Teprenone (Geranylgeranylacetone)
(Synonyms: 替普瑞酮; Geranylgeranylacetone) 目录号 : GC33663
An inducer of Hsp expression
Cas No.:6809-52-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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Cell experiment: |
Human umbilical vein endothelial cells (HUVECs) are seeded onto 48-well plates at a density of 1 × 102 cells/well before Teprenone and/or radiation treatment. Cell viability is determined at 48 h after treatment using 0.5 mg/mL MTT solution in serum-free media. This solution is incubated with the cells for 2 h in the 37°C humidified atmosphere containing 5% CO2. Then, the MTT solution is removed, and the cells are dissolved in 100 µL of DMSO. Optical densities of the supernatants are measured at 540 nm with an ELISA spectrophotometer[3]. |
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Animal experiment: |
Male Wister strain rats weighing approximately 250 g are individually housed in wire-mesh cages in a room maintained at 23°C on a 12-hour light-dark cycle. Rats are allowed free access to a standard laboratory chow. Teprenone (200 mg/kg; as emulsion with 5% gum arabic and 0.008% α-tocopherol) or vehicle (5% gum arabic emulsion containing 0.008% α-tocopherol) is given orally in a volume of 5 mL/kg through a metal tubing attached to a 6-mL syringe. Two hours later, rats are placed in restraint cages and then vertically immersed in water at 23°C to the level of the xyphoid process. The rats are killed by decapitation at the indicated times[1]. |
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References: [1]. Hirakawa T, et al. Geranylgeranylacetone induces heat shock proteins in cultured guinea pig gastric mucosal cells and rat gastric mucosa. Gastroenterology. 1996 Aug;111(2):345-57. |
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Geranylgeranylacetone is an inducer of heat shock protein (Hsp) expression that has been shown to increase Hsp70 (also known as Hsp72 and HspA1A), Hsp22 (HspB8), Hsp27 (HspB1), Hsp90 (HspC), and Hsp105 (HspH1) levels in various cells and tissues.1,2,3 It is orally bioavailable and has diverse effects in vivo, including hepatoprotective, neuroprotective, and antiulcerative effects.4,5 The effects of geranylgeranylacetone on Hsp expression are more pronounced under stress conditions.2
1.Fudaba, Y., Tashiro, H., Ohdan, H., et al.Efficacy of HSP72 induction in rat liver by orally administered geranylgeranylacetoneTranspl. Int.13(Suppl 1)S278-S281(2000) 2.Katsuno, M., Sang, C., Adachi, H., et al.Pharmacological induction of heat-shock proteins alleviates polyglutamine-mediated motor neuron diseaseProc. Natl. Acad. Sci. USA102(46)16801-16806(2005) 3.Marunouchi, T., Inomata, S., Sanbe, A., et al.Protective effect of geranylgeranylacetone via enhanced induction of HSPB1 and HSPB8 in mitochondria of the failing heart following myocardial infarction in ratsEur. J. Pharmacol.730140-147(2014) 4.He, W., Zhuang, Y., Wang, L., et al.Geranylgeranylacetone attenuates hepatic fibrosis by increasing the expression of heat shock protein 70Mol. Med. Rep.12(4)4895-4900(2015) 5.Kawasaki, Y., Fujiki, M., Uchida, S., et al.A single oral dose of geranylgeranylacetone upregulates vascular endothelial growth factor and protects against kainic acid-induced neuronal cell death: Involvement of the phosphatidylinositol-3 kinase/Akt pathwayPathobiology(2017)
| Cas No. | 6809-52-5 | SDF | |
| 别名 | 替普瑞酮; Geranylgeranylacetone | ||
| Canonical SMILES | CC(CC/C=C(C)/CC/C=C(C)/CC/C=C(C)/CC/C=C(C)\C)=O | ||
| 分子式 | C23H38O | 分子量 | 330.55 |
| 溶解度 | Ethanol : 50 mg/mL (151.26 mM);DMSO : 5 mg/mL (15.13 mM);Water : < 0.1 mg/mL (insoluble) | 储存条件 | Store at -20°C,stored under nitrogen |
| 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 | 3.0253 mL | 15.1263 mL | 30.2526 mL |
| 5 mM | 0.6051 mL | 3.0253 mL | 6.0505 mL |
| 10 mM | 0.3025 mL | 1.5126 mL | 3.0253 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。
Protection of teprenone against hypoxia and reoxygenation stress in stomach and intestine of Lateolabrax maculatus
Fish Physiol Biochem 2020 Apr;46(2):575-584.PMID:31900796DOI:10.1007/s10695-019-00732-4.
Teprenone (Geranylgeranylacetone) is one kind of safe and effective agent in gastrointestinal mucosa, which have been widely used in human and veterinary, but rarely used in aquaculture animals. In this study, Lateolabrax maculatus, an important economic fish species in southern China, was taken as the object of study to investigate the protective effect of teprenone on intestinal stress. The present study was designed to investigate the potential mechanism underlying the protection offered by teprenone to protect the gastrointestinal tract against hypoxia and reoxygenation injury of L. maculatus. (a) For oxidative stress parameters, SOD, CAT, and T-AOC in control group were higher than those in teprenone group. MDA content was significantly higher than that in teprenone group at N and 12h time points in intestine (P < 0.05), and at 12, 24, and 48 h time points in stomach. (b) For immune-associated proteins, LZM activity in the control group was lower than that in the teprenone group, and the difference between the two groups in stomach and intestine was significant at 12.48 h and 6.48 h time points, respectively (P < 0.05). Compared with time point N, the content of HSP70 in the control group increased at 0 h in intestine. At 0-48 h, intestine HSP70 content in the control group showed a gradually decreasing trend, which was higher than that in the teprenone group. (c) For apoptosis-related factors, the activity of Cyt-C, caspase9, and caspase3 increased first and then decreased in both groups. The content of Cyt-C in the control group was significantly higher than that in the teprenone group at N-3.6 h, and 3.48 h time points in stomach and intestine, respectively (P<0.05). The activity of caspase9 and caspase3 was higher than that in the teprenone group at N-48 h. Results indicated that acute hypoxia and reoxygenation cause the expression levels of oxidative stress and apoptosis-related factors in the stomach and intestine increased first and then decreased within 0-48 h. Acute hypoxia and reoxygenation also that causes the level of nonspecific immunity decreased first and then increased. A total of 400-mg/kg treatment of teprenone can protect stomach and intestinal tissues to a certain extent. It can effectively protect oxidative stress and apoptosis within 0-48 h after acute hypoxia and reoxygenation and enhance non-specific immunity.
Teprenone improves gastric mucosal injury and dyspeptic symptoms in long-term nonsteroidal anti-inflammatory drug users
J Gastroenterol Hepatol 2019 Aug;34(8):1344-1350.PMID:30681185DOI:10.1111/jgh.14614.
Background and aim: Nonsteroidal anti-inflammatory drugs (NSAIDs) are a major cause of gastric mucosal lesions. In China, Teprenone is frequently prescribed as a mucoprotective agent, but the literature regarding their efficacy is limited. Our purpose was to address the effects of Teprenone on long-term NSAID-associated gastric mucosal lesions. Methods: This study examined 369 patients taking NSAIDs for at least 12 weeks. Patients without gastroduodenal ulcer and without Helicobacter pylori infection on endoscopy at baseline were randomized to receive either NSAID plus Teprenone (150 mg/day) or NSAID only for 12 weeks. Lanza scores were examined using endoscopy before and after treatment, and dyspeptic symptom scores are also analyzed. Results: A total of 158 patients were randomized to the Teprenone group (n = 74) or the control group (n = 84) for 12 weeks. Seventy-one of patients in the Teprenone group and 79 of patients in the control group were analyzed finally. After treatment, the Lanza scores and dyspeptic symptom scores decreased significantly in the Teprenone group while increased in the control group (P < 0.05). The changes of Lanza scores and dyspeptic symptom scores were higher in the Teprenone group than in the control group (P < 0.05). For subgroup analysis, the change in Lanza scores and dyspeptic symptom scores improved significantly in the Teprenone group receiving long-term low-dose aspirin treatment, as well as in the Teprenone group receiving other NSAIDs treatment (P < 0.05). Conclusions: Teprenone may be an effective treatment choice of gastric mucosal injuries and dyspepsia symptoms in patients who used NSAIDs chronically without H. pylori infection or history of gastroduodenal ulcer.
Effects of Geranylgeranylacetone upon cardiovascular diseases
Cardiovasc Ther 2018 Aug;36(4):e12331.PMID:29656548DOI:10.1111/1755-5922.12331.
Heat shock proteins (HSPs) are an important family of protective proteins. They are involved actively in an array of cellular processes, including protective effects on the cardiovascular system in response to various stimuli. Increasing evidence shows that pharmacologic interventions that induce expression of HSPs may be a novel approach for the treatment of cardiovascular diseases. However, agents that induce expression of HSPs used previously are toxic or have harmful side effects, which limit their clinical application. Geranylgeranylacetone (GGA) is not only a widely used antiulcer agent in Asia, but also a nontoxic inducer of HSPs expression. It increases the expression of HSPs rapidly in the presence of ischemia, anoxia, oxidative stress, and toxicants, thereby having significant protective effects. The cardioprotective effects of GGA have been corroborated by experiments in vivo and in vitro. Importantly, several derivatives of GGA have been synthesized that have improved pharmaco-chemical and HSPs-boosting properties. In this review, the current knowledge and potential cardioprotective mechanisms of GGA are summarized comprehensively. We discuss the protective effects of GGA in cardiovascular diseases and myocardial injury induced by physical or chemical injury. Currently available information suggests that GGA could be employed as a novel pharmacologic intervention against cardiovascular disease.
Teprenone for the prevention of low-dose aspirin-induced gastric mucosal injury in Helicobacter pylori-negative patients
Scand J Gastroenterol 2019 Oct;54(10):1199-1204.PMID:31591940DOI:10.1080/00365521.2019.1672781.
Objectives: Low-dose aspirin is the standard treatment for the prevention of cardiovascular events in at-risk patients. We performed a randomized, placebo-controlled study to determine the efficacy of Teprenone for primary prevention of gastrointestinal injury in patients taking LDA for vascular protection.Methods: Patients were eligible for enrollment if they required aspirin 100 mg/day. Aspirin- naïve patients without gastroduodenal ulcer and Helicobacter pylori infection were randomized to receive Teprenone 150 mg/day or placebo for 12 weeks. Primary outcome was assessed by the incidence rate of gastroduodenal ulcer. Secondary outcomes were assessed by the incidence rate of gastric mucosal injury, the improvement in modified Lanza score (MLS), gastrointestinal symptom rating scale (GSRS) and the change of gastric immunohistochemical expression for COX-1.Results: Total of 130 patients were randomized, 64 in Teprenone group and 66 in placebo group. There was no incidence of ulcer after 12 weeks in both groups. Incidence of gastric mucosal injury was higher in placebo group than in Teprenone group (40.0 vs. 13.38%, p = .039). Mean change of MLS was higher in placebo group than in Teprenone group (0.767 ± 0.467 vs. 0.271 ± 0.158, p = .003). Scores of mucosal edema, hyperemia and hemorrhage and the change of GSRS were not different between the two groups. Change of COX-1 immunoreactive score was higher in placebo group than in Teprenone group (2.433 ± 1.476 vs. 1.233 ± 0.955, p = .001). There were no treatment-related adverse events.Conclusions: Teprenone is effective in preventing gastric mucosal injury in patients taking LDA. Preventive effects of Teprenone on LDA-related gastroduodenal ulcers require further investigation.
A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy of Teprenone in Patients with Alzheimer's Disease
J Alzheimers Dis 2019;71(4):1187-1199.PMID:31498121DOI:10.3233/JAD-190305.
Background: Teprenone (Geranylgeranylacetone), an anti-ulcer agent, has been reported to inhibit amyloid-β increase, senile plaque formation, and neuronal degeneration, and improve memory in mouse models of Alzheimer's disease (AD). Objective: We conducted a randomized, double-blind, placebo-controlled study to ascertain teprenone's therapeutic ability for AD. Methods: Patients with mild to moderate AD, with a Mini-Mental State Examination (MMSE) score of 13 to 26, were randomly allocated into two groups depending on the administered drug: donepezil + placebo (placebo group) and donepezil + teprenone (teprenone group). The primary and secondary endpoints included changes in scores of the Japanese version of the AD Assessment Scale-cognitive subscale (ADAS-J cog) and other evaluations, respectively, including MMSE scores, during a 12-month period after the first administration. Results: Forty-two and thirty-seven patients were allocated to the teprenone and placebo groups, respectively. ADAS-J cog score changes were not different between groups (placebo, 0.6±0.8; teprenone, 0.4±0.8; p = 0.861). However, MMSE scores significantly improved in the teprenone group (placebo, - 1.2±0.5; teprenone, 0.2±0.5; p = 0.044). Subgroup analysis considering the severity of medial temporal area atrophy revealed that this improvement by teprenone was significant in patients with mild (p = 0.013) but not with severe atrophy (p = 0.611). Adverse events were observed in 17.8 and 10.4% of patients in the placebo and teprenone group, respectively. Conclusion: Teprenone may be effective for AD when administered before atrophy progression in the medial temporal areas. Trial registration: UMIN ID: UMIN000016843.