PMID: 

Artif Cells Nanomed Biotechnol. 2018 ;46(sup2):668-674. Epub 2018 Sep 5. PMID: 30183380

Abstract Title: 

Improved oral bioavailability of magnolol by using a binary mixed micelle system.

Abstract: 

The aim of this study was to prepare two novel magnolol (MO)-loaded binary mixed micelles (MO-M) using biocompatible copolymers of Soluplus (SOL) and SolutolHS15 (HS15), SOL and d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS), to improve magnolol's poor solubility and its oral bioavailability. The organic solvent evaporation method was used to obtain two MO-M by optimization; one was prepared by using SOL and HS15 (MO-H), and the other was prepared by using SOL and TPGS (MO-T). The entrapment efficiency (EE%) and drug loading (DL%) of MO-T were 94.61 ± 0.91% and 4.03 ± 0.19%, respectively, and the MO-H has higher EE% and DL% (98.37 ± 1.23%, 4.12 ± 0.16%). TEM results showed that the morphology of MO-M was homogeneous and was spherical in shape. The dilution stability of MO-M did not undergo significant changes. Permeabilityof MO-M across a Caco-2 cell monolayer was enhanced in Caco-2 cell transport models. The pharmacokinetics study showed that the relative oral bioavailability of MO-T and MO-H increased by 2.39- and 2.98-fold, respectively, compared to that of raw MO. This indicated that MO-H and MO-T could promote absorption of MO in the gastrointestinal tract. Collectively, the mixed micelles demonstrated greater efficacy as a drug delivery system. The development of these novel mixed micelles is valuable for resolving the poor solubility and bioavailability of drugs.

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PMID: 

Int Immunopharmacol. 2019 May ;70:117-124. Epub 2019 Feb 22. PMID: 30798160

Abstract Title: 

Magnolol prevents ossified tendinopathy by inhibiting PGE2-induced osteogenic differentiation of TDSCs.

Abstract: 

Magnolol is a compound that is extracted from magnolia, is used in Chinese medicine and is a type of lignan. Magnolol has various anti-inflammation, anti-proliferation and pro-autophagy effects. Ossified tendinopathy affects many athletes and people with repetitive tendon injuries. Ossified tendinopathy is a tremendous economic burden, and no effective and safe drugs are available to prevent the pathogenesis of ectopic ossification. In this study, we aimed to study how magnolol affects ossified tendinopathy by evaluating its effects on osteogenic differentiation of tendon-derived stem cells (TDSCs). Our data suggested that magnolol attenuated ectopic ossification in the Achilles tendon caused by Achilles tenotomy. Magnolol inhibited PGE2-induced ALP activity and prevented calcium deposits in TDSCs in vitro. Magnolol also exerted inhibitory effects on expression of osteogenic factors, such as Runx2, OCN, and BMP2 in vivo. Further investigation revealed the underlying mechanism by which magnolol prevents PGE2-induced ectopic ossification. Specifically, magnolol inhibits PGE2-induced PI3K/AKT/β-catenin pathway activation in TDSCs. Our findings demonstrated that magnolol inhibited ossified tendinopathy through preventing osteogenic differentiation of TDSCs via downregulation PGE2-induced PI3K/AKT/β-catenin pathways.

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PMID: 

Brain Res Bull. 2019 Jul ;149:156-167. Epub 2019 Apr 9. PMID: 30978383

Abstract Title: 

Magnolia officinalis reduces the long-term effects of the status epilepticus induced by kainic acid in immature rats.

Abstract: 

During critical periods of neurodevelopment, the immature brain is susceptible to neuronal hyperexcitability, alterations such as hyperthermia, hypoxia, brain trauma or a preexisting neuroinflammatory condition can trigger, promote and prolong epileptiform activity and facilitate the development of epilepsy. The goal of the present study was to evaluate the long-term neuroprotective effects Magnolia officinalis extract, on a model of recurrent status epilepticus (SE) in immature rats. Sprague-Dawley rats were treated with kainic acid (KA) (3 mg/kg, dissolved in saline solution) beginning at day 10 P N every 24 h for five days (10 P N-14PN). Two experimental groups (KA) received two treatments for 10 days (14-24 P N): one group was treated with 300 mg/kg Magnolia Officinalis (MO) (KA-MO), and another was treated with 20 mg/kg of celecoxib (Clbx) (KA-Clbx) as a control drug. A SHAM control group at day 90 P N was established. Seizure susceptibility was analyzed through an after-discharge threshold (ADT) evaluation, and electroencephalographic activity was recorded. The results obtained from the ADT evaluation and the analysis of the electroencephalographic activity under basal conditions showed that the MO and Clbx treatments protected against epileptiform activity, and decreases long-term excitability. All rats in the KA-MO and KA-Clbx groups presented a phase I seizure on the Racine scale, corresponding to the shaking of a wet dog. In contrast, the KA group showed phase V convulsive activity on the Racine scale. Similarly, MO and Clbx exerted neuroprotective effects on hippocampal neurons and reduced gliosis in the same areas. Based on these results, early intervention with MO and Clbx treatments to prevent the inflammatory activity derived from SE in early phases of neurodevelopment exerts neuroprotective effects on epileptogenesis in adult stages.

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PMID: 

Front Pharmacol. 2019 ;10:393. Epub 2019 Apr 16. PMID: 31040782

Abstract Title: 

The Protective Effect of Magnolol in Osteoarthritis:andStudies.

Abstract: 

Osteoarthritis (OA), defined as a long-term progressive joint disease, is characterized by cartilage impairment and erosion. In recent decades, magnolol, as a type of lignin extracted from, has been proved to play a potent anti-inflammatory role in various diseases. The current research sought to examine the latent mechanism of magnolol and its protective role in alleviating the progress of OAas well asexperimentations., the over-production of Nitric oxide (NO), prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6), induced by interleukin-1 beta (IL-1β), were all inhibited notably by magnolol in a concentration-dependent manner. Moreover, magnolol could also downregulate the expression of metalloproteinase 13 (MMP13) and thrombospondin motifs 5 (ADAMTS5). All these changes ultimately led to the deterioration of the extracellular matrix (ECM) induced by IL-1β. Mechanistically, magnolol suppressed the activation of PI3K/Akt/NF-κB pathway. Furthermore, a powerful binding capacity between magnolol and PI3K was also revealed in our molecular docking research. In addition, magnolol-induced protective effects in OA development were also detected in a mouse model. In summary, this research suggested that magnolol possessed a new therapeutic potential for the development of OA.

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PMID: 

J Cell Biochem. 2019 Jun 3. Epub 2019 Jun 3. PMID: 31155771

Abstract Title: 

Magnolol induces apoptosis in osteosarcoma cells via G0/G1 phase arrest and p53-mediated mitochondrial pathway.

Abstract: 

Osteosarcoma is a highly invasive primary malignancy of bone. Magnolol is biologically active, which shows antitumor effects in a variety of cancer cell lines. However, it has not been elucidated magnolol's effects on human osteosarcoma cells (HOC). This study aimed to determine antitumor activity of magnolol and illustrate the molecular mechanism in HOC. Magnolol showed significant inhibition effect of growth on MG-63 and 143B cells and induced apoptosis and cell cycle arrest at G0/G1. In osteosarcoma cells, magnolol upregulated expressions of proapoptosis proteins and suppressed expressions of antiapoptosis proteins. Additionally, under the pretreatment of pifithrin-a (PFT-a, a p53 inhibitor), the magnolol-induced apoptosis was significantly reversed. The results above indicated that magnolol induces apoptosis in osteosarcoma cells may via G0/G1 phase arrest and p53-mediated mitochondrial pathway.

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PMID: 

Molecules. 2019 Jun 6 ;24(11). Epub 2019 Jun 6. PMID: 31174300

Abstract Title: 

Antifungal Effect of Magnolol and Honokiol fromonCausing Tobacco Brown Spot.

Abstract: 

In this study, two phenol compounds, magnolol and honokiol, were extracted fromand identified by LC-MS,H- andC-NMR. The magnolol and honokiol were shown to be effective against seven pathogenic fungi, including(Fr.) Keissl,(Link) Thom,f.sp. solani,J. Sheld,Schltdl.,Miyabe&G. Yamada, andJ.G. Kühn, with growth inhibition of more than 57%. We also investigated the mechanisms underlying the potential antifungal activity of magnolol and honokiol. The results showed that they inhibited the growth ofin a dose-dependent manner. Moreover, magnolol and honokiol treatment resulted in distorted mycelia and increased the cell membrane permeability of, as determined by conductivity measurements. These results suggest that magnolol and honokiol are potential antifungal agents for application against plant fungal diseases.

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PMID: 

Biomed Res Int. 2019 ;2019:1847130. Epub 2019 May 23. PMID: 31240205

Abstract Title: 

Insights on the Multifunctional Activities of Magnolol.

Abstract: 

Over years, various biological constituents are isolated from Traditional Chinese Medicine and confirmed to show multifunctional activities. Magnolol, a hydroxylated biphenyl natural compound isolated from, has been extensively documented and shows a range of biological activities. Many signaling pathways include, but are not limited to, NF-B/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.

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PMID: 

Korean J Physiol Pharmacol. 2019 Jul ;23(4):251-261. Epub 2019 Jun 25. PMID: 31297009

Abstract Title: 

Magnolol exerts anti-asthmatic effects by regulating Janus kinase-signal transduction and activation of transcription and Notch signaling pathways and modulating Th1/Th2/Th17 cytokines in ovalbumin-sensitized asthmatic mice.

Abstract: 

Allergic asthma, is a common chronic inflammatory disease of the airway presenting with airway hyperresponsiveness and airway remodelling. T helper cells-derived cytokines are critically associated with asthma pathogenesis. Janus kinase-signal transduction and activation of transcription (JAK/STAT) signaling is found to be involved in asthma. Magnolol is a plant-derived bioactive compound with several pharmacological effects. The study aimed to assess the effects of magnolol in ovalbumin (OVA)-induced asthmatic model. BALB/c mice were sensitized and challenged with OVA. Magnolol (12.5, 25, or 50 mg/kg body weight) was administered to separate groups of animals. Dexamethasone was used as the positive control. Cellular infiltration into the bronchoalveolar lavage fluid (BALF) were reduced on magnolol treatment. The levels of Th2 and Th17 cytokines were reduced with noticeably raised levels of interferon gamma. Lung function was improved effectively along with restoration of bronchial tissue architecture. OVA-specific immunoglobulin E levels in serum and BALF were decreased by magnolol. Magnolol reduced Th17 cell population and effectively modulated the JAK-STAT and Notch 1 signaling. The results suggest the promising use of magnolol in therapy for allergic asthma.

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PMID: 

Wound Repair Regen. 2019 May 30. Epub 2019 May 30. PMID: 31145533

Abstract Title: 

A systematic review of Calendula officinalis extract for wound healing.

Abstract: 

Use of complementary and alternative medicine for wound healing is influencing mainstream medical practice. This systematic review evaluates the role of Calendula officinalis flower extract as monotherapy compared to control for wound healing in vivo. Searches were conducted in PubMed, EMBASE, Cochrane Central Register of Controlled Trials, CINAHL, and Scopus (up to April 2018) with 14 studies meeting the inclusion criteria, comprising 7 animal experiments and 7 clinical trials. Findings from the review on acute wound healing showed faster resolution of the inflammation phase with increased production of granulation tissue in the test groups treated with extract. These findings were consistent in five animal studies and one randomized clinical trial. Chronic wound healing studies were varied. Two clinical control studies on venous ulcers demonstrated decreased ulcer surface area compared to controls. Another randomized clinical trial demonstrated no improvement for the calendula group in diabetic leg ulcer healing. Burn healing similarly showed mixed results. Two animal studies demonstrated a prophylactic effect for the administration of calendula extract prior to burn injury. A randomized clinical trial of patients suffering from partial to full thickness burns demonstrated no benefit for topical application of calendula extract compared to controls. Two randomized clinical trials assessed the potential for extract to prevent acute post radiation dermatitis, with one study showing improvements compared to trolamine, while the other found no improvement compared to aqua gel cream. Animal studies provide moderate evidence for improved recovery from the inflammation phase and increased production of granulation tissue in calendula extract treatment groups. This review identified some evidence for the beneficial effects of C. officinalis extract for wound healing, consistent with its role in traditional medicine. There is a need for larger, well-designed randomized control trials to assess the effect of calendula on wound healing including complications.

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PMID: 

Chem Biol Interact. 2019 Jul 16 ;310:108757. Epub 2019 Jul 16. PMID: 31323226

Abstract Title: 

Characterizing fucoxanthin as a selective dopamine D/Dreceptor agonist: Relevance to Parkinson's disease.

Abstract: 

Fucoxanthin and fucosterol are archetypal lipid components of edible brown algae that provide several health benefits. Lately, their protective role in Aβ-induced cognitive dysfunction in animal models has been reported (Alghazwi et al., 2019; Oh et al., 2018). However, their role in the aminergic system and as a prime treatment approach for multifactorial neurodegenerative diseases still requires exploration. The main aims of the present study are to characterize the role of fucoxanthin and fucosterol in the aminergic pathway via in vitro human monoamine oxidase (hMAO) inhibition and cell-based functional G-protein coupled receptor (GPCR) assays and to underline their possible mechanisms of action via in silico molecular docking studies. Fucoxanthin displayed weak inhibition with ICvalues of 197.41 ± 2.20 and 211.12 ± 1.17 μM over two isoenzymes hMAO-A and hMAO-B, respectively. Fucosterol remained inactive up to 500 μM. In functional assay results, fucoxanthin showed a concentration-dependent agonist effect on dopamine Dand Dreceptors. The half maximal effective concentration (EC) of fucoxanthin for dopamine Dand Dreceptors was 16.87 ± 3.41 and 81.87 ± 6.11 μM, respectively. For dopamine as a reference agonist, the ECvalues for these two receptors were 3.7 and 24 nM, respectively. Fucosterol showed no agonist activity on any of the tested receptors. Similarly, fucoxanthin showed a mild antagonist effect on dopamine Dand tachykinin (NK) receptor with inhibition of control agonist response by approximately 40% at 100 μM. Fucosterol displayed mild antagonist effects only on dopamine Dand Dreceptors. In silico studies revealed potential mechanisms by which fucoxanthin binds to dopamine receptors to exert its agonist effects, including low binding energy and H-bond interactions with Ser196 and Thr115 at the Dreceptor and with Ser196 and Asp115 at the Dreceptor. Our results collectively suggest that fucoxanthin is a potential D/Dagonist for the management of neurodegenerative diseases, such as Parkinson's disease.

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