Cerebroprotective effect of Aloe Emodin: In silico and in vivo studies

Pasala, Praveen Kumar; Shaik, Rizwaan Abbas; Rudrapal, Mithun; Khan, Johra; Alaidarous, Mohammad A.; Khairnar, Shubham Jagdish; Bendale, Atul R.; Naphade, Vaishali D.; Sahoo, Ranjan Kumar; Zothantluanga, James H.; Walode, Sanjay G.

doi:10.1016/j.sjbs.2021.09.077

Cited by 36 publications

(12 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A bioactive molecule isolated from Tripterygium wilfordii , namely celastrol, protected the cerebral region of the brain from an acute episode of cerebral ischemia by suppressing oxidative stress via phosphorylation of the c-Jun-N-terminal kinase (p-JNK) and NF-κB which aided in the reduction of ROS in the brain [ 92 ]. Emodin, a bioactive compound extracted from Polygonum multiforum considerably decreased the volume of infarct by activating the signaling of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT), which considerably improved the functioning of motor functions of the brain and prevented damage induced by ischemic stroke [ 93 ]. Another bioactive benzoquinoe derivative, namely Z-ligustilide, which is isolated from Angelica sinensis , protected the disruption of blood brain barrier by alleviating neuroinflammation and oxidative stress after an acute episode of ischemic stroke [ 94 ].…”

Section: Natural Products and Their Protective Role In Management Of ...mentioning

confidence: 99%

Insights into the Explicit Protective Activity of Herbals in Management of Neurodegenerative and Cerebrovascular Disorders

et al. 2022

View full text Add to dashboard Cite

The longstanding progressive neurodegenerative conditions of the central nervous system arise mainly due to deterioration, degradation and eventual neuronal cell loss. As an individual ages, the irreversible neurodegenerative disorders associated with aging also begin to develop, and these have become exceedingly prominent and pose a significant burden mentally, socially and economically on both the individual and their family. These disorders express several symptoms, such as tremors, dystonia, loss of cognitive functions, impairment of motor activity leading to immobility, loss of memory and many more which worsen with time. The treatment employed in management of these debilitating neurodegenerative disorders, such as Parkinson’s disease (which mainly involves the loss of dopaminergic neurons in the nigrostriatal region), Alzheimer’s disease (which arises due to accumulation of Tau proteins causing diffusive atrophy in the brain), Huntington’s disease (which involves damage of striatal and spinal neurons, etc.), have several adverse effects, leading to exploration of several lead targets and molecules existing in herbal drugs. The current review highlights the mechanistic role of natural products in the treatment of several neurodegenerative and cerebrovascular diseases such as Parkinson’s disease, Alzheimer’s disease, ischemic stroke and depression.

show abstract

Section: Natural Products and Their Protective Role In Management Of ...mentioning

confidence: 99%

Insights into the Explicit Protective Activity of Herbals in Management of Neurodegenerative and Cerebrovascular Disorders

et al. 2022

View full text Add to dashboard Cite

show abstract

“…First, although we confirmed the anti-seizure effects of aloesone, other potential compounds, such as isoeleutherol glucosiden qt and anthranol, were not evaluated due to the limitation of their synthesis. Second, as few studies have been conducted on the effects of aloesone in rats, we chose doses of 50 and 100 mg/kg aloesone for PTZ rats based on other compounds of Aloe vera, such as aloeemodin, which exhibited similar anti-oxidative effects as aloesone in the brain (Lucini et al, 2015;Arcella et al, 2018;Xian et al, 2021;Pasala et al, 2022). However, concentrations below 50 mg/kg were not included in the present study.…”

Section: Aloesone Inhibited Ptz-induced Acute and Chronic Seizuresmentioning

confidence: 99%

Up-and-coming anti-epileptic effect of aloesone in Aloe vera: Evidenced by integrating network pharmacological analysis, in vitro, and in vivo models

Wang

Li²,

Xiong³

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Background:Aloe vera is a medically valuable plant with anti-epileptic activity; however, its mechanism of action remains unknown. In this study, network pharmacological, in vitro, and in vivo experiments were carried out to explore the potential anti-epileptic components and targets of Aloe vera.Methods: The main active components of Aloe vera were identified by searching the Traditional Chinese Medicine System Pharmacology database. Targets of Aloe vera were predicted using SwissTargetPrediction, whereas information about the epilepsy disease targets was obtained from Gene Cards. The protein–protein interaction network and core targets were screened according to the topological structure and CytoNCA plugin. The glutamate-induced HT22 cell line and pentylenetetrazol-induced seizure rats were used to confirm the effect of aloesone by detecting reactive oxygen species (ROS) and apoptosis, and predicting the targets.Results: A total of 14 core active components were selected based on the screening criteria of oral bioavailability ≥30% and drug-likeness ≥ 0.10. Four compounds, namely linoleic acid, aloesone, isoeleutherol glucosiden qt, and anthranol, demonstrated the potential ability of crossing the blood-brain barrier. A total of 153 targets associated with epilepsy were predicted for the four compounds. Moreover, after network analysis with CytoNCA, 10 targets, namely, MAPK1, SRC, MARK3, EGFR, ESR1, PTGS2, PTPN11, JAK2, PPKCA, and FYN, were selected as the core genes, and SRC, which has been predicted to be the target of aloesone and anthranol, exhibited the highest subgraph centrality value. In vitro experiments confirmed that aloesone treatment significantly inhibited the glutamate-induced neuronal injury by reducing the intracellular ROS content and the early phase of apoptosis. Additionally, treatment with 50 mg/kg aloesone resulted in anti-seizure effects by reducing the seizure score and prolonging the latent period in acute and chronic rats. Furthermore, aloesone treatment increased the phosphorylation of c-SRC at Y418 and reduced the phosphorylation at Y529, simultaneously activating c-SRC.Conclusion: Integrating network pharmacology with in vitro and in vivo experiments demonstrated that aloesone, which inhibited seizure by activating c-SRC, is a potential anti-seizure compound present in Aloe vera.

show abstract

“…Mitochondria are important organelles that can generate oxidative stress and dysfunction in response to ischemia and hypoxia events (3)(4)(5)(6). This series of pathological processes decreases the anti-apoptotic protein Bcl-2 level, increases the pro-apoptotic protein Bax level and enhances the expression of cleaved caspase-3 (7)(8)(9)(10). Neuronal cells with high energy depletion undergo large-scale apoptosis (11).…”

Section: Introductionmentioning

confidence: 99%

Para‑hydroxybenzaldehyde against transient focal cerebral ischemia in rats via mitochondrial preservation

et al. 2022

View full text Add to dashboard Cite

Gastrodia elata (GE) Blume has been widely used for thousands of years to treat various central and peripheral nervous disorders. P-hydroxybenzaldehyde (PHBA) is a chemical component of GE. However, its role and mechanism in transient focal cerebral ischemia remain unclear. The present study aimed to investigate the protective effect of PHBA on middle cerebral artery occlusion (MCAO) rats. A total of 56 Sprague-Dawley male rats were randomly divided into control, model, PHBA-high dose (PHBA-H) and PHBA-low dose (PHBA-L) groups. The MCAO injury model was replicated in all rats except for the control group. In the control group, only the right common carotid artery was isolated without embolization. After treatment with PHBA, the protective effects (neurological deficit score, cerebral index, weight and cerebral infarct) were analyzed. Western blotting was performed to estimate the protein levels of Bcl-2, Bax and Caspase-3. Apoptotic cells were detected using hematoxylin-eosin staining and TUNEL immunofluorescence assay. Mitochondrial oxidative stress indicators, including reactive oxygen species (ROS), malondialdehyde (MDA) and total superoxide dismutase (T-SOD), while dysfunction indicators, including mitochondrial permeability transition pore (MPTP), ATP and cytochrome C oxidase, were measured using commercial kits. The ultrastructure of mitochondria was observed under an electron microscope. Once the model was successful established, the rats in the MCAO group suffered neurological damage (P<0.001), increased cerebral index (P<0.001), decreased body weight (P<0.001) and had severe cerebral infarction (P<0.001). Moreover, the number of apoptotic cells and the levels of ROS (P<0.001) and MDA (P<0.05) in mitochondria and the protein levels of Bax (P<0.001) and cleaved caspase-3 (P<0.001) were increased. The activities of T-SOD (P<0.001) and cytochrome C oxidase (P<0.001) in the mitochondria, ATP content (P<0.05) and Bcl-2 protein level (P<0.001) decreased, MPTP was stimulated to open and mitochondrial structures were damaged (P<0.001). PHBA treatment resulted in a decrease of the neurological deficit score (PHBA-H 24 h, P<0.001; PHBA-H 6 h and PHBA-L 24 h, P<0.01; PHBA-L 6 h, P<0.05), apoptotic cell number (P<0.001), mitochondrial ROS (P<0.001) and MPTP opening (P<0.001), Bax (P<0.01, P<0.001) and cleaved caspase-3 protein expression (P<0.001) in rats. And the expression of Bcl-2 protein (P<0.001) was increased. In addition, the cerebral index (P<0.05), weight loss (P<0.05), infarction rate (P<0.01) and MDA content (P<0.001) were decrease in the PHBA-H group. The level of ATP (P<0.05) and cytochrome C oxidase (P<0.05) and T-SOD activity (P<0.05) of PHBA-H group rats increased, but no significant difference was observed in the PHBA-L group. Overall, PHBA had a protective effect on transient focal cerebral ischemia in normal rats, regulated the expression of Bcl-2, Bax and cleaved caspase-3 proteins and improved the oxidative stress and dysfunction of mitochondria.

show abstract

Cerebroprotective effect of Aloe Emodin: In silico and in vivo studies

Cited by 36 publications

References 43 publications

Insights into the Explicit Protective Activity of Herbals in Management of Neurodegenerative and Cerebrovascular Disorders

Insights into the Explicit Protective Activity of Herbals in Management of Neurodegenerative and Cerebrovascular Disorders

Up-and-coming anti-epileptic effect of aloesone in Aloe vera: Evidenced by integrating network pharmacological analysis, in vitro, and in vivo models

Para‑hydroxybenzaldehyde against transient focal cerebral ischemia in rats via mitochondrial preservation

Contact Info

Product

Resources

About