Effects of Different Molecular Weight Polysaccharides From Dendrobium officinale Kimura & Migo on Human Colorectal Cancer and Transcriptome Analysis of Differentially Expressed Genes.

We investigated the antitumor effects of four fractions of Dendrobium officinale Kimura & Migo (D. officinale) polysaccharides with different molecular weights (Mw), Astragalus membranaceus polysaccharides (APS) and Lentinus edodes polysaccharides (LNT) on colorectal cancer (CRC) using a zebrafish xenograft model. Transcriptome sequencing was performed to further explore the possible antitumor mechanisms of D. officinale polysaccharides. Fractions of D. officinale polysaccharides, LNT, and APS could significantly inhibit the growth of HT-29 cells in a zebrafish xenograft model. One fraction of D. officinale polysaccharides called DOPW-1 (Mw of 389.98 kDa) exhibited the strongest tumor inhibition. Compared with the control group, RNA-seq revealed that the DOPW-1-treated experimental group had 119 differentially expressed genes (DEGs), of which 45 had upregulated expression and 74 had downregulated expression. Analyses using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes suggested that the pathway "apoptosis-multiple species" was the most significantly enriched. Our data indicated that 1) fractions of D. officinale polysaccharides of Mw 389.98 kDa were most suitable against CRC; 2) DOPW-1 could be developed into a clinical agent against CRC; and 3) an apoptosis pathway is important for DOPW-1 to inhibit the proliferation of HT-29 cells.

Gigantol inhibits proliferation and enhances DDP-induced apoptosis in breast-cancer cells by downregulating the PI3K/Akt/mTOR signaling pathway.

AIMS: Gigantol is a bibenzyl compound isolated from orchids of the genus Dendrobium. Gigantol has been demonstrated to possess various pharmacologic (including anticancer) effects. Cisplatin (DDP) has been used and studied as the first-line agent for breast cancer (BC) treatment. Often, its efficacy is jeopardized due to intolerance and organ toxicity. We investigated if gigantol could enhance the anticancer effects of DDP in BC cells and its underlying mechanism of action. MAIN METHODS: The potential pathway of gigantol in BC cells was detected by network-pharmacology and molecular-docking studies. The proliferation and apoptosis of BC cell lines were measured by the MTT assay, colony formation, Hoechst-33342 staining, and flow cytometry. Protein expression was measured by western blotting. KEY FINDINGS: Gigantol could inhibit proliferation of BC cells and enhance DDP-induced apoptosis. According to the results of western blotting, gigantol reinforced DDP-induced anticancer effects through downregulation of the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway in BC cells. The effects were consistent with those of the pathway inhibitor LY294002. SIGNIFICANCE: Our data might provide new insights into the underlying antitumor effect of gigantol in BC cells. This enhancement effect in the combination of gigantol and DDP may provide many therapeutic benefits in clinical treatment regimens against BC.

PPAR-γ Promotes Hematoma Clearance through Haptoglobin-Hemoglobin-CD163 in a Rat Model of Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: PPAR-γ is a transcriptional factor which is associated with promoting hematoma clearance and reducing neurological dysfunction after intracerebral hemorrhage (ICH). Haptoglobin- (Hp-) hemoglobin- (Hb-) CD163 acts as a main pathway to Hb scavenging after ICH. The effect of PPAR-γ on the Hp-Hb-CD163 signaling pathway has not been reported. We hypothesized that PPAR-γ might protect against ICH-induced neuronal injury via activating the Hp-Hb-CD163 pathway in a rat ICH model. METHODS: 107 Sprague-Dawley rats were used in this research. They were randomly allocated to 4 groups as follows: sham group, vehicle group, monascin-treated group, and Glivec-treated group. Animals were euthanized at 3 days after the model was established successfully. We observed the effects of PPAR-γ on the brain water content, hemoglobin levels, and the expressions of CD163 and Hp in Western blot and real-ime PCR; meanwhile, we measured hematoma volumes and edema areas by MRI scanning. RESULT: The results showed that PPAR-γ agonist significantly reduced hematoma volume, brain edema, and hemoglobin after ICH. It also enhanced CD163 and Hp expression while PPAR-γ antagonist had the opposite effects. CONCLUSIONS: PPAR-γ promotes hematoma clearance and plays a protective role through the Hp-Hb-CD163 pathway in a rat collagenase infusion ICH model.

The effect of monascin on hematoma clearance and edema after intracerebral hemorrhage in rats.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is a particularly devastating form of stroke with high mortality and morbidity. Hematomas are the primary cause of neurologic deficits associated with ICH. The products of hematoma are recognized as neurotoxins and the main contributors to edema formation and tissue damage after ICH. Finding a means to efficiently promote absorption of hematoma is a novel clinical challenge for ICH. Peroxisome proliferator-activated receptor gamma (PPARγ) and nuclear factor erythroid 2-related factor 2 (Nrf2), had been shown that, can take potential roles in the endogenous hematoma clearance. However, monascin, a novel natural Nrf2 activator with PPARγ agonist, has not been reported to play a role in ICH. This study was designed to evaluate the effect of monascin on neurological deficits, hematoma clearance and edema extinction in a model of ICH in rats. METHODS: 164 adult male Sprague-Dawley (SD) rats were randomly divided into sham; vehicle; monascin groups with low dosages (1mg/kg/day), middle dosages (5mg/kg/day) and high dosages (10mg/kg/day) respectively. Animals were euthanized at 1, 3 and 7days following neurological evaluation after surgery. We examined the effect of monascin on the brain water contents, blood brain barrier (BBB) permeability and hemoglobin levels, meanwhile reassessed the volume of hematoma and edema around the hematoma by Magnetic Resonance Imaging (MRI) in each group. RESULTS: The high dosage of monascin significantly improved neurological deficits, reduced the volume of hematoma in 1-7days after ICH, decreased BBB permeability and edema formation in 1-3days following ICH. CONCLUSION: Our study demonstrated that the high dosage of monascin played a neuroprotective role in ICH through reducing BBB permeability, edema and hematoma volume.