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Brain inflammation and apoptosis play crucial roles in the pathogenesis of various neurodevelopmental disorders. Probiotics have been shown to confer protection against many stresses, including apoptosis and inflammation, by modulating the gut function. The short‐chain fatty acid, propionic acid (PPA), plays an important intermediate of cellular metabolism. Although PPA exhibits numerous beneficial biological effects, its accumulation is neurotoxic. This study focused on the therapeutic potency of probiotics against PPA‐induced apoptosis and neuroinflammation in hamsters. Five groups of male golden Syrian hamsters were treated as follows: Group I as control; Group II as PPA‐treated with three doses of 250 mg PPA/kg/day; Group III as clindamycin‐treated with a single dose of 30 mg clindamycin/kg; Group IV as PPA–probiotic; and Group V as clindamycin–probiotic were two therapeutic groups which were treated with the same doses of PPA and clindamycin, respectively, followed by treatment with 0.2 g kg‐1 d−1 of probiotic (ProtexinR, Probiotics International Limited) for three weeks. Proapoptotic markers, such as caspases 3 and 7; neuroinflammation markers, such as interleukins 1β and 8; and heat shock protein 70 were measured in the brain. Significant increase of all measured markers (p ˂ .001) was observed in PPA and clindamycin‐treated hamsters compared with controls. Probiotics significantly reduced the damages and ameliorated all the test markers in both therapeutic groups compared with the control. Our results confirmed that probiotics can be utilized as a feasible strategy for managing apoptotic and inflammation‐related stresses in brain disorders by retaining the gut function., This study ascertained the role of neuroinflammation and apoptosis as neurotoxic effects in the PPA‐induced rodent model of autism. Clindamycin showed relatively fewer neurotoxic effects compared with orally administered PPA. Moreover, our study showed that probiotics exert ameliorative effects and may be used as a novel noninvasive and safe treatment strategy.

In this study, the chemical compositions of the ethanolic and aqueous extracts of the leaves of Origanum syriacum and Salvia lanigera were identified based on GC-MS spectrometric analyses. The in vitro anti-inflammatory potential of the different extracts was evaluated by determining the membrane stabilization of human red blood cells and the percent inhibition of the COX1/2, 5LOX, and sPLA2-V enzymes. Both ethanolic extracts showed maximum membrane stabilization (≤ 91%, at 100 μg/mL) compared to the aqueous extracts (≤ 45%) and the reference drug diclofenac sodium (90.75%). The membrane-stabilizing effects of the ethanolic extracts could be directly correlated to their anti-inflammatory activity. While both ethanolic fractions strongly inhibited the 5LOX and COX-1 enzymes at 100 μg/mL, only the O. syriacum ethanolic extract selectively inhibited sPLA2-V (99.35%, at 50 μg/mL). The differences in the pharmacological efficiencies of the different extracts could be attributed to the variation in their chemical compositions particularly the content of oxygenated monoterpenoids. Additionally, none of the ethanolic extracts demonstrated cytotoxicity to human colorectal cancer cell lines (HCT-116 and Lovo), even at the highest concentration tested (200 μg/mL). The safe profiles of these extracts towards the tested cell lines may be due to the absence of the toxic phthalic acid ester substances. Collectively, these findings clearly suggest that the studied ethanolic extracts of O. syriacum and S. lanigera can be considered interesting candidates for the treatment of human inflammatory diseases related to oxidative stress and microbial infections.

Introduction Nanoparticles are at the forefront of rapidly developing nanotechnology and have gained much attention for their application as an effective drug delivery system and as a mediated therapeutic agent for cancer. However, the cytotoxicity of nanoparticles is still relatively unknown and, therefore, additional study is required in order to elucidate the potential toxicity of these nanoparticles on cells. Materials and methods Thus, the following work aimed to investigate the capability of Beta vulgaris (beetroot) water extract (BWE; 200 mg/kg) to protect hepatic tissue following silver nanoparticles (AgNPs; 80 mg/kg; >100 nm) intoxication in male rats. Results AgNPs-intoxication elevated the liver function markers - including serum transaminases and alkaline phosphatase activities - and decreased serum levels of albumin and total proteins, in addition to disturbing the oxidation homeostasis. This is evidenced by the increased lipid peroxidation, the depleted glutathione, and the suppressed activity of superoxide dismutase and catalase. In addition, an apoptotic reaction was observed following AgNPs treatment, as indicated by the up-regulation of p53 and down-regulating Bcl-2 expressions, examined by the immunohistochemistry method. Furthermore, AgNPs exhibited a marked elevation in liver DNA damage that was indicated by an increase in tail length, tail DNA% and tail movement. However, BWE eliminated the biochemical and histological alterations, reflecting its hepatoprotection effect in response to AgNPs. Discussion Collectively, the present data suggest that BWE could be used following AgNPs as a potential therapeutic intervention to minimize AgNPs-induced liver toxicity.

We aimed in the current study, the identification of a marine bacterial amylase produced by Bacillus pacificus, which was associated with Turbinaria ornata. Cultural conditions were optimized for the highest amylase production on Tryptic soy broth media supplemented with starch 1% at initial pH 9, 55 &deg, C for 24 h. The newly purified amylase was characterized for a possible biotechnological application. Data indicated that the obtained amylase with a molecular weight of 40 kD and the N-terminal sequence of the first 30 amino acids of amBp showed a high degree of homology with known alpha amylase, and was stable at 60 &deg, C of pH 11. Among the tested substrate analogs, amBp was almost fully active on Alylose and Alylopectine (97%), but moderately hydrolyzed glycogen &lt, sucrose &lt, maltose &lt, lactose. Therefore, the current amylase mainly generated maltohexaose from starch. Mg2+ and Zn2+ improved amylase activity up to 170%. While ethylenediamine tetraacetic acid (EDTA) similarly induced the greatest activity with purified amylase, PCMB had the least effect. Regarding all these characteristics, amylase from marine bacterial symbionts amBp has a new promising feature for probable therapeutic, industrial, and nutritional applications.

The present study investigated the combined effects of mixed probiotic and bee pollen on brain intoxication induced by propionic acid (PPA) in rat pups. Thirty western albino rats were divided into five groups, six animals each: (1) Control group receiving phosphate‐buffered saline; (2) Probiotic and bee pollen‐treated group being administered at the same dose with 200 mg/kg body weight; (c) PPA‐treated group receiving a neurotoxic dose 250 mg/kg body weight of PPA for 3 days; (d) Therapeutic group being administered the neurotoxic dose of PPA followed by probiotic and bee pollen treatment 200 mg/kg body weight; (e) Protective group receiving probiotic and bee pollen mixture treatment followed by neurotoxic dose of PPA. Selected biochemical parameters linked to oxidative stress, energy metabolism, and neurotransmission were investigated in brain homogenates from all the five groups. PPA treatment showed an increase in oxidative stress markers like lipid peroxidation coupled with a significant decrease in glutathione level. Impaired energy metabolism was ascertained via the alteration of creatine kinase (CK) and lactate dehydrogenase (LDH) activities. Dramatic increase of Na+ and K+ concentrations together with a decrease of GABA and IL‐6 and an elevation of glutamate levels in PPA‐treated rat's pups confirmed the neurotoxicity effect of PPA. Interestingly, the mixed probiotic and bee pollen treatment were effective in restoring the levels of glutamate, GABA, and IL‐6 in addition to normalizing the levels of lipid peroxidation and glutathione and the activities of CK and LDH. The present study indicates that mixed probiotic and bee pollen treatment can improve poor detoxification, oxidative stress, and neuroinflammation as mechanisms implicated in the etiology of autism., The present study indicates that mixed probiotic and bee pollen treatment can improve poor detoxification, oxidative stress, and neuroinflammation as mechanisms implicated in the etiology of autism.

This study was conducted to identify a new alkaline and thermophilic protease (Ba.St.Pr) produced from Bacillus stearothermophilus isolated from olive oil mill sols and to evaluate its culture conditions, including temperature, pH, carbon and nitrogen sources, and incubation time. The optimum culture conditions for cell growth (10 g/L) and protease production (5050 U/mL) were as follows: temperature 55 °C, pH 10, inoculation density 8 × 108 CFU/mL, and incubation time 24 h. The use of 3% yeast extract as the nitrogen sources and galactose (7.5 g/L) as the carbon sources enhanced both cell growth and protease production. Using reversed-phase analytical HPLC on C-8 column, the new protease was purified with a molecular mass of approximately 28 kDa. The N-terminal sequence of Ba.St.Pr exhibited a high level of identity of approximately 95% with those of Bacillus strains. Characterization under extreme conditions revealed a novel thermostable and alkaline protease with a half-life time of 187 min when incubated with combined Ca2+/mannitol. Ba.St.Pr demonstrated a higher stability in the presence of surfactant, solvent, and Ca2+ ions. Consequently, all the evaluated activity parameters highlighted the promising properties of this bacterium for industrial and biotechnological applications.

Many venomous species, especially snakes, contain a variety of secreted phospholipases A2 that contribute to venom toxicity and prey digestion. We characterized a novel highly toxic phospholipase A2 of group II, WaPLA2-II, from the snake venom of Saudi Walterinnesia aegyptia (W. aegyptia). The enzyme was purified using a reverse phase C18 column. It is a monomeric protein with a molecular weight of approximately 14 kDa and an NH2-terminal amino acid sequence exhibiting similarity to the PLA2 group II enzymes. WaPLA2-II, which contains 2.5% (w/w) glycosylation, reached a maximal specific activity of 1250 U/mg at pH 9.5 and 55 &deg, C in the presence of Ca2+ and bile salts. WaPLA2-II was also highly stable over a large pH and temperature range. A strong correlation between antimicrobial and indirect hemolytic activities of WaPLA2 was observed. Additionally, WaPLA2-II was found to be significantly cytotoxic only on cancerous cells. However, chemical modification with para-Bromophenacyl bromide (p-BPB) inhibited WaPLA2-II enzymatic activity without affecting its antitumor effect, suggesting the presence of a separate &lsquo, pharmacological site&rsquo, in snake venom phospholipase A2 via its receptor binding affinity. This enzyme is a candidate for applications including the treatment of phospholipid-rich industrial effluents and for the food production industry. Furthermore, it may represent a new therapeutic lead molecule for treating cancer and microbial infections.

Plants of the Euphorbia genus present a wide range of therapeutic applications. This study is aimed at investigating new antidigestive enzyme agents from Euphorbia cyparissias through inhibition of lipid and carbohydrate absorption, to evaluate their potential applications for the treatment of metabolic syndrome. Lipase, phospholipase, protease, α-amylase, β-glucosidase, and xanthine oxidase activities under treatment with aqueous and ethanolic extracts of Euphorbia cyparissias were observed to evaluate the inhibitory effect of these extracts, as well as their antioxidant and cytotoxic effects. Results showed that ethanolic and aqueous extracts exhibited important inhibitory activity in a concentration-related manner on digestive enzymes, which is more effective than the commercial drugs used as controls. Results also showed that, out of the two extracts tested, the ethanolic extract presented the most promising results in inhibiting the activities of all digestive enzymes used. Moreover, the two extracts displayed a higher reducing power than that of the positive control used. The obtained results, together with previous reports in the literature, strongly suggest that Euphorbia cyparissias extracts may be natural inhibitors of the digestive enzymes and thus a potential new drug for metabolic syndrome treatment.

Metabolites of proper fatty acids modulate the inflammatory response and are essential for normal brain development; equally, abnormal fatty acid metabolism plays a critical role in the pathology of autism. Currently, dietary supplements are often used to improve the core symptoms of Autism spectrum disorder (ASD). The present study analyzed the effects of orally supplemented omega-3 (ω-3) and vitamin B12 on ameliorating oxidative stress and impaired lipid metabolism in a propionic acid (PPA)-induced rodent model of autism, together with their effect on the gut microbial composition, where great fluctuations in the bacterial number and strains were observed; interestingly, polyunsaturated fatty acids such as omega-3 induced higher growth of the gram-positive bacterium Staphylococcus aureus and decreased the survival rates of Clostridia sp. as well as other enteric bacterial strains. Thirty-five young male western albino rats were divided into five equal groups. The first group served as the control; the second group was given an oral neurotoxic dose of PPA (250 mg/kg body weight/day) for 3 days. The third group received an oral dose of ω-3 (200 mg/kg body weight/day) for 30 days after the 3-day PPA treatment. Group four was given an oral dose of vitamin B12 (16.7 mg/kg/day) for 30 days after PPA treatment. Finally, group five was given a combination of both ω-3 and vitamin B12 at the same dose for the same duration after PPA treatment. Biochemical parameters related to oxidative stress and impaired fatty acid metabolism were investigated in the brain homogenates of each group. The effects of the dietary supplements on the gut microbiota were also observed. The PPA-treated autistic model expressed significantly higher levels of lipid peroxides and 5-lipoxygenase (5-LOX) and significantly less glutathione (GSH), glutathione S-transferase (GST), and cyclooxygenase 2 (COX2) than the control group. However, a remarkable amelioration of most of the impaired markers was observed with oral supplementation with ω-3 and vitamin B12, either alone or in combination. Our results concluded that impairment at various steps of the lipid metabolic pathways may contribute to the development of autism; however, supplementation with ω-3 and vitamin B12 can result in a positive therapeutic effect.

The gut and the liver are closely linked to each other, as changes in the gut microbiota can play a significant role in the development of many liver diseases. Gut bacteria respond rapidly to changes in diet and thus can affect the liver through their metabolites. The impact of a high lipid diet on the liver in the presence of an altered gut flora modulated by ampicillin was investigated. The study was performed on 30 male Western albino rats randomly divided into 3 groups: control (phosphate buffered saline treated), group II (ampicillin 50 mg/kg for three weeks to induce microbiota alterations and fed on standard diet) and group III (same dose of ampicillin and fed on a lipid rich diet). Stool samples were collected for qualitative determination of bacteria. Serum hepato-specific markers, in addition to Glutathione (GSH), Lipid peroxidase (MDA), Glutathione-S- transferase(GST), and vitamin C in liver tissues, were measured. Altered gut microbiota significantly increased the level of the hepato-specific marker MDA and reduced the GST, GSH and vitamin C levels. However, animals fed a lipid rich diet displayed a more significant shift in hepatic markers and antioxidants. Moreover, a new switch in composition of the gut bacteria was observed by feeding the lipid rich diet. Our study showed that bacterial overgrowth in the gut can be associated with liver dysfunction and that a high lipid diet can promote the overgrowth of some liver damaging microflora during antibiotic treatment.

Background Abnormal phospholipid metabolism is a major component of many neurodevelopmental disorders including autism. Oral administration of propionic acid (PPA) can produce behavioral abnormalities and biochemical features in rodents similar to those observed in autism and can thus be used as a model to understand impaired brain fatty acid metabolism in autism. Methods The present study was designed to understand alterations in phospholipid metabolism in the brain of a rodent model of autism and to explore omega-3 and vitamin B12 as remedies. Five groups of rats were selected: Group 1 was the control. Group 2 was the rodent model of autism treated with a neurotoxic dose of PPA. Group 3 was given vitamin B12 cobalamin (16.7 mg/kg/day) for 30 days after PPA treatment. Group 4 was given pharmaceutical grade Omega-3 (200 mg cholesterol free-DHA/kg body weight/day), a product of Madre lab, Germany, for 30 days after PPA treatment for 3 days. Group 5 was given a combined dose of ω-3 + Vitamin B12 for the same duration post-PPA treatment. Phospholipid levels and Phospholipase A2 were measured in the brain homogenates of all the groups. ELISA and western blotting were used to detect the cPLA2 protein level. Results A significant decrease in phospholipid levels and a significant increase in cPLA2 were found in brain tissue of PPA-treated rats; however, both ω-3 and vitamin B12 were efficient in ameliorating the neurotoxic effect of PPA. Conclusion Both ω-3 and vitamin B12 may play a role in ameliorating impaired phospholipid metabolism in autism; however, proper clinical trials are needed.