An Ethanolic Extract of Cucurbita pepo L. Seeds Modifies Neuroendocrine Disruption in Chronic Stressed Rats and Adrenal Expression of Inflammatory Markers and HSP70.

Background: Pumpkins (Cucurbita pepo L.) were described to have antioxidant, anti-inflammatory, anti-fatigue, and antidepressant-like effect. The adrenal gland is an important stress-responsive organ that maintains homeostasis during stress. Objectives: This study aimed to assess the efficacy of the administration of Cucurbita pepo L. (CP) extract in relieving behavioral, biochemical, and structural changes in the adrenal gland induced by exposure to chronic unpredictable mild stress (CUMS) and to explore the mechanism behind this impact. Materials and Methods: Forty male albino rats were divided into 4 groups (n = 10): control, CUMS, fluoxetine-treated, and CP-treated groups. Behavioral changes, corticosterone level, pro-inflammatory cytokines TNF-α and IL-6, and oxidant/antioxidant profile were assessed in the serum at the end of the experiment. Adrenal glands were processed for histopathological and immunohistochemical assessment. Gene expression of caspase-3 and Ki67 and heat shock protein 70 (HSP70) were assessed in adrenal glands using RT-PCR. Results: The CP extract significantly reduced the corticosterone level (p < 0.001), immobility time (p < 0.001), and inflammatory and oxidative changes associated with CUMS-induced depression compared to the untreated group. The CP extract alleviated CUMS-induced adrenal histopathological changes and significantly reduced apoptosis (p < 0.001) and significantly upregulated antioxidant levels in the serum. Conclusion: Cucurbita pepo L. effectively ameliorated the chronic stress-induced behavioral, biochemical, and adrenal structural changes mostly through its antioxidant and anti-inflammatory effects.

Synergistic Anti-inflammatory and Neuroprotective Effects of Cinnamomum cassia and Zingiber officinale Alleviate Diabetes-Induced Hippocampal Changes in Male Albino Rats: Structural and Molecular Evidence.

Background: Depression has been reported as a common comorbidity in diabetes mellitus although the underlying mechanism responsible for this is not well known. Although both ginger and cinnamon has anti-diabetic, antioxidant, and neuroprotective properties, their efficacy in inhibiting neuroinflammation, when simultaneously administrated, has not been investigated yet. Objectives: The study was designed to assess the synergistic effect of Cinnamomum cassia and Zingiber officinale on regulating blood glucose, improve hippocampal structural changes and depressive-like alternations in diabetic rats, and try to identify the mechanism behind this effect. Materials and Methods: Thirty male Sprague-Dawley rats were divided into five equal groups (n = 6): the normal control, untreated streptozotocin (STZ)-diabetic, cinnamon-treated diabetic [100 mg/kg of body weight (BW)/day for 6 weeks], ginger-treated diabetic (0.5 g/kg BW/day for 6 weeks), and ginger plus cinnamon-treated diabetic groups. Forced swim test and elevated plus maze behavioral tests were performed at the end of the experiment. HOMA-IR, HOMA ß-cells, blood glucose, insulin, corticosterone, pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and IL-6), and total anti-oxidant capacity (TAC) were assessed in the serum. BDNF mRNA level was assessed in hippocampus using qRT-PCR. Hippocampal histopathological changes were also assessed, and immunoexpression of glial fibrillary acidic protein (GFAP), caspase-3, and Ki-67 was measured. Results: Diabetes-induced depressive-like changes in the STZ group were biochemically confirmed by assessing serum corticosterone level, as well as behaviorally using FST and EPM tests. Diabetes also induced degenerative changes in the hippocampus. Treatment of diabetic rats with ginger, cinnamon, or the combination of these alleviated the degenerative structural changes and significantly up-regulated serum insulin, TAC, hippocampal BDNF mRNA, and hippocampal immunoexpression of ki67, while they significantly reduced serum blood glucose, IL-6, TNF-α, IL1ß, as well as hippocampal immunoexpression of GFAP and Caspase-3 compared to the untreated diabetic group. Improvement induced by the combination of ginger and cinnamon was superior to the single administration of either of these. Conclusion: Cinnamomum cassia and Zingiber officinale have synergistic anti-diabetic, antioxidant, anti-inflammatory, antidepressant-like, and neuroprotective effects. The use of a combination of these plants could be beneficial as alternative or complementary supplements in managing DM and decreasing its neuronal and psychiatric complications.

Combined Oral and Topical Application of Pumpkin (Cucurbita pepo L.) Alleviates Contact Dermatitis Associated With Depression Through Downregulation Pro-Inflammatory Cytokines.

Background: Depression and contact dermatitis (CD) are considered relatively common health problems that are linked with psychological stress. The antioxidant, anti-inflammatory, and antidepressant activities of pumpkin were previously reported. Objectives: This study aimed to evaluate the efficacy of the combined topical and oral application of pumpkin fruit (Cucurbita pepo L.) extract (PE) in relieving CD associated with chronic stress-induced depression and compare it to the topical pumpkin extract alone and to the standard treatment. Materials and Methods: Forty male albino rats were exposed to chronic unpredictable mild stress (CUMS) for 4 weeks for induction of depression and then exposed to (1-fluoro-2, 4-dinitrofluorobenzene, DNFB) for 2 weeks for induction of CD. Those rats were assigned into 4 groups (n = 10 each); untreated, betamethasone-treated, PE-treated and pumpkin extract cream, and oral-treated groups. Treatments were continued for 2 weeks. All groups were compared to the negative control group (n = 10). Depression was behaviorally and biochemically confirmed. Serum and mRNA levels of pro-inflammatory cytokines, such as TNF-α, IL-6, COX-2, and iNOS, were assessed. Oxidant/antioxidant profile was assessed in the serum and skin. Histopathological and immunohistochemical assessments of affected skin samples were performed. Results: Pumpkin extract, used in this study, included a large amount of oleic acid (about 56%). The combined topical and oral administration of PE significantly reduced inflammatory and oxidative changes induced by CD and depression compared to the CD standard treatment and to the topical PE alone. PE significantly alleviated CD signs and the histopathological score (p < 0.001) mostly through the downregulation of pro-inflammatory cytokines and the upregulation of antioxidants. Conclusion: Pumpkin extract, applied topically and orally, could be an alternative and/or complementary approach for treating contact dermatitis associated with depression. Further studies on volunteer patients of contact dermatitis are recommended.

Thymoquinone Upregulates Catalase Gene Expression and Preserves the Structure of the Renal Cortex of Propylthiouracil-Induced Hypothyroid Rats.

BACKGROUND: The association between hypothyroidism and renal diseases has been described in many studies. Nigella Sativa was among the recently reported natural product that has the potential to prevent renal tissue damage and fibrosis. The aim of this study was to evaluate the possible protective effect of thymoquinone on the structure of the renal cortex of hypothyroid rats and explore the mechanism behind it. METHODS: An experimental model of hypothyroidism was induced in adult male Wistar rats by administration of propylthiouracil (6 mg/kg/body weight). One hypothyroid group was treated with thymoquinone at the dose of 50 mg/kg/body weight and compared to the untreated group. Thyroid function and oxidant/antioxidant status were assessed in the serum. Catalase gene expression was assessed using the real-time polymerase chain reaction. The kidney was assessed both histologically and immunohistochemically. RESULTS: Administration of propylthiouracil resulted in a significant decrease in the serum levels of nitric oxide, reduced glutathione, and superoxide dismutase activity while the level of malondialdehyde significantly (p < 0.001) increased. Administration of thymoquinone alleviated this effect on the thyroid hormones and significantly increased the serum levels of antioxidants. Thymoquinone significantly (p < 0.001) upregulated catalase transcription by about 24-fold and could block the hypothyroidism-induced glomerular and tubular injury. CONCLUSION: Thymoquinone may have a potential protective effect against hypothyroidism-induced renal injury acting through the attenuation of the oxidative stress and upregulation of renal catalase gene expression.

Assessment of the Protective Effect of Lepidium sativum against Aluminum-Induced Liver and Kidney Effects in Albino Rat.

BACKGROUND AND OBJECTIVES: Environmental pollution with the different Aluminum (Al) containing compounds has been increased. Liver and kidney are two vital organs targeted by Al accumulation. The aim of this study was to assess the possible protective and curative effects of Lepidium sativum Linn (LS) against Al-induced impairment of liver and kidney in albino rat and to explore the mechanism behind this effect. MATERIALS AND METHODS: This experimental animal-based study included fifty albino rats divided into five groups, the control, LS-treated (20 mg/kg), AlCl3-treated (10 mg/kg), AlCl3 then LS, and AlCl3 plus LS-treated, simultaneously for 8 weeks. At the end of the experiment, hepatic and renal functions as well as the biomarkers of antioxidants activities were assessed in the serum. Both liver and kidney were dissected out and histopathologically examined. RESULTS: This study showed that administration of AlCl3 caused a significant (p<0.05) reduction in rats body weight. It significantly increased serum AST, ALT, ALP, bilirubin, urea, and creatinine levels and decreased total protein and albumin. AlCl3 significantly reduced enzymatic (catalase), nonenzymatic (reduced glutathione), and ferric reducing antioxidant power (FRAP) in the serum. Histopathologically, it induced necrosis and degeneration of hepatocytes, glomeruli, and renal tubules. Administration of LS after or along with AlCl3 significantly restored the serum biomarkers of liver and kidney functions to their near-normal levels and had the ability to overcome Al-induced oxidative stress and preserved, to some extent, the normal hepatic and renal structure. The coadministration of LS had a superior effect in alleviating Al-induced changes. CONCLUSION: Exposure to AlCl3 induced a set of functional and structural changes in the liver and kidney of rats evident through both biochemical and histopathological assessment. The antioxidant activity of LS seeds mediated a protective and curative effect of LS against such changes. Further study through a rigorous clinical trial to prove LS activity on human is recommended.

Red grape juice protects the rat thyroid gland against hypercholesterolemic changes. Ultrastructural and biochemical evidences.

OBJECTIVES: This study aimed to assess the impact of high cholesterol diet (HCD)-induced hypercholesterolemia on the rat thyroid gland and investigate the role of grape juice (GJ) in reducing such impact through biochemical and histopathological methods. MATERIALS AND METHODS: Thirty male Wistar rats sorted into three groups (the control, HCD-fed group, and the HCD+GJ fed group for 13 weeks) were used in this study. Lipid profile, blood glucose and insulin, thyroid hormones, some oxidants/antioxidants parameters were assessed. After the end of the experiment, thyroid glands were dissected out and processed for histopathological assessment using the light and electron microscopy. RESULTS: Based on the lipid profile, HCD induced hypercholesterolemia in rats after 13 weeks. This resulted in significant (p<0.001) increase of the levels of insulin, blood glucose, thyroid-stimulating hormone (TSH) (596.4±17 IU∕mL), thyroxine (T4) (202.8±14.1 ng∕mL) and malondialdehyde (MDA) (21.2±4.9 nmol∕mg protein), while the levels of triiodothyronine (T3) (12.6±1.9 ng∕mL) and total antioxidant capacity (TAOC) (21.2±4.9 U∕mg protein) decreased in HCD-fed rats compared to that of the controls. Structurally, thyroid gland follicles of HCD-fed rats showed cytoplasmic vacuolation, stratification and increased thickness of some lining cells. Ultrastructurally, some of follicular and parafollicular cells showed heterochromatic nuclei, degenerated mitochondria, intracytoplasmic lipid droplets and deposition of collagen fibers between the follicles. GJ could improve the lipid and antioxidants profiles, reduced blood glucose level, thyroid hormones, and alleviated the HCD-induced structural changes in the thyroid. CONCLUSIONS: GJ administrated simultaneously with HCD ameliorated the negative impact of the function and structure of the thyroid.

Histological and molecular techniques utilized to investigate animal models of depression. An updated review.

This review aimed to summarize the different histopathological techniques and procedures utilized during investigating the different animal models of depression in order to explore the pathophysiological aspect of depression and testing the efficacy of the antidepressant drugs or new treatments. This will be helpful while designing researches aiming to achieve these objectives. It was found that the major obstacle during investigating the animal models of depression was the restricted availability of validated animal models. The chronic stress models have face, construct, and predictive validity. It was found that the histological techniques used in investigating the animal models of depression that was described in the literatures fall under three categories; the light microscopic, the electron microscopic and the molecular biological studies. The light microscope studies were performed using the routine histological staining and immunohistochemical technique that aimed to describe the hippocampal histopathological changes induced by depression. Establishment of a preclinical behavioral science laboratory is highly recommended. It will encourage and support the conduction of high quality, multidisciplinary researches targeting anxiety and other psychiatric disorders and will indirectly improve the health care provided to the psychiatric patients. RESEARCH HIGHLIGHTS: Chronic stress models are valid ones. Light microscope was utilized to examine the routinely or immunohistochemically stained sections in hippocampus of animal models of depression while electron microscope was utilized to examine its ultrastructure.