Extract from mango mistletoes Dendrophthoe pentandra ameliorates TNBS-induced colitis by regulating CD4+ T cells in mesenteric lymph nodes.

BACKGROUND: Mango mistletoes Dendrophthoe pentandra (MMDP) extract has attracted interest due to its pharmacological properties, including gastro protective effects. The aim of this study was to investigate whether MMDP extract could increase Foxp3 regulatory T cells and inhibits development of Th17 cells. METHODS: Colitis was induced in Balb/c mice by rectal administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS). The mice were randomly divided into five groups comprising group1 receiving vehicle (the negative control), group 2-5 receiving TNBS, group 3-5 orally receiving either MMDP extract 150, 300 and 600 mg/kgBW for 7 days after TNBS administration. On day 8 of the experiment, the colon tissues were removed for histological examination, cytokine and myeloperoxidase (MPO) measurement. T-cells sub-population in mesenteric lymph nodes were analyzed by flow cytometer. RESULTS: MMDP extract potently suppressed colon shortening and MPO in mice with TNBS-induced colitis. Administration of the extract significantly decreased the severity of TNBS-induced colitis in a dose-dependent manner. The extract significantly attenuated the loss of body weight (p < 0.05). These effects were associated with a remarkable amelioration of the disruption of the colonic architecture, significant reduction of the colonic MPO (p < 0.05). The extract lowered the levels of Th17-associated cytokines but increased the production of Treg-associated cytokines in mesenteric lymph node cells. CONCLUSION: Our results suggest that MMDP has the therapeutic potential to ameliorate TNBS-induced colitis symptoms revealed by histological change and inhibit IL-17 production.

Dendrophthoe pentandra (L.) Miq extract effectively inhibits inflammation, proliferation and induces p53 expression on colitis-associated colon cancer.

BACKGROUND: Indonesian mistletoe grows on various trees. Mango Mistletoes (Dendrophthoe pentandra) is one type of mistletoe that grown on mango tree (.benalu mangga in bahasa Indonesia). Our study used mistletoe as a parasitic plant that has been used for traditional medicine. It has been known that Dendrophtoe pentandra extract (DPE) anti-inflammatory and anticancer. Furthermore, it is necessary to follow-up study in vivo to evaluate the response to treatment of new cancer therapeutic agents. This research aimed to determine the levels of IL-22, myeloperoxide (MPO), proliferation and wild-type p53 expression after the administration of DPE to murine models of CAC. METHODS: Mouse colitis associated colon cancer (CAC) was induced firstly by azoxymethane (AOM) and followed by administration of drinking water containing 5 % dextran sodium sulfate (DSS) in a cycle protocol, each cycle consisted of seven days of 5 % DSS in the drinking water and followed by seven days of regular water. This study consists of five treatment groups: I was treated water only (control), II was administrated by (DSS only, without DPE), (III-V) were administrated by DPE (125 mg/kg BW, 250 mg/kg BW and 500 mg/kg BW) respectively. The administrated of DPE were started from the 8th weeks, were continued until 21 weeks. At the end of 21 weeks of the experiment, mice were sacrificed, colon tissue was removed, and then subjected to ELISA, flow cytometry, real-time PCR and histology examination. RESULTS: Administration of DPE 250 mg/kgBW significantly reduce the levels of IL-22 and MPO compared with DSS only group (p < 0.001; p < 0.001). Colonic epithelial cells proliferation of group IV (DPE 250 mg/kgBW) were significantly lower than III and V groups. There was no significant change in the S phase in mice were treated DPE 125 mg/kg BW and 500 mg/kg BW, while administration of DPE 250 mg/kg BW was able to increase the percentage of cells in S phase. The expression of mRNA p53 was up regulated in mice received DPE 125 mg/kg BW. CONCLUSION: These findings indicate that the DPE could inhibit colonic epithelial cells proliferation through p53 pathway independently. This study also showed that DPE could be potential sources of new therapy.

Treatment of low doses curcumin could modulate Th17/Treg balance specifically on CD4+ T cell cultures of systemic lupus erythematosus patients.

INTRODUCTION: The balance between T helper 17 (Th17) and regulatory T cells (Treg) is a new paradigm in the pathogenesis of systemic lupus erythematosus (SLE). Currently, there are no drugs that able to modulate Th17/Treg balance specifically in SLE. Curcumin is a bioactive agent that has a specific action against hyperproliferative cells. However, its role in modulating Th17/Treg balance in SLE is still unknown. This research aimed to investigate the role of curcumin in modulating Th17/Treg balance on CD4+ T cell cultures of SLE patients. MATERIAL AND METHODS: CD4+ T cells from SLE 6 untreated patients and 6 healthy subjects were collected, stimulated with Th17 differentiating factors, and curcumin 0.1 and 1 µg/ml was added on cultures. After 72 hours incubation, cells were harvested and measured for Th17 and Treg percentages using flow cytometry and interleukin-17A (IL-17A) and transforming growth factor-ß1 (TGF-ß1) levels using ELISA. RESULTS: Administration of low doses of curcumin (0.1 and 1 µg/ml) could decrease Th17 percentages (p = 0.000 and p = 0.000 compared to control), reduce IL-17A productions (p = 0.000 and p = 0.000 compared to control), increase Treg percentages (p = 0.001 and p = 0.000 compared to control), and increase TGF-ß1 productions (p = 0.001 and p = 0.000 compared to control) on CD4+ T cells of SLE patients. Interestingly, these effects were not reproduced on CD4+ T cells cultures of healthy subjects. CONCLUSIONS: These data suggest that curcumin can modulate Th17/Treg balance specifically on CD4+ T cells of SLE patients without affecting healthy subjects.