Background: Alzheimer’s disease (AD) is a neurodegenerative disorder that is associated with abnormal cognition. AD is aided in its initiation and progression by hereditary and environmental factors. Aluminum (Al) is a neurotoxic agent that causes oxidative stress, which is linked to AD progression. Additionally, Nrf2/HO-1, APOE4/LRP1, Wnt3/β-catenin, and TLR4/NLRP3 are the main signaling pathways involved in AD pathogenesis. Several phytochemicals are promising options in delaying AD evolution. Objectives: This study aimed at studying the neuroprotective effects of some phytochemicals as morin (MOR), thymol (TML), and thymoquinone (TMQ) on physical and mental activities (PhM) in Al chloride (AlCl₃)-induced AD rat model. Another objective was to determine the specificity of phytochemicals to AD signaling pathways using molecular docking. Methods: Eighty male Dawley rats were divided into eight groups. Each group received: saline (control group), AlCl₃, (ALAD), PhM, either alone or with a combination of MOR, TML, and/or TMQ for five weeks. Animals were then subjected to behavioral evaluation. Brain tissues were used for histopathological and biochemical analyses to determine the extent of neurodegeneration. The effect of phytochemicals on AlCl₃-induced oxidative stress and the main signaling pathways involved in AD progression were also investigated. Results: AlCl₃ caused a decline in spatial learning and memory, as well as histopathological changes in the brains of rats. Phytochemicals combined with PhM restored antioxidant activities, increased HO-1 and Nrf2 levels, blocked inflammasome activation, apoptosis, TLR4 expression, amyloide-β generation, and tau hyperphophorylation. They also brought ApoE4 and LRP1 levels back to normal and regulated Wnt3/β-catenin/GSK3β signaling pathway. Conclusions: The use of phytochemicals with PhM is a promising strategy for reducing AD by modulating Nrf2/HO-1, TLR4/NLRP3, APOE4/LRP1, and Wnt3/β-catenin/GSK-3β signaling pathways.

Recently, an alternative disease treatment approach is the research of medicaments from traditional medicine. Plants with anti-oxidant capabilities are used as herbal treatments for ulcer diseases. Medicinal/herbal extracts containing phytoconstituents have significant anti-ulcer activities in in vivo experiments on animal models, compared to reference drugs. The current study aims to inspect gastro-protective as well as in vitro and in vivo anti-oxidant potential of Althaea officinalis and Solanum nigrum extracts on pyloric-ligation/indomethacin-induced gastric-ulceration in rats. Rats were divided into six groups: normal control, gastric ulcer control, two standard pretreatment groups receiving omeprazole and misoprostol, and two test pretreatment groups receiving Althaea officinalis and Solanum nigrum. Pretreatments were administrated orally for 14 days. On the 15th day, animals, excluding the normal control group, were exposed to pyloric-ligation followed by indomethacin injection. After four hours, the rat’s stomachs were removed and gastric juice and blood samples were collected. Pyloric-ligation/indomethacin administration caused considerable elevation in ulcer number, ulcer index, acid and pepsin productivity, aggressive factors, and gastric mucosal lipid-peroxide contents. Moreover, reduction in titratable acidity, gastric mucosal nitric-oxide, anti-oxidant contents, and protective factors accompanied gastric-ulceration. Additionally, elevation in pro-inflammatory cytokines content and reduction in cystathionine-β-synthase and heme-oxygenase-1 expression was witnessed. Omeprazole, misoprostol, Althaea officinalis, and Solanum nigrum pretreatments fixed blood and tissue biomarkers, thereby protecting them from pyloric-ligation/indomethacin-induced gastric-ulceration in rats, which is hopeful for clinical examinations.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder affecting the substantia nigra where functions controlling body movement take place. Manganese (Mn) overexposure is linked to a neurologic syndrome resembling PD. Sesamol, thymol, wheat grass (WG), and coenzyme Q10 (CoQ10) are potent antioxidants, anti-inflammatory, and anti-apoptotic nutraceuticals. We investigated the potential protective effects of these nutraceuticals alone or in combinations against MnCl₂-induced PD in rats. Seven groups of adult male Sprague Dawley rats were categorized as follows: group (I) was the control, while groups 2–7 received MnCl₂ either alone (Group II) or in conjunction with oral doses of sesamol (Group III), thymol (Group IV), CoQ10 (Group V), WG (Group VI), or their combination (Group VII). All rats were subjected to four behavioral tests (open-field, swimming, Y-maze, and catalepsy tests). Biochemical changes in brain levels of monoamines, ACHE, BDNF, GSK-3β, GABA/glutamate, as well as oxidative stress, and apoptotic and neuroinflammatory biomarkers were evaluated, together with histopathological examinations of different brain regions. Mn increased catalepsy scores, while decreasing neuromuscular co-ordination, and locomotor and exploratory activity. It also impaired vigilance, spatial memory, and decision making. Most behavioral impairments induced by Mn were improved by sesamol, thymol, WG, or CoQ10, with prominent effect by sesamol and thymol. Notably, the combination group showed more pronounced improvements, which were confirmed by biochemical, molecular, as well as histopathological findings. Sesamol or thymol showed better protection against neuronal degeneration and some behavioral impairments induced by Mn than WG or CoQ10, partly via interplay between Nrf2/HO-1, TLR4/NLRP3/NF-κB, GSK-3β and Bax/Bcl2 pathways.

Background: Gastric ulcer is one of the most serious diseases. Most classic treatment lines produce adverse drug reactions. Therefore, this study aimed to investigate the protective effects of two natural extracts, namely ginger and marshmallow extracts, on indomethacin-induced gastric ulcer in rats. Materials and Methods: Animals were divided into five groups; a normal control group, an ulcer control group, and three treatment groups receiving famotidine (20 mg/kg), ginger (100 mg/kg), and marshmallow (100 mg/kg). Treatments were given orally on a daily basis for 14 days prior to a single intra-peritoneal administration of indomethacin (20 mg/kg). Results: Indomethacin administration resulted in significant ulcerogenic effect evidenced by significant elevations in ulcer number, ulcer index, and blood superoxide dismutase activity accompanied by significant decreases in gastric mucosal nitric oxide and glutathione levels. In addition, elevations in gastric mucosal lipid peroxides and histamine content were observed. Alternatively, pretreatment with famotidine, ginger or marshmallow significantly corrected macroscopic and biochemical findings, supported microscopically by results of histopathological study. Conclusion: These results demonstrate that administration of either ginger or marshmallow extract could protect against indomethacin-induced peptic ulcer in rats presumably via their antioxidant properties and inhibition of histamine release.