Yue Hou

Anti-tumor activity of three ginsenoside derivatives in lung cancer is associated with Wnt/β-catenin signaling inhibition.

Numerous compounds isolated from Ginseng have been shown to exhibit various biological activities, including antioxidant, anti-carcinogenic, anti-mutagenic, and anti-tumor activities. Recent research has focused on the potential values of these compounds in the prevention and treatment of human cancers. The anti-tumor activity of 25-hydroxyprotopanaxadiol (25-OH-PPD), a natural compound isolated from Panax ginseng, has been established in previous study. In the current study, we investigated the anti-tumor activity of three derivatives of 25-OH-PPD, namely xl, 1c, and 8b with respect to lung cancer. All three compounds significantly inhibited the growth of the human lung cancer cells A549 and H460. Oral administration of these compounds significantly inhibited the growth of xenograft tumors in mice without affecting body weight. Further mechanistic study demonstrated that these compounds could decrease the expression levels of β-catenin and its downstream targets Cyclin D1, CDK4, and c-myc in lung cancer cells. Taken together, the results suggested that the anti-growth activity exerted by these 25-OH-PPD derivatives against lung cancer cells probably involved β-catenin-mediated signaling pathway, a finding that could have important implication for chemotherapeutic strategy aiming at the treatment of lung cancer.

Minocycline protects against lipopolysaccharide-induced cognitive impairment in mice.

RationaleThe role of glial cells, especially microglia and astrocytes, in neuroinflammation and cognition has been studied intensively. Lipopolysaccharide (LPS), a commonly used inducer of neuroinflammation, can cause cognitive impairment. Minocycline is known to possess potent neuroprotective activity, but its effect on LPS-induced cognitive impairment is unknown.ObjectivesThis study aims to investigate the effects of minocycline on LPS-induced cognitive impairment and glial cell activation in mice.MethodsBehavioral tests were conducted for cognitive function, immunohistochemistry for microglial and astrocyte response, and quantitative PCR for mRNA expression of proinflammatory cytokines.ResultsMinocycline significantly reversed the decreased spontaneous alternation induced by intrahippocampal administration of LPS in the Y-maze task. In the Morris water maze place navigation test, minocycline decreased the escape latency and distance traveled compared to LPS-treated mice. In the probe test, minocycline-treated mice spent more time in the target quadrant and crossed the platform area more frequently than animals in the LPS-treated group. Minocycline produced a significant decrease in the number of Iba-1- and GFAP-positive hippocampal cells compared to the LPS-treated group. Minocycline-treated mice had significantly reduced hippocampal TNF-α and IL-1β mRNA levels compared with LPS-treated animals. Minocycline caused a significant increase in hippocampal BDNF expression compared to the LPS-treated group.ConclusionsMinocycline can attenuate LPS-induced cognitive impairments in mice. This effect may be associated with its action to suppress the activation of microglia and astrocytes and to normalize BDNF expression. Since neuroinflammatory processes and cognitive impairments are implicated in neurodegenerative disorders, minocycline may be a promising candidate for treating such diseases.

Shikonin induces apoptosis in the human gastric cancer cells HGC-27 through mitochondria-mediated pathway.

Background: Gastric cancer (GC) is one of the most frequently occurring digestive tract cancers and fewer chemotherapeutic drugs for GC have shown promising results. In this study, we investigated the anti-tumor activity of shikonin, a natural compound isolated from the Chinese plant Lithospermum erythrorhizon, against the human GC cell line HGC-27. Materials and Methods: HGC-27 cells treated with shikonin at a concentration of 30μM or above showed significant growth inhibition compared to control cells. Shikonin-treated cells also underwent apoptosis as detected by flow cytometric analysis and microscopic examination of cellular morphology. Further investigation into the underlying mechanism of apoptosis by western blot showed that the shikonin promoted the activation of poly-(ADP-ribose)-polymerase, caspase-3 and caspase-9 following 24 h or 48 h of treatment time, as well as the activation of caspase-8, but only after 48 h of treatment time. Furthermore, the levels of mitochondrial membrane potential, B-cell lymphoma 2 (Bcl-2) and Bcl-extra large were reduced following shikonin treatment while the level of Bax was increased. In addition, shikonin also caused a significant reduction of the protein Survivin, while having little effect on the expression on X-linked inhibitor of apoptosis protein. Conclusion: Taken together, these results showed that the shikonin exhibited its anti-tumor activity against HGC-27 cells through inhibiting cell growth and promoting apoptosis by targeting mitochondrial-related signaling pathway. Our finding may represent a positive step in finding a natural and effective compound that could be important implication for future development of chemotherapeutic and/or chemopreventive agent against GC.

Bioactive phenols as potential neuroinflammation inhibitors from the leaves of Xanthoceras sorbifolia Bunge

Xanthoceras sorbifolia Bunge is a medicinal plant and also a valuable cash crop used for production of edible oil and biofuels in China. In our previous research, systematical phytochemical and bioactive profiles of different parts from X. sorbifolia have been obtained. Here we describe the effective phenols from the leaves of X. sorbifolia, which could function as natural neuroinflammation inhibitors. As a result, 23 compounds were characterized as the phenols from the leaves of X. sorbifolia by means of chromatographical methods and spectroscopic analysis. Among them, flavonoids quercetin3-O-β-d-glucopyarnoside (IC50 13.39±1.27μM), catechin (IC50 9.52±2.18μM), and phenylpropanoids syringaresinol-4-O-β-d-glucopyranoside (IC50 3.08±1.77μM), 4-O-β-d-glucopyranosyl-trans-p-coumaric acid (IC50 9.08±1.23μM) exhibited much stronger inhibiting effect on NO production than that of the positive control minocycline (IC50 37.04±2.09μM) in LPS-induced BV2 cells.

Okanin, effective constituent of the flower tea Coreopsis tinctoria , attenuates LPS-induced microglial activation through inhibition of the TLR4/NF-κB signaling pathways

The EtOAc extract of Coreopsis tinctoria Nutt. significantly inhibited LPS-induced nitric oxide (NO) production, as judged by the Griess reaction, and attenuated the LPS-induced elevation in iNOS, COX-2, IL-1β, IL-6 and TNF-α mRNA levels, as determined by quantitative real-time PCR, when incubated with BV-2 microglial cells. Immunohistochemical results showed that the EtOAc extract significantly decreased the number of Iba-1-positive cells in the hippocampal region of LPS-treated mouse brains. The major effective constituent of the EtOAc extract, okanin, was further investigated. Okanin significantly suppressed LPS-induced iNOS expression and also inhibited IL-6 and TNF-α production and mRNA expression in LPS-stimulated BV-2 cells. Western blot analysis indicated that okanin suppressed LPS-induced activation of the NF-κB signaling pathway by inhibiting the phosphorylation of IκBα and decreasing the level of nuclear NF-κB p65 after LPS treatment. Immunofluorescence staining results showed that okanin inhibited the translocation of the NF-κB p65 subunit from the cytosol to the nucleus. Moreover, okanin significantly inhibited LPS-induced TLR4 expression in BV-2 cells. In summary, okanin attenuates LPS-induced activation of microglia. This effect may be associated with its capacity to inhibit the TLR4/NF-κB signaling pathways. These results suggest that okanin may have potential as a nutritional preventive strategy for neurodegenerative disorders.

Characteristic α-Acid Derivatives from Humulus lupulus with Antineuroinflammatory Activities

Twenty compounds, including 14 new α-acid derivatives, a new chromone, and five known compounds, were identified from the pistillate inflorescence of Humulus lupulus (hops), and their structures were elucidated via physical data analysis. The absolute configurations of new α-acid derivatives 1-11b were determined by comparing their computed and experimental electronic circular dichroism spectra using TDDFT and NMR spectroscopic data. A putative biosynthetic pathway for the identified components was deduced. Their antineuroinflammatory effects were assayed systematically, and their structure-activity relationships are discussed briefly. Among the identified compounds, compound 14 displayed moderate inhibitory effects against nitric oxide production with an IC50 value of 7.92 μM.

Biotransformation of neuro-inflammation inhibitor kellerin using Angelica sinensis (Oliv.) Diels callus

Kellerin, a sesquiterpene coumarin derivative, has been identified as a major constituent of Ferula sinkiangensis K. M. Shen. It has been proved to be a potential natural therapeutic agent for Alzheimers disease because of its inhibition of inflammatory cytokines nitric oxide (NO), tumor necrosis factor-α (IL-6) (TNF-α), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in over-activated BV2 mouse microglial cells. Because of the multi chiral centers and the chemical instability of the sesquiterpene, coumarin, it is rather difficult to obtain this bioactive natural product by synthesis. Thus, biotransformation of kellerin was carried out to afford more novel derivatives using the callus of Angelica sinensis (Oliv.) Diels, which has an abundance of biosynthetic enzymes of phenylpropanoids. As a result, 14 products were obtained and identified, including four new sesquiterpene coumarin derivatives: 14′-hydroxy-(3′S,4′R,5′S,8′R,9′S,10′R)-kellerin (1), 5′,6′-ene-14′-hydroxy-(3′S,4′R,8′R,9′S,10′R)-kellerin (2), 5′,6′-ene-(3′R,8′R,9′S,10′R)-ferukrin (3), and 14′-hydroxy-(3′S,4′R,5′S,8′R,9′S,10′R)-deacetylkellerin (4), together with 10 other known compounds. Their structures were elucidated using comprehensive spectroscopic techniques and their possible biosynthetic pathways were proposed on the basis of the structural analyses. Furthermore, their anti-neuroinflammatory activities were assessed in BV2 cells by monitoring lipopolysaccharide-induced NO production, and the structure–activity relationships were discussed.

Novel cycloneolignans from Vernicia fordii with inhibitory effects on over-activation of BV2 cells in vitro.

Novel natural products 7R, 8R, 7′R, 9′S-verniciasin A (1a), 7S, 8S, 7′S, 9′R- verniciasin A (1b), 7R, 8R, 7′R, 9′S−7′-methoxylverniciasin A (2a) and 7S, 8S, 7′S, 9′R−7′-methoxylverniciasin A (2b) were characterized from the seed capsule of Vernicia fordii. And the unique 9-O-9′−7, 9′-cyclo-8, 1′-neolignan skeleton with a seven-membered ring, was identified by extensive spectroscopic analysis. Further the possible biosynthetic pathway was briefly discussed. Interestingly, 1a, 2a, 1b and 2b all exhibited significant stereoselective inhibitory effects on NO production in LPS-induced BV2 microglia cell. Then the primary mechanism of the bioactivities and stereoselectivity was explored by means of bioassay and molecular docking.

Tamarix hohenackeri Bunge exerts anti-inflammatory effects on lipopolysaccharide-activated microglia in vitro

BACKGROUND Tamarix species are well known as the main host plants of Herba Cistanches, a valuable Traditional Chinese Medicine. They are also traditional medicinal plants themselves and are used to treat spleen problems, leucoderma and ocular conditions. PURPOSE The aim of the present study was to investigate the anti-inflammatory effect of Tamarix hohenackeri Bunge. METHODS In the present study, BV-2 microglial cells were used and stimulated with lipopolysaccharide (LPS). Cell viability was tested using the MTT assay. The release of nitric oxide (NO) was determined using the Griess assay. The mRNA level of inducible nitric oxide synthase (iNOS), tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 were investigated by quantitative real-time PCR (qRT-PCR). The protein levels of phosphorylated of IκBα, ERK and MEK, as well as the cytoplasmic and nuclear NF-κB p65 were tested by Western blot analysis. The translocation of the NF-κB p65 subunit from the cytosol to the nucleus was investigated by immunofluorescence staining. RESULTS Ethyl acetate (EtOAc) extract of Tamarix hohenackeri Bunge significantly inhibited the release of NO. Phytochemical research was performed to produce 13 main constituents. Among them, compounds 6, 7, 10 and 13 were identified to be the effective components with anti-inflammatory activity. These compounds significantly inhibited the production of NO by LPS-activated BV-2 microglial cells. qRT-PCR showed that compounds 6 and 7 significantly suppressed the LPS-induced transcription of genes encoding pro-inflammatory mediators, including iNOS, TNF-α, IL-1β and IL-6. Western blot analysis showed that compound 7 inhibited the LPS-induced phosphorylation of IκBα and antagonized the LPS-induced reduction of cytoplasmic NF-κB p65 and the increase of nuclear NF-κB p65. Immunofluorescence staining showed that nuclear translocation of NF-κB p65 was suppressed by compound 7. Western blot analysis showed that compound 7 inhibited the LPS-induced phosphorylation of ERK and MEK. CONCLUSION The present study revealed, for the first time, the effective anti-inflammatory agents from T. Hohenackeri. Compound 7 exerted potent anti-inflammatory effects and its underlying mechanism may be associated with its capacity to inhibit NF-κB signaling pathway and the MEK/ERK activation in activated microglia. The compound may be potential candidate therapeutic agent for neurodegenerative diseases.