Friedelin
(Synonyms: 软木三萜酮) 目录号 : GC60169
Friedelin 是从 Maytenus ilicifolia(Mart) 的叶子中分离出来的。 Friedelin 是 CYP3A4 的非竞争性抑制剂，IC50 和 Ki 值分别为 10.79 μM 和 6.16 μM。 Friedelin 还是 CYP2E1 的竞争性抑制剂，IC50 和 Ki 值分别为 22.54 μM 和 18.02 μM。
Cas No.:559-74-0
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Friedelin is isolated from isolated from the leaves of Maytenus ilicifolia(Mart). Friedelin is a noncompetitive inhibitor of CYP3A4 with IC50 and Kivalues of 10.79 μM and 6.16 μM, respectively. Friedelin is also a competitive inhibitor of CYP2E1 with IC50 and Ki values of 22.54 μM and 18.02 μM, respectively[1].
[1]. Wei J, et al. In vitro inhibitory effects of Friedelin on human liver cytochrome P450 enzymes. Pharm Biol. 2018 Dec;56(1):363-367.
| Cas No. | 559-74-0 | SDF | |
| 别名 | 软木三萜酮 | ||
| Canonical SMILES | C[C@@]12[C@]([C@@]3([H])[C@](C)(CCC(C)(C)C3)CC1)(CC[C@]4(C)[C@]2([H])CC[C@@]([C@H]5C)(C)[C@@]4([H])CCC5=O)C | ||
| 分子式 | C30H50O | 分子量 | 426.72 |
| 溶解度 | THF : 7.14 mg/mL (16.73 mM; Need ultrasonic); DMSO : < 1 mg/mL (insoluble or slightly soluble) | 储存条件 | |
| 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.3435 mL | 11.7173 mL | 23.4346 mL |
| 5 mM | 0.4687 mL | 2.3435 mL | 4.6869 mL |
| 10 mM | 0.2343 mL | 1.1717 mL | 2.3435 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。
Friedelin, a novel inhibitor of CYP17A1 in prostate cancer from Cassia tora
J Biomol Struct Dyn 2022 Nov 14;1-26.PMID:36373336DOI:10.1080/07391102.2022.2145497.
In prostate cancer (PC), drugs targeting CYP17A1 have shown great success in regulating PC progression. However, successful drug molecules show adverse side effects and therapeutic resistance in PC. Therefore, we proposed to discover the potent phytochemical-based inhibitor against CYP17A1 using virtual screening. In this study, a phytochemicals library of ∼13800 molecules was selected to screen the best possible inhibitors against CYP17A1. A molecular modelling approach investigated detailed intermolecular interactions, their structural stability, and binding affinity. Further, in vitro and in vivo studies were performed to confirm the anticancer activity of identified potential inhibitor against CYP17A1. Friedelin from Cassia tora (CT) is identified as the best possible inhibitor from the screened library. MD simulation study reveals stable binding of Friedelin to conserved binding pocket of CYP17A1 with higher binding affinity than studied control, that is, Orteronel. Friedelin was tested on hormone-sensitive (22Rv1) and insensitive (DU145) cell lines and the IC50 value was found to be 72.025 and 81.766 µg/ml, respectively. CT extract showed a 25.28% IC50 value against 22Rv1, ∼92.6% increase in late Apoptosis/Necrosis, and three folds decrease in early apoptosis in treated cells compared to untreated cells. Further, animal studies show a marked decrease in prostate weight by 39.6% and prostate index by 36.5%, along with a reduction in serum PSA level by 71.7% and testosterone level by 92.4% compared to the testosterone group, which was further validated with histopathological studies. Thus, we propose Friedelin and CT extract as potential leads, which could be taken further for drug development in PC. Communicated by Ramaswamy H. Sarma.
Friedelin Attenuates Neuronal Dysfunction and Memory Impairment by Inhibition of the Activated JNK/NF-κB Signalling Pathway in Scopolamine-Induced Mice Model of Neurodegeneration
Molecules 2022 Jul 14;27(14):4513.PMID:35889382DOI:10.3390/molecules27144513.
Oxidative stress (OS) and c-Jun N-terminal kinase (JNK) are both key indicators implicated in neuro-inflammatory signalling pathways and their respective neurodegenerative diseases. Drugs targeting these factors can be considered as suitable candidates for treatment of neuronal dysfunction and memory impairment. The present study encompasses beneficial effects of a naturally occurring triterpenoid, Friedelin, against scopolamine-induced oxidative stress and neurodegenerative pathologies in mice models. The treated animals were subjected to behavioural tests i.e., Y-maze and Morris water maze (MWM) for memory dysfunction. The underlying mechanism was determined via western blotting, antioxidant enzymes and lipid profile analyses. Molecular docking studies were carried out to predict the binding modes of Friedelin in the binding pocket of p-JNK protein. The results reveal that scopolamine caused oxidative stress by (1) inhibiting catalase (CAT), peroxidase enzyme (POD), superoxide dismutase (SOD), and reduced glutathione enzyme (GSH); (2) the up-regulation of thiobarbituric acid reactive substances (TBARS) in mice brain; and (3) affecting the neuronal synapse (both pre- and post-synapse) followed by associated memory dysfunction. In contrast, Friedelin administration not only abolished scopolamine-induced oxidative stress, glial cell activation, and neuro-inflammation but also inhibited p-JNK and NF-κB and their downstream signaling molecules. Moreover, Friedelin administration improved neuronal synapse and reversed scopolamine-induced memory impairment accompanied by the inhibition of β-secretase enzyme (BACE-1) to halt amyloidogenic pathways of amyloid-β production. In summary, all of the results show that Friedelin is a potent naturally isolated neuro-therapeutic agent to reverse scopolamine-induced neuropathology, which is characteristic of Alzheimer's disease.
Friedelin exhibits antidiabetic effect in diabetic rats via modulation of glucose metabolism in liver and muscle
J Ethnopharmacol 2021 Mar 25;268:113659.PMID:33271243DOI:10.1016/j.jep.2020.113659.
Ethnopharmacological relevance: Demand for plant-based medications and therapeutics is increasing worldwide as of its potential effects and no toxic. Traditionally, so many medicinal plants are used to treat diabetes. Subsequently, investigation on medicinal plants was enduring to discover potential antidiabetic drugs. A. tetracantha is used traditionally to cure diabetes mellitus, cough, dropsy, chronic diarrhea, rheumatism, phthisis and smallpox. Scientifically, A. tetracantha has been reported as an antidiabetic agent. Friedelin, the isolated compound has been reported as hypolipidemic, antioxidant, scavenging of free radicals, antiulcer, anti-inflammatory, analgesic and antipyretic agent. Aim of the study: To scrutinize the mechanism of antidiabetic activity of Friedelin isolated from the leaves of A. tetracantha. Materials and methods: A. tetracantha leaves powder (5 kg) was soaked in hexane (15 L) to obtain hexane extract. Using column chromatography, the hexane extract was fractionated using a combination of solvents like hexane and ethyl acetate. 25 fractions were obtained and the fractions 13 and 14 yielded the compound, Friedelin. Friedelin at the doses of 20 and 40 mg/kg was used to treated STZ -induced diabetic rats for 28 days. Later 28 days of treatment, the bodyweight changes, levels of blood glucose, insulin, SGOT, SGPT, SALP, liver glycogen and total protein were assessed. Results: Friedelin significantly brought these altered levels to near normal. Moreover, Friedelin also enhanced the translocation as well as activation of GLUT2 and GLUT4 through PI3K/p-Akt signaling cascade in skeletal muscles and liver on diabetic rats. Conclusion: This finding proved that Friedelin has an anti-diabetic effect through insulin-dependent signaling cascade mechanism, thus it may lead to establishing a drug to treat type 2 diabetes mellitus.
Revealing the Mechanism of Friedelin in the Treatment of Ulcerative Colitis Based on Network Pharmacology and Experimental Verification
Evid Based Complement Alternat Med 2021 Nov 2;2021:4451779.PMID:34765000DOI:10.1155/2021/4451779.
Objectives: Ulcerative colitis (UC) is a chronic inflammatory disease affecting the colon, and its incidence is rising worldwide. This study was designed to uncover the healing effect of Friedelin, a bioactive compound against UC through bioinformatics of network pharmacology and experimental verification of UC model mice. Materials and methods: Targets of Friedelin and potential mechanism of Friedelin on UC were predicted through target searching, PPI network establishing, and enrichment analyzing. We explored effects of Friedelin on dextran sulfate sodium (DSS)-induced colitis. Severity of UC was investigated by body weight, disease activity index (DAI), and length of the colon. Inflammation severity was examined by determination of proinflammatory and anti-inflammatory cytokines. The numbers of autophagosome around the epithelial cells were observed by autophagy inhibition via a transmission electron microscope. The expressions of autophagy-related ATG5 protein and AMPK-mTOR signaling pathway were determined by immunofluorescence staining. Results: In this study, 17 potential targets of Friedelin and 1111 UC-related targets were identified. 10 therapeutic targets of Friedelin against UC were acquired from overlapped targets of UC and Friedelin. PPI network construction filtered 14 core targets through target amplification and confidence enhancement. The results of molecular docking showed that the docking scores of the top 5 active targets were higher than the threshold values. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were carried out, showing Friedelin alleviates UC through anti-inflammatory pathways and molecular function of autophagy. Subsequently, animal-based experiments revealed the intraperitoneal injection of Friedelin ameliorated DSS-induced body weight loss, DAI decrease, colon length shortening and colonic pathological damage with lower myeloperoxidase and proinflammatory cytokines (IL-1β and IL-6) and higher IL-10 levels, and more autophagosomes in transmission electron microscope results. The AMPK-mTOR signaling pathway plays important role in the Friedelin's effect in autophagy as KEGG pathway result and experiment verification. Furthermore, the 3 ma validated the role of autophagy as an improvement in the Friedelin's pharmacologic effect to UC model mice. Conclusions: Friedelin ameliorated DSS-induced colitis in mice through of inflammatory inhibition and regulation of autophagy.
Friedelin Alleviates the Pathogenesis of Collagenase-Induced Tendinopathy in Mice by Promoting the Selective Autophagic Degradation of p65
Nutrients 2022 Apr 18;14(8):1673.PMID:35458235DOI:10.3390/nu14081673.
With the development of an aging population, tendinopathy has become a common musculoskeletal disease in the elderly with a high recurrence rate and no curative treatment. The inflammation mediated by NF-κB signaling plays an important role in tendon senescence and degeneration. Friedelin (FR) is a triterpenoid derived from green plants, which has a variety of pharmacological functions, such as analgesia, anti-inflammation, antioxidation, and anti-tumor functions. However, the role and mechanism of FR in tendinopathy are unclear. Here, we found that FR improved the mechanical strength of the Achilles tendon, restored the orderly arrangement of collagen fibers, reduced inflammatory cell infiltration, and promoted tenogenesis, thereby blocking the progression of tendinopathy. Mechanistically, FR promoted the autophagic degradation of p65 by enhancing the interaction between p62 and p65 and effectively inhibited the activation of the NF-κB pathway, thus alleviating the inflammatory response of tenocytes. In addition, FR recruited E3 ubiquitin enzyme RNF182 to increase the K48-linked ubiquitination of p65 and promoted p62-mediated autophagic degradation. Furthermore, blocking ubiquitination reversed the degradation of p65 by FR. Therefore, these findings identify the new pharmacological mechanism of the anti-inflammatory effect of FR and provide a new candidate drug for the treatment of tendinopathy.