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Summary Magnolia officinalis, a representative tall aromatic tree of the Magnoliaceae family, is a medicinal plant that is widely used in diverse industries from medicine to cosmetics. We report a chromosome-scale draft genome of M. officinalis, in which ∼99.66% of the sequences were anchored onto 19 chromosomes with the scaffold N50 of 76.62 Mb. We found that a high proportion of repetitive sequences was a common feature of three Magnoliaceae with known genomic data. Magnoliids were a sister clade to eudicots-monocots, which provided more support for understanding the phylogenetic position among angiosperms. An ancient duplication event occurred in the genome of M. officinalis and was shared with Lauraceae. Based on RNA-seq analysis, we identified several key enzyme-coding gene families associated with the biosynthesis of lignans in the genome. The construction of the M. officinalis genome sequence will serve as a reference for further studies of Magnolia, as well as other Magnoliaceae., Graphical abstract, Highlights • We provide a chromosome-scale genome for Magnolia officinalis • We explore the phylogenetic position of Magnoliids • Analysis for lignan biosynthetic pathway is reported • We identify terpenes synthase in the floral fragrance composition of Magnolia, Biological sciences; Genetics; Evolutionary biology; Bioinformatics; Genomic analysis; Genomics

Alzheimer's disease (AD) is a common neurodegenerative disease characterized by neuronal degeneration and hyperphosphorylated Tau. Magnolol is an active component isolated from Magnolia officinalis with potential neuroprotection activity. However, the function and mechanism of magnolol in AD progression is largely uncertain. In present study, the biomarkers related to AD and magnolol were predicted by bioinformatics analyses. The key biomarker levels were predicted by GSE5281 and GSE36980 using AlzData. Cell viability was detected by CCK-8 assay. mRNA and protein levels were examined by qRT-PCR and western blotting assays. Cell apoptosis was investigated by caspase-3 activity and flow cytometry analyses. The cAMP/PKA/CREB signaling was evaluated by ELISA and western blotting analyses. The results showed that CHRM1 was a key biomarker for magnolol against AD progression. Magnolol attenuated Aβ-induced viability inhibition, Tau hyperphosphorylation and apoptosis in SH-SY5Y cells by upregulating CHRM1. In addition, the cAMP signaling might be a potential pathway of CHRM1 in AD. Magnolol contributed to activation of the cAMP/PKA/CREB pathway through enhancing CHRM1 level. Inactivation of the cAMP/PKA/CREB signaling reversed the suppressive effect of magnolol on Tau hyperphosphorylation and apoptosis in Aβ-treated SH-SY5Y cells. As a conclusion, magnolol mitigated Aβ-induced Tau hyperphosphorylation and neuron apoptosis by upregulating CHRM1 and activating the cAMP/PKA/CREB pathway.

La consommation de compléments alimentaires, conjointement à un régime nutritionnel habituel est en pleine croissance, motivée par une prise de conscience, de l’importance de la santé et la volonté de l’entretenir, voire de l’améliorer. Pour répondre à cet engouement, l’industrie a mis à disposition du public une multitude de produits, dont la plupart à base de plantes. L’arrêté du 24 juin 2014, fait partie des textes phares réglementant l’intégration des plantes dans les compléments alimentaires. Certaines espèces particulières sont autorisées sous conditions, en raison de la présence de molécules « à surveiller », source de difficultés d’interprétations, d’autant plus que les compléments alimentaires occupent une place frontière entre « aliment » et « médicament ». Magnolia officinalis, est un exemple de plante traditionnelle chinoise, autorisée dans les compléments alimentaires en France. Elle renferme des molécules à surveiller, considérées comme des « principes actifs » continuant à faire l’objet de nombreuses études, en raison de leurs potentielles actions à différents niveaux de l’organisme. Ce travail, aborde les compléments alimentaires ainsi que la place des plantes médicinales dans ces produits, les ambiguïtés concernant leurs usages ainsi que les limites et les risques émanant de leur consommation. Toutes ces notions, dépendent de plusieurs facteurs, et demandent une discussion au cas par cas, afin d’adapter au mieux l’offre, tout en plaçant la sécurité des consommateurs en tête des priorités.

(±)-Magoilgomer A [(±)-1] and magoilgomer B (2) were identified from the bark of Magnolia officinalis var. biloba. (+)-1 and (−)-1 were a pair of novel biphenyl derivatives featuring three C6-C3 subunits. 2 was an unprecedented adduct containing magnolol and honokiol. These three oligomers possessed new parallel mode which should be biosynthesized from the coupling of three or four C6-C3 subunits. The structures of (±)-1 and 2 were elucidated based on the spectroscopic data analyses and electronic circular dichroism (ECD) calculations. 2 exhibited neuroprotective effects of oxygen glucose deprivation-induced SK-N-SH cell injury.

Honokiol, a biphenolic neolignan with inappreciable toxicity isolated from Magnolia officinalis, has been reported to have antiangiogenic and antitumor properties in several tumor cell lines and tumor xenograft models. In our previous study, structural modification by chemical synthesis has been carried out to develop novel honokiol derivatives to improve antitumor activity and clarify the structure-activity relationship. Honokiol analogs, especially 3,5'-diformylated honokiol HK-(CHO)2, have been found to moderately block the newly grown segmental vessels from the dorsal aorta in the transgenic zebrafish-based assay, show antiangiogenic property, and exert medium cytotoxicity against two lung cell lines (Lewis lung carcinoma LL/2 cells and human non-small-cell lung cancer A549 cells). However, the in-vitro and in-vivo antitumor effects of formylated honokiol derivatives against lung carcinoma remained poorly understood. In the study, two formylated honokiol derivatives also showed potent antitumor effects in the Lewis lung carcinoma cells, K-ras-dirived lung adenocarcinoma mice, and a mouse lung tumor xenograft model, with HK-(CHO)2 being most efficacious. The potential mechanism was inhibiting cell proliferation and inducing apoptosis in lung cancer by the regulation of vascular endothelial growth factor A expression. These results further suggested that HK-(CHO)2 might be potential candidates for the treatment of lung carcinoma.

Magnolia officinalis subsp. officinalis and M. officinalis subsp. biloba are important medicinal plants in China. The bark of these two subspecies is commonly used in the production of a widely-used Chinese traditional medicine named ‘Houpu’. In recent years, M. o. subsp. officinalis and M. o. subsp. biloba have become increasingly threatened owing to the over-harvesting of their bark and the fragmentation of their habitats. In this study, we aimed to support the conservation and cultivation of these two subspecies in China by: (1) assessing the relationship between numerous environmental variables and the geographical distributions of the subspecies; (2) analysing the environmental characteristics of suitable habitats for both subspecies and predicting the spatial distribution of these habitats in China; and (3) identifying conservation areas of both subspecies in China via overlay analysis. We also assessed the degree of human disturbance within suitable habitats. We found that temperature was a major determinant for the distribution of M. o. subsp. officinalis. Conversely, the distribution of M. o. subsp. biloba was primarily dependent on precipitation rather than temperature. Distinct habitat preferences were observed between M. o. subsp. officinalis and M. o. subsp. biloba. Suitable habitats of M. o. subsp. officinalis were primarily distributed in the northern subtropical areas of China, with greater fluctuations in ambient temperature, lower extreme temperatures, less precipitation and greater fluctuations in precipitation. Habitats suitable for M. o. subsp. biloba were highly fragmented and were distributed in the central subtropical areas of China. We found that a large proportion of suitable habitats were not in the protected areas and that they were significantly disturbed by human activity. This analysis could provide useful information for the conservation of both M. o. subsp. officinalis and M. o. subsp. biloba and could aid in the selection of cultivation sites.

Magnolol, the most abundant bioactive constituent of the Chinese herb Magnolia officinalis, has been found with multiple biological activities, including anti-oxidative, anti-inflammatory and enzyme-regulatory activities. In this study, the inhibitory effects and inhibition mechanism of magnolol on human carboxylesterases (hCEs), the key enzymes responsible for the hydrolytic metabolism of a variety of endogenous esters as well as ester-bearing drugs, have been well-investigated. The results demonstrate that magnolol strongly inhibits hCE1-mediated hydrolysis of various substrates, whereas the inhibition of hCE2 by magnolol is substrate-dependent, ranging from strong to moderate. Inhibition of intracellular hCE1 and hCE2 by magnolol was also investigated in living HepG2 cells, and the results showed that magnolol could strongly inhibit intracellular hCE1, while the inhibition of intracellular hCE2 was weak. Inhibition kinetic analyses and docking simulations revealed that magnolol inhibited both hCE1 and hCE2 in a mixed manner, which could be partially attributed to its binding at two distinct ligand-binding sites in each carboxylesterase, including the catalytic cavity and the regulatory domain. In addition, the potential risk of the metabolic interactions of magnolol via hCE1 inhibition was predicted on the basis of a series of available pharmacokinetic data and the inhibition constants. All these findings are very helpful in deciphering the metabolic interactions between magnolol and hCEs, and also very useful for avoiding deleterious interactions via inhibition of hCEs.

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Background:Adenosine deaminase (ADA) is an important enzyme in purine metabolism and is known as a potential therapeutic target for the treatment of lymphoproliferative disorders and cancer. Traditional Chinese Herbal Medicine (TCHM) is widely used alone or in combination with chemotherapy to treat cancer, due to its ability to deliver a broad variety of bioactive secondary metabolites as promising sources of novel organic natural agents.Objective:In the present study, 29 varieties of medicinal plants were screened for the presence of ADA inhibitors.Result:Extracts from Reynoutria japonica, Glycyrrhiza uralensis, Lithospermum erythrorhizon, Magnolia officinalis, Gardenia jasminoides, Stephania tetrandra, Commiphora myrrha, Raphanus sativus and Corydalis yanhusuo demonstrated strong ADA inhibition with rates greater than 50%. However, Reynoutria japonica possessed the highest ADA inhibitory activity at 95.26% and so was used in our study for isolating the ADA inhibitor to be further studied. Eight compounds were obtained and their structures were identified. The compound H1 had strong ADA inhibitory activity and was deduced to be emodin by 1H and 13C-NMR spectroscopic analysis with an IC50 of 0.629 mM. The molecular docking data showed that emodin could bind tightly to the active site of ADA. Our results demonstrated that emodin displayed a new biological activity which is ADA inhibitory activity with high cytotoxic activity against K562 leukemia cells. The bioactivity of cordycepin was significantly increased when used in combination with emodin.Conclusion:Emodin may represent a good candidate anti-cancer therapy and adenosine protective agent.

An effective strategy based on high-speed counter-current chromatography (HSCCC) knockout combination with HPLC-DAD-QTOF-MS/MS analysis were developed to identify minor lignans, alkaloids, and phenylpropanoid glycosides in M. officinalis. Petroleum ether/ethyl acetate/methanol/water (8:4:7:5, v/v/v/v) as solvent system was firstly selected to separate the crude extract of M. officinalis. Two major lignans, honokiol and magnolol were knocked out, and minor components were enriched. Then, five standards (honokiol, magnolol, magnocurarine, magnoflorine and acteoside) were used as examples to discuss their fragmentation patterns for structural identification. By comprehensive screening, sixteen lignans, nine alkaloids, six phenylpropanoid glycosides were unambiguously or tentatively identified by comparing their retention time, UV spectra, accurate mass and fragmentation patterns with standards or reported components. Eight of them, as far as was known, were discovered from M. officinalis for the first time. The proposed method might provide a model for the effective identification of minor components from complex herbs. Additionally, this study laid a foundation for the study of quality control, and clinical applications of M. officinalis.

Over years, various biological constituents are isolated from Traditional Chinese Medicine and confirmed to show multifunctional activities. Magnolol, a hydroxylated biphenyl natural compound isolated fromMagnolia officinalis, has been extensively documented and shows a range of biological activities. Many signaling pathways include, but are not limited to, NF-κB/MAPK, Nrf2/HO-1, and PI3K/Akt pathways, which are implicated in the biological functions mediated by magnolol. Thus, magnolol is considered as a promising therapeutic agent for clinic research. However, the low water solubility, the low bioavailability, and the rapid metabolism of magnolol dramatically limit its clinical application. In this review, we will comprehensively discuss the last five-year progress of the biological activities of magnolol, including anti-inflammatory, antimicroorganism, antioxidative, anticancer, neuroprotective, cardiovascular protection, metabolism regulation, and ion-mediating activity.

Objective Maijunan (MJA) Tablets is a protected variety of traditional Chinese medicine (TCM) consisted of Pueraria lobata, hydrochlorothiazide (HTCZ), Uncaria rhynchophylla (366:1:980) and excipient. In the present work, MJA was consisted of the total flavones of P. lobata, HCTZ and total alkaloids of U. rhynchophylla (40:11:75). The combination of MJA and the total phenols of Magnolia officinalis (M-MJA) was consisted of the total flavones of P. lobata, the total phenols of M. officinalis, HCTZ and the total alkaloids of U. rhynchophylla (40:40:11:75). The aim of this work was to examine the effect and mechanism of M-MJA on the blood pressure of spontaneous hypertensive rats (SHRs). Methods Adult male SHRs were randomly divided into control group, MJA group (180 mg/kg·d), and the M-MJA group (218 mg/kg·d) (n = 5). SHRs were orally administered with M-MJA and MJA respectively once a day for 8 weeks, the blood pressure of SHRs was measured every two weeks, and the biochemical indicators related to blood pressures were detected at the last dosing. Results After oral administration of M-MJA to SHRs once a day for 8 weeks, the systolic and diastolic blood pressures of SHRs were deceased significantly. M-MJA affected renin-angiotensin-aldosterone system by decreasing the levels of Ren, Ang II and ALD, affected the endothelial function by decreasing the levels of ET-1 and 20-HETE, and increasing the level of eNOS, affected the oxidative stress by increasing the protein expression of Nrf2 and the activities of HO-1 and GSH-Px, and decreasing the protein expression of CYP2E1 and CYP4A, as well as the content of MDA. Conclusion These results indicated that M-MJA could regulate the renin-angiotensin-aldosterone system, improve endothelial function, and inhibit CYP4A activity to reduce the production of 20-HETE, alleviate the oxidative stress disorder of the visceral organs, and eventually exert antihypertensive effect. Additionally, the anti-oxidant ability, regulating the renin-angiotensin-aldosterone system and improving endothelial function of M-MJA are more powerful than that of MJA, suggesting that M-MJA may have a better anti-hypertensive effect than MJA.

As shown in a number of previous researches, the extracts of Magnolia officinalis exhibited broad-spectrum fungicidal and insecticidal activity. In our preliminary study, 5-arylbenzofuran neolignans, the secondary metabolite of Magnolia officinalis, was found to inherit the activity of Magnolia officinalis. For developing novel agrochemicals, natural 5-arylbenzofuran neolignan was selected as lead compound. After structural optimization, the fungicidal and insecticidal activity and selectivity were significantly improved. Compounds 5a, 5b, 6c and 6d displayed similar or equivalent activity compared with the positive controls against corresponding fungi or pests. Especially, compounds 6c and 6d exhibited the most promising insecticidal ability against Aphis fabae with the LC50 values of 3.56 mg/L and 5.96 mg/L, respectively. The preliminary structure-activity relationship was obtained, and the promising derivatives showed low toxicity in the model of human cells. The results of research indicated great potential of 5-arylbenzofuran neolignan derivatives in the field of fungicide and insecticide.

Most BRAF‐mutant melanoma patients experience a fulminate relapse after several months of treatment with BRAF/MEK inhibitors. To improve therapeutic efficacy, natural plant‐derived compounds might be considered as potent additives. Here, we show that magnolol, a constituent of Magnolia officinalis, induced G1 arrest, apoptosis and cell death in BRAF‐ and NRAS‐mutant melanoma cells at low concentration, with no effect in BRAF‐ and NRAS wild‐type melanoma cells and human keratinocytes. This was confirmed in a 3D spheroid model. The apoptosis‐inducing effect of magnolol was completely rescued by activating Akt suggesting a mechanism relying primarily on Akt signaling. Magnolol significantly downregulated the PI3K/Akt pathway which led to a global decrease of the active histone mark H3K4me3. Alongside, the repressive histone mark H3K9me3 was increased as a response to DNA damage. Magnolol‐induced alterations of histone modifications are reversible upon activation of the Akt pathway. Magnolol‐induced a synergistic effect in combination with either BRAF/MEK inhibitors dabrafenib/trametinib or docetaxel at a lower concentration than usually applied in melanoma patients. Combination of magnolol with targeted therapy or chemotherapy also led to analogous effects on histone marks, which was rescued by Akt pathway activation. Our study revealed a novel epigenetic mechanism of magnolol‐induced cell death in melanoma. Magnolol might therefore be a clinically useful addition to BRAF/MEK inhibitors with enhanced efficacy delaying or preventing disease recurrence.

Cryptocaryon irritans, a marine fish ectoparasite, causes mass economic loss in the mariculture and ornamental fish industries. It is important to find effective alternatives that may be both affordable and environmentally acceptable to control the damage of C. irritans. In this study, honokiol from Magnolia officinalis was screened from 36 phytochemical compounds for its significant antiparasitic activity against C. irritans theronts. Honokiol at a concentration of 1.00 μg/mL resulted in 100% mortality of C. irritans theronts within 30 min of exposure and >88.6% inhibition of tomont and protomont transformations post 8-h exposure to 1.00 and 4.00 μg/mL, respectively. Moreover, after exposure to 0.80, 1.00, and 4.00 μg/mL of honokiol solution for 30 min, 8 h, and 8 h, abnormal morphologies of theronts, tomonts, and trophonts were observed, respectively. After consecutively fed a diet containing 400 mg/kg of honokiol for 7 d, pompano (Trachinotus ovatus) were exposed to C. irritans theronts and the results showed that the number of C. irritans trophonts on the pompanos' gills was significantly lower than that in the control group 3 days later, while a similar efficacy was observed at doses above 100 mg/kg 8 days later. In addition, a dose of 200 mg/kg honokiol significantly reduced the chemotaxis of C. irritans theronts to the sera; meanwhile, the chemotaxis of C. irritans theronts to dorsal trunk muscle solutions was significantly reduced at doses above 100 mg/kg. Compared to the control group, a dose of 400 mg/kg honokiol increased the survival rate of the infected pompano by 65 ± 5% (mean ± SE). The results of hemolysis assay showed that the EC1 of honokiol to pompano erythrocytes was 6.36 μg/mL, 6.36 times the concentration that allowed honokiol to completely stop the movement of 100% C. irritans theronts in 30 min. Therefore, honokiol has the potential to be a safe and effective candidate, and could also serve as a leading compound in the development of a commercial drug to control C. irritans in mariculture.

Four new honokiol derivatives, namely 8′,9′-dihydroxymagnaldehyde E (1), 8′,9′-dihydroxyhonokiol (2), erythro-7-O-methylhonokitriol (3), and threo-7-O-methylhonokitriol (4), together with seven known compounds, erythro-honokitriol (5), threo-honokitriol (6), magnaldehyde E (7), magnotriol B (8), magnaldehyde B (9), honokiol (10), and magnolol (11), were isolated from the stem bark of Magnolia officinalis. Their structures were established on the basis of extensive 1D and 2D NMR experiments as well as HR-MS. All isolates were evaluated for their in vitro activities against acetylcholinesterase and butyrylcholinesterase, the results demonstrated that compound 8 possessed potent inhibitory activity.

Acute kidney injury (AKI) is one of the most common complications of sepsis, which largely contributes to the high mortality rate of sepsis. Honokiol, a natural polyphenol from the traditional Chinese herb Magnolia officinalis, is known to possess anti-inflammatory and antioxidant activity. Here, the underlying mechanism of honokiol-induced amelioration of sepsis-associated AKI was analyzed. The expression patterns of oxidative stress moleculars and TLRs-mediated inflammation pathway were examined to identify the response of NRK-52E cells incubated with septic rats' serum to honokiol. The levels of iNOS, NO, and myeloperoxidase in NRK-52E cells were increased during sepsis, which could be reversed by honokiol. The production of GSH and SOD as in vivo antioxidant was increased after honokiol treatment. The administration of honokiol significantly inhibited TLR2/4/MyD88 signaling pathway in AKI-induced NRK-52E cells. Furthermore, ZnPPIX, the HO-1 inhibitor, weakened honokiol-mediated morphological amelioration, and the reduced level of TNF-α, IL-1β, and IL-6 in kidneys of rats subjected to CLP. Finally, Honokiol was shown to connect with the Nrf2-Keap1 dimensionally. These findings suggest that honokiol plays its protective role on sepsis-associated AKI against oxidative stress and inflammatory signals.

Honokiol (HNK) is a small-molecule lignin extracted from Magnolia Officinalis, demonstrating high potency in promoting nonrapid eye movement (NREM) sleep by modulating the benzodiazepine site of the GABAA receptor. However, the clinical use of HNK in the treatment of insomnia is restricted by its extremely low oral bioavailability. In the present work, enhanced oral bioavailability of HNK was achieved by loading it into poly lactide–glycolide acid microparticles (HNK-MP). After oral administration, HNK-MP demonstrated 15-fold increase of AUC0–12 h in comparison to free HNK. The maximum blood concentration (Cmax) of HNK in HNK-MP-treated rats was 3.6 μg/mL at 2 h after oral administration, which was 6.5-fold of that in free HNK-treated rats. Oral administration of HNK-MP (20 mg/kg) efficiently increased NREM sleep by 60% by enhancing the transition from wakefulness to NREM sleep in rats. The biosafety of HNK-MP was assessed in vivo, and no damage occurred in the gastrointestinal tract. The present study pr...

Objectives The exposure of neurons to an excessive excitatory stimulation induces the alteration of the normal neuronal function. Mood disorders are among the first signs of alterations in the central nervous system function. Magnolia officinalis bark extract has been extensively used in the traditional medicine systems of several countries, showing several pharmacological activities. Honokiol, the main constituent of M. officinalis, is a GABA modulator and a CB1 agonist, which is deeply investigated for its role in modulating mood disorders. Methods Thus, we evaluated the possible neuroprotective effect of a standardized M. officinalis bark extract (MOE), enriched in honokiol, and its effect on animal mood behavioural tests and in an in vitro model of excitotoxicity. Key findings MOE showed neuroprotective effect using SH-SY5Y cells, by normalizing brain-derived neurotrophic factor release. Then, we tested the effect of MOE in different behavioural tests evaluating anxiety and depression and we observed a selective anxiolytic-like effect. Finally, we confirmed the involvement of CB1 in the final effect of MOE by the co-administration of the CB1 antagonist, AM251. Conclusion These results suggest that MOE could be considered an effective and safe anxiolytic candidate with neuroprotective activity.

Magnolia officinalis, a representative tall aromatic tree of the Magnoliaceae family, is a widely used medicinal plants with diverse medicinal values and applications, such as afforestation, ornamental and so on. We report a chromosome‑scale draft genome of M. officinalis, in which ~ 99.66% of the sequences were anchored onto 19 chromosomes with the scaffold N50 of 76.62 Mb. We found that a high proportion of repetitive sequences was a common feature of three Magnoliaceae with known genomic data, and M. officinalis was the plant in Magnoliaceae with the highest ratio of repetitive sequences found so far. Phylogenetic analyses reveal that magnoliids are as sister to the eudicots-monocots clade, which provides insight into the phylogenetic position between eudicots and monocots. WGD analysis showed that an ancient duplication event occurred in the M. officinalis genome, is shared by Lauraceae. Based on gene functional annotations and RNA-seq, we identified several key enzyme-coding gene families associated with the biosynthesis of lignan in the genome. In addition, the floral fragrance of M. officinalis is mainly attributed to its terpenes, we classified many putative genes involved in the biosynthesis of terpene synthases. The construction of the M. officinalis genome sequence map will serve as a reference for further studies of Magnolia as well as other Magnoliaceae.

This chapter introduces 24 species of medicinal plants in 4 families, such as Liriodendron chinense, Magnolia coco, Magnolia denudata, Magnolia grindediflora, Magnolia officinalis, and Magnolia officinalis subsp. biloba of Magnoliaceae, Kadsura coccinea, and Schisandra chinensis of Schisandraceae.

Alzheimer disease is a neurologic disorder that causes cognitive decline and memory loss due to neurofibrillary tangles and senile plaques in the brain. Clinically used drugs only enable relief of symptoms; they do not prevent the development of Alzheimer disease. In folk medicine, various medicinal plants were reported to be used for the treatment of neurodegenerative diseases. Experiments have shown that medicinal plants could provide effective treatment for Alzheimer disease. Scientific research has been carried out to reveal these beneficial effects via in vitro and in vivo methods. Magnolia officinalis Rehder & E.H.Wilson (Magnoliaceae) is a deciduous tree and is commonly known as magnolia bark or houpu magnolia. In Korean, Chinese, and Japanese traditional medicine, M. officinalis has been utilized for the treatment of several health problems. Thanks to its phytoconstituents, the medicinal products containing its extracts are used worldwide as dietary supplements. In this chapter, we aim to present previous findings on the potential effect of M. officinalis and its active secondary metabolites on Alzheimer disease.

Lianpu drink (LPD) is a traditional Chinese medicine (TCM) formula for the treatment of chronic gastritis (CG), and its clinical effects have been effectively verified. However, due to the complexity of the chemical composition of TCM formulas, its mechanism of action has not yet been clearly explained. Many studies have shown that the principal drugs in the TCM formula play a major therapeutic role. Therefore, in this study, the principal drugs Coptidis Rhizoma (CR) and Magnolia officinalis Rehd. et Wils. (MOR) in LPD were used as the main research objects to predict the mechanism of LPD on CG. We contrasted a “compounds-targets-diseases” network and screened the putative targets of CR and MOR in LPD related to CG, respectively. Furthermore, common targets of CR and MOR related to CG were selected as candidate targets. In this study, the specific target proteins of CR, MOR, and CG were combined by protein-protein interaction (PPI) to construct a pharmacological network of “components-targets-diseases.” In addition, we investigated the effects of CR and MOR on the TNF signaling pathway, which mediated the remission of CG. This study preliminarily revealed that CR and MOR play a key role in the treatment of CG. Animal experiments also showed that CR and MOR could significantly improve CG by inhibiting MKK6/p38 and RIP/p38 pathway.

Magnolol, a hydroxylated biphenyl extracted from Magnolia officinalis, has recently drawn attention due to its anticancer potential. The present study was aimed to explore the effects of Magnolol on restraining the proliferation, migration and invasion of pancreatic cancer in vivo and in vitro. Magnolol showed significant anti-growth effect in an orthotopic xenograft nude mouse model, and immunohistochemical staining of the xenografts revealed that Magnolol suppressed vimentin expression and facilitated E-cadherin expression. The cytoactive detection using CCK-8 assay showed Magnolol inhibited PANC-1 and AsPC-1 concentration-dependently. Scratch healing assay and the Transwell invasion assay proved the inhibiting effects of Magnolol on cellular migration and invasion at a non-cytotoxic concentration. Western blot and rt-PCR showed that Magnolol suppressed epithelial-mesenchymal-transition by increasing the expression level of E-cadherin and decreasing those of N-cadherin and vimentin. Magnolol suppressed the TGF-β/Smad pathway by negatively regulating phosphorylation of Smad2/3. Moreover, TGF-β1 impaired the antitumor effects of Magnolol in vivo. These results demonstrated that Magnolol can inhibit proliferation, migration and invasion in vivo and in vitro by suppressing the TGF-β signal pathway and EMT. Magnolol could be a hopeful therapeutic drug for pancreatic malignancy.

Honokiol, a natural compound, derived from Magnolia officinalis, has been shown to have anti-cancer effect in several cancer types. However, the underlying molecular mechanism associated with its anti-cancer properties has not been fully elucidated. In the current study, we showed that honokiol inhibited the growth of melanoma cells in a dose and time-dependent manner. Mechanistically, it directly interacts with keratin 18 (KRT18) protein and induces its degradation through ubiquitination. Furthermore, the expression of KRT18 was found to be higher in melanoma tissues compared to the normal skin tissues. In addition, KRT18 overexpression significantly promoted melanoma cell proliferation and growth. Our results showed that honokiol treatment significantly decreased KRT18 protein level and suppressed the tumor growth in melanoma cell-derived xenograft mice models. Hence, KRT18 plays an oncogenic role in melanoma and honokiol can be an inhibitor for KRT18.

Background: Extracts of Scutellaria baicalensis root (SBR) and Magnolia officinalis barks (MOB) possess significant antioxidant, anti-inflammatory, and antimicrobial properties, however, these also exert adverse effects such as cytotoxicity. To overcome the adverse effects, we formulated a combination of the extracts, named GenoTX-407, with SBR and MOB extracts mixed in 5:1 ratio. The antioxidant, antimicrobial, and anti-inflammatory activities of SBR and MOB extracts and GenoTX-407 were evaluated. Methods: To optimize the extraction conditions of SBR and MOB, different ethanol concentrations and extraction times and treatments of the extracts with different solvents for varying time periods were tested. Anti-inflammatory activity was assessed via NO scavenging assay and analysis of anti-inflammatory activity-related gene expression in RAW 264.7 cells. Agar disk diffusion and microdilution assays were used to determine the antimicrobial activity. Antioxidant activity was evaluated through DPPH assay and analyses of peroxidation and antioxidant-related protein expression in HeLa cells. Results: Extraction with 0% ethanol for 2 h and 1.5% phosphoric acid for 0.5 h yielded maximum SBR extracts. For MOB, 50% ethanol extraction for 2 h followed by further extraction in hexane for 0.5 h yielded the highest extracts. SBR (46.1 &plusmn, 0.9 %) and MOB (48.9 &plusmn, 1.0 %) extracts effectively inhibited NO production, and dose-dependently reduced the expression of TNF-&alpha, iNOS, NF-&kappa, B, COX2, and IL-6. MOB and GenoTX-407 inhibited the growth of Escherichia coli, Staphylococcus aureus, Candida albicans, and Propionibacterium acnes, as evidenced in disk diffusion and microdilution assays. SBR (EC50, 107.7 &micro, g/mL and 38.3 &micro, g/mL), MOB (62.41 &micro, g/mL and 72.45 &micro, g/mL), and GenoTX-407 (7.7 &micro, g/mL and 26.4 &micro, g/mL) exhibited excellent antioxidant potency and could scavenge free radicals of DPPH and lipid peroxidation, additionally, SOD, CAT, HO-1, and Nrf2 expression was increased in HeLa cells. SBR showed more potent antioxidant activity than MOB. Contrastingly, MOB exhibited more potent anti-inflammatory and antimicrobial activities than SBR. Interestingly, GenoTX-407 was the most efficient in all the assays, compared with SBR and MOB. Conclusion: This study demonstrated that GenoTX-407, the combination of SBR and MOB, is a potential drug candidate exerting antioxidant and anti-inflammatory effects via the Nrf2/HO-1 and NF-&kappa, B signaling pathways.

Six new biphenyl-type neolignans (1–6), and eighteen known compounds (7–24) were isolated from the EtOH extract of Magnolia officinalis. Their structures were determined by 1D and 2D NMR, and by HRMS. The anti-tumor activities of the isolated compounds were evaluated on HepG2, HCT-116, H1975 and HUVEC cell lines. Among the isolated compounds, nine compounds (3, 5, 7, 8, 12, 14, 20, 22, and 24) showed moderate cytotoxicities, and compound 23 showed the best cytotoxicity with IC50 value lower than 10 μM.

Magnolol and honokiol are the two major active ingredients with similar structure and anticancer activity from traditional Chinese medicine Magnolia officinalis, and honokiol is now in a phase I clinical trial (CTR20170822) for advanced non-small cell lung cancer (NSCLC). In search of potent lead compounds with better activity, our previous study has demonstrated that magnolol derivative C2, 3-(4-aminopiperidin-1-yl)methyl magnolol, has better activity than honokiol. Here, based on the core of 3-(4-aminopiperidin-1-yl)methyl magnolol, we synthesized fifty-one magnolol derivatives. Among them, compound 30 exhibited the most potent antiproliferative activities on H460, HCC827, H1975 cell lines with the IC50 values of 0.63–0.93 μM, which were approximately 10- and 100-fold more potent than those of C2 and magnolol, respectively. Besides, oral administration of 30 and C2 on an H460 xenograft model also demonstrated that 30 has better activity than C2. Mechanism study revealed that 30 induced G0/G1 phase cell cycle arrest, apoptosis and autophagy in cancer cells. Moreover, blocking autophagy by the autophagic inhibitor enhanced the anticancer activity of 30 in vitro and in vivo, suggesting autophagy played a cytoprotective role on 30-induced cancer cell death. Taken together, our study implied that compound 30 combined with autophagic inhibitor could be another choice for NSCLC treatment in further investigation.

Magnolia officinalis, as a well-known herb worldwide, has been widely used to treat multiple diseases for a long time. In this study, the petroleum ether extract from M. officinalis showed effective antifungal activity against seven plant pathogens (particularly against R. solani with an inhibition rate of 100.00% at 250 μg/mL). Honokiol and magnolol, isolated by the bioassay-guided method, exhibited greater antifungal activity than tebuconazole (EC50 = 3.07 μg/mL, p ≤ 0.001) against R. solani, which EC50 values were 2.18 μg/mL and 3.48 μg/mL, respectively. We used transcriptomics to explore the mechanism of action of honokiol against R. solani. Results indicated that honokiol may exert antifungal effects by blocking the oxidative phosphorylation metabolic pathway. Further studies indicated that honokiol induced ROS overproduction, disrupted the mitochondrial function, affected respiration, and blocked the TCA cycle, which eventually inhibited ATP production. Besides, honokiol also damaged cell membranes and caused morphological changes. This study demonstrated that the lignans isolated from M. officinalis possess the potential to be developed as botanical fungicides.

Honokiol (HK), an active compound derived from Magnolia officinalis Rehd. et Wils, possesses many beneficial biological activities for human beings. However, its poor solubility and low bioavailability severely limits its application. In this way, to improve the pharmaceutical properties, the HK was complexed in hydroxypropyl-β-cyclodextrin (HP-β-CD) and its oral bioavailability and antitumor effects were evaluated. The HK/HP-β-CD inclusion complex (1:1) was prepared by saturated aqueous solution method. The inclusion complex (HK-HP-β-CD) obtained had a higher solubility, about 1497 times that of the free HK. The dissolution rate and the oral bioavailability of HK was also significantly higher from inclusion complex than from free HK. Furthermore, the HK-HP-β-CD exhibited higher antitumor activity against Human Hepatoma Cell Line (HepG2) than free HK. More cells were arrested in the sub-G1 phase of the cell cycle and were induced to undergo late apoptosis when treated with the HK-HP-β-CD than when treated with free HK.

Magnolia officinalis is widely used in Southeast Asian countries for the treatment of fever, headache, diarrhea, and stroke. Magnolol is a phenolic compound extracted from M. officinalis, with proven antibacterial, antioxidant, anti-inflammatory, and anticancer activities. In this study, we modified magnolol to synthesize a methoxylated derivative, 2-O-methylmagnolol (MM1), and investigated the use of MM1, and magnolol in the treatment of liver cancer. We found that both magnolol and MM1 exhibited inhibitory effects on the growth, migration, and invasion of hepatocellular carcinoma (HCC) cell lines and halted the cell cycle at the G1 phase. MM1 also demonstrated a substantially better tumor-suppressive effect than magnolol. Further analysis suggested that by inhibiting class I histone deacetylase expression in HCC cell lines, magnolol and MM1 induced p21 expression and p53 activation, thereby causing cell cycle arrest and inhibiting HCC cell growth, migration, and invasion. Subsequently, we verified the significant tumor-suppressive effects of magnolol and MM1 in an animal model. Collectively, these findings demonstrate the anti-HCC activities of magnolol and MM1 and their potential for clinical use.

Cancer chemotherapy induces sarcopenia, which is a rapid loss of muscle mass that directly restricts daily activities and leads to poor quality of life and increased mortality. Although hormone-related therapies have been used to improve appetite and nutritional status, current treatments are considered palliative. Thus, the protection of skeletal muscle loss without adverse effects is essential to allow the maintenance of chemotherapy in cancer patients. Magnolol from Magnolia officinalis has several pharmacological effects including anti-cancer and anti-inflammatory activities, but the protection from muscle atrophy is not well-understood. In the present study, we investigated the effects of magnolol on muscle wasting and macrophage subtypes in a cisplatin-induced sarcopenia mouse model. We showed that magnolol significantly attenuated the body weight and the muscle loss induced by cisplatin injection. The diameter of the tibialis anterior muscle was markedly increased after magnolol treatment in cisplatin-treated mice. Importantly, magnolol increased macrophage infiltration into skeletal muscle while not affecting proliferation of macrophages. Magnolol attenuated the imbalance of M1/M2c macrophages by increasing CD206+CD163+ M2c tissue reparative macrophages. Further, magnolol increased insulin-like growth factor (IGF)-1 expression. This effect was also observed in bone marrow-derived macrophages upon magnolol treatment. Taken together, magnolol may be a promising chemoprotective agent for the prevention of muscle atrophy through the upregulating M2c macrophages, which are a major source of IGF-1.

Honokiol, a natural bioactive neolignan isolated from the bark and leaf of Magnolia officinalis and Magnolia obovata, exhibits many important biological properties. In continuation of our interest in discovery of the agrochemicals derived from the natural sources, thirty-seven new 8/8′-alkylthiol-benzoxazole and N-alkyl/sulfonyl-benzoxazolone derivatives of honokiol were prepared and their insecticidal activities were evaluated against the larvae of Mythimna separata Walker and Plutella xylostella Linnaeus. The results showed that eleven derivatives exhibited potent insecticidal activity against M. separata when compared with the positive control. Particularly, compound 5h displayed the most promising insecticidal activity against M. separata with the final mortality rate (FMR) of 58.6%. Meanwhile, compounds 7n (FMR = 65.3%), 7p (FMR = 61.5%), and 8c (FMR = 65.3%) demonstrated a greater insecticidal activity against P. xylostella than toosendanin, a well-known botanical insecticide. Additionally, the preliminary structure-activity relationships (SARs) were also discussed. This study indicates that these honokiol derivatives could be used as leads for the further derivation and development of the potential pesticide candidates for crop protection.

Background: Neuroinflammation induced in response to damage caused by status epilepticus (SE) activates the interleukin (IL)1-β pathway and proinflammatory proteins that increase vulnerability to the development of spontaneous seizure activity and/or epilepsy. Objectives: The study aimed to assess the short-term anti-inflammatory and neuroprotective effects of Magnolia officinalis (MO) on recurrent SE in immature rats. Methods: Sprague-Dawley rats at PN day 10 were used; n = 60 rats were divided into two control groups, SHAM and KA, and two experimental groups, MO (KA-MO) and Celecoxib (KA-Clbx). The anti-inflammatory effect of a single dose of MO was evaluated at 6 and 24 hr by Western blotting and on day 30 PN via a subchronic administration of MO to assess neuronal preservation and hippocampal gliosis by immunohistochemistry for NeunN and GFAP, respectively. Results: KA-MO caused a decrease in the expression of IL1-β and Cox-2 at 6 and 24 h post-treatment, a reduction in iNOS synthase at 6 and 24 hr post-treatment and reduced neuronal loss and gliosis at postnatal day 30, similar to Clbx. Conclusion: The results indicating that Magnolia officinalis is an alternative preventive treatment for early stages of epileptogenesis are encouraging.

Objective: The objective of this experiment was to compare conventional antioxidants and plant extracts for oxidative stress control in lambs fed a high-concentrate diet.Methods: Forty-eight male Dorper×Santa Ines lambs with an initial weight of 20±1.49 kg and 60 days of age, were used to evaluate the effects of feeding a combination of Macleaya cordata and Magnolia officinalis plant extracts (0 vs 320 mg/kg dry matter [DM]) in combination with selenium+vitamin E (0 vs 100 IU/kg DM of vitamin E and 0.1 mg/kg DM of selenium) in a completely randomized block design in a 2×2 factorial arrangement. The animals were housed in individual pens and received a high-concentrate diet consisting of 80% whole corn and 20% protein pellet for 60 days. The animals were weighed at the beginning of the experiment and every 14 days for performance monitoring. Three blood samplings were performed during the experimental period for the evaluation of oxidative and protein parameters.Results: The treatments with vitamin E and selenium as additives had a positive influence on final weight, daily weight gain, carcass weight, and selenium content in longissimus muscle (p = 0.01). Plant extracts tended to improve final weight (p = 0.064) and daily weight gain (p = 0.059), showing similar effect as selenium and vitamin E. There was no effect of treatment on blood proteins, indicating that the animals were healthy throughout the experiment.Conclusion: The use of plant extracts had a similar effect as the addition of selenium and vitamin E, with dietary inclusion of additives resulting in better performance of lambs but both supplements did not have strong influence on oxidative stress.

Alcoholic liver damage (ALD) is a toxic liver damage caused by excessive drinking. Oxidative stress is one of the most crucial pathogenic factors leading to ALD. Magnolol is one of the main active constituents of traditional Chinese medicine Magnolia officinalis, which has been reported to possess many pharmacological effects including anti-inflammatory, anti-oxidant, and anti-tumor. However, the effects of magnolol on ALD remain unclear. In this study, we firstly evaluated the protective effects of magnolol on ALD, and then tried to clarify the mechanism underlying the pharmacological activities. AST, ALT, GSH-Px, and SOD were detected by respective kits. Histopathological changes of liver tissue were analyzed by H&E staining. The activities of PI3K, Nrf2, and NLRP3 signaling pathways activation were detected by western blotting analysis. It was showed that alcohol-induced ALT and AST levels were significantly reduced by magnolol, but the antioxidant enzymes of GSH-Px and SOD levels were significantly increased. Magnolol attenuated alcohol-induced pathologic damage such as decreasing hepatic cord swelling, hepatocyte necrosis, and inflammatory cell infiltration. Furthermore, it was found that magnolol inhibited oxidative stress through up-regulating the activities of HO-1, Nrf2, and PPARγ and the phosphorylation of PI3K and AKT. And magnolol also decreased inflammatory response by inhibiting the activation of NLRP3inflammasome, caspase-1, and caspase-3 signaling pathway. Above results showed that magnolol could prevent alcoholic liver damage, and the underlying mechanism was through activating PI3K/Nrf2/PPARγ signaling pathways as well as inhibiting NLRP3 inflammasome, which also suggested magnolol might be used as a potential drug for ALD.

EGFR T790 M accounts for 50% to 60% of cases of non-small-cell lung carcinoma (NSCLC) resistance to the first-generation EGFR tyrosine kinase inhibitors (TKIs). Hence, identifying novel compounds with activity against TKIs resistant is of great value. In this study, twenty honokiol and magnolol derivatives were isolated from the EtOH extract of Magnolia officinalis and the antiproliferative activity was evaluated on HCC827 (19del EGFR mutation), H1975 (L858 R/T790 M EGFR mutation), and H460 (KRAS mutation) cell lines. Among the isolated compounds, piperitylmagnolol (a 3-substituted magnolol derivative) showed the best antiproliferative activity against those three cell lines with the IC50 values of 15.85, 15.60 and 18.60 μM, respectively, which provided a direction for the structural modification of magnolol. Further structural modification led to the synthesis of thirty-one magnolol derivatives, and compounds A13, C1, and C2 exhibited significant and broad-spectrum antiproliferative activity with the IC50 values ranging from 4.81 to 13.54 μM, which were approximately 4- and 8-fold more potent than those of honokiol and magnolol, respectively. Moreover, their aqueous solubility was remarkably improved with 12-, 400- and 105 fold greater than those of honokiol and magnolol. Anti-tumor mechanism research revealed that these three compounds were able to induce cell cycle arrest at G0/G1 phase, cause efficient apoptosis in H1975 cells, and also prevent the migration of HUVECs in a dose-dependent manner through Cdk2, Cdk4, Cyclin E, and Cyclin D1 inhibition as well as up-regulation of cleaved-PARP and cleaved-caspase 3 levels. In in vivo antitumor activity, C2 (10, 30 and 100 mg/kg, po) dose-dependently inhibited the tumor growth in H1975 xenograft model with the tumor inhibition rate of 46.3%, 59.3% and 61.2% respectively, suggesting that C2 is a potential oral anticancer agent deserving further investigation.

Honokiol, a bioactive compound isolated from the cone and bark of Magnolia officinalis, has been shown to have various activities including inhibition of the growth of Candida albicans. We investigated the roles of the Hsp90-calcineurin pathway in the antifungal activity of honokiol. The pharmacologic tool was employed to evaluate the effects of Hsp90 and calcineurin in the antifungal activity of honokiol. We also evaluated the protective effects of the calcineurin inhibitor cyclosporin A (CsA) on honokiol-induced mitochondrial dysfunction by the fluorescence staining method. The Hsp90 inhibitor potentiated the antifungal activity of honokiol. A C. albicans strain with the calcineurin gene deleted displayed enhanced sensitivity to honokiol. However, co-treatment with calcineurin inhibitor CsA attenuated the cytotoxic activity of honokiol due to the protective effect on mitochondria. Our results provide insight into the action mechanism of honokiol.

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. Neolignans, particularly magnolol and honokiol, are the main substances responsible for the beneficial properties of the magnolia bark extract (MBE). The content of magnolol and honokiol in MBE depends on different factors, including the Magnolia plant species, the area of origin, the part of the plant employed, and the method used to prepare the extract. The biological and pharmacological activities of magnolol and honokiol have been extensively investigated. Here we review the safety and toxicological properties of magnolol and honokiol as pure substances or as components of concentrated MBE, including the potential side-effects in humans after oral intake. In vitro and in vivo genotoxicity studies indicated that concentrated MBE has no mutagenic and genotoxic potential, while a subchronic study performed according to OECD (Organisation for Economic Co-operation and Development) guidelines established a no adverse effect level for concentrated MBE > 240 mg/kg b.w/d. Similar to other dietary polyphenols, magnolol and honokiol are subject to glucuronidation, and despite a relatively quick clearance, an interaction with pharmaceutical active principles or other herbal constituents cannot be excluded. However, intervention trials employing concentrated MBE for up to 1 y did not report adverse effects. In conclusion, over the recent years different food safety authorities evaluated magnolol and honokiol and considered them safe.

Magterpenoid A (1), possessing a rare 4,6,11-trioxatricyclo[5.3.1.01,5]undecane framework with an irregular monoterpenoid moiety, magterpenoid B (2), with an unprecedented 6/6/6/6 polycyclic skeleton, and magterpenoid C (3), a novel terpenoid quinone with a C6–C3 unit, were isolated from the bark of Magnolia officinalis var. biloba. Plausible biogenetic pathways of 1-3 are presented. Compounds 1 and 3 exhibited significant PTP1B inhibitory activities with IC50 values of 1.44 and 0.81 μM, respectively.

BACKGROUND The cortex of Magnolia officinalis has long been used as an element of traditional Chinese medicine for the treatment of anxiety, chronic bronchitis, and gastrointestinal dysfunction. This study aimed to elucidate the underlying mechanism of its functional ingredients (magnolol and honokiol) in modifying the secretion and absorption homeostasis and protecting mucosal integrity in an Enterotoxigenic Escherichia coli (ETEC)-induced diarrhea mouse model. MATERIAL AND METHODS This study established a diarrhea mouse model infected by ETEC at a dosage of 0.02 ml/g live body weight (BW) in vivo. Magnolol or honokiol was followed by an intraperitoneal administration at dosages of 100, 300, and 500 mg/kg BW according to a 3×3 factorial arrangement. The useful biomarkers for evaluating the integrity of intestinal tract and histologic injury were analyzed and morphological development (including villus height, crypt depth, and ratio of villus height to crypt depth) and the expressions of inflammatory cytokines were determined by real-time PCR. RESULTS The results showed that magnolol and honokiol (500 mg/kg BW) reduced the concentrations of NO, DAO, and DLA, and iNOS activity, and the mRNA expressions of the interferon gamma (IFN-γ) and interleukin 10 (IL-10), and inhibited intestinal epithelial cell apoptosis. Magnolol and honokiol (300 mg/kg BW) elongated the villus height and crypt depth and decreased the number of goblet cells and the ratio of villus height to crypt depth. CONCLUSIONS The current results indicate that magnolol and honokiol enhance the intestinal anti-inflammatory capacities, elongate the villus height and crypt depth, and reduce goblet cell numbers to inhibit the intestinal epithelium apoptosis and effectively protect the intestinal mucosa. These results show that magnolol and honokiol protect the intestinal mucosal integrity and regulate gastrointestinal dysfunction.

Glioblastoma is a primary malignant brain tumor with a poor prognosis. An effective treatment for glioblastoma is needed. Magnolol is a natural compound from Magnolia officinalis suggested to have antiproliferative activity. The aim of this research was to investigate the anticancer effects of magnolol in glioma, with an emphasis on migration and the underlying mechanism. Magnolol decreased the expression of focal adhesion-related proteins and inhibited LN229 and U87MG glioma cell migration. The levels of phosphorylated myosin light chain (p-MLC), phosphorylated myosin light chain kinase and myosin phosphatase target subunit 1 were reduced in response to magnolol treatment. In addition, immunostaining and membrane fractionation showed that the distribution of N-cadherin at the glioma cell membrane was decreased by magnolol. In an orthotropic xenograft animal model, magnolol treatment not only inhibited tumor progression but also reduced p-MLC and N-cadherin protein expression. In conclusion, magnolol reduces cell migration, potentially through regulating focal adhesions and N-cadherin in glioma cells. Magnolol is a potential candidate for glioma treatment.

Magnolol, the main and active ingredient of the Magnolia officinalis, has been widely used in traditional prescription to the human disorders. Magnolol has been proved to have several pharmacological properties including anti-bacterial, anti-oxidant and anti-inflammatory activities. However, the effects of magnolol on ulcerative colitis (UC) have not been reported. The aim of this study was to investigate the protective effects and mechanisms of magnolol on dextran sulphate sodium (DSS)-induced colitis in mice. The results showed that magnolol significantly alleviated DSS-induced body weight loss, disease activities index (DAI), colon length shortening and colonic pathological damage. In addition, magnolol restrained the expression of TNF-α, IL-1β and IL-12 via the regulation of nuclear factor-κB (NF-κB) and Peroxisome proliferator-activated receptor-γ (PPAR-γ) pathways. Magnolol also enhanced the expression of ZO-1 and occludin in DSS-induced mice colonic tissues. These results showed that magnolol played protective effects on DSS-induced colitis and may be an alternative therapeutic reagent for colitis treatment.