Antidiabetic Activity of Ficusonolide, a Triterpene Lactone from Ficus foveolata (Wall. ex Miq.): In Vitro, In Vivo, and In Silico Approaches

Ala Ud Din; Maria Khan; Muhammad Zahir Shah; Abdur Rauf; Umer Rashid; Anees Ahmed Khalil; Khair Zaman; Yahya S Al-Awthan; Mohammed A Al-Duais; Omar Bahattab; Adil A H Mujawah; Naveed Muhammad

doi:10.1021/acsomega.1c04230

Antidiabetic Activity of Ficusonolide, a Triterpene Lactone from Ficus foveolata (Wall. ex Miq.): In Vitro, In Vivo, and In Silico Approaches

ACS Omega. 2021 Oct 5;6(41):27351-27357. doi: 10.1021/acsomega.1c04230. eCollection 2021 Oct 19.

Authors

Ala Ud Din¹, Maria Khan¹, Muhammad Zahir Shah², Abdur Rauf³, Umer Rashid⁴, Anees Ahmed Khalil⁵, Khair Zaman⁶, Yahya S Al-Awthan^{7

8}, Mohammed A Al-Duais^{9

10}, Omar Bahattab⁷, Adil A H Mujawah¹¹, Naveed Muhammad¹²

Affiliations

¹ Department of Chemistry, Bacha Khan University Charsadda, Charsadda 24420, Khyber Pakhtunkhwa, Pakistan.
² Key Laboratory of Synthetic and Natural Fucntional Molecule, North West University, Xian 710127, P. R. China.
³ Department of Chemistry, University of Swabi, Anbar 23430, Khyber Pakhtunkhwa, Pakistan.
⁴ Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan.
⁵ University Institute of Diet and Nutritional Sciences, Faculty of Allied Health Sciences, The University of Lahore, 54590 Lahore, Pakistan.
⁶ Department of Chemistry, Abdul Wali Khan University, Mardan 23200, Khyber Pakhtunkhwa, Pakistan.
⁷ Department of Biology, Faculty of Science, University of Tabuk, Tabuk 71491, Saudi Arabia.
⁸ Department of Biology, Faculty of Science, Ibb University, Ibb 70270, Yemen.
⁹ Department of Biochemistry, Faculty of Science, University of Tabuk, Tabuk 71491, Saudi Arabia.
¹⁰ Biochemistry Unit, Chemistry Department, Faculty of Science, Ibb University, Ibb 70270, Yeme.
¹¹ Department of Chemistry, College of Science and Arts, Qassim University, Ar Rass 51921, Saudi Arabia.
¹² Department of Pharmacy, Abdul Wali Khan University, Mardan 23200, Khyber Pakhtunkhwa, Pakistan.

Abstract

Diabetes is a chronic condition which is locally managed through the stem of Ficus foveolata. To find the exact chemical constituent responsible for this activity, a triterpene lactone (ficusonolide) isolated from F. foveolata was studied for antidiabetic potential through the in vitro antidiabetic paradigm employing L-6 cells and an in vivo antidiabetic assay against non-insulin-dependent rats. The results on glucose uptake in the L-6 cell line indicated that ficusonolide has enhanced the uptake of glucose by 53.27% over control at a dose of 100 μg/mL, while at doses of 50 and 25 μg/mL, the glucose uptake was enhanced by 22.42 and 14.34%, respectively. The extract of F. foveolata (100 mg/kg) and ficusonolide (50 mg/kg) demonstrated a significant (p < 0.001) decline in streptozotocin-induced hyperglycemia of diabetic rats. Ficusonolide displayed conspicuous inhibitory activity against the molecular docking studies with proteins such as dipeptidyl peptidase-IV (DPP-IV), protein tyrosine phosphatase 1B (PTP-1B), α-glucosidase, and α-amylase subjected to molecular targets. Detailed computational and structural insights affirmed promising interactions between target proteins and ficusonolide. In conclusion, the plant and its isolated compound have significant antidiabetic activity with a possible mechanism of interaction with DPP-IV, PTP-1B, α-glucosidase, and α-amylase.