Magnolia bark extract
Information on nutritional supplements people with ALS have been taking
Contents
Effects on ALS
Magnolia is a PPAR-gamma activator [Wikipedia] and GABA-alpha receptor agonist [2].
Honokiol and magnolol potently enhance the potentiating effect of 200 nM GABA on [3H]FNM binding with EC50 values of 0.61 microM and 1.6 microM using rat forebrain membranes, with maximal enhancements of 33 and 47%, respectively. [2]
Studies using human U937 promonocytes cells suggested that magnolol, a low molecular weight lignan isolated from Magnolia officinalis, differentially down-regulated the pharmacologically induced expression of NF-kappaB-regulated inflammatory gene products MMP-9, IL-8, MCP-1, MIP-1alpha, TNF-alpha. [1]
Honokiol significantly enhances ERK1/2 phosphorylation in a concentration-dependent manner [3] and downregulates Klf4 expression in rat spinal cord injury [4].
Discussion threads on the ALSTDI forum
Regulated pathways
Downregulates MMP-9, IL-8, MCP-1, MIP-1alpha, TNF-alpha.
Potentiates GABA.
References
[1] <bibtex> @article{Tse2007, abstract = {The mis-regulation of nuclear factor-kappa B (NF-kappaB) signal pathway is involved in a variety of inflammatory diseases that leds to the production of inflammatory mediators. Our studies using human U937 promonocytes cells suggested that magnolol, a low molecular weight lignan isolated from the medicinal plant Magnolia officinalis, differentially down-regulated the pharmacologically induced expression of NF-kappaB-regulated inflammatory gene products MMP-9, IL-8, MCP-1, MIP-1alpha, TNF-alpha. Pre-treatment of magnolol blocked TNF-alpha-induced NF-kappaB activation in different cell types as evidenced by EMSA. Magnolol did not directly affect the binding of p65/p50 heterodimer to DNA. Immunoblot analysis demonstrated that magnolol inhibited the TNF-alpha-stimulated phosphorylation and degradation of the cytosolic NF-kappaB inhibitor IkappaBalpha and the effects were dose-dependent. Mechanistically, a non-radioactive IkappaB kinases (IKK) assay using immunoprecipitated IKKs protein demonstrated that magnolol inhibited both intrinsic and TNF-alpha-stimulated IKK activity, thus suggesting a critical role of magnolol in abrogating the phosphorylation and degradation of IkappaBalpha. The involvement of IKK was further verified in a HeLa cell NF-kappaB-dependent luciferase reporter system. In this system magnolol suppressed luciferase expression stimulated by TNF-alpha and by the transient transfection and expression of NIK (NF-kappaB-inducing kinase), wild type IKKbeta, constitutively active IKKalpha and IKKbeta, or the p65 subunit. Magnolol was also found to inhibit the nuclear translocation and phosphorylation of p65 subunit of NF-kappaB. In line with the observation that NF-kappaB activation may up-regulate anti-apoptotic genes, it was shown in U937 cells that magnolol enhanced TNF-alpha-induced apoptotic cell death. Our results suggest that magnolol or its derivatives may have potential anti-inflammatory actions through IKK inactivation.}, author = {Tse, Anfernee Kai-Wing and Wan, Chi-Keung and Zhu, Guo-Yuan and Shen, Xiao-Ling and Cheung, Hon-Yeung and Yang, Mengsu and Fong, Wang-Fun}, doi = {10.1016/j.molimm.2006.12.004}, issn = {0161-5890}, journal = {Molecular immunology}, keywords = {Anti-Inflammatory Agents, Non-Steroidal,Anti-Inflammatory Agents, Non-Steroidal: pharmacol,Apoptosis,Apoptosis: drug effects,Biphenyl Compounds,Biphenyl Compounds: pharmacology,Cell Line, Tumor,Cytokines,Cytokines: genetics,Dimerization,Down-Regulation,Gene Expression Regulation,Gene Expression Regulation: drug effects,Humans,I-kappa B Kinase,I-kappa B Kinase: antagonists \& inhibitors,I-kappa B Kinase: metabolism,Lignans,Lignans: pharmacology,Lipopolysaccharides,Lipopolysaccharides: pharmacology,Matrix Metalloproteinase 9,Matrix Metalloproteinase 9: genetics,NF-kappa B,NF-kappa B p50 Subunit,NF-kappa B p50 Subunit: antagonists \& inhibitors,NF-kappa B p50 Subunit: metabolism,NF-kappa B: drug effects,NF-kappa B: metabolism,Phosphorylation,Phosphorylation: drug effects,Transcription Factor RelA,Transcription Factor RelA: antagonists \& inhibitor,Transcription Factor RelA: metabolism,Tumor Necrosis Factor-alpha,Tumor Necrosis Factor-alpha: genetics,Tumor Necrosis Factor-alpha: pharmacology}, mendeley-groups = {magnolia}, month = apr, number = {10}, pages = {2647--58}, pmid = {17240450}, title = Template:Magnolol suppresses NF-kappaB activation and NF-kappaB regulated gene expression through inhibition of IkappaB kinase activation., url = {http://www.ncbi.nlm.nih.gov/pubmed/17240450}, volume = {44}, year = {2007} } </bibtex>
[2] <bibtex> @article{Squires1999, abstract = {1. The bark of the root and stem of various Magnolia species has been used in Traditional Chinese Medicine to treat a variety of disorders including anxiety and nervous disturbances. The biphenolic compounds honokiol (H) and magnolol (M), the main components of the Chinese medicinal plant Magnolia officinalis, interact with GABA(A) receptors in rat brain in vitro. We compared the effects of H and M on [3H]muscimol (MUS) and [3H]flunitrazepam (FNM) binding using EDTA/water dialyzed rat brain membranes in a buffer containing 150 mM NaCl plus 5 mM Tris-HCl, pH 7.5 as well as [35S]t-butylbicyclophosphorothionate (TBPS) in 200 mM KBr plus 5 mM Tris-HCl, pH 7.5. H and M had similar enhancing effects on [3H]MUS as well as on [3H]FNM binding to rat brain membrane preparations, but H was 2.5 to 5.2 times more potent than M. 2. [3H]FNM binding. GABA alone almost doubled [3H]FNM binding with EC50 = 450 nM and 200 nM using forebrain and cerebellar membranes, respectively. In the presence of 5 microM H or M the EC50 values for GABA were decreased to 79 and 89 nM, respectively, using forebrain, and 39 and 78 nM, using cerebellar membranes. H and M potently enhanced the potentiating effect of 200 nM GABA on [3H]FNM binding with EC50 values of 0.61 microM and 1.6 microM using forebrain membranes, with maximal enhancements of 33 and 47\%, respectively. Using cerebellar membranes, the corresponding values were 0.25 and 1.1 microM, and 22 and 34\%. 3. [3H]MUS binding. H and M increased [3H]MUS binding to whole forebrain membranes about 3-fold with EC50 values of 6.0 and 15 microM. Using cerebellar membranes, H and M increased [3H]MUS binding approximately 68\% with EC50 values of 2.3 and 12 microM, respectively. Scatchard analysis revealed that the enhancements of [3H]MUS binding were due primarily to increases in the number of binding sites (Bmax values) with no effect on the high affinity binding constants (Kd values). The enhancing effect of H and M were not additive. 4. [35S]TBPS binding. H and M displaced [35S]TBPS binding from sites on whole rat forebrain membranes with IC50 values of 7.8 and 6.0 microM, respectively. Using cerebellar membranes, the corresponding IC50 values were 5.3 and 4.8 microM. These inhibitory effects were reversed by the potent GABA(A) receptor blocker R5135 (10 nM), suggesting that H and M allosterically increase the affinity of GABA(A) receptors for GABA and MUS by binding to sites in GABA(A) receptor complexes. 5. Two monophenols, the anesthetic propofol (2,6-diisopropylphenol, P) and the anti-inflammatory diflunisal (2',4'-difluoro-4-hydroxy-3-biphenyl carboxylic acid, D) also enhanced [3H]MUS binding, decreased the EC50 values for GABA in enhancing [3H]FNM binding and potentiated the enhancing effect of 200 nM GABA on [3H]FNM binding, although enhancements of [3H]MUS binding for these monophenols were smaller than those for H and M, using forebrain and cerebellar membranes. The enhancing effect of P and D on [3H]MUS binding were almost completely additive. 2,2'-biphenol was inactive on [3H]MUS and [3H]FNM binding. These, and other preliminary experiments, suggest that appropriate ortho (C2) and para (C4) substitution increases the GABA-potentiating activity of phenols. 6. The potentiation of GABAergic neurotransmission by H and M is probably involved in their previously reported anxiolytic and central depressant effects.}, author = {Squires, R F and Ai, J and Witt, M R and Kahnberg, P and Saederup, E and Sterner, O and Nielsen, M}, issn = {0364-3190}, journal = {Neurochemical research}, keywords = {Allosteric Regulation,Androstanes,Androstanes: pharmacology,Animals,Azasteroids,Azasteroids: pharmacology,Binding Sites,Biphenyl Compounds,Biphenyl Compounds: pharmacology,Cell Membrane,Cell Membrane: drug effects,Cell Membrane: metabolism,Central Nervous System Depressants,Central Nervous System Depressants: pharmacology,Cerebellum,Cerebellum: metabolism,Diflunisal,Diflunisal: pharmacology,Drugs, Chinese Herbal,Drugs, Chinese Herbal: pharmacology,Flunitrazepam,Flunitrazepam: pharmacokinetics,GABA Antagonists,GABA Antagonists: pharmacology,Kinetics,Lignans,Muscimol,Muscimol: pharmacokinetics,Picrotoxin,Picrotoxin: pharmacokinetics,Propofol,Propofol: pharmacology,Prosencephalon,Prosencephalon: metabolism,Rats,Receptors, GABA-A,Receptors, GABA-A: drug effects,Receptors, GABA-A: metabolism,Tritium,gamma-Aminobutyric Acid,gamma-Aminobutyric Acid: pharmacology}, mendeley-groups = {magnolia}, month = dec, number = {12}, pages = {1593--602}, pmid = {10591411}, title = {{Honokiol and magnolol increase the number of [3H] muscimol binding sites three-fold in rat forebrain membranes in vitro using a filtration assay, by allosterically increasing the affinities of low-affinity sites.}}, url = {http://www.ncbi.nlm.nih.gov/pubmed/10591411}, volume = {24}, year = {1999} } </bibtex>
[3] <bibtex> @article{Zhai2005, abstract = {We have found that honokiol [4-allyl-2-(3-allyl-4-hydroxy-phenyl)-phenol] can promote neurite outgrowth and mobilize intracellular Ca2+ store in primary cultured rat cortical neurons. In this study, we examined the effects of honokiol on extracellular signal-regulated kinases (ERK1/2) and Akt, and their possible relationship to neurite outgrowth and Ca2+ mobilization. Honokiol-induced neurite outgrowth in the cultured rat cortical neurons was significantly reduced by PD98059, a mitogen-activated protein kinase kinase (MAPKK, MAPK/ERK kinase MEK, direct upstream of ERK1/2) inhibitor, but not by LY294002, a phosphoinositide 3-kinase (PI3K, upstream of Akt) inhibitor. Honokiol also significantly enhanced the phosphorylation of ERK1/2 in a concentration-dependent manner, whereas the effect of honokiol on Akt phosphorylation was characterized by transient enhancement in 10 min and lasting inhibition after 30 min. The phosphorylation of ERK1/2 enhanced by honokiol was inhibited by PD98059 as well as by KN93, a Ca2+/calmodulin-dependent kinase II (CaMK II) inhibitor. Moreover, the products of the phosphoinositide specific phospholipase C (PLC)-derived inositol 1,4,5-triphosphate (IP3) and 1,2-diacylglycerol (DAG) were measured after honokiol treatment. Together with our previous findings, these results suggest that the signal transduction from PLC, IP3, Ca2+, and CaMK II to ERK1/2 is involved in honokiol-induced neurite outgrowth.}, author = {Zhai, Haifeng and Nakade, Kousuke and Oda, Masataka and Mitsumoto, Yasuhide and Akagi, Masaaki and Sakurai, Jun and Fukuyama, Yoshiyasu}, doi = {10.1016/j.ejphar.2005.04.035}, issn = {00142999}, journal = {European Journal of Pharmacology}, keywords = {Animals,Benzylamines,Benzylamines: pharmacology,Biphenyl Compounds,Biphenyl Compounds: pharmacology,Blotting, Western,Calcium-Calmodulin-Dependent Protein Kinases,Calcium-Calmodulin-Dependent Protein Kinases: anta,Calcium-Calmodulin-Dependent Protein Kinases: meta,Cells, Cultured,Cerebral Cortex,Chromones,Chromones: pharmacology,Diglycerides,Diglycerides: biosynthesis,Dose-Response Relationship, Drug,Drugs, Chinese Herbal,Drugs, Chinese Herbal: pharmacology,Enzyme Activation,Enzyme Activation: drug effects,Female,Fetus,Flavonoids,Flavonoids: pharmacology,Inositol 1,4,5-Trisphosphate,Inositol 1,4,5-Trisphosphate: biosynthesis,Lignans,Lignans: pharmacology,Mitogen-Activated Protein Kinase 1,Mitogen-Activated Protein Kinase 1: antagonists \& ,Mitogen-Activated Protein Kinase 1: metabolism,Mitogen-Activated Protein Kinase 3,Mitogen-Activated Protein Kinase 3: antagonists \& ,Mitogen-Activated Protein Kinase 3: metabolism,Models, Biological,Morpholines,Morpholines: pharmacology,Neurites,Neurites: drug effects,Neurites: physiology,Neurons,Neurons: cytology,Neurons: drug effects,Neurons: metabolism,Phosphatidylinositol 3-Kinases,Phosphatidylinositol 3-Kinases: antagonists \& inhi,Phosphorylation,Phosphorylation: drug effects,Pregnancy,Protein Kinase Inhibitors,Protein Kinase Inhibitors: pharmacology,Rats,Rats, Sprague-Dawley,Sulfonamides,Sulfonamides: pharmacology}, mendeley-groups = {magnolia}, month = jun, number = {2}, pages = {112--117}, pmid = {15922325}, title = Template:Honokiol-induced neurite outgrowth promotion depends on activation of extracellular signal-regulated kinases (ERK1/2), url = {http://www.ncbi.nlm.nih.gov/pubmed/15922325}, volume = {516}, year = {2005} } </bibtex>
[4] <bibtex> @article{Liu2015, abstract = {STUDY DESIGN: Randomized experimental study.
OBJECTIVE: To investigate the neuroprotective effect of honokiol (HNK) on rats subjected to traumatic spinal cord injury (SCI) and the molecular mechanisms.
SUMMARY OF BACKGROUND DATA: Inflammation contributes to the secondary injury to the spinal cord. Honokiol has been used as a neuroprotective agent because of its strong antioxidant and anti-inflammatory properties. Kruppel-like factor 4 (Klf4) is a newly identified critical target for the anti-inflammatory effect of HNK. Whether HNK can inhibit inflammatory response in rat model of SCI through mediating the expression of Klf4 has yet to be elucidated.
METHODS: Eighty-four adult female Sprague-Dawley rats were randomly divided into 4 groups as sham, SCI, SCI + Vehicle (0.1\% propylene glycol in saline, intraperitoneally), and SCI + HNK (20 mg/kg, intraperitoneally) groups. The influences of HNK on the proinflammatory cytokines, microglial activation, neutrophil infiltration, histological changes, and improvement in motor function were assessed.
RESULTS: In the SCI group, proinflammatory cytokines, microglial activation, neutrophil infiltration, and Klf4 expression levels were increased compared with the sham group (P < 0.001). HNK intervention downregulated the expression of Klf4, reduced the production of proinflammatory cytokines, inhibited microglial activation, and neutrophil infiltration (P < 0.05). Furthermore, HNK also reduced histopathology and improved functional outcome after traumatic SCI.
CONCLUSION: HNK reduces secondary tissue damage and improves locomotor function recovery after SCI through suppressing inflammatory response, and can be used as a potential therapeutic agent for SCI.
LEVEL OF EVIDENCE: NA.}, author = {Liu, Jia and Zhang, Changmeng and Liu, Zhi and Zhang, Jianzheng and Xiang, Zimin and Sun, Tiansheng}, doi = {10.1097/BRS.0000000000000758}, issn = {1528-1159}, journal = {Spine}, mendeley-groups = {magnolia}, month = mar, number = {6}, pages = {363--8}, pmid = {25774462}, title = Template:Honokiol downregulates Kruppel-like factor 4 expression, attenuates inflammation, and reduces histopathology after spinal cord injury in rats., url = {http://www.ncbi.nlm.nih.gov/pubmed/25774462}, volume = {40}, year = {2015} } </bibtex>
