Exploring the efficacy and mechanism of Bailing capsule to improve polycystic ovary syndrome in mice based on intestinal-derived LPS-TLR4 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with reproductive dysfunction and metabolic abnormalities, particularly characterized by insulin resistance and chronic low-grade inflammation. Multiple clinical studies have clearly demonstrated the significant efficacy and safety of the combination of Bailing capsules (BL) in the treatment of PCOS, but its pharmacological effects and mechanisms still require further study. AIM OF THE STUDY: To evaluate the effect of BL on improving PCOS in mice and explore the mechanism. METHODS: In this study, Dehydroepiandrosterone (DHEA) injection was administered alone and in combination with a high-fat and high-sugar diet to induce PCOS-like mouse. They were randomly divided into five groups: normal group (N), PCOS group (P), Bailing capsule low-dose group (BL-L), Bailing capsule high-dose group (BL-H) and Metformin + Daine-35 group (M + D). Firstly, the effects of BL on ovarian lesions, serum hormone levels, HOMA-IR, intestinal barrier function, inflammation levels, along with the expression of IRS1, PI3K, AKT, TLR4, Myd88, NF-κB p65, TNF-α, IL-6, and Occludin of the ovary, liver and colon were investigated. Finally, the composition of the gut microbiome of fecal was tested. RESULTS: The administration of BL significantly reduced body weight, improved hormone levels, improved IR, and attenuated pathological damage to ovarian tissues, up-regulated the expression of IRS1, PI3K, and AKT in liver. It also decreased serum LPS, TNF-α, and IL-6 levels, while downregulating the expression of Myd88, TLR4, and NF-κB p65. Additionally, BL improved intestinal barrier damage and upregulated the expression of Occludin. Interestingly, the abundance of norank_f__Muribaculacea and Lactobacillus was down-regulated, while the abundance of Akkermansia was significantly up-regulated. CONCLUSION: The results of the study showed that BL exerts a treatment PCOS effect, which may be related to the modulation of the gut microbiota, the improvement of insulin resistance and the intestinal-derived LPS-TLR4 inflammatory pathway. Our research will provide a theoretical basis for the clinical treatment of PCOS.

Integrated bioinformatics and network pharmacology to explore the therapeutic target and molecular mechanisms of Bailing capsule on polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder that is common in women of reproductive age. The clinical features of PCOS include hyperandrogenemia and polycystic ovarian changes. Bailing capsule (BL), a proprietary Chinese medicine that contains fermented Cordyceps sinensis powder, has been applied to treat PCOS. However, the specific active ingredients of BL and its mechanisms of action are yet to be elucidated. METHODS: Initially, the effectiveness of BL on PCOS model mice was evaluated. Subsequently, the active ingredients of BL were searched in the TCMSP and TCM Systems Pharmacology databases, and their targets were predicted using Swiss Target Prediction and SEA databases. Furthermore, the GEO gene database was used to screen for differentially expressed genes (DEGs) related to PCOS. Data from Gene Card, OMIM, DDT, and Drugbank databases were then combined to establish a PCOS disease gene library. Cross targets were imported into the STRING database to construct a protein-protein interaction network. In addition, GO and KEGG pathway enrichment analyses were performed using Metascape and DAVID databases and visualized using Cytoscape software and R 4.2.3. The core targets were docked with SYBYL-X software, and their expressions in PCOS mice were further verified using qPCR. RESULTS: The core active ingredients of BL were identified to be linoleyl acetate, cholesteryl palmitate, arachidonic acid, among others. Microarray data sets from four groups containing disease and normal samples were obtained from the GEO database. A total of 491 DEGs and 106 drug-disease cross genes were selected. Estrous cycle and ovarian lesions were found to be improved in PCOS model mice following BL treatment. While the levels of testosterone, progesterone, and prolactin decreased, that of estradiol increased. qPCR findings indicated that the expressions of JAK2, PPARG, PI3K, and AKT1 were upregulated, whereas those of ESR1 and IRS1 were downregulated in PCOS model mice. After the administration of BL, the expressions of associated genes were regulated. This study demonstrated that BL exerted anti-PCOS effects via PIK3CA, ESR1, AKT, PPARG, and IRS1 targets affecting PI3K-Akt signaling pathways. DISCUSSION: This research clarified the multicomponent, multitarget, and multichannel action of BL and provided a theoretical reference for further investigations on its pharmacological basis and molecular mechanisms against PCOS.

Effects of a Macroporous Resin Extract of Dendrobium officinale Leaves in Rats with Hyperuricemia Induced by Anthropomorphic Unhealthy Lifestyle.

Aim: Hyperuricemia (HUA) has received increased attention in the last few decades due to its global prevalence. Our previous study found that administration of a macroporous resin extract of Dendrobium officinale leaves (DoMRE) to rats with HUA that was induced by exposure to potassium oxazine combined with fructose and a high-purine diet led to a significant reduction in serum uric acid (SUA) levels. The aim of this study was to explore the effects of DoMRE on hyperuricemia induced by anthropomorphic unhealthy lifestyle and to elucidate its possible mechanisms of action. Methods: Dosages (5.0 and 10.0 g/kg/day) of DoMRE were administered to rats daily after induction of HUA by anthropomorphic unhealthy lifestyle for 12 weeks. The levels of UA in the serum, urine, and feces; the levels of creatinine (Cr) in the serum and urine; and the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum were all measured using an automatic biochemical analyzer. The activities of xanthine oxidase (XOD) and adenosine deaminase (ADA) in the serum, liver, and intestine tissue supernatant were measured using appropriate kits for each biological target. The expressions levels of UA transporters (ABCG2 and GLUT9), tight junction (TJ) proteins (ZO-1 and occludin), and inflammatory factors (IL-6, IL-8, and TNF-α) in the intestine were assayed by immunohistochemical (IHC) staining. Hematoxylin and eosin (H&E) staining was used to assess histological changes in the renal and intestinal tissues. Results: DoMRE treatment significantly reduced SUA levels and concomitantly increased fecal UA (FUA) levels and the fractional excretion of UA (FEUA) in HUA rats. Furthermore, DoMRE significantly reduced both the XOD activity in the serum, liver, and intestine and the ADA activity in the liver and intestine. DoMRE also effectively regulated the expression of GLUT9 and ABCG2 in the intestine, and it significantly upregulated the expression of the intestinal TJ proteins ZO-1 and occludin. Therefore, DoMRE reduced the damage to the intestinal barrier function caused by the increased production of inflammatory factors due to HUA to ensure normal intestinal UA excretion. Conclusion: DoMRE demonstrated anti-HUA effects in the HUA rat model induced by an anthropomorphic unhealthy lifestyle, and the molecular mechanism appeared to involve the regulation of urate transport-related transporters (ABCG2 and GLUT9) in the intestine, protection of the intestinal barrier function to promote UA excretion, and inhibition of XOD and ADA activity in the liver and intestine to inhibit UA production in the HUA-induced rats.

G-CSF/GM-CSF-induced hematopoietic dysregulation in the progression of solid tumors.

There are two types of abnormal hematopoiesis in solid tumor occurrence and treatment: pathological hematopoiesis, and myelosuppression induced by radiotherapy and chemotherapy. In this review we primarily focus on the abnormal pathological hematopoietic differentiation in cancer induced by tumor-released granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). As key factors in hematopoietic development, G-CSF/GM-CSF are well-known facilitators of myelopoiesis and mobilization of hematopoietic stem cells (HSCs). In addition, these two cytokines can also promote or inhibit tumors, dependent on tumor type. In multiple cancer types, hematopoiesis is greatly enhanced and abnormal lineage differentiation is induced by these two cytokines. Here, dysregulated hematopoiesis induced by G-CSF/GM-CSF in solid tumors and its mechanism are summarized, and the prognostic value of G-CSF/GM-CSF-associated dysregulated hematopoiesis for tumor metastasis is also briefly highlighted.

Effects of Macroporous Resin Extract of Dendrobium officinale Leaves in Rats with Hyperuricemia Induced by Fructose and Potassium Oxonate.

AIMS AND OBJECTIVES: Fructose, as a ubiquitous monosaccharide, can promote ATP consumption and elevate circulating Uric Acid (UA) levels. Our previous studies have confirmed that the macroporous resin extract of Dendrobium officinale leaves (DoMRE) could reduce the UA level of rats with hyperuricemia induced by a high-purine diet. This study aimed to investigate whether DoMRE had a UA-lowering effect on rats with hyperuricemia caused by fructose combined with potassium oxonate, so as to further clarify the UA-lowering effect of DoMRE, and to explore the UAlowering effect of DoMRE on both UA production and excretion. MATERIALS AND METHODS: Rats with hyperuricemia induced by fructose and potassium oxonate were administered with DoMRE and vehicle control, respectively, to compare the effects of the drugs. At the end of the experiment, the Serum Uric Acid (SUA) and Creatinine (Cr) levels were measured using an automatic biochemical analyzer, the activities of xanthine oxidase (XOD) were measured using an assay kit, and the protein expressions of Urate Transporter 1 (URAT1), glucose transporter 9 (GLUT9), and ATP-Binding Cassette Superfamily G member 2 (ABCG2) were assessed using immune-histochemical and western blot analyses. Hematoxylin and eosin staining was used to assess the histological changes in the kidney, liver, and intestine. RESULTS: Fructose and potassium induced hyperuricemia in rats. Meanwhile, the activities of XOD were markedly augmented, the expression of URAT1 and GLUT9 was promoted, and the expression of ABCG2 was reduced, which were conducive to the elevation of UA. However, exposure to DoMRE reversed these fructose- and potassium oxonate-induced negative alternations in rats. The activities of XOD were recovered to the normal level, reducing UA formation; the expressions of URAT1, ABCG2, and GLUT9 returned to the normal level, resulting in an increase in renal urate excretion. CONCLUSION: DoMRE reduces UA levels in rats with hyperuricemia induced by fructose combined with potassium oxonate by inhibiting XOD activity and regulating the expression of ABCG2, URAT1, and GLUT9. DoMRE is a potential therapeutic agent for treating hyperuricemia through inhibiting UA formation and promoting UA excretion.

Medical Plant Extract Purification from Cadmium(II) Using Modified Thermoplastic Starch and Ion Exchangers.

Pure compounds extracted and purified from medical plants are crucial for preparation of the herbal products applied in many countries as drugs for the treatment of diseases all over the world. Such products should be free from toxic heavy metals; therefore, their elimination or removal in all steps of production is very important. Hence, the purpose of this paper was purification of an extract obtained from Dendrobium officinale Kimura et Migo and cadmium removal using thermoplastic starch (S1), modified TPS with poly (butylene succinate); 25% of TPS + 75% PBS (S2); 50% of TPS + 50% PLA (S3); and 50% of TPS + 50% PLA with 5% of hemp fibers (S4), as well as ion exchangers of different types, e.g., Lewatit SP112, Purolite S940, Amberlite IRC747, Amberlite IRC748, Amberlite IRC718, Lewatit TP207, Lewatit TP208, and Purolite S930. This extract is used in cancer treatment in traditional Chinese medicine (TCM). Attenuated total reflectance-Fourier transform infrared spectroscopy, thermogravimetric analysis with differential scanning calorimetry, X-ray powder diffraction, gel permeation chromatography, surface analysis, scanning electron microscopy with energy dispersive X-ray spectroscopy, and point of zero charge analysis were used for sorbent and adsorption process characterization, as well as for explanation of the Cd(II) sorption mechanism.

Anti-inflammatory effect of Ganluyin, a Chinese classic prescription, in chronic pharyngitis rat model.

BACKGROUND: Ganluyin (GLY) is a famous classical prescription with a long history of use as a treatment for inflammatory conditions such as chronic pharyngitis (CP) in many parts of China. However, it has not been developed as a modern pharmaceutic and its anti-inflammatory mechanisms remain unclear. The aim of this study was to assess the anti-inflammatory efficacy of GLY and potential mechanisms in a rat model of CP. METHODS: The chemical profile of GLY was analyzed by HPLC-UV. We used a mouse model of ear edema and a rat model of paw edema. Specifically, xylene was used to induce edema on the surface of one ear in mice, and carrageenan was injected subcutaneously into the right hind paws of rats to induce paw edema. The paw thickness, ear weight, and ear perfusion were measured and recorded. The CP model in rats was induced by irritating the throat with 5% ammonia and was used to evaluate the therapeutic efficacy of GLY. Levels of interleukin-6 (IL-6), interleukin-1ß (IL-1ß), tumor necrosis factor (TNF-α), and prostaglandin E2 (PGE2) were measured by ELISA in serum, and protein expression of cyclooxygenase-2 (COX-2) and nuclear factor kappa-B p65 (NF-κB p65) in the throat were detected by immunohistochemistry and Western blot to evaluate the anti-inflammatory mechanism of GLY. Hematological assays were also conducted. RESULTS: There were four flavonoids identified in GLY: naringin, neohesperidin, baicalin, and wogonoside. The oral administration of GLY showed a significant inhibitory effect on xylene-induced ear swelling and ear blood flow in mice and significantly ameliorated rat right hind paw edema at doses of 6.2 and 12.4 g/kg. Mechanistic studies found that the anti-inflammatory activity of GLY was related to the inhibition of pro-inflammatory cytokines such as IL-1ß, IL-6, TNF-α, and PGE2 and that GLY reduced the expression of COX-2 and NF-κB p65 proteins in the throat, attenuated throat injury, and reduced inflammatory exudates. Hematological analysis showed that treatment with GLY prevented increases in white blood cell (WBC), neutrophil (NEUT), lymphocyte (LYMPH) and monocyte (MONO) levels. CONCLUSIONS: These studies indicated that GLY has beneficial anti-inflammatory effects on CP and that it acts through reducing pro-inflammatory factors such as IL-1ß, IL-6, TNF-α, and PGE2, as well as decreasing WBC, NEUT, LYMPH and MONO levels and decreasing the expression of COX-2 and NF-κB p65 proteins. These findings may lay the groundwork for further studies of GLY as a suitable candidate for the treatment of inflammatory diseases such as CP.

Soporific Effect of Modified Suanzaoren Decoction and Its Effects on the Expression of CCK-8 and Orexin-A.

Suanzaoren decoction (SZRT), a classic Chinese herbal prescription, has been used as a treatment for insomnia for more than a thousand years. However, recent studies have found no significant effects of SZRT as a treatment for insomnia caused by gastric discomfort. Herein, we studied the effects of modified Suanzaoren decoction (MSZRD) on gastrointestinal disorder-related insomnia. The main constituents of MSZRD were spinosin (2.21 mg/g) and 6-feruloylspinosin (0.78 mg/g). A pentobarbital-induced animal model of insomnia showed that MSZRD shortened sleep latency and prolonged sleep time of the male Institute of Cancer Research (ICR) mice treated for 7 days with oral MSZRD. Sprague-Dawley male rats were treated daily with oral MSZRD or placebo for 11 days and then deprived of sleep for the last 4 days to establish a model of insomnia. Of note, MSZRD-treated animals had significantly improved body weight, organ index scores, and fecal moisture relative to placebo-treated animals, as well as reduced temperature. Sleep-deprived rats exhibited more exploratory behaviors in an open-field anxiety test; however, this effect was significantly reduced in MSZRD-treated animals. We found that MSZRD treatment decreased gastric acid pH, decreased the production of gastrin, pepsin, and Orexin-A, and increased the expression of MTL and CCK-8. Importantly, serum GABA concentration was increased by treatment with MSZRD, as reflected by a decreased Glu/GABA ratio. Treated animals had increased the expression of GAD1, GABARA1, and CCKBR but decreased the expression of Orexin R1. In summary, these results suggest that MSZRD has soporific and gastroprotective effects that may be mediated by differential expression of CCK-8 and Orexin-A.

Effects and Mechanisms of Dendrobium officinalis Six Nostrum for Treatment of Hyperuricemia with Hyperlipidemia.

Objectives. Hyperuricemia (HUA) is a disease caused by increased production of uric acid (UA) or reduced excretion of UA in the body. Results of an epidemiological survey show that 60% of patients with HUA have hyperlipidemia (HPA). Dendrobium officinalis (DOF) six nostrum (DOS) is based on the theory of traditional Chinese medicine for the transformation of the traditional Chinese nostrum Si Miao Wan. In this article, we aim to discuss the efficacy and mechanism of DOS in reducing UA and regulating lipid metabolism. The rat model of HUA with HPA was induced by potassium oxonate (PO) combined with high-fat sorghum feed. We monitored the serum UA and blood lipids. Liver xanthine oxidase (XOD), adenosine deaminase (ADA), lipoprotein lipase (LPL), and fatty acid-binding protein (FABP1) activities were measured by enzyme-linked immunosorbent assay (ELISA) after the last administration of DOS. We performed a histopathological examination of rat kidney and intestine. Immunohistochemistry (IHC) was used to detect the expression of renal inflammatory proteins NLRP3 / Caspase-1 and intestinal inflammatory proteins TLR4 / NLRP3. We used western blot for measurement of liver hypoxanthine-guanine phosphoribosyl transferase (HPRT1) protein expression and renal PDZ domain protein kidney 1 (PDZK1) protein expression. DOS administration significantly reduced serum UA, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-c) level, and improved liver steatosis in the model rat. At the same time, DOS treatment effectively inhibited liver XOD and ADA, increased the level of liver HPRT1, and reduced the production of UA. Additional studies had shown that DOS can restore normal UA excretion function in the intestine and kidney and regulated liver lipids metabolism. IHC and histopathological sections showed that DOS reduced the level of kidney, intestinal inflammatory body (NLRP3, Caspase-1, and TLR4), improved inflammation of the kidney and intestinal tract in rats. DOS is a promising drug that can effectively reduce serum UA and lipid level in the model rat. The mechanism of action may be related to inhibition of UA production, promotion of UA excretion, regulation of lipids metabolism, and anti-inflammatory response.

Beneficial Effects of Macroporous Resin Extract of Dendrobium candidum Leaves in Rats with Hyperuricemia Induced by a High-Purine Diet.

Objectives. The incidence of hyperuricemia (HUA) is increasing year by year, and there are no ideal drugs for the treatment; the existing ones can cause serious liver and kidney damage. We have confirmed that the water extract of Dendrobium candidum leaves could reduce the level of uric acid in rats, but the active ingredients remain unknown, and the mechanism is not well understood. This research investigated the therapeutic effect of the macroporous resin extract of the Dendrobium candidum leaf (DLE) on hyperuricemia. In this study, hyperuricemia was induced in rats by a 5-week high-purine diet. After that, DLE was administered continuously for 9 weeks. The result showed that biochemical parameters of liver and kidney function, especially serum uric acid (UA) levels, were significantly improved with DLE, which may relate to the reduction of xanthine oxidase (XOD) and adenosine deaminase (ADA) in the liver. Moreover, DLE could significantly prevent kidney and liver from damage, and intestinal injury and reduce inflammation in hyperuricemic rats by inhibiting the expression of both NF-κB and TLR4 proteins. These results showed that the macroporous resin extract of the Dendrobium candidum leaves may be effective for the treatment of hyperuricemia in rats by inhibiting uric acid production and decreasing inflammation.

[Relaxation effect of buddleoside combined with luteolin on isolated vessels in vivo and its mechanism].

To study the relaxation effect of buddleoside combined with luteolin on aortic rings in SD rats and its mechanism. The effect of buddleoside alone(7.5×10⁻6g•mL⁻¹), luteolin alone(7.5×10⁻6g•mL⁻¹) and the combination of buddleoside and luteolin(1∶4) on norepinephrine-induced contractility of complete, endothelium-denuded, and L-NAME and indomethacin-pretreated thoracic aorta in SD rats were observed in the in vitro ring tension test. Western blot was used to detect p-Akt and p-eNOS protein expressions in the thoracic aorta. The experimental results showed that buddleoside combined with luteolin could significantly increase the relaxation rate of blood vessels and endothelium and L-NAME-pretreated vascular rings compared with the two single administrations. And buddleoside combined with luteolin could also significantly increase p-Akt and p-eNOS protein expressions.The results suggested that the combination of buddleoside and luteolin could effectively relax the blood vessel, and the mechanism may be to increase the synthesis and release of NO and reach the role of relaxing blood vessel by activating PI3K/Akt/NO signaling pathway and enhancing the activity of eNOS.

Linarin Enriched Extract Attenuates Liver Injury and Inflammation Induced by High-Fat High-Cholesterol Diet in Rats.

The aim of this study was to explore the potential beneficial effects of linarin enriched Flos Chrysanthemi extract (Lin-extract) on nonalcoholic steatohepatitis (NASH) induced by high-fat high-cholesterol (HFHC) diet in rats. SD rats received normal diet, HFHC diet, or HFHC diet plus different doses of Lin-extract. The liver content of triglyceride and total cholesterol markedly increased in HFHC diet-fed model rats while middle and high dose of Lin-extract lowered liver cholesterol significantly. The expression of stearoyl-CoA desaturase (SCD1) was upregulated by HFHC diet and further elevated by high dose Lin-extract. High dose of Lin-extract also markedly lowered the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and inhibited the activation of c-Jun N-terminal kinase (JNK) induced by HFHC in livers. The HFHC-increased mRNA levels of hepatic inflammation cytokines, including monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), and chemokine (C-X-C motif) ligand 1 (CXCL1), were suppressed by Lin-extract dose-dependently. Furthermore, pathology evaluation showed that high dose Lin-extract greatly improved lobular inflammation. Our results suggest that Lin-extract could attenuate liver injury and inflammation induced by HFHC diet in rats. Its modulatory effect on lipid metabolism may partially contribute to this protective effect.

Epimedin C Promotes Vascularization during BMP2-Induced Osteogenesis and Tumor-Associated Angiogenesis.

Epimedin C is one of the chemical markers and major flavonoids in Herba Epimedii (Yinyanghuo), which is traditionally used to treat bone diseases and gonadal dysfunction in China. Our previous study indicated that epimedin C could induce endothelial-like, but not osteogenic differentiation of C3H/10T1/2 cells in vitro. As vasculogenesis plays a pivotal role in bone formation, this study used the bone morphogenetic protein 2 (BMP2) induced ectopic bone formation model and mice 4T1 breast cancer cells co-implanted with luciferase labeled C3H/10T1/2 cells (4T1 [Formula: see text] C3H/10T1/2-Luc) model to examine the in vivo effects of Epimedin C on vasculogenesis. As a result, Epimedin C significantly increased the bone weight and blood perfusion of mice in the BMP2 induced ectopic osteogenesis model, and the bone in Epimedin C [Formula: see text] BMP2 group was more mature than that in BMP2 group. In addition, the tumor weight, blood perfusion and tumor-associated angiogenesis were also significantly increased in the Epimedin C treated 4T1 tumor bearing mice. The mRNA levels of endothelial markers, such as the platelet endothelial adhesive factor-1(CD31), the endothelial cell specific molecule-1(ESM-1), and the vascular von Willebrand factor (vWF) in mouse 4T1 mammary tumor tissue, were commonly found to occur alongside the luciferase (labeled in C3H/10T1/2 cells) expression and significantly increased after Epimedin C treatment. Taken together, Epimedin C can effectively promote vascularization both in the BMP2-depended bone formation model and in the 4T1 mammary tumor-bearing model by inducing an endothelial-like differentiation of C3H/10T1/2 in BALB/c nude mice.

Hypoxia pathway and hypoxia-mediated extensive extramedullary hematopoiesis are involved in ursolic acid's anti-metastatic effect in 4T1 tumor bearing mice.

Hypoxic in the tumor mass is leading to the myeloproliferative-like disease (leukemoid reaction) and anemia of body, which characterized by strong extensive extramedullary hematopoiesis (EMH) in spleen. As the key transcription factor of hypoxia, hypoxia-inducible factor-1 (HIF-1) activates the expression of genes essential for EMH processes including enhanced blood cell production and angiogenesis. We found ursolic acid (UA), a natural pentacyclic triterpenoid carboxylic acid, inhibited growth of breast cancer both in vivo and in vitro. The suppression was mediated through the inhibition of multiple cell pathways linked to inflammation, proliferation, angiogenesis, and metastasis. UA also suppressed the leukemoid reaction and the EMH phenomenon of the tumor bearing mice without any significant suppression on body weight (i.p. by 20 mg/kg for 28 days). This is associated with the significant decrease in white blood cells (WBC), platelets (PLT) and spleen weight. During this process, we also detected the down-regulation of cell proliferative genes (PCNA, and ß-catenin), and metastatic genes (VEGF, and HIF-1α), as well as the depression of nuclear protein intensity of HIF-1α. Furthermore, the expression of E2F1, p53 and MDM2 genes were increased in UA group when the VEGF and HIF-1α was over-expressed. Cancer cells were sensitive to UA treating after the silencing of HIF-1α and the response of Hypoxic pathway reporter to UA was suppressed when HIF-1α was over expressed. Overall, our results from experimental and predictive studies suggest that the anticancer activity of UA may be at least in part caused by suppressing the cancer hypoxia and hypoxia-mediated EMH.

[Effect of extracts from Dendrobii ifficinalis flos on hyperthyroidism Yin deficiency mice].

Some unhealthy life habits, such as long-term smoking, heavy drinking, sexual overstrain and frequent stay-up could induce the Yin deficiency symptoms of zygomatic red and dysphoria. Stems of Dendrobii officinalis flos (DOF) showed the efficacy of nourishing Yin. In this study, the hyperthyroidism Yin deficiency model was set up to study the yin nourishing effect and action mechanism of DOF, in order to provide the pharmacological basis for developing DOF resources and decreasing resource wastes. ICR mice were divided into five groups: the normal control group, the model control group, the positive control group and DOF extract groups (6.4 g · kg(-1)). Except for the normal group, the other groups were administrated with thyroxine for 30 d to set up the hyperthyroidism yin deficiency model. At the same time, the other groups were administrated with the corresponding drugs for 30 d. After administration for 4 weeks, the signs (facial temperature, pain domain, heart rate and autonomic activity) in mice were measured, and the facial and ear micro-circulation blood flow were detected by laser Doppler technology. After the last administration, all mice were fasted for 12 hours, blood were collected from their orbits, and serum were separated to detect AST, ALT, TG and TP by the automatic biochemistry analyzer and test T3, T4 and TSH levels by ELISA. (1) Compared with the normal control group, the model control group showed significant increases in facial and ear micro-circulation blood flow, facial temperature and heart rate (P < 0.05, P < 0.01), serum AST, ALT (P < 0.01), T3 level (P < 0.05), TSH level (P < 0.05) and notable deceases in pain domain (P < 0.01), TG level (P < 0.01). (2) Compared with the model control group, extracts from DOF (6 g · kg(-1)) could notably reduce facial and ear micro-circulation blood flow, facial temperature and heart rate (P < 0.05, P < 0.01) and AST (P < 0.05) and enhance pain domain (P < 0.01) and TG (P < 0.01). Extracts from DOF (4 g · kg(-1)) could remarkably reduce AST and ALT levels (P < 0.01, 0.05). Extracts from DOF (6 g · kg(-1) 4 g · kg(-1)) could significantly reduce T3 and increase serum TSH level (P < 0.05). DOF could improve Yin deficiency symptoms of zygomatic red and dysphoria in mice as well as liver function injury caused by overactive thyroid axis. According to its action mechanism, DOF may show yin nourishing and hepatic protective effects by impacting thyroxin substance metabolism, improving micro-circulation and reducing heart rate.

[Study on anti-angiogenesis effect of three curcumin pigments and expression of their relevant factors].

To study the in vitro anti-angiogenesis effect of three curcumin pigments (curcumin, demethoxycurcumin, bisdemethoxycurcumin). In the study, the inhibitory effect of the three curcumin pigments on proliferation of HUVEC cells induced by OX-LDL and the effect on migration of HUVEC cells were detected. The effect on neovascularization was observed by chorioallantoic membrane (CAM) test. The effect on cell adhesion factors ICAM-1 and VCAM-1 of HUVECs were tested by Real-time RT-PCR. It was found that the three curcumins could inhibit the proliferation of HUVEC cells induced by OX-LDL within the dosage range 4, 8, 16 mg x L(-1), with a dose-dependence. The proliferative effect of curcumins on HUVECs was greater than the other two derivatives (P < 0.01). All of the three curcumin pigments inhibited the migration of HUVEC cells and the angiogenesis of chick chorioallantoic membrane (CAM). The migration inhibition rate of curcumins at middle and high concentrations was greater than the other two (P < 0.01). All of the three curcumin could down-regulate the expression of VEGF and ICAM-1, and curcumins showed more obvious effect in down-regulating VEGF than demethoxycurcumin and bisdemethoxycurcumin(P < 0.01); Bisdemethoxycurcumin showed the most significant effect in down-regulating ICAM-1 (P < 0.01). All of the three showed no remarkable effect on expression of VCAM-1, and only bisdemethoxycurcumin showed the down-regulating effect (P < 0.05). According to the findings, all of the three curcumin pigments could resist angiogenesis by inhibiting proliferation and migration of endothelial cells and down-regulating the expression of VEGF and adhesion molecules ICAM-1.

Curcumin inhibits lung cancer cell migration and invasion through Rac1-dependent signaling pathway.

Curcumin, a natural and crystalline compound isolated from the plant Curcuma longa with low toxicity in normal cells, has been shown to protect against carcinogenesis and prevent tumor development. However, little is known about antimetastasis effects and mechanism of curcumin in lung cancer. Rac1 is an important small Rho GTPases family protein and has been widely implicated in cytoskeleton rearrangements and cancer cell migration, invasion and metastasis. In this study, we examined the influence of curcumin on in vitro invasiveness of human lung cancer cells and the expressions of Rac1. The results indicate that curcumin at 10 µM slightly reduced the proliferation of 801D lung cancer cells but showed an obvious inhibitory effect on epidermal growth factor or transforming growth factor ß1-induced lung cancer cell migration and invasion. Meanwhile, we demonstrated that the suppression of invasiveness correlated with inhibition of Rac1/PAK1 signaling pathways and matrix metalloproteinase (MMP) 2 and 9 protein expression by combining curcumin treatment with the methods of Rac1 gene silence and overexpression in lung cancer cells. Laser confocal microscope also showed that Rac1-regulated actin cytoskeleton rearrangement may be involved in anti-invasion effect of curcumin on lung cancer cell. At last, through xenograft experiments, we confirmed the connection between Rac1 and the growth and metastasis inhibitory effect of curcumin in vivo. In summary, these data demonstrated that low-toxic levels of curcumin could efficiently inhibit migration and invasion of lung cancer cells through inhibition of Rac1/PAK1 signaling pathway and MMP-2 and MMP-9 expression, which provided a novel insight into the molecular mechanism of curcumin against lung cancer.

Tetrandrine Suppresses Cancer Angiogenesis and Metastasis in 4T1 Tumor Bearing Mice.

Metastasis remains the most deadly aspect of cancer and still evades direct treatment. Thus, there is a great need to develop new treatment regimens to suppress tumor cells that have escaped surgical removal or that may have already disseminated. We have found that tetrandrine (TET) exhibits anticolon cancer activity. Here, we investigate the inhibition effect of TET to breast cancer metastasis, angiogenesis and its molecular basis underlying TET's anticancer activity. We compare TET with chemotherapy drug doxorubicin in 4T1 tumor bearing BALB/c mice model and find that TET exhibits an anticancer metastatic and antiangiogenic activities better than those of doxorubicin. The lung metastatic sites were decreased by TET, which is confirmed by bioluminescence imaging in vivo. On the other hand, laser doppler perfusion imaging (LDI) was used for measuring the blood flow of tumor in 4T1-tumor bearing mice. As a result, the local blood perfusion of tumor was markedly decreased by TET after 3 weeks. Mechanistically, TET treatment leads to a decrease in p-ERK level and an increase in NF- κ B levels in HUVECs. TET also regulated metastatic and angiogenic related proteins, including vascular endothelial growth factor, hypoxia-inducible factor-1 α , integrin ß 5, endothelial cell specific molecule-1, and intercellular adhesion molecule-1 in vivo.

Ginseng saponin metabolite 20(S)-protopanaxadiol inhibits tumor growth by targeting multiple cancer signaling pathways.

Plant-derived active constituents and their semi-synthetic or synthetic analogs have served as major sources of anticancer drugs. 20(S)-protopanaxadiol (PPD) is a metabolite of ginseng saponin of both American ginseng (Panax quinquefolius L.) and Asian ginseng (Panax ginseng C.A. Meyer). We previously demonstrated that ginsenoside Rg3, a glucoside precursor of PPD, exhibits anti-proliferative effects on HCT116 cells and reduces tumor size in a xenograft model. Our subsequent study indicated that PPD has more potent antitumor activity than that of Rg3 in vitro although the mechanism underlying the anticancer activity of PPD remains to be defined. Here, we investigated the mechanism underlying the anticancer activity of PPD in human cancer cells in vitro and in vivo. PPD was shown to inhibit growth and induce cell cycle arrest in HCT116 cells. The in vivo studies indicate that PPD inhibits xenograft tumor growth in athymic nude mice bearing HCT116 cells. The xenograft tumor size was significantly reduced when the animals were treated with PPD (30 mg/kg body weight) for 3 weeks. When the expression of previously identified Rg3 targets, A kinase (PRKA) anchor protein 8 (AKAP8L) and phosphatidylinositol transfer protein α (PITPNA), was analyzed, PPD was shown to inhibit the expression of PITPNA while upregulating AKAP8L expression in HCT116 cells. Pathway-specific reporter assays indicated that PPD effectively suppressed the NF-κB, JNK and MAPK/ERK signaling pathways. Taken together, our results suggest that the anticancer activity of PPD in colon cancer cells may be mediated through targeting NF-κB, JNK and MAPK/ERK signaling pathways, although the detailed mechanisms underlying the anticancer mode of PPD action need to be fully elucidated.

[Review of pharmacological activities of Dendrobium officinale based on traditional functions].

This review firstly made a summary of ancient literature on traditional functions of Dendrobium, combined with literature of modern pharmacological research and clinical application of D. officinale from CNKI search system, it was summarized that D. officinale had broad bioactivities including immunomodulation, antifatigue activity, antioxidation, digest-promotion, stimulation of salivary secretion, lowering hyperglycemia, anti-hypertension, anti liver injury and antitumor activity, etc. Furthermore, public healty needs and present situation of cooperative product development were analyzed base on tradtional functions, pharmacological actions and related clinical applications of D. officinale, could provide a reference for the further industrial development.