Rheic Acid (Rhein; Monorhein)   中文名称: 大黄酸

大黄酸以剂量依赖性方式降低 NB4 细胞活力（0-80 μM，72 小时）[2]。大黄酸（5 μM，72 小时）可增强 ATRA 激活的 NB4 细胞以及半贴壁巨噬细胞样细胞中 ROS 的形成和吞噬作用，以及 CD11b、CD14、CCR-1 和 CCR- 的表达。 2 [2]。大黄酸（5 μM，72 小时）抑制 mTOR 通路并引发 NB4 细胞凋亡 [2]。在 MCF-7 和 MDA-MB-435 细胞中，大黄酸（50-200 μM，48 小时）可抑制血管生成 [4]。大黄酸（0-50 μM，24 小时）可抑制 HUVEC 增殖、迁移、侵袭和管形成（抑制上清液中的 VEGF165、EGF 和核提取物中的 HIF-1α）[4]。

在大鼠中，大黄酸（10-40 mg/kg，ig）可以预防对乙酰氨基酚引起的肝脏和肾脏损伤[3]。

RT-PCR[2]
细胞类型：急性早幼粒细胞白血病 (APL) 细胞（NB4 细胞）
测试浓度： 5 μM
孵育时间：72 小时
实验结果：PU.1、C/EBPA 和 C/EBPE 的 mRNA 表达增加。 ATRA 激活的 CCR1 和 CCR2 mRNA 表达增加。

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蛋白质印迹分析[2]
细胞类型： NB4 细胞
测试浓度： 0-40 μM
孵育时间：48 和 72 小时
实验结果：增加了 cleaved caspase-3、Bax 的表达。减少Bcl-xl、procaspase-3的表达。

Animal/Disease Models: 2.5 g/kg APAP (ig) induced rats[3]
Doses: 10, 20 and 40 mg/kg
Route of Administration: ig
Experimental Results: Ameliorated histopathological damage of liver and kidney. decreased GPT, GOT, UREA and CREA levels and ROS production. Restored NO, MDA, GSH contents.

Absorption, Distribution and Excretion
Tmax of 1.6-2.6 hours.
37% is excreted in urine and 53% in feces as estimated in rats.
15-60L.
Total CL is 1.5 L/h and renal CL is 0.1 L/h.

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Metabolism / Metabolites
Metabolized primarily to rhein glucuronide and rhien sulfate.

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Biological Half-Life
4-10h.

Protein Binding
99% bound to plasma proteins.

[1]. The Drug-Drug Effects of Rhein on the Pharmacokinetics and Pharmacodynamics of Clozapine in Rat Brain Extracellular Fluid by In Vivo Microdialysis. J Pharmacol Exp Ther. 2015 Oct;355(1):125-34.

[2]. Rhein augments ATRA-induced differentiation of acute promyelocytic leukemia cells. Phytomedicine. 2018 Oct 1;49:66-74.

[3]. Rhein protects against acetaminophen-induced hepatic and renal toxicity. Food Chem Toxicol. 2011 Aug;49(8):1705-10.

[4]. Rhein inhibits angiogenesis and the viability of hormone-dependent and -independent cancer cells under normoxic or hypoxic conditions in vitro. Chem Biol Interact. 2011 Jul 15;192(3):220-32.

Pharmacodynamics
**Liver: **Reverses animal models of non-alcoholic fatty liver disease by lowering liver lipids and reducing inflammation. Also reverses and prevents fibrosis in liver injury. **Kidney: **Protects against fibrosis in nephropathy models and improves epithelial tight junction function. **Bone and joint:** Decreases inflammation and cartilage destruction and also corrects altered osteoblast acitivity. **Lipid lowering and anti-obesity:** Reduces body weight and fat content, and lowers high density lipoprotein and low density lipoprotein. May prevent adipocyte differentiation. **Anti-oxidant/Pro-oxidant**: Reduces levels of reactive oxygen species (ROS) at concentrations of about 2-16 microM but induces the generation of ROS at concentrations of 50 microM and above. **Anti-cancer:** Rhein has been observed to produce DNA damage and suppress DNA repair in cancer cells. It induces apoptosis via ER stress, calcium, and mitochondria mediated pathways. Rhein also prevents cancer cell invasion into systemic circulation by preventing angiogenesis and breakdown of the extracellular matrix. Finally, rhein suppresses the activation of several tumor promoting signalling pathways. **Anti-inflammatory: ** Suppresses the production of pro-inflammatory cytokines such as interleukin-1beta and interleukin-6. **Anti-diabetic: **Lowers plasma glucose and increases survival of islet beta cells in type 2 diabetes mellitus models. **Anti-microbial:** Inhibits arylamine N-acteyltransferase and cell growth in Helicobacter pylori. Rhien also appears to be effective against many genotypes of Staphylococcus aureus. **Anti-allergenic:** Inhibits production of leukotrienes and the release of histamine from mast cells.

C15H8O6

284.22

284.032

478-43-3

10168

Light yellow to yellow solid powder

1.7±0.1 g/cm3

597.8±50.0 °C at 760 mmHg

≥300 °C(lit.)

329.4±26.6 °C

0.0±1.8 mmHg at 25°C

1.761

4.58

111.9

3

6

1

21

487

0

FCDLCPWAQCPTKC-UHFFFAOYSA-N

InChI=1S/C15H8O6/c16-9-3-1-2-7-11(9)14(19)12-8(13(7)18)4-6(15(20)21)5-10(12)17/h1-5,16-17H,(H,20,21)

4,5-Dihydroxyanthraquinone-2-carboxylic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: 1.67 mg/mL (5.88 mM) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 悬浮液；超声助溶。
例如，若需制备1 mL的工作液，可将100 μL 16.7 mg/mL澄清的DMSO储备液加入到400 μL PEG300中，混匀；再向上述溶液中加入50 μL Tween-80 +，混匀；然后加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。