Totarol
(Synonyms: 桃柁酚,NSC 299936, (+)-Totarol, trans-Totarol) 目录号 : GC40043
A diterpene with diverse biological activities
Cas No.:511-15-9
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
Totarol is a diterpene originally isolated from P. totara that has diverse biological activities, including antibacterial, antioxidant, and neuroprotective properties.[1] It is active against Gram-positive bacteria, including P. acnes, S. mutans, B. subtilis, and B. ammoniagenes (MICs = 0.39, 0.78, 1.56, and 0.78 µg/ml, respectively), as well as penicillin-resistant and -susceptible strains of S. aureus (MICs = 0.78 and 1.56 µg/ml, respectively).[2] It inhibits mitochondrial respiration in P. aeruginosa, inhibiting NADH-cytochrome c, NADH-DPIP, and NADH-coenzyme Q reductases but not cytochrome c oxidase.[3] Totarol inhibits Fe(III)-ADP/NADPH-induced lipid oxidation in rat liver microsomes and mitochondria (IC50s = 4.79 and 0.47 µM, respectively) and autooxidation of linoleic acid with an IC50 value of 9.8 µM.[4] In rat primary cerebellar granule cells, totarol increases Akt and GSK-3β phosphorylation when used at a concentration of 5 µM and prevents neuronal death induced by glutamate or oxygen and glucose deprivation.[5] It also reduces infarct volume in a rat model of acute cerebral ischemic injury when administered at doses of 1 and 10 microgram/kg.
Reference:
[1]. Short, W.F., and Stromberg, H. Totarol. Part I. J. Chem. Soc. 0, 516-520 (1937).
[2]. Kubo, I., Muroi, H., and Himehima, M. Antibacterial activity of totarol and its potentiation. J. Nat. Prod. 55(10), 1436-1440 (1992).
[3]. Haraguchi, H., Oike, S., Muroi, H., et al. Mode of antibacterial action of totarol, a diterpene from Podocarpus nagi. Planta Med. 62(2), 122-125 (1996).
[4]. Haraguchi, H., Ishikawa, H., and Kubo, I. Antioxidative action of diterpenoids from Podocarpus nagi. Planta Med. 63(3), 213-215 (1997).
[5]. Gao, Y., Xu, X., Chang, S., et al. Totarol prevents neuronal injury in vitro and ameliorates brain ischemic stroke: Potential roles of Akt activation and HO-1 induction. Toxicol. Appl. Pharmacol. 289(2), 142-154 (2015).
| Cas No. | 511-15-9 | SDF | |
| 别名 | 桃柁酚,NSC 299936, (+)-Totarol, trans-Totarol | ||
| 化学名 | (4bS,8aS)-4b,5,6,7,8,8a,9,10-octahydro-4b,8,8-trimethyl-1-(1-methylethyl)-2-phenanthrenol | ||
| Canonical SMILES | OC(C=C1)=C(C(C)C)C2=C1[C@]3(C)[C@](CC2)([H])C(C)(C)CCC3 | ||
| 分子式 | C20H30O | 分子量 | 286.5 |
| 溶解度 | 2mg/mL in ethanol, 10mg/mL in DMSO, 2.5mg/mL in DMF | 储存条件 | Store at -20°C |
| 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 | 3.4904 mL | 17.452 mL | 34.904 mL |
| 5 mM | 0.6981 mL | 3.4904 mL | 6.9808 mL |
| 10 mM | 0.349 mL | 1.7452 mL | 3.4904 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。
Totarol, a natural diterpenoid, induces selective antitumor activity in SGC-7901 human gastric carcinoma cells by triggering apoptosis, cell cycle disruption and suppression of cancer cell migration
J BUON 2021 Mar-Apr;26(2):640.PMID:34077024doi
Retraction of: 'Totarol, a natural diterpenoid, induces selective antitumor activity in SGC-7901 human gastric carcinoma cells by triggering apoptosis, cell cycle disruption and suppression of cancer cell migration', by Tong Xu, Lunhua Huang, Zhiqiang Liu, Dongwen Ma, Guowei Zhang, Xiaofei Ning, Xinyang Lu, Hongsheng Liu, Biao Jiang JBUON 2019;24(2):686-692; PMID:31128024. Following the publication of the above article, readers drew to our attention that part of the data was unreliable. The authors were requested to provide the raw data to prove the originality, but were unable to do so. After an investigation, the Editors of JBUON decided to retract this article. We thank the readers for bringing this matter to our attention. We apologize for any inconvenience it may cause.
Totarol, a natural diterpenoid, induces selective antitumor activity in SGC-7901 human gastric carcinoma cells by triggering apoptosis, cell cycle disruption and suppression of cancer cell migration
J BUON 2019 Mar-Apr;24(2):686-692.PMID:31128024doi
Purpose: Totarol is a plant-derived natural product and has been reported to exhibit important pharmacological activities. However, the anticancer activity of Totarol has not been evaluated yet. Therefore, the present research work was designed to evaluate the antitumor effects of Totarol in SGC-7901 human gastric cancer cells and human gastric epithelial mucosa cell line GES-1 (used as normal cell line model) together with examining its effects on induction of apoptosis, cell cycle phase distribution and cell migration. Methods: The effect of Totarol on cell cytotoxicity was evaluated by MTT cell viability assay. Inverted phase contrast microscopy was used to identify the effects on cell morphology, while transmission electron microscopy indicated the apoptosis-driven morphological changes in cancer cells. The effects on cell apoptosis were also evaluated by annexin V/PI staining, while cell cycle analysis was done by flow cytometry. In vitro wound healing assay estimated the effects of Totarol on cell migration. Results: The results indicated that Totarol induced selective cytotoxic effects in SGC-7901 human gastric cancer cells concentration-dependently and exhibited lower toxicity in GES-1 normal cells. The totarol-treated cells showed significant alterations in cell morphology including rounding and cellular shrinkage. Untreated SGC-7901 cells exhibited normal cellular morphology with undamaged plasma membrane. However, treating cells with Totarol led to damaged plasma membrane along with appearance of rounded protrusions (apoptotic bodies) containing damaged and broken chromatin material. Treatment with different doses of Totarol led to profound suppression of wound healing. Totarol treatment also led to G2/M phase cell cycle arrest in these cells in a concentration-dependent manner. Conclusions: The present study indicated that Totarol diterpene has the tendency to show selective anticancer effects in SGC-7901 human gastric cancer cells along with inducing apoptosis, cell cycle arrest and inhibition of cell migration.
Application of Totarol as natural antibacterial coating on dental implants for prevention of peri-implantitis
Mater Sci Eng C Mater Biol Appl 2020 May;110:110701.PMID:32204015DOI:10.1016/j.msec.2020.110701.
Peri-implantitis is the most important issue threatening the long-term survival rate of dental implants. Various efforts have been made to reduce implant surface plaque formation, which is one of the essential causes of peri-implantitis. In our study, we applied the natural antibacterial agent Totarol as a coating on experimental silicon wafer and titanium implant surfaces. To analyze the interaction between the Totarol coating and the oral primary colonizer S. gordonii and isolates of mixed oral bacteria, samples were incubated in a model system simulating the oral environment and analyzed by Live/Dead staining, crystal violet staining and scanning electron microscopy (SEM). After 4 d, 8 d, 12 d, 16 d, and 24 d salivary incubation, the stability and antibacterial efficiency of Totarol coating was evaluated through SEM. The results indicated that Totarol coatings on both silicon wafer and Ti surfaces caused efficient contact killing and an inhibition effect towards S. gordonii and mixed oral bacterial film growth after 4 h, 8 h, 24 h, and 48 h incubation. After longtime salivary incubation of 12 d, the bactericidal effect started to weaken, but the anti-adhesion and inhibition effect to biofilm development still exist after 24 d of salivary incubation. The application of a Totarol coating on implant or abutment surfaces is a promising potential prophylactic approach against peri-implantitis.
Totarol prevents neuronal injury in vitro and ameliorates brain ischemic stroke: Potential roles of Akt activation and HO-1 induction
Toxicol Appl Pharmacol 2015 Dec 1;289(2):142-54.PMID:26440581DOI:10.1016/j.taap.2015.10.001.
The natural product Totarol, a phenolic diterpenoid and a major constituent isolated from the sap of Podocarpus totara, has been reported to have a potent antimicrobial activity. In this study, we determined whether Totarol possessed an additional neuroprotective activity in vitro and in vivo. We found that Totarol prevented glutamate- and oxygen and glucose deprivation-induced neuronal death in primary rat cerebellar granule neuronal cells and cerebral cortical neurons. Totarol increased Akt and GSK-3β phosphorylation, Nrf2 and heme oxygenase-1 (HO-1) protein expressions and suppressed oxidative stress by increasing GSH and SOD activities. The PI3K/Akt inhibitor LY294002 prevented Totarol neuroprotective effect by suppressing the totarol-induced changes in HO-1 expression and the activities of GSH and SOD. The HO-1 inhibitor ZnPPIX also prevented totarol-increased GSH and SOD activities. In a model of acute cerebral ischemic injury in Sprague-Dawley rats, produced by occlusion of the middle cerebral artery for 2h followed by 22 h or 46 h of reperfusion, Totarol significantly reduced infarct volume and improved the neurological deficit. In this model, Totarol increased HO-1 expression and the activities of GSH and SOD. These observations suggest that Totarol may be a novel activator of the Akt/HO-1 pathway protecting against ischemic stroke through reduction of oxidative stress.
Totarol inhibits bacterial cytokinesis by perturbing the assembly dynamics of FtsZ
Biochemistry 2007 Apr 10;46(14):4211-20.PMID:17348691DOI:10.1021/bi602573e.
Totarol, a diterpenoid phenol, has been shown to inhibit the proliferation of several pathogenic Gram-positive bacteria including Mycobacterium tuberculosis. In this study, Totarol was found to inhibit the proliferation of Bacillus subtilis cells with a minimum inhibitory concentration of 2 microM. It did not detectably perturb the membrane structure of B. subtilis; it strongly induced the filamentation in B. subtilis cells, suggesting that it inhibits bacterial cytokinesis. Totarol (1.5 microM) reduced the frequency of the Z-ring occurrence per micrometer of the bacterial cell length but did not affect the nucleoid frequency, suggesting that it blocks cytokinesis by inhibiting the formation of the Z-ring. The assembly dynamics of FtsZ is thought to play an important role in the formation and functioning of the Z-ring, a machine that engineers cytokinesis in bacteria. Since Totarol was shown to inhibit the proliferation of M. tuberculosis, we examined the effects of Totarol on the assembly dynamics of M. tuberculosis FtsZ (MtbFtsZ) in vitro. Totarol decreased the assembly of MtbFtsZ protofilaments and potently suppressed the GTPase activity of MtbFtsZ. It bound to MtbFtsZ with a dissociation constant of 11 +/- 2.3 microM. It increased the fluorescence intensity of the MtbFtsZ-1-anilinonaphthalene-8-sulfonic acid complex and inhibited the fluorescence intensity of N-(1-pyrene)maleimide-labeled MtbFtsZ, suggesting that Totarol induces conformational changes in MtbFtsZ. The results indicated that Totarol can perturb the assembly dynamics of FtsZ protofilaments in the Z-ring. Totarol exhibited extremely weak inhibitory effects on HeLa cell proliferation. It did not affect microtubule organization in HeLa cells. The results suggest that Totarol inhibits bacterial proliferation by targeting FtsZ and it may be useful as a lead compound to develop an effective antitubercular drug.