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

A new species of arbuscular mycorrhizal fungi (Glomeromycota), Acaulospora koreana, was isolated from forest soils in South Korea. This novel fungus was collected from the rhizosphere of Lindera obtusiloba and Styrax obassia in forest and propagated with Sorghum bicolor in pot. Morphological characteristics of spores of A. koreana are rarely distinguished from Acaulospora mellea, which is reported as one of the most abundant mycorrhizal species in Korea. However, molecular evidence of rDNA sequence using improved primers for glomeromycotan fungal identification strongly supported that A. koreana is different from A. mellea but also any other species belonging to the genus Acaulospora. This is the first novel glomeromycatan fungus introduced in South Korea, but it suggests that there is a high possibility for discovering new arbuscular mycorrhizal fungi considering the abundance of plant species and advanced phylogenetic analysis technique.
DNA, Ribosomal ; Forests ; Fungi* ; Glomeromycota ; Korea* ; Lindera ; Plants ; Rhizosphere ; Soil ; Sorghum ; Spores ; Styrax

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

Lindera obtusiloba has been used in traditional herbal medicine for the treatment of blood stasis and inflammation. The leaves of Lindera obtusiloba have been reported to exhibit various physiological activities. However, there is little information available on their antiplatelet and antithrombotic activities. Thus, the present study aimed to evaluate the effect of Lindera obtusiloba leaf extract (LLE) on platelet activities, coagulation and thromboembolism. In a platelet aggregation study, LLE significantly inhibited various agonist-induced platelet aggregations in vitro and ex vivo. Furthermore, LLE significantly inhibited collagen-induced thromboxane A2 (TXA2) production in rat platelets. In addition, oral administration of LLE was protective in a mouse model of pulmonary thromboembolism induced by intravenous injection of a mixture of collagen and epinephrine. Interestingly, LLE did not significantly alter prothrombin time (PT) and activated partial thromboplastin time (aPTT). This study indicates that the antithrombotic effects of LLE might be due to its antiplatelet activities rather than anticoagulation. Taken together, these results suggest that LLE may be a candidate preventive and therapeutic agent in cardiovascular diseases associated with platelet hyperactivity.
Administration, Oral ; Animals ; Blood Platelets ; Cardiovascular Diseases ; Collagen ; Epinephrine ; Herbal Medicine ; In Vitro Techniques ; Inflammation ; Injections, Intravenous ; Lindera* ; Mice ; Partial Thromboplastin Time ; Platelet Aggregation ; Prothrombin Time ; Pulmonary Embolism ; Rats ; Thromboembolism ; Thrombosis ; Thromboxane A2

Lindera obtusiloba has been widely used as a traditional medicine for the treatment of lots of diseases, including abdominal pain, bruise, and hepatocirrhosis. Here in this study, we elucidated the lifespan-extending effect of methanolic extract of Lindera obtusiloba (MLO) using Caenorhabditis elegans model system. We found that MLO has potent lifespan extension activities under normal culture condition. Then, we determined the protective effects of MLO on the stress conditions such as osmotic, thermal and oxidative stress. To reveal possible mechanism of MLO-mediated lifespan, we further investigated the effect of MLO on the antioxidant enzyme activities and intracellular ROS levels. Our results demonstrated that superoxide dismutase and catalase activities were significantly up-regulated by MLO treatment, resulted in reduced intracellular ROS levels. In this work, we also tested whether MLO-mediated longevity activity was associated with aging-related factors such as food intake and growth. Our data revealed that both of pharyngeal pumping rate and body length were significantly shifted by MLO treatment, indicating these factors were involved in MLO's lifespan-extension effects. Although MLO induces reduction in food intake, the body movement of MLO-fed aged worms was not decreased, compared to untreated control worms, indicating MLO might extend lifespan without affecting healthspan.
Abdominal Pain ; Caenorhabditis elegans* ; Caenorhabditis* ; Catalase ; Contusions ; Eating ; Lindera* ; Longevity ; Medicine, Traditional ; Methanol ; Oxidative Stress ; Superoxide Dismutase

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

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

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