Neuroprotective Effect of Chrysophanol as a PI3K/AKT/mTOR Signaling Inhibitor in an Experimental Model of Autologous Blood-induced Intracerebral Hemorrhage

Jadaun, Kuldeep Singh; Mehan, Sidharth; Sharma, Aarti; Siddiqui, Ehraz Mehmood; Kumar, Sumit; Alsuhaymi, Naif

doi:10.1007/s11596-022-2496-x

Cited by 19 publications

(9 citation statements)

References 98 publications

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“…The MWM test is a robust and reliable test strongly correlated with hippocampal synaptic plasticity and cognitive dysfunctions. This task was performed to evaluate spatial learning and memory in rats [47]. The working memory of the rats was analysed by assessing their escape latency time (ELT) on the protocol schedule's 39th, 40th and 41st days.…”

Section: Morris Water Maze (Mwm) Taskmentioning

confidence: 99%

“…Moreover, the concentration of Bcl-2 protein was also evaluated in rat brain homogenate [67] and blood plasma [68] obtained from rats. The caspase-3 level was measured in brain homogenate as nM/mg protein and blood plasma as ng/mL [47]. The level of Bax/Bcl-2 in brain homogenate and blood plasma were represented in ng/mg and ng/mL, respectively.…”

Section: Assessment Of Apoptotic Markersmentioning

confidence: 99%

“…The nitrite (NO 2 ) level was determined by a colourimetric assay using a Greiss reagent, and the absorbance was determined at 540 nm with a UV spectrometer. The nitrite concentration in the supernatant was determined via a sodium nitrite standard curve and expressed as µM/mg protein [47].…”

Section: Assessment Of Oxidative Stress Markersmentioning

confidence: 99%

“…Recently, Mehan and co-workers successfully explored the neuroprotective potential of 4-HI in intracerebral haemorrhage [47]. Previous studies have demonstrated that 4-HI dosedependently promotes GLP-1-dependent cAMP production and GLP-1R endocytosis [48].…”

Section: Introductionmentioning

confidence: 99%

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Activation of IGF-1/GLP-1 Signalling via 4-Hydroxyisoleucine Prevents Motor Neuron Impairments in Experimental ALS-Rats Exposed to Methylmercury-Induced Neurotoxicity

et al. 2022

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Amyotrophic lateral sclerosis (ALS) is a severe adult motor neuron disease that causes progressive neuromuscular atrophy, muscle wasting, weakness, and depressive-like symptoms. Our previous research suggests that mercury levels are directly associated with ALS progression. MeHg+-induced ALS is characterised by oligodendrocyte destruction, myelin basic protein (MBP) depletion, and white matter degeneration, leading to demyelination and motor neuron death. The selection of MeHg+ as a potential neurotoxicant is based on our evidence that it has been connected to the development of ALS-like characteristics. It causes glutamate-mediated excitotoxicity, calcium-dependent neurotoxicity, and an ALS-like phenotype. Dysregulation of IGF-1/GLP-1 signalling has been associated with ALS progression. The bioactive amino acid 4-hydroxyisoleucine (HI) from Trigonella foenum graecum acts as an insulin mimic in rodents and increases insulin sensitivity. This study examined the neuroprotective effects of 4-HI on MeHg+-treated adult Wistar rats with ALS-like symptoms, emphasising brain IGF1/GLP-1 activation. Furthermore, we investigated the effect of 4-HI on MBP levels in rat brain homogenate, cerebrospinal fluid (CSF), blood plasma, and cell death indicators such as caspase-3, Bax, and Bcl-2. Rats were assessed for muscular strength, locomotor deficits, depressed behaviour, and spatial learning in the Morris water maze (MWM) to measure neurobehavioral abnormalities. Doses of 4-HI were given orally for 42 days in the MeHg+ rat model at 50 mg/kg or 100 mg/kg to ameliorate ALS-like neurological dysfunctions. Additionally, neurotransmitters and oxidative stress markers were examined in rat brain homogenates. Our findings suggest that 4-HI has neuroprotective benefits in reducing MeHg+-induced behavioural, neurochemical, and histopathological abnormalities in ALS-like rats exposed to methylmercury.

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Section: Morris Water Maze (Mwm) Taskmentioning

confidence: 99%

Section: Assessment Of Apoptotic Markersmentioning

confidence: 99%

Section: Assessment Of Oxidative Stress Markersmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Activation of IGF-1/GLP-1 Signalling via 4-Hydroxyisoleucine Prevents Motor Neuron Impairments in Experimental ALS-Rats Exposed to Methylmercury-Induced Neurotoxicity

et al. 2022

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“…Chrysophanol is found in many traditional Chinese herbal medicines, such as Radix et Rhizoma Rhei , Cassia obtusifolia L., and Polygonum multiflorum , with great medicinal value [ 148 ]. In the autologous blood ICH model, chrysophanol could decrease MDA expression and increase SOD, GSH, and CAT expression [ 88 ].…”

Section: Targeted Therapy Of Oxidative Stress With Natural Productsmentioning

confidence: 99%

Targeting Oxidative Stress in Intracerebral Hemorrhage: Prospects of the Natural Products Approach

Zheng

Fan

2022

Antioxidants

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Intracerebral hemorrhage (ICH), the second most common subtype of stroke, remains a significant cause of morbidity and mortality worldwide. The pathological mechanism of ICH is very complex, and it has been demonstrated that oxidative stress (OS) plays an important role in the pathogenesis of ICH. Previous studies have shown that OS is a therapeutic target after ICH, and antioxidants have also achieved some benefits in the treatment of ICH. This review aimed to explore the promise of natural products therapy to target OS in ICH. We searched PubMed using the keywords “oxidative stress in intracerebral hemorrhage” and “natural products in intracerebral hemorrhage.” Numerous animal and cell studies on ICH have demonstrated the potent antioxidant properties of natural products, including polyphenols and phenolic compounds, terpenoids, alkaloids, etc. In summary, natural products such as antioxidants offer the possibility of treatment of OS after ICH. However, researchers still have a long way to go to apply these natural products for the treatment of ICH more widely in the clinic.

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Chrysophanol‐Loaded Composites with Xanthan Gum/Polycaprolactone for Drug Release Enhancement

Thu Vu,

Thuy Nguyen,

Tra Duong

et al. 2024

ChemistrySelect

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This work focused on synthesizing novel chrysophanol‐loaded composites with varied ratios of polycaprolactone/xanthan gum to enhance the release of chrysophanol. The characteristics of the obtained composites were analyzed by infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, differential scanning calorimetry, rhermogravimetric analysis and dynamic light scattering methods. The xanthan gum/polycaprolactone/chrysophanol (XPC) composites were obtained in the powdery form with particle sizes ranging from 80–100 nm. The results of hydrophilic and hydrophobic tests of the composites were discussed. Chrysophanol, polycaprolactone and xanthan gum can interact and are compatible to each other. XPC composites exhibit high stability and don't cause the negative effect on cells. Additionally, the chrysophanol release and kinetic model of chrysophanol release from the XPC composites in different pH buffer solutions were investigated and evaluated. Using drug carriers such as xanthan gum and polycaprolactone can enhance the release of chrysophanol in both pH 2.0 and pH 7.4 buffer solutions. In the presence of biopolymers, the distribution ability of chrysophanol in aqueous solutions such as pH 2.0 buffer, pH 7.4 buffer solutions, and 0.9 % NaCl solution was enhanced significantly. This will be favorable for an increase in the absorption of chrysophanol in the human body.

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Neuroprotective Effect of Chrysophanol as a PI3K/AKT/mTOR Signaling Inhibitor in an Experimental Model of Autologous Blood-induced Intracerebral Hemorrhage

Cited by 19 publications

References 98 publications

Activation of IGF-1/GLP-1 Signalling via 4-Hydroxyisoleucine Prevents Motor Neuron Impairments in Experimental ALS-Rats Exposed to Methylmercury-Induced Neurotoxicity

Activation of IGF-1/GLP-1 Signalling via 4-Hydroxyisoleucine Prevents Motor Neuron Impairments in Experimental ALS-Rats Exposed to Methylmercury-Induced Neurotoxicity

Targeting Oxidative Stress in Intracerebral Hemorrhage: Prospects of the Natural Products Approach

Chrysophanol‐Loaded Composites with Xanthan Gum/Polycaprolactone for Drug Release Enhancement

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