A dual-response drug delivery system with X-ray and ROS to boost the anti-tumor efficiency of TPZ via enhancement of tumor hypoxia levels.

The selective anti-tumor activity and less toxic nature of hypoxia-activated prodrugs including tirapazamine (TPZ) are harbored by hypoxia levels in tumors, the inadequacy of which leads to failure in clinical trials. Thus, the development of effective clinical applications of TPZ requires advanced strategies to intensify hypoxia levels in tumors effectively and safely. In this study, we designed and fabricated a paclitaxel (PTX)-loaded dual-response delivery system with a low dose (e.g., 2 Gy) of X-ray and reactive oxygen species on the basis of diselenide block copolymers. Upon the external X-ray stimulus, the system accurately released encapsulated PTX at tumor sites and remarkably improved tumor hypoxia levels by causing severe damage to tumor blood vessels. Subsequently, these enhanced tumor hypoxia levels effectively activated the reduction of TPZ into benzotriazinyl free radicals, which significantly improved the antitumor efficacy of our system against 4T1 breast cancer cells with an initial tumor volume of 500 mm3. Moreover, the dual-stimulus coordinated and controlled release of PTX was found to largely avoid the off-target effects of PTX on normal cells while exhibiting very limited side effects in experimental mice. The current novel strategy for regulating tumor hypoxia levels offers an effective and safe way to activate TPZ for the treatment of large solid tumors.

Ginsenoside Rg5: A Review of Anticancer and Neuroprotection with Network Pharmacology Approach.

Ginsenoside Rg5 (G-Rg5) is a rare ginsenoside isolated from ginseng (Panax ginseng C.A. Meyer), and this compound is increasingly known for its potent pharmacological activities. This study aimed to provide a comprehensive review of the main activities and mechanisms of G-Rg5 by adopting network pharmacological analysis combined with a summary of published articles. The 100 target genes of G-Rg5 were searched through available database, subjected to protein-protein interaction (PPI) network generation and then core screening. The results showed that G-Rg5 has promising anticancer and neuroprotective effects. By summarizing these two pharmacological activities, we found that G-Rg5 exerts its therapeutic effects mainly through PI3K/AKT, MAPK signaling pathways, and the regulation of apoptosis and cell cycle. And these results were corroborated by KEGG analysis. Likewise, molecular docking of the related proteins was performed, and the binding energies were all less than [Formula: see text]7.0[Formula: see text]kJ/mol, indicating that these proteins had excellent binding capacity with G-Rg5. The network pharmacology results revealed many potential G-Rg5 mechanisms, which need to be further explored. We expect that the network pharmacology approach and molecular docking techniques can help us gain a deeper understanding of the therapeutic mechanisms of different ginsenosides and even the ginseng plant, for further developing their therapeutic potential as well as clinical applications.

Antidepressant-like effect of ginsenoside Rb1 on potentiating synaptic plasticity via the miR-134-mediated BDNF signaling pathway in a mouse model of chronic stress-induced depression.

Background: Brain-derived neurotrophic factor (BDNF)-tropomyosin-related kinase B (TrkB) plays a critical role in the pathogenesis of depression by modulating synaptic structural remodeling and functional transmission. Previously, we have demonstrated that the ginsenoside Rb1 (Rb1) presents a novel antidepressant-like effect via BDNF-TrkB signaling in the hippocampus of chronic unpredictable mild stress (CUMS)-exposed mice. However, the underlying mechanism through which Rb1 counteracts stress-induced aberrant hippocampal synaptic plasticity via BDNF-TrkB signaling remains elusive. Methods: We focused on hippocampal microRNAs (miRNAs) that could directly bind to BDNF and are regulated by Rb1 to explore the possible synaptic plasticity-dependent mechanism of Rb1, which affords protection against CUMS-induced depression-like effects. Results: Herein, we observed that brain-specific miRNA-134 (miR-134) could directly bind to BDNF 3'UTR and was markedly downregulated by Rb1 in the hippocampus of CUMS-exposed mice. Furthermore, the hippocampus-targeted miR-134 overexpression substantially blocked the antidepressant-like effects of Rb1 during behavioral tests, attenuating the effects on neuronal nuclei-immunoreactive neurons, the density of dendritic spines, synaptic ultrastructure, long-term potentiation, and expression of synapse-associated proteins and BDNF-TrkB signaling proteins in the hippocampus of CUMS-exposed mice. Conclusion: These data provide strong evidence that Rb1 rescued CUMS-induced depression-like effects by modulating hippocampal synaptic plasticity via the miR-134-mediated BDNF signaling pathway.

Low-Dose X-ray-Responsive Diselenide Nanocarriers for Effective Delivery of Anticancer Agents.

X-ray-responsive nanocarriers for anticancer drug delivery have shown great promise for enhancing the efficacy of chemoradiotherapy. A critical challenge remains for development of such radiation-controlled drug delivery systems (DDSs), which is to minimize the required X-ray dose for triggering the cargo release. Herein, we design and fabricate an effective DDS based on diselenide block copolymers (as nanocarrier), which can be triggered to release their cargo with a reduced radiation dose of 2 Gy due to their sensitivity to both X-ray and the high level of reactive oxygen species (ROS) in the microenvironment of cancer cells. The underlying molecular mechanism is further illustrated by proton nuclear magnetic resonance (1H NMR) experiments and density functional theory (DFT) calculations. In vivo experiments on tumor-bearing mice validated that the loaded drugs are effectively delivered to the tumor site and exert remarkable antitumor effects (minimum tumor volume/weight) along with X-ray. Furthermore, the diselenide nanocarriers exhibit no noticeable cytotoxicity. These findings provide new insights for the de novo design of radiation-controlled DDSs for cancer chemoradiotherapy.

Compatibility effects of ginseng and Ligustrum lucidum Ait herb pair on hematopoietic recovery in mice with cyclophosphamide-induced myelosuppression and its material basis.

BACKGROUND: Ginseng (G) and Ligustrum lucidum Ait (LLA) are core traditional Chinese medicines in treating myelosuppression formula. The present study was designed to profile effect of G and LLA herb pair (G-LLA) on myelosuppressed mice. METHODS: The mice myelosuppression model was established by intraperitoneal (i.p.) injection of cyclophosphamide (Cy). Hematopoietic function of bone marrow was measured by hemopoietic progenitor cell culture and peripheral blood count, and serum hemopoietic factors were tested by enzyme-linked immunosorbent assay. Bone marrow cell cycle was performed by flow cytometry. HPLC was used to measure 20 potential chemical components related to myelosuppression, including ginsenoside Rg1, Re, Rb1, Rc, Rb2, Rb3, Rd, Rk3, Rh4, 20 (S)-Rg3, 20 (R)-Rg3, Rk1, Rg5, salidroside, and so on. RESULTS: G, LLA, and G-LLA improved the amount of peripheral blood cells and bone marrow cells of myelosuppressed mice (P < 0.01). They significantly increased the colony quantity of colony-forming unit-granulocyte macrophage, burst-forming unit-erythroid, colony-forming unit-erythroid, and colony-forming unit-megakaryocyte and amount of G2/M and S phase cells (P < 0.01). They also significantly decreased the amount of hematopoiesis-related cytokines (P < 0.01). The content of chemical components in G-LLA changed, and the change of rare saponin was the most obvious. CONCLUSION: These results show that G-LLA herb pair might produce synergistic or complementary compatibility effects on bone marrow suppression after chemotherapy. It suggests that the substance basis of G-LLA for treating bone marrow suppression may be effective chemical components.

Studies of the effects and mechanisms of ginsenoside Re and Rk3 on myelosuppression induced by cyclophosphamide.

BACKGROUND: Ginsenoside Re (Re) is one of the major components of Panax ginseng Meyer. Ginsenoside Rk3 (Rk3) is a secondary metabolite of Re. The aim of this study was to investigate and compare the effects and underlying mechanisms of Re and Rk3 on cyclophosphamide-induced myelosuppression. METHODS: The mice myelosuppression model was established by intraperitoneal (i.p.) injection of cyclophosphamide. Peripheral blood cells, bone marrow nucleated cells, and colony yield of hematopoietic progenitor cells in vitro were counted. The levels of erythropoietin, thrombopoietin, and granulocyte macrophage colony-stimulating factor in plasma were measured by enzyme-linked immunosorbent assay. Bone marrow cell cycle was performed by flow cytometry. The expression of apoptotic protein bcl-2, bax, and caspase-3 was detected by Western blotting. RESULTS: Both Re and Rk3 could improve peripheral blood cells, bone marrow nucleated cell counts, thymus index, and spleen index. Furthermore, they could enhance the yield of colonies cultured in vitro and make the levels of granulocyte macrophage colony-stimulating factor, erythropoietin, and thrombopoietin normal, reduce the ratio of G0/G1 phase cells, and increase the proliferation index. Finally, Re and Rk3 could upregulate the expression of bcl-2, whereas they could downregulate the expression of bax and caspase-3. CONCLUSION: Re and Rk3 could improve the hematopoietic function of myelosuppressed mice. The effect of Rk3 was superior to that of Re at any dose. Regulating the levels of cytokines, promoting cells enter the normal cell cycle, regulating the balance of bcl-2/bax, and inhibiting the expression of caspase-3 may be the effects of Re and Rk3 on myelosuppression.

Rb1, the Primary Active Ingredient in Panax ginseng C.A. Meyer, Exerts Antidepressant-Like Effects via the BDNF-Trkb-CREB Pathway.

Panax ginseng C.A. Meyer (Araliaceae), a popular tonic and dietetic herbal medicine, has been traditionally prescribed in China and other countries to treat affective disorders. The medicinal parts of ginseng, the roots and flower buds, have become increasingly popular as dietary supplements due to the current holistic healthcare trend. We have investigated for the first time the antidepressive actions of the different medicinal parts, namely, the main roots, fibrous roots, and flower buds (in water extract and powder), of garden-cultivated ginseng through behavioral and drug-induced tests in mice. The water extracts, but not the powders of ginseng fibrous roots, flower buds, and main roots (1.5 g of crude drug per kilogram, p.o.), significantly reduced the immobility time in the forced swim test (FST) and tail suspension test (TST); moreover, the water extracts enhanced the 5-hydroxytryptophan (5-HTP)-induced head-twitch response and antagonized the action of reserpine in the mouse. We then explored the antidepressive mechanism of action of the ginsenoside Rb1 (Rb1) related to the brain-derived neurotrophic factor (BDNF) and its downstream proteins in mice exposed to chronic unpredictable mild stress (CUMS). Treatment with Rb1 (20 mg/kg, p.o.) for 21 days significantly attenuated the CUMS-induced decrease in the activities of BDNF, tropomyosin-related kinase B (TrkB), protein kinase B (AKT), extracellular regulatory protein kinase (ERK), and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) in the mouse hippocampal CA3 region and prefrontal cortex (PFC). Interestingly, treatment with the novel TrkB antagonist ANA-12 (0.5 mg/kg, i.p.) did not alter the level of BDNF but significantly blocked the antidepressive effects of Rb1 on proteins downstream of BDNF in CUMS-treated mice. These results suggest that BDNF-TrkB-CREB signaling may be involved in the antidepressive mechanism of the action of Rb1.

Study of the Effects and Mechanisms of Ginsenoside Compound K on Myelosuppression.

Ginsenoside compound K (CK) is not a ginsenoside that naturally exists in Panax ginseng Meyer. However, CK is a major metabolite of ginsenoside Rb1, Rb2, or Rc in the intestine under the effects of bacteria. In this study, we first investigated the effects of CK on myelosuppression in mice induced by cyclophosphamide (CTX). The respective quantities of white blood cells, blood platelets, and bone marrow nucleated cells (BMNCs) were determined to be 8.54 ± 0.91 (109/L), 850.90 ± 44.11 (109/L), and 1.45 ± 0.22 (109/L) in the CK-H group by detecting peripheral blood cells and BMNCs. CK-H and CK-L both increased the thymus index by up to 0.62 ± 0.06 (mg/g) and 0.52 ± 0.09 (mg/g), respectively, and significantly increased the yields of colony formation units-granulocyte monocyte and colony formation units-megakaryocytic. According to our study, CK could control apoptosis and promote cells to enter the normal cell cycle by the bcl-2/bax signaling pathway and MEK/ERK signaling pathway. Therefore, the BMNCs could proliferate and differentiate normally after entering the normal cell cycle. So the peripheral blood cells could show a trend of returning to normal. The recovery of peripheral blood cells resulting in the level of cytokines tended to normal. This process may be the mechanisms of CK on myelosuppression. This study provides a reference for ginseng in the treatment of myelosuppression.

Hepatoprotective effect of chiisanoside from Acanthopanax sessiliflorus against LPS/D-GalN-induced acute liver injury by inhibiting NF-κB and activating Nrf2/HO-1 signaling pathways.

BACKGROUND: In China, Acanthopanax sessiliflorus is a delicious wild vegetable. It is also used to treat inflammation and pain. Chiisanoside (CSS) is the main constituent of the leaf of A. sessiliflorus. Combined use of lipopolysaccharide and d-galactosamine (LPS/D-GalN) can induce acute liver failure in human beings, and there are no reports on the protective effect of CSS against LPS/D-GalN-induced acute liver injury in mice. RESULTS: Chiisanoside pretreatment evidently reduced the activities of alanine transaminase (ALT) and aspartate transaminase (AST) in the changes induced by LPS/D-GalN, and these histopathological changes induced by LPS/GalN were significantly weakened. Catalase (CAT), glutathione (GSH), and superoxide dismutase (SOD) activities increased, and malondialdehyde (MDA) activity decreased after CSS treatment compared with LPS/D-GalN treatment. Pretreatment with CSS also inhibited the expression levels of inflammatory factors. The administration of CSS prevented the phosphorylated expression of inhibitor kappa B (IκB) kinase, and led to a significant increase in heme oxygenase-1 (HO-1) expression and nuclear factor erythroid 2-related factor2 (Nrf2) nuclear translocation. CONCLUSION: The protective effects of CSS are attributed to its antioxidative effect and inflammatory suppression in Nuclear factor kappa beta (NF-κB) and Nrf2/HO-1 signaling pathways. Chiisanoside might therefore be a potential ingredient for drug and food development against acute liver injury in the future. © 2018 Society of Chemical Industry.

Study on the simultaneous degradation of five pesticides by Paenibacillus polymyxa from Panax ginseng and the characteristics of their products.

The quality and safety of ginseng products were seriously affected due to the slow metabolism and long-term residual pesticides in ginseng. Microbial degradation is an effective method to degrade pesticide residues. In this study, ginseng endophytic Paenibacillus polymyxa was used to degrade pesticide residues. A method of simultaneous determination of fluazinam, BHC, PCNB, chlorpyrifos and DDT in ginseng roots and ginseng stems and leaves by GC was established. The sample was extracted with n-hexane and purified by Florisil solid phase extraction column. The limit of quantitation was 0.01 µg mL-1, the linear relationship was good (r ≥ 0.9901). 7 days after inoculated with P. polymyxa, the degradation rates of fluazinam, BHC, PCNB, chlorpyrifos, and DDT in the medium were 94.77%, 70.34%, 77.92%, 78.30%, 66.70%, respectively (P < 0.05). The safety of 5 pesticide degradation products was investigated by GC-MS. The results showed that after 7 days degradation, the main degradation products were alkanes, which are non-toxic and can't cause secondary pollution to the environment. The actual degradation results were verified by field experiments. The results indicated that after sprayed 5 times with P. polymyxa, the degradation rates of fluazinam, BHC, PCNB, chlorpyrifos and DDT in the ginseng roots were 66.07%, 46.24%, 21.05%, 72.40%, 54.21%, respectively (P < 0.05). The degradation rates in ginseng stems and leaves were 74.18%, 55.61%, 73.65%, 58.13%, 46.91%, respectively (P < 0.05). The results indicated that Paenibacillus polymyxa was an effective degradation strain of 5 pesticides.

Protective effects of Acanthopanax senticosus - Ligustrum lucidum combination on bone marrow suppression induced by chemotherapy in mice.

This study investigated the combination effects of the Acanthopanax senticosus - Ligustrum lucidum (AS-LL) herb pair on bone marrow suppression caused by chemotherapy. A bone marrow suppression model was established by intraperitoneal injection (i.p.) of cyclophosphamide (CTX, 100 mg/kg). The changes in chemical composition between the AS-LL decocted together and single were analyzed, and their effects on the bone marrow nucleated cells, peripheral blood, thymus and spleen indices, in vitro hematopoietic cell culture, ELISA and cell cycle were detected. The results showed that the contents of the main active components, such as salidroside, isofraxidin and specnuezhenide in the sample of AS-LL decocted together, increased significantly compared to singles. Moreover, AS-LL decocted together exhibited a significantly better therapeutic effect on myelosuppression induced by CTX than AS and LL alone. AS-LL decocted together significantly increased the number of bone marrow nucleated cells and displayed a good regulatory effect on peripheral blood (p < 0.01), while significantly increased the thymus index (p < 0.01) and decreased the spleen index (p < 0.01). AS-LL significantly promoted the formation of cell colonies (p < 0.05), the proliferation and differentiation of hematopoietic progenitor cells, and played a positive regulatory role in hematopoietic factors. AS-LL also reduced the proportion of G0/G1 cells, increased the ratio of S and G2/M cells, and increased the cell proliferation index (PI). All these results implied that AS-LL decocted together might be a promising food additives and therapeutic agent for myelosuppression induced by chemotherapy.

Hepatoprotective effect of chiisanoside against acetaminophen-induced acute liver injury in mice.

This study was designed to investigate the hepatoprotective effect of chiisanoside (CSS) and its possible mechanisms on acetaminophen (APAP)-induced acute liver damage in mice. The serum activities of alanine transaminase (ALT), aspartate transaminase (AST), tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), and the hepatic levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and malondialdehyde (MDA) were determined using the commercially available assay kits. The hepatic mRNA levels were measured by RT-PCR. The hepatic protein expressions of nuclear factor-kappa B (NF-κB), MAPK and their phosphorylated isoforms were evaluated by western blot assays. The results indicated that CSS (240 mg/kg) exhibited the hepatoprotective effects by inhibiting oxidative stress and inflammation on APAP-induced acute liver injury. Furthermore, the anti-inflammatory activity of CSS is largely related to the regulation of the NF-κB and MAPKs signaling pathways. These findings suggested that CSS possessed hepatoprotective effect against APAP-induced hepatotoxicity in mice.

Kidney Protection Effect of Ginsenoside Re and Its Underlying Mechanisms on Cisplatin-Induced Kidney Injury.

BACKGROUND/AIMS: Cisplatin (CDDP) was the first platinum-containing anti-cancer drug. However, CDDP causes nephrotoxicity as a side effect, which limits its clinic application. The aim of this study was to investigate the renoprotective effect of ginsenoside Re (G-Re) in a murine model of CDDP-induced acute kidney injury. METHODS: Male ICR mice were divided into 4 groups. G-Re was administered to the mice by oral gavage once a day at a dose of 25 mg/kg for 10 days. On the 7th day, a single injection of CDDP (25 mg/kg) was given at 1 h after G-Re treatment. RESULTS: CDDP administration resulted in renal dysfunction, as evidenced by an increase in the serum levels of creatinine and urea nitrogen. Oxidative stress in the CDDP group was reflected by an increase of malondialdehyde and a depletion of reduced glutathione and catalase in renal tissue. These findings were supported by increased 4-hydroxynonenal expression, which was significantly reduced by G-Re. Simultaneously, the overexpression of cytochrome P450 E1 was inhibited. G-Re inhibited the inflammatory response by the reduction of the protein expression of cyclooxygenase-2 and inducible nitric oxide synthase. Furthermore, CDDP increased the expression of Bax and decreased Bcl-2 expression in renal tissue. Hematoxylin and eosin, Hoechst 33258, and TUNEL staining also confirmed the presence of acute tubular necrosis and apoptosis. G-Re significantly decreased the levels of indicators of renal dysfunction, inflammatory cytokines, apoptosis, and malondialdehyde in the kidney and also significantly attenuated the histopathological changes associated with acute renal failure. CONCLUSIONS: Collectively, the results of this study suggest that the nephroprotective potential of G-Re may, in part, be related to its anti-oxidant, anti-inflammatory, and anti-apoptotic effects.

Beta-sitosterol and its derivatives repress lipopolysaccharide/d-galactosamine-induced acute hepatic injury by inhibiting the oxidation and inflammation in mice.

Beta-sitosterol (Sit) widely exists in natural plants, is classed as phytosterol and known as the "key of life". Most pharmacological studies and clinical applications are limited because of the fact that Sit is difficult to be solved. Therefore, it is viable to enhance pharmacologic activities of Sit by using its derivatives which can be obtained through the modification of Sit. In this study, 4 kinds of new Sit derivatives were obtained by the esterification reaction. Further, the hepatoprotective effects of Sit and its derivatives were investigated against acute liver injury induced by lipopolysaccharide/d-galactosamine (LPS/GalN) in mice and its mechanism was illustrated by western blot analysis and real-time PCR. The results demonstrated that among its derivatives, 2-naphthoyl Sit ester (Sit-N) (50 mg/kg) showed the strongest activities against acute liver injury. Final experimental results showed that Sit-N significantly decreased the serum activity of aspartate transaminase (AST) and alanine aminotransferase (ALT); Sit-N also markedly reduced tumor necrosis factor (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) levels. Meanwhile, Sit-N drastically improved the activities of antioxidant enzymes such as superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT), and suppressed the expression of malondialdehyde (MDA). Results also displayed that over-expression of Toll like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) induced by LPS/Gal N were inhibited by Sit-N. Meanwhile, the expression of nuclear respiratory factor2 (Nrf2) and heme oxygenase-1 (HO-1) were enhanced. The results all above verified the effectiveness of Sit-N against acute liver injury induced by LPS/GalN mediated by TLR4 and Nrf2 pathways.

Ameliorative effects and possible molecular mechanisms of action of fibrauretine from Fibraurea recisa Pierre on d-galactose/AlCl3-mediated Alzheimer's disease.

Fibrauretine is one of the main active ingredients from the rattan stems of Fibraurea recisa Pierre It exhibits a series of significant pharmacological effects. The present study aimed to evaluate the potential anti Alzheimer's disease (AD) effects of fibrauretine on a d-galactose/AlCl3-induced mouse model, and the underlying mechanisms of action were further investigated for the first time. Our results showed that pretreatment with fibrauretine significantly improved the ability of spatial short-term working memory in the model mice during the Y-maze test, as well as the abilities of spatial learning and memory during the Morris water maze. The levels of brain tissue amyloid (Aß), P-Tau, Tau and acetylcholinesterase (AchE) were evidently increased in d-galactose/AlCl3-intoxicated mice, and these effects were reversed by fibrauretine. In contrast, a significant increase in the levels of the neurotransmitter acetylcholine (Ach) and choline acetyl transferase (ChAT) was observed in the fibrauretine-treated groups compared with the model group. Neuronal oxidative stress, evidenced by increased malondialdehyde (MDA) and nitric oxide (NO) levels and a decline in glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) activity, was significantly alleviated by fibrauretine pretreatment. The suppression of the neuroinflammatory response by fibrauretine was realized not only by the decrease in the levels of tumour necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in the brain tissues and by the enzyme-linked immunosorbent assay (ELISA) but also by the protein expression levels of nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS), which were measured by immunohistochemistry and western blotting. In addition, the protein expression levels of inflammatory factors interleukin-33 (IL-33) and ST2 in the brain tissues were detected by immunohistochemistry. Furthermore, the effects of western blotting demonstrated that the administration of fibrauretine significantly suppressed the protein expression levels of caspase-3, cleaved caspase-3, and Bax and increased the protein expression levels of Bcl-2, and the results of the H&E and TUNEL assay all suggested the inhibition of apoptosis in the neurons. The results clearly suggest that the underlying molecular mechanisms of action of the fibrauretine-mediated alleviation of d-galactose/AlCl3-induced Alzheimer's disease may involve antioxidant, anti-inflammatory, and anti-apoptotic effects.

2-Naphthoic acid ergosterol ester, an ergosterol derivative, exhibits anti-tumor activity by promoting apoptosis and inhibiting angiogenesis.

Phytosterol is a natural component of vegetable oil and includes ergosterol (ER) and ß-sitosterol. In this study, three new ergosterol monoester derivatives were obtained from the reflux reaction with ergosterol, organic acids (furoic acid, salicylic acid, and 2-naphthoic acid), EDCI, and DMAP in dichloromethane. The chemical structures were defined by IR and NMR. On the basis of the results, 2-naphthoic acid ergosterol ester (NE) had the highest tumor inhibition rate and was selected to study anti-tumor activity and its mechanism at doses of 0.025mmol/kg and 0.1mmol/kg in H22-tumor bearing mice. Compared with ER, NE exhibited more stronger anti-tumor activity in vivo. Furthermore, biochemical parameters of ALT, AST, BUN, and CRE showed that NE had little toxicity to mice. NE significantly improved serum cytokine levels of IFN-γ and decreased VEGF levels. Moreover, H&E staining, TUNEL assay, immunohistochemistry, and western blotting indicated that NE exhibited anti-tumor activity in vivo by promoting apoptosis and inhibiting angiogenesis. In brief, the present study provided a method to improve ER anti-tumor activity and a reference for a new anti-tumor agent.

Flavored black ginseng exhibited antitumor activity via improving immune function and inducing apoptosis.

The objective of this project was to examine saponin and carbohydrate conversion, and to evaluate the antitumor activity of a novel ready-to-eat flavored black ginseng (FBG). The results of chemical experiments showed that common saponins in ginseng such as ginsenoside Re, Rg1, Rb1, etc., are almost completely converted to rare saponins and aglycones such as ginsenoside Rg5, protopanaxadiol (PPD), etc., and non-reducing sugars such as starch are almost completely degraded into reducing sugars as affected by garlic juice and high temperature processing. Furthermore, pharmacological experimental results showed that this novel FBG could inhibit the growth of tumors in H22 tumor-bearing mice dose-dependently at the dosage of 250, 500 and 1000 mg kg-1; meanwhile, the results of ELISA, H&E staining, western blotting and qRT-PCR show that FBG could improve immune function and induce tumor cell apoptosis.

Intravenous leiomyomatosis with right atrium extension in two patients: A case report.

Intravenous leiomyomatosis (IVL) is a rare benign tumor of the uterus mesoderm, which can spread via the vein, from the micro-vein to the inferior vena cava, and even to the right atrium. IVL was first described this disease in 1896 and the first presented case of IVL with right atrium extension in the autopsy was described in 1907. On rare occasions, the tumors may extend into the regional and systemic veins, thus reaching the heart. This may subsequently cause intracardiac leiomyomatosis (ICL), which may lead to congestive heart failure and on occasion, sudden fatalities. Due to its rarity and diffuse symptoms, the misdiagnosis of ICL is common and as a result, the condition may be under-reported. The present study reported two cases of IVL resected at the General Hospital of Shenyang Military Command. A hysteromyomectomy for uterine fibroids was performed on each patient (Case 1, 41 years ago; Case 2, 3 years ago). One patient presented with chest pain following a period of activity and the other presented with heart neoplasm during a routine health examination.

A Method of Effectively Improved α-Mangostin Bioavailability.

α-Mangostin, a major xanthone isolated from the pericarp of Garcinia mangostana, exhibits anti-inflammatory and antitumor effects. Its absolute bioavailability is low, with minimal oral absorption. In this article, a soft capsule, with vegetable oil as the dispersion matrix, was prepared to improve the bioavailability of α-mangostin. Its pharmacokinetics and tissue distribution were determined in rats. An HPLC assay was established to determine the concentration of α-mangostin in biological samples. The validated method was used successfully to support pharmacokinetic and tissue distribution studies of α-mangostin in rats after intravenous (i.v.) and oral administration. The pharmacokinetic study found the absolute bioavailabilities of low, medium and high doses were 61.1, 51.5 and 42.5 %, respectively, indicating that the absolute bioavailability was effectively improved.

Diosgenin inhibits the migration of human breast cancer MDA-MB-231 cells by suppressing Vav2 activity.

Diosgenin, a naturally occurring steroidal saponin, possess tumor therapeutic potential. However, the effect of diosgenin on cancer metastasis remains poorly understood. In this study, we performed in vitro experiments to investigate the inhibitory activity of diosgenin on human breast cancer MDA-MB-231 cell migration, and reveal the possible mechanism. Diosgenin caused a marked inhibition of cell migration in MDA-MB-231 cell by transwell assay. In addition, diosgenin significantly impacted MDA-MB-231 cell migratory behavior under real-time observation. We also found diosgenin significantly inhibited actin polymerization, Vav2 phosphorylation and Cdc42 activation, which might be, at least in part, attributed to the anti-metastatic potential of diosgenin. These findings reveal a new therapeutic potential of diosgenin for human breast cancer metastasis therapy.