Protective effects of berberine as a natural antioxidant and anti-inflammatory agent against nephrotoxicity induced by cyclophosphamide in mice.

PURPOSE: Cyclophosphamide is an alkylating agent with nephrotoxicity that constrains its clinical application. Berberine is an isoquinoline derivative alkaloid with biological functions like antioxidant and anti-inflammatory. The current research intended to examine the nephroprotective impacts of berberine against cyclophosphamide-stimulated nephrotoxicity. METHODS: Forty animal subjects were randomly separated into five categories of control (Group I), cyclophosphamide (200 mg/kg, i.p., on 7th day) (Group II), and groups III and IV that received berberine 50 and 100 mg/kg orally for seven days and a single injection of cyclophosphamide on 7th day. Group V as berberine (100 mg/kg, alone). On day 8, blood samples were drawn from the retro-orbital sinus to determine serum levels of blood urea nitrogen (BUN), creatinine (Cr), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) as biomarkers for kidney injury. Nitric oxide (NO), malondialdehyde (MDA) and glutathione (GSH) levels, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) activities as oxidative stress factors, tumor necrosis factor-α (TNF-α) and interleukin 1 beta (IL-1ß) levels as inflammatory mediators were assessed in kidney tissue. RESULTS: The results of this study demonstrated that berberine was able to protect remarkably the kidney from CP-induced injury through decreasing the level of BUN, Cr, NGAL, KIM-1, NO, MDA TNF-α, IL-1ß and increasing the level of GSH, CAT, SOD, and GPx activities. CONCLUSION: Berberine may be employed as a natural agent to prevent cyclophosphamide-induced nephrotoxicity through anti-oxidant and anti-inflammatory effects.

Chrysin attenuates sodium arsenite-induced nephrotoxicity in rats by suppressing oxidative stress and inflammation.

BACKGROUND: We aimed to study the beneficial property of chrysin (CHR) by targeting its antioxidant and anti-inflammatory effects on nephrotoxicity induced by sodium arsenite (SA). MATERIALS & METHODS: We have used the 35 male Wistar rats in five equal groups (n = 7). Normal saline in (5 ml/kg; p.o.; 21 days) was given to the control group. Sodium arsenite (10 mg/kg; p.o.; 14 days) was given to the SA group. CHR (25, 50 and 100 mg/kg; p.o.; 21 days) and SA (10 mg/kg; p.o.; 14 days from the 7th day of the experiment) was given to the SA + CHR 25, 50 and 100 groups. On the 22nd day of the experiment, the animals' bloods and kidneys were taken, and then we have performed functional, biochemical and histological assessment. RESULTS: CHR pre- and alongside administration (more potently at dose of 100 mg/kg) with SA reduced the SA-induced alterations in serum creatinine and blood urine nitrogen levels. Increased levels of protein carbonyl, myeloperoxidase, malondialdehyde and nitric oxide in kidney tissue were decreased by CHR treatment. CHR administration increased the levels of glutathione and activities of glutathione peroxidase, catalase and superoxide dismutase in renal tissue. Moreover, treatment with CHR reduced the levels of inflammatory mediators including interleukin 1 beta and tumor necrosis factor alpha in renal tissue. The renal histological lesions induced SA were mitigated by CHR treatment in dose dependent manner. CONCLUSION: The results of present study suggested that administration of CHR before and alongside with SA attenuated the renal toxic effects of SA via antioxidative stress and anti-inflammatory effects.

Zingerone Mitigates Carrageenan-Induced Inflammation Through Antioxidant and Anti-inflammatory Activities.

Inflammation is the body's response against various pathogens and has a critical role in numerous diseases. Zingerone (Zing), a bioactive substance derived from ginger root, has a variety of pharmacological properties, such as reducing inflammation, and antioxidant effects. We aimed to evaluate the beneficial effects of Zing in a carrageenan-induced inflammation model. Paw edema induced by carrageenan (100 µl of 1%) was used to induce acute inflammation in rats. Different doses of Zing (10, 20, and 40 mg/kg) were administered intraperitoneally. Paw tissue levels of MDA, NO, CAT, SOD, GPx, GSH, COX-2, PGE2, TNF-α, and IL-1ß were estimated. Our results showed that Zing, especially at the highest dose of 40 mg/kg, significantly reduced paw swelling in carrageenan-injected animals. Zing significantly increased paw enzymatic and nonenzymatic antioxidants except CAT. It also decreased paw levels of MDA, NO, COX-2, PGE2, TNF-α, and IL-1ß. The results of this study show that Zing may provide an alternative for the clinical control of inflammation through antioxidant and anti-inflammatory activities.

Attenuation of Bleomycin-Induced Pulmonary Fibrosis in Wistar Rats by Combination Treatment of Two Natural Phenolic Compounds: Quercetin and Gallic Acid.

The present study aimed to investigate the protective effects of two potent natural antioxidants, gallic acid and quercetin as single or combination treatment against bleomycin-induced pulmonary fibrosis (PF). A total of 50 Wistar rats were randomly divided into 5 groups. Group 1 and 2 intratracheally received saline and bleomycin (7.5 UI/kg), respectively, on day 7, accompanied by oral saline administration for 28 day. Groups 3, 4, and 5 received a single dose of bleomycin on day 7, accompanied by oral administration of gallic acid, quercetin, and their combination, respectively, for 28 day. Finally, the lungs were removed for biochemical and histopathological tests. The combination treatment demonstrated a remarkable decrease in lung hydroxyproline and TNF-α level and increase in catalase activity as compared with both single phytochemical-treated groups. The combination treatment significantly enhanced lung SOD activity and GSH level and decreased NO and IL-6 levels as compared with quercetin-treated group. However, only combination treatment could decrease the lung index and completely reversed histopathological changes in the bleomycin-treated group. In sum, when compared to a single exposure, the combination treatment might be a more effective approach for PF treatment because of its superior efficacy in reversing lung histological changes in the bleomycin-treated group.

Mechanisms involved in the possible protective effect of chrysin against sodium arsenite-induced liver toxicity in rats.

Arsenic as a one of the most important toxic metals could induce hepatotoxicity. Previous reports revealed the significance of oxidative stress in promoting of arsenic-induced liver toxicity. The aim of the present investigation is to evaluate the effect of chrysin (CHR), a natural flavonoid with potent antioxidant activity, against sodium arsenite (SA)-induced hepatotoxicity. Thirty male Wistar rats were divided into four groups: Group 1: received normal saline (2 ml/kg/day, orally for 21 days), Group 2: received SA (10 mg/kg/day, orally for 14 days), Group 3, 4 and 5: received CHR (25, 50 and 100 mg/kg/day, respectively, orally for 21 days) and SA (10 mg/kg/day, orally for 14 days) from the 7th day. Serum levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase were evaluated. Moreover, liver glutathione peroxidase and myeloperoxidase activity as well as levels of protein carbonylation, malondialdehyde, glutathione, catalase, nitric oxide, superoxide dismutase, tumor necrosis factor-α and interleukin-1ß were evaluated. Moreover, histological evaluation was done. Our results revealed that treatment with CHR (more potentially at the dose of 100 mg/kg/day) before and alongside with SA significantly mitigated the SA-induced hepatotoxicity. Also, the hepatoprotective effect of CHR was verified by the histological evaluation of the liver. The results of current study demonstrated that CHR (100 mg/kg/day) could mitigate the oxidative stress and inflammation induced by SA in liver tissue.

Crocin: a protective natural antioxidant against pulmonary fibrosis induced by bleomycin.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic and fibrotic lung disease of unknown causes. Given the crucial role of oxidative stress in the progression of IPF, antioxidant therapy may be speculated to be an efficient therapeutic approach. Therefore, the present study aimed to evaluate the protective effects of Crocin as a potent, natural antioxidant against Bleomycin-induced PF in male Wistar rats. METHODS: Forty male Wistar rats were randomly divided into four groups. Group 1 received intratracheal saline on day 7 and oral gavage of saline for 28 days. Group 2 received a single dose of Bleomycin on day 7 and oral gavage of saline for 28 days. Groups 3 received a single dose of Bleomycin on day 7, accompanied with oral administration of Crocin for 28 days. Group 4 orally received Crocin for 28 days. Finally, the lungs were removed for measuring the biochemical and histopathological markers. RESULTS: The results showed that Crocin therapy remarkably decreased TNF-α, MDA and NO levels in the lungs of Bleomycin-exposed rats. Furthermore, a significant increase was seen in lung GSH content, catalase, and GPx activities in the Crocin/Bleomycin-treated group as compared with Bleomycin-treated group. However, Crocin could not markedly change the lung index and SOD activity. Histopathological changes, fibrosis and hydroxyproline content of lungs also significantly decreased by Crocin therapy in the Crocin/Bleomycin-treated group. CONCLUSION: In sum, Crocin therapy could modulate biochemical and histological changes induced by Bleomycin; therefore, it might be considered as an effective therapeutic approach against IPF.

A Double-Blind, Placebo-Controlled Study of the Aqueous Extract of Echium amoenum for Patients with General Anxiety Disorder.

The aim of this study was to assess the efficacy and tolerability of the aqueous extract of Echium amoenum in combination with SSRIs in patients with General Anxiety Disorder (GAD). The study was an 8-week double-blind randomized clinical trial. Thirty-seven adult outpatients who met the DSM-IV-TR criteria for GAD based on the structured clinical interview participated in the trial. In this study, patients were randomly assigned to receive the aqueous extract (500 mg) plus fluoxetine or fluoxetine (20 mg/day) plus placebo. The results showed significant difference between the two groups in the treatment of GAD. Moreover, there was not any significant difference between the two groups in terms of observed side effects. E. amoenum is effective on anxiety disorder, especially in higher dosage, without any serious side effects.