Neuroprotective potential of Erigeron bonariensis ethanolic extract against ovariectomized/D-galactose-induced memory impairments in female rats in relation to its metabolite fingerprint as revealed using UPLC/MS.

Erigeron bonariensis is widely distributed throughout the world's tropics and subtropics. In folk medicine, E. bonariensis has historically been used to treat head and brain diseases. Alzheimer's disease (AD) is the most widespread form of dementia initiated via disturbances in brain function. Herein, the neuroprotective effect of the chemically characterized E. bonariensis ethanolic extract is reported for the first time in an AD animal model. Chemical profiling was conducted using UPLC-ESI-MS analysis. Female rats underwent ovariectomy (OVX) followed by 42 days of D-galactose (D-Gal) administration (150 mg/kg/day, i.p) to induce AD. The OVX/D-Gal-subjected rats received either donepezil (5 mg/kg/day) or E. bonariensis at 50, 100, and 200 mg/kg/day, given 1 h prior to D-Gal. UPLC-ESI-MS analysis identified 42 chemicals, including flavonoids, phenolic acids, terpenes, and nitrogenous constituents. Several metabolites, such as isoschaftoside, casticin, velutin, pantothenic acid, xanthurenic acid, C18-sphingosine, linoleamide, and erucamide, were reported herein for the first time in Erigeron genus. Treatment with E. bonariensis extract mitigated the cognitive decline in the Morris Water Maze test and the histopathological alterations in cortical and hippocampal tissues of OVX/D-Gal-subjected rats. Moreover, E. bonariensis extract mitigated OVX/D-Gal-induced Aß aggregation, Tau hyperphosphorylation, AChE activity, neuroinflammation (NF-κBp65, TNF-α, IL-1ß), and apoptosis (Cytc, BAX). Additionally, E. bonariensis extract ameliorated AD by increasing α7-nAChRs expression, down-regulating GSK-3ß and FOXO3a expression, and modulating Jak2/STAT3/NF-ĸB p65 and PI3K/AKT signaling cascades. These findings demonstrate the neuroprotective and memory-enhancing effects of E. bonariensis extract in the OVX/D-Gal rat model, highlighting its potential as a promising candidate for AD management.

Preparation of pumpkin oil-based nanoemulsion as a potential estrogen replacement therapy to alleviate neural-immune interactions in an experimental postmenopausal model.

As estrogen production decreases during menopause; the brain's metabolism tends to stall and become less effective. Estrogen most likely protects against neurodegeneration. Consequently, a comprehensive study of the benefits of hormone replacement therapy as a neuroprotective effect is urgently required. This study was designed to fabricate pumpkin seed oil nanoparticles (PSO) in nanoemulsion form (PSO-NE) and investigate their potential role in attenuating the neural-immune interactions in an experimental postmenopausal model.Sixty female white albino rats were divided into six groups: control, sham, ovariectomized (OVX), and three OVX groups treated with 17ß-estradiol, PSO, and PSO-NE respectively. Transmission Electron Microscopy (TEM), and particle size analyzer were performed for nanoemulsion evaluation. Serum levels of estrogen, brain amyloid precursor protein (APP), serum levels of nuclear factor kappa B (NF-κß), interleukin 6 (IL-6), transthyretin (TTR), and synaptophysin (SYP) were evaluated. The expression of estrogen receptors (ER-α, ß) in the brain tissue was estimated. The findings revealed that the approached PSO-NE system was able to reduce the interfacial tension, enhance the dispersion entropy, lower the system free energy to an extremely small value, and augment the interfacial area. PSO-NE, showed a significant increase in the levels of estrogen, brain APP, SYP, and TTR accompanied with a significant increased in the expression of brain ER-α, ß compared to the OVX group. In conclusion, the phytoestrogen content of PSO exhibited a significant prophylactic effect on neuro-inflammatory interactions, ameliorating both estrogen levels and the inflammatory cascades.

Pomegranate Seeds Extract Possesses a Protective Effect against Tramadol-Induced Testicular Toxicity in Experimental Rats.

Tramadol is a centrally acting opioid analgesic that is extensively used. The chronic exposure to tramadol induces oxidative stress and toxicity especially for patients consuming it several times a day. Previously, we and others reported that tramadol induces testicular damage in rats. This study was conducted to investigate the possible protective effect of pomegranate seed extract (PgSE) against tramadol-induced testicular damage in adult and adolescent rats. Male rats were orally treated with tramadol or in a combination with PgSE for three weeks. Testes were then dissected and analyzed. Histological and ultrastructural examinations indicated that tramadol induced many structural changes in the testes of adult and adolescent rats including hemorrhage of blood vessels, intercellular spaces, interstitial vacuoles, exfoliation of germ cells in lumen, cell apoptosis, chromatin degeneration of elongated spermatids, and malformation of sperm axonemes. Interestingly, these abnormalities were not observed in tramadol/PgSE cotreated rats. The morphometric analysis revealed that tramadol disrupted collagen metabolism by elevating testicular levels of collagen fibers but that was protected in tramadol/PgSE cotreatment at both ages. In addition, DNA ploidy revealed that S phase of the cell cycle was diminished when adult and adolescent rats were treated with tramadol. However, the S phase had a normal cell population in the cotreated adult rats, but adolescent rats had a lower population than controls. Furthermore, the phytochemistry of PgSE revealed a high content of total polyphenols and total flavonoids within this extract; besides, the DPPH free radical scavenging activity was high. In conclusion, this study indicated that PgSE has a prophylactic effect against tramadol-induced testicular damage in both adult and adolescent ages, although the tramadol toxicity was higher in adolescent age to be completely protected. This prophylactic effect might be due to the high antioxidant compounds within the pomegranate seeds.

Inhibitory activity of black mulberry (Morus nigra) extract against testicular, liver and kidney toxicity induced by paracetamol in mice.

Black mulberry (Morus nigra) leaves is broadly used in traditional medicine worldwide. However, there are no scientific reports regarding testicular protection, hepato-and nephroprotective activities of M. nigra leaves. The present investigation was assessed the protective mechanism by which methanol extract from M. nigra leaves suppressed the damaging effects induced by paracetamol (APAP) in different mouse tissues. Male mice were orally given APAP (500 mg/kg) with or without M. nigra extract (150, 300, and 500 mg/kg) for four consecutive days. The results showed that crude extract possessed potent antioxidant activity (EC50 = 42.97 µg extract/mL) due to the presence of a high amount of polyphenol and flavonoid compounds. Gallic acid, chlorogenic acid, catechin, and rutin were isolated from the n-butanol fraction of M. nigra extract. Unexpectedly, oral administration of APAP did not induce chromosomal aberrations in mouse bone marrow; however, it produced damaging effects on testis, liver, and kidney tissues. Interestingly, M. nigra extract suppressed APAP-induced genotoxicity by lowering meiotic chromosomal aberrations in spermatocytes, morphological sperm abnormalities, and % DNA damage in comet tail in the liver and kidney tissues. The altered levels of glutathione S transferase activity, lipid peroxidation, liver, and kidney functions were significantly reversed when M. nigra was given to APAP group. The restoring of the histo-architectural distortions and decreasing over-expression of p53 protein as determined by immunohistochemistry in the liver, kidney, and testis sections were strengthened the protective activity of M. nigra extract. Conclusion, the bioactive components in the leaves of black mulberry appear to be a good candidate for genetic protection, treatment of oxidative stress-induced organotoxicity.

Genotoxicity of carbon tetrachloride and the protective role of essential oil of Salvia officinalis L. in mice using chromosomal aberration, micronuclei formation, and comet assay.

The present work was conducted to evaluate the genotoxic effect of carbon tetrachloride (CCl4) in mouse bone marrow and male germ cells. The safety and the modulating activity of sage (Salvia officinalis L.) essential oil (SEO) against the possible genotoxic effect of CCl4 were also evaluated. A combination of in vivo mutagenic endpoints was included: micronucleus (MN), apoptosis using dual acridine orange/ethidium bromide (AO/EB) staining, comet assay, chromosomal aberrations (CAs), and sperm abnormalities. Histological examination of testis tissues was also studied. The extracted SEO was subjected to gas chromatography-mass spectrometry (GC-MS) for identifying its chemical constituents. Safety/genotoxicity of SEO was determined after two consecutive weeks (5 days/week) from oral treatment with different concentrations (0.1, 0.2, and 0.4 mL/kg). For assessing genotoxicity of CCl4, both acute (once) and subacute i.p. treatment for 2 weeks (3 days/week) with the concentrations 1.2 mL/kg (for acute) and 0.8 mL/kg (for subacute) were performed. For evaluating the protective role of SEO, simultaneous treatment with SEO plus CCl4 was examined. In sperm abnormalities, mice were treated with the subject materials for five successive days and the samples were collected after 35 days from the beginning of treatment. Based on GC-MS findings, 22 components were identified in the chromatogram of SEO. The results demonstrated that the three concentrations of SEO were safe and non-genotoxic in all the tested endpoints. Negative results were also observed in bone marrow after acute and subacute treatment with CCl4. In contrast, CCl4 induced testicular DNA damage as evidenced by a significant increase of CAs in primary spermatocytes, sperm abnormalities, and histological distortion of testis. A remarkable reduction in these cells was observed in groups treated with SEO plus CCl4 especially with the two higher concentrations of SEO. In conclusion, SEO is safe and non-genotoxic under the tested conditions and can modulate genetic damage and histological alteration induced by CCl4 in the testes.

Citric acid effects on brain and liver oxidative stress in lipopolysaccharide-treated mice.

Citric acid is a weak organic acid found in the greatest amounts in citrus fruits. This study examined the effect of citric acid on endotoxin-induced oxidative stress of the brain and liver. Mice were challenged with a single intraperitoneal dose of lipopolysaccharide (LPS; 200 µg/kg). Citric acid was given orally at 1, 2, or 4 g/kg at time of endotoxin injection and mice were euthanized 4 h later. LPS induced oxidative stress in the brain and liver tissue, resulting in marked increase in lipid peroxidation (malondialdehyde [MDA]) and nitrite, while significantly decreasing reduced glutathione, glutathione peroxidase (GPx), and paraoxonase 1 (PON1) activity. Tumor necrosis factor-alpha (TNF-α) showed a pronounced increase in brain tissue after endotoxin injection. The administration of citric acid (1-2 g/kg) attenuated LPS-induced elevations in brain MDA, nitrite, TNF-α, GPx, and PON1 activity. In the liver, nitrite was decreased by 1 g/kg citric acid. GPx activity was increased, while PON1 activity was decreased by citric acid. The LPS-induced liver injury, DNA fragmentation, serum transaminase elevations, caspase-3, and inducible nitric oxide synthase expression were attenuated by 1-2 g/kg citric acid. DNA fragmentation, however, increased after 4 g/kg citric acid. Thus in this model of systemic inflammation, citric acid (1-2 g/kg) decreased brain lipid peroxidation and inflammation, liver damage, and DNA fragmentation.

Therapeutic effect of Acacia nilotica pods extract on streptozotocin induced diabetic nephropathy in rat.

The aim of the present study was to examine the effect of aqueous methanol extract (150 and 300 mg/kg body weight) of Acacia nilotica pods in streptozotocin-induced diabetic rats for 60 days, and its biochemical, histopathological and histochemical study in the kidney tissues. Diabetic rats exhibited hyperglycemia, elevated of serum urea and creatinine. Significant increase in lipid peroxidation (LPO), superoxide dismutase (SOD) and reduced glutathione (GSH) was observed in diabetic kidney. Histopathological examination revealed infiltration of the lymphocytes in the interstitial spaces, glomerular hypertrophy, basement membrane thickening and tubular necrosis with loss of their brush border in some of the proximal convoluted tubules in diabetic rats. Acacia nilotica extract lowered blood glucose levels, restored serum urea and creatinine. In addition, Acacia nilotica extract attenuated the adverse effect of diabetes on LPO, SOD and GSH activity. Treatment with Acacia nilotica was found to almost restore the normal histopathological architecture of kidney of streptozotocin-induced diabetic rats. However, glomerular size and damaged area showed ameliorative effect after treatment with the extract. In conclusion, the antioxidant and antihyperglycemic properties of Acacia nilotica extract may offer a potential therapeutic source for the treatment of diabetes.

Mushroom insoluble polysaccharides prevent carbon tetrachloride-induced hepatotoxicity in rat.

UNLABELLED: The aim of the present study was to investigate the effect of mushroom insoluble non-starch polysaccharides (MINSP) on the carbon tetrachloride (CCl(4))-induced hepatic damage in rat. MINSP (100 and 200 mg/kg) administered daily orally for 15 days before CCl(4) (1.5 ml/kg). The effect of MINSP treatment was also examined in normal rats. Normal groups treated with MINSP showed significant decrease in serum activities of the liver enzymes, lipid peroxides and nitric oxide (NO) in the liver. Reduced glutathione (GSH) and total proteins (TP) contents in liver homogenate also increased after treatment with only MINSP for 15 days. In CCl(4)-treated rats, significant elevation in serum liver enzymes, increased lipid peroxides and NO in the liver, and depletion of hepatic-GSH level were observed. Pre-treatment with MINSP significantly ameliorated the tested parameters when compared with CCl(4)-treated group. It improved the antioxidant activity of the liver in a dose-dependent manner. Histopathological examination of hepatic tissue revealed that MINSP administration alone protected hepatocytes from the damage induced by CCl(4). CONCLUSION: MINSP are safe; it could be used as fat replacer in processing low fat diet. MINSP represents a good functional food and liver supporter for patient suffering from various liver diseases.

Zizyphus spina-christi extract protects against aflatoxin B1-initiated hepatic carcinogenicity.

Aflatoxins (AF), a group of closely related, extremely toxic mycotoxins, produced by Aspergillus flavus and A. parasiticus can occur as natural contaminants of foods and feeds. Aflatoxins have been shown to be hepatotoxic, carcinogenic, mutagenic, and teratogenic to different animal species. Zizyphus spina-christi L. extract was investigated for its antifungal and antimicrobial activities. The aim of the present work was to evaluate the antioxidant activity of the methanol extract of Z. spina-christi L. leaves against the oxidative stress of aflatoxin in rats. Fourty male Sprague-Dawley male rats were divided into four groups including the control group, the group fed aflatoxin-contaminated diet (3 mg/kg diet) and the groups treated with Zizyphus extract (5 mg/kg b.w) alone or in combination with AF for 15 days. Biochemical analysis revealed that treatment with AF resulted in a significant increase in ALT, AST, cholesterol, triglycerides, uric acid, TNFa, LPO, NO and CEA, whereas it decrease significantly GPX and SOD. The histopathological examination of the liver, kidney and testis showed sever histological changes typical to those reported for aflatoxicosis. Animals treated with Zizyphus extract alone or plus AF showed a significant improvement in all biochemical parameters and histological picture of liver, kidney and testis. It could be concluded that Zizyphus extract have a power protective role against aflatoxicosis.