Inhibitory Effect Of Magnolol Research Articles

The Inhibitory Effect of Magnolol on the Human TWIK1 Channel Is Related to G229 and T225 Sites.

TWIK1 (K2P1.1/KCNK1) belongs to the potassium channels of the two-pore domain. Its current is very small and difficult to measure. In this work, we used a 100 mM NH4+ extracellular solution to increase TWIK1 current in its stable cell line expressed in HEK293. Then, the inhibition of magnolol on TWIK1 was observed via a whole-cell patch clamp experiment, and it was found that magnolol had a significant inhibitory effect on TWIK1 (IC50 = 6.21 ± 0.13 μM). By molecular docking and alanine scanning mutagenesis, the IC50 of TWIK1 mutants G229A, T225A, I140A, L223A, and S224A was 20.77 ± 3.20, 21.81 ± 7.93, 10.22 ± 1.07, 9.55 ± 1.62, and 7.43 ± 3.20 μM, respectively. Thus, we conclude that the inhibition of the TWIK1 channel by magnolol is related to G229 and T225 on the P2- pore helix.

"Inhibitory Effect of Magnolol on Activation of EGFR L858R/T790M/G796R"

"Inhibitory Effect of Magnolol on Activation of EGFR L858R/T790M/G796R"

Magnolol Inhibits RANKL-induced osteoclast differentiation of raw 264.7 macrophages through heme oxygenase-1-dependent inhibition of NFATc1 expression.

Magnolol (1) isolated from Magnolia officinalis exhibits many beneficial effects such as anti-inflammatory and antioxidant activity. The aim of this study was to evaluate the effects of magnolol (1) on RANKL-induced osteoclast differentiation and investigate the underlying molecular mechanisms. Treatment with magnolol (1) significantly inhibited osteoclast differentiation of RAW 264.7 macrophages and bone-resorbing activity of osteoclasts in the RANKL-induced system. Moreover, RANKL-activated JNK/ERK/AP-1 and NF-κB signaling, ROS formation, and NFATc1 activation were attenuated by magnolol (1). A novel finding of this study is that magnolol (1) can increase heme oxygenase-1 (HO-1) expression and Nrf2 activation in RANKL-stimulated cells. Blocking HO-1 activity with tin protoporphyrin IX markedly reversed magnolol (1)-mediated inhibition of osteoclast differentiation, NFATc1 nuclear translocation, and MMP-9 activity, suggesting that HO-1 contributes to the attenuation of NFATc1-mediated osteoclastogenesis by magnolol (1). Therefore, the inhibitory effect of magnolol (1) on osteoclast differentiation is due to inhibition of MAPK/c-fos/AP-1 and NF-κB signaling as well as ROS production and up-regulation of HO-1 expression, which ultimately suppresses NFATc1 induction. These findings indicate that magnolol (1) may have potential to treat bone diseases associated with excessive osteoclastogenesis.

Magnolol reduces UVB-induced photodamage by regulating matrix metalloproteinase activity

In this study, we evaluated the anti-photoaging activity of magnolol in UV-irradiated hairless mice, and hypothesized that magnolol would prevent photoaging in these animals. The inhibitory effect of magnolol on wrinkle formation was determined by analyzing the skin replica, histologically examining the epidermal thickness, and identifying damage to the collagen fibers. The protective effects of magnolol on UVB-induced skin photoaging were examined by determining the level of MMPs and mitogen-activated protein kinases (MAPKs). Exposure to UVB radiation significantly increased skin thickness and wrinkle grade, but magnolol treatment significantly reduced the average length and depth of wrinkles, and this was correlated with the inhibition of collagen fiber loss. The magnolol-treated group had remarkably decreased activity levels of MMP-1, -9, and -13 compared to the corresponding levels in the vehicle-treated UVB-irradiated group. These results indicate that magnolol prevents skin photoaging in UVB-irradiated hairless mice.

Role of magnolol in the proliferation of vascular smooth muscle cells

Proliferation of vascular smooth muscle cells (VSMCs) contributes to the development of vascular remodeling. Recently, magnolol has been reported to have a potential role in regulating tumor necrosis factor α-induced proliferation of VSMCs. However, the role of magnolol in platelet-derived growth factor (PDGF)-induced proliferation of VSMCs remains unknown. Our purpose was to elucidate the effect of magnolol on the proliferation of VSMCs induced by PDGF-BB and to investigate the underlying molecular mechanisms. Our data demonstrated that magnolol inhibited rat VSMC proliferation and DNA synthesis stimulated by 20 ng/ml PDGF-BB without causing cell cytotoxicity. Flow cytometric analysis showed that magnolol inhibited S-phase entry of VSMCs. We also demonstrated that magnolol caused this effect by inhibiting the mRNA and protein expression of cyclin D1, cyclin E, and cyclin-dependent kinases 2 and 4 in PDGF-BB-stimulated VSMCs. Further analysis showed that the inhibitory effect of magnolol on the proliferation of VSMCs was associated with the inhibition of the PDGF-BB-stimulated production of intracellular reactive oxygen species (ROS) and Ras, MEK, and ERK1/2 activation. These results demonstrate that magnolol can block the proliferation of VSMCs through inhibition of intracellular ROS production and Ras-MEK-ERK1/2 pathways. Magnolol, therefore, has a potential application in preventing atherosclerosis and restenosis.

Anti-inflammatory effect of magnolol, isolated from Magnolia officinalis, on A23187-induced pleurisy in mice.

In the present study, A23187-induced pleurisy in mice was used to investigate the anti-inflammatory effect of magnolol, a phenolic compound isolated from Chinese medicine Hou p'u (cortex of Magnolia officinalis). A23187-induced protein leakage was reduced by magnolol (10 mg kg-1, i.p.), indomethacin (10 mg kg-1, i.p.) and BW755C (30 mg kg-1, i.p.). A23187-induced polymorphonuclear (PMN) leucocyte infiltration in the pleural cavity was suppressed by magnolol and BW755C, while enhanced by indomethacin. Like BW755C, magnolol reduced both prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) levels in the pleural fluid of A23187-induced pleurisy, while indomethacin reduced PGE2 but increased LTB4 formation. In the rat isolated peripheral neutrophil suspension, magnolol (3.7 microM) and BW755C (10 microM) also suppressed the A23187-induced thromboxane B2 (TXB2) and LTB4 formation. These results suggest that magnolol, like BW755C, might be a dual cyclo-oxygenase and lipoxygenase inhibitor. The inhibitory effect of magnolol on the A23187-induced pleurisy is proposed to be, at least partly, dependent on the reduction of the formation of eicosanoids mediators in the inflammatory site.

T1795 Involvement of BKCa Channel in the Inhibitory Effect of Magnolol On Rat Colonic Spontaneous Contractility

T1795 Involvement of BKCa Channel in the Inhibitory Effect of Magnolol On Rat Colonic Spontaneous Contractility

Mechanism underlying the inhibitory effect of magnolol on smooth muscular spontaneous contraction in rat colon

Mechanism underlying the inhibitory effect of magnolol on smooth muscular spontaneous contraction in rat colon

The inhibitory effect of magnolol from Magnolia officinalis on glucosyltransferase

Dental caries has been an intractable disease in spite of intense dental research. Glucosyltransferase (GTF) enzyme plays the most important role in the development of dental caries. In our previous studies, magnolol, a compound from Magnolia officinalis Rehder et Wilson (Magnoliaceae), was shown to possess a strong anti-GTF activity. The purpose of the present study was to examine the effect of magnolol on the functional domains of GTF for the purpose of defining its anti-GTF activity mechanism. GTF-I which was prepared from Streptococcus milleri transformant KSB8 cells expressing the gtfB gene was used. The results demonstrated magnolol reduced total glucan synthesis, depending on the magnolol concentration. There were no significant differences in Michaelis constant (K(m)) values between the presence and absence of magnolol as determined by Lineweaver-Burk plot, and maximum velocity (V(m)) in the presence of magnolol was lower than that in its absence. Magnolol significantly inhibited both sucrose hydrolysis and glucosyl transfer to glucan by GTF-I. Free glucose in the presence of magnolol was reduced by 33-48% as compared to in its absence, while the quantity of glucan was reduced by 75-82%. These findings suggested that magnolol inhibited both two sequential reaction phases of GTF non-competitively by operating on the glucan-binding domain, but not on the catalytic domain. Magnolol could be a valuable resource for the exploration of novel bioactive compounds in natural products.

Effects of magnolol and honokiol derived from traditional Chinese herbal remedies on gastrointestinal movement

To study the effects of magnolol and honokiol on isolated smooth muscle of gastrointestinal tract and their relationship with Ca2+, and on the gastric emptying and the intestinal propulsive activity in mice. Routine experimental methods using isolated gastric fundus strips of rats and isolated ileum segments of guinea pigs were adopted to measure the smooth muscle tension. The effects of magnolol 10(-3), 10(-4), 10(-5) mol/L, and honokiol 10(-4), 10(-5), 10(-6) mol/L on the contractility of gastric fundus strips of rats and ileum of guinea pigs induced by acetylcholine (Ach) and 5-hydroxytryptamine (5-HT) was assessed respectively. The method using nuclein and pigment methylene blue was adopted to measure the gastric retention rate of nuclein and the intestinal propulsive ratio of a nutritional semi-solid meal for assessing the effect of magnolol and honokiol (0.5, 2, 20 mg/kg) on gastric emptying and intestinal propulsion. Magnolol and honokiol significantly inhibited the contractility of isolated gastric fundus strips of rats treated with Ach or 5-HT and isolated ileum guinea pigs treated with Ach or CaCl2, and both of them behaved as non-competitive muscarinic antagonists. Magnolol and honokiol inhibited the contraction induced by Ach in Ca2+-free medium and extracellular Ca2+-dependent contraction induced by Ach. Each group of magnolol and honokiol experiments significantly decreased the residual rate of nuclein in the stomach and increased the intestinal propulsive ratio in mice. The inhibitory effect of magnolol and honokiol on contractility of the smooth muscles of isolated gastric fundus strips of rats and isolated ileum of guinea pigs is associated with a calcium-antagonistic effect. Magnolol and honokiol can improve the gastric emptying of a semi-solid meal and intestinal propulsive activity in mice.

Effect of Magnolol onin VitroMitochondrial Lipid Peroxidation and Isolated Cold-Preserved Warm-Reperfused Rat Livers

Background/aim.A mechanism suggested to cause injury to preserved organs is the generation of oxygen free radicals. Lipid peroxidation is one of the biological damages caused by oxygen free radicals. It is our aim to investigate whether magnolol, a strong antioxidant, suppresses the generation of oxygen free radicals and improves the viability of cold-preserved warm-reperfused rat livers.Materials and methods. In vitrolipid peroxidation was induced in rat hepatic mitochondria with ADP and FeSO4. The inhibitory effect of magnolol on lipid peroxidation was measured with oxygen consumption and malondialdehyde (MDA) formation. Subsequently, we preserved and reperfused rat livers in preservation solutions that contained magnolol. The hepatic enzymes and liver MDA were measured to assess the protective effect of magnolol on isolated rat livers.Results.In rat hepatic mitochondria, magnolol was 470 times more potent than α-tocopherol in inhibiting oxygen consumption and 340 times more potent than α-tocopherol in inhibiting MDA formation. Addition of magnolol to Ringer's lactate solution had a protective effect, in terms of MDA formation and leakage of hepatic enzymes, on warm-reperfused but not cold-stored liver tissue. Addition of magnolol to University of Wisconsin (UW) solution, a widely used preservation solution, did not modify the effect of this solution on isolated liver tissues.Conclusions.We conclude that magnolol is an effective antioxidant and suppresses lipid peroxidation in rat liver mitochondria and can be used as a rinsing solution in protecting transplanted organs from lipid peroxidation during reperfusion, especially for those organs not preserved with UW solution.

Modulatory effects of magnolol on potassium-stimulated 5-hydroxytryptamine release from rat cortical and hippocampal slices

Magnolol, a phenolic constituent of magnolia bark, is a known central nervous system depressant. To examine the possibility that magnolol may elicit its depressant effect by modulating central serotonergic activity, its effect on 35 mM K +-stimulated 5-[ 3H]HT release from rat hippocampal and frontal cortical slices were examined. Inclusion of magnolol (1–100 μM) had no effect on 5-HT release in hippocampal slices but elicited a dose-related inhibition on 5-HT release from cortical slices. The inhibitory effect of magnolol on K +-stimulated 5-HT release from the cortex was not affected by either antagonists (metergoline, propranolol, and cyproheptadine) (0.01–10 μM) of various 5-HT receptor subtypes or the voltage-dependent sodium channel blocker tetrodotoxin (1 μM). It is concluded that the suppression of brain 5-HT release by magnolol is site-specific, and the suppression of cortical 5-HT release by magnolol is not via the 5-HT autoreceptors at the 5-HT terminals.