A Comprehensive and System Review for the Pharmacological Mechanism of Action of Rhein, an Active Anthraquinone Ingredient

Abstract

Rhein is a major medicinal ingredient isolated from several traditional Chinese medicines, including Rheum palmatum L., Aloe barbadensis Miller, Cassia angustifolia Vahl., and Polygonum multiflorum Thunb. Rhein has various pharmacological activities, such as anti-inflammatory, antitumor, antioxidant, antifibrosis, hepatoprotective, and nephroprotective activities. Although more than 100 articles in PubMed are involved in the pharmacological mechanism of action of rhein, only a few focus on the relationship of crosstalk among multiple pharmacological mechanisms. The mechanism of rhein involves multiple pathways which contain close interactions. From the overall perspective, the pathways which are related to the targets of rhein, are initiated by the membrane receptor. Then, MAPK and PI3K-AKT parallel signaling pathways are activated, and several downstream pathways are affected, thereby eventually regulating cell cycle and apoptosis. The therapeutic effect of rhein, as a multitarget molecule, is the synergistic and comprehensive result of the involvement of multiple pathways rather than the blocking or activation of a single signaling pathway. We review the pharmacological mechanisms of action of rhein by consulting literature published in the last 100 years in PubMed. We then summarize these pharmacological mechanisms from a comprehensive, interactive, and crosstalk perspective. In general, the molecular mechanism of action of drug must be understood from a systematic and holistic perspective, which can provide a theoretical basis for precise treatment and rational drug use.

Rhein Suppresses Lung Inflammatory Injury Induced by Human Respiratory Syncytial Virus Through Inhibiting NLRP3 Inflammasome Activation via NF-κB Pathway in Mice

“…It possesses two hydroxide residues, one carboxyl, and has very strong chemical polarity (Malterud et al, 1993). Although Rhein has antioxidant, antiviral, antiinflammatory, antitumor, anti-fibrosis, hepatoprotective, and nephroprotective activities (Sun et al, 2016;Bi et al, 2018), the anti-RSV pneumonia of Rhein has not yet been clearly defined. Furthermore, previous literature studies found that Rhein had the anti-inflammatory effect through intervention NLRP3 signal in RAW264.7 macrophages, and zebrafish .…”

Rhein and rhubarb similarly protect the blood-brain barrier after experimental traumatic brain injury via gp91phox subunit of NADPH oxidase/ROS/ERK/MMP-9 signaling pathway

“…Thus, it is reasonable to propose a hypothesis that rhein derived from rhubarb is responsible for most of the observed neuroprotection following TBI. Rhein has extensive pharmacological effects, including anti-inflammatory, antitumor, antifibrosis, hepatoprotective, nephroprotective, antimicrobial and anti-oxidant activities171819. Unfortunately, the molecular mechanism underlying the protective effects on TBI remains unknown.…”

Nasal Drug Delivery of Anticancer Drugs for the Treatment of Glioblastoma: Preclinical and Clinical Trials

“…Another natural compound, the anthranoid 4,5-dihydroxyanthraquinone-2-carboxylic acid (rhein) exhibits anti-inflammatory, antioxidant, antifibrosis, neuroprotective and antitumor activities [82,83]. The antitumor activity is attributed to the inhibition of MAPK, PI3K-AKT and HIF-1 signaling pathways and the down-regulation of VEGF signaling pathway [83,84]. Blacher and colleagues [85], aiming at demonstrating that the inhibition of the ectoenzyme CD38 in tumor microenvironment can attenuate glioma progression, conducted a study using a syngeneic mouse glioma progression model.…”