Rhein: A Review of Pharmacological Activities

Table 1

Summary of the in vitro and in vivo evidence for the biological activities of rhein.

Pharmacological effect	In vitro evidence	In vivo evidence
Hepatoprotective activity [2, 7, 10–12]		It modulates cytochrome P450 enzymes, protects hepatocyte from injury and prevents the progress of hepatic fibrosis in rats, alleviates glucose and lipid metabolism, increases energy expenditure, and restrains proinflammatory cytokine expression in mice.
Nephroprotective activity [15–20]	It abolishes the α-smooth muscle actin (α-SMA) and fibronectin expression of NRK-49F cells.	It alleviates renal fibrosis in mice. It reduces intestinal permeability and protects the intestinal mucosa in immune globulin A nephropathy (IgAN), halts the progression of IgAN, prevents the development of glomerulosclerosis, improves renal function, reduces renal fibrosis and interstitial inflammation, and inhibits the hypertrophy of renal proximal tubular epithelial cells in rats.
Chondroprotective activity [3, 21, 25, 26, 28–35]	It inhibits cytokines (IL-1β, LPS, TNF-α, and rhIL-1α)-induced effects in human osteoarthritic (OA) chondrocytes, human chondrosarcoma cell line HEM-C55, human OA cartilage and synovial tissue cultures, human umbilical vein endothelial cells (HUVECs), and bovine and rabbit articular chondrocytes. In particular, it stimulates aggrecan production, promotes matrix formation, decreases the production of certain proinflammatory mediators (IL-1β, IL-6, IL-8, and prostaglandin E2), corrects the matrix metalloproteinases/metalloproteinases imbalance, decreases IL-1 converting enzyme protein production, inhibits proliferation of synoviocytes and chondrocytes, and suppresses cathepsin B activity and proteoglycan release.
Anti-inflammatory activity [36, 37]	It reduces the transcription and expression of endothelial cell adhesion molecules.	It inhibits nicotinamide adenine dinucleotide phosphate oxidase (p22phox gp91phox) and cytokines (matrix metalloproteinase-2, activating transcript factor 6, and p66Shc).
Antioxidant activity [38–41]	Antioxidant properties in human peripheral neutrophils, HUVECs, and beef heart submitochondrial particles.	It prevents the drug-induced oxidative damage in rats.
Anticancer activity [6–9, 42–52]	Anticarcinogenic effects in mouse epidermal cell JB6 line, human colon adenocarcinoma cells (Caco-2), human nasopharyngeal carcinoma (NPC) cells, HUVECs, and tongue cancer SCC-4 cells induce apoptosis in human hepatocellular carcinoma BEL-7402 cells, human cervical cancer Ca Ski cells, human promyelocytic leukemia cells (HL-60), human NPC cells, human tongue cancer cell line (SCC-4), human hepatoblastomaG2 (HepG2) cells, KB cells, and A-549 human lung cancer cells.
Antidiabetic activity [4, 53–62]	It inhibits transforming growth factor and/or glucose transporter 1 overexpression in human and rat mesangial cells, inhibits glucose uptake in Ehrlich ascites tumor cells and human glomerular mesangial cells, and enhances glucose tolerance in 3T3-L1 adipocytes.	It decreases glucose concentrations, increases insulin secretion, and/or improves glucose tolerance in db/db mice.
Antimicrobial activity [63, 64]	Antimicrobial effects against bacterium Helicobacter pylori and staphylococcus aureus (S. aureus).
Purgative activity [49, 65, 66]	It induces ion secretion in human CaCo-2 monolayer cells and stimulates electrogenic chloride secretion in guinea pig colon.	It increases Na^+ and H2O flow in rat colon in-situ.
Lipid-lowering activity [67, 68]	It regulates cholesterol homeostasis and lipid and energy metabolism in 3T3-L1 and HepG2 cells.	It protects against obesity in mice.