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In the present study, we investigated the protective effect of magnolin (MAG) against oxidative stress induced by cyclophosphamide (CP) and its role in the Nrf2/HO-1 signaling pathway. Rats were administered MAG (1 mg/kg, i.p.) for 14 days and CP (75 mg/kg, i.p.) on the 14th day. CP administration increased tissue damage, as evidenced by elevated levels of transaminases (aspartate and alanine), alkaline phosphatase, and renal parameters (blood urea nitrogen and creatinine). Additionally, 8-hydroxy-2′-deoxyguanosine and malondialdehyde levels were increased, whereas glutathione levels, along with catalase and superoxide dismutase activities, decreased in CP-treated rats. CP also down-regulated the expression of Bcl-2, HO-1, Nrf2, and NQO-1 , while up-regulating Bax, Cas-3, TNF- α , Cox-2, iNOS, IL-6, IL-1β, and NFκB in liver and kidney tissues. In addition, CP treatment caused histopathological changes in heart, lung, liver, kidney, brain, and testis tissues. Treatment with MAG improved biochemical and oxidative stress parameters and prevented histopathological changes in CP-treated rats. Moreover, MAG suppressed the expression of inflammatory cytokines and apoptosis markers. In conclusion, MAG effectively prevented CP-induced toxicity by reducing oxidative stress, inflammation, and apoptosis, with its protective efficacy associated with the up-regulation of Nrf2/HO-1 signaling. [ABSTRACT FROM AUTHOR]

Abstract Inflammatory bowel disease (IBD) is a chronic and incurable disorder associated with higher cancer risk and currently faces unsatisfactory treatment outcomes. Ferroptotic cells secrete damage‐associated molecular patterns (DAMPs) that recruit and activate immune cells, particularly macrophages. Magnolin has excellent antioxidant and anti‐inflammatory properties, but its effect on IBD has not yet been clearly understood. This study aimed to investigate the therapeutic effects and mechanism of magnolin in IBD. For this purpose, in vivo and in vitro colitis models were established using dextran sulfate sodium (DSS), followed by optimization of magnolin concentration 2.5 μg/mL in vitro and 5 mg/kg in vivo. Bioinformatics analysis identified potential magnolin target sites and evaluated ferroptosis‐associated gene expressions. Body weight, food intake, disease activity index (DAI), pathological changes, and inflammation levels were assessed. The effect of magnolin on ferroptosis and macrophages was evaluated using quantitative real time‐polymerase chain reaction (qRT‐PCR), immunofluorescent staining, flow cytometry, enzyme‐linked immunosorbent assay (ELISA), and western blotting. Results indicated that magnolin at a lower dose (5 mg/kg) alleviated DSS‐induced colitis symptoms and reduced inflammation in mice. The bioinformatics analysis showed arachidonate 5‐lipoxygenase (ALOX5) as a potential magnolin target. Furthermore, magnolin inhibited the expression of ALOX5 with no effect on GPX4. Moreover, magnolin regulated macrophage differentiation into the M2 phenotype and suppressed pro‐inflammatory factors, that is, interleukin‐6 and tumor necrosis factor‐α (IL‐6 and TNFα). These results suggested that magnolin possesses significant therapeutic potential in treating IBD by suppressing ALOX5‐mediated ferroptosis, inhibiting M1 while promoting M2 macrophages, which is envisaged to provide novel strategies for treating IBD.

Inflammatory bowel disease (IBD) is a chronic and incurable disorder associated with higher cancer risk and currently faces unsatisfactory treatment outcomes. Ferroptotic cells secrete damage‐associated molecular patterns (DAMPs) that recruit and activate immune cells, particularly macrophages. Magnolin has excellent antioxidant and anti‐inflammatory properties, but its effect on IBD has not yet been clearly understood. This study aimed to investigate the therapeutic effects and mechanism of magnolin in IBD. For this purpose, in vivo and in vitro colitis models were established using dextran sulfate sodium (DSS), followed by optimization of magnolin concentration 2.5 μg/mL in vitro and 5 mg/kg in vivo. Bioinformatics analysis identified potential magnolin target sites and evaluated ferroptosis‐associated gene expressions. Body weight, food intake, disease activity index (DAI), pathological changes, and inflammation levels were assessed. The effect of magnolin on ferroptosis and macrophages was evaluated using quantitative real time‐polymerase chain reaction (qRT‐PCR), immunofluorescent staining, flow cytometry, enzyme‐linked immunosorbent assay (ELISA), and western blotting. Results indicated that magnolin at a lower dose (5 mg/kg) alleviated DSS‐induced colitis symptoms and reduced inflammation in mice. The bioinformatics analysis showed arachidonate 5‐lipoxygenase (ALOX5) as a potential magnolin target. Furthermore, magnolin inhibited the expression of ALOX5 with no effect on GPX4. Moreover, magnolin regulated macrophage differentiation into the M2 phenotype and suppressed pro‐inflammatory factors, that is, interleukin‐6 and tumor necrosis factor‐α (IL‐6 and TNFα). These results suggested that magnolin possesses significant therapeutic potential in treating IBD by suppressing ALOX5‐mediated ferroptosis, inhibiting M1 while promoting M2 macrophages, which is envisaged to provide novel strategies for treating IBD. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of anti-cancer drugs. The main symptoms often include sensory disturbances and neuropathic pain, and currently there is no effective treatment for this condition. This study aimed to investigate the suppressive effects of magnolin, an extracellular signal-regulated kinase (ERK) inhibitor substance derived from a 95% EtOH extract of the seeds of Magnolia denudata, on the symptoms of CIPN. A taxol-based anti-cancer drug paclitaxel (PTX) was repeatedly injected (2 mg/kg/day, total 8 mg/kg) into mice to induce CIPN. A neuropathic pain symptom was assessed using a cold allodynia test that scores behaviors of licking and shaking paw after plantar administration of acetone drop. Magnolin was administered intraperitoneally (0.1, 1, or 10 mg/kg) and behavioral changes to acetone drop were measured. The effect of magnolin administration on ERK expression in the dorsal root ganglion (DRG) was investigated using western blot analysis. The results showed that the repeated injections of PTX induced cold allodynia in mice. Magnolin administration exerted an analgesic effect on the PTX-induced cold allodynia and inhibited the ERK phosphorylation in the DRG. These results suggest that magnolin could be developed as an alternative treatment to suppress paclitaxel-induced neuropathic pain symptoms. [ABSTRACT FROM AUTHOR]

Magnolin is a naturally occurring, multi-bioactive lignan molecule with inherent anticancer effects. This study aims to summarize the botanical origins and anticancer properties of magnolin. For this, a recent (as of March 2023) literature review was conducted using various academic search engines, including PubMed, Springer Link, Wiley Online, Web of Science, Science Direct, and Google Scholar. All the currently available information about this phytochemical and its role in various cancer types has been gathered and investigated. Magnolin is a compound found in many different plants. It has been demonstrated to have anticancer activity in numerous experimental models by inhibiting the cell cycle (G1 and G2/M phase); inducing apoptosis; and causing antiinvasion, antimetastasis, and antiproliferative effects via the modulation of several pathways. In conclusion, magnolin showed robust anticancer activity against many cancer cell lines by altering several cancer signaling pathways in various non- and pre-clinical experimental models, making it a promising plant-derived chemotherapeutic option for further clinical research. [ABSTRACT FROM AUTHOR]

Periodontitis, a disease caused by inflammation of oral bacteria, contributes to the loss of alveolar bone and destruction of connective tissues. Porphyromonas gingivalis, a Gram-negative bacterium, is known to possess important pathogenic factors for periodontal disease. In this study, we investigated the anti-periodontitis effects of Magnolia kobus extract (MKE) and magnolin as a component of Magnolia kobus (MK) in murine macrophage RAW 264.7 cells stimulated with Porphyromonas gingivalis lipopolysaccharide (LPS). Effects of MKE and magnolin on the mechanism of RAW 264.7 cellular inflammation were determined by analyzing nitric oxide (NO) production and Western blot protein expression (n = 3). MKE/magnolin inhibited NO production without affecting cell survival. MKE/magnolin treatment inhibited LPS-induced pro-inflammatory cytokines, expression levels of matrix metalloproteinases (MMPs such as MMP-1, 3, 8, 9, and 13), and protein levels of inflammatory mediators (such as TNF-α, IL-1β, and mPGES-1). MKE/magnolin also suppressed NF-κB activation by inhibiting the TLR4 signaling pathway. These findings suggest that MKE has a therapeutic effect on inflammatory periodontal disease caused by oral bacterium P. gingivalis and that magnolin is a major functional component in the anti-inflammatory effect of MKE.

Backgrounds: Lignan is ubiquitous within the plant kingdom and present in almost all plants, including Magnolia fargesii Cheng. and Magnolia fargesii. Lignan has been used for the treatment of human health complications, including allergic rhinitis. Magnolin is a lignan class phytochemical abundantly present in Magnolia spp. and has been widely used as an oriental medicine to treat human disorders. Magnolin is an active furofuranoid lignans found to be present in the Magnolia biondii which exhibit anti-inflammatory, anti-cancer, anti-oxidant, and vasodilatory effect in medicine. Methods: The overview of the present work is to analyze the scientific information of magnolin, in order to provide a comprehensive insight into the preventive and therapeutic potential of magnolin in medicine. Scopus, PubMed, Science Direct and Google Scholar databases have been searched to collect all the scientific information of magnolin using the term herbal medicine, lignan, magnolin, and phytochemical. Analytical data of magnolin has also been collected and analyzed in the present work. Results: Scientific data analysis revealed the biological importance and therapeutic potential of magnolin in medicine. Scientific data of present work revealed the therapeutic effectiveness of magnolin in medicine for the treatment of prostate cancer, ovarian cancer, lung cancer, breast cancer, hepatocellular carcinoma, colorectal cancers, inflammation, melanogenesis, nephropathy and allergic diseases. Further, its antiplasmodial activity and effect on histamine release and human liver enzymes has also been discussed in the present work. Analytical data of magnolin signified their importance in both qualitative and quantitative tools of magnolin. Conclusion: Present work summarized the medicinal importance and therapeutic potential of magnolin for the treatment of human disorders as preventive and therapeutic measures.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of anti-cancer drugs. The main symptoms often include sensory disturbances and neuropathic pain, and currently there is no effective treatment for this condition. This study aimed to investigate the suppressive effects of magnolin, an extracellular signal-regulated kinase (ERK) inhibitor substance derived from a 95% EtOH extract of the seeds of Magnolia denudata, on the symptoms of CIPN. A taxol-based anti-cancer drug paclitaxel (PTX) was repeatedly injected (2 mg/kg/day, total 8 mg/kg) into mice to induce CIPN. A neuropathic pain symptom was assessed using a cold allodynia test that scores behaviors of licking and shaking paw after plantar administration of acetone drop. Magnolin was administered intraperitoneally (0.1, 1, or 10 mg/kg) and behavioral changes to acetone drop were measured. The effect of magnolin administration on ERK expression in the dorsal root ganglion (DRG) was investigated using western blot analysis. The results showed that the repeated injections of PTX induced cold allodynia in mice. Magnolin administration exerted an analgesic effect on the PTX-induced cold allodynia and inhibited the ERK phosphorylation in the DRG. These results suggest that magnolin could be developed as an alternative treatment to suppress paclitaxel-induced neuropathic pain symptoms.

• MGL significantly ameliorated CD-like colitis. • MGL protected the intestinal barrier through inhibiting IEC apoptosis. • The effect of MGL might be partly mediated via suppressing PI3K/AKT signalling pathway in IECs. Previous reports have shown that preventing excessive intestinal epithelial cell (IEC) apoptosis is a crucial approach for protecting the intestinal barrier in patients with Crohn's disease (CD). Magnolin (MGL) has various biological activities, including antiapoptotic activities, but its role in CD has largely not been determined. This study investigated how MGL impacts CD-like colitis and the underlying mechanism involved. Mice were treated with TNBS to establish a disease model, and these mice were used to assess the therapeutic effects of MGL on CD-like colitis. TNF-α-treated colon organoids were used to evaluate the impact of MGL on intestinal barrier function and IEC apoptosis. Enrichment analysis was performed to examine the potential pathways through which MGL inhibits IEC apoptosis. Finally, rescue experiments showed the mechanism by which MGL suppresses IEC apoptosis. The animal experiments demonstrated that MGL treatment alleviated the weight loss, colon shortening, elevated disease activity index (DAI) scores, increased colitis histological scores and upregulated inflammatory factor expression that were observed in model mice. MGL ameliorated intestinal barrier dysfunction and the loss of tight junction (TJ) proteins (ZO-1 and Claudin-1) by inhibiting IEC apoptosis in both TNBS-treated mice and TNF-α-treated colon organoids. MGL inhibited the PI3K/AKT signalling pathway, thus safeguarding the intestinal barrier and alleviating CD-like colitis in vivo and in vitro. MGL improves the intestinal barrier integrity and prevents CD-like colitis by inhibiting IEC apoptosis. The potential mechanism of its anti-apoptotic impact on IECs could be associated with the PI3K/AKT pathway, presenting novel approaches and avenues for the clinical management of CD. [ABSTRACT FROM AUTHOR]

Magnolin is a naturally occurring, multi-bioactive lignan molecule with inherent anticancer effects. This study aims to summarize the botanical origins and anticancer properties of magnolin. For this, a recent (as of March 2023) literature review was conducted using various academic search engines, including PubMed, Springer Link, Wiley Online, Web of Science, Science Direct, and Google Scholar. All the currently available information about this phytochemical and its role in various cancer types has been gathered and investigated. Magnolin is a compound found in many different plants. It has been demonstrated to have anticancer activity in numerous experimental models by inhibiting the cell cycle (G1 and G2/M phase); inducing apoptosis; and causing antiinvasion, antimetastasis, and antiproliferative effects via the modulation of several pathways. In conclusion, magnolin showed robust anticancer activity against many cancer cell lines by altering several cancer signaling pathways in various non- and pre-clinical experimental models, making it a promising plant-derived chemotherapeutic option for further clinical research.

Objective To establish a HPLC fingerprints of Biyuanjing capsules. Methods The column was Agilent SB-C18( 4.6mm×250 mm, 5 μm). The mobile phase was acetonitrile-water with gradient elution at a flow rate of 1.0 ml/min. The detection wavelength was 210 nm. The detection time was 80 min. Results The HPLC fingerprints of Biyuanjing capsules were established. Twenty common peaks were confirmed, of which, 15 peaks were belonging to each crude drug and 5 peaks were identified as chemical components. The overall similarity of the fingerprints of 10 batches of samples was above 90% comparing with the control. Conclusion　This method can be used for the quality control of Biyuanjing capsules. [ABSTRACT FROM AUTHOR]

Magnolin (MGL), a compound derived from the magnolia plant, has inhibitory effects on tumor cell invasion and growth. His study aims to explore the antitumor effect and underlying molecular mechanism of MGL against human cervical cancer. We found that MGL inhibited the proliferation, migration, and invasiveness of cervical cancer cells in vitro and in vivo. The underlying mechanism was shown to involve MGL-induced inhibition of JNK/Sp1-mediated MMP15 transcription and translation. Overexpression of JNK/Sp1 resulted in significant restoration of MMP15 expression and the migration and invasion capabilities of MGL-treated cervical cancer cells. MGL modulated the cervical cancer microenvironment by inhibiting cell metastasis via targeting IL-10/IL-10 receptor B (IL-10RB) expression, thereby attenuating JNK/Sp1-mediated MMP15 expression. Analysis of the gut microbiota of mice fed MGL revealed a significant augmentation in Lachnospiraceae bacteria, known for their production of sodium butyrate. In vivo experiments also demonstrated synergistic inhibition of cervical cancer cell metastasis by MGL and sodium butyrate co-administration. Our study provides pioneering evidence of a novel mechanism by which MGL inhibits tumor growth and metastasis through the IL-10/IL-10RB targeting of the JNK/Sp1/MMP15 axis in human cervical cancer cells. • MGL effectively inhibited the proliferation and metastasis of cervical cancer cells in vitro and in vivo. • MGL decreased the cervical cancer cell metastasis via modulating JNK/Sp1/MMP15 expression. • MGL affects the tumor microenvironment by targeting IL10-RB/p-JNK/Sp1/MMP15 expression-regulated cervical metastasis. • MGL-mediated inhibition of cervical cancer metastasis is associated with alterations in gut microbiota distribution in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Eudesmin, fargesin, epimagnolin A, magnolin, and yangambin are tetrahydrofurofuranoid lignans with various pharmacological activities found in Magnoliae Flos. The inhibition potencies of eudesmin, fargesin, epimagnolin A, magnolin, and yangambin on six major human uridine 5′-diphospho-glucuronosyltransferase (UGT) activities in human liver microsomes were evaluated using liquid chromatography–tandem mass spectrometry and cocktail substrates. Eudesmin, fargesin, epimagnolin A, magnolin, and yangambin inhibited UGT1A1 and UGT1A3 activities, but showed negligible inhibition of UGT1A4, UGT16, UGT1A9, and UGT2B7 activities at 200 μM in pooled human liver microsomes. Moreover, eudesmin, fargesin, epimagnolin A, magnolin, and yangambin noncompetitively inhibited UGT1A1-catalyzed SN38 glucuronidation with Ki values of 25.7, 25.3, 3.6, 26.0, and 17.1 μM, respectively, based on kinetic analysis of UGT1A1 inhibition in pooled human liver microsomes. Conversely, the aforementioned tetrahydrofurofuranoid lignans competitively inhibited UGT1A3-catalyzed chenodeoxycholic acid 24-acyl-glucuronidation with 39.8, 24.3, 15.1, 37.6, and 66.8 μM, respectively in pooled human liver microsomes. These in vitro results suggest the necessity of evaluating whether the five tetrahydrofurofuranoid lignans can cause drug–drug interactions with UGT1A1 and UGT1A3 substrates in vivo.

Magnolin, epimagnolin A, dimethyllirioresinol, eudesmin, and fargesin are pharmacologically active tetrahydrofurofuranoid lignans found in Flos Magnoliae. The inhibitory potentials of dimethyllirioresinol, epimagnolin A, eudesmin, fargesin, and magnolin on eight major human cytochrome P450 (CYP) enzyme activities in human liver microsomes were evaluated using liquid chromatography–tandem mass spectrometry to determine the inhibition mechanisms and inhibition potency. Fargesin inhibited CYP2C9-catalyzed diclofenac 4’-hydroxylation with a Ki value of 16.3 μM, and it exhibited mechanism-based inhibition of CYP2C19-catalyzed [S]-mephenytoin 4’-hydroxylation (Ki, 3.7 μM; Kinact, 0.102 min−1), CYP2C8-catalyzed amodiaquine N-deethylation (Ki, 10.7 μM; Kinact, 0.082 min−1), and CYP3A4-catalyzed midazolam 1’-hydroxylation (Ki, 23.0 μM; Kinact, 0.050 min−1) in human liver microsomes. Fargesin negligibly inhibited CYP1A2-catalyzed phenacetin O-deethylation, CYP2A6-catalyzed coumarin 7-hydroxylation, CYP2B6-catalyzed bupropion hydroxylation, and CYP2D6-catalyzed bufuralol 1’-hydroxylation at 100 μM in human liver microsomes. Dimethyllirioresinol weakly inhibited CYP2C19 and CYP2C8 with IC50 values of 55.1 and 85.0 μM, respectively, without inhibition of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, and CYP3A4 activities at 100 μM. Epimagnolin A, eudesmin, and magnolin showed no the reversible and time-dependent inhibition of eight major CYP activities at 100 μM in human liver microsomes. These in vitro results suggest that it is necessary to investigate the potentials of in vivo fargesin-drug interaction with CYP2C8, CYP2C9, CYP2C19, and CYP3A4 substrates. [ABSTRACT FROM AUTHOR]

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 48 h 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. [ABSTRACT FROM AUTHOR]

Periodontitis, a disease caused by inflammation of oral bacteria, contributes to the loss of alveolar bone and destruction of connective tissues. Porphyromonas gingivalis , a Gram-negative bacterium, is known to possess important pathogenic factors for periodontal disease. In this study, we investigated the anti-periodontitis effects of Magnolia kobus extract (MKE) and magnolin as a component of Magnolia kobus (MK) in murine macrophage RAW 264.7 cells stimulated with Porphyromonas gingivalis lipopolysaccharide (LPS). Effects of MKE and magnolin on the mechanism of RAW 264.7 cellular inflammation were determined by analyzing nitric oxide (NO) production and Western blot protein expression ( n = 3). MKE/magnolin inhibited NO production without affecting cell survival. MKE/magnolin treatment inhibited LPS-induced pro-inflammatory cytokines, expression levels of matrix metalloproteinases (MMPs such as MMP-1, 3, 8, 9, and 13), and protein levels of inflammatory mediators (such as TNF-α, IL-1β, and mPGES-1). MKE/magnolin also suppressed NF-κB activation by inhibiting the TLR4 signaling pathway. These findings suggest that MKE has a therapeutic effect on inflammatory periodontal disease caused by oral bacterium P. gingivalis and that magnolin is a major functional component in the anti-inflammatory effect of MKE., Competing Interests: The authors declare no conflict of interest.

A preparative high-speed counter-current chromatography (HSCCC) method for separation and purification of biondnoid I and magnolin from the Chinese medicinal plant Flos Magnoliae was successfully established by using light petroleum-ethyl acetate-methanol-water (3:7:4:6, v/v) as the two-phase solvent system. From 500 mg of crude extracts of Flos Magnoliae 48 mg of biondnoid I with a purity of 99.3% and 135 mg of magnolin with a purity of 98.7% were separated in a one-step separation. The structures of biondnoid I and magnolin were identified by 1H-NMR. [ABSTRACT FROM PUBLISHER]

This study was first conducted to characterize the intravenous and oral pharmacokinetics of magnolin, a major pharmacologically active ingredient of Magnolia fargesii, at various doses in rats. Magnolin was administered to rats by intravenous injection (0.5, 1 and 2 mg/kg doses) and oral administration (1, 2 and 4 mg/kg doses), and serial plasma and urine samples were harvested. Magnolin concentrations were determined by a validated LC/MS/MS assay. After both intravenous and oral administration, the AUCs were linearly increased as the dose increased. Other pharmacokinetic parameters of magnolin (except the V ss after the intravenous administration) were also independent of the doses. The extent of absolute oral bioavailability ranged from 54.3–76.4% for the oral doses examined. Magnolin was considerably bound to rat plasma proteins and the binding value was constant (71.3–80.5%) over a concentration ranging from 500 to 10000 ng/mL. The pharmacokinetic parameters of magnolin were doseindependent after both intravenous and oral administration. When given orally, magnolin was rapidly absorbed. [ABSTRACT FROM AUTHOR]

Abstract: A purified extract isolated from the dried flower buds of Magnolia fargesii (NDC-052) is currently being evaluated for phase III clinical trials as a new anti-asthma drug. A rapid, sensitive and selective liquid chromatography–tandem mass spectrometric (LC/MS/MS) method for the simultaneous determination of magnolin and epimagnolin A, the major bioactive components of NDC-052, in rat plasma was developed. After liquid–liquid extraction with tolterodine as an internal standard, magnolin and epimagnolin A were separated on a Luna phenyl-hexyl column with the mobile phase of 70% methanol in 10mM ammonium formate. The analytes were detected by an electrospray ionization tandem mass spectrometry in the multiple-reaction-monitoring mode. The standard curves were linear over the concentration range of 50–2500ng/mL for magnolin and epimagnolin A in rat plasma. The intra- and inter-day coefficients of variation and relative errors for magnolin and epimagnolin A at four QC concentrations were 1.5–11.4% and 5.9–12.5%, respectively. The lower limits of quantification for magnolin and epimagnolin A were 50.0ng/mL using 50μL of plasma. This method was successfully applied to the pharmacokinetic study of magnolin and epimagnolin A after an oral administration of NDC-052 in male Sprague–Dawley rats. [Copyright &y& Elsevier]

Abstract: Flos Magnoliae (FM) is a commonly used Chinese medicinal herb for symptomatic relief of allergic rhinitis, sinusitis and headache. A number of FM species have been used as substitutes or adulterants for clinical application, although the differences in their pharmacological actions have not been reported. The present study investigated the effects of six identified FM species M. biondii, M. denudata, M. kobus, M. liliflora, M. sargentiana and M. sprengeri, as well as the marker compounds magnolin and fargesin on compound 48/80-induced histamine release in rat peritoneal mast cells (RPMC) in vitro. Ethanolic extracts of all FM species produced a concentration-dependent inhibition of compound 48/80-induced histamine release in RPMC. The rank order of the IC50s was M. biondii

Eudesmin, fargesin, epimagnolin A, magnolin, and yangambin are tetrahydrofurofuranoid lignans with various pharmacological activities found in Magnoliae Flos. The inhibition potencies of eudesmin, fargesin, epimagnolin A, magnolin, and yangambin on six major human uridine 5′-diphospho-glucuronosyltransferase (UGT) activities in human liver microsomes were evaluated using liquid chromatography–tandem mass spectrometry and cocktail substrates. Eudesmin, fargesin, epimagnolin A, magnolin, and yangambin inhibited UGT1A1 and UGT1A3 activities, but showed negligible inhibition of UGT1A4, UGT16, UGT1A9, and UGT2B7 activities at 200 μM in pooled human liver microsomes. Moreover, eudesmin, fargesin, epimagnolin A, magnolin, and yangambin noncompetitively inhibited UGT1A1-catalyzed SN38 glucuronidation with Ki values of 25.7, 25.3, 3.6, 26.0, and 17.1 μM, respectively, based on kinetic analysis of UGT1A1 inhibition in pooled human liver microsomes. Conversely, the aforementioned tetrahydrofurofuranoid lignans competitively inhibited UGT1A3-catalyzed chenodeoxycholic acid 24-acyl-glucuronidation with 39.8, 24.3, 15.1, 37.6, and 66.8 μM, respectively in pooled human liver microsomes. These in vitro results suggest the necessity of evaluating whether the five tetrahydrofurofuranoid lignans can cause drug–drug interactions with UGT1A1 and UGT1A3 substrates in vivo. [ABSTRACT FROM AUTHOR]

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 was found to inhibit IgE/Ag-induced anaphylactoid reactions with a dose-dependent manner in vitro and in vivo. • Magnolin may inhibit the anaphylactoid reactions by decreasing the phosphorylation of Lyn, Fyn, PLCγ1, Akt, P38 and ERK. • Magnolin may be a candidate for preventing and delaying mast cell-mediated allergic diseases. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the effects of Magnolin (MGL) on inhibition of human breast cancer cells, and explore the underlying molecular mechanisms. The viability of the treated cells was assessed with the Cell Counting Kit-8 (CCK-8) assay, and the proliferation was analyzed in terms of EdU uptake, colony formation, and flow cytometry. The in vitro invasion and migration were determined by the transwell and wound healing assays respectively. The mRNA and protein levels of relevant factors was evaluated by quantitative real-time PCR and Western blotting respectively. MGL significantly decreased the viability and promoted apoptosis of MDA-MB-231 cells, along with reducing EdU incorporation rate as well as the colony forming capacity compared to the untreated control cells. In addition, the in vitro invasion and migration were also significantly inhibited by MGL. Furthermore, MGL suppressed the phosphorylation of MEK1/2, extracellular signal-regulated kinase (ERK)1/2 and significantly downregulated the expression of cyclin-dependent kinase 1 (CDK1), the anti-apoptotic B-cell lymphoma 2 (BCL2) and metastasis-associated matrix metalloproteases (MMPs) 2 & 9, and upregulated the cleaved caspases 3 and 9. After ERK was completely inhibited with the small interfering RNA (siRNA), MGL had no effect on these factors, indicating that ERK is essential for MGL action in breast cancer. In conclusion, MGL inhibits proliferation and invasion of and induces apoptosis in breast cancer cells through the ERK pathway.

The prognosis of patients with advanced hepatocellular carcinoma (HCC) remains obscure. From a clinical point of view, the ERK MAPK pathway and the PI3K/AKT pathway are activated in the majority of liver cancer. In addition, long term used to single agent treatment of HCC, frequently results in reverse activation of the ERK MAPK pathway or the PI3K/AKT pathway, leading to drug resistance. Thus, it is important to research the mechanism of combination agents that could suppress different pathways to treat HCC. Here, we found that combination natural product magnolin with BRAF inhibitor SB590885 synergistically suppressed the proliferation, promoted cell cycle arrest and apoptosis in hepatocellular carcinoma cells Bel-7402 and SK-Hep1. Furthermore, we demonstrated that the magnolin and the SB590885 combination led to increased impaired proliferation via inhibition of the ERK MAPK pathway and the PI3K/AKT pathway. These findings highlight the important role of agent combination and provided the approaches of therapeutic improvement for patients with advanced HCC., Competing Interests: None.

Magnolin, epimagnolin A, dimethyllirioresinol, eudesmin, and fargesin are pharmacologically active tetrahydrofurofuranoid lignans found in Flos Magnoliae. The inhibitory potentials of dimethyllirioresinol, epimagnolin A, eudesmin, fargesin, and magnolin on eight major human cytochrome P450 (CYP) enzyme activities in human liver microsomes were evaluated using liquid chromatography-tandem mass spectrometry to determine the inhibition mechanisms and inhibition potency. Fargesin inhibited CYP2C9-catalyzed diclofenac 4'-hydroxylation with a Ki value of 16.3 μM, and it exhibited mechanism-based inhibition of CYP2C19-catalyzed [S]-mephenytoin 4'-hydroxylation (Ki, 3.7 μM; kinact, 0.102 min-1), CYP2C8-catalyzed amodiaquine N-deethylation (Ki, 10.7 μM; kinact, 0.082 min-1), and CYP3A4-catalyzed midazolam 1'-hydroxylation (Ki, 23.0 μM; kinact, 0.050 min-1) in human liver microsomes. Fargesin negligibly inhibited CYP1A2-catalyzed phenacetin O-deethylation, CYP2A6-catalyzed coumarin 7-hydroxylation, CYP2B6-catalyzed bupropion hydroxylation, and CYP2D6-catalyzed bufuralol 1'-hydroxylation at 100 μM in human liver microsomes. Dimethyllirioresinol weakly inhibited CYP2C19 and CYP2C8 with IC50 values of 55.1 and 85.0 μM, respectively, without inhibition of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, and CYP3A4 activities at 100 μM. Epimagnolin A, eudesmin, and magnolin showed no the reversible and time-dependent inhibition of eight major CYP activities at 100 μM in human liver microsomes. These in vitro results suggest that it is necessary to investigate the potentials of in vivo fargesin-drug interaction with CYP2C8, CYP2C9, CYP2C19, and CYP3A4 substrates.

Background/aims: There is a need for new anti-asthmatic medications with fewer side effects. NDC-052, an extract of the medicinal herb Magnoliae flos, which has a long history of clinical use, was recently found to have anti-inflammatory effects. Herein, we evaluated the effects of NDC-052 as an add-on therapy in patients with mild to moderate asthma using inhaled corticosteroids (ICS)., Methods: In a non-comparative, multi-center trial, 148 patients taking ICS received NDC-052 for eight weeks. We evaluated their forced expiratory volume in one second (FEV1), morning and evening peak expiratory flow rate (AM and PM PEFR), AM/PM asthma symptom scores, visual analogue symptom (VAS) scores, night-time wakening, frequency of short-acting β2-agonist usage, and adverse events., Results: After eight weeks, both AM and PM PEFRs were significantly improved. Asthma symptom scores, VAS scores, the frequency of nights without awakening, and the frequency of β2-agonist use were also reduced. Most of the adverse drug reactions were mild and resolved spontaneously., Conclusions: The addition of NDC-052 to ICS had a beneficial effect on asthma control in patients with mild to moderate asthma, with good tolerability and fewer side effects. Further studies are necessary to evaluate the effects of NDC-052 in patients with severe and/or refractory asthma.