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

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.

Network pharmacology, molecular docking, and experimental verification reveal the mechanism of San-Huang decoction in treating acute kidney injury

“…Studies ( Ma et al, 2018 ) have found that emodin can inhibit the expression of transforming growth factor β1, block the TGF-β1/Smad signaling pathway, and inhibit the transdifferentiation of human renal tubular epithelial cells (HK-2), thereby reducing epithelial-myofibroblast transdifferentiation (TEMT). Rhein and its derivatives, analogs, and compound preparations protect against various kidney diseases, particularly diabetic nephropathy (DN) and drug-induced AKI ( Zhu et al, 2022 ). In the research of Luo Yan et al, Rhein was found to restrain the SHH-Gli1-Snail signal pathway, extenuating renal fibrosis in rhein-treated UUO rats ( Luo et al, 2022 ).…”

Anthraquinone Removal from Cassia obtusifolia Seed Water Extract Using Baking, Stir-Frying, and Adsorption Treatments: Effects on the Chemical Composition, Physicochemical Properties of Polysaccharides, and Antioxidant Activities of the Water Extract

“…On the other hand, anthraquinones could reduce toxicity and enhance protective effects by the compatibility of traditional Chinese medicine. 62 This study suggested that BT, ST, and AT could effectively decrease the anthraquinone content of CWEs by 35.9, 27.3, and 93.8%, respectively. Therefore, the treatment method can be adjusted according to the final anthraquinone content, which could exert the biological activity of the anthraquinones and decrease negative effects.…”

“…Zhu et al clarified that rhein regulated the function of the kidney in both a positive and negative way and further proposed the methods of using rhein reasonably and safely. 62 Qu et al evaluated the acute and subchronic toxicity of anthraquinones and found that the lowest observed adverse effect level was 5.44 mg/kg body weight and that there were no observed adverse effects at 1.36 mg/kg body weight. 63 These results demonstrated that anthraquinones played a dual role in bioactivities, and so the use of anthraquinones should be treated cautiously.…”

“…There is no denying that anthraquinones have various bioactivities, while concerns have been raised with their widespread and frequent use. Zhu et al clarified that rhein regulated the function of the kidney in both a positive and negative way and further proposed the methods of using rhein reasonably and safely . Qu et al evaluated the acute and subchronic toxicity of anthraquinones and found that the lowest observed adverse effect level was 5.44 mg/kg body weight and that there were no observed adverse effects at 1.36 mg/kg body weight .…”

Rhein Improves Sepsis Rats by Reducing Inflammatory Reaction and Regulating AQP2 Acute Renal Injury

“…In recent decades, rhein has been widely used in the treatment of sepsis and other critical and critical fields [5]. Studies have found that [6,7], rhein can down regulate proinflammatory cytokines and signal transduction through NF-KB and other signal pathways. Previous experiments have established that Rhein is effective in inhibiting fibronectin and the excessive inhibition of TGF-H, thereby reducing the accumulation of extracellular matrix, protecting renal function, and improving renal histological changes, which suggests that rhein may also play a protective role in renal injury.…”