Ellagic acid reduces hepatic lipid contents through regulation of SIRT1 and AMPK in old rats.

OBJECTIVE: Ellagic acid is used in traditional medicine for the treatment of lipid disorders. In this study, the effects of ellagic acid on key regulators of lipid metabolism, and histopathological alterations in aged liver were examined. METHODS: A total of 21 male Wistar rats were divided into three groups, including young control, old control, and old ellagic acid. After one month of treatment with ellagic acid, the expression levels of hepatic SIRT1, AMPK, SREBP-1c, PPAR-α, and phosphorylated AMPK (p-AMPK) were evaluated. The levels of several serum biochemical factors, and hepatic triglyceride, and cholesterol contents were assessed. RESULTS: Ellagic acid elevated the levels of SIRT1, p-AMPK, and PPAR-α and reduced SREBP-1c level in the liver of old rats. It decreased triglyceride and cholesterol contents in the aged liver and improved histopathological changes. CONCLUSIONS: The results demonstrated that ellagic acid can exert protective effects against hepatic lipid metabolism disorders induced by ageing.

The effect of combining basil seeds and gum Arabic on the healing process of experimental acetic acid-induced ulcerative colitis in rats.

Background & aim: Ulcerative colitis (UC) is a chronic recurrent inflammatory disease of the large intestine and rectum that oxidative stress and severe inflammation are the main features of this disease. Previous studies have shown that separate consumption of basil and gum arabic can reduce inflammation and oxidative stress. The aim of the study was evaluating the effect of treatment with basil seeds given together with gum arabic on healing, inflammation and oxidative stress in the course of experimental colitis in rats. Experimental procedure: A total number of 50 male rats were used, randomly assigned to five groups of 10 rats each. Colitis was induced in rats by enemas with 4% solution od acetic acid. Four days after induction of colitis, rats were treated for next 4 days with saline or combination of basil seeds plus gum arabic (1 mg/kg) or sulfasalazine (100 mg/g) rectally. The experiment was terminated after last dose of treatment. Rats without induction of colitis were used as a sham group. Results: Acetic acid-induced colitis increased the macroscopic and histopathological damage scores of the colon as well as colon levels of MDA(Malondialdehyde), MPO(Myeloperoxidase), TNFα(Tissue necrosis factor α), IL6 (Interleukin 6)and IL17(Interleukin 17) and decreased SOD(Superoxide Dismutase), GPx (Glutathione Peroxidase) and IL10 (Interleukin 10) levels compared with the control group(P < 0.001). Treatment with basil and gum arabic reduced macroscopic and histopathological damage scores (P < 0.01) of the colon, MDA, MPO, TNFα, IL6(P < 0.001) and IL17 (P < 0.01) levels of the colon and increased SOD, GPx and IL10 levels compared to the colitis group (P < 0.01). Conclusion: Rectal administration of combination of basil seeds plus gum arabic after induction of colitis, exhibits antioxidant and anti-inflammatory effects, and accelerates the healing of the colon in experimental colitis evoked by acetic acid.

Spiritual Well-being in Patients with Chronic Diseases: A Systematic Review and Meta-analysis.

As a significant health challenge, chronic disease can have critical spiritual consequences for patients. Therefore, the study of spiritual well-being as an aspect of health is essential but has been less considered with regard to chronic diseases. Thus, this systematic review and meta-analysis were conducted to investigate spiritual well-being in patients with chronic diseases. For this purpose, in the initial search that was performed of valid databases, a total of 615 descriptive studies published between 2000 and 2018 were found. After carefully assessing these, only 24 studies were included in the review. Overall, the spiritual well-being of 3289 patients with chronic disease was investigated. This study showed that the total mean score of the spiritual well-being of patients with chronic diseases was 86.65 (P < 0.001, 95%, CI: 80.34-92.96), indicating a moderate level of spiritual well-being in these patients. Thus, patients with chronic diseases are recommended to consider spiritual consultation programs.

Protective Roles of Shilajit in Modulating Resistin, Adiponectin, and Cytokines in Rats with Non-alcoholic Fatty Liver Disease.

OBJECTIVE: To evaluate the effect of Shilajit, a medicine of Ayurveda, on the serum changes in cytokines and adipokines caused by non-alcoholic fatty liver disease (NAFLD). METHODS: After establishing fatty liver models by feeding a high-fat diet (HFD) for 12 weeks, 35 Wistar male rats were randomly divided into 5 groups, including control (standard diet), Veh (HFD + vehicle), high-dose Shilajit [H-Sh, HFD + 250 mg/(kg·d) Shilajit], low-dose Shilajit [L-Sh, HFD + 150 mg/(kg·d) Shilajit], and pioglitazone [HFD + 10 mg/(kg·d) pioglitazone] groups, 7 rats in each group. After 2-week of gavage administration, serum levels of glucose, insulin, interleukin 1beta (IL-1ß), IL-6, IL-10, tumor necrosis factor-alpha (TNF-α), adiponectin, and resistin were measured, and insulin resistance index (HOMA-IR) was calculated. RESULTS: After NAFLD induction, the serum level of IL-10 significantly increased and serum IL-1ß, TNF-α levels significantly decreased by injection of both doses of Shilajit and pioglitazone (P<0.05). Increases in serum glucose level and homeostasis model of HOMA-IR were reduced by L-Sh and H-Sh treatment in NAFLD rats (P<0.05). Both doses of Shilajit increased adiponectin and decreased serum resistin levels (P<0.05). CONCLUSION: The probable protective role of Shilajit in NAFLD model rats may be via modulating the serum levels of IL-1ß, TNF-α, IL-10, adipokine and resistin, and reducing of HOMA-IR.

Improving SIRT1 by trehalose supplementation reduces oxidative stress, inflammation, and histopathological scores in the kidney of aged rats.

The aging process leads to progressive loss of kidney function. Sirtuin1 (SIRT1) exerts renoprotective effects by conferring resistance to cellular stresses. Trehalose potentially displayed various beneficial effects to promote health span. In this study, we investigated the effects of trehalose on renal SIRT1 and kidney function in senescent rats. Trehalose (2% w/v) was administrated in drinking water for 1 month to male aged rats (24 months). Then, the level of SIRT1 mRNA and protein, malondialdehyde, total antioxidant capacity, tumor necrosis factor α as well as parameters related to the function and histology of the kidneys were evaluated. Trehalose supplementation increased the level of SIRT1, whereas alleviated the level of oxidative stress, inflammation, and histopathology scores in senescent tissues. However, trehalose administration did not alter kidney function indices in old rats. Collectively, these findings suggested that trehalose was an effective intervention to ameliorate some aspects of age-associated injury in the old kidneys. PRACTICAL APPLICATIONS: Aging is associated with impairment in renal structure and function. Trehalose is a natural disaccharide, which is widely distributed in many organisms. The consumption of trehalose as a dietary supplement is increasing worldwide. This study showed that trehalose administration to aged rats had renoprotective effects through reducing oxidative stress and inflammation, which was mediated by SIRT1. Our results provide useful information for individuals using this sugar as a supplement.

Marijuana and ß-estradiol interactions on spatial learning and memory in young female rats: Lack of role of the G protein-coupled estrogen receptor (GPR30).

It has been shown that 17ß-estradiol (E2) hormone is an essential biological factor for increasing the sensitivity of women to drug abuse. Recent studies have shown a potential overlap between the molecular pathways of cannabinoids and ovarian hormones. The current study evaluated the interference between the marijuana and E2 effect on spatial learning and memory and the role of the G protein-coupled estrogen receptor (GPR30) in young female rats. The animals were separated into two main groups: intact-ovary and ovariectomized (OVX) rats. The latter group received intraperitoneal injections of E2, G-1 (GPR30 agonist), G-15 (GPR30 antagonist), marijuana, and different combinations of these substances for 28 days. Spatial learning and memory were evaluated by the Morris water maze (MWM) test. We also assessed the BDNF (brain-derived neurotrophic factor) concentration and the hippocampal level of GPR30. The results showed a significant reduction of spatial learning and memory in OVX rats compared to intact-ovary rats, which were restored by E2 replacement. Moreover, treatment with G-1 mimicked E2 effects on spatial learning and memory. Marijuana impaired spatial learning and memory in intact-ovary rats, while improved in OVX rats. We also found that treatment with M + E2 induced significant impairment in spatial learning and memory; however, treatment with M + G1 and M + G15 + E2 showed no significant difference. No significant differences in BDNF expression were observed in experimental groups. These results suggest that marijuana and E2 interact in their effect on spatial learning and memory in young female rats, but GPR30 seems to play no role in this interaction.

Hepatoprotective effects of Shilajit on high fat-diet induced non-alcoholic fatty liver disease (NAFLD) in rats.

Background Non-alcoholic fatty liver disease (NAFLD) is the main common cause of chronic liver disease. The aim of this study is to evaluate the effect of Shilajit, a medicine of Ayurveda, on the liver damage caused by NAFLD. Materials and methods Forty male Wistar rats, after being established as fatty liver models by feeding a high-fat diet (HFD, 12 weeks), were divided randomly into five groups as follows: control (standard diet), vehicle (HFD + distilled water), high-dose Shilajit (HFD + 250 mg/kg Shilajit), low-dose Shilajit (HFD + 150 mg/kg Shilajit) and pioglitazone (HFD + 10 mg/kg pioglitazone). The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), glucose and liver glutathione peroxidase (GPx), superoxide dismutase (SOD) activity, malondialdehyde (MDA) levels, liver weight, and histopathological manifestation outcomes were measured after the 2-week intervention. Results Shilajit treatment significantly reduced the values of AST and ALT, TG, TC, LDL, glucose, liver weight, and steatosis, and instead, increased high-density lipoprotein (HDL) compared with the vehicle group (p < 0.05). Further, Shilajit treatment improved the adverse effects of HFD-induced histopathological changes in the liver as compared with the vehicle group (p < 0.001). MDA level and GPx activity increased but SOD activity decreased in the vehicle group compared with the control group (p < 0.05), while treatment with Shilajit restored the antioxidant/oxidant balance toward a significant increase in the antioxidant system in the Shilajit group (p < 0.05). Conclusions These findings suggest that Shilajit improved the histopathological NAFLD changes in the liver and indicated the potential applicability of Shilajit as a potent agent for NAFLD treatment.

What is the combined effect of intense intermittent exercise and Ginkgo biloba plant on the brain neurotrophic factors levels, and learning and memory in young rats?

BACKGROUND: The present study was conducted to investigate the effect of intense intermittent exercise and Ginkgo biloba on the hippocampal levels of brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4) and also memory and learning in young rats. METHODS: Forty two eight-week-old rats were randomly divided into six groups including control, low dose of Ginkgo biloba (65 mg/kg), high dose of Ginkgo biloba (100 mg/kg), exercise, exercise + low dose of Ginkgo biloba, exercise + high dose of Ginkgo biloba. The exercise protocol or Ginkgo biloba administration was six days a week for six weeks. The hippocampal levels of BDNF and NT-4 were measured by ELISA method, and learning and memory were evaluated by Morris water maze test in all groups. Data were analyzed using SPSS software. RESULTS: Increase in hippocampal levels of BDNF and NT-4 appeared following exercise (p < 0.01). The levels do not change following exercise + Ginkgo biloba administration. However, the NT-4 level decreased in the high dose of Ginkgo biloba group (p < 0.01). Disorder in learning and memory was indicated following the use of low dose of Ginkgo biloba or exercise + low dose Ginkgo biloba administration (p < 0.001). Learning elevated in the exercise group (p < 0.05). CONCLUSIONS: Exercise in young rats may increase brain neurotrophin levels and lead to improved learning. The preventative or protective role of Ginkgo biloba against some diseases has been suggested, but its consumption in young athletes is recommended with caution.

Effect of fruit extract on renal stone formation and kidney injury in rats.

This study investigated the effect of oral administration of Cactus fruit extracts on calcium oxalate deposition, malondialdehyde (MDA) and superoxide dismutase (SOD) activity in rat model. About 42 rats were used for the study. The animals were divided into seven groups. Control group maintained on regular rat food and drinking water throughout the study period, whereas in other groups nephrolithiasis was induced by ethylene glycol. Rats in kidney stone group were sacrificed after 28 days and all remaining groups after 58 days. Treatment groups were treated with 1 and 100 mg/kg of aqueous and ethanolic extracts of Cactus fruit for 30 days. After treatment, SOD activity was increased and MDA was decreased significantly. CaOx depositions were decreased significantly, especially in ethanolic extract of Cactus fruit in high dose (100 mg/kg).

Vitamin D Modulates the Expression of IL-27 and IL-33 in the Central Nervous System in Experimental Autoimmune Encephalomyelitis (EAE).

BACKGROUND: It has been reported that vitamin D has broad anti-inflammatory and immunomodulatory effects. OBJECTIVE: To evaluate the effects of vitamin D on the expression of IL-27 and IL-33 in a model of experimental autoimmune encephalomyelitis (EAE). METHODS: EAE was induced in C57BL/6 mice by immunization with myelin oligodendroglial glycoprotein mixed with complete Freund's adjuvant. The mice were administered with PBS or olive oil, intraperitoneally, in the control groups and vitamin D (200 ng every two days) in the treatment group, from day +3 to +30. At day 31, the mice were scarified and their spinal cords and brains were harvested. The expression of the IL-27 and IL-33 mRNA in the spinal cord was measured using real time-PCR. RESULTS: In PBS- or olive oil-treated EAE mice the expression of IL-27 P28 mRNA was significantly lower than that in the healthy control group (p<0.002). In both PBS- and olive oil-treated EAE groups, the expression of IL-27 EBI3 mRNA was also lower than that observed in the healthy group, but the differences were not significant. In vitamin D-treated EAE group, the expression of IL-27 P28 and IL-27 EBI3 were significantly higher compared with the olive oil-treated EAE groups (p<0.002 and p<0.04, respectively). The expression of IL-33 was significantly higher in PBS-or olive oil-treated EAE groups compared with healthy mice (p<0.05 and p<0.02, respectively). Vitamin D significantly decreased the expression of IL-33 compared with PBS- or olive oil-treated EAE mice (p<0.04, p<0.02, respectively). The PBS- or olive oil -treated EAE mice showed the clinical symptoms of EAE at days 9 and 10, respectively. The vitamin D-treated EAE group exhibited the symptoms at day 12 post immunization. The maximum mean clinical score and mean pathological scores were also significantly lower in vitamin D-treated EAE group, in comparison with PBS- or olive oil treated EAE mice (p<0.001). CONCLUSION: Vitamin D may modulate the expression of IL-27 and IL-33 in the spinal cord of EAE mice and also ameliorate the clinical symptoms of the disease.

Ulcer healing activity of Mumijo aqueous extract against acetic acid induced gastric ulcer in rats.

OBJECTIVE: Gastric ulcer is an important clinical problem, chiefly due to extensive use of some drugs. The aim was to assess the activity of Mumijo extract (which is used in traditional medicine) against acetic acid induced gastric ulcer in rats. MATERIALS AND METHODS: The aqueous extract of Mumijo was prepared. Animals were randomly (n = 10) divided into four groups: Control, sham-operated group (received 0.2 ml of acetic acid to induce gastric ulcer), Mumijo (100 mg/kg/daily) were given for 4 days postacetic acid administration, and ranitidine group (20 mg/kg). The assessed parameters were pH and pepsin levels (by Anson method) of gastric contents and gastric histopathology. Ranitidine was used as reference anti-ulcer drug. RESULTS: The extract (100 mg/kg/daily, p.o.) inhibited acid acetic-induced gastric ulceration by elevating its pH versus sham group (P < 0.01) and decreasing the pepsin levels compared to standard drug, ranitidine (P < 0.05). The histopathology data showed that the treatment with Mumijo extract had a significant protection against all mucosal damages. CONCLUSION: Mumijo extract has potent antiulcer activity. Its anti-ulcer property probably acts via a reduction in gastric acid secretion and pepsin levels. The obtained results support the use of this herbal material in folk medicine.

Effect of sex steroid hormones on brain edema, intracranial pressure, and neurologic outcomes after traumatic brain injury.

Recent studies have reported that estrogen and progesterone have a neuroprotective effect after traumatic brain injury (TBI); however, the mechanism(s) for this effect have not yet been elucidated. The aim of the present study was to investigate the role of sex steroid hormones on changes in brain edema, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) after TBI in ovariectomized (OVX) rats. In this study, 50 female rats were divided into 5 groups: control (intact), sham, and 3 TBI groups consisting of vehicle, estrogen (1 mg/kg), and progesterone (8 mg/kg). TBI was induced by the Marmarou method, and the hormones were injected i.p. 30 min after TBI. ICP was measured in the spinal cord, and CPP was calculated by subtracting the mean arterial pressure (MAP) from ICP. The results revealed that brain water content after TBI was lower (p < 0.001) in the estrogen and progesterone groups than in the vehicle group. After trauma, ICP was significantly higher in TBI rats (p < 0.001). The ICP in the estrogen and progesterone groups decreased at 4 and 24 h after TBI compared with vehicle (p < 0.001 and p < 0.05, respectively). The CPP in the estrogen and progesterone groups increased after 24 h compared with vehicle (p < 0.001). Also after TBI, the neurological score (veterinary coma scale) was significantly higher than vehicle at 1 h (p < 0.01) and 24 h (p < 0.001) in the group treated with estrogen. In conclusion, pharmacological doses of estrogen and progesterone improved ICP, CPP, and neurological scores after TBI in OVX rats, which implies that these hormones play a neuroprotective role in TBI.

The effect of saffron consumption on biochemical and histopathological heart indices of rats with myocardial infarction.

This study was designed to assess the effects of saffron (Crocus sativus) on rats' heart with isoproterenol-induced myocardial injury. Animals were divided randomly into four groups: vehicle-control group (CTL); ISO group, administrated with Isoproterenol 85 mg/kg s.c.; saffron group; and finally combined Saffron + ISO group. Basal and final serum levels of heart troponin I, heart tissue antioxidants and histopathological indices were assessed in all groups. Isoproterenol administration significantly increased serum level of troponin I when compared to control group (3.46 +/- 0.77 vs. 0.53 +/- 0.35 ml in ng/ml, P < 0.001) and reduced significantly the glutathione peroxidase activity of heart muscle (1.63 +/- 0.21 vs. 4.01 +/- 0.64 nmol/mg protein, P < 0.05). The grade of heart muscle damages was severe in more than 70% of ISO group animals. Saffron + ISO group showed remarkably decreased intensity of tissue destruction and significantly decreased serum levels of heart troponin I, when compared to ISO group (1.25 +/- 0.23 vs. 3.46 +/- 0.77 ng/ml, P < 0.05). The level of glutathione peroxidase activity in Saffron + ISO animals did not have significant decline compared to saffron alone. These results suggest the protective role of saffron on ischemic hearts by biochemical and histopathological findings.

Opium can differently alter blood glucose, sodium and potassium in male and female rats.

To determine the effects of opium on serum glucose, potassium and sodium in male and female Wistar rat, opium solution (60 mg/kg) injected intraperitoneally and the same volume of distilled water was used as control (7 rats in each group). Blood samples were collected at 0, 30, 60, 120, 240 and 360 minutes after injection from orbit cavity and the values of serum glucose, sodium (Na(+)) and potassium (K(+)) were measured. The data were then analyzed by the repeated measure ANOVA based on sex and case-control group. P < 0.05 considered as significant difference. Serum glucose increased significantly at 30, 60, 120 and 240 minutes after opium solution injection, in female rats compared to a control group. However, the male rats had this rise at 30, 60 and 120 minutes after opium solution injection compared to control group. While serum glucose in male rats was significantly higher than females at 30, 60 and 120 minutes, this value was higher in the female rats at 360 minutes. Therefore, serum glucose alterations following opium injection was significantly different in groups and in the sexes at different times. Sodium (Na(+)) rose at 60, 240 and 360 minutes significantly in all rats compared to control group. However, sodium alteration following opium injection was significantly different only between treated and control groups but sex-independent at all times. Potassium (K(+)) increased significantly at 60, 120, 240 and 360 minutes in male rats, compared to a control group. In female rats K(+) significantly raised at 30, 120, 240 and 360 minutes. Therefore, the alteration of K(+) in male and female rats was found time dependent and sex independent. According to our results, opium increased serum glucose in male and female rats differently, and it interferes with metabolic pathways differently on a gender dependent basis. Opium raised serum Na(+) and K(+), thus it interfere with water regulation and blood pressure via different mechanism.

Effects of opium addiction on some serum factors in addicts with non-insulin-dependent diabetes mellitus.

The aim of this study was to determine the effect of opium on biochemical parameters in addicts with non-insulin-dependent diabetes mellitus (NIDDM). Twenty-three males and 26 females between 35 and 65 years of age, with NIDDM, addicted to opium, were selected as the case group. Twenty-three males and 26 females with NIDDM and no opium addiction served as controls. Fasting glucose, glycated haemoglobin (HbA1c), total cholesterol, high density lipoproteins-cholesterol (HDL-c), triglycerides (TGs), sodium (Na(+)), potassium (K(+)), calcium (Ca(2+)), iron (Fe(2+)), total iron binding capacity (TIBC), serum total protein, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), uric acid and urea were measured in the serum of the two groups. Serum protein electrophoresis was also carried out. Compared to the control group, in addicted males with NIDDM, HbA1c, K(+) and Fe(2+) were higher, and serum total protein, ALT and HDL-c were lower. No significant difference was observed between other factors. Albumin was lower in addicts, but no significant difference was observed between the albumin/globulin ratios. In addicted females with NIDDM, serum total protein, TIBC, ALT and AST were lower compared to non-addicts. Cholesterol tends to be lower in diabetic addicted males, HbA1c in addicted females and uric acid in addicted males was higher compared to non-addicted diabetics. Their differences, however, were not significant. According to our results, smoking opium increases serum glucose and decreases HDL-c, and thus adds to metabolic disorders in NIDDM patients. It also increases potassium and Fe(2) in males and decreases TIBC in females, and could therefore potentially interfere with water and iron metabolism.