Comprehensive reutilization of herbal waste:Coproduction of magnolol,honokiol,and β-amyrin from Magnolia officinalis residue

Herbal extraction residues(HERs)cause serious environmental pollution and resource waste.In this study,a novel green route was designed for the comprehensive reutilization of all components in HERs,taking Magnolia officinalis residues(MOR)as an example.The reluctant structure of MOR was first destroyed by alkali pretreatment to release the functional ingredients(magnolol and honokiol)originally remaining in MOR and to make MOR more accessible for hydrolysis.A metal–organic frame material MIL-101(Cr)with a maximum absorption capacity of 255.64 mg g^(-1)was synthesized to absorb the released honokiol and magnolol from the pretreated MOR solutions,and 40 g L^(-1)reducing sugars were obtained with 81.8%enzymatic hydrolysis rate at 10%MOR solid loading.Finally,382 mg L-1β-amyrin was produced from MOR hydrolysates by an engineered yeast strain.In total,1 kg honokiol,8 kg magnolol,and 7.64 kg β-amyrin could produce from 1 ton MOR by this cleaner process with a total economic output of 170,700 RMB.

Antibacterial Activity and Mechanisms of Ethanol Extracts from Scutellaria baicalensis Georgi and Magnolia officinalis against Phytophthora nicotianae

Phytophthora nicotianae causes substantial economic losses in most countries where tobacco is produced.At present,the control of P.nicotianae mainly depends on chemical methods,with considerable environmental and health issues.We investigated the effects of ethanol extracts from Scutellaria baicalensis Georgi(SBG)and Magnolia officinalis(MO).On mycelial growth,sporangium formation,and zoospore release of P.nicotianae.Both extracts inhibited the growth of P.nicotianae,with mycelial growth inhibition rates of 88.92%and 93.92%,respectively,at 40 mg/mL,and EC50 values of 5.39 and 5.74 mg/mL,respectively.The underlying mechanisms were the inhibition of sporangium formation,the reduction of zoospore number,and the destruction of the mycelium structure.At an SBG extract concentration of 16.17 mg/mL,the inhibition rates for sporangia and zoospores were 98.66%and 99.39%,respectively.At an MO extract concentration of 2.87 mg/mL,the production of sporangia and zoospores was completely inhibited.The hyphae treated with the two plant extracts showed different degrees of deformation and damage.Hyphae treated with SBG extract showed adhesion and local swelling,whereas treatment with MO extract resulted in broken hyphae.Mixture of the extracts resulted in a good synergistic effect.

Three unprecedented biphenyl derivatives bearing C6-C3 carbon skeleton from the bark of Magnolia officinalis var.biloba

(+)-Magoilgomer A[(±)-1]and magoilgomer B(2)were identified from the bark of Magnolia officinalis var.biloba.(+)-1 and(-)-1 were a pair of novel biphenyl derivatives featuring three C6-C3 subunits.2 was an unprecedented adduct containing magnolol and honokiol.These three oligomers possessed new parallel mode which should be biosynthesized from the coupling of three or four C6-C3 subunits.The structures of(±)-1 and 2 were elucidated based on the spectroscopic data analyses and electronic circular dichroism(ECD)calculations.2 exhibited neuroprotective effects of oxygen glucose deprivation-induced SK-N-SH cell injury.

New oligomeric neolignans from the leaves of Magnolia officinalis var. biloba

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 IC50 values of 6.04 and 3.26μmol·L^(−1),respectively.

Deep sequencing of Magnoliae officinalis reveals upstream genes related to the lignan biosynthetic pathway

Magnoliae officinalis is the plant source of houpo, a widely used traditional Chinese medicine to treat symptoms of gastrointestinal diseases. Its main active components, magnolol (MG) and honokiol (HK), have excellent pharmacological actions, but little research has focused on the functional genes involved in the MG and HK metabolic pathways. In this study, using RNA-seq and gene expression profile, we present the first transcriptome characterization of M. officinalis leaves, twigs and stems. Based on similarity search against nonredundant protein databases, 30,660 contigs had at least a significant alignment to existing public database. Pathway analysis showed that 8707 contigs were assigned to 317 KEGG pathways. A second skeleton pathway with 14 putative homologous genes was also identified as involved in lignan biosynthesis. Expression profiles of these 14 genes showed that leaves and twigs seem to have higher transcript levels for lignan components than in stem tissue; this result was then verified by qRT-PCR. Our work will immensely facilitate metabolic research on lignan biosynthesis in M. officinalis.

厚朴中总鞣质提纯工艺及抗菌活性研究

通过响应面设计优化厚朴(Magnolia officinalis Rehd.et Wils.)中总鞣质的提取工艺,并进一步纯化。结果表明,厚朴中总鞣质的最佳提取工艺为料液比1∶13、提取时间100 min、乙醇浓度80%、超声功率80 W,厚朴总鞣质提取量为0.1810 mg/g,与理论值0.1888 mg/g差距小。利用正交试验考察明胶溶液沉淀法对厚朴总鞣质的最佳纯化工艺为浓缩液比重1.5 mg/mL、明胶溶液浓度4%、明胶溶液添加量8 mL/100 mg,厚朴总鞣质提取量为2.743 mg/g。利用最小抑菌浓度测定法比较总鞣质对金黄色葡萄球菌和大肠埃希菌的抗菌活性,表明厚朴中总鞣质具有一定的抗菌活性。

New botanical drug, HL tablet, reduces hepatic fat as measured by magnetic resonance spectroscopy in patients with nonalcoholic fatty liver disease: A placebo-controlled, randomized, phase Ⅱ trial

AIM To evaluate the efficacy and safety of HL tablet extracted from magnolia officinalis for treating patients with nonalcoholic fatty liver disease(NAFLD).METHODS Seventy-four patients with NAFLD diagnosed by ultrasonography were randomly assigned to 3 groups given high dose(400 mg) HL tablet, low dose(133.4 mg) HL tablet and placebo, respectively, daily for 12 wk. The primary endpoint was post-treatment change of hepatic fat content(HFC) measured by magnetic resonance spectroscopy. Secondary endpoints included changes of serum aspartate aminotransferase, alanine aminotransferase(ALT), cholesterol, triglyceride, free fatty acid, homeostasis model assessment-estimated insulin resistance, and body mass index(BMI).RESULTS The mean HFC of the high dose HL group, but not of the low dose group, declined significantly after 12 wk of treatment(high dose vs placebo, P = 0.033; low dose vs placebo, P = 0.386). The mean changes of HFC from baseline at week 12 were-1.7% ± 3.1% in the high dose group(P = 0.018),-1.21% ± 4.97% in the low dose group(P = 0.254) and 0.61% ± 3.87% in the placebo group(relative changes compared to baseline, high dose were:-12.1% ± 23.5%, low dose:-3.2% ± 32.0%, and placebo: 7.6% ± 44.0%). Serum ALT levels also tended to decrease in the groups receiving HL tablet while other factors were unaffected. There were no moderate or severe treatment-related safety issues during the study.CONCLUSION HL tablet is effective in reducing HFC without any negative lipid profiles, BMI changes and adverse effects.

Sensitive determination of 4-O-methylhonokiol in rabbit plasma by high performance liquid chromatography and application to its pharmacokinetic investigation

A novel high performance liquid chromatographic method was developed for the determination of 4-O- methylhonokiol in rabbit plasma and was applied to its pharmacokinetic investigation. Plasma samples were treated by one-fold volume of methanol and acetonitrile to remove the interference proteins. A reverse phase column of SHIM- PACK VP-ODS （150 mm × 4.6 mm, 5.0 μm） was used to separate 4-O-methylhonokiol in the plasma samples. The detection limit of 4-O-methylhonokiol was 0.2 μg/L and the linear range was 0. 012 - 1. 536 mg/L. The good extraction recoveries were obtained for the spiked samples （84.7%, 89.3% and 87.7% for low, middle and high concentrations of added standards, respectively）. The relative standard deviation of intra-day and inter-day precisions was in the range from 0.6% to 13.5%. The pharmacokinetic study of 4-O-methylhonokiol was made and the results from the plasmaconcentration curve of 4-0-methylhonokiol showed a two-apartment open model. This work developed a sensitive, stable and rapid HPLC method for the determination of 4-O-methylhonokiol and the developed method has been successfully applied to a pharmacokinetic study of 4-O-methylhonokiol.

Honokiol attenuates acetaminophen-induced acute liver injury by inhibiting hepatic CYP1A2 activity and improving liver mitochondrial dysfunction

Objective:Acetaminophen(APAP)overdose is a common cause of liver injury.This study aimed to investigate the protective effect of honokiol(Hon)against APAP-induced hepatotoxicity and its potential mechanism.Methods:C57BL/6 mice were administrated with Hon(10 and 30 mg/kg)after APAP(300 mg/kg)treatment.On 1.5 h and 5 h after Hon treatment,mice were sacrificed.Serum and liver were collected.And then,liver injury-related indexes,APAP metabolism-related indexes,mitochondrial respiratory chain function-related indexes,and mitochondrial membrane function-related protein expression were evaluated.Results:It was found that Hon significantly decreased serum alanine aminotransferase(ALT)/aspartate aminotransferase(AST)activity and glutathione(GSH)depletion,increased hepatic catalase(CAT)and GSH peroxidase(GSH-Px)activities,reduced hepatic MDA and 3-nitrotyrosine contents,inhibited hepatic CYP1A2 activity and APAP protein adducts(APAP-CYS)formation.Meanwhile,oxidative phosphorylation capacity of complex I and electron transfer capacity of complex IV in mitochondrial respiratory chain was increased,whereas the release of H2O2 in the mitochondria was decreased following Hon treatment.Furthermore,Hon markedly down-regulated p-JNK in both cytosol and mitochondria,and obviously inhibited the release of apoptosis inducing factor(AIF)and endonuclease G(EndoG)from mitochondria to cytosol.Conclusion:Hon alleviated APAP-induced liver injury through the following pathways:Reducing the production of APAP-CYS by inhibiting CYP1A2 activity;Ameliorating hepatic oxidative stress by increasing the levels of hepatic CAT,GSH-Px and GSH;Improving mitochondrial respiratory chain function by promoting oxidative phosphorylation capacity of complex I and electron transfer capacity of complex IV;Improving the function of mitochondrial membrane by inhibiting p-JNK and its translocation to mitochondria,thereby reducing the release of AIF and EndoG.