Chrysophanol

Chrysophanol was first noted from Rheum rhabarbarum which is a plant belonging to the Polygonaceae family.{{cite journal | vauthors = Yusuf MA, Singh BN, Sudheer S, Kharwar RN, Siddiqui S, Abdel-Azeem AM, Fernandes Fraceto L, Dashora K, Gupta VK | display-authors = 6 | title = Chrysophanol: A Natural Anthraquinone with Multifaceted Biotherapeutic Potential | journal = Biomolecules | volume = 9 | issue = 2 | pages = 68 | date = February 2019 | pmid = 30781696 | doi = 10.3390/biom9020068 | pmc = 6406798 | doi-access = free }} It has since been discovered to be present in various families such as Liliaceae, Meliaceae, Asphodelaceae and Fabaceae among more. As of 2019, it has been observed in 65 species from 14 genera, not just in plants but animals and microbes as well.

Chrysophanol has been shown to exhibit a variety of effects. It was shown in 2015 to lower cholesterol and triglyceride levels in zebrafish, as well as increase the frequency of peristalsis. This could therefore be used for lipid metabolic disorders in a clinical setting.{{cite journal | vauthors = Chen K, Wang CQ, Fan YQ, Xie YS, Yin ZF, Xu ZJ, Zhang HL, Cao JT, Wang Y | display-authors = 6 | title = Application of chrysophanol in zebrafish to reduce dietary introduced lipid and its possible mechanism | journal = International Journal of Clinical and Experimental Medicine | volume = 8 | issue = 7 | pages = 10558–67 | date = 2015-07-15 | pmid = 26379845 | pmc = 4565228 }} Chrysophanol has also been shown to exhibit the same properties lipid lowering in rats in 2013.

It also has the potential to stimulate osteoblast differentiation.{{cite journal | vauthors = Lim YJ, Kim KM, Jang WG | title = Chrysophanol increases osteoblast differentiation via AMPK/Smad1/5/9 phosphorylation in vitro and in vivo | journal = Clinical and Experimental Pharmacology & Physiology | volume = 48 | issue = 4 | pages = 515–523 | date = April 2021 | pmid = 33300218 | doi = 10.1111/1440-1681.13443 | s2cid = 228087337 }} as well as alleviate diabetic nephropathy {{cite journal | vauthors = Guo C, Wang Y, Piao Y, Rao X, Yin D | title = Chrysophanol Inhibits the Progression of Diabetic Nephropathy via Inactivation of TGF-β Pathway | journal = Drug Design, Development and Therapy | volume = 14 | pages = 4951–4962 | date = 2020-11-16 | pmid = 33235436 | pmc = 7678702 | doi = 10.2147/DDDT.S274191 | doi-access = free }} Furthermore, it can protect bronchial cells from cigarette smoke extract induced apoptosis.{{cite journal | vauthors = Wu G, Yuan T, Zhu H, Zhang H, Su J, Guo L, Zhou Q, Xiong F, Yu Q, Yang P, Zhang S, Mo B, Zhao J, Cai J, Wang CY | display-authors = 6 | title = Chrysophanol protects human bronchial epithelial cells from cigarette smoke extract (CSE)-induced apoptosis | journal = International Journal of Molecular Epidemiology and Genetics | volume = 11 | issue = 3 | pages = 39–45 | date = 2020-12-15 | pmid = 33488953 | pmc = 7811954 }} Chrysophanol can also improve the condition of renal interstitial fibrosis.{{cite journal | vauthors = Dou F, Ding Y, Wang C, Duan J, Wang W, Xu H, Zhao X, Wang J, Wen A | display-authors = 6 | title = Chrysophanol ameliorates renal interstitial fibrosis by inhibiting the TGF-β/Smad signaling pathway | journal = Biochemical Pharmacology | volume = 180 | pages = 114079 | date = October 2020 | pmid = 32511988 | doi = 10.1016/j.bcp.2020.114079 | s2cid = 219552025 }}

Chrysophanol has also been used to inhibit T-Cell activation and protect mice from dextran sulphate sodium induced inflammatory bowel disease.{{cite journal | vauthors = Lee HS, Jeong GS | title = Chrysophanol Attenuates Manifestations of Immune Bowel Diseases by Regulation of Colorectal Cells and T Cells Activation In Vivo | journal = Molecules | volume = 26 | issue = 6 | date = March 2021 | page = 1682 | pmid = 33802855 | pmc = 8002617 | doi = 10.3390/molecules26061682 | doi-access = free }} It was shown to have attenuated the pro-inflammatory cytokines that were present in the colon tissue due to sulphate sodium induced inflammatory bowel disease.

Chrysophanol can alleviate diabetic nephropathy by inactivating TGF-β/EMT signalling. It also has the potential to protect bronchial cells from cigarette smoke extract by repressing CYP1A expression which is usually produced due to excessive reactive oxygen species. Chrysophanol can increase osteoblast differentiation by inducing AMP-activated protein kinase as well as Smad1/5/9. Chrysophanol acts to improve renal interstitial fibrosis by downregulating TGF-β1 and phospho-Smad3 and by upregulating Smad7.

Chrysophanol can also aid in treatment for inflammatory bowel disease by inhibiting inflammation by targeting pro-inflammatory cytokines that are in tumour necrosis factor α. It has also been shown that it inhibits the mitogen-activated protein kinase pathway.

Chrysophanol blocks the proliferation of colon cancer cells in vitro.{{cite journal | vauthors = Lee MS, Cha EY, Sul JY, Song IS, Kim JY | title = Chrysophanic acid blocks proliferation of colon cancer cells by inhibiting EGFR/mTOR pathway | journal = Phytotherapy Research | volume = 25 | issue = 6 | pages = 833–7 | date = June 2011 | pmid = 21089180 | doi = 10.1002/ptr.3323 | s2cid = 2937534 }} It induces the necrosis of cells via a reduction in ATP levels.{{cite journal | vauthors = Burnstock G, Di Virgilio F | title = Purinergic signalling and cancer | journal = Purinergic Signalling | volume = 9 | issue = 4 | pages = 491–540 | date = December 2013 | pmid = 23797685 | pmc = 3889385 | doi = 10.1007/s11302-013-9372-5 }} Chrysophanol attenuates the effects of lead exposure in mice by reducing hippocampal neuronal cytoplasmic edema, enhancing mitochondrial crista fusion, significantly increasing memory and learning abilities, reducing lead content in blood, heart, brain, spleen, kidney and liver, promoting superoxide dismutase and glutathione peroxidase activities and reducing malondialdehyde level in the brain, kidney and liver.{{cite journal | vauthors = Zhang J, Yan C, Wang S, Hou Y, Xue G, Zhang L | title = Chrysophanol attenuates lead exposure-induced injury to hippocampal neurons in neonatal mice | journal = Neural Regeneration Research | volume = 9 | issue = 9 | pages = 924–30 | date = May 2014 | pmid = 25206913 | pmc = 4146226 | doi = 10.4103/1673-5374.133141 | doi-access = free }}

Chrysophanol can act as an antineoplastic drug. This has been shown in multiple organisms. It has been reported that chrysophanol causes necrosis-like cell death in renal cancer cells.{{cite journal | vauthors = Choi JS | title = Chrysophanic Acid Induces Necrosis but not Necroptosis in Human Renal Cell Carcinoma Caki-2 Cells | journal = Journal of Cancer Prevention | volume = 21 | issue = 2 | pages = 81–7 | date = June 2016 | pmid = 27390736 | pmc = 4933431 | doi = 10.15430/JCP.2016.21.2.81 }} It also has expressed the capability to be classes as an ATC code A10 drug due to its effect on diabetic nephropathy as well as being able to lower lipid absorption.

Chrysophanol is naturally made by a variety of plant species. The most intake is from consumption of rhubarb.

Chrysophanol has been shown to be able to be co-administered with atorvastatin, to lower cholesterol levels. This is due to the different mechanisms for each, with chrysophanol thought to bind to the stomach to disturb lipid absorption, while atorvastatin decreases cholesterol production in the liver.

Anthraquinones, chrysophanol derivatives among them, have been shown to be hepatotoxic.{{cite journal | vauthors = Lin L, Yuan F, Liu Y, Zhong M, Xie T, Ni J, Li H | title = Hepatotoxicity and mechanism study of chrysophanol-8-O-glucoside in vitro | journal = Biomedicine & Pharmacotherapy | volume = 120 | pages = 109531 | date = December 2019 | pmid = 31648163 | doi = 10.1016/j.biopha.2019.109531 | doi-access = free }} They can cause apoptosis in normal human liver cells. Chrysophanol derivatives such as chrysophanol-8-o-glucoside, have also been shown to possess anti-coagulant and anti-platelet properties.{{cite journal | vauthors = Seo EJ, Ngoc TM, Lee SM, Kim YS, Jung YS | title = Chrysophanol-8-O-glucoside, an anthraquinone derivative in rhubarb, has antiplatelet and anticoagulant activities | journal = Journal of Pharmacological Sciences | volume = 118 | issue = 2 | pages = 245–54 | date = 2012 | pmid = 22302018 | doi = 10.1254/jphs.11123fp | doi-access = free }} The derivatives also have potential to cause abnormal oxidative phosphorylation which can result in decreased mitochondrial membrane potential, as well as an increase in abundance of reactive oxygen species, and ultimately will lead to mitochondrial damage and eventual apoptosis.

There is also evidence that chrysophanol could cause damage to DNA. This has been demonstrated in two strains of Salmonella (strains TA 2637 and 1537). It is also important to note, that in treating liver cancer cells, it does so in a way that induced necrosis-like cell death.{{cite journal | vauthors = Ni CH, Chen PY, Lu HF, Yang JS, Huang HY, Wu SH, Ip SW, Wu CT, Chiang SY, Lin JG, Wood WG, Chung JG | display-authors = 6 | title = Chrysophanol-induced necrotic-like cell death through an impaired mitochondrial ATP synthesis in Hep3B human liver cancer cells | journal = Archives of Pharmacal Research | volume = 35 | issue = 5 | pages = 887–95 | date = May 2012 | pmid = 22644856 | doi = 10.1007/s12272-012-0514-z | s2cid = 5631532 }} Necrosis damages the cellular environment, meaning that while it may treat potential issues, it can also damage the surrounding tissue.

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{{cite journal | vauthors = Trybus W, Król T, Trybus E, Stachurska A, Król G | title = The potential antitumor effect of chrysophanol in relation to cervical cancer cells | journal = Journal of Cellular Biochemistry | volume = 122 | issue = 6 | pages = 639–652 | date = June 2021 | pmid = 33417255 | doi = 10.1002/jcb.29891 | s2cid = 231193505 }}

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{{Purinergics}}

Category:Dihydroxyanthraquinones

Category:Plant toxins