Optimization of extraction of flavonoids from Lonicera rupicola and analysis of its effects in resisting inflammation, relieving pain, enhancing immunity, and inhibiting pyroptosis / 中国中药杂志

The present study optimized the extraction of flavonoids from Lonicera rupicola Hook. f. et Thoms(LRH) and explored its pharmacological effects, such as resisting inflammation, relieving pain, enhancing immunity, and inhibiting pyroptosis, aiming to provide data support and scientific basis for the development and utilization of LRH. Response surface methodology(RSM) was applied to optimize the extraction of flavonoids from LRH based on the results of single-factor experiments. Anti-inflammatory and analgesic effects of LRH flavonoids were evaluated via inflammation and pain models in mice, such as xylene-induced ear swelling, carrageenan-induced footpad swelling, writhing caused by acetic acid, and paw licking. The effect of LRH flavonoids on the carbon clearance index of monocytes and serum immunoglobulin A(IgA) and IgM levels was analyzed on the immunosuppression model induced by cyclophosphamide in mice. The anti-oxidative effect in vivo of LRH flavonoids on liver superoxide dismutase(SOD), catalase(CAT), and malondialdehyde(MDA) levels was determined based on the chronic/subacute aging model in mice induced by D-galactose. The levels of cysteinyl aspartate specific proteinase-1(caspase-1), interleukin-1β(IL-1β), and IL-18 in the supernatant of J774 A.1 mononuclear phagocytes were detected to evaluate the effect of LRH flavonoids on the pyroptosis of mononuclear phagocytes in mice induced by the combination of lipopolysaccharide(LPS) and adenosine triphosphate(ATP). Meanwhile, the effect of LRH flavonoids on the cAMP-PKA signaling pathway was also explored. The optimum conditions for the extraction of LRH flavonoids are listed below: extraction temperature of 65 ℃, the ethanol concentration of 50%, extraction time of 60 min, a material-liquid ratio at 1∶25, and the yield of LRH flavonoids of 0.553%. RSM determined the multiple quadratic regression equation model of response value and variables as follows: the yield of LRH flavonoids=0.61-0.48A+0.1B+0.029C-0.014D+0.32AB+0.04AC-0.012AD-0.02BC+0.037BD-0.031CD-0.058A~2-0.068B~2-0.069C~2-0.057D~2. LRH flavonoids could effectively inhibit ear swelling and footpad swelling, reduced acetic acid-induced writhing, and delayed the paw licking response time in mice. Additionally, LRH flavonoids could improve the carbon clearance index in immunosuppressed mice, potentiate the activities of SOD and CAT and reduce MDA levels in the liver of aging mice induced by D-galactose, and effectively inhibit macrophage pyroptosis by decreasing the levels of caspase-1, IL-1β, and IL-18. The results reveal that LRH flavonoids possess excellent pharmacological activities such as resisting inflammation and oxidation, relieving pain, and enhancing immunity. They can inhibit pyroptosis by enhancing the cAMP-PKA signaling pathway. The results of this study can underpin the pharmacological research, development, and utilization of LRH.

Study on the Effects of Ginseng Root Extract on Autophagy ，Proliferation and Cytokine Secretion of Mice Splenic Lymphocytes and Its Mechanism / 中国药房

OBJECTIVE：To study the effects of gin seng root extract on autophagy ，proliferation and cytokine of splenic lymphocyte of mice ，and to study its mechanism. METHODS ：The splenic lymphocyte of mice were divided into blank control group，positive control group （concanavalin A ，5 μg/mL），different concentration of ginseng root extract groups （32，125，500 μg/mL，by lyophilized powder ）. After 48 h of culture with the corresponding medicine ，acridine orange staining method was used to detect autophagy of splenic lymphocyte ；CCK-8 assay was used to detect the cell proliferation ；ELISA assay was used to determine the levels of IL- 4，IL-6 and TNF-α in cell culture；Western blotting method was used to detect the expression of LC 3B and Beclin- 1，as well as the phosphorylation of AMPK ，AKT and mTOR. RESULTS ：Compared with blank control group ，32， 125，500 μg/mL ginseng root extract could increase the number of acidic autophagosomes in splenic lymphocytes of mice（P＜0.05 or P＜0.01）；125，500 μg/mL Ginseng root extract could significantly enhance the survival rate of splenic lymphocytes，the levels of IL- 4，IL-6 and TNF-α and the transformation of LC3BⅠ to LC 3BⅡ，significantly increased the protein expression of Beclin- 1， quinacrine cationic liposomes for treating non-small cell @163.com lung cancer[J]. J Drug Target ，2015，23（3）：232-243. the phosphorylation of AMPK protein ，and significantly reduced the phosphorylation level of AKT and mTOR proteins ，with statistical significance （P＜0.05 or P＜0.01）. CONCLUSIONS ：Ginseng root extract can induce autophagy of mice splenic lymphocytes，activate the activity of splenic lymphocytes ，regulate the secretion of cytokine by activating AMPK and inhibiting the activation of AKT which can inhibit the activity of mTOR ，so as to exert immune enhancement effect.

Implantable sandwich PHBHHx film for burst-free controlled delivery of thymopentin peptide

Sustained release and non-parental formulations of peptides and protein drugs are highly desirable because of enhanced therapeutic effects as well as improved patient compliance. This is especially true for small peptides such as thymopentin (TP5). To this end, implantable sandwich poly (hydroxybutyrate--hydroxyhexanoate) (PHBHHx) films were designed to prolong release time and to inhibit burst release phenomenon of TP5 by a simple volatilization method. release studies revealed that sandwich films had nearly no burst release. release time of sandwich films was prolonged to 42 days. Pharmacodynamic evaluation demonstrated that TP5 sandwich films significantly increased survival rates in a rat immunosuppressive model and normalized CD4/CD8 values. These results suggest that TP5 released from sandwich films can attenuate cyclophosphamide's immunosuppressive activity, and possibly achieve results comparable to daily TP5 injection therapy. Thus, sandwich PHBHHx films show excellent potential as a sustained, burst-free release system for small molecular weight, hydrophilic peptide drugs.

Effects of enteral immunonutrition emulsion on immune function in critically ill patients with mechanical ventilation / 中国中西医结合急救杂志

Objective To observe the intervention effect of immune-enhancing enteral nutrition (EN) emulsion on immune function of critically ill patients with mechanical ventilation (MV). Methods One hundred and twenty critically ill patients with MV admitted to the Department of Emergency Intensive Care Unit (EICU) of Taizhou First People's Hospital from July 2015 to June 2017 were enrolled, and they were divided into immune-enhancing EN group and standard EN group by random numbers generated by a computer. Ultimately, 76 cases were enrolled in the study, among them, 36 cases were in the immune-enhancing nutrition group and 40 cases were in the standard nutrition group. The differences of acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ), the sequential organ function evaluation (SOFA) score on 1, 3, 7 days and immunity indexes (secretory immuno-globulins IgA, IgG, IgM), lymphocyte subpopulation (CD4 and CD8), duration of MV and the length of ICU stay on the 1, 7 days after EN were compared. Results Comparisons between the immune-enhancing EN group and standard EN group showed: APACHE Ⅱ score had no statistically significant difference between the two groups at each time point, SOFA score on 7 days after EN treatment was significantly decreased in the immune-enhancing EN group (2.56±1.38 vs. 3.68±2.96, P < 0.05); IgA, IgG, IgM were obviously higher in the immune-enhancing EN group than those in standard EN group on 7 days after treatment [IgA (mg/L): 2 967.6±635.6 vs. 2 525.0±592.7, IgG (mg/L): 14 982.5±2 899.7 vs. 12 996.4±2 875.9, IgM (mg/L): 1 206.8±233.3 vs. 1 093.2±165.1, all P < 0.05], CD4 (0.45±0.06 vs 0.37± 0.10) and CD8 (0.20±0.03 vs. 0.18±0.04) were significantly higher than those in standard EN group (both P < 0.05). The MV time (hours): 122.33±63.91 vs. 155.69±77.06) and ICU stay time (hours): 197.57±70.60 vs. 239.61±84.83) of the immuno-enhancing EN group were markedly shorter than those of the standard EN group (both P < 0.05). Conclusion Compared with standard EN, the immune-enhancing EN emulsion can improve the immune function of critically ill patients with MV, and shorten the duration of MV support and the length of ICU stay.

Effects of polysaccharide-containing aqueous extracts of Cistanche deserticola Y. C. Ma on T lympho-cyte subsets and duration of antibody response / 中华微生物学和免疫学杂志

Objective To study the effects of aqueous extracts of cultivated Cistanche deserticola Y. C. Ma (AECCD) on T cell responses and the duration of antibody response and to investigate its immunoen-hancing activities in mice. Methods Two batches of female ICR mice were used in this study with 30 from each batch. Each batch of mice was randomly divided into six groups (n=5). Low, medium and high doses of AECCD in combination with ovalbumin ( OVA) were used to set up three experimental groups, while 0. 9% NaCl, OVA alone and aluminium adjuvant were respectively used as blank, negative and positive controls. All mice were intramuscularly injected twice at an interval of two weeks. Flow cytometry was used to detect the ex-pression of T lymphocyte subsets, cytokines and surface molecules of dendritic cells (DC). Indirect ELISA was used to detect IgG antibody levels. Results AECCD could significantly increase the percentage of CD4+and CD8+T lymphocytes in spleen (P<0. 05), up-regulate the expression of CD4+CD44+and CD8+CD44+effector T lymphocytes (P<0. 05), promote the secretion of IFN-γ in T lymphocytes and enhance the expression of CD40 and CD80 on the surface of DC (P<0. 05). ELISA results showed that high-dose AECCD could significantly prolong the duration of IgG antibody response induced by OVA (P<0. 05). Conclusion AECCD could en-hance the T lymphocyte immune response induced by OVA and keep it maintained at a high level, which might help to improve the body′s immune response.

Survey of Irrational Use of Anti-tumor Immune Enhancement Drugs / 中国药师

Objective:To investigate and analyze the rational use of anti-tumor immune enhancement drugs in our hospital. Meth-ods:The annual use data of anti-tumor immune enhancement drugs in our hospital in 2015 were collected, and then statistically ana-lyzed and evaluated combing with the medical history information. Results: There were 12 varieties and 19 specifications of adjuvant anti-tumor immune enhancement drugs in our hospital, which accounted for 15. 87% of the total sum. Totally 25 481 patients used ad-juvant anti-tumor immune enhancement drugs, which occupied 29. 84% of the total medicine afford. The adjuvant anti-tumor immune enhancement drugs showed lots of irrational use in clinics, and the main irrationity was overuse and off-label use. Conclusion: It is necessary to strengthen prescription evaluation for anti-tumor immune enhancement drugs, which needs controlled and rational use.

Progress on the anti-tumor activity of seaweed polysaccharides / 药学实践杂志

Seaweed polysaccharides are not only a direct inhibitory effect on tumor cells ,but also an indirect therapeutic effected by enhancing immune function or inhibiting tumor cell metastasis .Seaweed polysaccharides could inhibit the growth of tumor cells due to reducing tumor chemotherapy drug resistance and inhibiting free radical generation ,accelerating free radical scavenging .Moreover ,seaweed polysaccharides have a synergistic effect with chemotherapy drugs to reduce their side effects and protest patients from radiotherapy-induced immune cell damage .Therefore ,seaweed polysaccharide could be used as adju-vant therapeutic agents .the antitumor activity and mechanism of seaweed polysaccharides were summarized ,covering 28 arti-cles published in the years from 2004 to 2015 .

Crude polysaccharides extracted from cultivated Artemisia rupestris L. in Xinjiang enhances the effi-cacy of OVA / 中华微生物学和免疫学杂志

Objective To investigate the efficacy of using crude polysaccharides extracted from cultivated Artemisia rupestris L. ( CARCP) in Xinjiang as an immunologic adjuvant for ovalbumin ( OVA) . Methods The mice were subcutaneously immunized twice with OVA vaccine formulated with CARCP. ELISA assay was performed to measure the levels of IgG, IgG1 and IgG2a antibodies. Flow cytometry analy-sis was performed to detect the percentages of different T lymphocyte subsets ( CD3+CD4+ and CD3+CD8+T cells, CD4+CD44+ and CD8+CD44+T cells) in splenocytes as well as the expression of intracellular cyto-kines ( CD4+IFN-γ, CD8+IFN-γ) and CD4+CD25+Foxp3+Treg cells. Results The levels of IgG, IgG1 and IgG2a antibodies in serum, the percentages of CD3+CD4+, CD3+CD8+, CD4+CD44+ and CD8+CD44+T cells as well as the ratio of CD4+/CD8+T lymphocytes increased significantly in mice immunized with OVA in combination with CARCP (P<0. 05). Moreover, CARCP enhanced the expression of CD4+IFN-γand CD8+IFN-γ( P<0. 05 ) , but inhibited the expression of CD 4+CD 2 5+Foxp 3+Treg cells ( P<0. 05 ) . Conclusion As an adjuvant for OVA, CARCP enhanced the humoral and cellular immune responses, especially the T cell immune responses.

Antiviral effect of dietary germanium biotite supplementation in pigs experimentally infected with porcine reproductive and respiratory syndrome virus

Germanium biotite (GB) is an aluminosilicate mineral containing 36 ppm germanium. The present study was conducted to better understand the effects of GB on immune responses in a mouse model, and to demonstrate the clearance effects of this mineral against Porcine reproductive and respiratory syndrome virus (PRRSV) in experimentally infected pigs as an initial step towards the development of a feed supplement that would promote immune activity and help prevent diseases. In the mouse model, dietary supplementation with GB enhanced concanavalin A (ConA)-induced lymphocyte proliferation and increased the percentage of CD3+CD8+ T lymphocytes. In pigs experimentally infected with PRRSV, viral titers in lungs and lymphoid tissues from the GB-fed group were significantly decreased compared to those of the control group 12 days post-infection. Corresponding histopathological analyses demonstrated that GB-fed pigs displayed less severe pathological changes associated with PRRSV infection compared to the control group, indicating that GB promotes PRRSV clearance. These antiviral effects in pigs may be related to the ability of GB to increase CD3+CD8+ T lymphocyte production observed in the mice. Hence, this mineral may be an effective feed supplement for increasing immune activity and preventing disease.

T-helper epitope peptide improves immunological effects of the B cell epitopes of human heparanase protein / 中华微生物学和免疫学杂志

Objective To explore available immune strategy to improve immunological effects of the B cell epitopes of human heparanase protein.Methods Based on predicted potential B cell epitopes of human heparanase protein,three candidates of multiple antigenic peptides(MAP)with 8-branches were synthesized and identified by conjugation to antibody against full human heparanase protein.C57BL/6 mice were immunized with the 8-branch MAPs mixed with or without the universal human T-helper IL-1β peptide.The antibody titers of immune serum was assayed by ELISA.Results Most potential epitopes of human heparanase protein were predicted as No.1-15(MAP1),279-293(MAP2)and 175-189(MAP3)in large subunit of human heparanase protein.All three synthesized MAPs mixed with the T-helper epitope induced higher titers of antibodies than them without the T-helper epitope.Conclusion The three B cell epitopes of human heparanase protein could he its B cell preponderant epitopes.The 8-branch MAPs mixed TH cell epitope may be an available and optimizing immune strategy.

Anti-tumor and immunoenhancement effects of effective combination of extraction from edible fungi on C26 xenograft mice / 中国癌症杂志

Background and purpose:Edible fungi has shown powerful potential in health care. This study aimed to explore the anti-tumor and immunoenhancement effects of combination of extraction from edible fungi. Methods:C26 cells has been xenografted into mice, and the animal models were randomly divided into control group, prevention group, treatment group and cyclophosphamide group. Mice were given the combination of extraction from edible fungi every day after vaccination of C26 cells into mice, except the prevention group which has been given the combination of extraction from edible fungi two weeks before vaccination. Two weeks after being planted, all the mice were killed and the tumor inhibition rates were studied. The immune function was measured by T lymphocyte transforming assay and NK killing assay. Results:There were signif icant difference in terms of tumor weight between prevention group and control group. The prevention group mice display improved T lymphocyte transforming assay and NK killing ability. Conclusions:The combination of extraction from edible fungi has remarkable inhibitory effects on C26 carcinoma in mice and can enhance immunity against mice with C26 carcinoma.

The anti-tumour effect of Wuxing soup and its effect on the immunity of melanoma mice / 中国癌症杂志

Background and purpose:Wuxing soup is popular for it's anti-cancer effect in folk medicine and deserved to be further studied by modern scientific methods.This research aimed to explore its anti-cancer effect and to study the influence on the immunity of melanoma in mice. Methods :Inhibition of different ingredients and concentrations of Wuxing soup on the growth of the mouse melanoma B16 cells was detected by MTT in vitro.Animal experiment was performed to determine its anti-cancer effect in vivo.C57/BL6 mice were randomly divided into three groups after vaccination of B16 cell,and then given intragastrically with different soups for 25 days.All mice were killed on day 26 after inoculation.The weight of tumors were recorded.The anti-tumor immune function was measured by T lymphocyte transforming assay and NK killing assay.The different effect of different ingredients was also observed. Results :Our result showed that different ingredients soup exerted different inhibition on B16 cell growth and Wuxing soup was the strongest one of all and in dose-dependent manner in vitro.The animal experiment indicated that different ingredients soup has different inhibition on melanoma,the soup-treated mouse display improved T lymphocyte transforming assay and NK killing ability.Among the different soups,Wuxing soup showed the strongest anti-cancer effect and immune enhancement. Conclusions :Wuxing soup is an effective anti-cancer agent in melanoma mice and can enhance the immunity of the mice with melanoma.

EFFECTS AND MECHANISM OF SFPS ON RBC IMMUNE ENHANCEMENT OF P_(388) MICE / 中国海洋药物

In this paper,the effects of SFPS on red blood cell immune function of P388mice is presented. The results suggest that SFPS' enhancing the immune function of red blood cells of P388 mice may be related to decreasing the content of LPO of red blood cell membranes inhibiting the formation of HMP by protein of red blood cell membranes and systolic protein,increasing the sealing degree of red bold cell menbranes and the content of sialic acid and enhancing the activities of SOD, CAT, and Na+, K+-ATPase of red blood cell membranes.