Manool
(Synonyms: (4AR)-反式-5-(1,5,5,8AS-四甲基-2-亚甲基十氢-1-萘基)-(3R)-甲基-1-戊烯-3-醇) 目录号 : GC61028
Manool是丹参中的二萜。Manool在癌细胞中诱导选择性的细胞毒性。Manool使癌细胞停滞在细胞周期的G(2)/M期。
Cas No.:596-85-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Manool is a diterpene from Salvia officinalis. Manool induces selective cytotoxicity in cancer cells. Manool arrests the cancer cells at the G(2)/M phase of the cell cycle[1][2].
Manool exhibits higher cytotoxic activity against HeLa (IC50=6.7 µg/mL) and U343 (IC50=6.7 µg/mL) cells[1].Manool exhibits a protective effect against chromosome damage induced by MMS in HepG2 cells[3].
[1]. de Oliveira PF, et al. Manool, a Salvia officinalis diterpene, induces selective cytotoxicity in cancer cells. Cytotechnology. 2016;68(5):2139-2143. [2]. Pratsinis H, et al. Antiproliferative activity of Greek propolis. J Med Food. 2010;13(2):286-290. [3]. Nicolella HD, et al. Differential effect of manool--a diterpene from Salvia officinalis, on genotoxicity induced by methyl methanesulfonate in V79 and HepG2 cells. Food Chem Toxicol. 2014;72:8-12.
| Cas No. | 596-85-0 | SDF | |
| 别名 | (4AR)-反式-5-(1,5,5,8AS-四甲基-2-亚甲基十氢-1-萘基)-(3R)-甲基-1-戊烯-3-醇 | ||
| Canonical SMILES | CC(CCC1)(C)[C@]([C@@]1(C)[C@H]2CC[C@](O)(C)C=C)([H])CCC2=C | ||
| 分子式 | C20H34O | 分子量 | 290.48 |
| 溶解度 | 储存条件 | 4°C, stored under nitroge | |
| 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 | 3.4426 mL | 17.2129 mL | 34.4258 mL |
| 5 mM | 0.6885 mL | 3.4426 mL | 6.8852 mL |
| 10 mM | 0.3443 mL | 1.7213 mL | 3.4426 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。
Antitumor Effect of Manool in a Murine Melanoma Model
J Nat Prod 2022 Feb 25;85(2):426-432.PMID:35157797DOI:10.1021/acs.jnatprod.1c01128.
The Manool diterpene, found in abundance in Salvia officinalis L., showed a selective cytotoxic effect against murine melanoma cells. Therefore, the present study aimed to evaluate the antitumor potential of Manool in a murine melanoma model, administered by three routes: oral, subcutaneous, and intraperitoneal. In addition, the antimelanoma effect of Manool (orally) combined with cisplatin (subcutaneous) was evaluated. The results obtained revealed that Manool, administered by the three routes, was able to significantly decrease the mass and frequency of mitosis of the tumor tissue. The data obtained revealed that Manool, at a dose of 20 mg/kg, was able to significantly decrease the tumor mass when administered by the three routes, with the percentages of reduction being equivalent to 62.4% (oral), 48.5% (intraperitoneal), and 38.8% (subcutaneous), without toxic effects. The treatment of Manool plus cisplatin led to 86.7% reduction in tumor mass, higher than that observed in treatment with Manool or cisplatin alone (50.7%), although signs of toxicity have been observed. The results also showed that treatments with Manool (20 mg/kg orally) and/or cisplatin did not alter the activity of caspase 3 cleaved in tumor tissue. Therefore, Manool revealed a promising antimelanoma effect, but without involvement of the caspase 3 cleaved pathway.
Manool, a diterpene from Salvia officinalis, exerts preventive effects on chromosomal damage and preneoplastic lesions
Mutagenesis 2021 May 31;36(2):177-185.PMID:33512444DOI:10.1093/mutage/geab001.
The present study aimed to evaluate the effect of the Manool diterpene on genomic integrity. For this purpose, we evaluated the influence of Manool on genotoxicity induced by mutagens with different mechanisms of action, as well as on colon carcinogenesis. The results showed that Manool (0.5 and 1.0 µg/ml) significantly reduced the frequency of micronuclei induced by doxorubicin (DXR) and hydrogen peroxide in V79 cells but did not influence genotoxicity induced by etoposide. Mice receiving Manool (1.25 mg/kg) exhibited a significant reduction (79.5%) in DXR-induced chromosomal damage. The higher doses of Manool (5.0 and 20 mg/kg) did not influence the genotoxicity induced by DXR. The anticarcinogenic effect of Manool (0.3125, 1.25 and 5.0 mg/kg) was also observed against preneoplastic lesions chemically induced in rat colon. A gradual increase in Manool doses did not cause a proportional reduction of preneoplastic lesions, thus demonstrating the absence of a dose-response relationship. The analysis of serum biochemical indicators revealed the absence of hepatotoxicity and nephrotoxicity of treatments. To explore the chemopreventive mechanisms of Manool via anti-inflammatory pathways, we evaluated its effect on nitric oxide (NO) production and on the expression of the NF-kB gene. At the highest concentration tested (4 μg/ml), Manool significantly increased NO production when compared to the negative control. On the other hand, in the prophylactic treatment model, Manool (0.5 and 1.0 μg/ml) was able to significantly reduce NO levels produced by macrophages stimulated with lipopolysaccharide. Analysis of NF-kB in hepatic and renal tissues of mice treated with Manool and DXR revealed that the mutagen was unable to stimulate expression of the gene. In conclusion, Manool possesses antigenotoxic and anticarcinogenic effects and its anti-inflammatory potential might be related, at least in part, to its chemopreventive activity.
Manool, a Salvia officinalis diterpene, induces selective cytotoxicity in cancer cells
Cytotechnology 2016 Oct;68(5):2139-43.PMID:26547581DOI:10.1007/s10616-015-9927-0.
Manool, a diterpene isolated from Salvia officinalis, was evaluated by the XTT colorimetric assay for cytotoxicity and selectivity against different cancer cell lines: B16F10 (murine melanoma), MCF-7 (human breast adenocarcinoma), HeLa (human cervical adenocarcinoma), HepG2 (human hepatocellular carcinoma), and MO59J, U343 and U251 (human glioblastoma). A normal cell line (V79, Chinese hamster lung fibroblasts) was used to compare the selectivity of the test substance. Manool exhibited higher cytotoxic activity against HeLa (IC50 = 6.7 ± 1.1 µg/mL) and U343 (IC50 = 6.7 ± 1.2 µg/mL) cells. In addition, in the used experimental protocols, the treatment with Manool was significantly more cytotoxic for different tumor cell lines than for the normal cell line V79 (IC50 = 49.3 ± 3.3 µg/mL), and showed high selectivity. These results suggest that Manool may be used to treat cancer without affecting normal cells.
Effect of Diterpene Manool on the Arterial Blood Pressure and Vascular Reactivity in Normotensive and Hypertensive Rats
Arq Bras Cardiol 2020 Oct;115(4):669-677.PMID:33111868DOI:10.36660/abc.20190198.
Background: Many studies have shown that the diterpenoid classes exert a significant effect on the cardiovascular system. Diterpenes, in particular, are among the main compound links to cardiovascular properties such as vasorelaxant, inotropic, diuretic and hypotensive activity. While the Manool vasorelaxation mechanism is visible, its effect on blood pressure (BP) is still unknown. Objective: To evaluate the in vivo hypotensive effect of Manool and check the ex vivo vasorelaxation effect in rat aortic rings. Methods: The animals were divided randomly into two groups: normotensive and hypertensive. The normotensive group was sham-operated, and the 2K1C model was adopted for the hypertensive group. Invasive BP monitoring was performed for Manool tests at different doses (10, 20 and 40 mg/kg). Concentration-response curves for Manool were obtained in the aorta rings, with endothelium, pre-contracted with phenylephrine (Phe) after incubation with Nω-nitro-L-arginine methyl ester(L-NAME) or oxadiazole [4,3-a]quinoxalin-1-one (ODQ). Nitric oxide (NOx) plasma levels were measured by chemiluminescence assay. Results: After Manool administration, BP was reduced in normotensive and hypertensive groups, and this effect was inhibited by L-NAME in hypertensive animals only in 10 mg/kg dose. Ex vivo Manool promoted vasorelaxation, which was inhibited by L-NAME and ODQ incubation or endothelium removal. NOx plasma levels increased in the hypertensive group after Manool administration. Manool elicits endothelium-dependent vascular relaxation in rat aorta mediated by the NO/cGMP signaling pathway and BP reduction, also by NOx plasma increase. These combined effects could be involved in modulating peripheral resistance, contributing to the antihypertensive effect of diterpene. Conclusion: These effects together could be involved in modulating peripheral resistance, contributing to the antihypertensive effect of diterpene.
The diterpene Manool extracted from Salvia tingitana lowers free radical production in retinal rod outer segments by inhibiting the extramitochondrial F1 Fo ATP synthase
Cell Biochem Funct 2021 Jun;39(4):528-535.PMID:33472276DOI:10.1002/cbf.3618.
Uncontrolled oxidative stress production, especially in the outer retina is one of the causes of retinal degenerations. Mitochondria are considered the principal source of oxidative stress. However, a Reactive Oxygen Intermediates (ROI) production in the retinal photoreceptor layer seems to depend also on the expression of an extramitochondrial oxidative phosphorylation (OxPhos) machinery in the rod outer segments (OS). In fact, OS conduct aerobic metabolism, producing ATP through oxygen consumption, although it is devoid of mitochondria. As diterpenes display an antioxidant effect, we have evaluated the effect Manool, extracted from Salvia tingitana, on the extramitochondrial OxPhos and the ROI production in the retinal rod OS. Results confirm that the OxPhos machinery is ectopically expressed in the OS and that F1 Fo -ATP synthase is a target of Manool, which inhibited the OS ATP synthesis, binding the F1 moiety with high affinity, as analysed by molecular docking. Moreover, the overall slowdown of OxPhos metabolism reduced the ROI production elicited in the OS by light exposure, in vitro. In conclusion, data are consistent with the antioxidant properties of Salvia spp., suggesting its ability to lower oxidative stress production, a primary risk factor for degenerative retinal diseases. SIGNIFICANCE OF THE STUDY: Here we show that Manool, a diterpene extracted from Salvia tingitana has the potential to lower the free radical production by light-exposed rod outer segments in vitro, by specifically targeting the rod OS F1 Fo -ATP synthase belonging to the extramitochondrial OxPhos expressed on the disk membrane. The chosen experimental model allowed to show that the rod OS is a primary producer of oxidative stress linked to the pathogenesis of degenerative retinal diseases. Data are also consistent with the antioxidant and anti-inflammatory action of Salvia spp., suggesting a beneficial effect also in vivo.