Hydroalcoholic extract of Scrophularia striata has a significant therapeutic effect on thioacetamide-induced liver cirrhosis in rats.

OBJECTIVES: Liver cirrhosis is one of the most important causes of death from liver diseases. Nowadays, the use of herbal medicines has increased due to its availability, less side effects and cheapness for the treatment of liver diseases. The present study was conducted to examine therapeutic effects of hydroalcoholic extract of Scrophularia striata (S. striata) on thioacetamide-induced liver cirrhosis in rats through evaluate its effects on oxidative stress markers and the expression of metalloproteinase 1 (TIMP 1), toll-like receptor-4 (TLR-4), and Mitofusin (MFN2) genes. METHODS: 24 male rats were selected by simple random sampling. Rats were randomly assigned to four groups: group I: healthy rats, group II: thioacetamide (TAA) injected rats, group III: TAA injected rats+100 mg/kg bw of S. striata and group IV: TAA injected rats+200 mg/kg bw of S. striata. Liver cirrhosis was induced in rats by a 300 mg/kg bw TAA administration twice with an interval of 24 h. After 8 weeks of treatment by S. striata at doses of 100 and 200 mg/kg bw, biochemical factors and oxidative stress markers (SOD, TAC, GPX, CAT and MDA) were measured using spectrophotometric methods. Also, gene expression of TIMP 1, TLR-4, and MFN2 were analyzed using real-time PCR. ANOVA and Bonferroni post hoc test analysis were applied to evaluate the data. RESULTS: The results showed the S. striata extract significantly improve the serum ALT, AST and ALP levels, TIMP 1, TLR-4, and MFN2 genes and oxidative stress markers (SOD, TAC, GPX, CAT and MDA) in the liver tissues when compared to control group (p<0.05). Also, it was found that the beneficial effects of the S. striata were dose-dependent. CONCLUSIONS: Based on the results obtained S. striata by reducing the expression of TIMP 1, TLR-4, and MFN2 genes and improving oxidative stress might be used as adjuvant treatment for liver cirrhosis.

Protective effects of paraoxonase-1, vitamin E and selenium, and oxidative stress index on the susceptibility of low density lipoprotein to oxidation in diabetic patients with/without coronary artery disease.

BACKGROUND: The oxidative modification of low density lipoprotein (LDL) is closely associated with an increased risk for coronary artery disease (CAD) in diabetic patients. The purpose of this study is to investigate the relation between serum vitamin E and selenium, paraoxonase-1 (PON1) activity, total antioxidant capacity (TAC), total oxidant status (TOS), malondialdehyde (MDA), and oxidative stress index (OSI) values with the susceptibility of LDL to oxidative modification and the possibility of CAD in diabetic patients. METHOD: This study was designed as a case control survey of 82 diabetes patients divided into two groups including T2DM alone (as group I) and both T2DM and CAD (as group II). Fasting blood samples were taken to the assay of fasting blood glucose (FBG), HbA1c, total cholesterol (TC), TAC, TOS, MDA, OSI, vitamin E, selenium, oxidized low density lipoprotein (Ox-LDL), and activity of PON1. RESULTS: Ox-LDL, MDA, TOS, and OSI values in groups II were significantly higher compared with group I (all with P value = 0.000). TAC, vitamin E, selenium, and PON1 activity values were significantly lower in group II compared with groups I (P value = 0.000; P value = 0.000; P value = 0.007; P value = 0.003, respectively). There were significant relationships between the amounts of TAC, TOS, OSI, and vitamin E with the amounts of PON1 activity and Ox-LDL (p < 0.05). But Ox-LDL and PON1 activity correlated weakly with together (p = 0.094). CONCLUSION: Results of this study support the belief that oxidative stress might be an important etiologic factor which makes some diabetics more susceptible to CAD. Increased oxidative stress may be a potential therapeutic target in the prevention and management of CAD in diabetic patients.

Amelioration of STZ-induced nephropathy in diabetic rats by saffron hydro alcoholic extract.

OBJECTIVES: Type 1 diabetes is one of the most important causes of microvascular complications such as nephropathy. On other hand, the use of herbal medicines is more affordable and has fewer side effects. Therefore, this study was conducted to assessment the therapeutic effect of saffron in diabetic nephropathy by regulating the expression of CTGF and RAGE genes as well as oxidative stress in rats with type 1 diabetes. METHODS: In this study, we used 24 Wistar rats in four groups. To induce diabetes, we used a 55 mg/kg.bw dose of streptozotocin intraperitoneally. Type 1 diabetic rats were administered saffron (20 and 40 mg/kg/day) by gavage once daily for 42 days. Finally, serum urea, creatinine, albumin and SOD, MDA levels in kidney tissue were measured using spectrophotometric methods and CTGF and RAGE gene expression in kidney tissue was measured using real-time PCR method. RESULTS: Diabetes significantly increases serum FBG, urea, creatinine and decreases albumin (p<0.001). AS well as increased the CTGF and RAGE genes expression, MDA level and decreased the SOD activity in the kidney tissue (p<0.001). Serum urea, creatinine, albumin was significantly ameliorated by saffron (p<0.001). It was shown the saffron significantly decrease the kidney expression CTGF and RAGE genes and MDA level and increased the SOD activity (p<0.001). Also, it was found that the beneficial effects of the saffron were dose-dependent (p<0.05). CONCLUSIONS: The results of this study suggest that saffron as an adjunct therapy may prevent development and treatment of diabetic nephropathy by regulating the expression of the CTGF and RAGE genes and oxidative stress.

Piroxicam reduces acute and chronic pain response in type 1 diabetic rats.

OBJECTIVES: Pain associated with various underlying pathologies is a major cause of morbidity and diminished life quality in diabetic patients. Effective control of pain requires the use of analgesics with the best efficacy and with minimal side effects. Therefore, our aim in this study was to investigate the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on pain in diabetic rats. METHODS: In this study, we investigated the analgesic effects of drugs belonging to three different classes of NSAIDs in a rat model of diabetes. Four diabetic groups received normal saline, diclofenac, piroxicam and ketorolac, respectively, and four non-diabetic groups received normal saline, diclofenac, piroxicam and ketorolac. Type 1 diabetes was induced in rats by a single injection of streptozotocin (60 mg/kg bw). Formalin (50 µL of 2.5%) nociception assay was used to examine the effect of treatment with diclofenac, piroxicam and ketorolac on acute and chronic pain in healthy and diabetic rats. RESULTS: Piroxicam showed significant analgesic effects both in the acute phase of pain (5-10 min after injection of formalin into the left hind paw), and in the chronic phase (20-60 min after formalin injection) in healthy as well as diabetic rats. Diclofenac and ketorolac also reduced pain scores in healthy rats. However, these two drugs failed to diminish pain in diabetic rats. CONCLUSION: Our data point for better efficacy of piroxicam in controlling pain in diabetes.

Effect of Artemisia absinthium ethanolic extract on oxidative stress markers and the TLR4, S100A4, Bax and Bcl-2 genes expression in the kidney of STZ-induced diabetic rats.

OBJECTIVES: The present study was conducted to examine antidiabetic effects of Artemisia absinthium ethanolic extract [A. absinthium] and to investigate its effects on oxidative stress markers and the expression of TLR4, S100A4, Bax and Bcl-2 genes in the kidney of STZ-induced diabetic rats. METHODS: Thirty six rats (weight 200-250 g) were randomly divided into diabetes and control groups. Induction of diabetes was performed using STZ (55 mg/kg.bw). Biochemical parameters and oxidative stress markers (SOD and MDA) were measured using spectrophotometry after 60 days of treatment. The expression of TLR4, S100A4, Bax and Bcl-2 were analyzed by real-time PCR. One-way analysis of variance (ANOVA) and Bonferroni post hoc test were used to compare the data. RESULTS: Diabetes significantly impairs the serum fasting blood glucose (FBG), lipid profile, urea, creatinine and albumin. At the end of treatment with A. absinthium extract, these parameters were close to the normal range. The results showed that the A. absinthium extract significantly decreased the kidney expression of TLR4, S100A4, Bax and increased the expression of Bcl-2 and improved oxidative stress markers (SOD and MDA) in the kidney tissues of treated rats. Also, all of these beneficial effects of the A. absinthium were dose-dependent. CONCLUSIONS: The extract of A. absinthium possesses antidiabetic effects. A. absinthium decreased the expression of TLR4, S100A4, Bax and increased the expression of Bcl-2 and improved oxidative stress. Therefore, this herbal extract can be used as an adjuvant treatment for diabetic complications.

Improving the endothelial dysfunction in type 2 diabetes with chromium and vitamin D3 byreducing homocysteine and oxidative stress: A randomized placebo-controlled trial.

BACKGROUND: Chromium picolinate (CrPic) and vitamin D3 are known as two antioxidant micronutrients. Through inducing endothelial dysfunction, oxidants such as homocysteine (Hct) and malondialdehyde (MDA) lead to cardiovascular disease in type 2 diabetes mellitus (T2DM). No published data has directly examined the effects of these two antioxidants on improving the endothelial dysfunction in T2DM throughreducing homocysteine and oxidative stress. METHODS: Subjects (n = 92) in this randomized, double blind, placebo-control study were randomly assigned to receive oral placebo (group I), D3 (group II: 50,000 IU/ week), chromium picolinate (CrPic) (group III: 500 µg/day), and both vitamin D3 and CrPic (group IV) for four months. Fasting blood samples were drawn at study baseline and following intervention to determine Hct, MDA, total antioxidant capacity (TAC), total thiol groups (SHs), vascular cell adhesion molecule- 1 (VCAM-1), and plasminogen activator inhibitor-1 (PAI-1). RESULTS: After intervention, MDA significantly decreased in groups II and IV; TAC significantly increased in group IV, and SHs significantly augmented in group III; Hct was significantly reduced in groups II, III, and IV; and VCAM-1 significantly decreased in groups III and IV and PAI-1 was significantly reduced in groups II, III, and IV. CONCLUSION: Our findings suggest that through reducing homocysteine and oxidative stress and improving endothelial dysfunction, chromium and vitamin D3 co-supplementation might be predictive and preventive of cardiovascular diseasesassociated with T2DM. IRCT, IRCT20190610043852N1, registered 21 October 2019, https://fa.irct.ir/user/trial/42293/view.

The effect of novel simple saffron syrup on fatigue reduction in patients with multiple sclerosis.

Objectives Multiple sclerosis (MS) is a progressive and often debilitating neurological disorder. This chronic disease has a high prevalence in the world and also in Iran. Fatigue is a common symptom of the disease, which causes serious mental and psychological discomfort. Simple saffron syrup, contains some compounds that can be effective in relieving the symptom. The object of this study is to investigate the effect of simple saffron syrup on fatigue in patients with MS. Methods This study is a pre-post study which evaluates the fatigue rate of MS patients (30 participants) according to the FSS scale. The participants were given a saffron simple syrup to consume a tablespoon (7.5 cc) every 8 h for two months. After 60 days of prescribing, patients are assessed for fatigue based on fatigue severity scale (FSS) criteria. Results One-way ANOVA showed that there was a notable difference between the mean score of fatigue in MS patients before and after the intervention (p<0.001). So, the fatigue severity of the subjects after saffron syrup consumption dropped dramatically for two months. (p<00.01). Conclusions According to the outcomes of this study, simple saffron syrup can be effective as an adjunct therapy for fatigue reduction in patients with MS due to effectiveness besides no significant side effects.

The effect of silymarin on liver enzymes in patients taking isotretinoin: A randomized clinical trial.

The aim of the present study was to investigate the effect of silymarin (Livergol) on liver enzymes in patients taking isotretinoin (Roaccutane). In this double-blind clinical trial, 74 patients with acne and taking isotretinoin were randomly assigned into intervention (N = 37) and control (N = 37) groups. The intervention group received a 140 mg Livergol capsule per day for 30 days. The control group received a starch-containing capsule as a placebo once a day for 30 days. Liver enzyme levels were measured before and after the intervention. The data were analyzed using chi-square test, Independent t test, paired sample t test and analysis of covariance (ANCOVA). The results showed no statistically significant difference between the intervention and control groups at the beginning of study in levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) (p > .05). At the end of the study, a statistically significant difference was observed between the two groups in levels of AST and ALT (p < .05). Livergol prevented liver enzymes from increasing, so it can be used as an effective, low-cost, and low-complication treatment for the problem of increased levels of liver enzymes following the use of isotretinoin.

Protective Effects of Pomegranate Juice on Nephrotoxicity Induced by Captopril and Gentamicin in Rats.

INTRODUCTION: Nephrotoxicity is an important side effects of captopril and gentamicin. This study investigated the prophylactic and protective effects of pomegranate juice (PJ) on the kidney exposed to nephrotoxicity induced by these medications. MATERIALS AND METHODS: Wistar male rats received drinking water (groups 1 to 3) or PJ at doses of 4 mL/kg (group 4), 10 mL/kg (groups 5 and 7), and 15 mL/kg (group 6) for 14 days. Captopril and gentamicin were administrated on days 10 and 14 to groups 1 and 2, respectively, while groups 3 to 6 received both. Group 7 did not receive anything. The serum, urine, and renal tissue parameters were measured after the experiment. RESULTS: Group 1 (captopril) had a higher malondialdehyde level than groups 4, 5, 6, and 7 with PJ (P <0.05), and group 3 (captopril and gentamicin) showed the most significant malondialdehyde level compared to other groups (P < .001). Group 5 (captopril, gentamicin, and PJ, 10 mL/kg) had the most significant sodium excretion compared to other groups (P < .001), and group 2 (gentamicin) showed the highest potassium absolute excretion (P < .001). The instability of the renal index was observed during the experiment for the groups receiving drinking water, while no significant changes were observed in the groups receiving PJ. CONCLUSIONS: The prophylactic consumption of PJ for 14 days could show nephroprotective effects by reducing oxidative stress and potassium depletion. It could also lead to the stabilization of kidney function during this period despite using captopril and gentamicin.

Relationship of Dopamine of the Nucleus Accumbens with Intra-infralimbic Apomorphine Microinjection.

OBJECTIVE(S): The dopamine level of the nucleus accumbens changes during some stereotyped behaviors. To study dopamine level of the nucleus accumbens in intra infralimbic apomorphine-induced climbing, microdialysis probes were implanted into the nucleus accumbens shell of male Sprague Dawley rats weighting 275-400 g. MATERIALS AND METHODS: The rats were divided into two groups (apomorphine and control) of least eleven rats in each group. Apomorphine at dose of 5 µg/0.5 µl or its vehicle was microinjected into the infralimbic in apomorphine and control groups respectively. Then, changes in dopamine levels in the nucleus accumbens shell were monitored. The concentration of dopamine was measured by High-Performance Liquid Chromatography-Electochemical (HPLC-ECD). Finally, the stereotyped behaviors were recorded. RESULTS: The mean of dopamine levels for all of after microinjection period in control and drug groups were 450% and 150% respectively compared to those of before microinjection period. However, there was no significant difference between groups of apomorphine and control. In addition, the return of dopamine level to the baseline was faster in apomorphine group than the control group. CONCLUSION: The intra infralimbic apomorphine -induced climbing at dose of 5 µg/0.5 µl was not modulated via the increase of dopamine level in the nucleus accumbens area.

Beneficial Effects of Rosmarinus Officinalis for Treatment of Opium Withdrawal Syndrome during Addiction Treatment Programs: A Clinical Trial.

BACKGROUND: Withdrawal syndrome may influence patient's motivation for participation in addiction treatment programs. Management of the symptoms can improve the success rate of addiction treatment programs. In the present study, we have evaluated the efficiency of an herbal product as adjunct therapy for alleviation of withdrawal syndrome in opium abuse. METHODS: In the present clinical trial, 81 patients were assigned into case and control groups. The control group was treated with methadone and placebo for 4 weeks. The case group was treated with methadone and powdered dried leaves of Rosmarinus officinalis for the same interval. Occurrence of withdrawal syndrome was compared between groups on days 3, 7, and 14 after beginning of the treatment, and the possible signs and symptoms of withdrawal syndrome were checked. The clinical opioid withdrawal scale (COWS) was used for evaluation of withdrawal syndrome in the patients. FINDINGS: Patients in the case group experienced less severe withdrawal syndrome compared to those in the control group; chiefly bone pain, perspiration, and insomnia. CONCLUSION: The present study showed that rosemary can be used as an optional extra drug for treatment of withdrawal syndrome during treatment programs for opium addiction and possibly addiction to other opioids.