The present study examined effects of alpha-mangostin (α-MG) supplementation on the retinal microvasculature, including ocular blood flow (OBF) and blood-retinal barrier (BRB) permeability in a type 2 diabetic animal model. Male Sprague-Dawley rats were divided into four groups: normal control and diabetes with or without α-MG supplementation. Alpha-mangostin (200 mg/Kg/day) was administered by gavage feeding for 8 weeks. The effects of α-MG on biochemical and physiological parameters including mean arterial pressure (MAP), OBF, and BRB leakage were investigated. Additionally, levels of retinal malondialdehyde (MDA), advance glycation end products (AGEs), receptor of advance glycation end products (RAGE), tumour necrosis factor alpha (TNF-α), and vascular endothelial growth factor (VEGF) were evaluated. The elevated blood glucose, HbA1c, cholesterol, triglyceride, serum insulin, and HOMA-IR were observed in DM2 rats. Moreover, DM2 rats had significantly decreased OBF but statistically increased MAP and leakage of the BRB. The α-MG-treated DM2 rats showed significantly lower levels of retinal MDA, AGEs, RAGE, TNF-α, and VEGF than the untreated group. Interestingly, α-MG supplementation significantly increased OBF while it decreased MAP and leakage of BRB. In conclusion, α-MG supplementation could restore OBF and improve the BRB integrity, indicating its properties closely associated with antihyperglycemic, antioxidant, anti-inflammatory, and antiglycation activities.
Introduction: In Thailand, Leishmania martiniquensis is the predominant species causing cutaneous and visceral leishmaniasis. Its incidence has been increasing among immunocompetent and immunocompromised hosts. We developed a prototype DNA vaccine using a partial consensus sequence of the cysteine protease B (cpb) gene derived from L. martiniquensis from Thai patients.
Methodology: The laboratory inbred strain of albino BALB/c mice were immunized intramuscularly three times at 2-week intervals (weeks 0, 2, and 4) with cpb plasmid DNA (pcDNA_cpb) with or without the adjuvant, monoolein (pcDNA_cpb-MO). Mice were challenged at week 6 with L. martiniquensis promastigotes. Sera were analysed for IgG1, IgG2a, interferon gamma and interleukin 10 (IFN-γ and IL-10, respectively) levels at weeks 0, 4, and 9. Additionally, livers and spleens were also analysed for parasite burden using immunohistochemistry and real-time polymerase chain (qPCR) assays.
Results: Three weeks after promastigote challenge, vaccinated mice showed significantly increased levels of IgG2a and IFN-γ while IL-10 level was significantly reduced when compared with those in the control group (p < 0.01). Parasite burden in the livers and spleens of vaccinated mice significantly decreased. In addition, a significant increase in mature granuloma formation in the livers when compared with those of the control group (p < 0.05) was found, indicating increased T-helper cells (Th1)-induced inflammation and destruction of amastigotes. Monoolein produced a booster effect to enhance the mouse Th1 protective immunity.
Conclusions: The prototype DNA vaccine could induce a Th1 immune response that conferred potential protection to the L. martiniquensis promastigote challenge in BALB/c mice.
By using streptozotocin-induced diabetic rats as a studied model, our previous experimental results have indicated that daily oral feeding of garlic extract (100 mg/kg BW) could increase the cardiovascular functions in streptozotocin (STZ) rats; the abnormality of lipid profile was prevented; and garlic extract could increase fibrinolitic activities with the decrease of platelet aggregation. Moreover, the plasma insulin level was increased concomitantly with the decrease of plasma glucose level. However, due to the high incidence of atherosclerosis in diabetes, the present study has been continued for further investigation of the effect of garlic extract on the coronary vascular ultrastructural changes. In addition, to identify the possible mechanism(s) of garlic's therapeutic effects, the cyclooxygenase inhibitor, aspirin, has been included in this present study. By using transmission electron microscopic studies, 16 weeks of daily oral feeding of garlic extract (100 mg/kg BW) caused as an antiatherosclerotic agent at the coronary arteriolar (15-30 microns) wall in STZ-rats. Interestingly, the thickening of coronary capillary (5-10 microns) basement membrane also was significantly attenuated within the group of STZ-rats treated with garlic extract. However, the possible direct action of garlic through the cyclooxygenase pathway has not been confirmed by the results of aspirin: The daily oral feeding of aspirin (10 mg/kg BW) in 16-week STZ-rats has not showed reduced arteriolar vascular wall abnormalities. The irregular patterns of fiber matrix, arranging the basement membrane at the arteriolar walls, were still recognized in the same manner as in STZ-rats. Interestingly, the thickening of the capillary basement membrane occurred in 16-week STZ-rats seems to be attenuated by the aspirin received. At present, garlic extract may open the new era in the medicinal use of garlic to prevent diabetic cardiovascular complications.
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