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Showing papers in "Journal of Natural Medicines in 2019"


Journal ArticleDOI
TL;DR: The antiviral effect of luteolin against IAV and its novel antiviral mechanism is demonstrated and a time-of-addition assay indicated that this compound interfered with viral replication at the early stage of infection.
Abstract: Influenza is an acute transmissible respiratory infectious disease in humans and animals with high morbidity and mortality. It was reported that luteolin, extracted from Chinese herbs, could potently inhibit influenza virus replication in vitro. To assess the effect and explore the fundamental mechanism of luteolin, we infected several cell lines with two subtypes of influenza A virus (IAV), including A/Jiangxi/312/2006 (H3N2) and A/Fort Monmouth/1/1947 (H1N1) and demonstrated that luteolin suppressed the replication of IAV by cytopathic effect reduction method, qRT-PCR, immunofluorescence and Western blot assays. A time-of-addition assay indicated that this compound interfered with viral replication at the early stage of infection. In addition, we found that luteolin suppressed coat protein I complex expression, which was related to influenza virus entry and endocytic pathway. Overall, our findings demonstrated the antiviral effect of luteolin against IAV and its novel antiviral mechanism.

62 citations


Journal ArticleDOI
TL;DR: The results demonstrated that ARA exerted beneficial gastroprotective effects on alcohol- and aspirin-induced gastric ulcer in mice, which was related to suppressing H+/K+-ATPase activity as well as pro-apoptotic protein expression, and promoting anti-APoptoticprotein expression, thus alleviating gastric mucosal injury and cell death.
Abstract: The aim of this study was to elucidate the gastroprotective activity and possible mechanism of involvement of araloside A (ARA) against ethanol- and aspirin-induced gastric ulcer in mice. The experimental mice were randomly divided into control, model, omeprazole (20 mg/kg, orally) and ARA (10, 20 and 40 mg/kg, orally). Gastric ulcer in mice was induced by intragastric administration of 80% ethanol (10 mL/kg) containing 15 mg/mL aspirin 4 h after drug administration on day 7. The results indicated that ARA could significantly raise gastric juice volume and acidity; ameliorate gastric mucosal blood flow, gastric binding mucus volume, ulcer index and ulcer inhibition rate; suppress H+/K+-ATPase activity, which was confirmed by computer-aided docking simulations; inhibit the release of mitochondrial cytochrome c into the cytoplasm; inhibit caspase-9 and caspase-3 activities and down-regulate mRNA expression levels; down-regulate the mRNA and protein expressions of apoptosis protease-activating factor-1 and protein expression of cleaved poly(ADP ribose) polymerase-1; and up-regulate Bcl-2 mRNA and protein expressions and down-regulate Bax mRNA and protein expressions, thus elevating the Bcl-2/Bax ratio in a dose-dependent manner. Histopathological observations further provided supportive evidence for the aforementioned results. The results demonstrated that ARA exerted beneficial gastroprotective effects on alcohol- and aspirin-induced gastric ulcer in mice, which was related to suppressing H+/K+-ATPase activity as well as pro-apoptotic protein expression, and promoting anti-apoptotic protein expression, thus alleviating gastric mucosal injury and cell death.

36 citations


Journal ArticleDOI
TL;DR: The in vitro proliferation inhibition effect of SAN was determined using CCK-8 assay, and the in vivo antitumor effect of San was evaluated in mice with xenotransplanted tumor, indicating that SAN may inhibit the proliferation of BGC-823 cells through the inhibition ofmiR-96-5p and miR-29c-3p expression, and subsequent activation of the MAPK/JNK signaling pathway.
Abstract: Sanguinarine (SAN), a quaternary benzophenanthridine alkaloid extracted from the root of Papaveraceae plants, has shown antitumour effects in multiple cancer cells. However, the therapeutic effects and the underlying mechanisms of SAN in gastric cancer (GC) remain elusive. In this study, the in vitro proliferation inhibition effect of SAN in GC cells was determined using CCK-8 assay, the in vivo antitumor effect of SAN was evaluated in mice with xenotransplanted tumor. The mechanism underlying the antitumor activity of SAN was explored by gene microarray assay and bioinformatics analysis. The levels of differentially expressed miRNAs and target genes were verified by real-time RT-PCR and immunohistochemistry. SAN inhibited the proliferation of BGC-823 cells in a concentration-dependent manner in vitro and in vivo. The miR-96-5p and miR-29c-3p were significantly upregulated in untreated BGC-823 cells and significantly downregulated in SAN treated cells. The mRNA and protein expression of their target gene MAP4K4 were upregulated in SAN treated xenotransplanted tumors, and pMEK4 and pJNK1 proteins in the MAPK/JNK signaling pathway were also upregulated by SAN. These indicate that SAN may inhibit the proliferation of BGC-823 cells through the inhibition of miR-96-5p and miR-29c-3p expression, and subsequent activation of the MAPK/JNK signaling pathway.

30 citations


Journal ArticleDOI
TL;DR: Two new quassinoids, (16R)-methoxyjavanicin B (1) and (16S)- methoxy javanic in B (2), along with seven known compounds, were isolated during the phytochemical investigation of the CHCl3 soluble portion of the MeOH extract of P. javanica wood.
Abstract: Picrasma javanica Blume (Simaroubaceae) is a medium-sized tree that is distributed widely in tropical Asia. In our previous study, we isolated quassinoids from P. javanica bark collected in Myanmar, and reported their antiproliferative activities. In our ongoing research for the discovery of bioactive compounds from Myanmar medicinal plants, two new quassinoids, (16R)-methoxyjavanicin B (1) and (16S)-methoxyjavanicin B (2), along with seven known compounds (3–9), were isolated during the phytochemical investigation of the CHCl3 soluble portion of the MeOH extract of P. javanica wood. The structures of the new compounds were elucidated by analyses of their spectroscopic data (1D- and 2D-NMR, HRESIMS, and CD). A cytotoxicity assay revealed that compound 8 showed moderate activities against all tested cancer cell lines, the human lung (A549), breast (MCF7), and cervical (HeLa), and the normal fibroblast cell line, with IC50 values ranging from 48.6 to 65.9 μM. Furthermore, the antibacterial assay demonstrated that 1 and 2 had the highest activities (MIC value of 1.6 μM each), followed by 5 and 3 (MIC values of 3.1 and 6.3 μM, respectively) against the Gram-positive bacterium B. subtilis.

26 citations


Journal ArticleDOI
TL;DR: The present findings suggested that XYJY has an ameliorative effect on PSD in rats via modulation of BNDF, cannabinoid receptors and CRF in VTA-NAc tissue.
Abstract: A stroke is a severe life-threatening disease with high fatality and disability rate. This investigation aimed to study the effect of Xiaoyao-jieyu-san (XYJY) on post-stroke depression (PSD) and its potential mechanisms. PSD rats were prepared using middle cerebral artery embolization (MCAO) and chronic unpredictable mild stress (CUMS), and divided into six groups (n = 10)—sham; MCAO; MCAO + CUMS (PSD); PSD + fluoxetine (1.84 mg/kg/day, 4 weeks); and PSD + XYJY (450 mg/kg/day and 900 mg/kg/day, 4 weeks). Body weight recording, despair swimming test, and sucrose preference test were performed at 0, 3 and 7 weeks. Histopathological examination and levels of 5-hydroxytryptamine (5-HT), norepinephrine (NE) and brain-derived neurotrophic factor (BDNF) in ventral tegmental area-nucleus accumbens (VTA-NAc) tissue were determined at the end of a 7-week period. Real-time polymerase chain reaction PCR was used to determine mRNA expression of 5-HT1AR and 5-HT2AR, and Western blot was performed to determine expression of BDNF, corticotrophin-releasing factor (CRF), and cannabinoid receptors (CB1R and CB2R) in VTA-NAc tissue. High-performance liquid chromatography coupled with electrospray mass spectroscopy revealed that the constituents of XYJY are mainly paeoniflorin, imperatorin, naringin, arnesene, 2,3,5,4′-tetrahydroxyl-diphenylethylene-2-O-glucoside, kaempferol-3-O-rutinoside, quercetin, hesperidin, cycloastragenol and atractylenolide III. XYJY (900 mg/kg) increased the body weight of PSD rats, while XYJY (450 mg/kg and 900 mg/kg) shortened the duration of immobility and enhanced the sucrose preference of PSD rats. XYJY (450 mg/kg and 900 mg/kg) increased the levels of 5-HT, NE and BNDF, up-regulated mRNA expression of 5-HT1AR, down-regulated 5-HT2AR, and up-regulated BNDF, CB1R, and CB2R expression in the VTA-NAc tissue of PSD rats but down-regulated CRF. Collectively, the present findings suggested that XYJY has an ameliorative effect on PSD in rats via modulation of BNDF, cannabinoid receptors and CRF in VTA-NAc tissue.

25 citations


Journal ArticleDOI
TL;DR: In this paper, the role of miR-21 in aloin's inhibitory effect on osteoclast differentiation was investigated and it was shown that miR21 suppression resulted in upregulation of osteoclastic suppressor programmed cell death protein 4 (PDCD4) and downregulation of OCC marker cathepsin K.
Abstract: Osteopenic disorders such as osteoporosis and rheumatoid arthritis are characterized by excessive bone resorption by osteoclasts relative to bone formation by osteoblasts. MicroRNAs are emerging as key players in bone remodeling, modulating the functions of both osteoblasts and osteoclasts. Among them, miR-21 is highly expressed in osteoclast precursors and is known to regulate genesis, differentiation, and apoptosis of osteoclasts. The pro-osteoclastogenic nature of miR-21 makes it a potential candidate as a therapeutic target to treat bone disorders. We had previously demonstrated that anthroglycoside aloin derived from Aloe vera was effective in promoting osteoblastogenesis and inhibiting osteoclastogenesis. The present study investigated the role of miR-21 in aloin’s inhibitory effect on osteoclast differentiation. Aloin effectively suppressed receptor activator of nuclear factor kappa-B (NFĸB) ligand (RankL)-induced miR-21 expression via repression of NFĸB activation. MiR-21 suppression resulted in upregulation of osteoclast suppressor programmed cell death protein 4 (PDCD4), and downregulation of osteoclast marker cathepsin K. Knockdown or gain-of-function studies revealed that miR-21 was pivotal to aloin’s inhibitory effect on osteoclastogenesis. This study also highlights the dynamic potential of aloin as a therapeutic agent to treat osteopenic disorders.

21 citations


Journal ArticleDOI
TL;DR: In conclusion, polydatin effectively inhibited hypoxia- and AMI-induced myocardial damage by promotion of Nrf2/HO-1 signaling.
Abstract: Polydatin is a traditional Chinese medicine that provides myocardial protection after acute myocardial infarction (AMI) The study aim was to investigate the myocardial protection polydatin in H9c2 myocardial cells cultured in a hypoxic atmosphere and in a rat AMI model induced by ligating the left anterior descending coronary artery and treated with polydatin 100 mg/kg/day for 30 days The involvement of Nrf2 in mediating the effects of polydatin was investigated in H9c2 cells following Nrf2 knockdown by transfection of siRNA Polydatin suppressed hypoxia-induced H9c2 cell apoptosis and reactive oxygen species (ROS) generation by promoting Nrf2/HO-1 signaling Nrf2 knockdown reversed the protective effects of polydatin against hypoxia-induced myocardial cell injury The in vivo results were consistent with polydatin suppression of apoptosis and ROS generation in myocardial tissue by promotion of Nrf2/HO-1 signaling In conclusion, polydatin effectively inhibited hypoxia- and AMI-induced myocardial damage by promotion of Nrf2/HO-1 signaling

21 citations


Journal ArticleDOI
TL;DR: The data suggest that andrographolide may impair cholestatic liver injury via anti-inflammatory and anti-oxidative stress.
Abstract: To investigate if andrographolide impairs cholestatic liver injury. All rats were randomly divided into six groups—(1) control (n = 6), (2) control + 200 mg/kg andrographolide (n = 6), (3) alpha-naphthylisothiocyanate (ANIT)-control (n = 6), (4) ANIT + 50 mg/kg andrographolide (n = 6), (5) ANIT + 100 mg/kg andrographolide (n = 6), and (6) ANIT + 200 mg/kg andrographolide (n = 6). We gavaged 50 mg/kg ANIT to mimic cholestatic liver injury in rats. Seven days after treatment, all the rats were killed. Serum biochemistry and hepatic histopathological assays were performed to evaluate liver injury. We observed that 200 mg/kg andrographolide significantly decreased the level of alanine transaminase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyltranspeptidase, total bilirubin, and total bile acid in the blood. It also markedly decreased hepatic interleukin-6 and tumor necrosis factor α. Furthermore, 200 mg/kg andrographolide significantly decreased malondialdehyde but increased superoxide dismutase, glutathione, and erythrocyte glutathione peroxidase. Moreover, 200 mg/kg andrographolide effectively increased the accumulation of sirtuin 1 and nuclear erythroid 2-related factor-2. It also attenuated the level of nuclear factor kappa-light-chain-enhancer of activated B and cyclooxygenase-2. These data suggest that andrographolide may impair cholestatic liver injury via anti-inflammatory and anti-oxidative stress.

20 citations


Journal ArticleDOI
TL;DR: Two new flavonoid glycosides were isolated from the 75% EtOH extract of the dried roots of Glycyrrhiza uralensis Fisch and evaluated for in vitro hepatoprotective activity against d-galactosamine-induced toxicity in human hepatoma HepG2 cells.
Abstract: Two new flavonoid glycosides, 2′,4′-dihydroxydihydrochalcone-4-O-β-d-glucopyranoside (1) and medicarpin-3-O-β-d-apiofuranosyl (1 → 2)-β-d-glucopyranoside (2), together with 34 known flavonoids were isolated from the 75% EtOH extract of the dried roots of Glycyrrhiza uralensis Fisch. Their structures were elucidated on the basis of spectroscopic analyses. The flavonoids were classified into ten sub-types, namely, dihydrochalcone (1), pterocarpans (2–4), flavones (5–6), flavanones (7–11), chalcones (12–15), retro-chalcones (16–18), isoflavans (19–21), isoflavones (22–28), 3-arylcoumarins (29–30), and coumestans (31–36). The isolated flavonoids were evaluated for in vitro hepatoprotective activity against d-galactosamine-induced toxicity in human hepatoma HepG2 cells.

19 citations


Journal ArticleDOI
TL;DR: The anti-inflammatory effects of the prenylated flavanoids SPF1 and SPF2, which were previously isolated from root of Sophora tonkinensis and identified as potent ligands for RXR, and potential mechanisms involved are investigated, shedding light on the mechanism of the anti- inflammation effect via RXR/LXR heterodimer.
Abstract: Retinoid X receptor (RXR) ligands have a wide range of beneficial effects in mouse models of Alzheimer’s disease (AD). Recently accumulated evidence suggests that early neuroinflammation may be a therapeutic target for AD treatment. We therefore investigated the anti-inflammatory effects of the prenylated flavanoids SPF1 and SPF2, which were previously isolated from root of Sophora tonkinensis and identified as potent ligands for RXR, and potential mechanisms involved. SPF1 and SPF2 efficiently reduced interleukin (IL)-1β messenger RNA (mRNA) and IL-6 mRNA levels in lipopolysaccharide-stimulated and tumor necrosis factor-α-stimulated RAW264.7 cells, whereas SPF3—which has a structure similar to SPF1 and SPF2 but no RXR ligand activity—did not exhibit such effects. Intriguingly, the liver X receptor (LXR) ligand T0901317 reduced proinflammatory cytokine mRNA levels, and these effects were potentiated by SPF1. With regard to the mechanism underlying the anti-inflammatory effects, SPF1 induced significant amounts of activating transcription factor 3 (ATF3) mRNA and protein, and this effect was potentiated by T0901317. SPF1 also reduced translocation of nuclear factor κB (NF-κB) into nuclei. The production of proinflammatory cytokines was significantly inhibited by SPF1, and this effect was primarily exerted via RXR/LXR heterodimers. The effects of SPF1 may partly depend on the induction of ATF3, which may bind to the p65 subunit of NF-κB, resulting in reduced translocation of NF-κB into nuclei and reduced NF-κB transcription. Although inflammatory effects mediated by RXR/LXR heterodimers have not been thoroughly investigated, the above-described results shed light on the mechanism of the anti-inflammatory effect via RXR/LXR heterodimer.

19 citations


Journal ArticleDOI
TL;DR: Sakuranetin may be primarily responsible for the anti-inflammatory effects of Pruni Cortex in the liver after monitoring nitric oxide production in rat hepatocytes that were treated with the pro-inflammatory cytokine, interleukin (IL)-1β.
Abstract: Pruni Cortex is a herbal drug from the bark of the Japanese flowering cherries, Prunus jamasakura or Prunus verecunda, and is included in the traditional Japanese herbal (Kampo) formula Jumihaidokuto, which is administered orally to patients suffering from inflammatory skin diseases. The flavanones contained in Pruni Cortex (e.g., sakuranetin and naringenin) have potent anti-inflammatory, anti-allergic, and anti-microbial activities. Although the effects of Pruni Cortex on skin disease have been well studied, reports regarding its pharmacological effects on the liver are limited. In this study, we extracted the bark of Prunus jamasakura and purified it to isolate the pharmacologically active constituents by monitoring nitric oxide (NO) production in rat hepatocytes that were treated with the pro-inflammatory cytokine, interleukin (IL)-1β. Sakuranetin and (−)-naringenin, which were present in an ethyl acetate-soluble fraction of the bark extract, significantly inhibited NO induction and inducible nitric oxide synthase (iNOS) expression. These two flavanones decreased the expression of type 1 IL-1 receptor gene and phosphorylation of Akt, also known as protein kinase B, which is regulated by phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K). Furthermore, sakuranetin decreased the phosphorylation of the activator isoforms of CCAAT/enhancer-binding protein β (C/EBPβ), which synergistically activates the transcription of the iNOS gene with nuclear factor κB (NF-κB). Therefore, sakuranetin inhibited the co-activating activity of C/EBPβ with NF-κB, leading to the suppression of iNOS gene expression in hepatocytes. Taken together, sakuranetin in Pruni Cortex downregulated the iNOS gene by inhibiting PI3K/Akt signal transduction and the phosphorylation of C/EBPβ. These results imply that sakuranetin may be primarily responsible for the anti-inflammatory effects of Pruni Cortex in the liver.

Journal ArticleDOI
TL;DR: Six new sarpagine-type indole alkaloids isolated from the bark of Tabernaemontana macrocarpa Jack showed antiplasmodial activities against Plasmodium falciparum 3D7 and cytotoxic activities against human cell line, HepG2 cells.
Abstract: Two new sarpagine-type indole alkaloids (1 and 2), together with five known alkaloids; 12-methoxy-4-methylvoachalotine (3), 16-demethoxycarbonylvoacamine (4), isositsirikine (5), affinisine (6), affinine (7), were isolated from the bark of Tabernaemontana macrocarpa Jack. The structures of these alkaloids were determined based on spectroscopic data, chemical correlation, and comparison with the literature. 16-Demethoxycarbonylvoacamine (4) showed antiplasmodial activities against Plasmodium falciparum 3D7 and cytotoxic activities against human cell line, HepG2 cells.

Journal ArticleDOI
TL;DR: Aloin promotes osteogenic differentiation of BMSCs through activation of the ERK1/2-Runx2 signaling pathway and effectively attenuated Runx2 activation in these cells and also suppressed osteoblastic differentiation.
Abstract: Osteoporosis is characterized by low bone mass and the degeneration of bone structure, conditions which increase the risk of fracture. Aloin has been shown to affect bone metabolism, but its role in osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) remains unclear. The aim of our study was to determine whether aloin promotes the proliferation and osteogenic differentiation of BMSCs and, if so, whether it acts via activation of the ERK1/2-Runx2 signaling pathway. We found that the different concentrations of aloin tested had no obvious cytotoxic effects on the viability of BMSCs. Under osteogenic induction conditions, aloin increased cellular alkaline phosphatase activity, promoted BMSC mineralization, and increased osteogenic-related gene expression. In addition, treating the BMSCs with the signal transduction inhibitor PD98059 (ERK1/2) effectively attenuated Runx2 activation in these cells and also suppressed osteoblastic differentiation. Overall, our study demonstrates that aloin promotes osteogenic differentiation of BMSCs through activation of the ERK1/2-Runx2 signaling pathway.

Journal ArticleDOI
TL;DR: It is found that RS significantly enhances inhibition of thrombin and factor Xa in the presence of antithrombin as well as heparin, and that RS inhibits tissue factor expression and von Willebrand factor release from the endothelial cells treated with or without lipopolysaccharide, tumor necrosis factor-α, or throm bin.
Abstract: Rhamnan sulfate (RS) is a polysaccharide with a rhamnose backbone isolated from Monostroma nitidum. Like heparin, it exerts anticoagulant activity in the presence of antithrombin. Endothelial cells facilitate the crosstalk between blood coagulation and vascular inflammation. In this study, we compared the effect of RS with that of heparin on blood coagulation and vascular endothelial cells in the presence or absence of inflammatory factors, using human umbilical vein endothelial cells. We found that RS significantly enhances inhibition of thrombin and factor Xa in the presence of antithrombin as well as heparin, and that RS inhibits tissue factor expression and von Willebrand factor release from the endothelial cells treated with or without lipopolysaccharide, tumor necrosis factor-α, or thrombin. Heparin did not show any effects on endothelial cell inflammation. Our findings suggest that RS, like heparin, is an antithrombin-dependent anticoagulant and, unlike heparin, is a potent anti-inflammatory agent acting on vascular endothelial cells.

Journal ArticleDOI
TL;DR: In this review, several examples of recent studies that used computer technology to facilitate the discovery and structure determination of various natural products are provided.
Abstract: Computer hardware development coupled with the development of quantum chemistry, new computational models and algorithms, and user-friendly interfaces have lowered the barriers to the use of computation in the discovery and structure elucidation of natural products. Consequently, the use of computational chemistry software as a tool to discover and determine the structure of natural products has become more common in recent years. In this review, we provide several examples of recent studies that used computer technology to facilitate the discovery and structure determination of various natural products.

Journal ArticleDOI
TL;DR: The study found that mitogen-activated protein kinase/extracellular signal-regulated kinase may be involved in the effects of betulinic acid on liver fibrosis and could serve as a promising new agent for treating hepatic fibrosis.
Abstract: The present study was designed to investigate the effects of betulinic acid on human hepatic stellate cells in vitro and C57BL/6 mice in vivo, as well as the signaling pathways involved. In this study, we explored the effects of betulinic acid on expression of alpha smooth muscle actin and autophagy-related proteins. Betulinic acid reduced pathological damage associated with liver fibrosis, as well as serum platelet-derived growth factor and serum hydroxyproline levels. Furthermore, betulinic acid downregulated the expression of alpha smooth muscle actin and type I collagen in mouse liver and upregulated the expression of microtubule-associated protein light chain 3B and autophagy-related gene 7 at the gene and protein levels. LC3II expression was increased and alpha smooth muscle actin expression was decreased in betulinic acid-treated hepatic stellate cells. Interventions with bafilomycin A1 and mCherry-GFP-LC3 adenoviruses promoted the formation of autophagosomes in hepatic stellate cells and the development of autophagic flow. Our study found that mitogen-activated protein kinase/extracellular signal-regulated kinase may be involved in the effects of betulinic acid on liver fibrosis. The present study suggests that betulinic acid has anti-hepatic fibrosis activity by inducing autophagy and could serve as a promising new agent for treating hepatic fibrosis.

Journal ArticleDOI
TL;DR: Chalcone 9, homoisoflavane 5 and flavone 12–14 are considered to be responsible for the anti-neuroinflammatory effects of Chinese Dragon’s blood, which could inhibit neuroinflammation by reducing the expressions of iNOS, IL-6 and TNF-α in over-activated microglial.
Abstract: Our previous research revealed resin of Dracaena cochinchinensis as a candidate for therapy of neurodegenerative diseases. In the present study, the material basis of Chinese Dragon’s blood and the primary mechanism of the effective components are discussed. Multiple chromatography and spectra analysis were utilized to identify effective constituents. The production of NO was determined using nitrite assay in BV-2 microglial cells stimulated with lipopolysaccharide (LPS). Cell viability was tested using MTT assay. The mRNA level of inducible nitric oxide synthase (iNOS) was investigated by quantitative real-time PCR (qRT-PCR), and the production of IL-6 and TNF-α in the cell supernatants was tested by ELISA. The bioassay-directed separation of the effective extract of D. cochinchinensis afforded two new compounds, a stilbene-flavane dimer (2) and a quinoid flavonoid (11), in addition to 25 known compounds. The evaluation of their anti-neuroinflammatory activities showed that 5, 9, 12, 13, and 14 could exhibit significant anti-neuroinflammatory effects without cytotoxities at the tested concentration, compared to a positive control, minocycline (21.87 ± 2.36 µM). A primary mechanistic study revealed that the effective components could inhibit over-activation of microglial through decreasing the expressions of iNOS, proinflammatory cytokines IL-6 and TNF-α in LPS- induced BV2 microglial cells. Chalcone 9, homoisoflavane 5 and flavone 12–14 are considered to be responsible for the anti-neuroinflammatory effects of Chinese Dragon’s blood. These could inhibit neuroinflammation by reducing the expressions of iNOS, IL-6 and TNF-α in over-activated microglial. Furthermore, the SAR is briefly discussed.

Journal ArticleDOI
TL;DR: Nortriptonoterpene (1), a new C19-norabietane diterpenoid, together with six other known abietane-type diterPenoids (2–7) and five known kaurane- type diter penoids (8–12) were isolated and identified from the EtOAc extract of C. orbiculatus.
Abstract: Celastrus orbiculatus is a medicinal plant belonging to the Celastraceae family. In this survey on the secondary metabolites of plants for obtaining antitumor substances, the chemical constituents of the stems of C. orbiculatus were investigated. Nortriptonoterpene (1), a new C19-norabietane diterpenoid, together with six other known abietane-type diterpenoids (2–7) and five known kaurane-type diterpenoids (8–12) were isolated and identified from the EtOAc extract of C. orbiculatus. Their structures were elucidated on the basis of extensive spectroscopic methods, including UV, IR, HR-ESI–MS, ECD, and NMR experiments, and by comparison with literature data. Compound 1 is a new C19-norabietane diterpenoid with 19 carbons. All compounds except for 10 and 11 were isolated from C. orbiculatus for the first time. The NMR data of 9 were reported for the first time. Compounds 1, 7 and 11 showed cytotoxicities against SGC-7901 with IC50 values of 63.2, 80.9 and 56.7 μM, respectively.

Journal ArticleDOI
TL;DR: Koumine exerted both analgesic and anti-inflammatory effects on the CIA rat model that were apparently mediated by inhibiting astrocyte reactivation and pro-inflammatory cytokine production.
Abstract: Gelsemium elegans Benth. is a toxic plant that has been used as an ancient Chinese herbal remedy for rheumatoid arthritis (RA) and nervous pain, spasticity, skin ulcers, and cancers. Koumine, one of its representative alkaloids, shows numerous promising pharmacological activities, including anti-inflammatory and analgesic activities. Here, we investigated the analgesic effect of koumine on the collagen-induced arthritis (CIA) rat model of RA and explored the potential pharmacological mechanisms underlying the analgesia. In the CIA rats, repeated koumine treatments significantly reduced pain compared to controls and attenuated the collagen-induced increase in levels of glial fibrillary acidic protein (GFAP) and the pro-inflammatory cytokines tumour necrosis factor α (TNF-α) and interleukin 1β (IL-1β). Cultured astrocytes showed reduced astrocyte reactivation and decreased production of both tested cytokines. Based on our results, koumine exerted both analgesic and anti-inflammatory effects on the CIA rat model that were apparently mediated by inhibiting astrocyte reactivation and pro-inflammatory cytokine production.

Journal ArticleDOI
TL;DR: It is demonstrated that the headspace air of living basil plants could effectively reduce the locomotor activity of mice.
Abstract: The sedative effects of the essential oil released by living Ocimum basilicum (basil) plants were investigated using a mouse activity monitoring system. Ocimum basilicum plants were grown in a hydroponic chamber, and either the headspace air from the hydroponic chamber or the essential oil extracted from mature plants was administered by the inhalation route to mice in an open field test. The most effective dose of O. basilicum essential oil for reducing the locomotor activity of the mice was found to be 4.0 × 10−3 mg per cage. The headspace air was administered to mice held in a glass cage via a Teflon tube connected to a hydroponic chamber containing O. basilicum plants. A significant decrease in locomotor activity was observed when the hydroponic chamber contained nine plants. The results of this study demonstrate that the headspace air of living basil plants could effectively reduce the locomotor activity of mice.

Journal ArticleDOI
TL;DR: Taberniacins A and B, new indole alkaloids, were isolated from the stems of Tabernaemontana divaricata and showed vasorelaxant activity against phenylephrine-induced contraction of isolated rat aorta.
Abstract: Taberniacins A (1) and B (2), new indole alkaloids, were isolated from the stems of Tabernaemontana divaricata (Apocynaceae). Structure elucidation of 1 and 2 was based on spectroscopic methods and total synthesis. Each alkaloid showed vasorelaxant activity against phenylephrine-induced contraction of isolated rat aorta.

Journal ArticleDOI
TL;DR: A new triterpene named klodorol B (1), together with six known compounds, were isolated from the green walnut husks of Juglans mandshurica Maxim and evaluated for their cytotoxic activities on human gastric carcinoma, liver cancer and human lung cancer cell lines.
Abstract: A new triterpene named klodorol B (1), together with six known compounds, were isolated from the green walnut husks of Juglans mandshurica Maxim. Their structures were determined using spectroscopic methods on the basis of 1D and 2D NMR, and high-resolution electrospray ionization mass spectrometry. The isolated compounds were evaluated for their cytotoxic activities on human gastric carcinoma (BGC-823), human liver cancer (HepG-2) and human lung cancer (A549) cell lines. .

Journal ArticleDOI
TL;DR: Chaga mushrooms, the sclerotium of Inonotus obliquus, have been used in Mongolia as a traditional hair shampoo to maintain healthy hair and appeared to be potential candidates of new agents possibly used for hair-care with a stimulative effect on hair growth.
Abstract: Chaga mushrooms, the sclerotium of Inonotus obliquus, have been used in Mongolia as a traditional hair shampoo to maintain healthy hair. Bioassay-guided fractionations of the extract of Chaga mushrooms using a proliferation assay on human follicle dermal papilla cells (HFDPCs) gave five lanostane-type triterpenes (1–5), whose structures were identified by spectroscopic evidence. Among these, lanosterol (1), inotodiol (3), lanost-8,24-diene-3β,21-diol (4), and trametenolic acid (5) demonstrated proproliferative effects on HFDPCs more potent than minoxidil, an anti-alopecia agent, used as the positive control. The lanostane-type triterpenes (1, 3, 4, and 5) appeared to be potential candidates of new agents possibly used for hair-care with a stimulative effect on hair growth.

Journal ArticleDOI
TL;DR: Investigation of the anti-inflammatory effects of an extract from Cynara scolymus L. and its pharmacologically effective compound cynaropicrin on human gingival fibroblasts stimulated by LPS and the potential anti-osteoclastogenic effects on RAW264.7 cells suggested that cynaropyrin may be useful for preventing periodontal diseases.
Abstract: Periodontal diseases are a major public health problem affecting over half of the adult population worldwide Lipopolysaccharide (LPS) produced by the periodontopathic bacterium Porphyromonas gingivalis induces the expression of inflammatory cytokines that promote inflammatory bone destruction Mounting evidence supports that periodontal diseases are involved in the onset and progression of several systemic diseases, such as aspiration pneumonia and diabetes Although treatment of periodontal diseases by removing the periodontopathic bacteria by brushing is a standard practice, it has limitations and is not effective in all cases Therefore, a new method to replace or complement brushing is needed for the treatment of periodontal diseases In this study, we investigated the anti-inflammatory effects of an extract from Cynara scolymus L and its pharmacologically effective compound cynaropicrin, a sesquiterpene lactone, on human gingival fibroblasts (HGFs) stimulated by LPS and the potential anti-osteoclastogenic effects on RAW2647 cells induced by receptor activator of NF-κB ligand (RANKL) We found that cynaropicrin inhibited IL-8 and IL-6 mRNA and protein synthesis in LPS-stimulated HGFs in a dose-dependent manner P gingivalis LPS-induced degradation of IκBα and phosphorylation of NF-κB p65 were also suppressed by cynaropicrin, as was LPS-stimulated NF-κB transactivation Thus, cynaropicrin’s inhibition of P gingivalis LPS-induced IL-8 and IL-6 expression may be due to the inhibition of the NF-κB pathway Furthermore, we showed that cynaropicrin dramatically reduced RANKL-induced osteoclast differentiation These results suggest that cynaropicrin may be useful for preventing periodontal diseases and could prove valuable in the development of more effective preventative approaches for periodontal diseases

Journal ArticleDOI
TL;DR: This study establishes that oral administration of 1 has potent anti-allodynic effect in addition to the activity of intraperitoneally administered 1 reported previously, which will support the development of novel therapies for the management of CIPN in cancer patients.
Abstract: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the dose-limiting side effects of cancer chemotherapy. Although the control of CIPN is important, it is difficult to manage with currently available therapeutic drugs. Therefore, there is a need for novel therapeutic agents for treating CIPN. Goshajinkigan (GJG) is a Kampo formula composed of ten crude drugs. While GJG has been used for the treatment of CIPN, the active constituents of GJG and their underlying mechanisms of pharmacological effects are still unknown. Our previous study revealed that repetitive oral administration of the water extract of Plantaginis Semen, a crude drug ingredient of GJG, inhibited the mechanical allodynia induced by an intraperitoneal injection of paclitaxel in mice. To elucidate the active compounds of Plantaginis Semen, activity-guided separation of the water extract of Plantaginis Semen was performed. From the active fraction, four iridoids (1–4) were identified. Repetitive oral administration of aucubin (1) at 100 or 30 mg/kg and 100 mg/kg of the fraction crude 3 [primarily comprised of pedicularis-lactone (3)], showed anti-allodynic activity, suggesting 1 and 3 could be some of the active compounds responsible for the anti-allodynic property of Plantaginis Semen and GJG. Our study establishes that oral administration of 1 has potent anti-allodynic effect in addition to the activity of intraperitoneally administered 1 reported previously. Identification of active anti-allodynic compounds found in Kampo formulations will support the development of novel therapies for the management of CIPN in cancer patients.

Journal ArticleDOI
TL;DR: Two new bisindole alkaloids, leucophyllinines A and B consisting of eburnane and quebrachamine-type skeletons were isolated from the bark of Leuconotis eugeniifolia and showed antiplasmodial activities against Plasmodium falciparum 3D7.
Abstract: Two new bisindole alkaloids, leucophyllinines A (1) and B (2) consisting of eburnane and quebrachamine-type skeletons were isolated from the bark of Leuconotis eugeniifolia, and their structures were elucidated on the basis of spectroscopic data. Leucophyllinines A and B showed antiplasmodial activities against Plasmodium falciparum 3D7.

Journal ArticleDOI
TL;DR: Findings revealed a novel role of goniothalamin derivatives in reversing P-gp-mediated chemotherapy resistance and indicated these compounds to inhibit P- gp by acting as transporter substrates.
Abstract: Overexpression of efflux transporters of the ATP-binding cassette (ABC) transporter family, primarily P-glycoprotein (P-gp), is a frequent cause of multidrug resistance in cancer and leads to failure of current chemotherapies. Thus, identification of selective P-gp inhibitors might provide a basis for the development of novel anticancer drug candidates. The natural product goniothalamin and 21 derivatives were characterized regarding their ability to inhibit ABC transporter function. Among the goniothalamins, selective inhibitors of P-gp were discovered. The two most potent inhibitors (R)-3 and (S)-3 displayed the ability to increase intracellular accumulation of doxorubicin, thereby sensitizing P-gp-overexpressing tumor cells to chemotherapy by decreasing doxorubicin IC50 value up to 15-fold. Molecular docking studies indicated these compounds to inhibit P-gp by acting as transporter substrates. In conclusion, our findings revealed a novel role of goniothalamin derivatives in reversing P-gp-mediated chemotherapy resistance.

Journal ArticleDOI
Chun Wu, Li-Jun He1, Xue Yi, Juan Qin1, Yao-Lan Li1, Yu-Bo Zhang1, Guo-Cai Wang1 
TL;DR: This is the first report of β-carboline alkaloid in the plant of genus Sophora, and the cytotoxic activities against HepG2 cells of compounds 1–5 were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay.
Abstract: A new β-carboline alkaloid (1) and two new matrine-type alkaloids (2 and 3), together with two known alkaloids (4 and 5), were isolated from the roots of Sophora tonkinensis. The new structures were elucidated via extensive analyses of the spectroscopic data (IR, UV, HRESIMS, NMR) and X-ray crystallography. The absolute configuration of 1 was established by electronic circular dichroism data. Herein, is the first report of β-carboline alkaloid in the plant of genus Sophora. In addition, the cytotoxic activities against HepG2 cells of compounds 1–5 were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Among them, compounds 1, 4 and 5 showed a weak cytotoxic activity with IC50 values of 87.4 ± 7.1, 91.8 ± 3.5 and 48.9 ± 5.2 μM, respectively.

Journal ArticleDOI
TL;DR: The article Identification of β‑carboline and canthinone alkaloids as anti‑inflammatory agents but with different inhibitory profile on the expression of iNOS and COX‑2 in lipopolysaccharide‑activated RAW 264.7 macrophages was originally published electronically on the publisher’s internet portal (currently SpringerLink).
Abstract: A compound library, which consists of 75 natural β-carboline-type or canthinone-type alkaloids from Simaroubaceae plants and their chemical synthetic analogues, was screened for the anti-inflammatory activity by inhibition of the overproduction of inflammatory mediator nitric oxide (NO) in lipopolysaccharide (LPS)-activated RAW 264.7 macrophage cells. Six compounds, namely, benzalharman (23), kumujian (27), 1-ethyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (37), 1-acetophenone-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (42), cathin-6-one (46), and 9-methoxy-cathin-6-one (57), exhibited significant inhibitory activity on the overproduction of NO with good dose dependency. Further investigation demonstrated that all of the six compounds down-regulated the high expression of inducible nitric oxide synthase (iNOS) protein. Among them, two canthinone-type alkaloids (46 and 57) potently down-regulated cyclooxygenase-2 (COX-2) protein expression in a dose-dependent manner and also inhibited the overproduction of inflammatory mediator prostaglandin E2 (PGE2). However, the β-carboline-type alkaloids (23, 27, 37, and 42) exhibited no obvious inhibition on the overproduction of PGE2 and the expression of COX-2 protein. The results suggested that β-carboline-type alkaloids and canthinone-type alkaloids may exert an anti-inflammatory effect through different mechanism.

Journal ArticleDOI
TL;DR: In this paper, a screening program targeting Wnt signaling activity using a cell-based luciferase screening system assessing TCF/β-catenin transcriptional activity was proposed.
Abstract: Wnt signaling has been implicated in numerous aspects of development, cell biology, and physiology. When aberrantly activated, Wnt signaling can also lead to the formation of tumors. Thus, Wnt signaling is an attractive target for cancer therapy. Based on our screening program targeting Wnt signaling activity using a cell-based luciferase screening system assessing TCF/β-catenin transcriptional activity, we isolated a series of terpenoids and heterocyclic aromatic compounds that affect the Wnt signaling pathway at different points. Here, we describe our recent results in screening for natural products that inhibit or activate Wnt signaling.