Magnolia

Chinese Name: Yu-lan hua
Medical Name:
Latin Name: Magnoliae Officinalis
Origin:
Property: Warm
Taste: Pungent, sweet

Quotes from Chinese historical sources

THE BOOK OF TEA, MING DYNASTY, 1592AD: "The flowers of osmanthus, jasmine, rose, rose multiflora, orchid, lotus, tangerine, gardenia and wintersweet can all be used in tea. Pick the blossoms when they are just opening, so that the stamens retain all their aroma. Mix them with tea leaves, one part flowers to three of tea.

Western Research

Curr Med Chem. 2008;15(16):1616-27
Chemistry and bioactivity of Flos Magnoliae, a Chinese herb for rhinitis and sinusitis.
Shen Y, Li CG, Zhou SF, Pang EC, Story DF, Xue CC.
The RMIT Chinese Medicine Research Group, School of Health Sciences, RMIT University, Victoria, Australia.
Flos Magnoliae (FM, Chinese name: Xin-yi) is one of the most commonly used Chinese medicinal herbs. It has a long history of clinical use for managing rhinitis, sinusitis and headache. More than 20 different FM species have been used clinically, which makes species identification and evaluation of pharmacological effects of individual chemical ingredients difficult. In this review, we have summarized the current knowledge on FM phytochemistry and its bioactivity activities. The bioactive compounds in FM include both lipid and water-soluble components. More than 90% of the essential components of FM species are terpenoids, including monoterpenes and sesquiterpenes. Lignans and neolignans including tetrahydrofurofuran, tetrahydrofuran and aryltetralin are also present in FM species. A small number of water-soluble compounds have been isolated from Magnolia flower buds, including a benzylisoquinoline alkaloid magnoflorine, an ester ethyl-E-p-hydroxyl-cinnamate and a flavonoid biondnoid. A wide range of pharmacological actions of FM have been reported, including anti-allergy, anti-inflammation and anti-microbial activity. The structure-activity relationship analysis revealed the influence of methylation at position 5 on the 3,7-dioxabicyclo-(3,3,0)-octane backbone of six lignans in antagonistic activities against platelet-activating factor. In addition, the trans stereoisomer fargesin had a much lower bioactivity than the cis stereoisomer demethoxyaschantin. Recent studies have been directed towards the isolation of other bioactive compounds. Further studies on FM may help to develop new anti-inflammatory and anti-allergic drugs.

Int Arch Allergy Immunol. 2003 Jun;131(2):101-10
Magnoliae flos induces apoptosis of RBL-2H3 cells via mitochondria and caspase.
Kim GC, Lee SG, Park BS, Kim JY, Song YS, Kim JM, Yoo KS, Huh GY, Jeong MH, Lim YJ, Kim HM, Yoo YH.
Department of Oral Anatomy and Cell Biology, Busan National University College of Dentistry, Busan, South Korea.
BACKGROUND: Magnoliae flores (MF), the buds of Magnolia denudata Desrousseaux, have been successfully used for the management of allergic diseases in Korea. The purpose of the present study was to determine their causal role in inducing apoptosis of mast cells and to verify the underlying mechanism. METHODS: The viability of mast cells was assessed by the trypan blue exclusion test. Induction of apoptosis was confirmed by DNA fragmentation, nuclear staining and DNA hypoploidy. Western blotting and immunofluorescent staining were performed to study the alterations in expression level and translocation of apoptosis-related proteins. Mitochondrial membrane potential (MMP) change and cytochrome C release were assayed. RESULTS: We present several lines of evidence indicating that MF induce apoptosis. Changes in cell morphology, generation of DNA fragmentation, cell cycle arrest, activation of caspase-3, and PARP and DFF degradations were demonstrated. The reduction of MMP and the release of cytochrome C to cytosol were also shown. Either PTP blockers, bongkrekic acid and cyclosporin A, or pancaspase inhibitors, Boc.D-fmk and zVAD-fmk, did not prevent the release of cytochrome C. Bax protein content was increased, and Bax was translocated from cytosol into mitochondria at early time points after MF treatment. CONCLUSIONS: We have demonstrated that MF induce mitochondria- and caspase-dependent mast cell apoptosis. Our observations contribute new insights to the role of MF and support the view that the clinical effect of MF may depend on their pharmacological efficacy in regulating mast cell apoptosis. Copyright 2003 S. Karger AG, Basel

Planta Med. 1985 Aug;51(4):291-3
Anti-Inflammatory Effect of Neolignans Newly Isolated from the Crude Drug "Shin-i" (Flos Magnoliae).
Kimura M, Suzuki J, Yamada T, Yoshizaki M, Kikuchi T, Kadota S, Matsuda S.
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, Japan.
The anti-inflammatory effects of the major components of the dried flower buds of MAGNOLIA SALICIFOLIA were determined using the pouch granuloma method in mice. Though alkaloids, fatty acids, essential oils, and lignans had no anti-inflammatory effects, neolignans (magnoshinin and magnosalin) significantly inhibited the granuloma tissue formation. The inhibitory effect of magnoshinin was particularly strong, being nearly half of that of hydrocortisone acetate when administered orally. Some differences were noted in the mode of action between the neolignans and the steroidal drugs as the neolignans selectively inhibited the granuloma tissue formation but did not affect the exudation of pouch fluid. The structural specificity of neolignans was also found on their anti-inflammatory effect.

Chem Biol Interact. 2006 May 15;161(1):1-13.
Protective effects of honokiol against oxidized LDL-induced cytotoxicity and adhesion molecule expression in endothelial cells.
Ou HC, Chou FP, Lin TM, Yang CH, Sheu WH.
Division of Endocrinology and Metabolism, Department of Education and Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan; Institute of Biochemistry, Chung Shan Medical University, Taichung, Taiwan.
Honokiol, a compound extracted from Chinese medicinal herb Magnolia officinalis, has several biological effects. However, its protective effects against endothelial injury remain unclarified. In this study, we examined whether honokiol prevented oxidized low-density lipoprotein (oxLDL)-induced vascular endothelial dysfunction. Incubation of oxLDL with honokiol (2.5-20muM) inhibited copper-induced oxidative modification as demonstrated by diene formation, thiobarbituric acid reactive substances (TBARS) assay and electrophoretic mobility assay. Expression of adhesion molecules (ICAM, VCAM and E-selectin) and endothelial NO synthase (eNOS) affected by oxLDL was investigated by flow cytometry and Western blot. We also measured the production of reactive oxygen species (ROS) using the fluorescent probe 2',7'- dichlorofluorescein acetoxymethyl ester (DCF-AM). Furthermore, several apoptotic phenomena including increased cytosolic calcium, alteration of mitochondrial membrane potential, cytochrome c release and activation of caspase-3 were also investigated. Apoptotic cell death was characterized by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) stain. The results showed that honokiol prevented the copper- induced oxidative modification of LDL. Honokiol also ameliorated the oxLDL-diminished eNOS protein expression and reduced the oxLDL-induced adhesion molecules and the adherence of THP-1 cells to HUVECs. Furthermore, honokiol attenuated the oxLDL-induced cytotoxicity, apoptotic features, ROS generation, intracellular calcium accumulation and the subsequent mitochondrial membrane potential collapse, cytochrome c release and activation of caspase-3. Our results suggest that honokiol may have clinical implications in the prevention of atherosclerotic vascular disease.

Br J Pharmacol. 2006 Mar 6;
Herbal remedy magnolol suppresses IL-6-induced STAT3 activation and gene expression in endothelial cells.
Chen SC, Chang YL, Wang DL, Cheng JJ.
Institute of Clinical Medicine, National Yang-Ming University and Division of Cardiovascular Medicine, Taipei Medical University-Wan-Fang Hospital, Taipei, Taiwan.
Magnolol (Mag), an active constituent isolated from the Chinese herb Hou p'u (Magnolia officinalis) has long been used to suppress inflammatory processes. Chronic inflammation is well known to be involved in vascular injuries such as atherosclerosis in which interleukin (IL)-6 may participate. Signal transducer and activator of transcription protein 3 (STAT3), a transcription factor involved in inflammation and the cell cycle, is activated by IL-6. In this study, we evaluated whether Mag can serve as an anti-inflammatory agent during endothelial injuries. The effects of Mag on IL-6-induced STAT3 activation and downstream target gene induction in endothelial cells (ECs) were examined. Pretreatment of ECs with Mag dose dependently inhibited IL-6-induced Tyr705 and Ser727 phosphorylation in STAT3 without affecting the phosphorylation of JAK1, JAK2, and ERK1/2. Mag pretreatment of these ECs dose dependently suppressed IL-6-induced promoter activity of intracellular cell adhesion molecule (ICAM)-1 that contains functional IL-6 response elements (IREs). An electrophoretic mobility shift assay (EMSA) revealed that Mag treatment significantly reduced STAT3 binding to the IRE region. Consistently, Mag treatment markedly inhibited ICAM-1 expression on the endothelial surface. As a result, reduced monocyte adhesion to IL-6-activated ECs was observed. Furthermore, Mag suppressed IL-6-induced promoter activity of cyclin D1 and monocyte chemotactic protein (MCP)-1 for which STAT3 activation plays a role. In conclusion, our results indicate that Mag inhibits IL-6-induced STAT3 activation and subsequently results in the suppression of downstream target gene expression in ECs. These results provide a therapeutic basis for the development of Mag as an anti- inflammatory agent for vascular disorders including atherosclerosis.British Journal of Pharmacology advance online publication, 6 March 2006; doi:10.1038/sj.bjp.0706647.

Blood. 2005 Sep 1;106(5):1794-800.
Honokiol overcomes conventional drug resistance in human multiple myeloma by induction of caspase-dependent and -independent apoptosis.
Ishitsuka K, Hideshima T, Hamasaki M, Raje N, Kumar S, Hideshima H, Shiraishi N, Yasui H, Roccaro AM, Richardson P, Podar K, Le Gouill S, Chauhan D, Tamura K, Arbiser J, Anderson KC.
Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA.
Honokiol (HNK) is an active component purified from magnolia, a plant used in traditional Chinese and Japanese medicine. Here we show that HNK significantly induces cytotoxicity in human multiple myeloma (MM) cell lines and tumor cells from patients with relapsed refractory MM. Neither coculture with bone marrow stromal cells nor cytokines (interleukin-6 and insulin-like growth factor-1) protect against HNK- induced cytotoxicity. Although activation of caspases 3, 7, 8, and 9 is triggered by HNK, the pan-caspase inhibitor z-VAD-fmk does not abrogate HNK-induced apoptosis. Importantly, release of an executioner of caspase-independent apoptosis, apoptosis-inducing factor (AIF), from mitochondria is induced by HNK treatment. HNK induces apoptosis in the SU-DHL4 cell line, which has low levels of caspase 3 and 8 associated with resistance to both conventional and novel drugs. These results suggest that HNK induces apoptosis via both caspase-dependent and - independent pathways. Furthermore, HNK enhances MM cell cytotoxicity and apoptosis induced by bortezomib. In addition to its direct cytotoxicity to MM cells, HNK also represses tube formation by endothelial cells, suggesting that HNK inhibits neovascurization in the bone marrow microenvironment. Taken together, our results provide the preclinical rationale for clinical protocols of HNK to improve patient outcome in MM.

Blood. 2005 Jul 15;106(2):690-7
The natural product honokiol induces caspase-dependent apoptosis in B-cell chronic lymphocytic leukemia (B-CLL) cells.
Battle TE, Arbiser J, Frank DA.
Department of Medical Oncology, Mayer 522B, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA.
B-cell chronic lymphocytic leukemia (B-CLL) remains an incurable disease that requires innovative new approaches to improve therapeutic outcome. Honokiol is a natural product known to possess potent antineoplastic and antiangiogenic properties. We examined whether honokiol can overcome apoptotic resistance in primary tumor cells derived from B-CLL patients. Honokiol induced caspase-dependent cell death in all of the B-CLL cells examined and was more toxic toward B-CLL cells than to normal mononuclear cells, suggesting greater susceptibility of the malignant cells. Honokiol-induced apoptosis was characterized by the activation of caspase-3, -8, and -9 and cleavage of poly(adenosine diphosphate-ribose) polymerase (PARP). Exposure of B-CLL cells to honokiol resulted in up-regulation of Bcl2-associated protein (Bax) and down-regulation of the expression of the key survival protein myeloid-cell leukemia sequence 1 (Mcl-1), which is associated with response to treatment in B-CLL patients. In addition, B-CLL cells pretreated with interleukin-4 (IL-4), a cytokine known to support B-CLL survival, underwent apoptosis when subsequently incubated with honokiol, indicating that honokiol could also overcome the prosurvival effects of IL-4. Furthermore, honokiol enhanced cytotoxicity induced by fludarabine, cladribine, or chlorambucil. These data indicate that honokiol is a potent inducer of apoptosis in B-CLL cells and should be examined for further clinical application either as a single agent or in combination with other anticancer agents.

Anticancer Drugs. 2003 Mar;14(3):211-7.
Magnolol induces apoptosis in human leukemia cells via cytochrome c release and caspase activation.
Zhong WB, Wang CY, Ho KJ, Lu FJ, Chang TC, Lee WS.
Graduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Magnolol, isolated from the stem bark of Magnolia officnalis, was found to inhibit proliferation of human HL-60 cells and Jurkat T leukemia cells via inducing apoptosis in a dose- and time-dependent manner. By contrast, magnolol did not cause apoptosis in neutrophils and peripheral blood mononuclear cells of healthy donors. Apoptosis was determined by detection of DNA fragmentation in gel electrophoresis, morphological alternations by flow cytometry, quantification of phosphatidylserine externalization by Annexin V labeling and oligonucleosomal DNA content by TUNEL labeling. Activation of caspase-9, -3 and -2, and the proteolytic cleavage of poly(ADP-ribose) polymerase were found during apoptosis induced by magnolol. In addition, both pan- caspase and selective caspase-9 inhibitor blocked magnolol-induced apoptosis. The apoptosis could also be partially attenuated by caspase-3 and -2 inhibitors. Magnolol induced the reduction of mitochondrial transmembrane potential and the release of cytochrome c into cytoplasm. In conclusion, our findings indicate that magnolol-induced apoptotic signaling is carried out through mitochondria alternations to caspase-9 and that then the downstream effector caspases are activated sequentially. Magnolol could be a potentially effective drug for leukemia with low toxicity to normal blood cells and it merits further investigation. Copyright 2003 Lippincott Williams & Wilkins.