Effects of garlic (Allium sativum L) and Citrullus colocynthis (L.) Schrad individually and in combination on male reproductive damage due to diabetes: suppression of the AGEs/RAGE/Nox-4 signaling pathway.

BACKGROUND: Diabetes Mellitus is associated with disturbances in male reproductive function and fertility. Studies have shown that oxidative stress with the subsequent inflammation and apoptosis cause these complications in diabetes. Garlic (G) (Allium sativum L) and Citrullus colocynthis (L.) Schrad (C) both have antidiabetic and antioxidant properties. Recently, we demonstrated their synergistic effects in alleviating reproductive complications when administered concomitantly. However, as even medicinal plants in long term usage may lead to some unwanted side effects of their own, we examined whether with half the original doses of these two medicinal plants we could achieve the desired results. METHODS: Thirty-five male Wistar rats were divided into five groups (n = 7/group): Control, Diabetic, Diabetic + G (0.5 ml/100 g BW), Diabetic + C (5 mg/kg BW) and Diabetic + GC (0.5 ml/100 g BW of garlic and 5 mg/kg BW of C. colocynthis) groups. The experimental period was 30 days. RESULTS: Oxidative stress, advanced glycation end products (AGEs), immunoexpression of caspase-3, and expression of mRNAs for receptor for advanced glycation end products (RAGE), NADPH oxidase-4 (NOX-4) and nuclear factor kappa B increased in testis of diabetic rats. Treatment with garlic and C. colocynthis alone showed some beneficial effects, but in the combination form the effectiveness was more profound. CONCLUSIONS: We conclude that the combination therapy of diabetic rats with lower doses is still as efficient as higher doses; therefore, the way forward for reducing complications in long term consumption.

Synergistic properties of garlic and Citrullus colocynthis on reproductive injury caused by diabetes in male rats: Structural and molecular evidence.

This study evaluates the synergistic effect of garlic and Citrullus colocynthis on diabetic reproductive damage by suppressing the AGEs/RAGE/Nox-4 signaling pathway. Thirty-five male Wistar rats were divided into five groups (n = 7/group): Control, Diabetic, Diabetic+G (Garlic, 1 mL/100 g b.w), Diabetic+C (C. colocynthis, 10 mg/kg b.w) and Diabetic+GC (Garlic, 1 mL/100 g b.w and C. colocynthis, 10 mg/kg b.w) groups. At the end of the experimental period (30 days), in diabetic rats, glucose increased, and body & testis weight, luteinizing hormone (LH) and testosterone levels, and sperm count decreased significantly and histopathological injuries were observed. In addition, they have increased testicular apoptosis and oxidative stress. Also, the mechanism based on advanced glycation end products (AGEs)/receptors for advanced glycation end products (RAGE)/NADPH oxidase-4 (Nox-4) was activated in diabetic rats. Separate consumption of garlic and C. colocynthis in Diabetic+G and Diabetic+C groups alleviated the negative adverse effect of diabetes to some extent, but when they were used in the combination form (Diabetic+GC) improvement was profound. Testis histopathology, increased body and testis weight, and enhanced capacity in protecting diabetic reproductive injury was seen. Decreases in testosterone and LH concentration and sperm count in diabetic rats were also reversed by combined administration of garlic and C. colocynthis. It regulated oxidative stress markers, meanwhile reducing caspase-3 immunoexpression. In addition, overexpression of RAGE, Nox-4 and nuclear transcription factor-κB (NF-κB) was inhibited by the combination of garlic and C. colocynthis. PRACTICAL APPLICATIONS: Diabetes mellitus is wide spread all around the world with variety of complications in body including reproductive system in which patients suffer from physical and psychological aspects. Despite many efforts in providing agents for controlling diabetes and its complications, economic conditions of some countries make it difficult for people to provide costly medicine and as a result, they have to bear the complications until they pass away. However, traditional medicine is still finding its way, especially in poor countries with emphasis on medicinal plants. There have been many studies on plants to alleviate diabetes or its side effects. But, using one plant for long term, may be not so effective. Here, we attempted to find whether two plants from two different species can show more efficacy than each one alone. We noticed garlic and Citrullus colocynthis despite having beneficial effects when used alone, they could show synergistic effects in combination.

Protective properties of Rydingia persica in reproductive complications induced by diabetes in male rats: An experimental study.

Background: In Iranian traditional medicine, Rydingia persica (R.P) is commonly used to treat diabetes mellitus (DM). Objective: We assessed the protective effects of R.P against testis and epididymis oxidative stress and the hormonal changes induced by DM. Materials and Methods: Forty male Wistar rats (12 wk old) weighing 230-270 gr were divided into five groups (n = 8/each): 1. Control (C); 2. diabetic (D); 3. diabetic + R.P200 (D+R200); 4. diabetic + R.P400 (D+R400); and 5. diabetic + R.P600 (D+R600). Groups C and D received 2 ml of normal saline orally daily for two wk and groups D+R200, D+R400, and D+R600 received 200, 400, and 600 mg/kg body weight of R.P powder, respectively, orally daily for two wk. DM was induced by a single intraperitoneal injection of streptozotocin at 60 mg/kg body weight. We assessed malondialdehyde, glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase, hydrogen peroxide, and glutathione in both the testis and epididymis and also the histological changes of the testis. Results: Diabetic rats showed a significantly increased and decreased level of oxidant and antioxidant factors, respectively, and a significantly lower level of serum testosterone and luteinizing hormone than the control group. In the histological study of the testis, deteriorations were observed. Treatment with R.P reversed these changes toward the state of the control group with the highest effectiveness shown by group D+R600. Conclusion: The data obtained suggest that R.P powder has antioxidant effects on testis and epididymis tissues in diabetic rats and that it improves histological testicular structure in diabetics. It can also correct testosterone and luteinizing hormone changes induced by DM.

Additive effects of acupuncture in alleviating anxiety: A double-blind, three-arm, randomized clinical trial.

BACKGROUND: In this trial, additive effects of acupuncture to selective serotonin reuptake inhibitors (SSRIs) treatment for reducing anxiety, were investigated. METHODS: 112 patients with anxiety disorder were randomly divided into three groups including SSRIs alone (drug group), SSRIs with sham acupuncture (control group) and SSRI with acupuncture (acupuncture group), and treated for 4 weeks. At the beginning of the study and on day 28, Spielberger State-Trait Anxiety Inventory (STAI) questionnaire was completed and serum levels of cortisol were measured. RESULTS: 105 patients completed the treatment period. STAI score showed significant differences among the three groups at the end of the study; importantly, changes in STAI score in the acupuncture group were significantly larger than the other groups. A decrease in cortisol levels was observed in all groups; though statistically non-significant, this decrease in the acupuncture group was larger. CONCLUSION: Acupuncture combined with SSRIs can significantly improve anxiety state compared to anti-anxiety therapy using SSRIs alone.

Preventive effect of garlic juice on renal reperfusion injury.

INTRODUCTION: Renal reperfusion injury is associated with increased mortality and morbidity due to acute kidney failure. Oxidative stress induced with renal reperfusion affects glomeruli and tubular epithelium through reactive oxygen species; therefore, the use of medicinal plants appears rational for improvement of reperfusion effects. The aim of present study was to examine the preventive effect of garlic juice (Allium sativum) on renal reperfusion injury in rats. MATERIALS AND METHODS: A total of 30 male Wistar rats were divided into 5 groups: control, garlic, sham (right nephrectomy), reperfusion, and reperfusion + garlic groups. After right nephrectomy, renal ischemia and reperfusion were induced. At the end of the experiment, all rats were killed and kidney function tests and histopathological examination were performed. Results. Reperfusion increased serum urea and fractional excretion of sodium levels, while it decreased urine potassium levels and creatinine clearance. However, garlic juice significantly decreased serum urea levels in the reperfusion + garlic group compared with the reperfusion group (P < .001). Preteatment with garlic juice also resulted in significant increase in urine potassium (P = .03) compared to reperfusion. Fractional excretion of sodium and creatinine clearance were also improved. On histological examination, rats pretreated with garlic juice had nearly normal morphology. CONCLUSIONS: The results of this study showed that garlic juice significantly prevented renal reperfusion-induced functional and histological injuries.