Magnolia officinalis

• How It Works

  Magnolia bark extract has shown anti-inflammatory and anticancer effects in laboratory and animal studies, but clinical trials are needed to test its effects in humans.

  Magnolia officinalis is an herb commonly used in traditional medicine. The bark contains active compounds, honokiol and magnolol that may reduce inflammation, anxiety, or depression. A number of laboratory studies also suggest that bioactive compounds from magnolia bark extract may have anticancer properties, but no studies have been conducted in humans. In addition, this botanical has been shown to inhibit several enzymes or pathways by which many drugs are metabolized. Therefore, clinical trials are needed to determine safety and effectiveness.

• Research Evidence
  • To prevent cancer
    Laboratory studies suggest magnolia bark extract has anticancer properties, but clinical trials are needed to confirm these effects as well as safety.
  • To treat diabetes
    Magnolia bark extract and its active compounds lowered blood sugar in the lab, but human studies are needed.
  • To prevent inflammation
    Animal studies have shown that magnolia bark extract reduces pain and inflammation.
  • As an antibacterial agent
    Lab studies suggest magnolia bark extract may reduce the bacterium that causes acne and some types of infections, but no studies have been done in humans.
• Do Not Take If
  • You are taking diabetes medications: Magnolia bark extract may enhance their effects.
  • You are taking sleep or anxiety medications: Magnolia bark extract may increase their effects.
  • You are taking blood thinners: Magnolia bark extract may increase the risk of bleeding.
  • You are taking cytochrome P450 substrate drugs: Magnolia bark extract may alter the effects of these drugs.
  • You are taking P-glycoprotein substrate drugs: Magnolia bark extract may alter the effects of these drugs.
  • You are taking UDP-glucuronosyltransferase (UGT) substrate drugs: Magnolia bark extract may alter the effects of these drugs.
• Side Effects
  • Skin rash has been reported with the use of cosmetics containing magnolia bark extract.

  Because so few studies have been conducted in humans, other side effects are currently not known. However, lab studies suggest that this botanical may interact with a number of drugs. Therefore, clinical trials are needed to determine safety and side effects.

• Scientific Name

  Magnolia officinalis

• Clinical Summary

  Magnolia officinalis is an oriental flowering herb that has been used in traditional Chinese medicine to treat anxiety, depression, stress, nervousness, and sleep-related problems. The tree bark contains the active constituents magnolol and honokiol.

  In vitro and in vivo studies suggest these compounds have antimicrobial ^(1) (2), anti-inflammatory ^(3) (4) , antidiabetic ^(5) (6), antidepressant ⁽⁷⁾, anxiolytic ⁽⁸⁾, and neuroprotective ⁽⁹⁾ effects. Preclinical studies have evaluated their anticancer potential. Magnolol demonstrated activity against a variety of cancers, including bladder ^{(10) (11) (12)}, prostate ^{(13) (14) (15) (16)}, colorectal ^(17) (18), breast ^(19) (20), and lung ^(21) (22) cancers . Honokiol also showed antitumor and antiangiogenic effects ^{(23) (24) (25)} in leukemia ⁽²⁶⁾, lung ^(27) (28), bladder ⁽²⁹⁾, prostate ⁽³⁰⁾, melanoma ^(31) (32), breast ⁽³³⁾, glioblastoma ⁽³⁴⁾, neuroblastoma ⁽³⁵⁾, and oral cancer ⁽³⁶⁾ cells lines. Other animal studies suggest honokiol may enhance low-dose docetaxel treatment against prostate cancer growth and bone metastasis ⁽³⁷⁾.

  A few preliminary studies have been conducted in humans, and showed benefits for vasomotor symptoms ⁽³⁸⁾, weight management ⁽³⁹⁾, and oral health ⁽⁴⁰⁾, but these studies were performed in combination with other compounds. There are no clinical trials conducted in humans to evaluate magnolia bark extract for its cancer preventive properties.

  Magnolia bark extract and its constituents may inhibit several enzymes or pathways by which many drugs are metabolized, including cytochrome P450 (CYP450), UDP- glucuronosyltransferase (UGT), and P-glycoprotein (P-gp) expression ^(41) (42). Therefore, there is the potential for interactions with many medications.

• Purported Uses
  • Antibacterial
  • Anxiety
  • Cancer prevention
  • Depression
  • Diabetes
  • Inflammation
• Mechanism of Action

  In THP-1 cells, magnolol and honokiol reduced inflammatory TNF-α and interleukin-8 (IL-8) production induced by Propionibacterium acnes  ⁽³⁾. Other anti-inflammatory markers reduced by magnolia bark extract include IL-6 as well as matrix metalloproteinase 2 (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 the binding of transcription factor NF-kappaB to DNA to inhibit MMP9 expression ⁽¹²⁾. In prostate cancer cells, magnolol affected the expression of insulin-like growth factor-1 (IGF-1) and associated binding proteins ⁽¹³⁾, inhibited the EGFR/PI3K/Akt signaling pathway ⁽¹⁶⁾, and downregulated MMP2 and MMP9 protein and mRNA levels ⁽¹⁵⁾. Antitumor activity also occurred via MMP9 inhibition through the NF-kappaB pathway in breast cancer cells ⁽¹⁹⁾ and through AMPK activation in colorectal cancer cells ⁽¹⁸⁾.

  Antitumor and antiangiogenic properties of honokiol are attributed to nuclear factor kappa beta (NF-kB) inhibition and the consequent scavenging of reactive oxygen species ⁽²⁴⁾. In human endothelial cells, honokiol inhibited vascular endothelial growth factor receptor 2 (VEGFR2) 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 (P-gp) inhibitor, constituents of magnolia bark extract may reduce multi-drug resistance in cancer cells via P-gp downregulation ^(42) (43).

• Adverse Reactions

  Case Reports
  Contact dermatitis: In 4 patients with the application of magnolia extract-containing cosmetics ^(44) (45).

• Herb Lab Interactions
  • Cytochrome (CYP) P450 substrates: In vitro, honokiol inhibited CYP1A2, CYP2C8, CYP2C9, CYP2C19, and may alter activities of the drugs metabolized by these enzymes ⁽⁴¹⁾.
  • UDP-glucuronosyltransferase (UGT): Honokiol inhibited UGT1A9 in vitro, suggesting it may interfere with activities of drugs metabolized by this enzyme ⁽⁴¹⁾.
  • P-Glycoprotein (P-gp) substrates: Honokiol downregulates P-gp expression ⁽⁴²⁾ and may interfere with the metabolism of certain drugs.
  • Antiplatelet agents: In animal studies, magnolol also demonstrated antiplatelet activities ⁽⁴⁶⁾ and may therefore increase the risk of bleeding when used with these drugs.
  • Antidiabetic agents: Laboratory studies suggest that Magnolia bark extract and magnolol have hypoglycemic effects ^(5) (6) and may increase the effects of these medications.
  • Benzodiazepines: Magnolia bark extract and honokiol may increase the effects of these medications ⁽⁴⁷⁾.
• References

  1. Hu Y, Qiao J, Zhang X, et al. Antimicrobial effect of Magnolia officinalis extract against Staphylococcus aureus. J Sci Food Agric. Apr 2011;91(6):1050-1056.

  2. Wu XN, Yu CH, Cai W, et al. Protective effect of a polyphenolic rich extract from Magnolia officinalis bark on influenza virus-induced pneumonia in mice. J Ethnopharmacol. Mar 8 2011;134(1):191-194.

  3. Park J, Lee J, Jung E, et al. In vitro antibacterial and anti-inflammatory effects of honokiol and magnolol against Propionibacterium sp. Eur J Pharmacol. Aug 2 2004;496(1-3):189-195.

  4. Walker JM, Maitra A, Walker J, et al. Identification of Magnolia officinalis L. bark extract as the most potent anti-inflammatory of four plant extracts. Am J Chin Med. 2013;41(3):531-544.

  5. Sun J, Wang Y, Fu X, et al. Magnolia officinalis Extract Contains Potent Inhibitors against PTP1B and Attenuates Hyperglycemia in db/db Mice. Biomed Res Int. 2015;2015:139451.

  6. Choi SS, Cha BY, Lee YS, et al. Magnolol enhances adipocyte differentiation and glucose uptake in 3T3-L1 cells. Life Sci. Jun 19 2009;84(25-26):908-914.

  7. Xu Q, Yi LT, Pan Y, et al. Antidepressant-like effects of the mixture of honokiol and magnolol from the barks of Magnolia officinalis in stressed rodents. Prog Neuropsychopharmacol Biol Psychiatry. Apr 1 2008;32(3):715-725.

  8. Kuribara H, Kishi E, Maruyama Y. Does dihydrohonokiol, a potent anxiolytic compound, result in the development of benzodiazepine-like side effects? J Pharm Pharmacol. Aug 2000;52(8):1017-1022.

  9. Lee YJ, Choi DY, Han SB, et al. Inhibitory effect of ethanol extract of Magnolia officinalis on memory impairment and amyloidogenesis in a transgenic mouse model of Alzheimer’s disease via regulating beta-secretase activity. Phytother Res. Dec 2012;26(12):1884-1892.

  10. Chen MC, Lee CF, Huang WH, et al. Magnolol suppresses hypoxia-induced angiogenesis via inhibition of HIF-1alpha/VEGF signaling pathway in human bladder cancer cells. Biochem Pharmacol. May 1 2013;85(9):1278-1287.

  11. Lee SJ, Cho YH, Park K, et al. Magnolol elicits activation of the extracellular signal-regulated kinase pathway by inducing p27KIP1-mediated G2/M-phase cell cycle arrest in human urinary bladder cancer 5637 cells. Biochem Pharmacol. Jun 15 2008;75(12):2289-2300.

  12. Lee SJ, Park SS, Lee US, et al. Signaling pathway for TNF-alpha-induced MMP-9 expression: mediation through p38 MAP kinase, and inhibition by anti-cancer molecule magnolol in human urinary bladder cancer 5637 cells. Int Immunopharmacol. Dec 20 2008;8(13-14):1821-1826.

  13. McKeown BT, Hurta RA. Magnolol affects expression of IGF-1 and associated binding proteins in human prostate cancer cells in vitro. Anticancer Res. Nov 2014;34(11):6333-6338.

  14. McKeown BT, McDougall L, Catalli A, et al. Magnolol causes alterations in the cell cycle in androgen insensitive human prostate cancer cells in vitro by affecting expression of key cell cycle regulatory proteins. Nutr Cancer. 2014;66(7):1154-1164.

  15. Hwang ES, Park KK. Magnolol suppresses metastasis via inhibition of invasion, migration, and matrix metalloproteinase-2/-9 activities in PC-3 human prostate carcinoma cells. Biosci Biotechnol Biochem. 2010;74(5):961-967.

  16. Lee DH, Szczepanski MJ, Lee YJ. Magnolol induces apoptosis via inhibiting the EGFR/PI3K/Akt signaling pathway in human prostate cancer cells. J Cell Biochem. Apr 15 2009;106(6):1113-1122.

  17. Kang YJ, Park HJ, Chung HJ, et al. Wnt/beta-catenin signaling mediates the antitumor activity of magnolol in colorectal cancer cells. Mol Pharmacol. Aug 2012;82(2):168-177.

  18. Park JB, Lee MS, Cha EY, et al. Magnolol-induced apoptosis in HCT-116 colon cancer cells is associated with the AMP-activated protein kinase signaling pathway. Biol Pharm Bull. 2012;35(9):1614-1620.

  19. Liu Y, Cao W, Zhang B, et al. The natural compound magnolol inhibits invasion and exhibits potential in human breast cancer therapy. Sci Rep. 2013;3:3098.

  20. Zhou Y, Bi Y, Yang C, et al. Magnolol induces apoptosis in MCF-7 human breast cancer cells through G2/M phase arrest and caspase-independent pathway. Pharmazie. Sep 2013;68(9):755-762.

  21. Liu Y, Tong Y, Yang X, et al. Novel histone deacetylase inhibitors derived from Magnolia officinalis significantly enhance TRAIL-induced apoptosis in non-small cell lung cancer. Pharmacol Res. Jun 3 2016;111:113-125.

  22. Tsai JR, Chong IW, Chen YH, et al. Magnolol induces apoptosis via caspase-independent pathways in non-small cell lung cancer cells. Arch Pharm Res. Apr 2014;37(4):548-557.

  23. Fried LE, Arbiser JL. Honokiol, a multifunctional antiangiogenic and antitumor agent. Antioxid Redox Signal. May 2009;11(5):1139-1148.

  24. Dikalov S, Losik T, Arbiser JL. Honokiol is a potent scavenger of superoxide and peroxyl radicals. Biochem Pharmacol. Sep 1 2008;76(5):589-596.

  25. Bai X, Cerimele F, Ushio-Fukai M, et al. Honokiol, a small molecular weight natural product, inhibits angiogenesis in vitro and tumor growth in vivo. J Biol Chem. Sep 12 2003;278(37):35501-35507.

  26. Bi L, Yu Z, Wu J, et al. Honokiol Inhibits Constitutive and Inducible STAT3 Signaling via PU.1-Induced SHP1 Expression in Acute Myeloid Leukemia Cells. Tohoku J Exp Med. 2015;237(3):163-172.

  27. Song JM, Anandharaj A, Upadhyaya P, et al. Honokiol suppresses lung tumorigenesis by targeting EGFR and its downstream effectors. Oncotarget. Jul 21 2016.

  28. Lv X, Liu F, Shang Y, et al. Honokiol exhibits enhanced antitumor effects with chloroquine by inducing cell death and inhibiting autophagy in human non-small cell lung cancer cells. Oncol Rep. Sep 2015;34(3):1289-1300.

  29. Zhang Q, Zhao W, Ye C, et al. Honokiol inhibits bladder tumor growth by suppressing EZH2/miR-143 axis. Oncotarget. Nov 10 2015;6(35):37335-37348.

  30. Hahm ER, Singh KB, Singh SV. c-Myc is a novel target of cell cycle arrest by honokiol in prostate cancer cells. Cell Cycle. Jun 24 2016:1-12.

  31. Bonner MY, Karlsson I, Rodolfo M, et al. Honokiol bis-dichloroacetate (Honokiol DCA) demonstrates activity in vemurafenib-resistant melanoma in vivo. Oncotarget. Mar 15 2016;7(11):12857-12868.

  32. Prasad R, Kappes JC, Katiyar SK. Inhibition of NADPH oxidase 1 activity and blocking the binding of cytosolic and membrane-bound proteins by honokiol inhibit migratory potential of melanoma cells. Oncotarget. Feb 16 2016;7(7):7899-7912.

  33. Xie L, Jiang F, Zhang X, et al. Honokiol sensitizes breast cancer cells to TNF-alpha induction of apoptosis by inhibiting Nur77 expression. Br J Pharmacol. Jan 2016;173(2):344-356.

  34. Lin CJ, Chang YA, Lin YL, et al. Preclinical effects of honokiol on treating glioblastoma multiforme via G1 phase arrest and cell apoptosis. Phytomedicine. May 15 2016;23(5):517-527.

  35. Yeh PS, Wang W, Chang YA, et al. Honokiol induces autophagy of neuroblastoma cells through activating the PI3K/Akt/mTOR and endoplasmic reticular stress/ERK1/2 signaling pathways and suppressing cell migration. Cancer Lett. Jan 1 2016;370(1):66-77.

  36. Huang JS, Yao CJ, Chuang SE, et al. Honokiol inhibits sphere formation and xenograft growth of oral cancer side population cells accompanied with JAK/STAT signaling pathway suppression and apoptosis induction. BMC Cancer. 2016;16:245.

  37. Shigemura K, Arbiser JL, Sun SY, et al. Honokiol, a natural plant product, inhibits the bone metastatic growth of human prostate cancer cells. Cancer. Apr 1 2007;109(7):1279-1289.

  38. Mucci M, Carraro C, Mancino P, et al. Soy isoflavones, lactobacilli, Magnolia bark extract, vitamin D3 and calcium. Controlled clinical study in menopause. Minerva Ginecol. Aug 2006;58(4):323-334.

  39. Garrison R, Chambliss WG. Effect of a proprietary Magnolia and Phellodendron extract on weight management: a pilot, double-blind, placebo-controlled clinical trial. Altern Ther Health Med. Jan-Feb 2006;12(1):50-54.

  40. Campus G, Cagetti MG, Cocco F, et al. Effect of a sugar-free chewing gum containing magnolia bark extract on different variables related to caries and gingivitis: a randomized controlled intervention trial. Caries Res. 2011;45(4):393-399.

  41. Jeong HU, Kong TY, Kwon SS, et al. Effect of honokiol on cytochrome P450 and UDP-glucuronosyltransferase enzyme activities in human liver microsomes. Molecules. 2013;18(9):10681-10693.

  42. Han HK, Van Anh LT. Modulation of P-glycoprotein expression by honokiol, magnolol and 4-O-methylhonokiol, the bioactive components of Magnolia officinalis. Anticancer Res. Oct 2012;32(10):4445-4452.

  43. Thulasiraman P, Johnson AB. Regulation of Mucin 1 and multidrug resistance protein 1 by honokiol enhances the efficacy of doxorubicin-mediated growth suppression in mammary carcinoma cells. Int J Oncol. Aug 2016;49(2):479-486.

  44. Ghys K, De Palma A, Vandevenne A, et al. Magnolia officinalis bark extract, a recently identified contact allergen in ’anti-ageing’ cosmetics. Contact Dermatitis. Aug 2015;73(2):130-132.

  45. Raison-Peyron N, Cesaire A, Du-Thanh A, et al. Allergic contact dermatitis caused by Magnolia officinalis bark extract in a facial anti-ageing cream. Contact Dermatitis. Jun 2015;72(6):416-417.

  46. Teng CM, Yu SM, Chen CC, et al. EDRF-release and Ca+(+)-channel blockade by magnolol, an antiplatelet agent isolated from Chinese herb Magnolia officinalis, in rat thoracic aorta. Life Sci. 1990;47(13):1153-1161.

  47. Koetter U, Barrett M, Lacher S, et al. Interactions of Magnolia and Ziziphus extracts with selected central nervous system receptors. J Ethnopharmacol. Jul 30 2009;124(3):421-425.