Suthiluk Patumraj

Curcumin supplementation could improve diabetes-induced endothelial dysfunction associated with decreased vascular superoxide production and PKC inhibition

BackgroundCurcumin, an Asian spice and food-coloring agent, is known for its anti-oxidant properties. We propose that curcumin can improve diabetes-induced endothelial dysfunction through superoxide reduction.MethodsDiabetes (DM) was induced in rats by streptozotocin (STZ). Daily curcumin oral feeding was started six weeks after the STZ injection. Twelve weeks after STZ injection, mesenteric arteriolar responses were recorded in real time using intravital fluorescence videomicroscopy. Superoxide and vascular protein kinase C (PKC-βII) were examined by hydroethidine and immunofluorescence, respectively.ResultsThe dilatory response to acetylcholine (ACh) significantly decreased in DM arterioles as compared to control arterioles. There was no difference among groups when sodium nitroprusside (SNP) was used. ACh responses were significantly improved by both low and high doses (30 and 300 mg/kg, respectively) of curcumin supplementation. An oxygen radical-sensitive fluorescent probe, hydroethidine, was used to detect intracellular superoxide anion (O2●-) production. O2●- production was markedly increased in DM arterioles, but it was significantly reduced by supplementation of either low or high doses of curcumin. In addition, with a high dose of curcumin, diabetes-induced vascular PKC-βII expression was diminished.ConclusionTherefore, it is suggested that curcumin supplementation could improve diabetes-induced endothelial dysfunction significantly in relation to its potential to decrease superoxide production and PKC inhibition.

Comparative effects of garlic and aspirin on diabetic cardiovascular complications.

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 garlics 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.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 ultrastructual changes. In addition, to identify the possible mechanism(s) of garlics 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 mum) wall in STZ-rats. Interestingly, the thickening of coronary capillary (5-10 mum) 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.

Curcumin prevents indomethacin-induced gastropathy in rats

AIM To investigate the effects of curcumin on gastric microcirculation and inflammation in rats with indomethacin-induced gastric damage. METHODS Male Sprague-Dawley rats were randomly divided into three groups. Group 1 (control group, n = 5) was fed with olive oil and 5% NaHCO(3) (-) (vehicle). Group 2 [indomethacin (IMN) group, n = 5] was fed with olive oil 30 min prior to indomethacin 150 mg/kg body weight (BW) dissolved in 5% NaHCO(3) (-) at time 0th and 4th h. Group 3 (IMN + Cur group, n = 4) was fed with curcumin 200 mg/kg BW dissolved in olive oil 0.5 mL, 30 min prior to indomethacin at 0th and 4th h. Leukocyte-endothelium interactions at postcapillary venules were recorded after acridine orange injection. Blood samples were determined for intercellular adhesion molecule (ICAM)-1 and tumor necrosis factor (TNF)-α levels using enzyme linked immunosorbent assay method. Finally, the stomach was removed for histopathological examination for gastric lesions and grading for neutrophil infiltration. RESULTS In group 2, the leukocyte adherence in postcapillary venules was significantly increased compared to the control group (6.40 ± 2.30 cells/frame vs 1.20 ± 0.83 cells/frame, P = 0.001). Pretreatment with curcumin caused leukocyte adherence to postcapillary venule to decline (3.00 ± 0.81 cells/frame vs 6.40 ± 2.30 cells/frame, P = 0.027). The levels of ICAM-1 and TNF-α increased significantly in the indomethacin-treated group compared with the control group (1106.50 ± 504.22 pg/mL vs 336.93 ± 224.82 pg/mL, P = 0.011 and 230.92 ± 114.47 pg/mL vs 47.13 ± 65.59 pg/mL, P = 0.009 respectively). Pretreatment with curcumin significantly decreased the elevation of ICAM-1 and TNF-α levels compared to treatment with indomethacin alone (413.66 ± 147.74 pg/mL vs 1106.50 ± 504.22 pg/mL, P = 0.019 and 58.27 ± 67.74 pg/mL vs 230.92 ± 114.47 pg/mL, P = 0.013 respectively). The histological appearance of the stomach in the control group was normal. In the indomethacin-treated group, the stomachs showed a mild to moderate neutrophil infiltration score. Gastric lesions were erosive and ulcerative. In rats treated with indomethacin and curcumin, stomach histopathology improved and showed only a mild neutrophil infiltration score and fewer erosive lesions in the gastric mucosa. CONCLUSION The results indicate that curcumin prevents indomethacin-induced gastropathy through the improvement of gastric microcirculation by attenuating the level of ICAM-1 and TNF-α.

Curcumin by down-regulating NF-kB and elevating Nrf2, reduces brain edema and neurological dysfunction after cerebral I/R

BACKGROUND Oxidation, inflammation, and apoptosis are three critical factors for the pathogenic mechanism of cerebral ischemia/reperfusion (I/R) injury. Curcumin exhibits substantial biological properties via anti-oxidation, anti-inflammation and anti-apoptotic effects; however, the molecular mechanism underlying the effects of curcumin against cerebral I/R injury remains unclear. OBJECTIVE To investigate the effects of curcumin on cerebral I/R injury associated with water content, infarction volume, and the expression of nuclear factor-kappa-B (NF-κB) and nuclear factor-erythroid-related factor-2 (Nrf2). METHODS Middle cerebral artery occlusion (MCAO, 1-hour occlusion and 24-hour reperfusion) was performed in male Wistar rats (n=64) as a cerebral I/R injury model. In the MCAO+CUR group, the rats were administered curcumin (300mg/kg BW, i.p.) at 30min after occlusion. The same surgical procedures were performed in SHAM rats without MCAO occlusion. At 24h post-operation, the parameters, including neurological deficit scores, blood brain barrier (BBB) disruption, water content, and infarction volume, were determined. Brain tissue NF-κB and Nrf2 expression levels were assayed through immunohistochemistry. RESULTS Compared with the SHAM group, BBB disruption, neurological deficit, and increased brain water content and infarction volume were markedly demonstrated in the MCAO group. NF-κB expression was enhanced in the MCAO group. However, in the MCAO+CUR group, the upregulation of Nrf2, an anti-oxidation related protein, was consistent with a significant decline in the water content, infarction volume, and NF-κB expression. CONCLUSION The protective effects of curcumin against cerebral I/R injury reflect anti-oxidation, anti-inflammation and anti-apoptotic activities, resulting in the elevation of Nrf2 and down-regulation of NF-κB.

Antitumor and Antiangiogenic Activities of Curcumin in Cervical Cancer Xenografts in Nude Mice

To evaluate the effects of curcumin (CUR) on tumor progression and angiogenesis in cervical cancer- (CaSki-) implanted nude mice and on the angiogenic biomarkers: vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), and epidermal growth factor receptor (EGFR). CaSki cells were subcutaneously injected in nude mice to establish subcutaneous tumors. One month after injection, mice were orally administered vehicle or 500, 1,000, and 1,500 mg/kg of CUR daily × 30 consecutive days. Tumor volume was measured every 3-4 days. At the end of the study, tumor microvasculature was observed under confocal microscope, and immunohistochemical analyses were performed to detect CD31, VEGF, COX-2, and EGFR. CUR at the doses of 1,000 and 1,500 mg/kg showed significant tumor growth retardation (21.03% and 35.57%) versus CaSki + vehicle group. The microvascular density (MVD) in CaSki + vehicle group was significantly increased versus Control + vehicle group and significantly reduced by CUR (1,000 and 1,500 mg/kg). VEGF, COX-2, and EGFR expressions were upregulated in CaSki + vehicle group and attenuated significantly by CUR (1,000 and 1,500 mg/kg). In conclusion, high dose CUR inhibited tumor growth and angiogenesis in CaSki-implanted mice probably mediated by the downregulation of VEGF, COX-2 and EGFR. CUR may have a role in treating human cervical cancer and should be explored further.

Exercise Training Could Improve Age-Related Changes in Cerebral Blood Flow and Capillary Vascularity through the Upregulation of VEGF and eNOS

This study aimed to investigate the effect of exercise training on age-induced microvascular alterations in the brain. Additionally, the association with the protein levels of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) was also assessed. Male Wistar rats were divided into four groups: sedentary-young (SE-Young, n = 5), sedentary aged (SE-Aged, n = 8), immersed-aged (IM-Aged, n = 5), and exercise trained-aged (ET-Aged, 60 minutes/day and 5 days/week for 8 weeks, n = 8) rats. The MAPs of all aged groups, SE-Aged, IM-Aged, and ET-Aged, were significantly higher than that of the SE-Young group. The regional cerebral blood flow (rCBF) in the SE-Aged and IM-Aged was significantly decreased as compared to SE-Young groups. However, rCBF of ET-Aged group was significantly higher than that in the IM-Aged group (P < 0.05). Moreover, the percentage of capillary vascularity (%CV) and the levels of VEGF and eNOS in the ET-Aged group were significantly increased compared to the IM-Aged group (P < 0.05). These results imply that exercise training could improve age-induced microvascular changes and hypoperfusion closely associated with the upregulation of VEGF and eNOS.

OXIDATIVE STRESS AND HEMODYNAMIC MALADJUSTMENT IN CHRONIC RENAL DISEASE: A THERAPEUTIC IMPLICATION

Hemodynamic maladjustment with predominant constriction at the efferent arteriole has been encountered in a variety of clinical settings of glomerulonephropathy. In essence, it induces not only intraglomerular hypertension but also exaggeratedly reduces the peritubular capillary flow, which supplies the tubulointerstitial compartment. The hemodynamic maladjustment is believed to reflect a glomerular endothelial cell dysfunction. In this regard, oxidative stress and antioxidant defect are likely responsible for the glomerular endothelial dysfunction. Improvement in renal function was accomplished following the correction of oxidant and antioxidant imbalance with antioxidant therapy and vasodilators. Following such therapy, there was a correction in hemodynamic maladjustment with a decline in intraglomerular hydrostatic pressure and an increase in renal perfusion with a subsequent increase in renal functions namely creatinine clearance, glomerular filtration rate and a decline in FEMg.

Hyposerotonin-induced nitric oxide supersensitivity in the cerebral microcirculation.

Objective.–To investigate the relationship between hyposerotonin and cranial microvascular responses to nitric oxide (NO).

Vasculoprotective Effects of Combined Endothelial Progenitor Cells and Mesenchymal Stem Cells in Diabetic Wound Care: Their Potential Role in Decreasing Wound-Oxidative Stress

To investigate whether the combined endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) could enhance angiogenesis and wound healing in diabetic mice. Balb/c nude mice were divided into five groups, including a control group, diabetic group (DM), DM injected with 1 × 106  cells MSCs, DM injected with 1 × 106  cells EPCs, and DM injected with combined 0.5 × 106  cells MSCs and 0.5 × 106  cells EPCs. After seven weeks, the mice were anesthetized, and bilateral full-thickness excision skin wounds were made on the dorsorostral back. The percentage of wound closure in DM group decreased significantly than in control and all other treated groups on day 7 and day 14 (P < 0.005). On day 14, the percentage of capillary vascularity in combine-treated group was significantly higher than in DM (P < 0.005). In the present study, we have demonstrated that the combined EPCs and MSCs can increase vascular endothelial growth factor (VEGF) level and angiogenesis which resulted in reduced neutrophil infiltration, decreased malondialdehyde (MDA) levels, and enhanced wound healing in diabetic mice model.

Curcumin Attenuates Gastric Cancer Induced by N-Methyl-N-Nitrosourea and Saturated Sodium Chloride in Rats

To determine effects of curcumin on N-methyl-N-nitrosourea (MNU) and saturated sodium chloride (s-NaCl)-induced gastric cancer in rats. Male Wistar rats were divided into 5 groups: control (CO), control supplemented with 200 mg/kg curcumin (CC), MNU + s-NaCl, MNU + s-NaCl supplemented with 200 mg/kg curcumin daily for the first 3 weeks (MNU + s-NaCl + C3W), and MNU + s-NaCl supplemented with curcumin for 20 weeks (MNU + s-NaCl + C20W). To induce stomach cancer, rats except for CO and CC were orally treated with 100 mg/kg MNU on day 0 and 14, and s-NaCl twice-a-week for the first 3 weeks. The experiment was finished and rats were sacrificed at the end of 20 weeks. Cancers were found in forestomachs of all rats in MNU + s-NaCl. The expressions of phosphorylated inhibitor kappaB alpha (phospho-IκBα), 8-hydroxy-2′-deoxyguanosine (8-OHdG), and cyclin D1 significantly increased in MNU + s-NaCl compared with CO. Curcumin treatments for 3 and 20 weeks reduced the cancer incidence resulting in a decrease of phospho-IκBα expression in benign tumor-bearing rats compared with MNU + s-NaCl. Curcumin treatment for 20 weeks also decreased 8-OHdG expression in benign tumor-bearing rats compared with MNU + s-NaCl. Curcumin can attenuate cancer via a reduction of phospho-IκBα and 8-OHdG expressions, which may play a promising role in gastric carcinogenesis.