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Background Lung cancer is one of the leading causes of cancer related deaths worldwide. Marine microalgae are a source of biologically active compounds and are widely consumed as a nutritional supplement in East Asian countries. It has been reported that Chlorella or Chlorella extracts have various beneficial pharmacological compounds that modulate immune responses; however, no studies have investigated the anti-cancer effects of Chlorella sorokiniana (CS) on non-small cell lung cancer (NSCLC). Methods In this study, we evaluated the anti-cancer effects of CS in two human NSCLC cell lines (A549 and CL1-5 human lung adenocarcinoma cells), and its effects on tumor growth in a subcutaneous xenograft tumor model. We also investigated the possible molecular mechanisms governing the pharmacological function of CS. Results Our results showed that exposure of the two cell lines to CS resulted in a concentration-dependent reduction in cell viability. In addition, the percentage of apoptotic cells increased in a dose-dependent manner, suggesting that CS might induce apoptosis in human NSCLC cells. Western blot analysis revealed that exposure to CS resulted in increased protein expression of the cleaved/activated forms of caspase-3, caspase-9, and PARP, except caspase-8. ZDEVD (caspase-3 inhibitor) and Z-LEHD (caspase-9 inhibitor) were sufficient at preventing apoptosis in both A549 and CL1-5 cells, proving that CS induced cell death via the mitochondria-mediated apoptotic pathway. Exposure of A549 and CL1-5 cells to CS for 24 h resulted in decreased expression of Bcl-2 protein and increased expression of Bax protein as well as decreased expression of two IAP family proteins, survivin and XIAP. Conclusions We demonstrated that CS induces mitochondrial-mediated apoptosis in NSCLC cells via downregulation of Bcl-2, XIAP and survivin. In addition, we also found that the tumors growth of subcutaneous xenograft in vivo was markedly inhibited after oral intake of CS.

Neuroinflammation plays a central role in the pathophysiology of Alzheimer’s disease (AD). Compounds that suppress neuroinflammation have been identified as potential therapeutic targets for AD. Rhinacanthin C (RC), a naphthoquinone ester found in Rhinacanthus nasutus Kurz (Acanthaceae), is currently proposed as an effective molecule against inflammation. However, the exact role of RC on neuroinflammation remains to be elucidated. In the present study, we investigated RC effect on modulating lipopolysaccharides (LPS), amyloid-β peptide (Aβ), or interferon-γ- (IFN-γ-) evoked pathological events in neurons and glia. Our findings demonstrated that RC prevented Aβ-induced toxicity in rat hippocampal neurons and attenuated LPS-activated nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) expression, and NF-κB signaling in rat glia. Likewise, RC suppressed LPS-induced neuroinflammation by reducing NO production and iNOS, IL-1β, CCL-2, and CCL-5 mRNA levels in rat microglia. Further studies using BV-2 microglia revealed that RC inhibited LPS-, Aβ-, and IFN-γ-stimulated IL-6 and TNF-α secretion. Of note, NF-κB and ERK activation was abrogated by RC in BV-2 cell response to Aβ or IFN-γ. Moreover, RC protected neurons from Aβ-stimulated microglial conditioned media-dependent toxicity. Collectively, these data highlight the beneficial effects of RC on neuroprotection and support the therapeutic implications of RC to neuroinflammation-mediated conditions.

Background To identify a novel therapeutic agent for hepatocellular carcinoma (HCC), for which no promising therapeutic agent exists, we screened a panel of plants and found that Juniperus chinensis exhibited potential antiangiogenic and anti-HCC activities. We further investigated the antiangiogenic and anti-HCC effects of the active ingredient of J. chinensis extract, CBT-143-S-F6F7, both in vitro and in vivo. Methods A tube formation assay conducted using human umbilical vein endothelial cells (HUVECs) was first performed to identify the active ingredient of CBT-143-S-F6F7. A series of angiogenesis studies, including HUVEC migration, Matrigel plug, and chorioallantoic membrane (CAM) assays, were then performed to confirm the effects of CBT-143-S-F6F7 on angiogenesis. The effects of CBT-143-S-F6F7 on tumor growth were investigated using a subcutaneous and orthotopic mouse model of HCC. In vitro studies were performed to investigate the effects of CBT-143-S-F6F7 on the cell cycle and apoptosis in HCC cells. Moreover, protein arrays for angiogenesis and apoptosis were used to discover biomarkers that may be influenced by CBT-143-S-F6F7. Finally, nuclear magnetic resonance analysis was conducted to identify the compounds of CBT-143-S-F6F7. Results CBT-143-S-F6F7 showed significantly antiangiogenic activity in various assays, including HUVEC tube formation and migration, CAM, and Matrigel plug assays. In in vivo studies, gavage with CBT-143-S-F6F7 significantly repressed subcutaneous Huh7 tumor growth in severe combined immunodeficient (SCID) mice, and prolonged the survival of orthotopic Huh7 tumor-bearing SCID mice (a 40 % increase in median survival duration compared with the vehicle-treated mice). Immunohistochemical staining of subcutaneous Huh7 tumors in CBT-143-S-F6F7-treated mice showed a significantly decrease in the cell cycle regulatory protein cyclin D1, cellular proliferation marker Ki-67, and endothelial marker CD31. CBT-143-S-F6F7 caused arrest of the G2/M phase and induced Huh7 cell apoptosis, possibly contributing to the inhibition of HCC tumors. Protein array analysis revealed that several angiogenic and antiapoptotic factors were suppressed in CBT-143-S-F6F7-treated Huh7 cells. Finally, five compounds from CBT-143-S-F6F7 were identified. Conclusions According to these results, we report for the first time the antiangiogenic and anti-HCC activities of CBT-143-S-F6F7, the active fractional extract of J. chinensis. We believe that CBT-143-S-F6F7 warrants further evaluation as a new anti-HCC drug. Electronic supplementary material The online version of this article (doi:10.1186/s12906-016-1250-6) contains supplementary material, which is available to authorized users.

Chlorella sorokiniana(CS) is a unicellular green alga. The extracts ofChlorellahave been used as treatments for relieving hypertension and modulating immune response. The detailed mechanisms are not clear yet. In this study, we sought to study the molecular mechanisms for the polysaccharide fraction of CS-induced immune response. We pulsed dendritic cells (DCs) with CS and found that CS could maturate DCs. CS-maturated DC could activate naïve T cells and stimulate T-cell proliferation and IFN-γsecretion. Furthermore, CS activated PI3K and MAPKs signaling pathways in DCs by interacting with TLR4 receptor. These CS-activated signaling pathways could further activate NF-κB and induce IL-12 production in DCs. This study provides molecular mechanisms for CS-induced DCs activation and immune response.

Antrodia cinnamomea (A. cinnamomea) is a Chinese medicinal herb that possesses a broad range of bioactivities, including anti-inflammation. Given that the proinflammatory cytokine IL-17 plays a critical role in the pathogenesis of autoimmune diseases, we investigated whether A. cinnamomea could inhibit the development of Th17 cells, the main producer of IL-17, and exhibit therapeutic effects on an animal model of psoriasis. We found that A. cinnamomea extract (AC) inhibited the differentiation of Th17 cells as well as the production of IL-17A, IL-21, and IL-22 from these cells. This effect was associated with the inhibition of STAT3 phosphorylation and ROR[Formula: see text]t expression. Notably, the oral administration of AC reduced psoriasis-like inflammation in imiquimod-mediated dermal damage, repressed the expression of IL-17A, IL-22, and TNF-[Formula: see text] in skin lesions, and decreased the infiltration of CD4[Formula: see text] T cells, CD8[Formula: see text] T cells, and neutrophils into the dermis. Finally, serum levels of IL-17A were decreased in AC-treated mice with psoriasis-like skin inflammation. Taken together, these findings indicate that AC inhibits Th17 cell differentiation, suggesting a role for A. cinnamomea in the treatment of psoriasis and other Th17 cell-mediated inflammatory diseases.

The biphasic effects of Pu-Chung-I-Chi-Tang (PCT) on sedation and excitation in acute treatment or after one-week consecutive treatment were studied. The results indicated that PCT produces sedation in acute treatment and excitation after one-week consecutive treatment. The sedative mechanism of PCT in acute treatment might be due to an increase in serotonergic activity and a decrease in dopaminergic activity. However, the excitatory mechanism of PCT after one-week consecutive treatment might involve the increase in dopaminergic activity and the decrease in serotonergic activity.