6-shogaol against 3-Nitropropionic acid-induced Huntington's disease in rodents: Based on molecular docking/targeting pro-inflammatory cytokines/NF-κB-BDNF-Nrf2 pathway.

BACKGROUND: Huntington's disease (HD) is an extremely harmful autosomal inherited neurodegenerative disease. Motor dysfunction, mental disorder, and cognitive deficits are the characteristic features of this disease. The current study examined whether 6-shogaol has a protective effect against 3-Nitropropionic Acid (3-NPA)-induced HD in rats. METHODS: A total of thirty male Wistar rats received 6-shogaol (10 and 20 mg/kg, per oral) an hour before injection of 3-NPA (10 mg/kg i.p.) for 15 days. Behavioral tests were performed, including narrow beam walk, rotarod test, and grip strength test. Biochemical tests promoting oxidative stress were evaluated [superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT) and malondialdehyde (MDA)], including changes to neurotransmitters serotonin (5-HT), dopamine (DA), norepinephrine (NE), homovanillic acid (HVA), (3,4-dihydroxyphenylacetic acid (DOPAC), γ-aminobutyric acid (GABA), and 5-hydroxy indole acetic acid (5-HIAA), nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), interleukins-1ß (IL-1ß), IL-6, brain-derived neurotrophic factor (BDNF), and nuclear factor erythroid 2-related factor 2 (Nrf2). The 6-shogaol was docked to the active site of TNF-α (2AZ5), NF-κB (1SVC), BDNF) [1B8M], and Nrf2 [5FZN] proteins using AutoDock tools. RESULTS: The 6-shogaol group significantly improved behavioral activity over the 3-NPA-injected control rats. Moreover, 3-NPA-induced significantly altered neurotransmitters, biochemical and neuroinflammatory indices, which could efficiently be reversed by 6-shogaol. The 6-shogaol showed favorable negative binding energies at -9.271 (BDNF) kcal/mol. CONCLUSIONS: The present investigation demonstrated the neuroprotective effects of 6-shogaol in an experimental animal paradigm against 3-NPA-induced HD in rats. The suggested mechanism is supported by immunohistochemical analysis and western blots, although more research is necessary for definite confirmation.

A biochemical, theoretical and immunohistochemical study comparing the therapeutic efficacy of curcumin and taurine on T-2 toxin induced hepatotoxicity in rats.

Introduction: Foodborne trichothecene T-2 Toxin, is a highly toxic metabolite produced by Fusarium species contaminating animal and human food, causing multiple organ failure and health hazards. T-2 toxins induce hepatotoxicity via oxidative stress causing hepatocytes cytotoxicity and genotoxicity. In this study, curcumin and taurine were investigated and compared as antioxidants against T-2-provoked hepatotoxicity. Methods: Wistar rats were administrated T-2 toxin sublethal oral dose (0.1 mg/kg) for 2 months, followed by curcumin (80 mg/kg) and taurine (50 mg/kg) for 3 weeks. Biochemical assessment of liver enzymes, lipid profiles, thiobarbituric acid reactive substances (TBARs), AFU, TNF-α, total glutathione, molecular docking, histological and immunohistochemical markers for anti-transforming growth factor-ß1 (TGFß1), double-strand DNA damage (H2AX), regeneration (KI67) and apoptosis (Active caspase3) were done. Results and Discussion: Compared to T-2 toxin, curcumin and taurine treatment significantly ameliorated hepatoxicity as; hemoglobin, hematocrit and glutathione, hepatic glycogen, and KI-67 immune-reactive hepatocytes were significantly increased. Although, liver enzymes, inflammation, fibrosis, TGFß1 immunoexpressing and H2AX and active caspase 3 positive hepatocytes were significantly decreased. Noteworthy, curcumin's therapeutic effect was superior to taurine by histomorphometry parameters. Furthermore, molecular docking of the structural influence of curcumin and taurine on the DNA sequence showed curcumin's higher binding affinity than taurine. Conclusion: Both curcumin and taurine ameliorated T-2 induced hepatotoxicity as strong antioxidative agents with more effectiveness for curcumin.

Correlation between Antioxidant and Anti-Osteoporotic Activities of Shilajit Loaded into Chitosan Nanoparticles and Their Effects on Osteoporosis in Rats.

Various therapies for osteoporosis successfully reduce bone loss and fractures, but they mostly do not contribute to new bone structures and adversely affect patients. Shilajit is a natural mineral substance comprised of multi-components, with proved efficacy to improve immunity, antioxidant activity, and disease resistance. In the present study, various effects of shilajit water extract (SWE) on bone development and its management were determined in experimental glucocorticoid-induced osteoporotic rats. The fabrication of nanochitosan (NCT) and NCT conjugation with SWE were conducted and evaluated as enhanced formulations for treating osteoporosis. NCT and SWE/NCT had mean particle diameters of 196.4 and 248.4 nm, respectively, with high positivity charging and stability. The biochemical and anti-osteoporotic effects of SWE and SWE/NCT conjugates were investigated on different groups of compromised rats. Five groups each including six adult albino female rats were formed and treated for a duration of eight weeks with SWE and SWE/NCT conjugate. Significantly improved serum calcium, phosphorus, osteocalcin, and calcitonin levels but decreased hydrogen peroxide, IL-6, and antioxidant biomarkers were recorded in all SWE- and SWE/NCT-treated groups; the SWE/NCT treatment was most effectual treatment. These results suggest that SWE and SWE/NCT may cause anti-osteoporotic activity by reducing oxidative stress, IL-6, and H2O2 while restoring antioxidant levels. The conjugation of SWE onto NCT is highly recommended for augmenting their activities.

Shilajit potentiates the effect of chemotherapeutic drugs and mitigates metastasis induced liver and kidney damages in osteosarcoma rats.

Osteosarcoma is a primary malignant cancer of the bone identified by the direct formation of osteoid tissue or immature bone by cancer cells. The liver and kidneys represent two major secondary organs to which osteosarcoma metastasizes. In this study, we assessed Shilajit, a phytomineral diffusion traditionally used in Ayurvedic medicine, for its possible protective effects against metastasis induced liver and kidney damages in an osteosarcoma rat model. Osteosarcoma rats displayed typical dysregulation of serum levels of hepatic and renal functional markers (p < 0.05) including aspartate aminotransferase (AST)* and alanine aminotransferase (ALT), alkaline phosphatase (ALP), total proteins, albumin, bilirubin, creatinine, urea, and uric acid. Changes in functional markers were also positively correlated with marked histopathological alterations in liver and kidney tissues. Whereas Shilajit's treatment of osteosarcoma rates in combination with CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) chemotherapy drug cocktail significantly (p < 0.05) reversed the studied functional markers to their near-normal levels. Co-treatment of shilajit and drug cocktails also markedly alleviated histopathological changes in liver and kidney tissues. Correlation co-efficient analysis of hepatic and renal functional markers revealed a significant inter-association among these markers. Collectively, present data indicate that shilajit may potentiate the effects of chemotherapy drugs and mitigate the metastasis-induced liver and kidney damage in osteosarcoma. Thus, the findings of this study substantiate the beneficial health effects of shilajit and promote its regular consumption.

Biochemical and Histological Study of the Impact of Combined Lepidium sativum and Citric Acid on Liver and Kidney Functions in Rats.

The study aimed to determine the interaction of using LS and CA in combination on liver, kidney, and heart functions in rats and to evaluate the role of antioxidant effects of LS against CA-induced hepato-renal toxicity. This study was conducted on 36 male rats divided into four groups (n = 9). The groups were; the control, LS-treated (10 g/100 g of food), CA-treated (5 g/100 g of food), and combined LS plus CA-treated groups for 6 weeks. Kidney, liver and heart functions as well as oxidant/antioxidant profile were biochemically assessed in the serum using ELISA. The impact of LS and CA on kidney and liver was histopathologically assessed. Rats fed on diet supplemented with LS for 6 weeks showed no significant change in serum levels of the biochemical markers of liver, kidney and heart functions, while supplementation with CA significant increased (p < 0.001) the serum levels of these markers compared to the control group. Combined administration of LS and CA significantly reduced the serum levels of these parameters compared to CA-treated group. Oxidative markers significantly increased while the antioxidants one decreased in CA-treated group compared to the control. Combined LS and CA significantly improve the oxidant/antioxidant profile as well as histopathological impact compared to CA-treated group.

Effects of aluminum chloride and coenzyme Q10 on the molecular structure of lipids and the morphology of the brain hippocampus cells.

Aluminum chloride (AlCl3) is a neurotoxic substance, while coenzyme Q10 (CoQ10) is considered a lipid antioxidant. Herein, their effects on the molecular structure of lipids and the morphology of the hippocampus brain tissue were investigated. Three groups of Wistar albino male rats were used in this study. For four weeks, one group was kept as a control group; the second group was given AlCl3; the third group was given AlCl3/CoQ10. Fourier transform infrared (FTIR) and histopathological examinations were utilized to estimate alterations in the molecular structure of the lipids and the cell morphology, respectively. The FTIR spectra revealed considerable decreases in the CH contents and alterations in the molecular ratios of olefinic[double bond, length as m-dash]CH/νas(CH3), νas(CH2)/νas(CH3), and νas(CH2)/[νas(CH2) + νs(CH2)] in the group given AlCl3. However, no significant changes were detected in those rats given AlCl3/CoQ10. Histopathology images uncovered shrinking and dark centers in the pyramidal cells of brain tissue hippocampal cells. The diameters of the pyramidal cells were estimated to be 4.81 ± 0.55 µm, 4.04 ± 0.71 µm, and 4.63 ± 0.71 µm for the control, AlCl3, and AlCl3/CoQ10 groups, respectively. The study showed that the AlCl3 could cause a shrinking of around 16% in the hippocampus pyramidal cells; besides, CoQ10 is a powerful therapeutic antioxidant to help restore the hippocampal neurons to a regular state.

Correction: Effects of aluminum chloride and coenzyme Q10 on the molecular structure of lipids and the morphology of the brain hippocampus cells.

[This corrects the article DOI: 10.1039/D1RA03786B.].

Microalgal flocculation: Global research progress and prospects for algal biorefinery.

Microalgal research has made significant progress due to versatile and high-value industrial applications of microalgal biomass or its derivatives. However, to explore their full potential and to achieve commercial robustness, microalgal biorefinery needs cost-effective technologies to produce, harvest, and process the microalgal biomass on large scale as higher production and harvesting cost is one of the key hindrances in the commercialization of algae-based products. Among several other algal biomass harvesting technologies, self-flocculation seems to be an attractive, low-cost, and eco-friendly harvesting technology. This review covers various flocculation-based methods that have been employed to harvest microalgal biomass with a special emphasis on self-flocculation in microalgae. Moreover, genetic engineering approaches to induce self-flocculation in non-flocculating microalgae along with the factors affecting self-flocculation and recent research trends have also been discussed. It is concluded that self-flocculation is the most desired approach for the energy- and environment-efficient harvesting of microalgal biomass. However, its poorly understood genetic basis needs to be deciphered through detailed studies to harness its potential for the algal biorefinery.

Molecular Identification, Characterization and Antioxidant Activities of Some Bacteria Associated with Algae in the Red Sea of Jeddah.

BACKGROUND AND OBJECTIVE: Algae-associated bacteria produce secondary metabolites that have a great biological impact. The aim of this study was isolation, identification and evaluation the antioxidant activities of the associated bacteria of seven algae, Padina pavonica, Dictyota dichotoma, Cystoseira myrica, Halimeda opuntia, Ulva lactuca, Digenea simplex and Jania sp. The bacteria were isolated, characterized and identified. Identification was carried out using 16S rRNA gene sequencing. MATERIALS AND METHODS: The identified bacteria were belonging to 6 families, Alteromonadaceae, Bacillaceae, Lactobacillaceae, Pseudomonadaceae, Rhodobacteraceae and Vibrionaceae and 9 genera. The identified bacteria were belonging to genera, Alteromonas, Bacillus, Lysinibacillus Vibrio, Lactobacillus, Paracoccus, Leisingera, Pseudomonas and Pseudovibrio. The antioxidant activities of the bacterial ethyl acetate extracts was examined by scavenging DPPH (2,2-diphenyl-1-picrylhydrazyl) and FRAP (Ferric Reducing Antioxidant Power) methods. RESULTS: Out of the 17 isolated bacteria, Lactobacillus plantarum showed 95.7% free radical scavenging with EC50 = 17.7 µg mL-1, which is nearly similar to the positive control (Butylated Hydroxytoluene, BHT). The FRAP value of Lactobacillus extract was 2.00 mM ferric equivalent/mg of the extract. Phytochemical analysis of the bacterial extract revealed the presence of some secondary metabolites such as steroids, saponins, tannins, flavonoids, anthocyanin and betacyanin in all tested extracts. CONCLUSION: The Red Sea algal associated bacteria have a great antioxidant potential that can be used in pharmaceutical industries.

Current Status and Future Opportunities of Omics Tools in Mycotoxin Research.

Mycotoxins are toxic secondary metabolites of low molecular weight produced by filamentous fungi, such as Aspergillus, Fusarium, and Penicillium spp. Mycotoxins are natural contaminants of agricultural commodities and their prevalence may increase due to global warming. Dangerous mycotoxins cause a variety of health problems not only for humans, but also for animals. For instance, they possess carcinogenic, immunosuppressive, hepatotoxic, nephrotoxic, and neurotoxic effects. Hence, various approaches have been used to assess and control mycotoxin contamination. Significant challenges still exist because of the complex heterogeneous nature of food composition. The potential of combined omics approaches such as metabolomics, genomics, transcriptomics, and proteomics would contribute to our understanding about pathogen fungal crosstalk as well as strengthen our ability to identify, isolate, and characterise mycotoxins pre and post-harvest. Multi-omics approaches along with advanced analytical tools and chemometrics provide a complete annotation of such metabolites produced before/during the contamination of crops. We have assessed the merits of these individual and combined omics approaches and their promising applications to mitigate the issue of mycotoxin contamination. The data included in this review focus on aflatoxin, ochratoxin, and patulin and would be useful as benchmark information for future research.