Roselle ( L.) Extract As an Adjunct to Valsartan in Patients with Mild Chronic Kidney Disease: A Double-blind Randomized Controlled Clinical Trial

Overview

Journal Avicenna J Phytomed

Publisher Mashhad University of Medical Sciences

Date 2024 Jul 2

PMID 38952776

Authors

Behdad Dehkhoda

Ayesheh Enayati

Hassan Mirzaei

Somayeh Ghorbani

Mohammad Hadi Soleimani

Saeid Amirkhanlou

Amirhossein Sahebkar

Affiliations

Soon will be listed here.

Abstract

Objective: The objective of this study was to evaluate the effectiveness of L. extract (HS) as an adjunct to valsartan in the treatment of high blood pressure in patients with mild chronic kidney disease (CKD).

Materials And Methods: This trial was conducted in Gorgan, Iran. Seventy-two participants with CKD and high blood pressure were randomly assigned to either the HS group, receiving a 350 mg pill every 12 hr for 90 days along with 40 mg of valsartan every 12 hr, or the control group (40 mg valsartan + 12.5 mg hydrochlorothiazide). The primary objective was to assess the improvement of hypertension, while secondary objectives included the evaluation of proteinuria, albuminuria, kidney function, lipid profile, and electrolyte levels. Molecular docking analysis was performed to examine the mechanisms of action of the isolated components of HS.

Results: Out of 80 initial participants, 72 were included in the analysis. Both groups showed a significant reduction in blood pressure (p<0.001). The HS group demonstrated a statistically significant decrease in lipid profile (p<0.001). There were no statistically significant differences between the groups regarding the reduction of renal markers. Molecular docking analysis revealed that the compounds present in HS, particularly its anthocyanins and flavonoids, exhibited greater angiotensin-converting enzyme (ACE) inhibitory potential than hydrochlorothiazide in both domains. Moreover, the compounds met the criteria for drug likeness and Lipinski rules.

Conclusion: Adjunctive therapy with HS showed promising results in reducing hypertension and improving lipid profile in patients with CKD.

References

White C, Ghazan-Shahi S, Adams M . β-Trace protein: a marker of GFR and other biological pathways. Am J Kidney Dis. 2014; 65(1):131-46. DOI: 10.1053/j.ajkd.2014.06.038. View

Pugh D, Gallacher P, Dhaun N . Management of Hypertension in Chronic Kidney Disease. Drugs. 2019; 79(4):365-379. PMC: 6422950. DOI: 10.1007/s40265-019-1064-1. View

Dong Z, Dai H, Feng Z, Liu W, Gao Y, Liu F . Mechanism of herbal medicine on hypertensive nephropathy (Review). Mol Med Rep. 2021; 23(4). PMC: 7893801. DOI: 10.3892/mmr.2021.11873. View

Liyanage T, Toyama T, Hockham C, Ninomiya T, Perkovic V, Woodward M . Prevalence of chronic kidney disease in Asia: a systematic review and analysis. BMJ Glob Health. 2022; 7(1). PMC: 8796212. DOI: 10.1136/bmjgh-2021-007525. View

Perez-Torres I, Ruiz-Ramirez A, Banos G, El-Hafidi M . Hibiscus sabdariffa Linnaeus (Malvaceae), curcumin and resveratrol as alternative medicinal agents against metabolic syndrome. Cardiovasc Hematol Agents Med Chem. 2012; 11(1):25-37. DOI: 10.2174/1871525711311010006. View

Farjo K, Farjo R, Halsey S, Moiseyev G, Ma J . Retinol-binding protein 4 induces inflammation in human endothelial cells by an NADPH oxidase- and nuclear factor kappa B-dependent and retinol-independent mechanism. Mol Cell Biol. 2012; 32(24):5103-15. PMC: 3510526. DOI: 10.1128/MCB.00820-12. View

Caballero J . Considerations for Docking of Selective Angiotensin-Converting Enzyme Inhibitors. Molecules. 2020; 25(2). PMC: 7024173. DOI: 10.3390/molecules25020295. View

Aleksenko L, Akerstrom B, Hansson E, Erlandsson L, Hansson S . Pregnant alpha-1-microglobulin (A1M) knockout mice exhibit features of kidney and placental damage, hemodynamic changes and intrauterine growth restriction. Sci Rep. 2020; 10(1):20625. PMC: 7691512. DOI: 10.1038/s41598-020-77561-6. View

Cockwell P, Fisher L . The global burden of chronic kidney disease. Lancet. 2020; 395(10225):662-664. DOI: 10.1016/S0140-6736(19)32977-0. View

10.

Beck K, Thompson 3rd G, Odermatt A . Drug-induced endocrine blood pressure elevation. Pharmacol Res. 2019; 154:104311. DOI: 10.1016/j.phrs.2019.104311. View

11.

Manzano-Pech L, Guarner-Lans V, Soto M, Diaz-Diaz E, Caballero-Chacon S, Diaz-Torres R . Excessive Consumption L. Increases Inflammation and Blood Pressure in Male Wistar Rats via High Antioxidant Capacity: The Preliminary Findings. Cells. 2022; 11(18). PMC: 9497088. DOI: 10.3390/cells11182774. View

12.

Joven J, March I, Espinel E, Fernandez-Arroyo S, Rodriguez-Gallego E, Aragones G . Hibiscus sabdariffa extract lowers blood pressure and improves endothelial function. Mol Nutr Food Res. 2014; 58(6):1374-8. DOI: 10.1002/mnfr.201300774. View

13.

Izquierdo-Vega J, Arteaga-Badillo D, Sanchez-Gutierrez M, Morales-Gonzalez J, Vargas-Mendoza N, Gomez-Aldapa C . Organic Acids from Roselle ( L.)-A Brief Review of Its Pharmacological Effects. Biomedicines. 2020; 8(5). PMC: 7277581. DOI: 10.3390/biomedicines8050100. View

14.

Nwachukwu D, Aneke E, Nwachukwu N, Azubike N, Obika L . Does consumption of an aqueous extract of Hibscus sabdariffa affect renal function in subjects with mild to moderate hypertension?. J Physiol Sci. 2016; 67(1):227-234. PMC: 10717794. DOI: 10.1007/s12576-016-0458-z. View

15.

Muntner P, Anderson A, Charleston J, Chen Z, Ford V, Makos G . Hypertension awareness, treatment, and control in adults with CKD: results from the Chronic Renal Insufficiency Cohort (CRIC) Study. Am J Kidney Dis. 2009; 55(3):441-51. PMC: 2866514. DOI: 10.1053/j.ajkd.2009.09.014. View

16.

Kristiansson A, Davidsson S, Johansson M, Piel S, Elmer E, Hansson M . α-Microglobulin (A1M) Protects Human Proximal Tubule Epithelial Cells from Heme-Induced Damage In Vitro. Int J Mol Sci. 2020; 21(16). PMC: 7461577. DOI: 10.3390/ijms21165825. View

17.

Watanabe H, Fujimura R, Hiramoto Y, Murata R, Nishida K, Bi J . An acute phase protein α-acid glycoprotein mitigates AKI and its progression to CKD through its anti-inflammatory action. Sci Rep. 2021; 11(1):7953. PMC: 8041882. DOI: 10.1038/s41598-021-87217-8. View

18.

Hamrahian S, Falkner B . Hypertension in Chronic Kidney Disease. Adv Exp Med Biol. 2016; 956:307-325. DOI: 10.1007/5584_2016_84. View

19.

Argyropoulos C, Chen S, Ng Y, Roumelioti M, Shaffi K, Singh P . Rediscovering Beta-2 Microglobulin As a Biomarker across the Spectrum of Kidney Diseases. Front Med (Lausanne). 2017; 4:73. PMC: 5471312. DOI: 10.3389/fmed.2017.00073. View

20.

Alarcon-Alonso J, Zamilpa A, Aguilar F, Herrera-Ruiz M, Tortoriello J, Jimenez-Ferrer E . Pharmacological characterization of the diuretic effect of Hibiscus sabdariffa Linn (Malvaceae) extract. J Ethnopharmacol. 2011; 139(3):751-6. DOI: 10.1016/j.jep.2011.12.005. View