Chrysophanic acid appears as golden yellow plates or brown powder. Melting point 196°C. Slightly soluble in water. Pale yellow aqueous solutions turn red on addition of alkali. Solutions in concentrated sulfuric acid are red. (NTP, 1992)
颜色/状态：
Yellow hexagonal or monoclinic needles
蒸汽压力：
3.69X10-10 mm Hg at 25 °C (est)
稳定性/保质期：
按规格使用和贮存，不会发生分解，避免与氧化物接触。
分解：
Hazardous decomposition products formed under fire conditions. - Carbon oxides
The studies presented here were designed to elucidate the enzymes involved in the biotransformation of naturally occurring 1, 8-dihydroxyanthraquinones and to investigate whether biotransformation of 1,8-dihydroxyanthraquinones may represent a bioactivation pathway. We first studied the metabolism of emodin (1, 3,8-trihydroxy-6-methylanthraquinone), a compound present in pharmaceutical preparations. With rat liver microsomes, the formation of two emodin metabolites, omega-hydroxyemodin and 2-hydroxyemodin, was observed. The rates of formation of omega-hydroxyemodin were not different with microsomes from rats that had been pretreated with inducers for different cytochrome P450 enzymes. Thus, the formation of omega-hydroxyemodin seems to be catalyzed by several cytochrome P450 enzymes at low rates. The formation of 2-hydroxyemodin was increased in liver microsomes from 3-methylcholanthrene-pretreated rats and was inhibited by alpha-naphthoflavone, by an anti-rat cytochrome P450 1A1/2 antibody, and, to a lesser degree, by an anti-rat cytochrome P450 1A1 antibody. These data suggest the involvement of cytochrome P450 1A2 in the formation of this metabolite. However, other cytochrome P450 enzymes also seem to catalyze this reaction. The anthraquinone chrysophanol (1,8-dihydroxy-3-methylanthraquinone) is transformed, in a cytochrome P450-dependent oxidation, to aloe-emodin (1, 8-dihydroxy-3-hydroxymethylanthraquinone) as the major product formed. The mutagenicity of the parent dihydroxyanthraquinones and their metabolites was compared in the in vitro micronucleus test in mouse lymphoma L5178Y cells. 2-Hydroxyemodin induced much higher micronucleus frequencies, compared with emodin. omega-Hydroxyemodin induced lower micronucleus frequencies, compared with emodin. Aloe-emodin induced significantly higher micronucleus frequencies than did chrysophanol. These data indicate that the cytochrome P450-dependent biotransformation of emodin and chrysophanol may represent bioactivation pathways for these compounds.
Chrysophanol, a major anthraquinone component occurring in many traditional Chinese herbs, is accepted as important active component with various pharmacological actions such as antibacterial and anticancer activity. Previous studies demonstrated that exposure to chrysophanol induced cytotoxicity, but the mechanisms of the toxic effects remain unknown. In the present metabolism study, three oxidative metabolites (M1-M3, aloe-emodine, 7-hydroxychrysophanol, and 2-hydroxychrysophanol) and five GSH conjugates (M4-M8) were detected in rat and human liver microsomal incubations of chrysophanol supplemented with GSH, and the formation of the metabolites was NADPH dependent except M4 and M5. M4 and M5 were directly derived from parent compound chrysophanol, M6 arose from M2, and M7 and M8 resulted from the oxidation of M4 and M5. Metabolites M5 and M6 were also observed in bile of rats after exposure to chrysophanol, M1-M3 and one NAC conjugate (M9) were detected in urine of rats administrated chrysophanol, and urinary metabolite M9 originated from the degradation of biliary GSH conjugation M6. Recombinant P450 enzyme incubation and microsome inhibition studies demonstrated that P450 1A2 was the primary enzyme responsible for the metabolic activation of chrysophanol and that P450 2B6 and P450 3A4 also participated in the generation of the oxidative metabolites. ...
来源:Hazardous Substances Data Bank (HSDB)
毒理性
毒性总结
鉴定和使用：大黄酸是一种蒽醌化合物。它是传统医学中草药疗法的成分。它已被测试为实验性治疗。人体研究：大黄酚是韩国和中国传统医药制剂中的活性成分，在体外人细胞测试中起到抗炎作用。此外，大黄酚对某些类型的癌细胞表现出抗癌效果。在体外，用大黄酚处理的人肺腺癌A549细胞和人肝癌细胞显示出与坏死细胞死亡相关的细胞模式，而不是凋亡。大黄酚通过抑制固醇调节元件结合蛋白靶基因的mRNA表达，从而能够减少细胞内脂质积累，改善脂质代谢。动物研究：大黄酚具有轻微的细胞毒性和抗糖尿病特性，并可能在胰岛素刺激的葡萄糖运输途径中发挥代谢作用。当大鼠肝细胞原代培养暴露于大黄酚时，没有检测到氧化细胞损伤的迹象。然而，它确实立即增加了细胞内Ca2+浓度。大黄酚在中国仓鼠卵巢细胞中没有诱发断裂作用。大黄酚在代谢激活后，被发现是沙门氏菌typhimurium TA 1537株的移码突变剂。在彗星试验、微核试验和小鼠淋巴瘤L5178Y tk+/-细胞的突变试验中，大黄酚没有表现出致突变性。
IDENTIFICATION AND USE: Chrysophanic acid is an anthraquinone compound. It is ingredient of herbal remedies used in traditional medicine. It has been tested as experimental therapy. HUMAN STUDIES: Chrysophanol is an active component of traditional medicine preparations in Korea and China acting as anti-inflammatory agent when tested in vitro on human cells. In addition, chrysophanol exhibits anticancer effects on certain types of cancer cells. Human lung cancer A549 cells and human liver cancer cells treated with chrysophanol exhibited a cellular pattern associated with necrotic cell death and not apoptosis in vitro. Chrysophanol improved lipid metabolism through suppressing the mRNA expressions of sterol regulatory element-binding proteins target genes and thus capable to attenuate intracellular lipid accumulation. ANIMAL STUDIES: Chrysophanol, has mild cytotoxic and anti-diabetic properties and could play metabolic roles in the insulin-stimulated glucose transport pathway. No signs of oxidative cell damage were detected when the primary cultures of rat hepatocytes were exposed to chrysophanol. It did, however, cause an immediate increase in the intracellular Ca2+ concentration. Chrysophanol had no clastogenic activity in the Chinese hamster ovary cells. Chrysophanol was found to be a frame-shift mutagen for Salmonella typhimurium strain TA 1537 after metabolic activation. Chrysophanol was not mutagenic when tested in the comet assay, the micronucleus test and the mutation assay in mouse lymphoma L5178Y tk+/- cells.
The aim of this study is to evaluate the protective effects of chrysophanol (CH) against paraquat (PQ)-induced pulmonary injury. Fifty BALB/C mice were randomized into five groups: (1) control, (2) PQ, (3) PQ + dexamethasone (Dex, 2 mg/kg), (4) PQ + CH (10 mg/kg), and (5) PQ + CH (20 mg/kg). A single dose of PQ (50 mg/kg, i.p.) was intraperitoneally given to induce acute lung injury. Then mice were treated with CH (10 and 20 mg/kg/day, orally) for 7 days. At the end of the experiment, animals were euthanized and then bronchoalveolar lavage fluid (BALF) and lung tissues were collected for histological observation, biochemical analysis, and Western blot analysis. Malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), interleukin-6 (IL-6), IL-1beta, and tumor necrosis factor-a (TNF-a) levels in BALF were determined. The levels of SOD and MDA in the lung were also detected. The peroxisome proliferator-activated receptor (PPAR)-gamma and nuclear factor-kappaB (NF-kappaB) pathway proteins in the lung were determined by Western blot. Histological examination indicated that CH attenuated lung inflammation caused by PQ. Biochemical results showed that CH treatment significantly reduced the levels of MDA, MPO, and inflammatory cytokines and increased the level of SOD, compared to those in the PQ group. Meanwhile, Western Blot results revealed that CH increased PPAR-gamma expression and inhibited NF-kappaB pathway activation after PQ challenge. These findings suggested the potential therapeutic effects of CH which is derived from a natural product on PQ-induced pulmonary injury.
The aim of this study is to determine whether AST2017-01 which consists of Rumex crispus and Cordyceps militaris would improve atopic dermatitis (AD). We analyzed anti-AD effects of AST2017-01 and chrysophanol, a bioactive compound of AST2017-01, using a 2,4-dinitrofluorobenzene-induced AD murine model. AST2017-01 and chrysophanol relieved clinical severity in AD-like skin lesions and significantly decreased scratching behavior. The thickness of epidermis and infiltration of inflammatory cells in AD-like skin lesions were reduced by AST2017-01 or chrysophanol. AST2017-01 and chrysophanol significantly suppressed the levels of histamine, immunoglobulin E, thymic stromal lymphopoietin (TSLP), interleukin (IL)-4, IL-6, and tumor necrosis factor-a in serum of AD mice. The protein levels of TSLP, intercellular adhesion molecule-1, and macrophage inflammatory protein 2 were significantly inhibited in the skin lesions. The mRNA expressions of TSLP, thymus and activation-regulated chemokine/CCL17, and C-C chemokine receptor 3 were inhibited in the skin lesions by AST2017-01 or chrysophanol. In addition, AST2017-01 and chrysophanol significantly suppressed the expressions and activities of caspase-1 in the skin lesions. Taken together, these results suggest that AST2017-01 has beneficial effects on AD and may be used as a health functional food in AD.
Nitrosative/oxidative stress plays an important role in neuronal death following cerebral ischemia/reperfusion (I/R). Chrysophanol (CHR) has been shown to afford significant neuroprotection on ischemic stroke, however, whether its mechanism is related to attenuating nitrosative/oxidative stress is not clear. In the present study, we investigated the effect of CHR on neuronal injury related to nitric oxide (NO) production by using mouse middle cerebral artery occlusion (MCAO) model. Our results revealed that nitrite plus nitrate (NOx-) and 3-nitrotyrosine (3-NT) levels increased in ischemic brain 14 days after reperfusion, and were subsequently attenuated by CHR treatment. Moreover, 3-NT is colocalized with NeuN and TUNEL, suggesting that neuronal apoptosis following I/R is associated with 3-NT and CHR suppresses NO-associated neuronal cell death. Accordingly, cleaved caspase-3 expression in ischemic brain was decreased by CHR treatment. I/R also decreased the activity of total superoxide dismutase (SOD) and manganese-dependent SOD (MnSOD), whilst increased reactive oxygen species (ROS) production significantly. Interestingly, CHR reversed this decrease in total SOD, and MnSOD activity, and inhibited ROS generation in the ischemic brain. Taken together, our results provide direct evidence suggesting that CHR attenuates nitrosative/oxidative stress injury induced by I/R, providing a novel therapeutic target in the treatment of acute ischemic stroke.
Benign prostatic hyperplasia (BPH) is one of the most common chronic diseases in male population, of which incidence increases gradually with age. In this study, we investigated the effect of chrysophanic acid (CA) on BPH. BPH was induced by a 4-week injection of testosterone propionate (TP). Four weeks of further injection with vehicle, TP, TP + CA, TP + finasteride was carried on. In the CA treatment group, the prostate weight was reduced and the TP-induced histological changes were restored as the normal control group. CA treatment suppressed the TP-elevated prostate specific antigen (PSA) expression. In addition, 5a-reductase, a crucial factor in BPH development, was suppressed to the normal level close to the control group by CA treatment. The elevated expressions of androgen receptor (AR), estrogen receptor a and steroid receptor coactivator 1 by TP administration were also inhibited in the CA group when compared to the TP-induced BPH group. Then we evaluated the changes in three major factors of the mitogen-activated protein kinase chain during prostatic hyperplasia; extracellular signal-regulated kinase (ERK), c-Jun-N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38). While ERK was elevated in the process of BPH, JNK and p38 was not changed. This up-regulated ERK was also reduced as normal by CA treatment. Further in vitro studies with RWPE-1 cells confirmed TP-induced proliferation and elevated AR, PSA and p-ERK were all reduced by CA treatment. Overall, these results suggest a potential pharmaceutical feature of CA in the treatment of BPH.
A comparative oral pharmacokinetic study of five anthraquinones (aloe-emodin, emodin, rhein, chrysophanol and physcion) from the extract of Rheum palmatum L. was performed in normal and thrombotic focal cerebral ischemia (TFCI)-induced rats. The plasma samples were clarified through solid phase extraction prior to simultaneous determination of the anthraquinones with a validated high-performance liquid chromatography-fluorescence system. The results indicated that the Cmax, t(1/2) and AUC(0-t), of aloe-emodin, rhein, emodin and chrysophanol in TFCI-induced rats were nearly double, whereas the CL values were remarkably decreased (p < 0.05) over those of the normal rats. The plasma drug concentration-time data of five anthraquinones to rats fitted a two-compartment open model. The five anthraquinones in rat plasma were absorbed quickly and eliminated slowly in both groups. The obtained results could be helpful for evaluating the impact of the efficacy and safety of the drug in clinical applications.
ETHNOPHARMACOLOGICAL RELEVANCE: Quyu Qingre granules (QYQRGs) are useful traditional Chinese composite prescription in the treatment of blood stasis syndrome. Comparing differences of pharmacokinetic properties of compounds in QYQRG between normal and blood stasis syndrome rabbits can provide much helpful information. The primary objective of this study was to compare the pharmacokinetics of rhein and chrysophanol after orally administering 2.0 g/kg b.w. QYQRG in normal and acute blood stasis model rabbits. MATERIALS AND METHODS: The blood samples were collected subsequently at 5, 10, 15, 20, 30, 45, 60, 75, 90, 120, 240, 360 and 480 min after orally administrating QYQRG. The concentrations of rhein and chrysophanol in rabbit plasma were determined by HPLC and main pharmacokinetic parameters were obtained. RESULTS: The pharmacokinetic parameters AUC(0-infinity), T(lag), Cmax and K21 of both rhein and chrysophanol were markedly different in the acute blood stasis model rabbits. It was also found that parameters A, beta, MRT and T(1/2beta) of rhein and the parameters a and T1/2a of chrysophanol all exhibited significant difference between the normal and acute blood stasis model rabbits. CONCLUSIONS: The absorption time of rhein and chrysophanol was accelerated and the absorption amount of these two compounds was increased in rabbits with acute blood stasis, suggesting that rhein and chrysophanol would possibly be the two effective compounds in QYQRG.
AIM OF THE STUDY: The present study comparatively investigated the tissue distributions of rhubarb anthraquinone derivatives (AQs) to examine whether they undergo different uptakes in normal or CCl(4)-induced liver-damaged rats, to explore possible reasons for the different toxicities of AQs in pathological model rats and normal rats at the tissue distribution level. MATERIALS AND METHODS: The total rhubarb extract (14.49 g/kg of body weight per day based on the quantity of crude material) was administrated orally to normal and model rats for 12 weeks. The concentrations of free AQs in tissues were quantitated by liquid chromatography-tandem mass spectrometry (LC-MS). After drug withdrawal for 4 weeks, tissue distributions were again determined. RESULTS: The five free AQs-aloe-emodin, rhein, emodin, chrysophanol and physcion-were detected in the liver, kidney and spleen, while only rhein, aloe-emodin and emodin reached the quantitative limit. The tissue distributions of rhein (p < 0.001), aloe-emodin (p < 0.001) and emodin (p < 0.05) in normal rats were higher than those in model rats with rhein>aloe-emodin>emodin in kidney and spleen tissues and aloe-emodin > rhein > emodin in liver tissues. Free AQs were not detected in the tissues after drug withdrawal for 4 weeks. CONCLUSIONS: These results suggest that the tissue toxicity of AQs in normal animals is higher than that in pathological model animals with little accumulative toxicity of rhubarb. The results are concordant with the traditional Chinese theory of You Gu Wu Yun recorded first in Su Wen, a classical Chinese medical treatise.
处理SNU-C5细胞时，Chrysophanic acid能够抑制由表皮生长因子（EGF）诱导的EGFR磷酸化，并抑制下游信号分子如AKT、细胞外信号调节激酶(ERK)及哺乳动物类雷帕霉素靶蛋白(mTOR)/核糖体蛋白S6激酶(p70S6K)的活化。此外，在BGM(Buffalo green monkey)肾脏细胞中，Chrysophanic acid能够抑制Ⅱ和Ⅲ型脊髓灰质炎病毒（小RNA病毒科）及其诱导的细胞病理效应。
Rhein Conjugates, Preparation Method Thereof and Their Uses in Producing Medicines for Treating Diabetic Nephrosis, Intestinal Adhesion and Osteoarthritis
[EN] ISOTOPE ENHANCED AMBROXOL FOR LONG LASTING AUTOPHAGY INDUCTION<br/>[FR] AMBROXOL À ISOTOPE AMÉLIORÉ POUR INDUCTION D'AUTOPHAGIE DURABLE
申请人：STC UNM
公开号：WO2018148113A1
公开（公告）日：2018-08-16
The present invention is directed to 13C and/or 2H isotope enhanced ambroxol ("isotope enhanced ambroxol") and its use in the treatment of autophagy infections, especially mycobacterial and other infections, disease states and/or conditions of the lung, such as tuberculosis, especially including drug resistant and multiple drag resistant tuberculosis. Pharmaceutical compositions comprising isotope enhanced amhroxol, alone or in combination with an additional bioactive agent, especially rifamycin antibiotics, including an additional autophagy modulator (an agent which is active to promote or inhibit autophagy), thus being useful against, an autophagy mediated disease state and/or condition), especially an antophagy mediated disease state and/or condition which occurs in the lungs, for example, a Mycobacterium infection. Chronic Obstructive Pulmonary Disease (COPD), asthma, pulmonary fibrosis, cystic fibrosis, Sjogren's disease and lung cancer (small cell and non-small cell lung cancer, among other disease states and/or conditions, especially of the lung. Methods of treating autophagy disease states and/or conditions, especially including autophagy disease states or conditions which occur principally in the lungs of a patient represent a further embodiment of the present invention. An additional embodiment includes methods of synthesizing compounds according to the present invention as otherwise disclosed herein.
[EN] INHIBITORS OF CREATINE TRANSPORT AND USES THEREOF<br/>[FR] INHIBITEURS DE TRANSPORT DE CRÉATINE ET LEURS UTILISATIONS
申请人：RGENIX INC
公开号：WO2016176636A1
公开（公告）日：2016-11-03
This invention relates to compounds that inhibit creatine transport and/or creatine kinase, pharmaceutical compositions including such compounds, and methods of utilizing such compounds and compositions for the treatment of cancer.
This invention features compounds that modulate the activity of liver X receptors, pharmaceutical compositions including the compounds of the invention, and methods of utilizing those compositions for modulating the activity of liver X receptors in the treatment of cancer.
Intercalating agents with covalent bond forming capability. A novel type of potential anticancer agents. 2. Derivatives of chrysophanol and emodin
作者：Masao Koyama、Kiyobumi Takahashi、Ting Chao Chou、Zbigniew Darzynkiewicz、Jan Kapuscinski、T. Ross Kelly、Kyoichi A. Watanabe
DOI：10.1021/jm00127a032
日期：1989.7
Fifty-one new C-methyl-modified derivatives of the anthraquinones chrysophanol and emodin or their various methyl ethers were prepared for structure-activity relationship studies of anticancer activity against mouse leukemia L1210 and human leukemia HL-60 cells. Representative compounds were spectrophotometrically studied for their capacity to interact with natural and denatured DNA. In general, those
