Magnolol, a compound extracted from Magnolia officinalis, demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases. Its biological activities encompass anti-inflammatory, antioxidant, anticoagulant, and anti-diabetic effects. Growth/differentiation factor-15 (GDF-15), a member of the transforming growth factor β superfamily, is considered a potential therapeutic target for metabolic disorders. This study investigated the impact of magnolol on GDF-15 production and its underlying mechanism. The research examined the pharmacological effect of magnolol on GDF-15 expression in vitro and in vivo, and determined the involvement of endoplasmic reticulum (ER) stress signaling in this process. Luciferase reporter assays, chromatin immunoprecipitation, and in vitro DNA binding assays were employed to examine the regulation of GDF-15 by activating transcription factor 4 (ATF4), CCAAT enhancer binding protein γ (CEBPG), and CCCTC-binding factor (CTCF). The study also investigated the effect of magnolol and ATF4 on the activity of a putative enhancer located in the intron of the GDF-15 gene, as well as the influence of single nucleotide polymorphisms (SNPs) on magnolol and ATF4-induced transcription activity. Results demonstrated that magnolol triggers GDF-15 production in endothelial cells (ECs), hepatoma cell line G2 (HepG2) and hepatoma cell line 3B (Hep3B) cell lines, and primary mouse hepatocytes. The cooperative binding of ATF4 and CEBPG upstream of the GDF-15 gene or the E1944285 enhancer located in the intron led to full-power transcription of the GDF-15 gene. SNP alleles were found to impact the magnolol and ATF4-induced transcription activity of GDF-15. In high-fat diet ApoE^-/- mice, administration of magnolol induced GDF-15 production and partially suppressed appetite through GDF-15. These findings suggest that magnolol regulates GDF-15 expression through priming of promoter and enhancer activity, indicating its potential as a drug for the treatment of metabolic disorders.
Lignans/pharmacology* ; Growth Differentiation Factor 15/metabolism* ; Animals ; Biphenyl Compounds/pharmacology* ; Endoplasmic Reticulum Stress/drug effects* ; Activating Transcription Factor 4/genetics* ; Mice ; Humans ; Male ; Magnolia/chemistry* ; CCAAT-Enhancer-Binding Proteins/genetics* ; Mice, Inbred C57BL

Chronic cerebral hypoperfusion leads to white matter injury (WMI), which subsequently causes neurodegeneration and even cognitive impairment. However, due to the lack of treatment specifically for WMI, novel recognized and effective therapeutic strategies are urgently needed. In this study, we found that honokiol and magnolol, two compounds derived from Magnolia officinalis, significantly facilitated the differentiation of primary oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes, with a more prominent effect of the former compound. Moreover, our results demonstrated that honokiol treatment improved myelin injury, induced mature oligodendrocyte protein expression, attenuated cognitive decline, promoted oligodendrocyte regeneration, and inhibited astrocytic activation in the bilateral carotid artery stenosis model. Mechanistically, honokiol increased the phosphorylation of serine/threonine kinase (Akt) and mammalian target of rapamycin (mTOR) by activating cannabinoid receptor 1 during OPC differentiation. Collectively, our study indicates that honokiol might serve as a potential treatment for WMI in chronic cerebral ischemia.
Magnolia ; White Matter ; Brain Ischemia/metabolism* ; Oligodendroglia/metabolism*

The weight coefficients of appearance traits, extract yield of standard decoction, and total content of honokiol and magnolol were determined by analytic hierarchy process(AHP), criteria importance though intercrieria correlation(CRITIC), and AHP-CRITIC weighting method, and the comprehensive scores were calculated. The effects of ginger juice dosage, moistening time, proces-sing temperature, and processing time on the quality of Magnoliae Officinalis Cortex(MOC) were investigated, and Box-Behnken design was employed to optimize the process parameters. To reveal the processing mechanism, MOC, ginger juice-processed Magnoliae Officinalis Cortex(GMOC), and water-processed Magnoliae Officinalis Cortex(WMOC) were compared. The results showed that the weight coefficients of the appearance traits, extract yield of standard decoction, and total content of honokiol and magnolol determined by AHP-CRITIC weighting method were 0.134, 0.287, and 0.579, respectively. The optimal processing parameters of GMOC were ginger juice dosage of 8%, moistening time of 120 min, and processing at 100 ℃ for 7 min. The content of syringoside and magnolflorine in MOC decreased after processing, and the content of honokiol and magnolol followed the trend of GMOC>MOC>WMOC, which suggested that the change in clinical efficacy of MOC after processing was associated with the changes of chemical composition. The optimized processing technology is stable and feasible and provides references for the modern production and processing of MOC.
Ginger ; Magnolia/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Biphenyl Compounds/chemistry* ; Lignans/chemistry*

In this study, we employed Q Exactive to determine the main differential metabolites of Magnoliae Officinalis Cortex du-ring the "sweating" process. Further, we quantified the color parameters and determined the activities of polyphenol oxidase(PPO), peroxidase(POD), and tyrosinase of Magnoliae Officinalis Cortex during the "sweating" process. Gray correlation analysis was performed for the color, chemical composition, and enzyme activity to reveal the effect of enzymatic reaction on the color of Magnoliae Officinalis Cortex during the "sweating" process. Magnoliae Officinalis Cortex sweating in different manners showed similar metabolite changes. The primary metabolites that changed significantly included amino acids, nucleotides, and sugars, and the secondary metabolites with significant changes were phenols and phenylpropanoids. Despite the different sweating methods, eleven compounds were commonly up-regulated, including L-glutamic acid, acetylarginine, hypoxanthine, and xanthine; six compounds were commonly down-re-gulated, including L-arginine, L-aspartic acid, and phenylalanine. The brightness value(L~*), red-green value(a~*), and yellow-blue value(b~*) of Magnoliae Officinalis Cortex kept decreasing during the "sweating" process. The changes in the activities of PPO and POD during sweating were consistent with those in the color parameter values. The gray correlation analysis demonstrated that the main differential metabolites such as amino acids and phenols were closely related to the color parameters L~*, a~* and b~*; POD was correlated with amino acids and phenols; PPO had strong correlation with phenols. The results indicated that the color change of Magnoliae Officinalis Cortex during "sweating" was closely related to the reactions of enzymes dominated by PPO and POD. The study analyzed the correlations among the main differential metabolites, color parameters, and enzyme activities of Magnoliae Officinalis Cortex in the "sweating" process. It reveals the common law of material changes and ascertains the relationship between color changes and enzymatic reactions of Magnoliae Officinalis Cortex during "sweating". Therefore, this study provides a reference for studying the "sweating" mechanism of Magnoliae Officinalis Cortex and is of great significance to guarantee the quality of Magnoliae Officinalis Cortex.
Magnolia/chemistry* ; Quality Control ; Sweating

Magnoliae Officinalis Cortex, a common Chinese medicinal in clinic, should undergo "sweating" process in producing area according to Chinese Pharmacopoeia, which affects its genuineness and quality. In light of the concept and research mode of quality marker(Q-marker) for decoction pieces, the active components of Magnoliae Officinalis Cortex pieces which altered significantly before and after "sweating" were identified in this study. The main pharmacodynamic material basis was clarified by pharmacodynamic, pharmacokinetic and drug property research, followed by the prediction of Q-markers of Magnoliae Officinalis Cortex before and after "sweating", for better improving its quality standard.
Drugs, Chinese Herbal ; Magnolia

Honokiol is the dominant biphenolic compound isolated from the Magnolia tree, and has long been considered as the active constituent of the traditional Chinese herb, 'Houpo', which is widely used to treat symptoms due to 'stagnation of qi'. Pharmacological studies have shown that honokiol possesses a wide range of bioactivities without obvious toxicity. Honokiol protects the liver, kidneys, nervous system, and cardiovascular system through reducing oxidative stress and relieving inflammation. Moreover, honokiol shows anti-diabetic property through enhancing insulin sensitivity, and anti-obese property through promoting browning of adipocytes. In vivo and in vitro studies indicated that honokiol functions as an anti-cancer agent through multiple mechanisms: inhibiting angiogenesis, promoting cell apoptosis, and regulating cell cycle. A variety of therapeutic effects of honokiol may be associated with its physiochemical properties, which make honokiol readily cross the blood brain barrier and the blood-cerebrospinal fluid barrier, with high bioavailability. In the future, more clinical researches on honokiol are needed to fully authenticate its therapeutic values.
Apoptosis ; Biphenyl Compounds/pharmacology* ; Drugs, Chinese Herbal/pharmacology* ; Humans ; Lignans/pharmacology* ; Magnolia

Six new oligomeric neolignans including two trimeric neolignans (1 and 2) and four dimeric neolignans (3-6) were isolated from the leaves of Magnolia officinalis var. biloba. Their structures were determined based on HR-ESIMS and NMR data, as well as electronic circular dichroism (ECD) calculations. Compound 1 is formed from two obovatol moieties directly linked to an aromatic ring of the remaining obovatol moiety, which is an unprecedented type of linkage between monomers. All isolates were assessed for their inhibitory effects on NO production in LPS-stimulated RAW 264.7 macrophage cells. Compounds 1 and 3 showed significantly inhibitory activities with IC
Animals ; Lignans/pharmacology* ; Magnolia/chemistry* ; Mice ; Molecular Structure ; Phytochemicals/pharmacology* ; Plant Extracts/pharmacology* ; Plant Leaves/chemistry* ; RAW 264.7 Cells

Magnolia officinalis is a traditional Chinese medicine,with many years of cultivating process, M. officinalis leaves show more differentiation types due to the exchange of seeds from different provenances. "Da Ao"(DA), "Xiao Ao"(XA), "Chuan Hou"(CH),and "Liu Ye"(LY)are the main types of M. officinalis in Sichuan province of China,and there were obvious differences in growth rate,chemical composition,leaf shape and leaf colour. This study selected different types of M. officinalis leaves(DA,XA,LY and CH)from Sichuan to determine their chlorophyll content. Transcriptomic level sequencing of different types of M. officinalis leaf tissues was by high-throughput sequencing analysis and proteomics used an integrated approach involving TMT labelling and LC-MS/MS to quantify the dynamic changes of the whole proteome of M. officinalis. The results showed that CH had the lowest chlorophyll content while DA had the highest chlorophyll content. Furthermore,transcriptome and proteomics results showed that chlorophyll synthesis pathway in DA glutamine-tRNA reductase,urinary porphyrins decarboxylase(UROD),oxygen-dependent protoporphyrin(ODCO),the original-Ⅲ oxidase protoporphyrin oxidase(PPO),magnesium chelating enzyme subunit ChlD,protoporphyrin magnesium Ⅸ monomethyl ester [oxidative] cyclase(MPPMC)were significantly higher than CH,XA and LY,consistent in the results of determination of chlorophyll content(chlorophyll content was highest of 37.56 mg·g~(-1) FW). Some rate-limiting enzymes related to the chlorophyll synthesis,such as ODCO,PPO and MPPMC were tested by Parallel Reaction Monitoring(PRM),and the results showed that the rate-limiting enzyme content in DA was higher than that in other three types. Therefore,based on the differences in leaf color of four types of M. officinalis,the research conducted a preliminary study on the chlorophyll metabolism pathway in leaves of different types of M. officinalis,and explored relevant genes and proteins causing leaf color differences from the molecular level,so as to lay a foundation for studying the differences in growth and development of different types of M. officinalis.
China ; Chlorophyll ; Chromatography, Liquid ; Magnolia ; Plant Leaves ; Proteome ; Tandem Mass Spectrometry ; Transcriptome

Based on metabolomics,the effect of Magnolia officinalis before and after " sweating" on gastrointestinal motility disorder( rat) was compared. To study the mechanism of M. officinalis " sweating" increased the efficacy and reduced the toxicity. The rat model of gastrointestinal motility disorder was established by intraperitoneal injection of L-arginine. Pharmacodynamic indexes were relative residual rate of gastric pigment and intestinal propulsion ratio in rats. LC-MS metabolomics and multivariate statistical analysis were used to screen and identify biomarkers associated with gastrointestinal motility disorders,and MetPA database was used to analyze related metabolic pathways. The results showed that M. officinalis could improve gastrointestinal motility disorder whether it " sweating" or not,and the effect of " sweating" M. officinalis was stronger than that of " no sweating" M. officinalis. The metabolites of the experimental groups could be distinguished distinctly,and 15 different compounds and 17 related pathways were identified preliminarily. The mechanism of M. officinalis might be to improve gastrointestinal motility disorder by increasing the content of L-glutamate in the metabolic pathway of alanine,aspartate and glutamate and protecting gastrointestinal barrier. Before " sweating",M. officinalis could reduce taurine through metabolism of taurine and taurine and biosynthetic pathway of primary bile acid,increase the content of deoxycholic acid in glycine goose,and increase the risk of liver and kidney injury. After " sweating",M. officinalis could enhance gastrointestinal motility by increasing the contents of L-tryptophan and serotonin in the tryptophan pathway,and avoid the production of harmful metabolites to achieve synergistic and detoxifying effect.
Animals ; Gastrointestinal Motility ; Magnolia ; Metabolomics ; Rats ; Sweating ; Tandem Mass Spectrometry

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.
Biphenyl Compounds ; analysis ; China ; Drugs, Chinese Herbal ; analysis ; Lignans ; analysis ; Magnolia ; chemistry ; Phytochemicals ; analysis