Study of the effect of bezafibrate with ginkgo biloba extracts in an animal model of hepatotoxicity induced by doxorubicin.

This study aimed to evaluate the hepatoprotective effect of combining bezafibrate with ginkgo biloba in doxorubicin-induced hepatotoxicity in rats. Thirty Wister albino rats were allocated into five groups: The negative control group, the positive control group, both received 1 ml of D.W, bezafibrate group received (100 mg/kg), ginkgo biloba group received (60 mg/kg) and the fifth group received bezafibrate + ginkgo biloba. All the treatments were for 14 days along with doxorubicin on days 11-14 except for the negative control. Blood samples were used for the measurement of ALT, AST, ALP, total protein, total bilirubin, albumin, globulin, GSH, catalase, and IL-6. Liver tissue was sent for histopathological examination. The combination of ginkgo biloba and bezafibrate significantly decreased AST, ALP, AST/ALT ratio, albumin/globulin ratio, and IL-6 with significant elevations of catalase, and GSH. The combination group produced more hepatoprotection. This could be attributed to the additive anti-inflammatory and antioxidant effects of the combination.

Effect of Telmisartan and Quercetin in 5 Fluorouracil-Induced Renal Toxicity in Rats.

Purpose: The present study was designed to evaluate the possible synergistic effects of telmisartan and quercetin in 5 fluorouracil (5-FU) induced nephrotoxicity in rats. Methodology: Forty male rats were randomly divided into five groups: The negative control group, the positive control group that received 5-FU, the telmisartan group, receiving 10 mg/kg, the quercetin group, receiving 80 mg/kg, and the combination of telmisartan and quercetin group. All the treatments were given orally for 14 days. A single intraperitoneal injection of 5-FU (150 mg/kg) on day 13 of the experiment was given except for the negative control group. On the 15th day after scarification, approximately 5 mL of blood was collected and used for measurement of CBC, urea, creatinine, and uric acid. The kidneys were used for histopathological examination and for the measurement of kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), Cystatin C (Cys-C), and total antioxidant capacity (TAOC). Results: The combination therapy significantly attenuated the levels of tissue KIM-1, NGAL, Cys-C, and serum uric acid as well as blood inflammatory markers, Neutrophil/Lymphocyte (NLR), Monocyte/Lymphocyte (MLR), and Platelets/Lymphocyte ratios (PLR), and restored the TAOC. The histopathological findings greatly support the biochemical tests. Conclusion: The results strongly suggest the renoprotective effects of telmisartan and quercetin in combination against the nephrotoxic effect of 5-FU through decreasing the levels of KIM-1, NGAL, and cys-C, and the novel inflammatory markers of kidney injury like NLP, MLR, and PLR, as well as decreasing uric acid and restoring the TAOC. The proposed mechanism could be the additive inhibitory effect on RAS provided by both telmisartan and quercetin.

Gingko biloba extract improves the lipid profile, inflammatory markers, leptin level and the antioxidant status of T2DM patients poorly responding to metformin: A double- blind, randomized, placebo-controlled trial

Abstract The present study aims to evaluate the effects of Ginkgo biloba (GKB) extract as "add- on" therapy with metformin on the lipid profile, inflammatory markers, leptin and the total antioxidant capacity (TAOC) of patients with type 2 diabetes mellitus (T2DM). It is a multi- center, randomized, placebo-controlled double-blinded clinical study. Sixty patients were allocated into two groups: control and treatment groups; they received orally either 120 mg starch/capsule or 120mg GKB/capsule, respectively as an adjuvant with metformin for 90 days. Blood samples were obtained at zero time and after 90 days. The blood was utilized for analysis of the lipid profile, inflammatory markers, leptin, and TAOC. The GKB extract produced a significant decrease in the levels of TG, LDL-c, and CRP, with a significant increase in HDL-c compared to baseline values. There were no significant changes reported in the placebo-treated group. It also produced a significant decrease in the concentrations of IL-6, TNF-α, and leptin compared to baseline values and placebo-treated groups with a significant increase in TAOC compared to baseline values. In conclusion, GKB extract, as an adjuvant with metformin, decreases inflammatory mediators, leptin level and improves the antioxidant status and lipid profile of T2DM patients improperly managed with metformin

The Anti-Inflammatory Effect of Different Doses of Aliskiren in Rat Models of Inflammation.

OBJECTIVE: The present study was designed to evaluate the anti-inflammatory effects of different doses of aliskiren in two animal models of inflammation. METHODOLOGY: Sixty-six Wistar rats were allocated into five groups: the first group (six rats) was treated with the vehicle only, without induction of paw edema and granulomatous inflammation, and served as a negative control; the second group (12 rats) was allocated into two subgroups and treated with the vehicle only, with induction of paw edema and granulomatous inflammation, and served as a positive control; the third group (36 rats) was allocated into six subgroups and treated with different doses of aliskiren (15, 30, and 60 mg/kg) in both models; the fourth group (12 rats) was treated with dexamethasone (1 mg/kg) in both models of inflammation. Serum concentrations of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), vascular cell adhesion molecule-1 (VCAM-1), and high sensitivity C-reactive protein (hs-CRP) were measured. Skin samples were also sent for histopathological examination. RESULTS: Aliskiren, in a dose-dependent pattern, significantly decreased inflammation in rat models of inflammation, by attenuating the percentage of exudate, granuloma, and paw edema. Furthermore, it significantly reduced serum concentrations of TNF-α, VCAM-1, and hs-CRP and restored the serum concentration of IL-10. Additionally, significant improvement was seen in the histopathological findings. CONCLUSION: In the current study, aliskiren was successful in decreasing inflammation in both models. These findings suggest that aliskiren is a good candidate for the treatment of inflammatory diseases.

Effects of quercetin, sitagliptin alone or in combination in testicular toxicity induced by doxorubicin in rats.

OBJECTIVE: This study aimed to evaluate the effect of quercetin and/or sitagliptin on testicular damage induced by doxorubicin (DOX). METHODOLOGY: Twenty-five male Wistar rats, weighing 240±20 g, were randomly divided into five groups as follows: a negative control group; that was treated with 1 mL of 0.9% sodium chloride; a DOX-treated group received Intraperitoneal (I.P.) DOX injection (3 mg/kg); a group treated with quercetin 80 mg/kg + sitagliptin 10 mg/kg + DOX; a group treated with quercetin 80 mg/kg + DOX; and a group treated with sitagliptin 10 mg/kg+ DOX. All treatment were given orally daily for 21 days with I.P. DOX 3 mg/kg injection for the treatment groups at days 8, 10, 12, 15, 17, and 19. On day 22, blood was collected for analysis of testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), glutathione peroxidase (GPx), and total antioxidant capacity (TAOC). The testes were also removed and sent for histopathological examination. RESULTS: The study revealed that the combination of quercetin with sitagliptin produced a significant increase in testosterone and FSH levels with a non-significant increase in LH level. This combination also non-significantly decreased the level of ALP and LDH and restored the GPx level with enhancing TAOC. CONCLUSION: The results suggest quercetin/sitagliptin combination as a promising therapeutic modality for attenuation of DOX-induced testicular toxicity in rats, and the main mechanism involved in such effect could be due to the antioxidant and anti-inflammatory properties of both agents.

Efficacy and safety of Ginkgo biloba extract as an "add-on" treatment to metformin for patients with metabolic syndrome: a pilot clinical study.

BACKGROUND AND AIM: Ginkgo biloba (GKB) extract has shown to be beneficial in experimental models of metabolic and inflammatory disorders such as diabetes and metabolic syndrome (MTS). The objective of this pilot clinical study was to evaluate the effects of GKB extract as an "add-on" treatment with metformin (Met) in MTS patients. PATIENTS AND METHODS: We performed a randomized, placebo-controlled, double-blinded clinical study in subjects with MTS. Forty patients completed the 90-day clinical trial and were randomly allocated to administer either GKB extract (120 mg capsule/day) or placebo (120 mg starch/day) as an add-on treatment with their currently used doses of Met for 90 days. During the study, body mass index (BMI), waist circumference (WC), serum leptin, glycated hemoglobin (HbA1c), fasting serum glucose (FSG), insulin, insulin resistance (IR), visceral adiposity index (VAI), lipid profile, and the inflammatory markers high sensitive C-reactive protein (hsCRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were evaluated. RESULTS: GKB extract significantly decreases HbA1c, FSG and insulin levels, IR, BMI, WC, VAI, serum leptin, and the inflammatory markers compared to baseline values. Simultaneously, GKB did not negatively affect the functions of the liver, kidney, and hematopoietic system. CONCLUSION: The use of GKB extract as an adjuvant with Met was effective in improving the outcome of patients with MTS.

The efficacy and safety of Ginkgo biloba extract as an adjuvant in type 2 diabetes mellitus patients ineffectively managed with metformin: a double-blind, randomized, placebo-controlled trial.

BACKGROUND AND AIM: Type 2 diabetes mellitus (T2DM) is one of the major diseases confronting the health care systems. In diabetes mellitus (DM), combined use of oral hypoglycemic medications has been shown to be more effective than metformin (Met) alone in glycemic control. This study determined the effects of Ginkgo biloba (GKB) extract as an adjuvant to Met in patients with uncontrolled T2DM. SUBJECTS AND METHODS: Sixty T2DM patients were recruited in a randomized, placebo-controlled, double-blinded, and multicenter trial. The patients, currently using Met, were randomly grouped into those treated with either GKB extract (120 mg/day) or placebo (starch, 120 mg/day) for 90 days. Blood glycated hemoglobin (HbA1c), fasting serum glucose, serum insulin, body mass index (BMI), waist circumference (WC), insulin resistance, and visceral adiposity index (VAI) were determined before (baseline) and after 90 days of GKB extract treatment. RESULTS: GKB extract significantly decreased blood HbA1c (7.7%±1.2% vs baseline 8.6%±1.6%, P<0.001), fasting serum glucose (154.7±36.1 mg/dL vs baseline 194.4±66.1 mg/dL, P<0.001) and insulin (13.4±7.8 µU/mL vs baseline 18.5±8.9 µU/mL, P=0.006) levels, BMI (31.6±5.1 kg/m2 vs baseline 34.0±6.0 kg/m2, P<0.001), waist WC (102.6±10.5 cm vs baseline 106.0±10.9 cm, P<0.001), and VAI (158.9±67.2 vs baseline 192.0±86.2, P=0.007). GKB extract did not negatively impact the liver, kidney, or hematopoietic functions. CONCLUSION: GKB extract as an adjuvant was effective in improving Met treatment outcomes in T2DM patients. Thus, it is suggested that GKB extract is an effective dietary supplement for the control of DM in humans.