Research Progress on the Positive and Negative Regulatory Effects of Rhein on the Kidney: A Review of Its Molecular Targets

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2022 Oct 14

PMID 36235108

Authors

Yanna Zhu

Shilei Yang

Linlin Lv

Xiaohan Zhai

Guoyu Wu

Xiaolin Qi

Deshi Dong

Xufeng Tao

Affiliations

Soon will be listed here.

Abstract

Currently, both acute kidney injury (AKI) and chronic kidney disease (CKD) are considered to be the leading public health problems with gradually increasing incidence rates around the world. Rhein is a monomeric component of anthraquinone isolated from rhubarb, a traditional Chinese medicine. It has anti-inflammation, anti-oxidation, anti-apoptosis, anti-bacterial and other pharmacological activities, as well as a renal protective effects. Rhein exerts its nephroprotective effects mainly through decreasing hypoglycemic and hypolipidemic, playing anti-inflammatory, antioxidant and anti-fibrotic effects and regulating drug-transporters. However, the latest studies show that rhein also has potential kidney toxicity in case of large dosages and long use times. The present review highlights rhein's molecular targets and its different effects on the kidney based on the available literature and clarifies that rhein regulates the function of the kidney in a positive and negative way. It will be helpful to conduct further studies on how to make full use of rhein in the kidney and to avoid kidney damage so as to make it an effective kidney protection drug.

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References

Xiao Q, Yu X, Yu X, Liu S, Jiang J, Cheng Y . An integrated network pharmacology and cell metabolomics approach to reveal the role of rhein, a novel PPARα agonist, against renal fibrosis by activating the PPARα-CPT1A axis. Phytomedicine. 2022; 102:154147. DOI: 10.1016/j.phymed.2022.154147. View

Bi F, Chen F, Li Y, Wei A, Cao W . Klotho preservation by Rhein promotes toll-like receptor 4 proteolysis and attenuates lipopolysaccharide-induced acute kidney injury. J Mol Med (Berl). 2018; 96(9):915-927. DOI: 10.1007/s00109-018-1644-7. View

Guan Y, Wu X, Duan J, Yin Y, Guo C, Wei G . Effects and Mechanism of Combination of Rhein and Danshensu in the Treatment of Chronic Kidney Disease. Am J Chin Med. 2015; 43(7):1381-400. DOI: 10.1142/S0192415X15500780. View

Hoste E, Lameire N, Vanholder R, Benoit D, Decruyenaere J, Colardyn F . Acute renal failure in patients with sepsis in a surgical ICU: predictive factors, incidence, comorbidity, and outcome. J Am Soc Nephrol. 2003; 14(4):1022-30. DOI: 10.1097/01.asn.0000059863.48590.e9. View

Capolongo G, Capasso G, Viggiano D . A Shared Nephroprotective Mechanism for Renin-Angiotensin-System Inhibitors, Sodium-Glucose Co-Transporter 2 Inhibitors, and Vasopressin Receptor Antagonists: Immunology Meets Hemodynamics. Int J Mol Sci. 2022; 23(7). PMC: 8999762. DOI: 10.3390/ijms23073915. View

Wang G, Li Q, Chen D, Wu B, Wu Y, Tong W . Kidney-targeted rhein-loaded liponanoparticles for diabetic nephropathy therapy via size control and enhancement of renal cellular uptake. Theranostics. 2019; 9(21):6191-6208. PMC: 6735513. DOI: 10.7150/thno.37538. View

Boileau C, Tat S, Pelletier J, Cheng S, Martel-Pelletier J . Diacerein inhibits the synthesis of resorptive enzymes and reduces osteoclastic differentiation/survival in osteoarthritic subchondral bone: a possible mechanism for a protective effect against subchondral bone remodelling. Arthritis Res Ther. 2008; 10(3):R71. PMC: 2483463. DOI: 10.1186/ar2444. View

Wald R, Shariff S, Adhikari N, Bagshaw S, Burns K, Friedrich J . The association between renal replacement therapy modality and long-term outcomes among critically ill adults with acute kidney injury: a retrospective cohort study*. Crit Care Med. 2013; 42(4):868-77. DOI: 10.1097/CCM.0000000000000042. View

Du H, Shao J, Gu P, Lu B, Ye X, Liu Z . Improvement of glucose tolerance by rhein with restored early-phase insulin secretion in db/db mice. J Endocrinol Invest. 2012; 35(6):607-12. DOI: 10.1007/BF03345796. View

10.

Inker L, Astor B, Fox C, Isakova T, Lash J, Peralta C . KDOQI US commentary on the 2012 KDIGO clinical practice guideline for the evaluation and management of CKD. Am J Kidney Dis. 2014; 63(5):713-35. DOI: 10.1053/j.ajkd.2014.01.416. View

11.

Leon C, Raij L . Interaction of haemodynamic and metabolic pathways in the genesis of diabetic nephropathy. J Hypertens. 2005; 23(11):1931-7. DOI: 10.1097/01.hjh.0000188415.65040.5d. View

12.

Hu C, Cong X, Dai D, Zhang Y, Zhang G, Dai Y . Argirein alleviates diabetic nephropathy through attenuating NADPH oxidase, Cx43, and PERK in renal tissue. Naunyn Schmiedebergs Arch Pharmacol. 2011; 383(3):309-19. DOI: 10.1007/s00210-010-0593-7. View

13.

Henamayee S, Banik K, Sailo B, Shabnam B, Harsha C, Srilakshmi S . Therapeutic Emergence of Rhein as a Potential Anticancer Drug: A Review of Its Molecular Targets and Anticancer Properties. Molecules. 2020; 25(10). PMC: 7288145. DOI: 10.3390/molecules25102278. View

14.

van Es L, van den Wall Bake A, Valentijn R, Daha M . Composition of IgA-containing circulating immune complexes in IgA nephropathy. Am J Kidney Dis. 1988; 12(5):397-401. DOI: 10.1016/s0272-6386(88)80033-7. View

15.

Mazer M, Perrone J . Acetaminophen-induced nephrotoxicity: pathophysiology, clinical manifestations, and management. J Med Toxicol. 2008; 4(1):2-6. PMC: 3550099. DOI: 10.1007/BF03160941. View

16.

Perazella M . Pharmacology behind Common Drug Nephrotoxicities. Clin J Am Soc Nephrol. 2018; 13(12):1897-1908. PMC: 6302342. DOI: 10.2215/CJN.00150118. View

17.

Feng S, Li J, Qu L, Shi Y, Zhao D . Comparative pharmacokinetics of five rhubarb anthraquinones in normal and thrombotic focal cerebral ischemia-induced rats. Phytother Res. 2012; 27(10):1489-94. DOI: 10.1002/ptr.4890. View

18.

Pasmant E, Sabbagh A, Vidaud M, Bieche I . ANRIL, a long, noncoding RNA, is an unexpected major hotspot in GWAS. FASEB J. 2010; 25(2):444-8. DOI: 10.1096/fj.10-172452. View

19.

Radi Z, Stewart Z, ONeil S . Accidental and Programmed Cell Death in Investigative and Toxicologic Pathology. Curr Protoc Toxicol. 2018; 76(1):e51. DOI: 10.1002/cptx.51. View

20.

Chen H, Guh J, Chang J, Hsieh M, Shin S, Lai Y . Role of lipid control in diabetic nephropathy. Kidney Int Suppl. 2005; (94):S60-2. DOI: 10.1111/j.1523-1755.2005.09415.x. View