Methanolic Extract of Sambucus ebulus Ameliorates Clinical Symptoms in Experimental Type 1 Diabetes through Anti-Inflammatory and Immunomodulatory Actions.

OBJECTIVE: Sambucus ebulus (SE), a famous traditional Iranian medicine, is grown in the north of Iran. As a traditional medicine with anti-inflammatory effects, SE has been utilized against inflammatory joint diseases, insect bites, infectious wounds, edema, and eczema. Type1 diabetes, is an autoimmune disease, characterized by the destruction of pancreatic beta cells by the immune system. For the first time, we investigated the effect of methanolic extract of SE on CD4+, CD8+ and regulatory T cells in experimental type 1 diabetes (T1D). MATERIALS AND METHODS: In this experimental study, fifty-six C57BL\6 mice in 8 groups (G1-G8), were enrolled. Diabetes was induced by a multiple low-dose streptozotocin (MLDS) protocol and mice were daily treated with SE extract at 200 and 400 mg/kg doses, for 35 days. Fasting blood glucose was weekly measured by a glucometer. Islets insulin content was analyzed by immunohistochemistry. Percentage of CD4+, CD8+ and regulatory T cells and cytokines production levels were evaluated by flow cytometer and ELISA, respectively. RESULTS: The clinical symptoms of diabetes were significantly alleviated in G2 group mice which received 400 mg/ kg SE extract. Immunohistochemistry analysis showed that the insulin content of islets increased in G2 group mice. Immunophenotyping analysis indicated that the percentage of CD4+ and CD8+ T cells in G2 group mice was significantly decreased. SE extract significantly increased the percentage of regulatory T cells. The extract in G2 and G4 groups mice significantly decreased IFN-γ and IL-17levels. The extract significantly increased IL-10 in G2 group mice. CONCLUSION: The protective effect of SE extract in MLDS-induced diabetes could be partly due to a decrease of CD4+ and CD8+ T cells and an increase of Treg cells resulting in an inflammation reduction in the pancreatic islets.

Synergistic effect of aged garlic extract and naltrexone on improving immune responses to experimentally induced fibrosarcoma tumor in BALB/c mice.

BACKGROUND: Garlic, a medicinal plant, and Naltrexone (NTX), an opioid receptor antagonist, both have immunomodulatory and antitumor effects. Current study was designed to evaluate synergistic antitumor effects of aged garlic extract (AGE) and NTX. MATERIALS AND METHODS: WEHI-164 fibrosarcoma cells were implanted subcutaneously on day 0 into right flank of 80 BALB/c mice at age of 8 weeks. Mice were randomly categorized in four separate groups: The first group received AGE (100 mg/kg, i.p.), the second group received NTX (0.5 mg/kg, i.p.), the third group received both of them, and the fourth group received phosphate buffered saline as control group. Treatments were administered three times per week. Tumor growth was measured and morbidity was recorded. Subpopulations of CD4+/CD8+ T cells were determined using flowcytometery. WEHI-164 cell specific cytotoxicity of splenocytes and in vitro production of interferon-gamma (IFN-γ) and interleukin-4 (IL-4) cytokines were measured. All statistical analyses were conducted with SPSS 16 software and P < 0.05 was considered to be statistically significant. RESULTS: The mice who received AGE+NTX had significantly longer survival time compared with the mice treated with AGE or NTX alone. An enhanced inhibitory effect on tumor growth was seen in combination therapy group. The CD4+/CD8+ ratio and in vitro IFN-γ production of splenocytes were significantly increased in AGE+NTX and NTX groups. WEHI-164 specific cytotoxicity of splenocytes was also significantly increased at 25:1 E:T ratio in AGE+NTX treated mice. Coadministration of AGE with NTX resulted in improvement of immune responses against experimentally implanted fibrosarcoma tumors in BALB/c mice. CONCLUSIONS: AGE showed synergistic effects with NTX on inhibition of tumor growth and increment of survival times.

Immunomodulatory activity of aged garlic extract against implanted fibrosarcoma tumor in mice.

BACKGROUND: Garlic is known as a medicinal herb with broad therapeutic properties ranging from antibacterial to anticancer and even anticoagulant. AIM: Current study was designed to evaluate antitumor effects of aged garlic extract (AGE) on fibrosarcoma tumor in BALB/c mice. MATERIALS AND METHODS: WEHI-164 fibrosarcoma cells were implanted subcutaneously on day zero into right flank of 40 BALB/c mice aged eight weeks. Mice were randomly categorized in two separate groups: 1(st) received AGE (100 mg/kg, intraperitoneally), 2(nd) group as control received phosphate buffered saline, (PBS). Treatments were done three times per week. Tumor growth was measured and morbidity was recorded. Subpopulations of CD4+/CD8+ T cells were determined using flow cytometry. WEHI-164 cell specific cytotoxicity of splenocytes and in vitro production of gamma-interferon, (IFN-γ) and Interleukin-4, (IL-4) cytokines were measured. RESULTS: The mice received AGE had significantly longer survival time compared to control mice. The inhibitory effect on tumor growth was seen in AGE treated mice. The CD4+/CD8+ ratio and in vitro IFN-γ production of splenocytes were significantly increased in AGE group. CONCLUSIONS: Administration of AGE resulted in improved immune responses against experimentally implanted fibrosarcoma tumors in BALB/c mice. AGE showed significant effects on inhibition of tumor growth and longevity of survival times.