Berberine inhibits the expression of TNFalpha, MCP-1, and IL-6 in AcLDL-stimulated macrophages through PPARgamma pathway.

Macrophages are the main source of cytokines in atherosclerotic plaques. Modified low-density lipoproteins may stimulate macrophages to produce large quantities of proinflammatory cytokines that promote atherosclerosis. Berberine is the main component of the traditional Chinese medicine umbellatine, which has a widespread effect and was used to treat many diseases clinically. Our previous study found that berberine could increase adipophilin expression in macrophages, which is a target gene of PPARgamma. PPARgamma agonist could decrease proinflammatory cytokines in macrophage. In this study, we investigated the effects and the mechanism of action of berberine on the expression and secretion of TNFalpha, MCP-1, and IL-6 in vitro to identify new pharmacological actions of berberine. The results of RT-PCR and ELISA shows that berberine may inhibit the expression and secretion of the tumor necrosis factor alpha (TNFalpha), monocyte chemoattractant protein 1 (MCP-1), and interleukin-6 (IL-6) in macrophages stimulated by acetylated low-density lipoprotein (AcLDL), whereas the peroxisome proliferator-activated receptor gamma (PPARgamma) inhibitor GW9662 could attenuate this effect of berberine. This study demonstrates that berberine may inhibit the expression and production of TNF-alpha, MCP-1, and IL-6 in AcLDL-stimulated macrophages. This effect might be partially mediated through PPARgamma activity.

[The role of immune enhanced enteral nutrition on plasma amino acid, gut permeability and clinical outcome (a randomized, double blind, controlled, multi-center clinical trail with 120 cases)].

OBJECTIVE: To evaluate the role of arginine, RNA and omega 3 fatty acid enriched enteral nutrition. METHODS: The study was designed as a prospective, randomized, double blind, multi-central trial. It was an isocaloric and isonitrogenous intake in both groups. The protocol was approved by the Ethic Committee and, written informed consents were obtained. RESULTS: There were 120 patients enrolled in this protocol. After data were input to computer, open the code. 118 out of 120 patients completed the study and, 2 of them were dropped out. One is because the nasal jejunum tubes dropped and not willing to be replaced. Second patient had fistula of anastomosis on 4th days after operation. There were finally 60 patients in the study group and 58 in the control group. There were no liver or renal functions damage and, obvious adverse in both groups. Plasma amino acid profile: There was significant difference (delta) of plasma arginine levels pre- and after study [(33.7 +/- 58.5) mumol/L vs (-2.4 +/- 30.7) mumol/L] (P = 0.004). Intestinal Permeability (lactulose/mannitol ratio): The differences (delta) of lactulose/mannitol ratio pre- and after the study were 0.017 +/- 0.012 in study group and, 0.027 +/- 0.016 in control group. (P = 0.047). Immunological markers: Humoral immunity: The differences of IgM levels pre- and after the study were (0.6 +/- 0.4) g/L in study group and, (0.2 +/- 0.4) g/L in control group(P = 0.006). Cellular immunity: The differences (delta) of CD3 levels pre- and after the study were (3.8 +/- 5.2)% in study group and (0.3 +/- 6.5)% in control group (P = 0.01). In CD4, (3.4 +/- 5.3)% in study group and, (-0.3 +/- 5.7)% in control group (P = 0.032). Clinical Outcomes: There was no infection-related in study group and, 2 abdominal infection patients in control group. No significant difference was found between groups (P = 0.46). The hospital stays were (13 +/- 2.5) days in study group and, (14.5 +/- 3.0) days in control group (P = 0.004). The cost for full hospitalization was (15,122 +/- 6,279) Yuan in study group and, (17,403 +/- 7,091) Yuan in control group. There was 2,281 Yuan lower in study group (P = 0.07). The costs for nutritional drugs were (1,383 +/- 242) Yuan in study group and, (707 +/- 111) Yuan in control group. The difference was 676 Yuan higher in study (P = 0.001). CONCLUSION: Immune enhanced enteral nutrition had better plasma arginine level, intestinal permeability marker, IgM, CD3 and CD4. Also had less hospital stay and, less totaled hospital cost in study group.

Anti-aging effects of the traditional Chinese medicine bu-zhong-yi-qi-tang in mice.

Among the "alternative medicines," which may ably supplement modern Western medicine in the treatment of certain diseases, the holistic approach and mild nature of the majority of Traditional Chinese Medicine (TCM) may make it particularly suitable for the treatment of diseases associated with old age, as the general health of elderly patients is already compromised. The TCM formulation of bu-zhong-yi-qi-tang (B.Z.Y.Q.T.), prescribed mainly for the improvement of circulation and in particular that to the gastroenteric regions, may have anti-aging effects. In the present study, possible anti-aging effects of B.Z.Y.Q.T. were studied using normal (ICR) mice and the Dull, P/8 and R/1 strains of the Senescence Accelerated Mouse (S.A.M.). Following repeated oral administrations of B.Z.Y.Q.T. at 250 and 500 mg/kg the test mice were assessed for (1) endurance (2) learning and memory (3) neuromuscular coordination and (4) changes in the levels of monoamines in the brain. The results indicated that B.Z.Y.Q.T. improved endurance in all strains in a dose-dependent manner. At the higher dose of 500 mg/kg, it improved memory in the R/1 and P/8 S.A.M. mice. In prolonged rota-rod tests, which assessed both motor coordination and endurance, B.Z.Y.Q.T. significantly improved performance in the P/8 S.A.M. mice. Elevated dopamine and noradrenaline were observed in cortical tissues of the S.A.M./Dull and ICR mice respectively with the high dose of 500 mg/Kg, B.Z.Y.Q.T. Taken together, the results indicated that B.Z.Y.Q.T. appeared to exert anti-aging effects in mice and elevation in certain monoamines in brain cortical tissues. How and whether the monoamines changes after B.Z.Y.Q.T. treatment might be related to the behavioral effects await further investigation.

Deficient CD4+ T cell proliferation in the class 1 MHC-restricted 2C TCR-transgenic mouse.

A comparative study of immune function and marker expression of CD4+ T cells from MHC class 1-restricted 2C TCR-transgenic (2C+) and control transgene-negative littermate (2C-) mice was performed. While 2C+CD4+ T cells resembled memory T cells on the basis of CD44highCD45RBlow expression, the majority of 2C-CD4+ T cells were of the CD44lowCD45RBhigh naive phenotype. Slightly lower levels of TCR-beta and CD3 were found on 2C+CD4+ T cell than 2C-CD4+ T cells. Vigorous proliferation by 2C-CD4+ T cells was observed upon stimulation with 1) anti-CD3 mAb presented through the FcR of macrophages; 2) immobilized (plate-bound) anti-CD3 + anti-CD28 mAbs; and 3) PMA + ionomycin. In marked contrast, all three mitogenic stimuli stimulated highly deficient proliferative responses by 2C+CD4+ T cells. However, significant IL-2 production was detected both in anti-CD3 and in PMA + ionomycin-stimulated cultures of 2C+CD4+ T cells. While intracellular calcium in 2C-CD4+ T cells rapidly increased following anti-CD3 addition, no such increase was observed for similarly stimulated 2C+CD4+ T cells. Anti-CD28, PMA, and coculture with 2C-CD4+ T cells each failed to significantly correct the deficient 2C+CD4+ T cells proliferation as induced by anti-CD3. In addition, IL-2, IL-4, and IL-7 supplements also failed to reverse the deficient proliferation of 2C+CD4+ T cells despite expression of IL-2R component alpha-, beta-chains and the gamma-chain common also to IL-4R and IL-7R. Thymus CD4+8- T cells from the 2C-transgenic mouse were similarly deficient in proliferation as spleen CD4+ T cells. A small subpopulation of CD4+ T cell from the 2C-transgenic mouse expressed the transgenic TCR alpha:beta heterodimer as detected by the 1B2 anti-2C clonotypic mAb; both 1B2+ and 1B2- subpopulations proliferated poorly in response to anti-CD3 and to PMA + ionomycin. These results raise the possibility that TCR engagement with MHC class 1 molecules during early intrathymic development can result in the emergence of CD4+ T cells characterized by unusual marker expression and function.