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The level of ALT and ALP in all studied groups to confirm the accuracy of BDL surgery and its consequent cholestasis. **P < 0.01 in comparison with the control group, + P < 0.05 in comparison with the BDL group, using independent t-test
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Bile secretion is a physiological function that is disrupted following Bile Duct Ligation (BDL) and induces cholestasis. Cholestasis is a bile flow reduction that induces apoptosis, oxidative stress, and inflammation, and alters the expression of genes. Evidence shows the relationship between cholestasis and neuroinflammation. Cholestasis via atten...
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Cholestasis is a bile flow reduction that is induced following Bile Duct Ligation (BDL). Cholestasis impairs memory and induces apoptosis. Apoptosis consists of two pathways: intrinsic and extrinsic. The intrinsic pathway is modulated by BCL-2 (B cell lymphoma-2) family proteins. BCL-2 (a pro-survival BCL-2 protein) has anti-apoptotic effect, while...
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... There are some studies related to the effect of saffron constituents on neuroinflammation. For example, Eteghadi et al. showed that the administration of crocin could reduce neuroinflammation by decreasing pro-inflammatory cytokines, such as TNF-α and IL-1 in rats (Eteghadi et al. 2021). In another study, crocin attenuated neuroinflammation induced by methylphenidate ( Ebrahimzadeh et al. 2019). ...
Multiple sclerosis (MS) is an autoimmune disorder characterized by the degeneration of myelin and inflammation in the central nervous system. Trans sodium crocetinate (TSC), a novel synthetic carotenoid compound, possesses antioxidant, anti-inflammatory and neuroprotective effects. This study aimed to evaluate the protective effects of TSC against the development of experimental autoimmune encephalomyelitis (EAE), a well-established model for MS. Female BALB/C57 mice were divided into different groups, including control, EAE, vehicle, TSC-treated (25, 50, and 100 mg/kg, administered via gavage) + EAE, methyl prednisone acetate + EAE, and TSC-treated (100 mg/kg, administered via gavage for 28 days) groups. EAE was induced using MOG35-55, complete Freund’s adjuvant, and pertussis toxin. In the mice spinal cord tissues, the oxidative markers (GSH and MDA) were measured using spectrophotometry and histological evaluation was performed. Mitophagic pathway proteins (PINK1and PARKIN) and inflammatory factors (IL-1β and TNF-α) were evaluated by western blot. Following 21 days post-induction, EAE mice exhibited weight loss, and the paralysis scores increased on day 13 but recovered after TSC (100 mg/kg) administration on day 16. Furthermore, TSC (50 and 100 mg/kg) reversed the altered levels of MDA and GSH in the spinal cord tissue of EAE mice. TSC (100 mg/kg) also decreased microgliosis, demyelination, and the levels of inflammatory markers IL-1β and TNF-α. Notably, TSC (100 mg/kg) modulated the mitophagy pathway by reducing PINK1 and Parkin protein levels. These findings demonstrate that TSC protects spinal cord tissue against EAE-induced MS through anti-inflammatory, antioxidant, and anti-mitophagy mechanisms.
... It has been revealed that crocin reverses the increased level of corticosterone, cortical malondialdehyde (MDA), tumor necrosis factor-α, and IL-6 in rats exposed to chronic unpredictable mild stress (Abbaszade-Cheragheali et al., 2022). Previous research has also shown that crocin restores cholestasis-induced neuroinflammation in the striatum of male rats (Eteghadi et al., 2021). Therefore, crocin may suppress manic-like behaviors via attenuating inflammation. ...
Rapid-eye movement (REM) sleep deprivation (SD) can induce manic-like behaviors including hyperlocomotion. On the other hand, crocin (one of the main compounds of Crocus sativus L. or Saffron) may be beneficial in the improvement of mental and cognitive dysfunctions. Also, crocin can restore the deleterious effects of SD on mental and cognitive processes. In this study, we investigated the effect of REM SD on female rats’ behaviors including depression- and anxiety-like behaviors, locomotion, pain perception, and obsessive-compulsive-like behavior, and also, the potential effect of crocin on REM SD effects. We used female rats because evidence on the role of REM SD in modulating psychological and behavioral functions of female (but not male) rats is limited. REM SD was induced for 14 days (6h/day), and crocin (25, 50, and 75 mg/kg) was injected intraperitoneally. Open field test, forced swim test, hot plate test, and marble burying test were used to assess rats’ behaviors. The results showed REM SD-induced manic-like behavior (hyperlocomotion). Also, REM SD rats showed decreased anxiety- and depression-like behavior, pain subthreshold (the duration it takes for the rat to feel pain), and showed obsessive compulsive-like behavior. However, crocin at all doses partially or fully reversed REM SD-induced behavioral changes. In conclusion, our results suggested the possible comorbidity of OCD and REM SD-induced manic-like behavior in female rats or the potential role of REM SD in the etiology of OCD, although more studies are needed. In contrast, crocin can be a possible therapeutic choice for decreasing manic-like behaviors.
... It has been Mohammad Nasehi Nasehi@iricss.org 1 factor beta (TGF-β), in a rat model of cirrhosis (Wright et al. 2014). Studies have also shown that cholestasis can alter the function and the level of mitochondrial transcriptional factor A (TFAM) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), leading to cognitive decline (Eteghadi et al. 2021;Molaei et al. 2021;Xu et al. 2012;Wei et al. 2020). As we know, TFAM and PGC-1α are involved in transcription and maintenance of mitochondrial DNA and in mitochondrial biogenesis, respectively (Molaei et al. 2021;Kang et al. 2007;Liang and Ward 2006). ...
... As we know, TFAM and PGC-1α are involved in transcription and maintenance of mitochondrial DNA and in mitochondrial biogenesis, respectively (Molaei et al. 2021;Kang et al. 2007;Liang and Ward 2006). Furthermore, studies have reported that the level of catalase (CAT) and superoxide dismutase (SOD) are significantly decreased following cholestasis (Zheng et al. 2021;Park et al. 2021;Eteghadi et al. 2021). Of note, CAT and SOD play important roles in upregulating antioxidant pathways (Eteghadi et al. 2021). ...
... Furthermore, studies have reported that the level of catalase (CAT) and superoxide dismutase (SOD) are significantly decreased following cholestasis (Zheng et al. 2021;Park et al. 2021;Eteghadi et al. 2021). Of note, CAT and SOD play important roles in upregulating antioxidant pathways (Eteghadi et al. 2021). Therefore, restoring the function of these factors may be beneficial for the improvement of cognitive functions. ...
Large evidence has shown that cholestasis has a wide-range of deleterious effects on brain function, and also, on neurocognitive functions including learning and memory. On the other hand, crocin (derived from Crocus sativus) is a medicinal natural compound that induces neuroprotective and precognitive effects. In this study, we aimed to evaluate the effect of crocin on spatial learning and memory in cholestatic rats with respect to the level of mitochondrial transcriptional factor A (TFAM), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), catalase (CAT), and superoxide dismutase (SOD) in the hippocampus of male Wistar rats. Bile duct ligation (BDL) was used to induce cholestasis. Y-maze apparatus was used to assess spatial memory performance and real-time PCR was used to assess TFAM and PGC-1α gene expression. Also, crocin was injected intraperitoneal at the doses of 15, 20, and 30 mg/kg for thirty days. The results showed that BDL impaired spatial memory in rats. BDL also decreased SOD, TFAM, and PGC-1α level. In addition, crocin partially reversed the impairment effect of BDL on spatial memory. Crocin (30 mg/kg) also reversed the effect of BDL on SOD, TFAM, and PGC-1α. Of note, the effect of BDL on CAT activity was controversial. It seems that BDL can increase CAT activity. In addition, crocin (30 mg/kg) reversed the enhancement of CAT following BDL to its control level. In conclusion, crocin may induce a significant neuroprotective effect on cholestasis-induced memory impairment.
... Mitochondrial-encoded proteins can be co-translationally inserted into the IMM via OXA1. TOM translocases of the outer mitochondrial membrane, TIM translocase of the inner membrane, OMM outer mitochondrial membrane, IMS intermembrane space, IMM inner mitochondrial membrane, MPP mitochondrial processing peptidase, OXA1 oxidase assembly protein 1 by regulating the expression of related proteins [131,132]. Figure 2 illustrates the process of mitochondrial biogenesis. ...
Type 2 diabetes (T2DM) is a well known risk factor for Alzheimer’s disease. Mitochondria are the center of intracellular energy metabolism and the main source of reactive oxygen species. Mitochondrial dysfunction has been identified as a key factor in diabetes-associated brain alterations contributing to neurodegenerative events. Defective insulin signaling may act in concert with neurodegenerative mechanisms leading to abnormalities in mitochondrial structure and function. Mitochondrial dysfunction triggers neuronal energy exhaustion and oxidative stress, leading to brain neuronal damage and cognitive impairment. The normality of mitochondrial function is basically maintained by mitochondrial quality control mechanisms. In T2DM, defects in the mitochondrial quality control pathway in the brain have been found to lead to mitochondrial dysfunction and cognitive impairment. Here, we discuss the association of mitochondrial dysfunction with T2DM and cognitive impairment. We also review the molecular mechanisms of mitochondrial quality control and impacts of mitochondrial quality control on the progression of cognitive impairment in T2DM.
... It has neuroprotective properties as well as the ability to prevent mitochondrial dysfunction. Crocin significantly increases antioxidant activity, free radical removal, anti-inflammation activity, and immunity enhancement (Eteghadi et al., 2021). Bian et al. (2020) reviewed the potential of Saffron Extract as a neuroprotective agent. ...
Sofosbuvir is a novel drug candidate for the treatment of hepatitis C viral infection; however, vision loss is one of its growing adverse effects. Saffron is a natural biomolecule with a high antioxidant potential that has been efficiently used in some diseases caused by oxidative stress. This study evaluated Sofosbuvir's neurodegenerative effect on the retina of albino rat and examined the potential protective role of saffron aqueous extract. Twenty‐one adult male albino rats were randomly divided into three groups: Control, Sofosbuvir‐treated (41.1 mg/kg /day for 6 weeks), and Sofosbuvir + Saffron co‐treated groups. Retinal specimens were biochemically analyzed for malondialdehyde (MDA), interleukin‐6 (IL‐6), and tumor necrosis factor‐alpha (TNF‐α) levels. In addition, light and transmission electron microscopic examination, as well as immunohistochemical staining for Caspase‐3, COX‐2, and GFAP were performed. Sofosbuvir treatment caused a significant increase in retinal MDA, IL‐6, and TNF‐α levels coupling with a significant decrease in retinal total antioxidant capacity level. Histopathological findings revealed disturbed retinal architecture, detached pigment epithelium, vacuolated photoreceptors, in addition to a significant decrease in the thicknesses of both outer and inner nuclear layers, and the number of ganglionic cells. Ultrastructural examination revealed extensive degenerative changes in all retinal layers. Caspase‐3, COX‐2, and GFAP immunohistochemical expressions were significantly increased. Meanwhile, concomitant treatment with Saffron significantly improved retinal redox status, inflammation, histological, and ultrastructural parameters. Saffron may protect the retina from the hazardous effects of Sofosbuvir. Saffron could be used as an adjuvant therapy to protect patients receiving Sofosbuvir from retinal damage.
Crocin is a hydrophilic carotenoid that is synthesized in the flowers of the Crocus genus. Numerous in vitro and in vivo research projects have been published about the biological and pharmacological properties and toxicity of crocin. Crocin acts as a memory enhancer, anxiolytic, aphrodisiac, antidepressant, neuroprotective, and so on. Here, we introduce an updated and comprehensive review of crocin molecular mechanisms based on previously examined and mentioned in the literature. Different studies confirmed the significant effect of crocin to control pathological conditions, including oxidative stress, inflammation, metabolic disorders, neurodegenerative disorders, and cancer. The neuroprotective effect of crocin could be related to the activation of phosphatidylinositol 3‐kinase/protein kinase B (PI3K/AKT)/mammalian target of rapamycin (mTOR), Notch, and cyclic‐AMP response element‐binding protein signaling pathways. The crocin also protects the cardiovascular system through the inhibitory effect on toll‐like receptors. The regulatory effect of crocin on PI3K/AKT/mTOR, AMP‐activated protein kinase, mitogen‐activated protein kinases (MAPK), and peroxisome proliferator‐activated receptor pathways can play an effective role in the treatment of metabolic disorders. The crocin has anticancer activity through the PI3K/AKT/mTOR, MAPK, vascular endothelial growth factor, Wnt/β‐catenin, and Janus kinases‐signal transducer and activator of transcription suppression. Also, the nuclear factor‐erythroid factor 2‐related factor 2 and p53 signaling pathway activation may be effective in the anticancer effect of crocin. Finally, among signaling pathways regulated by crocin, the most important ones seem to be those related to the regulatory effect on the PI3K/AKT/mTOR pathway.
Crocins (CRs) and the related active constituents derived from Crocus sativus L. (Saffron) have demonstrated protective effects against cerebral ischemia and ischemic stroke, with various bioactivities including neuroprotection, anti-neuroinflammation, antioxidant, and cardiovascular protection. Among CRs, crocin (CR) has been shown to act on multiple mechanisms and signaling pathways involved in ischemic stroke, including mitochondrial apoptosis, nuclear factor kappa light chain enhancer of B cells pathway, S100 calcium-binding protein B, interleukin-6 and vascular endothelial growth factor-A. CR is generally safe and well-tolerated. Pharmacokinetic studies indicate that CR has poor bioavailability and needs to convert to crocetin (CC) in order to cross the blood-brain barrier. Clinical studies have shown the efficacy of saffron and CR in treating various conditions, including metabolic syndrome, depression, Alzheimer’s disease, and coronary artery disease. There is evidence supporting CR as a treatment for ischemic stroke, although further studies are needed to confirm their efficacy and safety in clinical settings.
