Withania coagulans extract attenuates oxidative stress-mediated apoptosis of cerebellar purkinje neurons after ischemia/reperfusion injury

Heidari, Zahra; Mahmoudzadeh‐Sagheb, Hamidreza; Sarbishegi, Maryam; Gorgich, Enam Alhagh Charkhat

doi:10.1007/s11011-021-00745-0

Cited by 6 publications

(7 citation statements)

References 40 publications

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“…WS has been demonstrated to have anxiolytic, antiangiogenic, antidepressive, anti-metastatic, anti-tumoral, cytotoxic, genotoxic, antibacterial, antifungal, and antidiabetic properties in several in vitro and in vivo experiments [ 13 , 14 , 15 ]. WS modulates cytotoxicity in cancer cells by accumulating intracellular reactive oxygen species (ROS) [ 16 , 17 , 18 ]. WS inhibits several aberrant pathways implicated in inflammation and proliferation (e.g., IL-6, TNF-α, and cycloxygenase-2 (COX-2)), angiogenesis and metastasis (e.g., VEGF, MMP9, TWIST, NF-κB, and STAT), cell survival (e.g., Bcl-2, Bcl-xL, survivin, and cIAP1/2), and regulation of the cell cycle (e.g., cyclin A, cyclin D1, Cdks, p21, and p53) [ 12 , 13 , 14 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

Withania somnifera: Progress towards a Pharmaceutical Agent for Immunomodulation and Cancer Therapeutics

et al. 2022

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Chemotherapy is one of the prime treatment options for cancer. However, the key issues with traditional chemotherapy are recurrence of cancer, development of resistance to chemotherapeutic agents, affordability, late-stage detection, serious health consequences, and inaccessibility. Hence, there is an urgent need to find innovative and cost-effective therapies that can target multiple gene products with minimal adverse reactions. Natural phytochemicals originating from plants constitute a significant proportion of the possible therapeutic agents. In this article, we reviewed the advances and the potential of Withania somnifera (WS) as an anticancer and immunomodulatory molecule. Several preclinical studies have shown the potential of WS to prevent or slow the progression of cancer originating from various organs such as the liver, cervix, breast, brain, colon, skin, lung, and prostate. WS extracts act via various pathways and provide optimum effectiveness against drug resistance in cancer. However, stability, bioavailability, and target specificity are major obstacles in combination therapy and have limited their application. The novel nanotechnology approaches enable solubility, stability, absorption, protection from premature degradation in the body, and increased circulation time and invariably results in a high differential uptake efficiency in the phytochemical’s target cells. The present review primarily emphasizes the insights of WS source, chemistry, and the molecular pathways involved in tumor regression, as well as developments achieved in the delivery of WS for cancer therapy using nanotechnology. This review substantiates WS as a potential immunomodulatory, anticancer, and chemopreventive agent and highlights its potential use in cancer treatment.

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Section: Introductionmentioning

confidence: 99%

Withania somnifera: Progress towards a Pharmaceutical Agent for Immunomodulation and Cancer Therapeutics

et al. 2022

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“…Next, we explored the underlying mechanism of TFCJ against IS. Previous studies ( Zhang et al, 2019 ; Heidari et al, 2021 ; Luo et al, 2021 ) have reported that oxidative stress and cell apoptosis may have the strongest correlation with IS. Li et al (2021) reported that miR-27A-3p reduces apoptosis and oxidative stress induced by oxygen-glucose deprivation/reoxygenation through FOXO1/p27 Kip1 signaling.…”

Section: Discussionmentioning

confidence: 83%

“…Next, we explored the underlying mechanism of TFCJ against IS. Previous studies (Zhang et al, 2019;Heidari et al, 2021; GSH-Px is the main antioxidant that interacts with lipid hydrogen peroxide (Zhang L. et al, 2021). The degree of cerebral ischemia, hypoxia, and necrosis is related to the level of GSH-Px.…”

Section: Discussionmentioning

confidence: 99%

Total Flavonoids of Chuju Decrease Oxidative Stress and Cell Apoptosis in Ischemic Stroke Rats: Network and Experimental Analyses

et al. 2021

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Background: Pharmacological research results showed that total flavonoids of Chuju (TFCJ) could be used to treat acute myocardial ischemia and myocardial ischemia-reperfusion injury. In this study, we explored the protective effect of TFCJ on ischemic stroke (IS) in the IS rat model. We hypothesized that TFCJ might exert its neuroprotective effects by suppressing apoptosis and oxidative stress that are closely related to PI3K/Akt/mTOR signaling pathway.Method: TFCJ (10, 20, and 40 mg/kg) was administered for 7 days. Rats (260 ± 20 g) were subjected to middle cerebral artery occlusion (MCAO) for 2 h and reperfusion for 24 h. The neuroprotective effect of TFCJ was substantiated in terms of neurological deficits, oxidative stress (superoxide dismutase, glutathione peroxidase, catalase, and malondialdehyde), pathomorphological changes (HE staining and TUNEL staining), and neurobehavioral functions in the rats. Then, we employed network pharmacology to reveal the potential mechanism of TFCJ against IS. Western blot was used to determine the levels of PI3K/AKT/mTOR pathway proteins. The expression of BCL-2, BAX, and cleaved-Caspase-3 was also measured by Western blots and RT-PCR.Results: The histopathological assessment showed that TFCJ reduced MCAO-induced brain damage. Besides, TFCJ exerted a protective role in MCAO rats by alleviating cell apoptosis and oxidative stress. Network pharmacology showed that TFCJ might be used against IS through the PI3K/AKT signaling pathway. TFCJ reduced cell apoptosis and oxidative stress by increasing the level of p-AKT and p-mTOR in MCAO rats, while the effect of TFCJ was significantly reversed when applying LY294002 (PI3k inhibitor).Conclusion: These results indicated that TFCJ might decrease oxidative stress and apoptosis that are closely related to PI3K/Akt/mTOR pathway in IS. TFCJ is a promising authentic traditional Chinese medicine for the management of IS.

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“…Additionally, Studies have shown that the cerebellum is vulnerable to oxidative damage caused by free radicals during ischemia and reperfusion injury (Almeida et al, 1999;Harry and Lefebvre d'Hellencourt, 2003). According to a study conducted by Heidari et al in 2021, there was an increase in the levels of MDA and a decrease in the activity levels of CAT, MDA, and GPX in the cerebellum tissue in the ischemia group compared to the sham group (Heidari et al, 2021). This study found similar levels of SOD, GPX, and CAT activity, as well as MDA amounts in the GCI group compared with sham and GCI+BBR groups.…”

Section: Discussionmentioning

confidence: 99%

Berberine Chloride Mitigates Cerebellar Damage in Global Cerebral Ischemia: A Comprehensive Study with stereological analysis, evaluation the Antioxidant response and Locomotor Function in Rat Models

Mehboodi,

Shahedi,

Namavar

et al. 2024

Preprint

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Global cerebral ischemia (GCI) leads to significant oxidative damage in the cerebellum, which mainly affects Purkinje cells. This study aimed to investigate the neuroprotective effects of Berberine chloride (BBR), a compound known for its antioxidant properties against GCI. 42 adult male Wistar rats were divided into three groups: Sham, GCI, and GCI+BBR. Rats received BBR (50mg/kg) 7 days before and 6 hours after inducing GCI via bilateral common carotid artery occlusion for 20 minutes. And assessed for locomotor activity by open field test, cerebellar biochemical factors malondialdehyde (MDA), superoxide dismutase (SOD), Catalase (CAT), Glutathione peroxidase (GPx), cerebellum volume and Purkinje neuron count by stereological analysis.The BBR treatment reduced the concentration of MDA(P<0.0001) and increased the activity of antioxidant enzymes SOD, CAT and GPx (P<0.0001, P<0.001 and P<0.001, respectively) in the cerebellum compared to the GCI group. Stereological analysis revealed higher Purkinje cell count (P<0.0001), cerebellum (P<0.001), white matter (P<0.01), and grey matter (P<0.0001) volume in the GCI+BBR group compared to the GCI group. Furthermore, GCI+BBR showed enhanced locomotor function compared to the GCI group. BBR showed therapeutic benefits and improved locomotor function, Showcased antioxidative effects by lowering MDA levels, boosting enzymatic activities, and significantly mitigating Purkinje cell death and cerebellar volume loss.

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Withania coagulans extract attenuates oxidative stress-mediated apoptosis of cerebellar purkinje neurons after ischemia/reperfusion injury

Cited by 6 publications

References 40 publications

Withania somnifera: Progress towards a Pharmaceutical Agent for Immunomodulation and Cancer Therapeutics

Withania somnifera: Progress towards a Pharmaceutical Agent for Immunomodulation and Cancer Therapeutics

Total Flavonoids of Chuju Decrease Oxidative Stress and Cell Apoptosis in Ischemic Stroke Rats: Network and Experimental Analyses

Berberine Chloride Mitigates Cerebellar Damage in Global Cerebral Ischemia: A Comprehensive Study with stereological analysis, evaluation the Antioxidant response and Locomotor Function in Rat Models

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