Chemoprotective potential of zingerone (vanillyl acetone) in cyclophosphamide-induced hepatic toxicity

Mir, Bilal Ahmad; Amin, Insha; Rehman, Muneeb U.; Razak, Rahil; Ali, Aarif; Baba, Omer Khalil; Fatima, Bilques; Ali, Rayeesa; Bilal, Sheikh; Muzamil, Showkeen; Hussain, Ishraq; Rashid, Shahzada Mudasir; Wali, Adil Farooq; Mir, Manzoor-ur Rahman

doi:10.4103/pm.pm_170_16

Cited by 7 publications

(8 citation statements)

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“…Treated with ZO for cancer bearing animals showed the oxidant/antioxidant activities were reverted back to the nearest standard levels. This could be due to the powerful antioxidant action of ZO and this is well in concurrence with the earlier report in hepatic toxicity …”

Section: Discussionsupporting

confidence: 92%

Zingerone induced caspase‐dependent apoptosis in MCF‐7 cells and prevents 7,12‐dimethylbenz(a)anthracene‐induced mammary carcinogenesis in experimental rats

Gan

Zhang

Zhou

et al. 2019

J Biochem & Molecular Tox

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Breast cancer is a prevalent of tumoregenesis in women and reports for the maximum mortality and morbidity in the global. Ginger (Zingiber officinale) is the mainly widespread spice and herbal remedies used in the world. Since antique periods, ginger has been used in Greece, India and China for the curing of upset stomach, nausea, diarrhea, colds, and headaches. The current work was planned to explore the anticancer properties of zingerone (ZO) toward 7,12‐dimethylbenz(a)anthracene (DMBA)‐treated mammary carcinogenesis in Sprague‐Dawley (SD) rats and MCF‐7 mammary cancer cells. The mammary carcinogenesis was produced through a single dosage of DMBA (20 mg/kg bwt) mixed in soya oil (1 mL) administrated intragastrically with a gavage. We found improved concentrations of lipid peroxidation (LOOH and TBARS), carcinoembryonic antigen, lowered levels of enzymatic (CAT, GPx, and SOD), and nonenzymatic (vitamin E, GSH, and vitamin C) antioxidant in mammary tissues and plasma of DMBA‐induced cancer bearing animals. Moreover, augmented concentrations of phase I (Cyt‐b5 and CYP450) and reduced levels of phase II (GR and GST) detoxification microsomal proteins in mammary tissues were noticed. ZO administrations significantly reverted back to all these parameters in this way, showing efficient of anticancer effect. Furthermore, our in vitro study also supported the anticancer effect of the treatment of ZO were noticed loss of cell viability, improved reactive oxygen species formation, and reduced MMP. Furthermore, the status of apoptosis proteins such as Bcl‐2, Bax, and Bid expressions was determined by using Western blot analysis techniques. Overall, these results proposed the anticancer effect of ZO toward DMBA‐induced mammary cancer in SD animals and Michigan cancer foundation‐7 mammary cancer cells.

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Section: Discussionsupporting

confidence: 92%

Zingerone induced caspase‐dependent apoptosis in MCF‐7 cells and prevents 7,12‐dimethylbenz(a)anthracene‐induced mammary carcinogenesis in experimental rats

Gan

Zhang

Zhou

et al. 2019

J Biochem & Molecular Tox

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“…This study demonstrated that zingerone (50 and 100 mg) could decrease the main product of lipid peroxidation (MDA), showing its ability to defeat oxidative damage in MTX-induced hepatotoxicity. Mir et al also showed that zingerone could attenuate MDA elevation induced by cyclophosphamide-induced liver injury, which confirms our results (34).…”

Section: Discussionsupporting

confidence: 92%

“…Therefore, we can conclude that zingerone shows a protective effect against cell apoptosis and possibly performs this protection via decreasing ROS in the liver. Mir et al also showed a result parallel to our results; they showed the protective effects of zingerone regarding reduced nitrite production in cyclophosphamide-induced hepatic injury (34). Moreover, RONS can oxidize proteins and give rise to the production of reactive molecules known as protein carbonyl (PC).…”

Section: Discussionsupporting

confidence: 88%

“…Although nitric oxide (NO) plays an important role in several vital physiological functions (38), it is also a poi- sonous, highly reactive, short-lived, and unstable free radical gas (39), which can induce apoptotic cell death in neuronal cells (7,34). When NO reacts with superoxide radicals, it yields peroxynitrite, which can cause membrane peroxidation, DNA damage, and GSH content depletion (34). The current study showed that zingerone (100 mg/kg) could significantly decrease the level of liver tissue NO in MTX-induced hepatic injury.…”

Section: Discussionmentioning

confidence: 99%

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Zingerone Attenuates Methotrexate-Induced Hepatotoxicity in Rats

Goudarzi

Basir

Malayeri

et al. 2021

Jundishapur J Nat Pharm Prod

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Background: Methotrexate (MTX) is mainly used for the chemotherapy of different types of malignancy and some autoimmune diseases like rheumatoid arthritis and inflammatory bowel disease. The MTX application is limited by its severe side effects, including several types of hepatic injury. Objectives: In this study, we decided to evaluate if zingerone (the main constituent of ginger) can reduce the hepatic side effects of MTX. Methods: Thirty-five rats were divided into five groups: Control group receiving normal saline (N/S), once daily, by gavage, for 10 days, and N/S intraperitoneally (i.p.), a single dose on the ninth day; Methotrexate (MTX) group receiving N/S, once daily, by gavage, for 10 days, and MTX (i.p.), a single dose (20 mg/kg) on the ninth day; Groups 3 (ZG25), 4 (ZG50), and 5 (ZG100) receiving zingerone (25, 50, and 100 mg/kg, respectively), once daily, by gavage, for 10 days, and MTX (i.p.), a single dose (20 mg/kg) on the ninth day. Results: The results showed a significant decrease in serum AST, ALT, and ALP, as well as the hepatic content of MDA, NO, PC, TNF-α, and IL-1β, in the ZG groups compared with the MTX group. The activity of SOD, CAT, and GPX, as well as the hepatic content of GSH, showed a significant increase in the ZG groups compared with the MTX group. Histopathological improvement in the hepatic tissue of ZG groups compared with the MTX group confirmed all other findings. Conclusions: It is concluded that zingerone can improve hepatic injury induced by MTX in rats regarding the redox system features, inflammation, and histological changes. This can make humans hopeful for using Ginger in the future for attenuating the hepatic side effects of MTX when used chronically.

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“…Our results reveal that NO content in the hippocampus is augmented following seizures, representative of epileptic seizures. However, zingerone treatment reduces NO content, alleviating inflammation and toxicity of NO on brain tissue, as reported previously by Mir et al [55].…”

Section: Discussionsupporting

confidence: 80%

Zingerone Targets Status Epilepticus by Blocking Hippocampal Neurodegeneration via Regulation of Redox Imbalance, Inflammation and Apoptosis

et al. 2021

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Epilepsy is an intricate neurological disease where the neurons are severely affected, leading to the mortality of millions worldwide. Status epilepticus (SE), induced by lithium chloride (LiCl) and pilocarpine, is the most accepted model for epilepsy. The current work aims to unravel the mechanisms underlying the anti-epileptic efficacy of zingerone (an active ingredient of ginger), which has beneficial pharmacological activities on seizure-induced behavioral, histological, neurochemical, and molecular patterns in mice. Zingerone restored cognitive function by diminishing seizure activity, escape latency, and subsequent hippocampal damage manifested in histology. Seizures are associated with local inflammation, redox imbalance, and neural loss, confirmed by the present study of SE, and was attenuated by zingerone treatment. Nuclear factor-kappa B and its downstream signaling molecules (TNF-α, IL-1β, IL-6, NO, MPO) were activated in the LiCl-and-pilocarpine-induced group leading to inflammatory signaling, which was substantially ameliorated by zingerone treatment. The intrinsic apoptotic process was triggered subsequent to SE, as demonstrated by augmentation of cleaved caspase-3, downregulation of Bcl-2. However, zingerone treatment downregulated caspase-3 and upregulated Bcl-2, increasing cell survival and decreasing hippocampal neural death, deciphering involvement of apoptosis in SE. Therefore, zingerone plays an essential role in neuroprotection, probably by precluding oxidative stress, inflammation, and obstructing the mitochondrial pathway of apoptosis.

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Chemoprotective potential of zingerone (vanillyl acetone) in cyclophosphamide-induced hepatic toxicity

Cited by 7 publications

References 0 publications

Zingerone induced caspase‐dependent apoptosis in MCF‐7 cells and prevents 7,12‐dimethylbenz(a)anthracene‐induced mammary carcinogenesis in experimental rats

Zingerone induced caspase‐dependent apoptosis in MCF‐7 cells and prevents 7,12‐dimethylbenz(a)anthracene‐induced mammary carcinogenesis in experimental rats

Zingerone Attenuates Methotrexate-Induced Hepatotoxicity in Rats

Zingerone Targets Status Epilepticus by Blocking Hippocampal Neurodegeneration via Regulation of Redox Imbalance, Inflammation and Apoptosis

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