In THP-1 cells, magnolol and honokiol reduced inflammatory TNF-α and IL-8 production induced by Propionibacterium acnes  ⁽³⁾. Other anti-inflammatory markers reduced by magnolia bark extract include IL-6 as well as MMP2 and MMP9 ⁽⁴⁾. Antihyperglycemic effects with magnolia bark extract are attributed to the inhibition of protein tyrosine phosphatase enzyme 1B, a negative regulator of the insulin signaling pathway, which increases ERK phosphorylation and GLUt4 translocation ⁽⁵⁾. Magnolol increased both insulin-stimulated glucose transport and production of GLUT1 and GLUT4 mRNA, and GLUT4 protein ⁽⁶⁾.

A combination of honokiol and magnolol normalized biochemical abnormalities in brain 5-HT and 5-HIAA, serum corticosterone levels, and platelet adenylyl cyclase activity, a biomarker for depression in chronically stressed rodents ⁽⁷⁾. Anxiolytic effects of honokiol are attributed to its selective stimulation of GABA-A receptors or its binding to anxiety-related sites ⁽⁸⁾.

A number of anticancer mechanisms have been identified with magnolol. In human bladder cancer cells, it induced p27KIP1-mediated G2/M-phase cell cycle arrest to activate the extracellular signal-regulated kinase pathway ⁽¹¹⁾, and decreased binding of transcription factor NF-kB to DNA to inhibit MMP9 expression ⁽¹²⁾. In prostate cancer cells, magnolol affected insulin-like growth factor-1 expression and associated binding proteins ⁽¹³⁾, inhibited the EGFR/PI3K/Akt signaling pathway ⁽¹⁶⁾, and downregulated MMP2 and MMP9 proteins and mRNA levels ⁽¹⁵⁾. Antitumor activity also occurred via MMP9 inhibition through the NF-kB pathway in breast cancer cells ⁽¹⁹⁾ and through AMPK activation in colorectal cancer cells ⁽¹⁸⁾.

Antitumor and antiangiogenic properties of honokiol are attributed to NF-kB inhibition and the consequent scavenging of reactive oxygen species ⁽²⁴⁾. In human endothelial cells, honokiol inhibited vascular endothelial growth factor receptor 2 phosphorylation ⁽²⁵⁾. It also blocked VEGF-induced Rac to prevent migration of malignant endothelial cells ⁽²⁵⁾, blocked signaling pathways in tumor cells with defective p53 ⁽²³⁾, and suppressed NF-kB overactivity ⁽²⁴⁾. In acute myeloid leukemia cells, honokiol inhibited STAT3 signaling via increased protein tyrosine phosphatase SHP1 expression ⁽²⁶⁾. In glioma cells, it induced autophagy and activated a p53/cyclin D1/CDK6/CDK4/E2F1-dependent pathway to induce apoptosis and cell cycle arrest ⁽³⁴⁾ and in prostate cancer cells, honokiol suppressed c-Myc protein expression ⁽³⁰⁾.

In animal models of prostate cancer with bone metastasis, honokiol induced apoptosis via caspase-3,-8, and -9 activation and poly (ADP-ribose) polymerase (PARP) cleavage ⁽³⁷⁾. As a potential P-glycoprotein inhibitor, constituents of magnolia bark extract may reduce multidrug resistance in cancer cells via P-gp downregulation ^(42) (43).