Bark Of Magnolia Officinalis Research Articles

Magnolol inhibits sodium currents in freshly isolated mouse dorsal root ganglion neurons.

The voltage-gated sodium channel (VGSC) currents in dorsal root ganglion (DRG) neurons contain mainly TTX-sensitive (TTX-S) and TTX-resistant (TTX-R) Na+ currents. Magnolol (Mag), a hydroxylated biphenyl compound isolated from the bark of Magnolia officinalis, has been well documented to exhibit analgesic effects, but its mechanism is not yet fully understood. The aim of the present study was to investigate whether the antinociceptive effects of Mag is through inhibition of Na+ currents. Na+ currents in freshly isolated mouse DRG neurons were recorded with the whole cell patch clamp technique. Results showed that Mag inhibited TTX-S and TTX-R Na+ currents in a concentration-dependent manner. The IC50 values for block of TTX-S and TTX-R Na+ currents were 9.4 and 7.0μmol/L, respectively. Therefore, TTX-R Na+ current was more susceptible to Mag than TTX-S Na+ current. For TTX-S Na+ channel, 10μmol/L Mag shifted the steady state inactivation curve toward more negative by 9.8mV, without affecting the activation curve. For TTX-R Na+ channel, 7μmol/L Mag shifted the steady state activation and inactivation curves toward more positive and negative potentials by 6.5 and 11.7mV, respectively. In addition, Mag significantly postponed recovery of TTX-S and TTX-R Na+ currents from inactivation, and produced frequency dependent blocks of both subtypes of Na+ currents. These results suggest that the inhibitory effects of Mag on Na+ channels may contribute to its analgesic effect.

The Therapeutic Effects of Magnolia Officinalis Extraction on an Antibiotics-Induced Intestinal Dysbacteriosis in Mice.

Magnolia officinalis bark is a traditional Chinese medicine for gastrointestinal tract disorders. In this study, we explored the effects of M. officinalis extraction on intestinal flora to reveal its mechanism. Thirty SPF mice were divided into five groups: C (control), M (M. officinalis), A (antibiotics: cefradine and gentamicin sulfate), A&M (antibiotics + M. officinalis) and A&N (antibiotics + natural recovery). Faecal samples of all groups were collected and the taxonomic composition and diversity of bacteria was characterized using the 16S rRNA gene (16S). Alpha diversity showed gut bacteria diversity significantly decreased in the A group of mice but increased markedly after administration of M. officinalis extract. Beta diversity indicated thatC,Mand A&M shared similar bacterial community structure while A and A&N exhibited a different bacterial community. Furthermore, RDA combined with spearman correlation heatmap suggested the five physiological indicators (weight, fur, activity and feces) were highly correlated with bacterial community structure and diversity. Finally, functional categorization of the assigned OTUs was performed using the PICRUSt tool. The changes in PICRUSt inferred that function profile and metabolic pathways were observed in A and A&M, therefore the M. officinalis extract improved the intestinal flora of A&M and normalized its metabolic pathways gradually, improving mouse weight, fur quality, activity and feces qualities.

Effectiveness in the Block by Honokiol, a Dimerized Allylphenol from Magnolia Officinalis, of Hyperpolarization-Activated Cation Current and Delayed-Rectifier K+ Current.

Background: Honokiol (HNK), a dimer of allylphenol obtained from the bark of Magnolia officinalis was demonstrated to exert an array of biological actions in different excitable cell types. However, whether or how this compound can lead to any perturbations on surface–membrane ionic currents remains largely unknown. Methods: We used the patch clamp method and found that addition of HNK effectively depressed the density of macroscopic hyperpolarization-activated cation currents (Ih) in pituitary GH3 cells in a concentration-, time- and voltage-dependent manner. By the use of a two-step voltage protocol, the presence of HNK (10 μM) shifted the steady-state activation curve of Ih density along the voltage axis to a more negative potential by approximately 11 mV, together with no noteworthy modification in the gating charge of the current. Results: The voltage-dependent hysteresis of Ih density elicited by long-lasting triangular ramp pulse was attenuated by the presence of HNK. The HNK addition also diminished the magnitude of deactivating Ih density elicited by ramp-up depolarization with varying durations. The effective half-maximal concentration (IC50) value needed to inhibit the density of Ih or delayed rectifier K+ current identified in GH3 cells was estimated to be 2.1 or 6.8 μM, respectively. In cell-attached current recordings, HNK decreased the frequency of spontaneous action currents. In Rolf B1.T olfactory sensory neurons, HNK was also observed to decrease Ih density in a concentration-dependent manner. Conclusions: The present study highlights the evidence revealing that HNK has the propensity to perturb these ionic currents and that the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel is proposed to be a potential target for the in vivo actions of HNK and its structurally similar compounds.

Suppression of PKCδ/NF-κB Signaling and Apoptosis Induction through Extrinsic/Intrinsic Pathways Are Associated Magnolol-Inhibited Tumor Progression in Colorectal Cancer In Vitro and In Vivo.

Magnolol is one of the hydroxylated biphenyl compounds from the root and stem bark of Magnolia officinalis, which shown to possess anti-colorectal cancer (CRC) effects. However, the regulatory mechanism of magnolol on apoptosis and NF-κB signaling in human CRC has not been elucidated. Thus, we investigated the inhibitory mechanism of magnolol on human and mouse CRC (HT-29 and CT-26) in vitro and in vivo. Results from reporter gene assay indicated that both magnolol and rottlerin (PKCδ inhibitor) reduced the endogenous NF-κB activity. In addition, indolactam V (PKCδ activator)-induced NF-κB signaling was significantly suppressed with both magnolol and rottlerin treatment. Results from Western blotting also indicated that phosphorylation of PKCδ and NF-κB -related proteins involved in tumor progression were effectively decreased by magnolol treatment. The invasion capacity of CRC cells was also attenuated by both magnolol and rottlerin. Furthermore, magnolol triggered Fas/Fas-L mediated extrinsic apoptosis and mitochondria mediated intrinsic apoptosis were validated by flow cytometry. Most importantly, tumor growth in both HT-29 and CT-26 bearing mice were suppressed by magnolol, but no pathologic change was detected in mice kidney, spleen, and liver. As confirmed by immunohistochemistry (IHC) staining from tumor tissue, PKCδ/NF-κB signaling and downstream proteins expression were decreased, while apoptotic proteins expression was increased in the magnolol treated group. According to these results, we suggest that the induction of apoptosis through extrinsic/intrinsic pathways and the blockage of PKCδ/NF-κB signaling are associated with the magnolol-inhibited progression of CRC.

Ethanol extract of Magnoliae cortex (EEMC) limits teratoma formation of pluripotent stem cells by selective elimination of undifferentiated cells through the p53-dependent mitochondrial apoptotic pathway

Background: Induced pluripotent stem cells (iPSCs) are regarded as the best potential cell source for cell-based regenerative medicine. To develop a safe and efficient iPSC-based cell therapy, it is very important to avoid possible teratoma formation, which can arise from undifferentiated iPSCs (USCs) remaining among differentiated cell products. Dried bark of Magnolia officinalis (Magnolia cortex, MC) has long been used in traditional medicine to treat gastrointestinal ailments and allergic diseases, and has shown have various pharmacological activities, including anti-bacterial, anti-inflammatory, and anti-cancer effects. However, its effects on iPSCs have not yet been examined. Purpose: In this study, we investigated the selective cytotoxic effects of ethanol extract of MC (EEMC) on undifferentiated iPSCs and elucidated the underlying apoptotic mechanisms in detail. We also investigated the inhibitory effects of EEMC on teratoma formation via in ovo experiments. Results: We found that EEMC greatly reduced cell growth and induced apoptotic cell death in USCs, but not in differentiated or normal cells. EEMC caused G2/M cell cycle arrest, mitochondrial damage, and caspase activation of USCs, accompanied by p53 accumulation. In p53KO human iPSCs, EEMC had no cytotoxicity, reinforcing that EEMC-mediated apoptosis of USCs is p53-dependent. EEMC did not cause DNA damage in iPSC-derived differentiated cells. In ovo teratoma formation assay revealed that EEMC treatment before injection efficiently eliminated USCs and prevented teratoma formation. Conclusions: These results collectively indicate that EEMC has potent anti-teratoma activity, and therefore can be used for the development of safe iPSC-based therapy.

Enhanced oral bioavailability of magnolol via mixed micelles and nanosuspensions based on Soluplus®-Poloxamer 188

Magnolol, known to have extensive biological activities, is the major bioactive ingredient isolated from the root and stem bark of Magnolia officinalis. However, the clinical application of magnolol is limited by poor aqueous solubility and absorption. The aim of this study is to develop novel mixed micelles and nanosuspensions composed of two biocompatible copolymers, Soluplus® and Poloxamer 188, and to improve the solubility and oral bioavailability of magnolol. The magnolol-loaded mixed micelles (MMs) and magnolol nanosuspensions (MNs) were prepared to use film hydration and antisolvent methods, respectively. The optimal MMs and MNs formulations were prepared to use magnolol, Soluplus®, and Poloxamer 188 in ratios of 1:12:5 and 2:1:1, respectively. The average particle size of MMs was 111.8 ± 14.6, and MNs was 78.53 ± 5.4 nm. The entrapment and drug loading efficiency for MMs were 89.58 ± 2.54% and 5.46 ± 0.65%, correspondingly. The drug loading efficiency of MNs was 42.50 ± 1.57%. In the in vitro release study, MMs showed a slow drug release while that of MNs was fast. The results of the Caco-2 transcellular transport study indicated that both MMs and MNs increased the permeation of magnolol. MMs and MNs markedly promoted gastrointestinal drug absorption by 2.85 and 2.27-fold, respectively, as shown in the pharmacokinetics study. These results indicated that both MMs and MNs formulations prepared with Soluplus® and Poloxamer 188 are promising drug delivery systems for improving the oral absorption of insoluble drugs in the gastrointestinal tract.

Geo-herbalism study of Magnoliae Officinalis Cortex

Magnoliae Officinalis Cortex( MOC),the stem bark of Magnolia officinalis( MO) and M. officinalis var. biloba( MOB),is a main ingredient in more than 200 types of Chinese formulae commonly used in clinics. MO and MOB are widely distributed in China,from Sichuan of the west to Zhejiang province of the east and from Shannxi province in the north to Guangxi province in the south. This review summarizes new findings on geo-heralism of MOC concerning textual research,plants taxonomy,genetic study,chemical study,and pharmacological activity,resulting in the following views. ①The original plants of MOC are suggested to be divided into three geographic clans according to the form of leave and the result of genetic research; ②Concentrations of magnolol,honokiol,magnoloside A,magnoloside B,magnoflorine,and β-eudesmol in samples collected from different geographic areas are varied;③Samples of MOC produced in Hubei and Sichuan were traditionally regarded as Dao-di herbs,which were called Chuanpo,and the pure haplotype of MOC produced in Hubei may become a genetic index.

Effects of the herbal medicines on voltage-dependent K+ 2 channels

Background: Identification of selective ion channel inhibitors is necessary for understanding the physiological role of these proteins. The voltage-dependent K+ (Kv) channels, Kv2.1 and Kv2.2, are expressed in pancreatic islets, and the development of selective Kv2.1 inhibitors that do not cross-inhibit Kv2.2 may be useful for the treatment of type 2 diabetes. Objective: The aim of this study was to evaluate whether herbal medicines, such as the fruit of Schisandra chinensis (SCF), Atractylodes macrocephala Koidzumi (AMK), Poria cocos Wolf (PCW), Citrus unshiu peel (CUP), Magnolia officinalis Bark (M. officinalis), Alisma canaliculatum (A. canaliculatum), Rehmanniae Radix (RR), and Corni fructus (C. fructus), modulate Kv2 channels and cause insulin secretion. Materials and Methods: We used the whole-cell patch-clamp technique to analyze the effect of these herbal medicines on Kv channels. In addition, human embryonic kidney 293 cells overexpressing Kv2.1 and Kv2.2 channels were used to confirm the role of Kv2 channels. Results: SCF, AMK, PCW, CUP, M. officinalis, A. canaliculatum, and RR inhibited Kv2.1 channel currents in a concentration-dependent manner (100–500 μg/mL). However, C. fructus had no effects on Kv2.1 channel currents. In addition, SCF, AMK, M. officinalis, and A. canaliculatum inhibited Kv2.2 channel currents in a concentration-dependent manner, but PCW, CUP, and RR had no effects on Kv2.2 channel currents. Furthermore, RR, CUP, and PCW increased insulin secretion. Conclusion: These findings suggested that the herbal medicines, RR, CUP, and PCW, are potential novel agents for the prevention and treatment of diabetes.

Four new honokiol derivatives from the stem bark of Magnolia officinalis and their anticholinesterase activities

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.

Induction of apoptosis by magnolol via the mitochondrial pathway and cell cycle arrest in renal carcinoma cells

Magnolol (Mag), an effective natural compound isolated from the stem bark of Magnolia officinalis, was found to have the potential for antitumor activity by inducing apoptosis in tumor cells. However, the effect of Mag on renal carcinoma cells and its molecular mechanism are unexplored. Our study provided evidence that Mag induced apoptosis in 786-O and OS-RC-2 cell lines via the mitochondrial pathway and cell cycle arrest. In this work, we found that Mag induced morphological changes and inhibited the proliferation of 786-O and OS-RC-2 cells in a dose- and time-dependent manner but exerted no notable inhibitory effects on normal human renal proximal tubular (HK-2) cells. Treatment with Mag suppressed the migration and invasion ability of renal carcinoma cells. Moreover, Mag caused the openness of mPTP, the accumulation of intracellular ROS and decreased △Ψm, leading to mitochondrial dysfunction. However, pretreatment with the antioxidant N-acetyl cysteine (NAC) reversed the apoptosis induced by Mag and decreased the generation of ROS. In addition, the increased proportion of the G1/G0 phase indicated that Mag caused cell cycle arrest. Further analyses suggested that magnolol-induced apoptosis was related to the abnormal expression of p53, Bax, Bcl-2, cytochrome c and caspase activation. Together, the results above revealed that Mag had antitumor effects in renal carcinoma cells via ROS production as well as cell cycle arrest and the apoptotic mitochondrial pathway was suppressed in part by NAC.

Evaluation of Tyrosinase Inhibitory, Antioxidant, Antimicrobial, and Antiaging Activities of Magnolia officinalis Extracts after Aspergillus niger Fermentation.

This study intended to improve physiological characteristics of Magnolia officinalis bark (MOB) extracts by Aspergillus niger fermentation. M. officinalis bark was extracted using distilled water, 95% ethanol, and methanol, and it was then fermented by A. niger. The physiological characteristics of the fermented extracts, namely, tyrosinase inhibitory activity, antioxidant activity, antibacterial activity, and anti-skin-aging activity, were evaluated and compared with those of unfermented extracts. To determine the safety of the fermented extracts, their cytotoxicity was analyzed by measuring the cell viability of CCD-966SK and human epidermal melanocytes (HEMn) after exposure. The fermented methanol extract exhibited the highest antityrosinase activity, total phenolic content, and antioxidant activity. The total phenolic content of the extracts fermented by A. niger was 3.52 times greater than that of the unfermented extracts. The optimal IC50 values for tyrosinase inhibition and 2,2-diphenyl-1-picrylhydrazyl (DPPH) removal by the A. niger-fermented extracts were 30 and 12 μg/mL, respectively. The fermented methanol extracts inhibited skin-aging-related enzymes such as collagenase, elastase, MMP-1, and MMP-2. Compared with the unfermented extracts, the fermented extracts also contained greater antibacterial activity against tested stains including MRSA. These results could be attributed to an increase in the concentration of original active compounds and the biosynthesis of new compounds during fermentation. In cytotoxicity assays, the A. niger-fermented extracts were nontoxic to CCD-966SK cells, even at 500 μg/mL. Hence, in general, methanol-extracted M. officinalis fermented by A. niger for 72 h has the most active antioxidant, skincare, or antiaging compounds for healthy food or cosmetics applications.

Efficacy of a Magnolia officinalis bark extract against grapevine downy mildew and apple scab under controlled and field conditions

In organic agriculture, the control of several diseases is largely depending on copper fungicides. Yet, copper can accumulate in the soil if the annual input exceeds annual uptake by plants, which can have a negative impact on soil fertility. Its use should thus be avoided or reduced. The aim of the present study was to evaluate the efficacy of a bark extract of Magnolia officinalis Rehder and Wilson to control three pathogens including Plasmopara viticola (Berk. & M.A. Curtis) Berl. & De Toni (causing grapevine downy mildew), Venturia inaequalis (Cooke) G. Winter (causing apple scab), and Phytophthora infestans (Mont.) De Bary (causing potato and tomato late blight) under controlled and field conditions, and to identify compounds responsible for the antifungal activity of the extract. Under controlled conditions, M. officinalis bark extract showed a mean efficacy of 97% (P. viticola) and 93% (V. inaequalis) at 1 mg mL−1, and EC50 between 0.14 and 0.20 mg mL−1. Efficacy against P. infestans was comparatively low (52% at 1 mg mL−1). Magnolol and honokiol were identified as the main active compounds, both with EC50 ≤ 0.08 mg mL−1 against P. viticola and V. inaequalis. Under field conditions, preliminary formulations reached efficacies up to 71% at 1–2 mg plant extract mL−1 against grapevine downy mildew, whereas activity against apple scab could not be confirmed. Magnolia officinalis is a promising candidate for the development of a sustainable plant protection product against grapevine downy mildew due to a combination of good efficacy, high availability of the raw material at affordable prices, reasonable extraction efficiency, and expected low human toxicity due to its longstanding use in traditional Chinese medicine.

Magnolol exerts anticancer activity in hepatocellular carcinoma cells through regulating endoplasmic reticulum stress-mediated apoptotic signaling.

IntroductionMagnolol (Mag), a biologically active compound isolated from the root and stem bark of Magnolia officinalis, has been reported to induce apoptosis in several cancer cell lines in vitro. In the present study, we aimed to determine the anticancer effects of Mag on hepatocellular carcinoma (HCC) cells.Materials and methodsThe HepG2 cells were treated with varying concentrations of Mag (10, 20, and 30 μM) for 48 hours. The effects of Mag on the proliferation, migration, invasion, apoptosis and cell cycle progression of HepG2 cells were respectively detected by MTT assay, transwell assays, and flow cytometric analysis. A HepG2 cell-based tumor-bearing model was established to evaluate the effect of Mag on HCC tumor growth in vivo. The protein expression levels were determined by Western blot analysis.ResultsOur results showed that Mag inhibited the proliferation, migration, and invasion of HepG2 cells in vitro in a dose-dependent manner. In addition, Mag reduced the HCC tumor volume and weight in the mouse xenograft model. Subsequent studies showed that Mag induced apoptosis in HepG2 cells, accompanied by a loss in mitochondrial membrane potential, cytochrome c release, and induction of endoplasmic reticulum stress. Furthermore, inhibition of the endoplasmic reticulum stress by CHOP knockdown restored the effects of Mag in HepG2 cells.ConclusionThe present study highlighted the possibility of using Mag as a novel therapeutic drug for HCC treatment.

Roles of the Hsp90-Calcineurin Pathway in the Antifungal Activity of Honokiol.

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.

Honokiol Alleviates Oxidative Stress-Induced Neurotoxicity via Activation of Nrf2.

Honokiol (Hon), a polyphenol and main active ingredient from the bark of Magnolia officinalis, has been documented as having multiple pharmacological functions, including neuroprotection. However, the mechanisms underlying its neuroprotective effects are not well-defined. In this study, we reported that Hon attenuates the H2O2- or 6-hydroxydopamine (6-OHDA)-induced apoptosis of PC12 cells by increasing the glutathione level and upregulating a multitude of cytoprotective proteins, including heme oxygenase 1, NAD(P)H:quinone oxidoreductase 1, thioredoxin 1, and thioredoxin reductase 1. Further studies reveal that Hon promotes transcription factor Nrf2 nuclear translocation and activation. Moreover, the cytoprotection of Hon was antagonized by silence of Nrf2 expression, highlighting the fact that Nrf2 is critically engaged in the cellular functions of Hon. Taken together, our study identified that Hon is an effective agonist of Nrf2 in the neuronal system and displays potent neuroprotection against oxidative stress-mediated PC12 cell damage. These findings indicate that Hon is promising for further development as a therapeutic drug against oxidative stress-related neurodegenerative disorders.

Modulation of Rat Hepatic CYP1A and 2C Activity by Honokiol and Magnolol: Differential Effects on Phenacetin and Diclofenac Pharmacokinetics In Vivo.

Honokiol (2-(4-hydroxy-3-prop-2-enyl-phenyl)-4-prop-2-enyl-phenol) and magnolol (4-Allyl-2-(5-allyl-2-hydroxy-phenyl)phenol) are the major active polyphenol constituents of Magnolia officinalis (Magnoliaceae) bark, which has been widely used in traditional Chinese medicine (Houpu Tang) for the treatment of various diseases, including anxiety, stress, gastrointestinal disorders, infection, and asthma. The aim of this study was to investigate the direct effects of honokiol and magnolol on hepatic CYP1A and 2C-mediated metabolism in vitro using rat liver microsomes and in vivo using the Sprague-Dawley rat model. Honokiol and magnolol inhibited in vitro CYP1A activity (probe substrate: phenacetin) more potently than CYP2C activity (probe substrate: diclofenac): The mean IC50 values of honokiol for the metabolism of phenacetin and diclofenac were 8.59 μM and 44.7 μM, while those of magnolol were 19.0 μM and 47.3 μM, respectively. Notably, the systemic exposure (AUC and Cmax) of phenacetin, but not of diclofenac, was markedly enhanced by the concurrent administration of intravenous honokiol or magnolol. The differential effects of the two phytochemicals on phenacetin and diclofenac in vivo pharmacokinetics could at least be partly attributed to their lower IC50 values for the inhibition of phenacetin metabolism than for diclofenac metabolism. In addition, the systemic exposure, CL, and Vss of honokiol and magnolol tended to be similar between the rat groups receiving phenacetin and diclofenac. These findings improve our understanding of CYP-mediated drug interactions with M. officinalis and its active constituents.

Growth-Promoting and Antioxidant Effects of Magnolia Bark Extract in Chickens Uninfected or Co-Infected with Clostridium perfringens and Eimeria maxima as an Experimental Model of Necrotic Enteritis

BackgroundMagnolia tree bark has been widely used in traditional Asian medicine. However, to our knowledge, no studies have been reported investigating the effects of dietary supplementation with magnolia bark extract in chickens. ObjectiveWe tested the hypothesis that dietary supplementation of chickens with a Magnolia officinalis bark extract would increase growth performance in uninfected and Eimeria maxima/Clostridium perfringens co-infected chickens. MethodsA total of 168 chickens were fed from hatch either a standard diet or a diet supplemented with 0.33 mg or 0.56 mg M. officinalis bark extract/kg (M/H low or M/H high, respectively) from days 1 to 35. At day 14, half of the chickens were orally infected with E. maxima, followed by C. perfringens infection at day 18 to induce experimental avian necrotic enteritis. Daily feed intake, feed conversion ratio, body weight gain, and final body weight were measured as indicators of growth performance. Serum α1-acid glycoprotein (AGP) concentrations were measured as an indicator of systemic inflammation, and intestinal lesion scores were determined as a marker of disease progression. Transcript levels for catalase, heme oxygenase 1, and superoxide dismutase in the intestine, liver, spleen, and skeletal muscle were measured as indicators of antioxidant status. ResultsGrowth performance increased between days 1 and 35 in uninfected and E. maxima/C. perfringens co-infected chickens fed M/H-low or M/H-high diets compared with unsupplemented controls. Gut lesion scores were decreased, whereas AGP concentrations were unchanged, in co-infected chickens fed magnolia-supplemented diets compared with unsupplemented controls. In general, transcripts for antioxidant enzymes increased in chickens fed magnolia-supplemented diets compared with unsupplemented controls, and significant interactions between dietary supplementation and co-infection were observed for all antioxidant enzyme transcript levels. ConclusionMagnolia bark extract might be useful for future development of dietary strategies to improve poultry health, disease resistance, and productivity without the use of antibiotic growth promoters.

RANKL-induced osteoclastogenesis is suppressed by 4-O-methylhonokiol in bone marrow-derived macrophages.

Magnolol, honokiol, and obovatol are well known bioactive constituents of the bark of Magnolia officinalis and have been reported to have beneficial effects in various diseases. We recently isolated a novel active compound, 4-O-methylhonokiol (4-O-MH) from the ethanol extract of M. officinalis, which was previously reported to have pharmacological effects including anti-inflammatory, anti-oxidative, and anti-aging activities. Here, we examined the pharmacological properties of 4-O-MH on osteoblast (bone-forming cells) and osteoclast (bone-resorbing cells) differentiation, and its underlying signaling pathways in primary cultured pre-osteoblasts and bone marrow macrophages. Our results showed that 4-O-MH did not affect cell viability in pre-osteoblasts and did not influence osteoblast differentiation and mineralized nodule formation, as assessed by alkaline phosphatase activity and Alizarin red staining. However, 4-O-MH significantly inhibited TRAP-positive multinuclear osteoclasts and F-actin ring formation during Receptor activator of NF-κB ligand (RANKL)-mediated osteoclastogenesis without cytotoxicity. In addition, 4-O-MH suppressed RANKL-induced critical factors (c-Fos, NF-ATc1, TRAP, and ITB3) for osteoclast differentiation and function. Furthermore, RANKL-mediated signaling, including ERK1/2, AKT, and NF-kB pathways was attenuated by 4-O-MH. Taken together, 4-O-MH has an inhibitory role in RANKL-mediated osteoclastogenesis but not osteoblast differentiation, and our findings also suggest that 4-O-MH is a potential therapeutic agent for bone-destructive diseases such as osteoporosis, alveolar bone resorption, and osteoarthritis.

Design, synthesis and antibacterial evaluation of honokiol derivatives

Staphylococcus aureus is a major and dangerous human pathogen that causes a range of clinical manifestations of varying severity, and is the most commonly isolated pathogen in the setting of skin and soft tissue infections, pneumonia, suppurative arthritis, endovascular infections, foreign-body associated infections, septicemia, osteomyelitis, and toxic shocksyndrome. Honokiol, a pharmacologically active natural compound derived from the bark of Magnolia officinalis, has antibacterial activity against Staphylococcus aureus which provides a great inspiration for the discovery of potential antibacterial agents. Herein, honokiol derivatives were designed, synthesized and evaluated for their antibacterial activity by determining the minimum inhibitory concentration (MIC) against S. aureus ATCC25923 and Escherichia coli ATCC25922 in vitro. 7c exhibited better antibacterial activity than other derivatives and honokiol. The structure-activity relationships indicated piperidine ring with amino group is helpful to improve antibacterial activity. Further more, 7c showed broad spectrum antibacterial efficiency against various bacterial strains including eleven gram-positive and seven gram-negative species. Time-kill kinetics against S. aureus ATCC25923 in vitro revealed that 7c displayed a concentration-dependent effect and more rapid bactericidal kinetics better than linezolid and vancomycin with the same concentration. Gram staining assays of S. aureus ATCC25923 suggested that 7c could destroy the cell walls of bacteria at 1×MIC and 4×MIC.

2-O-Methylmagnolol upregulates the long non-coding RNA, GAS5, and enhances apoptosis in skin cancer cells

Magnolol, a hydroxylated biphenol compound isolated from the bark of Magnolia officinalis, has been shown to exhibit anti-proliferative effect in various cancer cells, including skin cancer cells. Methoxylation of magnolol appears to improve its anti-inflammatory activity, yet the effect of this modification on the agent’s antitumor activity remains unknown. In this work, we report that 2-O-methylmagnolol (MM1) displays improved antitumor activity against skin cancer cells compared to magnolol both in vitro and in vivo. The increased antitumor activity of MM1 appears to correlate with its increased ability to induce apoptosis. DNA microarray and network pathway analyses suggest that MM1 affects certain key factors involved in regulating apoptosis and programmed cell death. Interestingly, the level of the long non-coding (lnc) RNA of growth arrest-specific 5 (GAS5) was increased in MM1-treated cells, and inhibition of lncRNA GAS5 inhibited MM1-induced apoptosis. Conversely, overexpression of lncRNA GAS5 inhibited cell proliferation and promoted cell apoptosis in skin cancer cells. The expression of lncRNA GAS5 in the skin cancer tissues was found to be lower than that in the adjacent normal tissues in a majority of patients. Taken together, our findings suggest that MM1 has improved antitumor activity in skin cancer cells, and that this is due, at least in part, to the upregulation of lncRNA GAS5 and the enhancement of apoptosis.