Curcumin attenuates cognitive impairment by enhancing autophagy in chemotherapy

Yi, Long; Dong, Shuqi; Wang, Shuangshuang; Chen, Min; Li, Cheng-Fu; Geng, Di; Zhu, Ji-Xiao; Liu, Qing; Cheng, Jie

doi:10.1016/j.nbd.2019.104715

Cited by 47 publications

(28 citation statements)

References 33 publications

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“…Either heterozygous deletion or mutation of Beclin 1 in mice decreases neuronal autophagy and results in neurodegeneration and disruption of lysosomes (Esteves et al, 2019; Lee & Gao, 2008; Pickford et al, 2008; La Spada et al, 2017). Activation of autophagy decreases Aβ pathology and alleviates cognitive dysfunction in various animal models (Steele et al, 2013; Yang et al, 2011a, 2011b; Yi et al, 2020; Yu et al, 2005). Therefore, reversing the autophagic dysfunction may serve as an innovative therapeutic target for the treatment of AD (Boland et al, 2008; Di Meco et al, 2017; Orr & Oddo, 2013; Yang et al, 2011b).…”

Section: Introductionmentioning

confidence: 99%

Activation of CREB‐mediated autophagy by thioperamide ameliorates β‐amyloid pathology and cognition in Alzheimer’s disease

Wang

Liu

et al. 2021

Aging Cell

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Alzheimer's disease (AD) is an age‐related neurodegenerative disease, and the imbalance between production and clearance of β‐amyloid (Aβ) is involved in its pathogenesis. Autophagy is an intracellular degradation pathway whereby leads to removal of aggregated proteins, up‐regulation of which may be a plausible therapeutic strategy for the treatment of AD. Histamine H3 receptor (H3R) is a presynaptic autoreceptor regulating histamine release via negative feedback way. Our previous study showed that thioperamide, as an antagonist of H3R, enhances autophagy and protects against ischemic injury. However, the effect of thioperamide on autophagic function and Aβ pathology in AD remains unknown. In this study, we found that thioperamide promoted cognitive function, ameliorated neuronal loss, and Aβ pathology in APP/PS1 transgenic (Tg) mice. Interestingly, thioperamide up‐regulated autophagic level and lysosomal function both in APP/PS1 Tg mice and in primary neurons under Aβ‐induced injury. The neuroprotection by thioperamide against AD was reversed by 3‐MA, inhibitor of autophagy, and siRNA of Atg7, key autophagic‐related gene. Furthermore, inhibition of activity of CREB, H3R downstream signaling, by H89 reversed the effect of thioperamide on promoted cell viability, activated autophagic flux, and increased autophagic‐lysosomal proteins expression, including Atg7, TFEB, and LAMP1, suggesting a CREB‐dependent autophagic activation by thioperamide in AD. Taken together, these results suggested that H3R antagonist thioperamide improved cognitive impairment in APP/PS1 Tg mice via modulation of the CREB‐mediated autophagy and lysosomal pathway, which contributed to Aβ clearance. This study uncovered a novel mechanism involving autophagic regulating behind the therapeutic effect of thioperamide in AD.

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Section: Introductionmentioning

confidence: 99%

Activation of CREB‐mediated autophagy by thioperamide ameliorates β‐amyloid pathology and cognition in Alzheimer’s disease

Wang

Liu

et al. 2021

Aging Cell

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“…Furthermore, curcumin has been exhibited to inhibit oxidative stress, inflammation, hyperuricemic in oxonate-induced [ 24 ], glycerol-induced [ 25 ], and heavy metal-induced [ 26 ] of kidney injury animal models. In addition, curcumin has shown significant potential in neuroprotective effects in cerebral ischemia-reperfusion and cognitive impairment by regulating autophagy [ 27 ]. Also, in an in vitro study conducted by Ali et al [ 28 ], curcumin significantly improved the renal damage and oxidative stress in adenine-induced chronic kidney disease in rats.…”

Section: Introductionmentioning

confidence: 99%

Curcumin Improves the Renal Autophagy in Rat Experimental Membranous Nephropathy via Regulating the PI3K/AKT/mTOR and Nrf2/HO-1 Signaling Pathways

Jin

et al. 2020

BioMed Research International

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Membranous nephropathy (MN, also known as membranous glomerulopathy) is one of the many glomerular diseases causing nephrotic syndrome. The literature indicates that autophagy is associated with the homeostasis of podocytes in glomeruli. Curcumin, the main active component in turmeric, has drawn attention for its effective bioactivities against chronic kidney disease. The current study was aimed at assessing the effects of curcumin and exploring the underlying mechanism that mediates autophagy in an animal model of passive Heymann nephritis (PHN) in rats. Passive Heymann nephritis (PHN) was induced in male SD rats by intraperitoneal injection of anti-Fx1A serum. The rats were divided into 3 groups: control ( n = 10 , normal diet), model group ( n = 10 , 0.5% sodium carboxymethylcellulose), and curcumin ( n = 10 , 300 mg/kg/d). The kidney function and oxidative stress indicators were measured using commercial diagnostic kits, and the histomorphology of renal tissues was observed. The number of podocytes was measured by immunohistochemistry. Meanwhile, the autophagosomes in podocyte were analyzed by transmission electron microscopy and the immunofluorescence assay pointing to p62, an autophagic marker. Western blot analyzed the levels of apoptosis, autophagy, PI3K/AKT/mTOR, and Nrf2/HO-1 pathway-associated proteins. The total cholesterol (TC), triglycerides (TG), creatinine (Scr), blood urea nitrogen (BUN), urine volume, and urine albumin of PHN rats were significantly reduced by the administration of curcumin and attenuated renal histomorphological changes in model rats. Meanwhile, curcumin improved the oxidative stress response by decreasing MDA and increasing SOD, GSH, and CAT levels in the kidney of PHN rats. Furthermore, curcumin significantly ameliorated the podocyte loss, along with the fusion, and increased the autophagic vacuoles compared to the PHN control rats. In addition, curcumin downregulated the expression of Bax, Caspase-3, p62, PI3K, p-AKT, and p-mTOR proteins and upregulated the Bcl-2, beclin1, LC3, Nrf2, and HO-1 levels in this animal model. The results provide a scientific basis that curcumin could significantly alleviate the development of MN by inducing autophagy and alleviating renal oxidative stress through the PI3K/AKT/mTOR and Nrf2/HO-1 pathways.

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“…For example, recent studies have demonstrated the neuroprotective potential of phytochemicals by reducing chemotherapy-induced CRCI in animal models. In addition, orally administered curcumin, at a dose of 100 mg/kg 1 h prior to cisplatin treatment, attenuated cisplatin-induced autophagy in the murine hippocampus accompanied by the activation of AMPK-JNK signaling [283] . Further, piceid, a resveratrol derivative, given orally at a dose of 50 mg/kg/d for 4 weeks, protected against doxorubicin-induced cognitive impairment concomitant with the up-regulation of Nrf2, inhibition of the NF-κB pathway, and reduction of apoptosis in the rat hippocampus [284] .…”

Section: Sequelaementioning

confidence: 98%

“…For example, it has been reported that breast cancer and childhood cancer survivors may experience cognitive dysfunction [282] . Notably, some chemopreventive agents are at least touted to improve this condition [283,284] .…”

Section: Sequelaementioning

confidence: 99%

Phytochemicals and cancer chemoprevention

Dave¹,

Parande²,

Park³

et al. 2020

JCMT

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The unending morbidity and mortality that results from cancer, as well as adverse reactions due to chemotherapy and the enormous economic burden of treatment and hospitalization, advocates for the necessity of chemopreventive measures. Cancer chemoprevention refers to the use of agents capable of reversing, reducing, or slowing down the pathology of cancer at various stages. Fortunately, a few therapeutic drugs with relatively low toxicity (e.g., tamoxifen, finasteride), and a sparse number of vaccines (hepatitis B, HPV), are used to prevent specific cancers. In the general population, however, therapeutic options for cancer prevention are not common. Nonetheless, it is generally agreed that diet affects the genesis of cancer, and phytochemicals have the capacity of functioning as cancer chemoprevention agents. This is supported by epidemiological studies and clearly documented with animal models designed to mimic human carcinogenesis. Additionally, some public health strategies, such as recommendations for greater consumption of fruits and vegetables, reflect the merits of cancer chemoprevention. Here, we focus on some well-established natural product cancer chemopreventive agents, including resveratrol (grapes), epigallocatechin-3-gallate (green tea), sulforaphane (cruciferous vegetables), anthocyanins (grapes and berries), curcumin (turmeric), silibinin (milk thistle), and lycopene (tomatoes). As aptly demonstrated by genomic analysis and other methods, the mechanistic underpinning is variable and complex. In addition, responses may be mediated through indirect mechanisms, such as interaction with the microbiome. Furthermore, ancillary applications of chemopreventive agents are worthy of consideration, such as management of sequelae induced by chemotherapy. Recognizing the loss of millions of cancer patients every year, it is obvious that negating malignant metastatic conditions remains of paramount importance. In meeting this objective, cancer chemoprevention offers great promise.

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Curcumin attenuates cognitive impairment by enhancing autophagy in chemotherapy

Cited by 47 publications

References 33 publications

Activation of CREB‐mediated autophagy by thioperamide ameliorates β‐amyloid pathology and cognition in Alzheimer’s disease

Activation of CREB‐mediated autophagy by thioperamide ameliorates β‐amyloid pathology and cognition in Alzheimer’s disease

Curcumin Improves the Renal Autophagy in Rat Experimental Membranous Nephropathy via Regulating the PI3K/AKT/mTOR and Nrf2/HO-1 Signaling Pathways

Phytochemicals and cancer chemoprevention

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