The plant genus Magnolia includes over 200 species of flowering plants that grow in Asia and the Americas. Magnolias have been around since the time of dinosaurs — before bees existed! — and are thus pollinated by beetles. In the American South, the trees are treasured for their fragrant blooms. But other aspects of magnolias appear to be even greater treasures.
“Magnolia officinalis and Magnolia obovata bark extracts have been used for thousands of years in Chinese and Japanese traditional medicines and are still widely employed as herbal preparations for their sedative, antioxidant, anti-inflammatory, antibiotic, and antispastic effects,” write A. Sarrica and colleagues in a review article. As the review points out, neolignans, and in particular magnolol and honokiol, are the main substances that explain the beneficial properties of the magnolia bark extract.1
Honokiol and magnolol were reported in 1975 to have a long-lasting muscle-relaxing effect in mice.2 This relaxing effect may be due to the compounds’ interaction with receptors for gamma aminobutyric acid (GABA), a key neurotransmitter.3 A randomized, placebo-controlled trial involving overweight, premenopausal women resulted in a reduction in mild transitory anxiety in those who received an extract of magnolia combined with the herb Phellodendron amurense.4
One of the most-promising areas of research involving honokiol is against cancer. “Investigations have demonstrated that honokiol possesses anticarcinogenic, anti-inflammatory, anti-oxidative, anti-angiogenic as well as inhibitory effect on malignant transformation of papillomas to carcinomas in vitro and in vivo animal models without any appreciable toxicity,” write R. Prasad and S. K. Katiyar in Advances in Experimental Medicine and Biology. The authors mention that honokiol affects multiple signaling pathways and that some of its molecular and cellular targets include nuclear factor-κB, STAT3, epidermal growth factor receptor, cell-survival-signaling pathways, the cell-division cycle, and cyclooxygenase. Additionally, its chemopreventive and therapeutic effects have been tested against chronic diseases, including various cancers.5
An extract of Magnolia officinalis as well as magnolol have shown inhibitory effects against skin carcinogenesis in mice.6 In human fibrosarcoma cells, magnolol and honokiol inhibited tumor invasiveness.7 In mice with colorectal cancer, honokiol inhibited tumor growth and prolonged life.8 In human colorectal carcinoma cells, honokiol inhibited cellular growth by inducing apoptosis (programmed cell death).9 The compound also has been shown to induce apoptosis in gastric cancer cells, in addition to decreasing tumor growth in mice that received transplanted gastric cancer cells.10 In a study that tested honokiol’s effects in B-cell chronic lymphocytic leukemia, honokiol induced apoptosis and enhanced the cytotoxicity of chemotherapy.11 In multiple myeloma cells, honokiol induced apoptosis in addition to enhancing apoptosis induced by the drug bortezomib.12 Honokiol has also induced apoptosis in prostate cancer cells and inhibited the growth of bone metastases in mice.13 Other research involving human breast cancer cells found induction of apoptosis and cell-cycle inhibition associated with exposure to honokiol.14
Honokiol has shown inhibitory effects against angiogenesis, the formation of new blood vessels that facilitate tumor growth.15 In human breast cancer cells, honokiol downregulated P-glycoprotein, whose expression is responsible for acquired cancer multidrug resistance.16 Honokiol and magnolol have also shown cytotoxic activity against human ovarian adenocarcinoma, hepatocellular carcinoma, and cancer of the cervix.17 These and many other studies suggest a potential role for the compounds in cancer prevention and treatment in humans.
In addition to their activity against cancer cells, honokiol and magnolol are active against a variety of undesirable microbes. Although less potent than chlorhexidine, honokiol and magnolol have shown activity against several periodontal microorganisms while demonstrating little toxicity in human gingival cells. The researchers involved in the study suggest that magnolol and honokiol may have a potential use as a safe oral antiseptic for preventing and treating periodontal disease.18 This activity may be responsible for magnolia bark’s ability to block bacteria responsible for oral malodor, which was demonstrated in a human study.19 Another trial that investigated magnolia’s oral effects showed a reduction in gingival inflammation in association with the use of a dentifrice that contained magnolia extract as compared to a control dentifrice.20Honokiol and magnolol also have shown activity against several species of fungi, including Candida albicans (responsible for oral “thrush”) and an antiviral effect against HIV-1 and hepatitis C.21-23
Honokiol and magnolol have antioxidant as well as anti-inflammatory effects.24 A recent study that evaluated the effects of magnolol and honokiol in the intestinal epithelium of mice with diarrhea resulting from E. coli bacteria found that the compounds enhanced intestinal anti-inflammatory capacities, inhibited intestinal epithelium apoptosis, and protected intestinal mucosa.25 In an asthmatic mouse model, honokiol inhibited eosinophil infiltration, decreased airway inflammation, and suppressed inflammatory cytokine production, prompting the authors of the study to recommend its possible use for yet another human disease.26
Honokiol has been identified by researchers as an inhibitor of aromatase, an enzyme that converts testosterone to estradiol.27 Theyalso found that honokiol inhibited 5-alpha-reductase-1, one of two enzymes that converts testosterone to dihydrotestosterone, a hormone that can contribute to male pattern hair loss. By reducing the activity of these enzymes, honokiol could help preserve healthy testosterone levels in men.
Honokiol can also benefit the brain. It can permeate the blood-brain barrier and the blood–cerebrospinal fluid barrier, thus increasing its bioavailability in brain tissue. “Various studies have reported the neuroprotective effects of honokiol in the central nervous system, which are due to its powerful antioxidant activity and its ability to ameliorate excitotoxicity, mainly related to the blockade of glutamate receptors and reduction in neuroinflammation. Other recent studies suggest that honokiol could attenuate neurotoxicity caused by abnormally aggregated amyloid beta in Alzheimer’s disease.28
In a mouse model of Alzheimer’s disease, honokiol given for six weeks decreased the production of amyloid beta (which forms the brain plaques that are characteristic of Alzheimer’s disease), reduced plaque deposition, reduced proinflammatory cytokine production, and improved spatial memory defects, all of which indicates that honokiol could be a promising treatment agent for the disease.29 Other research has found that honokiol promotes a transcription factor known as Nrf2, which suggests that honokiol could be developed as a treatment for oxidative stress–related neurodegenerative disorders.30
The Bottom Line
“Magnolia bark extract is a major constituent of currently marketed dietary supplements and cosmetic products,” note M. Poivre and M. Duez in a recent review. As the authors note, some of the important pharmacological activities that have been reported for this herb and its major compounds include antioxidant, anti-inflammatory, antibiotic, and antispasmodic effects.31
It is anticipated that the promising effects reported in preliminary studies of these ancient and beautiful plants will be the subject of further clinical research that will confirm magnolias’ numerous benefits in humans.
- Sarrica A et al. Planta Med. 2018 Jun 20.
- Watanabe K et al. Jpn J Pharmacol. 1975 Oct;25(5):605-7.
- Ai J et al. Pharmacology. 2001 Jul;63(1):34-41.
- Kalman DS et al. Nutr J. 2008 Apr 21;7:11.
- Adv Exp Med Biol. 2016;928:245-265.
- Konoshima T et al. J Nat Prod. 1991 May-Jun;54(3):816-22.
- Nagase H et al. Planta Med. 2001 Nov;67(8):705-8.
- Chen F et al. World J Gastroenterol. 2004 Dec 1;10(23):3459-63.
- Wang T et al. World J Gastroenterol. 2004 Aug 1;10(15):2205-8.
- Sheu ML et al. PLoS One. 2007 Oct 31;2(10):e1096.
- Battle TE et al. Blood. 2005 Jul 15;106(2):690-7.
- Ishitsuka K et al. Blood. 2005 Sep 1;106(5):1794-800.
- Shigemura K et al. Cancer. 2007 Apr 1;109(7):1279-89.
- Wolf I et al. Int J Oncol. 2007 Jun;30(6):1529-37.
- Bai X et al. J Biol Chem. 2003 Sep 12;278(37):35501-7.
- Xu D et al. Cancer Lett. 2006 Nov 18;243(2):274-80.
- Syu WJ et al. Chem Biodivers. 2004 Mar;1(3):530-7.
- Chang B et al. Planta Med. 1998 May;64(4):367-9.
- Greenberg M et al. J Agric Food Chem. 2007 Nov 14;55(23):9465-9.
- Hellström MK et al. Int J Dent Hyg. 2014 May;12(2):96-102.
- Amblard F et al. J Med Chem. 2006 Jun 1;49(11):3426-7.
- Bang KH et al. Arch Pharm Res. 2000 Feb;23(1):46-9.
- Lan KH et al. Liver Int. 2012 Jul;32(6):989-97.
- Lee J et al. Planta Med. 2005 Apr;71(4):338-43.
- Deng Y et al. Med Sci Monit. 2018 May 21;24:3348-3356.
- Hong T et al. Pak J Pharm Sci. 2018 Jul;31(4):1279-1284.
- Bernard P et al. Clin Interv Aging. 2012;7:351-61.
- Talarek S et al. Biofactors. 2017 Nov;43(6):760-769.
- Wang D et al. J Pharmacol Exp Ther. 2018 Jul 10.
- Hou Y et al. ACS Chem Neurosci. 2018 Jul 19.
- Poivre M et al. J Zhejiang Univ Sci B. 2017 Mar.;18(3):194-214.