Magnolol Attenuates Concanavalin A‐induced Hepatic Fibrosis, Inhibits CD4+ T Helper 17 (Th17) Cell Differentiation and Suppresses Hepatic Stellate Cell Activation: Blockade of Smad3/Smad4 Signalling

Abstract Magnolol is a pharmacological biphenolic compound extracted from Chinese herb Magnolia officinalis , which displays anti‐inflammatory and antioxidant effects. This study was aimed at exploring the potential effect of magnolol on immune‐related liver fibrosis. Herein, BALB /c mice were injected with concanavalin A (ConA, 8 mg/kg/week) up to 6 weeks to establish hepatic fibrosis, and magnolol (10, 20, 30 mg/kg/day) was given to these mice orally throughout the whole experiment. We found that magnolol preserved liver function and attenuated liver fibrotic injury in vivo . In response to ConA stimulation, the CD 4 + T cells preferred to polarizing towards CD 4 + T helper 17 (Th17) cells in liver. Magnolol was observed to inhibit Th17 cell differentiation in ConA‐treated liver in addition to suppressing interleukin ( IL )‐17A generation. Hepatic stellate cells were activated in fibrotic liver as demonstrated by increased alpha smooth muscle actin (α‐ SMA ) and desmin. More transforming growth factor ( TGF )‐β1 and activin A were secreted into the serum. Magnolol suppressed this abnormal HSC activation. Furthermore, the phosphorylation of Smad3 in its linker area (Thr179, Ser 204/208/213) was inhibited by magnolol. In vitro , the recombinant IL ‐17A plus TGF ‐β1 or activin A induced activation of human LX 2 HSC s and promoted their collagen production. Smad3/Smad4 signalling pathway was activated in LX 2 cells exposed to the fibrotic stimuli, as illustrated by the up‐regulated phospho‐Smad3 and the enhanced interaction between Smad3 and Smad4. These alterations were suppressed by magnolol. Collectively, our study reveals a novel antifibrotic effect of magnolol on Th17 cell‐mediated fibrosis.