Rotundic acid
(Synonyms: 铁冬青酸) 目录号 : GC38609
Rotundic acid (Rutundic acid), a natural compound, exhibit cytotoxic activities toward human hepatocellular carcinoma (HepG2), malignant melanoma (A375), SCLC (NCI-H446), breast cancer (MCF-7), and colon cancer (HT-29) cell lines.RA induces cell cycle arrest, DNA damage, and apoptosis by modulating the AKT/mTOR and MAPK pathways.
Cas No.:20137-37-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Rotundic acid (Rutundic acid), a natural compound, exhibit cytotoxic activities toward human hepatocellular carcinoma (HepG2), malignant melanoma (A375), SCLC (NCI-H446), breast cancer (MCF-7), and colon cancer (HT-29) cell lines.RA induces cell cycle arrest, DNA damage, and apoptosis by modulating the AKT/mTOR and MAPK pathways.
| Cas No. | 20137-37-5 | SDF | |
| 别名 | 铁冬青酸 | ||
| Canonical SMILES | C[C@@]1(CO)[C@@H](O)CC[C@]2(C)[C@@]3([H])CC=C4[C@]5([H])[C@](C)(O)[C@H](C)CC[C@@](C(O)=O)5CC[C@](C)4[C@@](C)3CC[C@@]12[H] | ||
| 分子式 | C30H48O5 | 分子量 | 488.7 |
| 溶解度 | Soluble in DMSO | 储存条件 | 4°C, protect from light |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0462 mL | 10.2312 mL | 20.4625 mL |
| 5 mM | 0.4092 mL | 2.0462 mL | 4.0925 mL |
| 10 mM | 0.2046 mL | 1.0231 mL | 2.0462 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Rotundic acid induces Cas3-MCF-7 cell apoptosis through the p53 pathway
Oncol Lett 2019 Jan;17(1):630-637.PMID:30655810DOI:10.3892/ol.2018.9616.
In the present study, the functions and mechanisms of Rotundic acid (RA) underlying its induction of apoptosis in caspase-3-transfected MCF-7 human breast cancer cells (Cas3-MCF-7 cells) were investigated. RA induced apoptosis in Cas3-MCF-7 cells more efficiently compared with that in MCF-7 cells transfected with control plasmid. The results from an MTT assay demonstrated that RA effectively inhibited Cas3-MCF-7 cell viability in a dose-dependent manner and induced cell apoptosis via caspase-3 activity within 12 to 48 h. Western blotting and fluorescence-activated cell sorting demonstrated that RA initiated Cas3-MCF-7 cell apoptosis via p53 activation. The silencing of the p53 gene in the Cas3-MCF-7 cell line led to decreased RA-induced Cas3-MCF-7 cell caspase-3 activity and cell apoptosis. Collectively, the results of the present study indicate that caspase-3 serves a critical function in rotundic acid-induced apoptosis, and suggest that caspase-3 deficiency may contribute to the chemotherapy-resistance of breast cancer. Reconstitution of caspase-3 sensitizes MCF-7 breast cancer cells to chemotherapy. RA has the potential for development as a novel drug combined with reconstitution of caspase-3 gene therapy for the treatment of human breast cancer with caspase-3 deficiency.
Rotundic acid Regulates the Effects of Let-7f-5p on Caco2 Cell Proliferation
Anticancer Agents Med Chem 2021;21(7):902-909.PMID:32748760DOI:10.2174/1871520620999200730165829.
Background & objective: Nowadays, the interaction between natural products and microRNAs provides a promising field for exploring the chemopreventive agents for various cancers. As a member of microRNAs, the expression of let-7f-5p is universally downregulated in Colorectal Cancer (CRC). The present study aimed to uncover the function of let-7f-5p in the proliferation of human colon cancer cell line Caco2 and explored chemopreventive agents from natural resources that can prevent the development of CRC. Methods: Herein, Caco2 cells were transfected with let-7f-5p mimic and inhibitor to manipulate let-7f-5p levels, and the expression of let-7f-5p was performed by RT-qPCR. Next, we determined how let-7f-5p regulates Caco2 cell proliferation by using MTT, wound-healing, cell cycle, and colony formation assays. Besides, to further understand the effect of let-7f-5p, we evaluated the protein level of AMER3 and SLC9A9 by using western blotting assays. Results: The results showed a suppressive function of let-7f-5p on Caco2 cell proliferation and then put forward a triterpenoid (Rotundic acid, RA) which significant antagonized the effect of cell proliferation, restitution after wounding, and colony formation caused by let-7f-5p. Moreover, the western blot results further indicated that the inhibitory effect of RA might be due to its suppressive role in let-7f-5p-targeted AMER3 and SLC9A9 regulation. Conclusion: Our validation study results confirmed that let-7f-5p was a potent tumor suppressor gene of Caco2 cell proliferation, and RA showed as a regulator of the effect of let-7f-5p on cell proliferation and then could be a potential chemopreventive agent for CRC treatment.
Intestinal absorption mechanism of Rotundic acid: Involvement of P-gp and OATP2B1
J Ethnopharmacol 2022 May 10;289:115006.PMID:35051604DOI:10.1016/j.jep.2022.115006.
Ethnopharmacological relevance: Ilicis Rotundae Cortex (IRC), the dried barks of Ilex rotunda Thunb. (Aquifoliaceae), has been used for the prevention or treatment of colds, tonsillitis, dysentery, and gastrointestinal diseases in folk medicine due to its antibacterial and anti-inflammatory effects. However, there is no report about the intestinal absorption of major compounds that support traditional usage. Aim of study: Considering the potential of Rotundic acid (RA) - major biologically active pentacyclic triterpenes found in the IRC, this study was purposed to uncover the oral absorption mechanism of RA using in situ single-pass intestinal perfusion (SPIP) model, in vitro cell models (Caco-2, MDCKII-WT, MDCKII-MDR1, MDCKII-BCRP, and HEK293-OATP2B1 cells) and in vivo pharmacokinetics studies in rats. Materials and methods: The molecular properties (solubility, lipophilicity, and chemical stability) and the effects of principal parameters (time, compound concentrations, pH, paracellular pathway, and the different intestinal segments) were analyzed by liquid chromatography-tandem mass spectrometry. The susceptibility of RA to various inhibitors, such as P-gp inhibitor verapamil, BCRP inhibitor Ko143, OATP 2B1 inhibitor rifampicin, and absorption enhancer EGTA were assessed. Results: RA was a compound with low water solubility (12.89 μg/mL) and strong lipophilicity (LogP = 4.1). RA was considered stable in all media during the SPIP and transport studies. The SPIP and cell experiments showed RA was moderate absorbed in the intestines and exhibited time, concentration, pH, and segment-dependent permeability. In addition, results from the cell model, in situ SPIP model as well as the in vivo pharmacokinetics studies consistently showed that verapamil, rifampicin, and EGTA might have significant effect on the intestinal absorption of RA. Conclusion: The mechanisms of intestinal absorption of RA might involve multiple transport pathways, including passive diffusion, the participation of efflux (i.e., P-gp) and influx (i.e., OATP2B1) transporters, and paracellular pathways.
UPLC-QTOF-MS Based Comparison of Rotundic acid Metabolic Profiles in Normal and NAFLD Rats
Metabolites 2022 Dec 26;13(1):38.PMID:36676962DOI:10.3390/metabo13010038.
Rotundic acid, the principal bioactive constituent of the herbal remedy "Jiubiying", has been considered as a candidate compound for treating non-alcoholic fatty liver disease (NAFLD). However, the in vivo and in vitro metabolism of Rotundic acid has remained unclear. With the aim of elucidating its metabolic profile, a reliable approach that used ultra-high performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was applied for screening and identifying Rotundic acid in vivo (plasma, feces, urine, and liver tissue of normal and NAFLD model rats) and in vitro (rat liver microsomes) metabolites. Herein, 26 metabolites of Rotundic acid were identified, including 22 metabolites in normal rats, 20 metabolites in NAFLD model rats, and eight metabolites in rat liver microsomes. Among them, 17 metabolites were identified for the first time. These data illustrate that the pathological status of NAFLD affects the metabolism of Rotundic acid. Furthermore, the major pathways of metabolism included phase Ⅰ (demethylation, desaturation, etc.) and phase Ⅱ (sulfation and glucuronidation) reactions, as well as a combined multiple-step metabolism. This work provides important information on the metabolism of Rotundic acid and lays the foundation for its future clinical application.
Rotundic acid reduces LPS-induced acute lung injury in vitro and in vivo through regulating TLR4 dimer
Phytother Res 2021 Aug;35(8):4485-4498.PMID:33977594DOI:10.1002/ptr.7152.
Acute lung injury (ALI) is a serious clinical disease. Rotundic acid (RA), a natural ingredient isolated from Ilex rotunda Thunb, exhibits multiple pharmacological activities. However, RA's therapeutic effect and mechanism on ALI remain to be elucidated. The present study aimed to further clarify its regulating effects on inflammation in vitro and in vivo. Our results indicated that RA significantly inhibited the overproduction of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). RA decreased ROS production and calcium influx. In addition, RA inhibited the activation of PI3K, MAPK, and NF-κB pathways and enhanced the activity of nuclear factor E2-related factor 2 (Nrf2) signaling. The cellular thermal shift assay and docking results indicated that RA bind to TLR4 to block TLR4 dimerization. Furthermore, RA pretreatment effectively inhibited ear edema induced by xylene and LPS-induced endotoxin death and had a protective effect on LPS-induced ALI. Our findings collectively indicated that RA has anti-inflammatory effects, which may serve as a potential therapeutic option for pulmonary inflammation.