The medicinal Lindera aggregata(Lindera, Lauraceae) boasts abundant resources, which is widely used in clinical settings. It has been found that the main chemical constituents of this medicinal species are sesquiterpenoids, alkaloids, sesquiterpenoid dimers, flavonoids, and phenolic acids. Some unreported novel structures, including lindenane-type sesquiterpene dimers and trimers, have been discovered from L. aggregata in recent years. The extracts and active components of L. aggregata have anti-tumor, anti-inflammatory, antalgic, liver-protecting, antioxidant, lipid-lowering, and glucose-lowering activities, and their mechanisms of action have been comprehensively investigated. This study summarizes the research on the chemical constituents and bioactivities of L. aggregata over the past decade, which is expected to serve as a reference for the future research and utilization of L. aggregata.
Lindera/chemistry* ; Alkaloids ; Flavonoids ; Antioxidants ; Sesquiterpenes/chemistry*

The present study explored the main active ingredients and the underlying mechanism of Linderae Radix the treatment of gastric cancer by network pharmacology, molecular docking, and in vitro cell experiments. TCMSP, OMIM and GeneCards database were used to obtain the active ingredients of Linderae Radix to predict the related targets of both Linderae Radix and gastric cancer. After screening the common potential action targets, the STRING database was used to construct the PPI network for protein interaction of the two common targets. Enrichment analysis of GO and KEGG by DAVID database. Based on STRING and DAVID platform data, Cytoscape software was used to construct an "active ingredient-target" network and an "active ingredient-target-pathway" network. Molecular docking was performed using the AutoDock Vina to predict the binding of the active components to the key action targets, and finally the key targets and pathways were verified in vitro. According to the prediction results, there were 9 active components, 179 related targets of Radix Linderae, 107 common targets of Linderae Radix and gastric cancer, 693 biological processes, 57 cell compositions, and 129 molecular functions involved in the targets, and 161 signaling pathways involved in tumor antigen p53, hypoxia-indu-cible factor 1, etc. Molecular docking results showed that the core component, jimadone, had high binding activity with TP53. Finally, in an in vitro experiment, the screened radix linderae active ingredient gemmadone is used for preliminarily verifying the core targets and pathways of the human gastric cancer cell SGC-7901, The results showed that germacrone could significantly inhibit the proliferation of gastric cancer cells and induce the apoptosis of SGC-7901 by regulating the expression of p53, Bax, Bcl-2 and other key proteins. In summary, Radix Linderae can control the occurrence and development of gastric cancer through multi-components, multi-targets and multi-pathways, which will provide theoretical basis for further clinical discussion on the mechanism of Radix Linderae in treating gastric cancer.
Antigens, Neoplasm ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Lindera/chemistry* ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Network Pharmacology ; Stomach Neoplasms/drug therapy* ; Tumor Suppressor Protein p53 ; bcl-2-Associated X Protein

Although the etiology of inflammatory bowel disease is still uncertain, increasing evidence indicates that the excessive activation of NLRP3 inflammasome plays a major role. Norisoboldine (NOR), an alkaloid isolated from Radix Linderae, has previously been demonstrated to inhibit inflammation and IL-1β production. The present study was to examine the effect of NOR on colitis and the underlying mechanism related to NLRP3 inflammasome activation. Our results showed that NOR alleviated colitis symptom in mice induced by 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). Moreover, it significantly reduced expressions of cleaved IL-1β, NLRP3 and cleaved Caspase-1 but not ASC in colons of mice. In THP-1 cells, NOR suppressed the expressions of NLRP3, cleaved Caspase-1 and cleaved IL-1β but not ASC induced by lipopolysaccharide (LPS) and adenosine triphosphate (ATP). Furthermore, NOR could activate aryl hydrocarbon receptor (AhR) in THP-1 cells, inducing CYP1A1 mRNA expression, and promoting dissociation of AhR/HSP90 complexes, association of AhR and ARNT, AhR nuclear translocation, XRE reporter activity and binding activity of AhR/ARNT/XRE. Both siAhR and α-naphthoflavone (α-NF) markedly diminished the inhibition of NOR on NLRP3 inflammasome activation. In addition, NOR elevated Nrf2 level and reduced ROS level in LPS- and ATP-stimulated THP-1 cells, which was reversed by either siAhR or α-NF treatment. Finally, correlations between activation of AhR and attenuation of colitis, inhibition of NLRP3 inflammasome activation and up-regulation of Nrf2 level in colons were validated in mice with TNBS-induced colitis. Taken together, NOR ameliorated TNBS-induced colitis in mice through inhibiting NLRP3 inflammasome activation via regulating AhR/Nrf2/ROS signaling pathway.
Alkaloids ; administration & dosage ; Animals ; Colitis ; chemically induced ; drug therapy ; genetics ; immunology ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Inflammasomes ; drug effects ; immunology ; Interleukin-1beta ; genetics ; immunology ; Lindera ; chemistry ; Male ; Mice ; Mice, Inbred BALB C ; NF-kappa B ; genetics ; immunology ; Receptors, Aryl Hydrocarbon ; agonists ; genetics ; metabolism ; Trinitrobenzenesulfonic Acid ; adverse effects

OBJECTIVETo study the anti-tumor metastatic constituents from Lindera glauca.

METHODConstituent isolation and purification was carried by repeated column chromatography (silica gel, Toyopearl HW-40 and preparative HPLC). Their structures were elucidated on the basis of spectral data analysis. The anti-tumor metastasis assay was applied to evaluate the isolated compounds of their activities.

RESULTTen compounds (1 - 10) were isolated and their structures were identified by comparison of their spectral data with literature values as follows: Laurotetanine (1), N-methyllaurotetanine (2), reticuline (3), pallidine (4), N-trans-feruloyltyramine (5), N-cis-feruloyltyramine (6), atheroline (7), norisosocorydine (8), [9,9,9-(2) H3]-(1S*, 3S*, 4S*, 8S*)-p-menthane-3,8-diol (9), [9,9,9-(2) H3 ]-(1S*, 3R*, 4S*, 8S*)-p-Menthane-3,8-diol (10). Compounds 1, 2, 4, 5, 7 and 9 showed positive anti-tumor metastatic activities,and compounds 1, 4, and 5 showed significant anti-tumor metastatic activities.

CONCLUSIONCompound 3 was isolated from this plant for the first time. Compounds 9 and 10 were isolated from Lindera genus for the first time. Compounds 1, 4, and 5 showed significant anti-tumor metastatic activities.

Alkaloids ; chemistry ; isolation & purification ; Antineoplastic Agents, Phytogenic ; chemistry ; isolation & purification ; Aporphines ; chemistry ; isolation & purification ; Benzylisoquinolines ; chemistry ; isolation & purification ; Cell Line, Tumor ; Chromatography, High Pressure Liquid ; methods ; Humans ; Lindera ; chemistry ; Monoterpenes ; chemistry ; isolation & purification ; Neoplasm Metastasis ; prevention & control ; Plant Extracts ; chemistry ; isolation & purification

OBJECTIVETo develop an HPLC method for simultaneous determination of four major alkaloids in Lindera aggregate.

METHODThe analysis was carried out on an Agilent ZORBAX SB-C18 column (4.6 mm x 250 mm, 5 microm) with gradient elution using acetonitrile-water (containing 0. 15% diethylamine, adjusted to pH = 3.0 with acetic acid) as mobile phase. Flow rate was 1.0 mL x min(-1) and the detection wavelength was at 289 nm.

RESULTThe calibration curves were linear over the range of 0.428-8.560 microg for boldine, 2.122-31.83 microg for norboldine, 0.760-15.20 microg for reticuline and 0.020 4-0.400 8 microg for linderegatine, respectively. The average recoveries were 99.18% for boldine, 101.0% for norboldine, 100.3% for reticuline and 99.17% for linderegatine, respectively. with RSD not more than 3.0%.

CONCLUSIONThe described method is reliable and convenient and could be used for the quality control of Lindera aggregate.

Alkaloids ; analysis ; Chromatography, High Pressure Liquid ; methods ; Lindera ; chemistry

OBJECTIVETo develop an HPLC method for simultaneous determination of three major sesquiterpene lactones in Radix Linderae.

METHODThe chromatographic separation was achieved on a Diamonsil C18 column (4.6 mm x 250 mm, 5 microm) using isocratic elution of acetonitrile-water (containing 0.1% H3 PO4) (45 : 55) at a flow rate of 1.0 mL x min(-1). Detection was carried out using a photodiode array detector at 220 nm.

RESULTThe calibration curves were linear in the range of 0.001 8-0.036 0 g x L(-1) for hydroxylinderstrenolide (R2 = 0.999 8), 0.016 2-0.323 2 g x L(-1) for neolinderalactone (R2 = 0.999 9), 0.010 5-0.209 9 g x L(-1) for linderane (R2 = 0.999 9), respectively. The average recoveries were 100.0% for hydroxylinderstrenolide, 98.8% for neolinderalactone and 98.9% for linderane with RSD not more than 3.3%.

CONCLUSIONThe established method was proved to be simple, sensitive and credible, and can be applied to quality control of Radix Linderae.

Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; analysis ; Lactones ; analysis ; Lindera ; chemistry ; Sesquiterpenes ; analysis

OBJECTIVETo develop a RP-HPLC method for quantitative determination of norisoboldine in Radix Linderae and to provide valuable data for quality control of Radix Linderae.

METHODThe separation was performed on a Phenomenex Gemini C18 column (4.6 mm x 250 mm, 5 microm) at 25 degrees C using a gradient elution of mobile phase A (0.5% formic acid, adjusted pH 2.25 with triethylamine) and mobile phase B (acetonitrile). The detection wavelength was 280 nm.

RESULTThe calibration curve showed a good linearity (r = 0.999 9) within test ranges of 0.015-1.509 microg. The average recovery was 99.58% with RSD 1.4%.

CONCLUSIONThe developed method is simple, accurate and reliable with good repeatability. It is suitable for quality evaluation of Radix Linderae.

Alkaloids ; analysis ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; analysis ; Lindera ; chemistry

Lindera erythrocarpa Makino (Lauraceae) is used as a traditional medicine for analgesic, antidote, and antibacterial purposes and shows anti-tumor activity. We studied the effects of Lindera erythrocarpa on the human ether-a-go-go-related gene (HERG) channel, which appears of importance in favoring cancer progression in vivo and determining cardiac action potential duration. Application of MeOH extract of Lindera erythrocarpa showed a dose-dependent decrease in the amplitudes of the outward currents measured at the end of the pulse (I(HERG)) and the tail currents of HERG (I(tail)). When the BuOH fraction and H2O fraction of Lindera erythrocarpa were added to the perfusate, both I(HERG) and I(tail) were suppressed, while the hexane fraction, CHCl3 fraction, and EtOAc fraction did not inhibit either I(HERG) or I(tail). The potential required for half-maximal activation caused by EtOAc fraction, BuOH fraction, and H2O fraction shifted significantly. The BuOH fraction and H2O fraction (100 microgram/mL) decreased gmax by 59.6% and 52.9%, respectively. The H2O fraction- and BuOH fraction-induced blockades of I(tail) progressively decreased with increasing depolarization, showing the voltage-dependent block. Our findings suggest that Lindera erythrocarpa, a traditional medicine, blocks HERG channel, which could contribute to its anticancer and cardiac arrhythmogenic effect.
Animals ; Butanols/chemistry/metabolism ; Ether-A-Go-Go Potassium Channels/*antagonists & inhibitors/metabolism ; Female ; Humans ; Lindera/*chemistry ; Oocytes/cytology/physiology ; Patch-Clamp Techniques ; Plant Extracts/*metabolism ; Potassium Channel Blockers/*metabolism ; Xenopus laevis

OBJECTIVEThe influence of spray drying technology on the damp proof effect of microcapsules and the mechanism were studied.

METHODThe microcapsules prepared with different spray drying parameters have been put in certain surroundings for 12 hours, then the hygroscopic curves were gotten; the mechanism was studied from the following aspects: solvent residue, film's shrink and particle size.

RESULTThe damp proof effect enhanced with the increase of inlet air temperature and the decrease of flow rate and air pressure. The properties of the wall, the solvent residue and particle size can influence the damp proof effect of the microcapsules.

CONCLUSIONThe physical properties of microcapsules are different because of the different spray drying parameters, which lead to different damp proof effect of microcapsules.

Acrylic Resins ; Capsules ; Desiccation ; methods ; Drug Compounding ; methods ; Lindera ; chemistry ; Particle Size ; Plants, Medicinal ; chemistry ; Solvents ; Tannins ; administration & dosage ; isolation & purification ; Temperature

AIMTo evaluate the antioxidant capacity and quality of traditional Chinese medicines using TLC-bioautography.

METHODSTwo chromatograms of each crude drug sample were obtained, after developing, by spraying with 1,1-diphenyl-2-picrylhydrazyl (DPPH) solution in ethanol and classical stained reagents, separately. The images sprayed with DPPH solution were captured under light after the plates were heated at 40 degrees C for 30 min, and scanned using video scan software to get peak areas of active compounds.

RESULTSTotal peak areas of the spots on TLC were calculated to evaluate the antioxidant capacity of the tested crude drugs from different habitats and sources. The results indicated that Radix Linderae cultivated in Tiantai (Zhejiang province), Cortex Magnoliae Officinalis cultivated in Liangshan (Sichuan province), and Fructus Perillae acquired in Shanghai have the highest scavenging properties towards DPPH in their respective TLC-autographic assays. Norisoboldine, magnolol and honokiol, luteolin, apigenin and an unknown compound "U" proved to be the major antioxidant components in the corresponding crude drugs as they contribute the dominating peak areas to the total ones.

CONCLUSIONTLC-bioautography can not only be used for screening of the components with antioxidant potency but also for the purpose of quality evaluation of traditional Chinese medicines at the same time, and the method proved to be selective, simple and reproducible.

Alkaloids ; isolation & purification ; pharmacology ; Antioxidants ; isolation & purification ; pharmacology ; Biphenyl Compounds ; chemistry ; isolation & purification ; pharmacology ; China ; Chromatography, Thin Layer ; methods ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Hydrazines ; chemistry ; Lignans ; isolation & purification ; pharmacology ; Lindera ; chemistry ; Luteolin ; isolation & purification ; pharmacology ; Magnolia ; chemistry ; Perilla ; chemistry ; Picrates ; Plants, Medicinal ; chemistry ; Quality Control ; Reproducibility of Results