Investigations of Limeum Indicum Plant for Diabetes Mellitus and Alzheimer's Disease Dual Therapy: Phytochemical, GC-MS Chemical Profiling, Enzyme Inhibition, Molecular Docking and In-Vivo Studies
Ms. Tahira Shamim
University College of Conventional Medicine, Faculty of Medicine & Allied Health Sciences, The Islamia University of Bahawalpur, 63100 Bahawalpur, Pakistan
Search for more papers by this authorCorresponding Author
Dr. Hafiz Muhammad Asif
University College of Conventional Medicine, Faculty of Medicine & Allied Health Sciences, The Islamia University of Bahawalpur, 63100 Bahawalpur, Pakistan
Search for more papers by this authorCorresponding Author
Dr. Syeda Abida Ejaz
- [email protected]
- [email protected]
- +92-3155289756 | Fax: +92-62-9250242
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The Islamia University of Bahawalpur, 63100 Bahawalpur, Pakistan
Search for more papers by this authorMr. Zahid Hussain
Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, 22060 Abbottabad, Pakistan
Center for Advance Drug Research, COMSATS University Islamabad, Abbottabad Campus, 22060 Abbottabad, Pakistan
Search for more papers by this authorProf. Dr. Tanveer A. Wani
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O.Box 2452, 11451 Riyadh, Saudi Arabia
Search for more papers by this authorMs. Laila Sumreen
University College of Conventional Medicine, Faculty of Medicine & Allied Health Sciences, The Islamia University of Bahawalpur, 63100 Bahawalpur, Pakistan
Search for more papers by this authorDr. Muhammad Abdullah
Cholistan Institute of Desert Studies, The Islamia University of Bahawalpur, 63100 Bahawalpur, Pakistan
Search for more papers by this authorMr. Zubair Ahmed
Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, 22060 Abbottabad, Pakistan
Search for more papers by this authorProf. Dr. Jamshed Iqbal
Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, 22060 Abbottabad, Pakistan
Center for Advance Drug Research, COMSATS University Islamabad, Abbottabad Campus, 22060 Abbottabad, Pakistan
Search for more papers by this authorProf. Dr. Song Ja Kim
College of Natural Sciences, Department of Biological Sciences, Kongju National University, 32588 Gongju, South Korea
Search for more papers by this authorDr. Muhammad Kamal Shah
Faculty of Veterinary and Animal Sciences, Gomal University, 29220 Dera Ismail Khan, Pakistan
Search for more papers by this authorMs. Tahira Shamim
University College of Conventional Medicine, Faculty of Medicine & Allied Health Sciences, The Islamia University of Bahawalpur, 63100 Bahawalpur, Pakistan
Search for more papers by this authorCorresponding Author
Dr. Hafiz Muhammad Asif
University College of Conventional Medicine, Faculty of Medicine & Allied Health Sciences, The Islamia University of Bahawalpur, 63100 Bahawalpur, Pakistan
Search for more papers by this authorCorresponding Author
Dr. Syeda Abida Ejaz
- [email protected]
- [email protected]
- +92-3155289756 | Fax: +92-62-9250242
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The Islamia University of Bahawalpur, 63100 Bahawalpur, Pakistan
Search for more papers by this authorMr. Zahid Hussain
Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, 22060 Abbottabad, Pakistan
Center for Advance Drug Research, COMSATS University Islamabad, Abbottabad Campus, 22060 Abbottabad, Pakistan
Search for more papers by this authorProf. Dr. Tanveer A. Wani
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O.Box 2452, 11451 Riyadh, Saudi Arabia
Search for more papers by this authorMs. Laila Sumreen
University College of Conventional Medicine, Faculty of Medicine & Allied Health Sciences, The Islamia University of Bahawalpur, 63100 Bahawalpur, Pakistan
Search for more papers by this authorDr. Muhammad Abdullah
Cholistan Institute of Desert Studies, The Islamia University of Bahawalpur, 63100 Bahawalpur, Pakistan
Search for more papers by this authorMr. Zubair Ahmed
Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, 22060 Abbottabad, Pakistan
Search for more papers by this authorProf. Dr. Jamshed Iqbal
Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, 22060 Abbottabad, Pakistan
Center for Advance Drug Research, COMSATS University Islamabad, Abbottabad Campus, 22060 Abbottabad, Pakistan
Search for more papers by this authorProf. Dr. Song Ja Kim
College of Natural Sciences, Department of Biological Sciences, Kongju National University, 32588 Gongju, South Korea
Search for more papers by this authorDr. Muhammad Kamal Shah
Faculty of Veterinary and Animal Sciences, Gomal University, 29220 Dera Ismail Khan, Pakistan
Search for more papers by this authorAbstract
Limeum indicum has been widely utilized in traditional medicine but no experimental work has been done on this herb. The primary objective of this study was to conduct a phytochemical analysis and assess the multifunctional capabilities of aforementioned plant in dual therapy for Alzheimer′s disease (AD) and Type 2 diabetes (T2D). The phytochemical screening of ethanol, methanol extract, and their derived fractions of Limeum indicum was conducted using GC-MS, HPLC, UV-analysis and FTIR. The antioxidant capacity was evaluated by DPPH method. The inhibitory potential of the extracts/fractions against α-, β-glucosidase acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and monoaminine oxidases (MAO-A & B) was evaluated. Results revealed that acetonitrile fraction has highest inhibitory potential against α-glucosidase (IC50=68.47±0.05 μg/mL), methanol extract against β-glucosidase (IC50=91.12±0.07 μg/mL), ethyl acetate fraction against AChE (IC50=59.0±0.02 μg/mL), ethanol extract against BChE (28.41±0.01 μg/mL), n-hexane fraction against MAO-A (IC50=150.5±0.31 μg/mL) and methanol extract for MAO-B (IC50=75.95±0.13 μg/mL). The docking analysis of extracts\fractions suggested the best binding scores within the active pocket of the respective enzymes. During the in-vivo investigation, ethanol extract produced hypoglycemic effect (134.52±2.79 and 119.38±1.40 mg/dl) after 21 days treatment at dose level of 250 and 500 mg/Kg. Histopathological findings further supported the in-vivo studies.
Graphical Abstract
Conflict of interests
There is no any financial or personal competing interest among authors.
Open Research
Data Availability Statement
Data will be available on request by the corresponding author.
Supporting Information
As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.
| Filename | Description |
|---|---|
| cbdv202301858-sup-0001-misc_information.pdf1 MB | Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1N. R. Jabir, M. T. Rehman, K. Alsolami, S. Shakil, T. A. Zughaibi, R. F. Alserihi, M. S. Khan, M. F. AlAjmi, S. Tabrez, Annals of Medicine 2021, 53(1), 2332–44.
- 2M. Zvěřová, Clin. Biochem. 2019, 72, 3–6.
- 3J. Jia, J. Xu, J. Liu, Y. Wang, Y. Wang, Y. Cao, Q. Guo, Q. Qu, C. Wei, W. Wei, J. Zhang, Neurosci. Bull. 2021, 37, 1025–38.
- 4M. A. Cole, G. R. Seabrook, Transl. Res. and Clin. Inter. 2020, 6(1), e12009.
- 5B. U. Islam, N. R. Jabir, S. Tabrez, J. Drug Targeting 2019, 27(9), 932–42.
- 6B. U. Islam, S. K. Zaidi, M. A. Kamal, S. Tabrez, Curr. Drug Metab. 2017, 18(9), 808–13.
- 7K. D. Fasae, A. O. Abolaji, T. R. Faloye, A. Y. Odunsi, B. O. Oyetayo, J. I. Enya, J. A. Rotimi, R. O. Akinyemi, A. J. Whitworth, M. Aschner, J. Trace Elem. Med. Biol. 2021, 67, 126779.
- 8H. Hampel, F. Caraci, A. C. Cuello, G. Caruso, R. Nisticò, M. Corbo, F. Baldacci, N. Toschi, L. Akman-Anderson, F. Hernández, P. L. Valenzuela, Front. Immunol. 2020, 11, 509494.
10.3389/fimmu.2020.00456 Google Scholar
- 9N. R. Jabir, F. R. Khan, S. Tabrez, CNS Neurosci. Ther. 2018, 24(9), 753–62.
- 10N. R. Jabir, S. Shakil, S. Tabrez, M. S. Khan, M. T. Rehman, B. A. Ahmed, J. Biomol. Struct. Dyn. 2021, 39(14), 5083–92.
- 11X. Q. Chen, W. C. Mobley, Front. Neurosci. 2019, 13, 451499.
- 12G. D. Stanciu, A. Luca, R. N. Rusu, V. Bild, S. I. Beschea Chiriac, C. Solcan, W. Bild, D. C. Ababei, Biomol. Eng. 2019, 10(1), 40.
- 13J. G. Fernández-Bolaños, Ó. López, Expert Opin. Ther. Pat. 2022, 32(8), 913–32.
- 14J. E. Lima, N. C. Moreira, E. T. Sakamoto-Hojo, Mutat. Res. Genet. Toxicol. Environ. Mutagen. 2022, 874, 503437.
- 15World Health Organization. Investing to overcome the global impact of neglected tropical diseases: third WHO report on neglected tropical diseases 2015. World Health Organization, 2015.
- 16M. Marušić, M. Paić, M. Knobloch, A. M. Liberati Pršo, Can. J. Gastroenterol. Hepatol. 2021, 2021.
10.1155/2021/6613827 Google Scholar
- 17J. M. Sanches, L. N. Zhao, A. Salehi, C. B. Wollheim, P. Kaldis, The FEBS Journal 2023, 290(3), 620–48.
- 18B. Giri, S. Dey, T. Das, M. Sarkar, J. Banerjee, S. K. Dash, Biomed. Pharmacother. 2018, 107, 306–28.
- 19M. F. Mahomoodally, D. Lobine, M. C. Picot-Allain, N. Sadeer, S. Jugreet, G. Zengin, Curr. Med. Chem. 2021, 28(23), 4638–69.
- 20M. Foretz, B. Guigas, B. Viollet, Nat. Rev. Endocrinol. 2019, 15(10), 569–89.
- 21Y. Chornenkyy, W. X. Wang, A. Wei, P. T. Nelson, Brain Pathol. 2019, 29(1), 3–17.
- 22P. Pritam, R. Deka, A. Bhardwaj, R. Srivastava, D. Kumar, A. K. Jha, N. K. Jha, .Villa, S. K. Jha, Biology 2022, 11(2), 212.
- 23L. Meng, X. Y. Li, L. Shen, H. F. Ji, Trends Mol. Med. 2020, 26(6), 597–614.
- 24S. Shah, Himal. J. Health Sci. 2019, 4(1), 13–33.
- 25H. Rasouli, R. Yarani, F. Pociot, J. Popović-Djordjević, Pharmacol. Res. 2020, 155, 104723.
- 26D. Tungmunnithum, A. Thongboonyou, A. Pholboon, A. Yangsabai, Medicine 2018, 5(3), 93.
- 27E. C. O'Connor, K. Kambara, D. Bertrand, Expert Opin. Drug Discovery 2024, 19(2), 173–87.
- 28A. M. Nazareth, Dement. Neuropsychol. 2017, 11(2), 105–13.
- 29F. J. Novaes, M. A. da Silva, D. C. Silva, F. R. Aquino Neto, C. M. Rezende, Plants 2023, 12(8), 1580.
- 30M. Sajid-ur-Rehman, H. Y. Aati, M. Hussain, M. Sohaib Khan, M. Ahmed, K. U. Khan, Front. Pharmacol. 2023, 14, 1136459.
- 31T. K. Patle, K. Shrivas, R. Kurrey, S. Upadhyay, R. Jangde, R. Chauhan, Spectrochim. Acta Part A 2020, 242, 118717.
- 32P. S. Were, W. Waudo, H. S. Ozwara, H. L. Kutima, Int. J. Pharmacogn. Phyto. Res. 2015, 7(2), 201–5.
- 33R. N. Oliveira, M. C. Mancini, F. C. Oliveira, T. M. Passos, B. Quilty, R. M. Thiré, G. B. McGuinness, Matéria (Rio de Janeiro) 2016, 21(03), 767–79.
- 34T. Rehman, S. Ahmad, Ind. J. Res. Homeo. 2019, 13(2), 36–49.
- 35M. Solangi, K. M. Khan, F. Saleem, S. Hameed, J. Iqbal, Z. Shafique, U. Qureshi, Z. Ul-Haq, M. Taha, S. Perveen, Bioorg. Med. Chem. 2020, 28(21), 115605.
- 36S. Daud, O. U. Abid, A. Sardar, S. Abdullah, W. Shahid, M. Ashraf, S. A. Ejaz, A. Saeed, B. A. Shah, B. Niaz, Arch. Pharm. 2022, 355(8), 2200013.
- 37F. Solangi, J. Bai, S. Gao, L. Yang, G. Zhou, W. Cao, Agronomy 2019, 9(11), 708.
- 38G. Y. Chen, H. Zhang, F. Q. Yang, Anal. Chim. Acta 2021, 1142, 19–27.
- 39S. A. Ejaz, M. Aziz, A. Fayyaz, T. A. Wani, S. Zargar, J. Serb. Chem. Soc. 2023, 89(2), 177–194.
- 40M. A. Abbasi, A. Saeed, K. M. Khan, M. Ashraf, S. A. Ejaz, Iran. J. Pharm. Res.: IJPR 2014, 13(1), 87.
- 41M. S. Shah, S. U. Khan, S. A. Ejaz, S. Afridi, S. U. Rizvi, M. Najam-ul-Haq, J. Iqbal, Biochem. Biophys. Res. Commun. 2017, 482(4), 615–24.
- 42B. A. Khan, S. S. Hamdani, B. A. Alsfouk, S. A. Ejaz, M. Aziz, P. A. Channar, F. S. Deniz, I. E. Orhan, S. Hameed, A. Saeed, S. Jalil, J. Mol. Struct. 2023, 1271, 134138.
- 43B. A. Khan, S. S. Hamdani, S. Jalil, S. A. Ejaz, J. Iqbal, A. M. Shawky, A. M. Alqahtani, G. A. Gabr, M. A. Ibrahim, P. A. Sidhom, Pharmaceuticals 2022, 16(1), 11.
10.3390/ph16010011 Google Scholar
- 44S. A. Ejaz, M. Zain-ul-Abideen, P. A. Channar, A. Saeed, A. Ahmed, N. S. Alsaiari, K. M. Katubi, Q. Abbas, K. A. Dahlous, H. Raza, S. J. Kim, J. Mol. Struct. 2023, 1282, 135225.
- 45A. Khalid, N. Arshad, P. A. Channar, A. Saeed, M. I. Mir, Q. Abbas, S. A. Ejaz, T. Hökelek, A. Saeed, A. Tehzeeb, RSC Adv. 2022, 12(27), 17194–207.
- 46K. Yamamoto, H. Miyake, M. Kusunoki, S. Osaki, The FEBS journal 2010, 277(20), 4205–14.
- 47A. Chen, D. Wang, C. Ji, Front. Microbiol. 2021, 12, 723678.
- 48F. Nachon, E. Carletti, C. Ronco, M. Trovaslet, Y. Nicolet, L. Jean, P. Y. Renard, Biochem. J. 2013, 453(3), 393–9.
- 49S. Y. Son, J. Ma, Y. Kondou, M. Yoshimura, E. Yamashita, T. Tsukihara, Proc. Natl. Acad. Sci. USA 2008, 105(15), 5739–44.
- 50C. Binda, J. Wang, L. Pisani, C. Caccia, A. Carotti, P. Salvati, D. E. Edmondson, A. Mattevi, J. Med. Chem. 2007, 50(23), 5848–52.
- 51M. Aziz, S. A. Ejaz, N. Tamam, F. Siddique, N. Riaz, F. A. Qais, S. Chtita, J. Iqbal, Sci. Rep. 2022, 12(1), 6404.
- 52S. A. Ejaz, M. Aziz, M. Fawzy Ramadan, A. Fayyaz, M. S. Bilal, Molecules 2023, 28(10), 4044.
- 53F. Javed, Q. Jabeen, N. Aslam, A. M. Awan, J. Ethnopharmacol. 2020, 259, 112966.
- 54M. Ahmad, F. Zaman, T. Sharif, M. Z. Ch, Scand. J. Lab. Anim. Sci. 2008, 35(1), 29–34.
- 55M. Saxena, J. Saxena, Int. J. Biol. Pharm. Res. 2012, 3(3), 498–501.
- 56M. Johnson, M. S. Fathima, J. Pharm. Pharm. Sci. 2018, 10(3), 124–32.
- 57C. Karpagasundari, S. Kulothungan, J. Pharamcog. Phytochem. 2014, 3(4), 196–201.
- 58K. Dhivya, K. Kalaichelvi, Int. J. Herb. Med. 2017, 5(6), 40–4.
- 59B. Renuka, B. Sanjeev, D. Ranganathan, J. Pharamcog. Phytochem. 2016, 5(2), 105–8.
- 60M. Johnson, M. S. Fathima, J. Pharm. Pharm. Sci. 2018, 10(3), 124–32.
- 61C. Karpagasundari, S. Kulothungan, J. Pharmacogn. Phytochem. 2014, 3(4), 196–201.
- 62K. Dhivya, K. Kalaichelvi, Int. J. Herb. Med. 2017, 5(6), 40–4.
- 63B. Renuka, B. Sanjeev, D. Ranganathan, J. Pharmacogn. Phytochem. 2016, 5(2), 105–8.
- 64Y. M. Wei, L. Yang, H. Wang, C. H. Cai, Z. B. Chen, H. Q. Chen, W. L. Mei, H. F. Dai, Phytochemistry 2022, 200, 113182.
- 65R. M. Perez Gutierrez, Food Sci. Biotechnol. 2016, 25(1), 229–39.
- 66A. Sargsyan, M. A. Herman, Curr. Diab. Rep. 2019, 19, 1–1.
- 67A. Doss, S. P. Anand, Biochem Anal Biochem. 2012, 1(115), 2161–1009.
