AIM OF THE STUDY: To evaluate the immune stimulatory effects of F3 from S. crispus in NMU-induced rat mammary tumor model.
MATERIALS AND METHODS: Immunohistochemistry analysis of cellular immune parameters (CD4+ or CD8+ T cells, CIITA, MHC-II and CD68) was performed on NMU-induced rat mammary tumor nodules, followed by evaluation of the serum level of 34 cytokines using the cytokine antibody array.
RESULTS: Significant increase in MHC-II, CD4+ and CD8+ T cell and CIITA expression by tumor cells was observed in F3-treated rats compared to the tumor control group. F3-treated rats also displayed a significant decrease in the serum level of CCL2 and CD68+ infiltrating macrophages. Serum IFN-γ level in this group was increased by 1.7-fold suggesting enhanced infiltration of T cells, and upregulation of CIITA and MHC-II expression in the tumor cells might be triggered by F3-induced production of IFN-γ.
CONCLUSION: Our findings demonstrated for the first time that a subfraction from S. crispus, F3, is capable of activating the immune system in rats-bearing NMU-induced mammary tumor, which may contribute to the anticancer effects of F3, and additionally support the traditional use of S. crispus leaves to boost the immune system.
METHODS: In vitro cytotoxicity of nordamnacanthal was tested using MTT, cell cycle and Annexin V/PI assays on human MCF-7 and MDA-MB231 breast cancer cells. Mice were orally fed with nordamnacanthal daily for 28 days for oral subchronic toxicity study. Then, the in vivo anti-tumor effect was evaluated on 4T1 murine cancer cells-challenged mice. Changes of tumor size and immune parameters were evaluated on the untreated and nordamnacanthal treated mice.
RESULTS: Nordamnacanthal was found to possess cytotoxic effects on MDA-MB231, MCF-7 and 4T1 cells in vitro. Moreover, based on the cell cycle and Annexin V results, nordamnacanthal managed to induce cell death in both MDA-MB231 and MCF-7 cells. Additionally, no mortality, signs of toxicity and changes of serum liver profile were observed in nordamnacanthal treated mice in the subchronic toxicity study. Furthermore, 50 mg/kg body weight of nordamncanthal successfully delayed the progression of 4T1 tumors in Balb/C mice after 28 days of treatment. Treatment with nordamnacanthal was also able to increase tumor immunity as evidenced by the immunophenotyping of the spleen and YAC-1 cytotoxicity assays.
CONCLUSION: Nordamnacanthal managed to inhibit the growth and induce cell death in MDA-MB231 and MCF-7 cell lines in vitro and cease the tumor progression of 4T1 cells in vivo. Overall, nordamnacanthal holds interesting anti-cancer properties that can be further explored.
METHOD: This MSBase cohort study of AQP4-IgG+NMOSD patients examined modifiers of relapse in a multivariable proportional hazards model and expanded disability status score (EDSS) using a mixed effects model.
RESULTS: 206 AQP4-IgG+ patients were included (median follow-up 3.7 years). Age (hazard ratio [HR] = 0.82 per decade, p = 0.001), brainstem onset (HR = 0.45, p = 0.009), azathioprine (HR = 0.46, p<0.001) and mycophenolate mofetil (HR = 0.09, p = 0.012) were associated with a reduced risk of relapse. A greater EDSS was associated with age (β = 0.45 (per decade), p<0.001) and disease duration (β = 0.07 per year, p<0.001). A slower increase in EDSS was associated with azathioprine (β = -0.48, p<0.001), mycophenolate mofetil (β = -0.69, p = 0.04) and rituximab (β = -0.35, p = 0.024).
INTERPRETATION: This study has demonstrated that azathioprine and mycophenolate mofetil reduce the risk of relapses and disability progression is modified by azathioprine, mycophenolate mofetil and rituximab. Age and disease duration were the only patient characteristics that modified the risk of relapse and disability in our cohort.
AIM OF THIS REVIEW: In this article, we have reviewed the literature on the phytochemicals of several Tinospora species, which have shown strong immunomodulatory effects and critically analyzed the reports to provide perspectives and instructions for future research for the plants as a potential source of new immunomodulators for use as medicinal agents or dietary supplements.
MATERIALS AND METHODS: Electronic search on worldwide accepted scientific databases (Google Scholar, Science Direct, SciFinder, Web of Science, PubMed, Wiley Online Library, ACS Publications Today) was performed to compile the relevant information. Some information was obtained from books, database on medicinal plants used in Ayurveda, MSc dissertations and herbal classics books written in various languages.
RESULTS: T. cordifolia, T. crispa, T. sinensis, T. smilacina, T. bakis, and T. sagittata have been reported to possess significant immunomodulatory effects. For a few decades, initiatives in molecular research on the effects of these species on the immune system have been carried out. However, most of the biological and pharmacological studies were carried out using the crude extracts of plants. The bioactive compounds contributing to the bioactivities have not been properly identified, and mechanistic studies to understand the immunomodulatory effects of the plants are limited by many considerations with regard to design, conduct, and interpretation.
CONCLUSION: The plant extracts and their active constituents should be subjected to more detail mechanistic studies, in vivo investigations in various animal models including pharmacokinetic and bioavailability studies, and elaborate toxicity study before submission to clinical trials.
METHODS: Raw 264.7 macrophages were used to asses G. cowa Roxb. immunomodulatory activity. The MTT assay was chosen to measure cell viability to evaluate the cytotoxic effect on cells. ELISA method was used to measure the concentration of Interleukin-6 (IL-6) and Tumor Necrosis Factor Alpha (TNF-α) secreted by cells after being treated with G. cowa Roxb. fraction. The neutral red uptake assay determined the effect of Garcinia cowa Roxb. on the phagocytic activity.
RESULTS: After Raw 264.7 macrophages were given the Hexan fraction (Hex) at concentrations of 12.5 and 25 μg/mL, there was a decrease in the concentration of IL-6, TNF-α, and the phagocytosis index of cells. Administration of the Ethyl Acetate fraction (EtOAc) at concentrations of 12.5 and 25 μg/mL on cells caused a decrease in IL-6 and TNF-α levels but did not affect the phagocytosis index. There was an increase in the level of TNF-α and the phagocytosis index after being given the Butanol fraction (BuOH) with concentrations of 12.5 and 25 μg/mL but there was a slight decrease in the level of IL-6.
CONCLUSIONS: Both Hex and EtOAc fractions could suppress immune responses through decreasing IL-6, TNF-α, and slightly decreased phagocytic activity. BuOH fraction could stimulate immunomodulatory activities through enhanced TNF-α levels and phagocytic index, but less potent in enhancing IL-6 production. The BuOH fraction could be developed as an immunostimulant.