M., & Saltan, G. (2010). Radical quenching activity, ferric reducing antioxidant power, and ferrous Ion-Chealting Capacity of 16 Ballota species and Their Total Phenol and Flavonid Content. Journal of Medicinal Food, 13(6), 1537-1543. https://doi.org/10.1089/jmf.2009.0237.
10. • Libby, P. (2007). Inflammatory mechanisms: molecular basis of inflammation and disease. Nutrition Reviews, 65(12:2), 140-146. https://doi.org/10.1111/j.1753-4887.2007.tb00352.x.
11. • Liu, X., Zhu, L., Tan, J., Zhou, X., Xiao, L., Yang, X., & Wang, B. (2014). Glucosidase inhibitory activity and antioxidant activity of flavonoid compound and triterpenoid compound from Agrimonia Pilosa Ledeb. BMC Complementary and Alternative Medicine, 14 (12), 2-10. https://bmccomplementmedtherapies.biomedcentral. com/articles/10.1186/1472-6882-14-12.
12. • Morteza-Semnani, K., & Ghanbarimasir, Z. (2019). A review on traditional uses, phytochemistry and pharmacological activities of the genus Ballota. Journal of Ethnopharmacology, 233, 197-217. https://doi.org/10.1016/j.jep.2018.12.001.
13. • Ozkan, G., Kamiloglu, S., Ozdal, T., Boyacioglu, D., & Capanoglu, E. (2016). Potential Use of Turkish Medicinal Plants in the Treatment of Various Diseases. Molecules, 21(3), 1-32. https://doi. org/10.3390/molecules21030257
14. • Özbek, H., Saltan Çitoğlu, G., Dülger, H., Uğraş, S., & Sever, B. (2004). Hepatoprotective and antiinflammatory activities of Ballota glandulosissima. Journal of Ethnopharmacology, 95: 143-149. https://www.sciencedirect.com/science/article/pii/ S0378874104003356?via%3Dihub
15. • Riccobono, L., Ben Jemia, M., Senatore, F., & Bruno, M. (2016). Chemical composition and biological activity of the essential oil of Ballota hispanica (L.) Benth. growing wild in Sicily. Plant Biosystems, 150(5), 1065-1071. https://doi.org/10.1080/11263504.2014. 1001462.
16. • Sever Yılmaz, B., & Saltan Çitoğlu, G. (2003). Chemical constituents of Ballota species. Ankara Üniversitesi Eczacılık Fakültesi Dergisi, 32(1), 37-53. https://dergipark.org.tr/tr/download/articlefile/ 424664
17. • Sever Yılmaz, B., Özbek, H., & Saltan Çitoğlu, G. (2006). Antinociceptive and Antiinflammatory activities of Ballota inaequidensis. Pharmaceutical Biology, 47(7), 653-658. https://doi. org/10.1080/13880200600897577
18. • Sever Yılmaz, B., Ergene, B., & Saltan Çitoğlu, G. (2015). Determination of total ortho-dihydroxycinnamic acid derivatives and flavonoid contents of Ballota species growing in Turkey. Turkish Journal of Pharmaceutical Sciences, 12(1), 67-74. http://cms.galenos.com. tr/Uploads/Article_12327/67-74.pdf
19. • Shinde, U., Phadke, A., Nair, A., Mungantiwar, A., Dikshit, V., & Saraf, M. (1999). Membrane stabilizing activity — a possible mechanism of action for the antiinflammatory activity of Cedrus deodara wood oil. Fitoterapia, 70(3), 251-257. https://doi.org/10.1016/ S0367-326X(99)00030-1.
20. • Singh, R., Patil, S.M., Pal, G., & Ahmad, M. (2012). Evaluation of invivo and in-vitro anti- inflammatory activity of Ajuga bracteosa Wall ex Benth. Asian Pacific Journal of Tropical Disease, 2(1), 404- 407. https://doi.org/10.1016/S2222-1808(12)60191-1.
21. • Şöhretoğlu, D., Sari, S., Barut, B., & Özel, A. (2018). Discovery of Potent α-glucosidase inhibitor flavonols: Insights into Mechanism of Action Through Inhibition Kinetics and Docking Simulations. Biorganic Chemistry, 79, 257-264. https://www.sciencedirect.com/ science/article/pii/S0045206818303328
22. • Tundis, R., Loizzo M. R., & Menichini, F. (2010). Natural Products as a-Amylase and a-glucosidase Inhibitors and their Hypoglycemic Potential in the Treatment of Diabetes: An Update. Mini-Reviews in Medicinal Chemistry, 10(4), 315-331. https://doi. org/10.2174/138955710791331007
23. • Uysal, S., Aumeeruddy-Elalfib, Z., Zengin, G., Aktumsek, A., Mocan, A., Custodio, L. ….. Mahomoodally, M. F. (2018). Insight into the biological properties and phytochemical composition of Ballota macrodonta Boiss. et Balansa, — an endemic medicinal plant from Turkey. Industrial Crops & Products, 113, 422-428. https://doi. org/10.1016/j.indcrop.2018.01.001
24. • Yalçın, C. Ö., Yılmaz Sarıaltın, S., & Çiçek Polat, D. (2020). Quantification of phenolic and flavonoid contents and some biological activities of Ornithogalum sigmoideum Freyn & Sint. Journal of Research In Pharmacy, 24(4), 487-496. https://doi.org/10.35333/ jrp.2020.197
25. • World Health Organization. (2016). Global Reports on Diabetes. Retrieved March 6, 2020 from https://apps.who.int/iris/bitstream/ handle/10665/204871/9789241565257_eng.pdf;jsession id=3DDCCCF6CF58A7EE0C9A0091DCE3EFDC?sequence=1