An insight into the anticancer potentials of lignan arctiin: A comprehensive review of molecular mechanisms.

Natural products are being developed as possible treatment options due to the rising prevalence of cancer and the harmful side effects of synthetic medications. Arctiin is a naturally occurring lignan found in numerous plants and exhibits different pharmacological activities, along with cancer. To elucidate the anticancer properties and underlying mechanisms of action, a comprehensive search of various electronic databases was conducted using appropriate keywords to identify relevant publications. The findings suggest that arctiin exhibits anticancer properties against tumor formation and various cancers such as cervical, myeloma, prostate, endothelial, gastric, and colon cancers in several preclinical pharmacological investigations. This naturally occurring compound exerts its anticancer effect through different cellular mechanisms, including mitochondrial dysfunction, cell cycle at different phases (G2/M), inhibition of cell proliferation, apoptotic cell death, and cytotoxic effects, as well as inhibition of migration and invasion of various malignant cells. Moreover, the study also revealed that, among the various cellular pathways, arctiin was shown to be more potent in terms of the PI3K/AKT and JAK/STAT signaling pathways. However, pharmacokinetic investigation indicated the compound's poor oral bioavailability. Because of these findings, arctiin might be considered a promising chemotherapeutic drug candidate.

A novel natural Syk inhibitor suppresses IgE-mediated mast cell activation and passive cutaneous anaphylaxis.

Spleen tyrosine kinase (Syk) plays a crucial role as a target for allergy treatment due to its involvement in immunoreceptor signaling. The purpose of this study was to identify natural inhibitors of Syk and assess their effects on the IgE-mediated allergic response in mast cells and ICR mice. A list of eight compounds was selected based on pharmacophore and molecular docking, showing potential inhibitory effects through virtual screening. Among these compounds, sophoraflavanone G (SFG) was found to inhibit Syk activity in an enzymatic assay, with an IC50 value of 2.2 µM. To investigate the conformational dynamics of the SYK-SFG system, we performed molecular dynamics simulations. The stability of the binding between SFG and Syk was evaluated using root mean square deviation (RMSD) and root mean square fluctuation (RMSF). In RBL-2H3 cells, SFG demonstrated a dose-dependent suppression of IgE/BSA-induced mast cell degranulation, with no significant cytotoxicity observed at concentrations below 10.0 µM within 24 h. Furthermore, SFG reduced the production of TNF-α and IL-4 in RBL-2H3 cells. Mechanistic investigations revealed that SFG inhibited downstream signaling proteins, including phospholipase Cγ1 (PLCγ1), as well as mitogen-activated protein kinases (AKT, Erk1/2, p38, and JNK), in mast cells in a dose-dependent manner. Passive cutaneous anaphylaxis (PCA) experiments demonstrated that SFG could reduce ear swelling, mast cell degranulation, and the expression of COX-2 and IL-4. Overall, our findings identify naturally occurring SFG as a direct inhibitor of Syk that effectively suppresses mast cell degranulation both in vitro and in vivo.

The protective effects of Arctiin in asthma by attenuating airway inflammation and inhibiting p38/NF-κB signaling.

Asthma is a common chronic inflammatory disease of the airways, which affects millions of people worldwide. Arctiin, a bioactive molecule derived from the traditional Chinese Burdock, has not been previously reported for its effects on asthma in infants. In this study, an asthma model was established in mice by stimulation with ovalbumin (OVA). Bronchoalveolar lavage (BALF) was collected from OVA-challenged mice and the cells were counted. Lung tissue was harvested for hematoxylin-eosin (HE) staining and measurement of Wet/Dry weight ratios. The expressions of proteins were detected using enzyme-linked immunosorbent assay (ELISA) and Western blots. The superoxide dismutase (SOD) activity in lung tissue was measured using a commercial kit. We found that Arctiin had beneficial effects on asthma treatment. Firstly, it attenuated OVA-challenged lung pathological alterations. Secondly, it ameliorated pro-inflammatory response by reducing the number of inflammatory cells and mitigating the imbalance of Th1/Th2 factors in the bronchoalveolar lavage (BALF) of OVA-challenged mice. Importantly, Arctiin ameliorated OVA-induced lung tissue impairment and improved lung function. Additionally, we observed that oxidative stress (OS) in the pulmonary tissue of OVA-challenged mice was ameliorated by Arctiin. Mechanistically, Arctiin prevented OVA-induced activation of p38 and nuclear factor-κB (NF-κB). Based on these findings, we conclude that Arctiin might serve as a promising agent for the treatment of asthma.

ARC@DPBNPs suppress LPS-induced acute lung injury via inhibiting macrophage pyroptosis and M1 polarization by ERK pathway in mice.

AIM OF THE STUDY: Exploring the protective effect of ARC@DPBNP on lipopolysaccharides (LPS)-induced ALI and its underlying mechanism. MATERIALS AND METHODS: ALI model was established by intransally administrating LPS (4 mg/kg) into C57BL/6 mice. The suppression effects of ALI was first compared between ARC (intragastric administrated, with doses ranging from 10 to 80 mg/kg) and ARC@BPBNPs (intratracheally administrated, with doses ranging from 1 to 4 mg/kg). Changes in lung histology post intratracheal intervention of 3 mg/kg ARC@DPBNPs were detected. The expression of pyrotosis pathway-related proteins in lungs as well as in RAW264.7 cells was detected by western blotting. The ASC expression in lung macrophages was examined using immune-fluorescent staining. The polarization of RAW264.7 cells and lung macrophages were detected by flow cytometry. The network pharmacology was constructed by Cytoscape, and the molecular docking was perfomed by AutoDock Vina. RESULTS: Docking predicted the high affinity of ARC to MAPK1 (ERK2). HE staining showed that ARC@DPBNPs attenuated LPS-induced ALI at a remarkably lower dose than ARC. The improved histopathological changes, lung W/D weight ratio, and decreased of inflammatory factor levels in lung collectively demonstrated the alleviation effects of ARC@DPBNPs. Compared with the LPS group, ARC@DPBNPs down-regulated the ERK pathway, resulted in a suppression of the macrophage pyroptosis and M1 polarization. This suppression effects could be removed by the ERK activator Ro 67-7476. CONCLUSION: ARC@DPBNPs attenuated ALI by suppressing LPS-induced macrophage pyroptosis and polarization, probably through down-regulation of the ERK pathway.

Evaluation of the effect of designed PLGA-arctiin nanoparticles modified with folic acid and chitosan on colon cancer cells.

In this study, we designed nanoparticles (NPs) based on polylactic acid glycolic acid modified with chitosan and folic acid to optimize the anti-cancer, anti-inflammatory, and antioxidant effects of arctiin (ARC), and we measured its effects on cancer cells, including colon cancer. NPs were synthesized using the W1/O/W2 double-emulsion solvent evaporation method. Physicochemical characteristics of synthesized NPs (ARC-PCF-NPs), including average particle size, dispersity index (PDI), zeta potential (ZP), field emission scanning electron microscope figures, and encapsulation efficiency (EE), were evaluated. 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP) methods were carried out to determine the antioxidant properties of NPs. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay was performed to investigate cytotoxicity effects on cancer cells and normal fibroblasts. Quantitative polymerase chain reaction was also performed on inflammatory and antioxidant genes. The obtained results indicated that the synthesized NPs have a size of 100 nm, a DPI of 0.36, a ZP of 26.30 mV, and EE was calculated at about 87.5%. The antioxidant influence of ARC-PCF-NPs was confirmed by inhibiting ABTS and DPPH free radicals and ferrous reduction in the FRAP method. Moreover, the reduction of inflammatory and antioxidant genes confirmed the anti-inflammatory and antioxidant properties of NPs. These results indicate the modification of the surface of NPs in order to increase the bioavailability, stability, and effectiveness of medicinal compounds in therapeutic applications.

Protective effect of arctiin against Toxoplasma gondii HSP70-induced allergic acute liver injury by disrupting the TLR4-mediated activation of cytosolic phospholipase A2 and platelet-activating factor.

Toxoplasma gondii (T. gondii)-derived heat shock protein 70 (T.g.HSP70) is a toxic protein that downregulates host defense responses against T. gondii infection. T.g.HSP70 was proven to induce fatal anaphylaxis in T. gondii infected mice through cytosolic phospholipase A2 (cPLA2) activated-platelet-activating factor (PAF) production via Toll-like receptor 4 (TLR4)-mediated signaling. In this study, we investigated the effect of arctiin (ARC; a major lignan compound of Fructus arctii) on allergic liver injury using T.g.HSP70-stimulated murine liver cell line (NCTC 1469) and a mouse model of T. gondii infection. Localized surface plasmon resonance, ELISA, western blotting, co-immunoprecipitation, and immunofluorescence were used to investigate the underlying mechanisms of action of ARC on T. gondii-induced allergic acute liver injury. The results showed that ARC suppressed the T.g.HSP70-induced allergic liver injury in a dose-dependent manner. ARC could directly bind to T.g.HSP70 or TLR4, interfering with the interaction between these two factors, and inhibiting activation of the TLR4/mitogen-activated protein kinase/nuclear factor-kappa B signaling, thereby inhibiting the overproduction of cPLA2, PAF, and interferon-γ. This result suggested that ARC ameliorates T.g.HSP70-induced allergic acute liver injury by disrupting the TLR4-mediated activation of inflammatory mediators, providing a theoretical basis for ARC therapy to improve T.g.HSP70-induced allergic liver injury.

Bacillus subtilis partially inhibits African swine fever virus infection in vivo and in vitro based on its metabolites arctiin and genistein interfering with the function of viral topoisomerase II.

IMPORTANCE: African swine fever virus (ASFV) is a highly fatal swine disease that severely affects the pig industry. Although ASFV has been prevalent for more than 100 years, effective vaccines or antiviral strategies are still lacking. In this study, we identified four Bacillus subtilis strains that inhibited ASFV proliferation in vitro. Pigs fed with liquid biologics or powders derived from four B. subtilis strains mixed with pellet feed showed reduced morbidity and mortality when challenged with ASFV. Further analysis showed that the antiviral activity of B. subtilis was based on its metabolites arctiin and genistein interfering with the function of viral topoisomerase II. Our findings offer a promising new strategy for the prevention and control of ASFV that may significantly alleviate the economic losses in the pig industry.

Arctiin attenuates iron overload­induced osteoporosis by regulating the PI3K/Akt pathway.

Iron overload is a prevalent pathological factor observed among elderly individuals and those with specific hematological disorders, and is frequently associated with an elevated incidence of osteoporosis. Although arctiin (ARC) has been shown to possess antioxidant properties and the ability to mitigate bone degeneration, its mechanism of action in the treatment of iron overload­induced osteoporosis (IOOP) remains incompletely understood. To explore the potential molecular mechanisms underlying the effects of ARC, the MC3T3­E1 cell osteoblast cell line was used. Cell Counting Kit was used to assess MC3T3­E1 cell viability. Alkaline phosphatase staining and alizarin red staining were assessed for osteogenic differentiation. Calcein AM assay was used to assess intracellular iron concentration. In addition, intracellular levels of reactive oxygen species (ROS), lipid peroxides, mitochondrial ROS, apoptosis rate and mitochondrial membrane potential changes in MC3T3­E1 cells were examined using flow cytometry and corresponding fluorescent dyes. The relationship between ARC and the PI3K/Akt pathway was then explored by western blotting and immunofluorescence. In addition, the effects of ARC on IOOP was verified using an iron overload mouse model. Immunohistochemistry was performed to evaluate expression of osteogenesis­related proteins. Micro-CT and H&E were used to analyze bone microstructural parameters and histomorphometric indices in the bone tissue. Notably, ARC treatment reversed the decreased viability and increased apoptosis in MC3T3­E1 cells originally induced by ferric ammonium citrate, whilst promoting the formation of mineralized bone nodules in MC3T3­E1 cells. Furthermore, iron overload induced a decrease in the mitochondrial membrane potential, augmented lipid peroxidation and increased the accumulation of ROS in MC3T3­E1 cells. ARC not only positively regulated the anti­apoptotic and osteogenic capabilities of these cells via modulation of the PI3K/Akt pathway, but also exhibited antioxidant properties by reducing oxidative stress. In vivo experiments confirmed that ARC improved bone microarchitecture and biochemical parameters in a mouse model of iron overload. In conclusion, ARC exhibits potential as a therapeutic agent for IOOP by modulating the PI3K/Akt pathway, and via its anti­apoptotic, antioxidant and osteogenic properties.

Arctiin alleviates functional constipation by enhancing intestinal motility in mice.

Functional constipation (FC), a common symptom that is primarily associated with intestinal motility dysfunction, is a common problem worldwide. Arctiin (Arc) is a lignan glycoside isolated from the Chinese herbal medicine Arctium lappa L., which is a health food in China. The present study aimed to evaluate the laxative effects of Arc against FC in mice. A model of FC induced by loperamide (5 mg/kg) was established in male Institute of Cancer Research (ICR) mice. Arc was administered at a dose of 100 mg/kg as a protective agent. The faecal status, intestinal motility and histological analyses were evaluated. Furthermore, the levels of gastrointestinal motility-associated neurotransmitters, such as motilin (MTL), nitric oxide (NO), and brain-derived neurotrophic factor (BDNF) and the protective effect of Arc on interstitial cells of Cajal (ICC) were assessed. Arc treatment reversed the loperamide-induced reduction in faecal number and water content and the intestinal transit ratio in ICR mice. Histological analysis confirmed that Arc administration mitigated colonic injury. Moreover, Arc treatment increased levels of motilin and brain-derived neurotrophic factor while decreasing nitric oxide levels and ICC injury in the colon of FC mice. Arc decreased inflammation induction and aquaporin expression levels. Owing to its pro-intestinal motility property, Arc was shown to have a protective effect against FC and may thus serve as a promising therapeutic strategy for the management of FC.

Arctiin-encapsulated DSPE-PEG bubble-like nanoparticles inhibit alveolar epithelial type 2 cell senescence to alleviate pulmonary fibrosis via the p38/p53/p21 pathway.

Background: Idiopathic pulmonary fibrosis is a severe and deadly form of diffuse parenchymal lung disease and treatment options are few. Alveolar epithelial type 2 (AEC2) cell senescence is implicated in the pathogenies of IPF. A major bioactive compound from the traditional Chinese medicine Fructus arctii, arctiin (ARC) has robust anti-inflammatory, anti-senescence, and anti-fibrosis functions. However, the potential therapeutic effects of ARC on IPF and the underlying mechanisms involved are still unknown. Methods: First of all, ARC was identified as an active ingredient by network pharmacology analysis and enrichment analysis of F. arctii in treating IPF. We developed ARC-encapsulated DSPE-PEG bubble-like nanoparticles (ARC@DPBNPs) to increase ARC hydrophilicity and achieve high pulmonary delivery efficiency. C57BL/6 mice were used to establish a bleomycin (BLM)-induced pulmonary fibrosis model for assessing the treatment effect of ARC@DPBNPs on lung fibrosis and the anti-senescence properties of AEC2. Meanwhile, p38/p53 signaling in AEC2 was detected in IPF lungs, BLM-induced mice, and an A549 senescence model. The effects of ARC@DPBNPs on p38/p53/p21 were assessed in vivo and in vitro. Results: Pulmonary route of administration of ARC@DPBNPs protected mice against BLM-induced pulmonary fibrosis without causing significant damage to the heart, liver, spleen, or kidney. ARC@DPBNPs blocked BLM-induced AEC2 senescence in vivo and in vitro. The p38/p53/p21 signaling axis was significantly activated in the lung tissues of patients with IPF, senescent AEC2, and BLM-induced lung fibrosis. ARC@DPBNPs attenuated AEC2 senescence and pulmonary fibrosis by inhibiting the p38/p53/p21 pathway. Conclusion: Our data suggest that the p38/p53/p21 signaling axis plays a pivotal role in AEC2 senescence in pulmonary fibrosis. The p38/p53/p21 signaling axis inhibition by ARC@DPBNPs provides an innovative approach to treating pulmonary fibrosis in clinical settings.

Synthesis, Structural Elucidation, and Anti-Inflammatory Activity of a Water-Soluble Derivative of Arctiin.

The poor oral bioavailability of arctiin caused by its low water solubility is the biggest obstacle in developing it as a drug. In this work, a new water-soluble glucuronide derivative of arctiin (arctigenin-4'-O-glucuronide) was synthesized through 2,2,6,6-tetramethylpiperidine 1-oxyl mediated oxidation reaction. Subsequently, its anti-inflammatory effect was evaluated by mice acute lung injury model in vivo. The results showed that the glucuronide derivative of arctiin not only had better water solubility but also displayed improved anti-inflammatory activity in vivo, thus serving as an innovative compound in the drug development of arctiin.

High Cholesterol-Induced Bone Loss Is Attenuated by Arctiin via an Action in Osteoclasts.

High cholesterol-induced bone loss is highly associated with oxidative stress, which leads to the generation of oxysterols, such as 7-ketocholesterol (7-KC). Here, we conducted in vivo and in vitro experiments to determine whether arctiin prevents high cholesterol diet-induced bone loss by decreasing oxidative stress. First, arctiin was orally administered to atherogenic diet (AD)-fed C57BL/6J male mice at a dose of 10 mg/kg for 6 weeks. Micro-computerized tomography (µCT) analysis showed that arctiin attenuated AD-induced boss loss. For our in vitro experiments, the anti-oxidant effects of arctiin were evaluated in 7-KC-stimulated osteoclasts (OCs). Arctiin decreased the number and activity of OCs and inhibited autophagy by disrupting the nuclear localization of transcription factor EB (TFEB) and downregulating the oxidized TFEB signaling pathway in OCs upon 7-KC stimulation. Furthermore, arctiin decreased the levels of reactive oxygen species (ROS) by enhancing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), catalase, and heme oxygenase 1 (HO-1), all of which affected OC differentiation. Conversely, silencing of Nrf2 or HO-1/catalase attenuated the effects of arctiin on OCs. Collectively, our findings suggested that arctiin attenuates 7-KC-induced osteoclastogenesis by increasing the expression of ROS scavenging genes in the Nrf2/HO-1/catalase signaling pathway, thereby decreasing OC autophagy. Moreover, arctiin inhibits the oxidation and nuclear localization of TFEB, thus protecting mice from AD-induced bone loss. Our findings thus demonstrate the therapeutic potential of arctiin for the prevention of cholesterol-induced bone loss.

Network pharmacology and computer-aided drug design to explored potential targets of Lianhua Qingwen and Qingfei Paidu decoction for COVID-19.

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2, has spread globally, affecting people's lives worldwide and hindering global development. Traditional Chinese Medicine (TCM) plays a unique role in preventing and treating COVID-19. Representative prescriptions for the COVID-19 treatment, Lianhua Qingwen (LHQW) and Qingfei Paidu Decoction (QFPD), effectively alleviate COVID-19 symptoms, delaying its progression and preventing its occurrence. Despite the extensive similarity in their therapeutic effects, the mechanisms and advantages of LHQW and QFPD in in treating mild-to-moderate COVID-19 remain elusive. To characterize the mechanisms of LHQW and QFPD in treating COVID-19, we used integrated network pharmacology and system biology to compare the LHQW and QFPD components, active compounds and their targets in Homo sapiens. LHQW and QFPD comprise 196 and 310 active compounds, some of which have identical targets. These targets are enriched in pathways associated with inflammation, immunity, apoptosis, oxidative stress, etc. However, the two TCM formulas also have specific active compounds and targets. In LHQW, arctiin, corymbosin, and aloe-emodin target neurological disease-related genes (GRM1 and GRM5), whereas in QFPD, isofucosterol, baicalein, nobiletin, oroxylin A, epiberberine, and piperlonguminine target immunity- and inflammation-related genes (mTOR and PLA2G4A). Our findings indicate that LHQW may be suitable for treating mild-to-moderate COVID-19 with nervous system symptoms. Moreover, QFPD may effectively regulate oxidative stress damage and inflammatory symptoms induced by SARS-CoV-2. These findings may provide references for the clinical application of LHQW and QFPD.

Chromatographic fingerprint combined with quantitative analysis of multi-components by single-marker for quality control of total lignans from Fructus arctii by high-performance liquid chromatography.

INTRODUCTION: The total lignans from Fructus arctii (TLFA) is a mixture of a series of lignans isolated from dried ripe fruit of Arctium lappa L. We previously reported on the pharmacological activity of TLFA that is related to diabetes. An accurate and practical TLFA quantitative analysis method for utilising it needs to be established. OBJECTIVE: This study aimed to develop an effective quantitative analysis method for assessing the TLFA quality. METHODS: A total of 11 marker components were confirmed by analysing the high-performance liquid chromatography fingerprints of 24 batches of TLFA samples. The samples were prepared from TLFA and structurally identified as lappaol H, lappaol C, arctiin, arctignan D, arctignan E, matairesinol, arctignan G, isolappaol A, lappaol A, arctigenin, and lappaol F. In the quantitative analysis of multi-components by the single-marker (QAMS) method and with arctiin as an internal reference substance, the content of these lignans in TLFA was simultaneously determined according to their relative correction factors with arctiin. RESULTS: There was no significant difference between results measured by the QAMS and traditional external standard methods. Hierarchical cluster and principal component analyses were performed to evaluate 24 TLFA batches based on the contents of 10 marker components. The results revealed that QAMS method combined with chemometric analyses could accurately measure and clearly distinguish the different quality samples of TLFA. CONCLUSION: The QAMS method is a reliable and promising quality control method for TLFA. It can provide a reference for promoting quality control of complex multi-component systems, especially for traditional Chinese medicine.

Arctiin-reinforced antioxidant microcarrier antagonizes osteoarthritis progression.

Loss of extracellular matrix (ECM) of cartilage due to oxidative stress injury is one of the main characteristics of osteoarthritis (OA). As a bioactive molecule derived from the traditional Chinese Burdock, arctiin exerts robust antioxidant properties to modulate redox balance. However, the potential therapeutic effects of arctiin on OA and the underlying mechanisms involved are still unknown. Based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) tool, Burdock-extracted small molecule arctiin was identified as a potential anti-arthritic component. In vitro, treatment using arctiin rescued the interleukin (IL)-1ß-induced activation of proteinases and promoted the cartilage ECM synthesis in human chondrocytes. In vivo, intraperitoneal injection of arctiin ameliorated cartilage erosion and encountered subchondral bone sclerosis in the post-traumatic OA mice. Transcriptome sequencing uncovered that arctiin-enhanced cartilage matrix deposition was associated with restricted oxidative stress. Mechanistically, inhibition of nuclear factor erythroid 2-related factor 2 (NRF2) abolished arctiin-mediated anti-oxidative and anti-arthritic functions. To further broaden the application prospects, a gellan gum (GG)-based bioactive gel (GG-CD@ARC) encapsulated with arctiin was made to achieve long-term and sustained drug release. Intra-articular injection of GG-CD@ARC counteracted cartilage degeneration in the severe (12 weeks) OA mice model. These findings indicate that arctiin may be a promising anti-arthritic agent. Furthermore, GG-modified bioactive glue loaded with arctiin provides a unique strategy for treating moderate to severe OA.

Arctiin elevates osteogenic differentiation of MC3T3-E1 cells by modulating cyclin D1.

Osteoporosis is a systemic disorder of bone metabolism. This study aimed to investigate the impacts and possible mechanisms of Arctiin, a lignin isolated from Arctium lappa on MC3T3-E1 osteoblast differentiation. In this study, after treatment with different concentrations of Arctiin, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to estimate the expression of osteogenesis markers. Then, the activity of alkaline phosphatase (ALP) was detected by an ALP assay kit and calcium nodules staining was evaluated by alizarin red staining (ARS). Additionally, the regulatory effects of Arctiin on cyclin D1 (Ccnd1) was assessed by measurement of protein expression. Subsequently, the functions of Ccnd1 silencing on the osteogenic differentiation was examined in Arctiin-treated MC3T3-E1 cells. Results indicated that Arctiin dose-dependently upregulated the expression of runt-related transcription factor 2 (RUNX2), collagen type 1 (COL1A1), osteocalcin (OCN) and osteopontin (OPN). Elevated ALP activity and calcification degree was prominently observed in the Arctiin-treated groups. Moreover, Ccnd1 expression was notably enhanced after Arctiin intervention. Importantly, Ccnd1-knockdown abrogated the impacts of Arctiin on osteogenic differentiation of MC3T3-E1. To conclude, findings in this study suggested that Arctiin could regulate MC3T3-E1 osteoblast differentiation via up-regulating Ccnd1, supporting that Arctiin might be a therapeutic target for osteoporosis.

Protective effect and possible mechanism of arctiin on broilers challenged by Salmonella pullorum.

This study was aimed to investigate the effects of dietary arctiin (ARC) supplementation (100, 200, and 400 mg/kg) on the growth performance and immune response of broilers after a Salmonella pullorum (S. pullorum) challenge, and we conducted in vitro antibacterial test to explore the bacteriostatic mechanism of ARC. The in vivo trial was randomly assigned to six groups: noninfected control (NC) group and positive control (PC) group received a basal diet; TET group, received a basal diet supplemented with 100 mg/kg chlortetracycline; ARC100, ARC200, and ARC400 groups received a basal diet containing 100, 200, and 400 mg/kg ARC, respectively. From days 14 to 16, all birds (except the NC group) were infected with 1 mL (1 × 108 CFU per mL) fresh S. pullorum culture by oral gavage per day. In vivo results showed that dietary supplementation of 200 mg/kg ARC significantly increased average daily gain (P < 0.05) and decreased feed-to-gain ratio of broilers vs. the PC group during days 15 to 28 after being challenged with S. pullorum (P < 0.05). The jejunal crypt depth (CD) was decreased by supplementing 100 or 200 mg/kg ARC in diets compared with PC birds at day 19 (P < 0.05). The jejunal villi height (VH) was increased by supplementing 100, 200, or 400 mg/kg ARC in diets compared with PC birds at day 28 (P < 0.05). Besides, dietary supplementation of 200 mg/kg ARC increased the jejunal VH to CD ratio than the PC group both at days 19 and 28 (P < 0.05). Notably, the broilers had lower serum lipopolysaccharide and diamine oxidase levels in the ARC100 and ARC200 groups at day 28 than those in the PC group (P < 0.05). Furthermore, in comparison to PC birds, the birds in ARC groups (100, 200, and 400 mg/kg) had higher serum contents of IgM and IL-10, and the birds in the ARC200 group had higher serum contents of IgA at day 19 (P < 0.05). At day 28, the birds in ARC groups (100, 200, and 400 mg/kg) had lower serum contents of IL-8, and the birds in the ARC200 group had lower serum contents of IFN-γ compared with PC birds (P < 0.05). The in vitro experiment showed that ARC significantly inhibited the biofilm formation and adhesion of S. pullorum (P < 0.05). Metabonomics analysis revealed that ARC can restrain the formation of the biofilm by affecting a variety of metabolic pathways of S. pullorum. Therefore, dietary supplementation of 200 mg/kg ARC might be a potential way to substitute antibiotics to control S. pullorum infection in broilers.

Pullorosis caused by Salmonella pullorum (S. pullorum) is a severe contagious disease and could cause great economic loss to the poultry industry. Antibiotics are usually used to control pullorosis, while prolonged use of antibiotics has led to the emergence of multidrug-resistant bacterial strains. Therefore, it is necessary to find safer and more effective alternatives to substitute antibiotics. In this study, we established a model of S. pullorum infection in broilers and conducted in vitro antibacterial test to explore the preventive effect and mechanisms of dietary arctiin (ARC) supplementation on S. pullorum infection in broilers. The results showed that ARC could not only improve the immune function of infected broilers by regulating the immune system but also directly inhibit the invasion of S. pullorum to broilers by inhibiting the formation and adhesion rate of S. pullorum biofilm. Dietary supplementation of 200 mg/kg ARC might be a potential way to substitute antibiotics to control S. pullorum infection in broilers.

Arctiin Inhibits Cervical Cancer Cell Migration and Invasion through Suppression of S100A4 Expression via PI3K/Akt Pathway.

Arctiin, a lignan glycoside, is isolated from Arctium lappa L. The anticancer effects of arctiin have been demonstrated in several studies. However, no research has been conducted on the anti-migration effect of arctiin in cervical cancer cells. The present study examined the effects of arctiin on cervical cancer cells and investigated the possible molecular mechanism. We demonstrated that arctiin exhibited low cytotoxicity and significantly inhibited cell migration and invasion in human cervical cancer cells. The S100A4 protein expression and mRNA levels were significantly reduced in HeLa and SiHa cells with arctiin treatment. Furthermore, silencing S100A4 by using small interfering RNA reduced cell migration, while overexpression of S100A4 mitigated the migration inhibition imposed by arctiin in cervical cancer cells. Western blotting revealed that arctiin significantly reduced phosphoinositide 3-kinase (PI3K) and phosphorylation of Akt in cervical cancer cells. Moreover, selective Akt induction by an Akt activator, SC-79, reverted cervical cancer cell migration and S100A4 protein expression, which were reduced in response to arctiin. Taken together, these results suggest that arctiin inhibits cervical cancer cell migration and invasion through suppression of S100A4 and the PI3K/Akt pathway.

The first high-quality chromosomal genome assembly of a medicinal and edible plant Arctium lappa.

Arctium lappa has a long medicinal and edible history with great economic importance. Here, the first high-quality chromosome-level draft genome of A. lappa was presented by the Illumina and PacBio sequencing data. The assembled genome was approximately 1.79 Gb with a N50 contig size of 6.88 Mb. Approximately 1.70 Gb (95.4%) of the contig sequences were anchored onto 18 chromosomes using Hi-C data; the scaffold N50 was improved to be 91.64 Mb. Furthermore, we obtained 1.12 Gb (68.46%) of repetitive sequences and 32,771 protein-coding genes; 616 positively selected candidate genes were identified. Among candidate genes related to lignan biosynthesis, the following were found to be highly correlated with the accumulation of arctiin: 4-coumarate-CoA ligase (4CL), dirigent protein (DIR), and hydroxycinnamoyl transferase (HCT). Additionally, we compared the transcriptomes of A. lappa roots at three different developmental stages and identified 8,943 differentially expressed genes (DEGs) in these tissues. These data can be utilized to identify genes related to A. lappa quality or provide a basis for molecular identification and comparative genomics among related species.

Effects of arctiin relieving inflammatory injury of human nasopharyngeal epithelial cells induced by lipopolysac- charide / 中国药房

OBJECTIVE To investigate the effect of arctiin （ARC）relieving lipopolysaccharide （LPS）induced inflammatory injury of human nasopharyngeal epithelial cells NP- 69. METHODS The effects of 24 h treatment of 0.000 1，0.001，0.01，0.1， 1.0，10 μmol/L ARC on the proliferation of NP-69 were determined by MTS method. After 0.01，0.1，and 1.0 μmol/L ARC was applied to NP- 69 for 24 h and NP- 69 was pre-treated with 0.01，0.1 and 1.0 μmol/L ARC for 24 h，and then stimulated with 1.0 μg/mL LPS for 24 h，scratch tests were used to detect cell migration in both experiments. LPS stimulated NP- 69 to establish an inflammation injury model. The levels of nitric oxide （NO），tumor necrosis factor α（TNF-α）interleukin-6（IL-6），and IL- 1β in cell supernatants were detected ，and mRNA and protein expression of zonula oecludens protein 1（ZO-1），β-defensin 3（BD3）， Janus kinase 1 （JAK1），signal transducer and activator of transcription 3 （STAT3） in cell supernatant were also detected. RESULTS Compared with normal group ，0.000 1，0.001，0.01，0.1，1.0，10 μmol/L ARC had no effect on the proliferation of NP-69 after 24 h treatment （P＞0.05）. ARC （0.1，1.0 μmol/L）could significantly promote the rate of cell migration （P＜0.05）. For the inflammatory injure of NP- 69 cells stimulated by LPS ，ARC（1.0 μmol/L）could significantly reduce the release of NO ， TNF-α and IL-6（P＜0.05），significantly increased mRNA and protein expression of ZO- 1 and BD 3 but decreased mRNA and protein expression of STAT 3（P＜0.01 or P＜0.05）. CONCLUSIONS ARC has the effect of reducing the inflammatory injury of NP-69 cells induced by LPS ，promoting the physical and immune defense ability of the nasal mucosa epithelial barrierunder inflammatory environment. The mechanism of action may be related to inhibiting IL- 6/JAK1/STAT3 signaling pathway.