Alzheimer's disease (AD) is a neurodegenerative disorder characterized by gradual cognitive decline. Strong antioxidants that inhibit free radicals, such as polyphenols, reduce the likelihood of ...developing oxidative stress-related degenerative diseases such as AD. Naringin, a flavonoid found in citrus fruit shown to be neuroprotective, reduce oxidative damage and minimize histopathological changes caused by ischemic reperfusion, enhance the long-term memory in AD animal models. This work aimed to comprehend the role of naringin in the defense of the cerebellum against aluminum chloride (AlCl
)-induced AD in rats by investigating the behavioral, neurochemical, immunohistochemical, and molecular mechanisms that underpin its possible neuroprotective effects. Twenty-four adult albino rats were divided into four groups (
= 6/group): (i) Control (C) received saline per oral (p.o.), (ii) Naringin(
)-received naringin (100 mg/kg/d) p.o, (iii) AlCl
-recived AlCl
(100 mg/kg/d) p.o and (iv) AlCl
+ Naringin (AlCl
+
) received both AlCl
and naringin p.o for 21 days. Behavioral tests showed an increase in the time to reach the platform in Morris water maze, indicating memory impairment in the AlCl
-treated group, but co-administration of naringin showed significant improvement. The Rotarod test demonstrated a decrease in muscle coordination in the AlCl
-treated group, while it was improved in the AlCl
+
group. Neurochemical analysis of the hippocampus and cerebellum revealed that AlCl
significantly increased lipid peroxidation and oxidative stress and decreased levels of reduced glutathione. Administration of naringin ameliorated these neurochemical changes
its antioxidant properties. Cerebellar immunohistochemical expression for microtubule assembly (tau protein) and oxidative stress (iNOS) increased in A1C1
-treated group. On the other hand, the expression of the autophagic marker (LC3) in the cerebellum showed a marked decline in AlCl
-treated group. Western blot analysis confirmed the cerebellar immunohistochemical findings. Collectively, these findings suggested that naringin could contribute to the combat of oxidative and autophagic stress in the cerebellum of AlCl
-induced AD.
Background: Parkinson’s disease (PD) is a neurological condition that typically shows up with aging. It is characterized by generalized slowness of movement, resting tremor or stiffness, and ...bradykinesia. PD patients’ brains mostly exhibit an increase in inflammatory mediators and microglial response. Nevertheless, a variety of non-steroidal anti-inflammatory medications (NSAIDS) offered neuroprotection in animal models and preclinical trials. Aim: The current systematic review and meta-analysis were designed to try to resolve the debate over the association of NSAID use with the development of PD because the results of several studies were somehow contradictory. Methods: An intense search was performed on Scopus, PubMed, and Web of Science databases for articles relating the incidence of PD to the use of NSAIDs. Statistical analysis of the included studies was carried out using Review Manager version 5.4.1 by random effect model. The outcome was identified as the development of PD in patients who were on NSAIDs, ibuprofen only, aspirin only, and non-aspirin NSAIDs. This was analyzed using pooled analysis of odds ratio (OR) at a significance level of ≤0.05 and a confidence level of 95%. A statistically significant decreased risk of PD was observed in patients taking NSAIDs, Ibuprofen, and non-aspirin NSAIDs. Results: The ORs of PD occurrence in patients who took NSAIDs, Ibuprofen, and non-aspirin NSAIDs were 0.88 95% CI (0.8–0.97), p = 0.01, 0.73 95% CI (0.53–1), p = 0.05 and 0.85 95% CI (0.75–0.97), p = 0.01. Meanwhile, the risk of PD in patients who took aspirin was not statistically significant. Conclusion: In conclusion, Ibuprofen, non-aspirin NSAIDs, and other types of NSAIDs could be associated with a reduction in PD risk. However, there was no association between aspirin intake and the development of PD.
In cancer management, drug resistance remains a challenge that reduces the effectiveness of chemotherapy. Several studies have shown that curcumin resensitizes cancer cells to chemotherapeutic drugs ...to overcome resistance. In the present study, we investigate the potential therapeutic role of curcumin in regulating the proliferation of drug-resistant cancers. Six drug-sensitive (MCF7, HCT116, and A549) and -resistant (MCF7/TH, HCT116R, and A549/ADR) cancer cell lines were treated with curcumin followed by an analysis of cytotoxicity, LDH enzyme, total reactive oxygen species, antioxidant enzymes (SOD and CAT), fibrosis markers (TGF-β1 protein, fibronectin, and hydroxyproline), and expression of cellular apoptotic markers (Bcl-2, Bax, Bax/Bcl-2 ratio, Annexin V, cytochrome c, and caspase-8). Additionally, the expression of cellular SIRT1 was estimated by ELISA and RT-PCR analysis. Curcumin treatment at doses of 2.7–54.3 µM significantly reduced the growth of sensitive and resistant cells as supported with decreased viability and increased cellular LDH enzyme of treated cells compared to controls non-treated cells. Curcumin also at doses of 2.7 and 54.3 µM regulated the fibrogenesis by reducing the expression of fibrotic markers in treated cells. Analysis of apoptotic markers indicated increased Bax, Bax, Bax/Bcl-2 ratio, Annexin V, caspase-8, and cytochrome c expression, while Bcl-2 expressions were significantly reduced. In curcumin-treated cells at 2.7 μM, non-significant change in ROS with significant increase in SOD and CAT activity was observed, whereas an increase in ROS with a reduction in respective antioxidant enzymes were seen at higher concentrations along with significant upregulation of SIRT1. In conclusion, the present study shows that curcumin induces anticancer activity against resistant cancer cell lines in a concentration- and time-dependent manner. The protective activities of curcumin against the growth of cancer cells are mediated by modulating oxidative stress, regulating fibrosis, SIRT1 activation, and inducing cellular apoptosis. Therefore, curcumin could be tested as an auxiliary therapeutic agent to improve the prognosis in patients with resistant cancers.
Pure and manganese-doped titanium dioxide nanoparticles (MnTiO2-NPs) were synthesized by the defect-oriented hydrothermal approach. The synthesized material was then characterized by X-ray ...diffraction (XRD), Scanning electron microscopy (SEM), Energy dispersive X-ray spectroscopy (EDX), and UV–visible spectroscopy (UV–Vis). The agar well diffusion method assessed the antibacterial efficiency of TiO2 and MnTiO2-NPs against E. coli and S. aureus. Zone of inhibition (ZOI) formed by pure TiO2 was observed as 12 mm and 11.5 mm against E. coli and S. aureus, while for MnTiO2-NPs it was observed as 19 mm (E. coli) and 21 mm (S. aureus). The concentration of synthesized nanoparticles (10 mg/ml, and 20 mg/ml) was used for antibacterial studies. The efficacy of the pure and MnTiO2-NPs as an active photocatalyst for the degradation of methylene blue (MB) dye was also assessed using a UV light. It was observed that the photodegradation efficiency of 1 g of MnTiO2-NPs was higher than the same amount of pure TiO2. The results suggest that the photocatalyst concentration directly impacts the photodegradation of MB dye. The pH value was found to influence the photodegradation of MB dye at higher pH values. Based on the obtained results, MnTiO2-NPs were observed as a promising agent for microbial resistance and water remediation.
•Highlights (for review).•Synthesized pure and manganese-doped TiO2-NPs via defect-oriented hydrothermal technique.•MnTiO2-NPs were found to have better antibacterial efficiency than TiO2.•MnTiO2-NPs were found as a promising agent for microbial resistance.•MnTiO2-NPs were found as an active photocatalyst for the degradation of methylene blue.
Aim of the current study was to prepare and estimate capsaicin loaded microemulgel (CaP-ME) for the treatment of inflammation. The preparation of CaP-ME was based on the pseudo ternary phase diagram ...by the phase titration method using various oils such as clove oil, cinnamon oil, turpent oil. To the CaP-ME, different combination of gelling agents was incorporated. CaP-ME was prepared by incorporating different gelling agent such as aerosil and chitosan in to a CaP-MEs. Various preparations were assessed for pH, physical appearance, spreadability, in vitro release and particle size (PS), etc. The results obtained from the preparation of CaP-ME exhibited globule size of 31.6 ± 1.11 nm, polydisperse index (0.441 ± 0.02), % transmittance, and drug content (95.5 ± 8.16%) were within in the range. From the performed pseudo ternary phase diagrams using various oils, 3 pseudo ternary phase diagram was selected based on the area of ME for the further formulation of MEs. Three MEs (F1, F2, F3) were prepared and the F3 shown the better results in all the parameters. The chitosan (G1)-based CaP-ME (F3) gel had a good transparency, better spreadability, extrudability, pH and in vitro release (94.76 ± 5.09%). Hence, it was concluded that turpentine oil is the best oil phase for the preparation of CaP-MEs when compared with other oils like clove oil and cinnamon oil and chitosan-based gel exhibits their efficient topical delivery.
The majority of the suggested experimental modalities for peripheral nerve injury (PNI) result in varying degrees of recovery in animal models; however, there are not many reliable clinical ...pharmacological treatment models available. To alleviate PNI complications, research on approaches to accelerate peripheral nerve regeneration is encouraged. Cerebrolysin, dexamethasone, and ascorbic acid (vitamin C) drug models were selected in our study because of their reported curative effects of different mechanisms of action.
A total of 40 adult male albino rats were used in this study. Sciatic nerve crush injury was induced in 32 rats, which were divided equally into four groups (model, Cerebrolysin, dexamethasone, and vitamin C groups) and compared to the sham group (
= 8). The sciatic nerve sensory and motor function regeneration after crushing together with gastrocnemius muscle histopathological changes were evaluated by the sciatic function index, the hot plate test, gastrocnemius muscle mass ratio, and immune expression of S100 and apoptosis cascade (BAX, BCL2, and BAX/BCL2 ratio).
Significant improvement of the behavioral status and histopathological assessment scores occurred after the use of Cerebrolysin (as a neurotrophic factor), dexamethasone (as an anti-inflammatory), and vitamin C (as an antioxidant). Despite these seemingly concomitant, robust behavioral and pathological changes, vitamin C appeared to have the best results among the three main outcome measures. There was a positive correlation between motor and sensory improvement and also between behavioral and histopathological changes, boosting the effectiveness, and implication of the sciatic function index as a mirror for changes occurring on the tissue level.
Vitamin C is a promising therapeutic in the treatment of PNI. The sciatic function index (SFI) test is a reliable accurate method for assessing sciatic nerve integrity after both partial disruption and regrowth.
Aquaporins (AQPs) are transmembrane channel proteins. Aquaporin 1 (AQP1), Aquaporin 3 (AQP3), and Aquaporin 7 (AQP7) are expressed in the jejunum. The purpose of this study was to ascertain how a ...high-fat high-fructose diet (HFFD) and intermittent fasting (IF) affect AQP1, AQP3, and AQP7 expression in the rat jejunum.
Sixteen adult male rats were divided into control rats (n = 4) fed on a basal diet and water ad libitum for 12 weeks; IF control rats (n = 4) followed the IF protocol, HFFD-fed rats (n = 8) fed HFFD for eight weeks, and rats were randomized into two groups: HFFD only or HFFD and IF protocol from the beginning of the 9th week until the end of the experiment. The lipid profile values were assessed after 12 weeks. Jejunal oxidative markers (malondialdehyde and reduced glutathione) and AQP1, AQP3, and AQP7 mRNA expression were measured. Jejunal sections were used for morphometric analysis of villus length and crypt depth. Immunohistochemical evaluation of AQP1, AQP3, and AQP7 expression was also performed.
IF ameliorates HFFD-induced lipid profile, oxidative stress, and jejunal morphometric changes. The results of both mRNA expression using PCR and immunohistochemistry showed a significant increase in AQP1, AQP3, and AQP7 expression in HFFD, whereas IF caused a decline in this expression.
These findings suggest that IF can reduce inflammation, and oxidative stress and restore jejunal morphology caused by HFFD.
•High Fat High fructose diet causes Jejunal histopathological changes and Jejunal oxidative stress.•Intermittent Fasting ameliorates the deleterious effect of the high fat on Jejunum.•Aquaporin1, Aquaporin3, and Aquaporin 7 expression increase in high-fat high fructose diet.•Intermittent fasting is an effective anti-obesity strategy.•Aquaporin1, Aquaporin3, and Aquaporin 7 can be used as therapeutic targets.
One of the most prevalent cardiovascular problems linked with type 2 diabetes mellitus (T2DM) is diabetic cardiomyopathy (DCM). DCM is associated with myocardial oxidative stress, inflammation, ...apoptosis, suppressed autophagy, extracellular matrix remodeling, and fibrosis. The current study aims to investigate the protective effect of sodium-glucose transport 2 inhibitor (SGLT2i) dapagliflozin and/or exercise on DCM. Thirty adult male Sprague Dawley rats are used. T2DM is induced by a 6-week high-fat diet (HFD) followed by a single intraperitoneal (IP) injection of 35 mg/kg streptozotocin (STZ). Rats are divided into five groups, control, diabetic (DM), DM + swimming, DM + dapagliflozin, and DM + dapagliflozin and swimming. Serum glucose, insulin, insulin resistance (HOMA-IR), and cardiac enzymes (CK-MB and lactate dehydrogenase (LDH) are measured. Heart specimens are used for evaluation of cellular oxidative stress markers malondialdehyde (MDA), antioxidant enzymes, glutathione (GSH), and catalase (CAT), as well as mRNA expression of TGF-β, MMP9, IL-1β, and TNF-α. Stained sections with haematoxylin and eosin (H & E) and Masson trichrome are used for histopathological evaluation and detection of fibrosis, respectively. Immunohistochemical staining for apoptosis (caspase-3), and autophagy (LC3) are also carried out. The combinations of SGLT2i and exercise exhibited the most significant cardioprotective effect. It improved diabetic-induced histopathological alterations in the myocardium and attenuated the elevation of serum blood glucose, CK-MB, LDH, myocardial MDA, and mRNA expression of TNF-α, IL-1β, TGF-β, MMP9, and the immune expression of caspase-3. Moreover, this combination increased the serum insulin, myocardial antioxidants GSH and CAT, and increase the immune expression of the LC-3. In conclusion, a combination of SGLT2i and exercise exerted a better antioxidant, anti-inflammatory, and antifibrotic effect in DCM. Moreover, the combination enhances the autophagic capacity of the heart.
Background: Nicotine is the active alkaloid in cigarettes. It was reported that tobacco smoking has many hazards; one of these hazards is the effect on the cognitive function of the prefrontal ...cortex. The aim of our study is to investigate the antioxidant effects of ginger, cinnamon oils, and their combination on morphological changes in the prefrontal cortex that were induced by nicotine. Materials and methods: Fifty adult male albino rats were divided into five groups: group I (control group), group II (nicotine), group III (nicotine + cinnamon), group IV (nicotine + ginger), and group V (nicotine + cinnamon + ginger). The coronal sections from the anterior part of the rat brain at the site of prefrontal cortex were examined by light microscope for (H&E and immunohistochemical staining with TNF-α and GFAP), while the ultrastructure morphology was examined by transmission electron microscopy. Levels of the oxidative stress markers (MDA, GSH) in the rats’ brain tissue homogenate were biochemically assessed. Results: Compared to the control group, the rats that were treated with nicotine (group II) showed a significant oxidative stress in the form of marked elevation of MDA and decrease in GSH, apoptotic changes especially in the pyramidal cells in the form of neuronal cell degeneration and pyknosis, and an elevation in the inflammatory marker TNF-α and GFAP expressions. These changes were observed to a lesser degree in rat group (III) and group (IV), while there was a marked improvement achieved by the combined usage of cinnamon and ginger oils, together compared to the nicotine group. Conclusions: Ginger and cinnamon are powerful antioxidants which ameliorate the degenerative and oxidative effects produced by nicotine on a rat’s prefrontal cortex.