Cardiovascular protection of magnolol: cell-type specificity and dose-related effects

Abstract

Magnolia officinalis has been widely used in traditional Chinese medicine. Magnolol, an active component isolated from Magnolia officinalis, is known to be a cardiovascular protector since 1994. The multiplex mechanisms of magnolol on cardiovascular protection depends on cell types and dosages, and will be reviewed and discussed in this article. Magnolol under low and moderate dosage possesses the ability to protect heart from ischemic/reperfusion injury, reduces atherosclerotic change, protects endothelial cell against apoptosis and inhibits neutrophil-endothelial adhesion. The moderate to high concentration of magnolol mainly acts on smooth muscle cells and platelets. Magnolol induces apoptosis in vascular smooth muscle cells at moderate concentration and inhibits proliferation at moderate and high concentration. High concentration of magnolol also abrogates platelet activation, aggregation and thrombus formation. Magnolol also serves as an smooth muscle relaxant only upon the high concentration. Oral intake of magnolol to reach the therapeutic level for cardiovascular protection is applicable, thus makes magnolol an agent of great potential for preventing cardiovascular diseases in high-risk patients.

Magnolol Reduces Renal Ischemia and Reperfusion Injury via Inhibition of Apoptosis

“…The reasons for such findings, i.e., that the higher dose of 0.01 mg/kg of magnolol did not provide protective effects against renal I/R injury while the lower doses of 0.003 mg/kg and 0.006 mg/kg did, are not certain. However, Ho and Hong (2012) previously reported that magnolol has different cardiovascular protective effects on different cell types and that the protective effects of magnolol are dose-related.…”

“…Magnolol (Fig. 1A) is an active component of the bark of Magnolia officinalis, which has traditionally been used in China as an herbal remedy to treat gastroenterological disease, cough, and allergy (Ho and Hong, 2012). Magnolol has strong anti-oxidant and anti-inflammatory effects (Yao et al, 2009;Liang et al, 2014).…”

Magnolol Causes Alterations in the Cell Cycle in Androgen Insensitive Human Prostate Cancer CellsIn Vitroby Affecting Expression of Key Cell Cycle Regulatory Proteins

“…Preclinical studies on the bioavailability of magnolol have previously been performed in mouse and rat models. Two methods of delivery were used in these previous studies, intravenous injection and oral administration, and of these 2 delivery methods it was found that an injected dose of 2-10 mg/kg could attain a maximum blood plasma concentration of 10 mg/ml or 40 mM magnolol, whereas oral administration at 20 mg/kg could attain a maximum blood plasma concentration of 0.1 mg/ml or 0.4 mM magnolol (16)(17)(18). The elimination half-life for magnolol was determined to be 15 min, with total body clearance at 72-75 ml/min/kg (17)(18)(19).…”

Biological activity and toxicity of the Chinese herb Magnolia officinalis Rehder & E. Wilson (Houpo) and its constituents

“…The potential of M. officinalis to afford cardiovascular protection was attributed to its antioxidant components, including lignans and, notably, honokiol and magnolol. Those effects are doserelated, and are the consequence of different molecular mechanisms' regulation (Ho and Hong, 2012).…”

“…Magnolia compounds have been known for more than 20 years to interfere in some major pathways of platelet activation/inhibition: (1) TBXs, some of the most powerful agonists for platelet activation and major contributors to thrombus formation; TXB2, whether induced by collagen, arachidonic acid, or thrombin, is inhibited by magnolol and honokiol; also five aporphine alkaloids isolated from leaves of M. obovata, N-acetylanonaine, N-acetylxylopine, Nformylanonaine, liriodenine, and lanuginosine, show potent antiplatelet activities, probably by interfering with TXA2 production and/or binding (Teng et al, 1988;Pyo et al, 2003;Ho and Hong, 2012); (2) the activation of PPAR isoforms (α, β/δ, and γ), a pathway known to inhibit platelet aggregation; magnolol (20-60 μmol/L) dose-dependently enhances the activity and intracellular level of PPAR-β/γ in platelets (Shih and Chou, 2012); and (3) the cytosolic Ca 2+ influx and/or mobilization from intracellular stores that plays a crucial role in the platelet responses to various agonists (Lee et al, 2011); the rise of intracellular calcium caused by arachidonic acid or collagen is suppressed by both magnolol and honokiol (Teng et al, 1988;Pyo et al, 2003;Lee et al, 2011).…”