Magnolin

Magnolin inhibits IgE/Ag-induced allergy in vivo and in vitro

Mast cells (MCs) play critical roles in allergic reactions and modulating the activation of MCs could be an effective strategy to treat allergic diseases, which cause a rapidly increasing threat to the public health. Herein, we described that Magnolin, a major component from Flos magnoliae could inhibit IgE-dependent MCs activation. We found Magnolin inhibited IgE/Ag-induced calcium mobilization, degranulation, and cytokines release in LAD2 cells. Magnolin was also found to attenuate IgE/Ag-induced mice paw swelling in a dose-dependent manner. Further mechanistic studies suggested a possible anti-allergic and anti-inflammatory effects of Magnolin in IgE/Ag-induced anaphylactic reactions. Thereby, Magnolin could be a potential therapeutic agent for preventing mast cell-related immediate and delayed allergic diseases.

Magnolin exhibits anti-inflammatory effects on chondrocytes via the NF-κB pathway for attenuating anterior cruciate ligament transection-induced osteoarthritis

Purpose: This study aimed to investigate whether magnolin (MGL) possesses the capability of suppressing inflammatory responses that can in turn alleviate osteoarthritis (OA).Methods: We investigated the effects of MGL on the viability of rat chondrocytes at concentrations of 5 to 100 ?M, and selected 10 ?M for further study. We elucidated the molecular mechanisms and signaling pathways mediating these effects via RNA sequencing, qRT-PCR, immunofluorescent staining, and Western blotting techniques. Following this, we established an anterior cruciate ligament (ACL) transection-induced OA rat model, and injected MGL into the knee articular cavities to verify the in vivo anti-inflammatory effects of MGL.Results: We found that MGL could recover the TNF-α-induced upregulation of IL-1β, COX2, ADAMTS-5, and MMP-1/3/13 at the gene/protein level, as well as the downregulation of cartilaginous ECM synthesis. Gene expression profiles of different groups identified 49 common differentially expressed genes (DEGs), which were mainly enriched in the structural constituents of the ribosome, the extracellular space, and inflammatory response. The NF-κB pathway was highly enriched, and the expression levels of DEGs associated with it (Nfkbia, Ptgs2, Rela, Tnfrsf1a, Tradd, Traf2) under TNF-α stimulation were reversed by MGL. Further studies proved that MGL simultaneously suppressed the cell nucleus translocation of p65 and the phosphorylation of IκBα. Moreover, in vivo, MGL suppressed cartilage matrix degradation, inhibited MMP-13 expression, and promoted cartilage matrix construction by upregulating SOX9 synthesis.Conclusion: MGL demonstrated significant anti-inflammatory bioactivity on chondrocytes by suppressing the activation of NF-κB pathway, which in turn exhibited a significant alleviation of OA.

(+)-Magnolin Enhances Melanogenesis in Melanoma Cells and Three-Dimensional Human Skin Equivalent; Involvement of PKA and p38 MAPK Signaling Pathways

Magnoliae Flos is a traditional herbal medicine used to treat nasal congestion associated with headache, empyema, and allergic rhinitis. In our preliminary screening of crude drugs used in Japanese Kampo formulas for melanin synthesis, the methanol extract of Magnoliae Flos was found to exhibit strong melanin synthesis activity. However, there have been no studies evaluating the effects of Magnoliae Flos or its constituents on melanogenesis. The present study aimed to isolate the active compounds from Magnoliae Flos that activate melanin synthesis in melanoma cells and three-dimensional human skin equivalent, and to investigate the molecular mechanism underlying melanin induction. The methanol extract of Magnoliae Flos induced an increase of melanin content in both B16-F1 and HMV-II cells. A comparison of melanin induction by three fractions prepared from the extract showed that the ethyl acetate fraction markedly induced melanin synthesis. Bioassay-guided separation of the ethyl acetate fraction resulted in the isolation of seven lignans (1: - 7: ). Among them, (+)-magnolin (5: ) strongly induced melanin synthesis and intracellular tyrosinase activity. Furthermore, the ethyl acetate fraction and 5: clearly induced melanin content in a three-dimensional human skin equivalent. Molecular analysis revealed that 5: triggered the protein expression of tyrosinase, tyrosinase-related protein-1, and tyrosinase-related protein-2. Further analysis of transcriptional factors and signaling pathways demonstrated that 5: induces the protein expression of tyrosinase, tyrosinase-related protein-1, and tyrosinase-related protein-2 activated by the protein kinase A- and p38 mitogen-activated protein kinase-dependent pathways, leading to cAMP-responsive element-binding protein phosphorylation and microphthalmia-associated transcription factor expression. These findings demonstrate the potential of 5: as a potent therapeutic agent for hypopigmentation.

Magnolin promotes autophagy and cell cycle arrest via blocking LIF/Stat3/Mcl-1 axis in human colorectal cancers

Magnolin is a multi-bioactive natural compound that possesses underlying anti-cancer properties. However, the mechanisms underlying remain to be elucidated. Here, we report the role of magnolin in suppressing human colorectal cancer (CRC) cells via activating autophagy and cell cycle arrest in vitro and in vivo. Pre-treatment of cells with specific autophagy inhibitor (3-methyladenine) or knockdown of endogenous LC-3B by siRNA significantly abrogates magnolin-induced cell cycle arrest. Molecular validation mechanistically shows that magnolin-induced autophagy and cell cycle arrest in CRC cells is correlated with decreased transcriptional levels of leukemia inhibitory factor (LIF), and we further find that inhibition of LIF decreases phosphorylation level of Stat3 and represses transcriptional expression of Mcl-1. Furthermore, magnolin-induced autophagy and cell cycle arrest suppress the growth of xenograft colorectal tumors without apparent toxicity. Finally, we evaluate the clinical correlation of LIF/Stat3/Mcl-1 in CRC patient tissues. As expected, LIF, p-Stat3, and Mcl-1 levels are high in CRC tissue but are scarcely found in normal colon tissue. High positive expressions of LIF or Mcl-1 are associated with poor prognosis. Doubly positive cases have shown the worst outcome. Taken together, our results have clarified a novel molecular mechanism whereby magnolin induces autophagy and cell cycle arrest through LIF/Stat3/Mcl-1 pathway in CRCs. Our results also have revealed that magnolin has a promising therapeutic potential in CRCs.

Magnolin inhibits prostate cancer cell growth in vitro and in vivo

Background: Magnolin is the most active ingredient in the herb Magnolia fargesii, which has been traditionally used in oriental medicine to treat headaches and nasal congestion. Recent researches demonstrate that Magnolin inhibits cancer cell migration and invasion.
Materials and methods: This study used cell culture and the BALB/c nu/nu mouse xenograft model to investigate whether or not magnolin can inhibit the growth of PC3 and Du145 prostate cancer cells. MTT assay and flow cytometry were performed to estimate the proliferation, cycle, and apoptosis of the cells in vitro. Clone formation assay was also conducted. In the animal study, Ki-67 immunostaining and TUNEL assay were carried out to evaluate cell proliferation and apoptosis, respectively. To elucidate the possible mechanism by which magnolin attenuates prostate cancer cell growth, we estimated the expression levels of Akt/p-Akt, P53, P21, BCL-2, and cleaved Caspase3 by using Western blot 48h after magnolin-treatment of the cells.
Results: Magnolin inhibited the proliferation and viability of the tumor cells by triggering cell cycle arrest via P53/P21 activation and inducing apoptosis in vitro and in vivo. Magnolin downregulated the phosphorylation of Akt protein kinase and upregulated cleaved Caspase3 during anti-proliferation and pro-apoptosis.
Conclusion: Magnolin may be a novel medicine for prostate cancer therapy.