Honokiol

Monday, 25/06/2012  |   Herb or Compound  |  no comments


The bioactive constituents isolated from the bark of Magnolia officinalis such as magnolol, honokiol and obovatol have anti-inflammatory properties through the inactivation of NF-kappaB which is an important factor in the regulation of inflammatory reaction. (1) Lymph nodes metastasis of tumor could be a crucial early step in the metastatic process. Induction of tumor lymphangiogenesis by vascular endothelial growth factor-D may play an important role in promoting tumor metastasis to regional lymph nodes and these processes can be inhibited by inactivation of the VEGFR-3 signaling pathway. Honokiol has been reported to possess potent antiangiogenesis and antitumor properties. liposomal honokiol significantly inhibited the tumor-associated lymphangiogenesis and metastasis in Lewis lung carcinoma model. A remarkable delay of tumor growth and prolonged life span were also observed. In in vitro study, honokiol inhibited VEGF-D-induced survival, proliferation and tube-formation of both human umbilical vein endothelial cells (HUVECs) and lymphatic vascular endothelial cells (HLECs). (2)

DNA mismatch repair is required for correcting any mismatches that are created during replication and recombination, and a defective mismatch repair system contributes to DNA damage-induced growth arrest. The colorectal cancer cell line HCT116 is known to have a mutation in the hMLH1 mismatch repair gene resulting in microsatellite instability and defective mismatch repair. Honokiol is a biphenolic compound that has been used in traditional Chinese medicine for treating various ailments including cancer. Cell cycle analyses revealed higher levels of dead cells in HCT116 cells. The combination treatment reduced expression of cyclin A1 and D1 and increased phosphorylated p53 in both cell lines, although there were significantly lower amounts of phosphorylated p53 in the HCT116-CH3 cells, suggesting that high levels of hMLH1 reduce radiosensitivity. These data demonstrate that honokiol is highly effective in radiosensitizing colorectal cancer cells, especially those with a mismatch repair defect. (3)

Much recent research has demonstrated that honokiol, a phenolic compound originally isolated from Magnolia officinalis, has potent anticancer activities; however, the detailed molecular mechanism of its anti-inflammatory activity has not yet been fully addressed. Honokiol inhibited lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha secretion in macrophages, without affecting the activity of the tumor necrosis factor-alpha converting enzyme. At the same time, honokiol not only inhibited nitric oxide expression in LPS-stimulated murine macrophages but also inhibited the LPS-induced phosphorylation of ERK1/2, JNK1/2, and p38. Honokiol inhibited lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha secretion in macrophages, without affecting the activity of the tumor necrosis factor-alpha converting enzyme. At the same time, honokiol not only inhibited nitric oxide expression in LPS-stimulated murine macrophages but also inhibited the LPS-induced phosphorylation of ERK1/2, JNK1/2, and p38. (4)

This herb was first described in the Shennong Bencao Jing (5) around 100 A.D., as follows:
houpu is bitter and warm, non-toxic, mainly treating wind-stroke, cold damage, headache, cold and heat, fright qi, blood impediment, and dead muscle. It removes the three kinds of worms. It grows in mountains and valleys.
This description differs markedly from that relied on in subsequent Chinese texts, in which the herb is mainly used for stagnation of qi and moisture circulation in the abdomen (associated with digestive disturbance) and tightness in the chest (associated with impaired breathing). However, the treatment of “fright qi” is one of the persisting indications for magnolia bark in the traditional prescriptions: it treats syndromes that are caused by emotional distress, such as plum pit qi, digestive disturbance associated with fear and anxiety, and shortness of breath due to emotional turmoil. Although magnolia bark is no longer used in the treatment of worms, its antibacterial properties are recognized and may be responsible for its ability to alleviate discomfort due to some intestinal bacterial infections. It may be prepared with ginger juice to enhance its digestive promoting effects. (6)
References:
1). Oh JH, Kang LL, Ban JO, Kim YH, Kim KH, Han SB, Hong JT. Anti-inflammatory effect of 4-O-methylhonokiol, a novel compound isolated from Magnolia officinalis through inhibition of NF-kappaB. Chem Biol Interact. 2009 Aug 14;180(3):506-14. Epub 2009 Mar 27.
2). 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. 2009 Jun 1;124(11):2709-18.
3). He Z, Subramaniam D, Ramalingam S, Dhar A, Postier RG, Umar S, Zhang Y, Anant S. Honokiol radiosensitizes colorectal cancer cells: enhanced activity in cells with mismatch repair defects. Am J Physiol Gastrointest Liver Physiol. 2011 Nov;301(5):G929-37. Epub 2011 Aug 11.
4). Hasegawa S, Yonezawa T, Ahn JY, Cha BY, Teruya T, Takami M, Yagasaki K, Nagai K, Woo JTHonokiol inhibits osteoclast differentiation and function in vitro. Biol Pharm Bull. 2010;33(3):487-92.
5) Yang Shou-zhong (translator), The Divine Farmer’s Materia Medica, 1998 Blue Poppy Press, Boulder, CO.
6). Subhuti Dharmananda. 2001 http://www.itmonline.org/arts/magnolia.htm

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