Gingko biloba extract improves the lipid profile, inflammatory markers, leptin level and the antioxidant status of T2DM patients poorly responding to metformin

A double- blind, randomized, placebo-controlled trial

Authors

  • Saad Abdulrahman Hussain Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Rafidain University College, Baghdad, Iraq https://orcid.org/0000-0002-1909-417X
  • Tavga Ahmed Aziz Department of Pharmacology and Toxicology, College of Pharmacy, University of Sulaimani, Kurdistan Region, Iraq
  • Taha Othman Mahwi Department of Medicine, College of Medicine, University of Sulaimani, Kurdistan Region, Iraq
  • Zheen Aorahman Ahmed Department of Pharmacology and Toxicology, College of Pharmacy, University of Sulaimani, Kurdistan Region, Iraq

DOI:

https://doi.org/10.1590/s2175-97902022e19516

Keywords:

Ginkgo biloba, Uncontrolled T2DM, Inflammatory markers, Leptin, Antioxidant status

Abstract

The present study aims to evaluate the effects of Ginkgo biloba (GKB) extract as “add- on” therapy with metformin on the lipid profile, inflammatory markers, leptin and the total antioxidant capacity (TAOC) of patients with type 2 diabetes mellitus (T2DM). It is a multi- center, randomized, placebo-controlled double-blinded clinical study. Sixty patients were allocated into two groups: control and treatment groups; they received orally either 120 mg starch/capsule or 120mg GKB/capsule, respectively as an adjuvant with metformin for 90 days. Blood samples were obtained at zero time and after 90 days. The blood was utilized for analysis of the lipid profile, inflammatory markers, leptin, and TAOC. The GKB extract produced a significant decrease in the levels of TG, LDL-c, and CRP, with a significant increase in HDL-c compared to baseline values. There were no significant changes reported in the placebo-treated group. It also produced a significant decrease in the concentrations of IL-6, TNF-α, and leptin compared to baseline values and placebo-treated groups with a significant increase in TAOC compared to baseline values. In conclusion, GKB extract, as an adjuvant with metformin, decreases inflammatory mediators, leptin level and improves the antioxidant status and lipid profile of T2DM patients improperly managed with metformin.

Downloads

Download data is not yet available.

References

Abd-Ellah MF, Mariee AD. Ginkgo biloba leaf extract (EGb 761) diminishes adriamycin-induced hyperlipidaemic nephrotoxicity in rats: association with nitric oxide production. Biotechnol Appl Biochem. 2007;46(Pt 1):35-40.

Abdel-Zaher AO, Farghaly HSM, El-Refaiy AEM, Abd- Eldayem AM. Protective effect of the standardized extract of ginkgo biloba (EGb761) against hypertension with hypercholesterolemia-induced renal injury in rats: Insights in the underlying mechanisms. Biomed Pharmacother. 2017;95:944-55.

Aziz TA, Hussain SA, Mahwi TO, Ahmed ZA, Rahman HS, Rasedee A. The efficacy and safety of Ginkgo biloba extract as an adjuvant in type 2 diabetes patients ineffectively managed with metformin: A double-blind, randomized placebo-controlled trial. Drug Design Develop Ther. 2018;12:735-42.

Banin RM, Hirata BK, Andrade IS, Zemdegs JC, Clemente AP, Dornellas AP, et al. Beneficial effects of Ginkgo biloba extract on insulin signaling cascade, dyslipidemia, and body adiposity of diet-induced obese rats. Braz J Med Biol Res. 2014;47(9):780-8.

Cheng SM, Yang SP, Ho LJ, Tsao TP, Juan TY, Chang DM, et al. Down-regulation of cjun N-terminal kinase-activator protein-1 signaling pathway by Ginkgo biloba extract in human peripheral blood T cells. Biochem Pharmacol. 2003;66(4):679-89.

Czelusniak KE, Brocco A, Pereira DF, Freitas GBL. Morpho-anatomy, phytochemistry and pharmacology of Mikania glomerata Sprengel: a brief literature review. Rev Bras Plantas Med. 2012;14(2):400-9.

Diamond BJ, Bailey MR. Ginkgo biloba: indications, mechanisms, and safety. Psychiatr Clin North Am. 2013;36(1):73-83.

Ding Y, Tanaka Y, Zhang W, Wu Y. Risk factors contributing to type 2 diabetes and recent advances in the treatment and prevention. Int J Med Sci. 2014;11(11):1185-200.

Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature. 1998;395(6704):763-70.

Gastaldelli A. Role of beta-cell dysfunction, ectopic fat accumulation and insulin resistance in the pathogenesis of type 2 diabetes mellitus. Diabetes Res Clin Pract. 2011;93(1):S60-5.

Hirata BK, Banin RM, Dornellas AP, de Andrade IS, Zemdegs JC, Caperuto LC, et al. Ginkgo biloba extract improves insulin signaling and attenuates inflammation in retroperitoneal adipose tissue depot of obese rats. Mediators Inflamm. 2015;2015:41910610.

Houstis N, Rosen ED, Lander ES. Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature . 2006;440(7086):944-8.

Ismail-Beigi F. Pathogenesis and glycemic management of type 2 diabetes mellitus: a physiological approach. Arch Iran Med. 2012;15(4):239-46.

Kaul K, Hodgkinson A, Tarr JM, Kohner EM, Chibber R. Is inflammation a common retinal-renal-nerve pathogenic link in diabetes? Curr Diabetes Rev. 2010;6(5):294-303.

Kaur S, Sharma N, Nehru B. Anti-inflammatory effects of Ginkgo biloba extract against trimethyltin-induced hippocampal neuronal injury. Inflammopharmacology. 2018;26(1):87-104.

Khokhar KK, Sidhu S, Kaur G. Relationship between serum leptin and type 2 diabetes mellitus and their association with obesity and menopausal status. Arch Appl Sci Res. 2013;5(5):38-44.

Kusmic C, Basta G, Lazzerini G, Vesentini N, Barsacchi R. The effect of Ginkgo biloba in isolated ischemic/ reperfused rat heart: a link between vitamin E preservation and prostaglandin biosynthesis. J Cardiovasc Pharmacol. 2004;44(3):356-62.

Lu Q, Hao M, Wu W, Zhang N, Isaac AT, Yin J, et al. Antidiabetic cataract effects of GbE, rutin and quercetin are mediated by the inhibition of oxidative stress and polyol pathway. Acta Biochim Pol. 2018;65(1):35-41.

Montague CT, Farooqi IS, Whitehead JP, Soos MA, Rau H, Wareham NJ, et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature . 1997;387(6636):903-8.

Montes P, Ruiz-Sanchez E, Rojas C, Rojas P. Ginkgo biloba extract 761: a review of basic studies and potential clinical use in psychiatric disorders. CNS Neurol. Disord Drug Targets. 2015;14(1):132-49.

Rehman K, Akash MS. Mechanisms of inflammatory responses and development of insulin resistance: how are they interlinked? J Biomed Sci. 2016;23(1):87.

Ren Q, Chen J, Ding Y, Cheng J, Yang S, Ding Z, et al. In vitro antioxidant and immunostimulating activities of polysaccharides from Ginkgo biloba leaves. Int J Biol Macromol. 2019;124:972-80.

Schofield JD, Liu Y, Rao-Balakrishna P, Malik RA, Soran H. Diabetes dyslipidemia. Diabetes Ther. 2016;7(2):203-19.

Tangvarasittichai S. Oxidative stress, insulin resistance, dyslipidemia and type 2 diabetes mellitus. World J Diabetes. 2015;6(3):456-80.

Wu L, Parhofer KG. Diabetic dyslipidemia. Metabolism. 2014;63(12):1469-79.

Yang Q, Zhao H, Zhou AZ, Lou ZH. Preventive and therapeutic effects of compound ginkgo extract in rats with nonalcoholic steatohepatitis induced by high-fat, high-fructose diet. Zhonghua Gan Zang Bing Za Zhi. 2016;24(11):852-8.

Zhao Q, Gao C, Cui Z. Ginkgolide A reduces inflammatory response in high-glucose-stimulated human umbilical vein endothelial cells through the STAT3-mediated pathway. Int Immunopharmacol. 2015;25(2):242-8.

Zhou X, Cui G, Tseng HH, Lee SM, Leung GP, Chan SW, et al. Vascular contributions to cognitive impairment and treatments with traditional Chinese medicine. Evid Based Complement Alternat Med. 2016;2016:9627258.

Zhou YH, Yu JP, Liu YF, Teng XJ, Ming M, Lv P, et al. Effects of Ginkgo biloba extract on inflammatory mediators (SOD, MDA, TNF-α, NF-κ Bp65, IL-6) in TNBS-induced colitis in rats. Mediators Inflamm . 2006;2006:92642.

Zozulinska D, Wierusz-Wysocka B. Type 2 diabetes mellitus as inflammatory disease. Diabetes Res Clin Pract . 2006;74(2):S12-S16.

Downloads

Published

2022-11-23

Issue

Section

Original Article

How to Cite

Gingko biloba extract improves the lipid profile, inflammatory markers, leptin level and the antioxidant status of T2DM patients poorly responding to metformin: A double- blind, randomized, placebo-controlled trial. (2022). Brazilian Journal of Pharmaceutical Sciences, 58. https://doi.org/10.1590/s2175-97902022e19516