Honokiol BENEFITS
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Honokiol is a sparingly water-soluble polyphenol, which is isolated from the cones, bark
and leaves of genus Magnolia. Magnolia grandifloris has been used in the traditional
Asian herbal medicine. Recently, honokiol has been found to have antiangiogenic,
anti-inflammatory and antitumor properties in preclinical models without appreciable
toxicity. [1]

Honkiol may benefit people at risk of cancers.

Fried L and Arbiser JL from Emory University, Georgia, explained two actions of honokiol
which may allow honokiol as an anti-cancer agent. Honokiol blocks signaling in tumors
with defective p53 function and activated ras by directly blocking the activation of
phospholipase D by activated ras. It also induces cyclophilin D, thus potentiating the
mitochondrial permeability transition pore, and causing death in cells with wild type p53. [1]

Some test-tube studies have demonstrated its potential benefits on animals or even
human at risk of cancers such as lymph nodes metastasis, melanoma, esophageal
adenocarcinoma, breast, lung, liver, colon, leukemia, cervical, stomach, ovarian, prostate
cancers, [2-11,17] Its anti-cancer activity has been shown to be related with the cell cycle
arrest and induction of apoptosis via modulating signal transduction pathways, such as
VEGFR-3. [3,5] A study has shown that liposomal honokiol also has an anti-tumor effect via
inducing apoptosis and inhibiting angiogenesis and liposomal honokiol intensified the
therapeutic effects of radiotherapy. In a study of mice, a 12 day-treatment of honokiol and
radiation decreased a tumor volume by 78%. [4] Combination of honokiol with the mTOR
inhibitor rapamycin presented synergistic effects on induction of apoptosis of breast
cancer cells. [7]

Honkiol may benefit people suffered from diabetes.

Researchers from National Chung Hsing University, Taiwan, reported that
supplementation of honokiol may benefit people at risk of diabetes. Angiopathy is a major
complication of diabetes. Abnormally high blood glucose is a crucial risk factor for
endothelial cell damage. Nuclear factor-kappaB (NF-kappaB) has been demonstrated as
a mediated signaling in hyperglycemia or oxidative stress-triggered apoptosis of
endothelial cells. In a test tube study, these researchers showed that honkiol prevented
NADPH oxidase-related oxidative stress in human umbilical vein endothelial cells
(HUVECs) under hyperglycemic conditions. [12]

Honkiol may benefit people suffered from depression.

Researchers from Nanjing University reported that mixture of honokiol and magnolol may
have antidepressant activities, based on a study of rodents. [13]

Honkiol can be a muscle-relaxant?

Magnolia officinalis is a commonly used traditional Chinese medicine for treating
gastrointestinal disorders. Researchers from Hong Kong observed that magnolol and
honokiol contents accounted for the anti-spasmodic effects of M. officinalis extracts in
guinea pig isolated ileum. [14]

Magnolia obovata has been used in the treatment of chest tightness and asthma for years.
In a study, the relaxant effects of honokiol on porcine tracheal smooth muscle was
associated with the blockade of Ca 2+ influx through voltage-operated Ca 2+ channels
instead of Ca 2+ release from intracellular Ca 2+ stores. [24]

Honkiol may have anti-inflammatory properties and benefit people suffered from arthritis or
other types of autoimmune diseases.

Researchers from Korea found honokiol has an inhibitory effect on the PI3K/Akt
pathway. [15]

In vivo, honokiol stabilized the severity of symptomatic collagen-induced arthritis in both
CD40-LMP1 transgenic mice and their congenic C57BL/6 counterparts. The nontoxic
anti-inflammatory properties of HNK could be valuable for blocking the autoimmune
response. [18]

Honokiol shows anxiolytic activities.

Honokiol has been shown to be an effective anxiolytic-like agent in mice when
administered for 7 days at 0.2 mg/kg/day prior to evaluation in an elevated plus-maze,
while 20 mg/kg is required for efficacy as a single oral dose. [19]

Honokiol is a potential antioxidant. It may benefit people suffered from various diseases.

Honokiol was reported to be 1000 times more potent than alpha-tocopherol in inhibiting
lipid peroxidation in rat heart mitochondria and liver cells from peroxidative injury. In a study
of rats, honokiol showed a protective effect against arrhythmia during myocardial ischemia,
probably related to an involvement of an increased nitric oxide
synthesis. [20-22]

Reactive oxygen species produced by neutrophils contribute to the pathogenesis of focal
cerebral ischemia/reperfusion injury and signal the inflammatory response. Researchers
have shown that honokiol has a protective effect against focal cerebral ischemia /
reperfusion injury in rats that paralleled a reduction in reactive oxygen species production
by neutrophils. [23]

They further found that honokiol, could exert its focal cerebral ischemia/reperfusion injury
protective effect by modulating enzyme systems related to reactive oxygen species
production or metabolism such as NADPH oxidase, myeloperoxidase, cyclooxygenase,
and GSH peroxidase in neutrophils. [23]

Researchers demonstrated the antimicrobial activities of honokiol against Actinobacillus
actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Micrococcus
luteus and Bacillus subtilis in vitro studies. Some researchers suggested to use honokiol
to treat periodontitis.[27]


Reference:

[1] Fried L, Arbiser JL. Honokiol, A Multifunctional Antiangiogenic and Antitumor Agent. Antioxid Redox
Signal. 2009 Feb 9. [2] Chen G, Izzo J, Demizu Y, Wang F, Guha S, Wu X, Hung MC, Ajani J, Huang P.
Different redox states in malignant and non-malignant esophageal epithelial cells and differential
cytotoxic responses to bile acid and honokiol. Antioxid Redox Signal. 2009 Jan 12. [3] Park EJ, Min HY,
Chung HJ, Hong JY, Kang YJ, Hung TM, Youn UJ, Kim YS, Bae K, Kang SS, Lee SK. Down-regulation
of c-Src/EGFR-mediated signaling activation is involved in the honokiol-induced cell cycle arrest and
apoptosis in MDA-MB-231 human breast cancer cells. Cancer Lett. 2009 Jan 8. [4] Hu J, Chen LJ, Liu L,
Chen X, Chen PL, Yang G, Hou WL, Tang MH, Zhang F, Wang XH, Zhao X, Wei YQ. Liposomal
honokiol, a potent anti-angiogenesis agent, in combination with radiotherapy produces a synergistic
antitumor efficacy without increasing toxicity. Exp Mol Med. 2008 Dec 31;40(6):617-28. [5] Wen J, Fu
AF, Chen LJ, Xie XJ, Yang GL, Chen XC, Wang YS, Li J, Chen P, Tang MH, Shao XM, Lu Y, Zhao X,
Wei YQ. Liposomal honokiol inhibits VEGF-D-induced lymphangiogenesis and metastasis in xenograft
tumor model. Int J Cancer. 2008 Dec 23. [6] Deng J, Qian Y, Geng L, Chen J, Wang X, Xie H, Yan S,
Jiang G, Zhou L, Zheng S. Involvement of p38 mitogen-activated protein kinase pathway in
honokiol-induced apoptosis in a human hepatoma cell line (hepG2). Liver Int. 2008 Dec;28(10):1458-64.
Epub 2008 May 26. [7] Liu H, Zang C, Emde A, Planas-Silva MD, Rosche M, Kühnl A, Schulz CO,
Elstner E, Possinger K, Eucker J. Anti-tumor effect of honokiol alone and in combination with other
anti-cancer agents in breast cancer. Eur J Pharmacol. 2008 Sep 4;591(1-3):43-51. Epub 2008 Jun 12.
[8] Dikalov S, Losik T, Arbiser JL. Honokiol is a potent scavenger of superoxide and peroxyl radicals.
Biochem Pharmacol. 2008 Sep 1;76(5):589-96. Epub 2008 Jul 2. [9] Luo H, Zhong Q, Chen LJ, Qi XR,
Fu AF, Yang HS, Yang F, Lin HG, Wei YQ, Zhao X. Liposomal honokiol, a promising agent for treatment
of cisplatin-resistant human ovarian cancer. J Cancer Res Clin Oncol. 2008 Sep;134(9):937-45. Epub
2008 Mar 19. [10] Jiang QQ, Fan LY, Yang GL, Guo WH, Hou WL, Chen LJ, Wei YQ. Improved
therapeutic effectiveness by combining liposomal honokiol with cisplatin in lung cancer model. BMC
Cancer. 2008 Aug 16;8:242. [11] Yang GL, Hou WL, Fu AF, Zhong ZH, Yin XH, Chen LJ. Effects of
honokiol on proliferation and apoptosis of human cervical carcinoma cell line Hela in vitro Sichuan Da
Xue Xue Bao Yi Xue Ban. 2008 Jul;39(4):558-62. [12] Sheu ML, Chiang CK, Tsai KS, Ho FM, Weng TI,
Wu HY, Liu SH. Inhibition of NADPH oxidase-related oxidative stress-triggered signaling by honokiol
suppresses high glucose-induced human endothelial cell apoptosis. Free Radic Biol Med. 2008 Jun
15;44(12):2043-50. Epub 2008 Apr 3. [13] Xu Q, Yi LT, Pan Y, Wang X, Li YC, Li JM, Wang CP, Kong
LD. Antidepressant-like effects of the mixture of honokiol and magnolol from the barks of Magnolia
officinalis in stressed rodents. Prog Neuropsychopharmacol Biol Psychiatry. 2008 Apr 1;32(3):715-25.
Epub 2007 Nov 28. [14] Chan SS, Zhao M, Lao L, Fong HH, Che CT. Magnolol and honokiol account for
the anti-spasmodic effect of Magnolia officinalis in isolated guinea pig ileum. Planta Med. 2008
Mar;74(4):381-4. [15] Kim BH, Cho JY. Anti-inflammatory effect of honokiol is mediated by PI3K/Akt
pathway suppression. Acta Pharmacol Sin. 2008 Jan;29(1):113-22. [16] Sheu ML, Liu SH, Lan KH.
Honokiol induces calpain-mediated glucose-regulated protein-94 cleavage and apoptosis in human
gastric cancer cells and reduces tumor growth. PLoS ONE. 2007 Oct 31;2(10):e1096. [17] Hahm ER,
Singh SV. Honokiol causes G0-G1 phase cell cycle arrest in human prostate cancer cells in association
with suppression of retinoblastoma protein level/phosphorylation and inhibition of E2F1 transcriptional
activity. Mol Cancer Ther. 2007 Oct;6(10):2686-95. [18] Munroe ME, Arbiser JL, Bishop GA. Honokiol, a
natural plant product, inhibits inflammatory signals and alleviates inflammatory arthritis. J Immunol.
2007 Jul 15;179(2):753-63. [19] Kuribara H, Kishi E, Kimura M, Weintraub ST, Maruyama Y.
Comparative assessment of the anxiolytic-like activities of honokiol and derivatives. Pharmacol Biochem
Behav. 2000 Nov;67(3):597-601. [20] Tsai SK, Huang SS, Hong CY. Myocardial protective effect of
honokiol: an active component in Magnolia officinalis. Planta Med. 1996 Dec;62(6):503-6. [21] Chiu JH,
Ho CT, Wei YH, Lui WY, Hong CY. In vitro and in vivo protective effect of honokiol on rat liver from
peroxidative injury. Life Sci. 1997;61(19):1961-71. [22] Tsai SK, Huang CH, Huang SS, Hung LM, Hong
CY. Antiarrhythmic effect of magnolol and honokiol during acute phase of coronary occlusion in
anesthetized rats: influence of L-NAME and aspirin. Pharmacology. 1999 Nov;59(5):227-33. [23] Liou
KT, Shen YC, Chen CF, Tsao CM, Tsai SK. The anti-inflammatory effect of honokiol on neutrophils:
mechanisms in the inhibition of reactive oxygen species production. Eur J Pharmacol. 2003 Aug
15;475(1-3):19-27. [24] Ko CH, Chen HH, Lin YR, Chan MH. Inhibition of smooth muscle contraction by
magnolol and honokiol in porcine trachea. Planta Med. 2003 Jun;69(6):532-6. [25] Hibasami H, Achiwa
Y, Katsuzaki H, Imai K, Yoshioka K, Nakanishi K, Ishii Y, Hasegawa M, Komiya T. Honokiol induces
apoptosis in human lymphoid leukemia Molt 4B cells. Int J Mol Med. 1998 Dec;2(6):671-3. [26] Chen F,
Wang T, Wu YF, Gu Y, Xu XL, Zheng S, Hu X. Honokiol: a potent chemotherapy candidate for human
colorectal carcinoma. World J Gastroenterol. 2004 Dec 1;10(23):3459-63. [27] Ho KY, Tsai CC, Chen
CP, Huang JS, Lin CC. Antimicrobial activity of honokiol and magnolol isolated from Magnolia
officinalis. Phytother Res. 2001 Mar;15(2):139-41.