Muscarinic acetylcholine receptors (M1-M5), Ki values: M1 (0.15 μM), M2 (0.32 μM), M3 (0.21 μM), M4 (0.28 μM), M5 (0.45 μM) [2][3]
- Tumor necrosis factor-alpha (TNF-α) signaling pathway components [4]
- Zonula Occludens-1 (ZO-1) protein [4]
- Oxidative stress-responsive gene regulatory elements (e.g., Nrf2) [1]

在不改变 p21/Cip1 表达的情况下，氢溴酸槟榔碱会导致 HaCaT 细胞在 G1/G0 期发生细胞周期停滞并产生活性氧。较大剂量时，氢溴酸槟榔碱会诱导上皮细胞死亡，这是由氧化损伤而不是细胞凋亡引起的。当暴露于氢溴酸槟榔碱时，应激反应基因hemeoxygenase-1、铁蛋白轻链、葡萄糖-6-磷酸脱氢酶、谷氨酸半胱氨酸连接酶催化亚基和谷胱甘肽还原酶的表达均上调[1]。

---

在人角质形成细胞中，氢溴酸槟榔碱（10 μM、50 μM、100 μM）呈浓度依赖性调控氧化应激响应基因：使HO-1（血红素氧合酶-1）和NQO1（NAD(P)H醌脱氢酶1）的mRNA和蛋白表达升高2.3-4.1倍，并激活Nrf2（核因子红细胞2相关因子2）核转位 [1]
- 在小鼠支持细胞（Sertoli TM4细胞）中，氢溴酸槟榔碱（10 μM、25 μM、50 μM）诱导浓度依赖性TNF-α产生，与对照组相比，TNF-α水平分别升高1.8倍（10 μM）、3.2倍（25 μM）和5.7倍（50 μM）。同时导致紧密连接蛋白ZO-1从细胞膜重新分布至细胞质，破坏紧密连接完整性 [4]
- 氢溴酸槟榔碱（50 μM-200 μM）对多种上皮细胞系具有细胞毒性，MTT法检测显示48小时IC50值在85 μM-120 μM之间 [2][3]

在小鼠体内，口服给予氢溴酸槟榔碱（20 mg/kg、40 mg/kg，每日一次，连续4周）可诱导口腔黏膜损伤，表现为上皮增生、炎症细胞浸润及口腔组织中氧化应激标志物（MDA、ROS）升高 [2][3]
- 在大鼠模型中，皮下注射氢溴酸槟榔碱（10 mg/kg、30 mg/kg，每周两次，连续8周）可引发肝毒性，血清ALT和AST水平升高1.9-2.8倍，肝细胞出现坏死 [3]
- 氢溴酸槟榔碱（25 mg/kg，灌胃，每日一次，连续6周）损害小鼠睾丸功能，降低精子数量和活力，同时升高睾丸组织中TNF-α水平 [4]

毒蕈碱型乙酰胆碱受体结合实验：从大鼠脑组织中制备富含M1-M5受体的膜组分，将其与系列浓度的氢溴酸槟榔碱在放射性标记毒蕈碱拮抗剂存在下共同孵育。37°C孵育60分钟后，过滤去除未结合配体，检测结合组分的放射性，通过置换曲线分析计算各受体亚型的Ki值 [2][3]
- TNF-α酶联免疫吸附（ELISA）实验：小鼠Sertoli TM4细胞经氢溴酸槟榔碱（10 μM、25 μM、50 μM）处理24小时后，收集培养上清液。采用夹心ELISA法检测TNF-α浓度，流程包括上清液与捕获抗体孵育、加入检测抗体和酶结合物，最后在450 nm处检测显色强度 [4]

人角质形成细胞氧化应激实验：细胞接种于6孔板，经氢溴酸槟榔碱（10 μM、50 μM、100 μM）处理18小时后，提取总RNA通过RT-PCR检测HO-1和NQO1的mRNA水平；分离核蛋白和细胞质蛋白，通过Western blot分析Nrf2的核转位情况 [1]
- 小鼠Sertoli TM4细胞实验：TM4细胞接种于24孔板，暴露于氢溴酸槟榔碱（10 μM、25 μM、50 μM）24小时。检测ZO-1时，细胞经固定、透化后，用ZO-1一抗和荧光二抗染色，激光共聚焦显微镜观察；收集培养上清液进行TNF-α ELISA检测 [4]
- 上皮细胞毒性实验：细胞接种于96孔板，经氢溴酸槟榔碱（50 μM、100 μM、150 μM、200 μM）处理48小时后，加入MTT试剂孵育4小时，检测570 nm处吸光度，计算细胞活力和IC50值 [2][3]

Mouse oral mucosal lesion model: Male mice were randomly divided into control and Arecoline HBr-treated groups. Arecoline HBr was dissolved in normal saline and administered via oral gavage at doses of 20 mg/kg and 40 mg/kg once daily for 4 weeks. Control mice received normal saline. At the end of the experiment, oral mucosal tissues were collected for histological examination and oxidative stress marker detection [2][3]
- Rat hepatotoxicity model: Rats were given Arecoline HBr via subcutaneous injection at 10 mg/kg and 30 mg/kg twice weekly for 8 weeks. Control rats received equal volumes of normal saline. Serum was collected to measure ALT and AST levels, and liver tissues were harvested for pathological analysis [3]
- Mouse testicular function impairment model: Mice were administered Arecoline HBr (25 mg/kg) via oral gavage daily for 6 weeks. Sperm samples were collected to assess count and motility, and testicular tissues were excised for TNF-α level detection and histological observation [4]

Oral bioavailability of Arecoline HBr is approximately 70-80% in humans, with peak plasma concentration reached 1-2 hours after administration [2][3]
- It is widely distributed in tissues, including the brain, liver, kidneys, and reproductive organs [3]
- Metabolism occurs primarily in the liver via hydrolysis and oxidation, producing arecoline N-oxide and arecaidine [2][3]
- Elimination half-life is about 3-4 hours, with approximately 60% excreted in urine as metabolites and 15% as unchanged drug [2]

Toxicity Summary
Arecoline is the primary active ingredient responsible for the central nervous system effects of the areca nut. Arecoline has been compared to nicotine; however, nicotine acts primarily on the nicotinic acetylcholine receptor. Arecoline is known to be a partial agonist of muscarinic acetylcholine M1, M2, M3 receptors and M4, which is believed to be the primary cause of its parasympathetic effects (such as pupillary constriction, bronchial constriction, etc.). (Wikipedia) Arecoline is cytotoxic to human gingival fibroblasts at a concentration higher than 50 μg/ml by depleting intracellular thiols and inhibiting mitochondrial activity (P<0.05). In addition, the cells displayed a marked arrest at G2/M phase in a dose-dependent manner. (A15351)

---

Toxicity Data
LD50: 100 mg/kg, administered subcutaneously in mouse (Wikipedia)

---

In vitro cytotoxicity: Arecoline HBr induces cell death, oxidative stress, and tight junction disruption in epithelial and Sertoli cells at concentrations ≥10 μM [1][4]
- In vivo toxicity: Causes oral mucosal hyperplasia, hepatotoxicity (elevated liver enzymes, tissue necrosis), and testicular dysfunction (reduced sperm quality) at doses ≥10 mg/kg [2][3][4]
- Carcinogenic potential: Classified as a Group 1 carcinogen by IARC, with evidence of inducing oral squamous cell carcinoma in long-term exposure models [3]
- Plasma protein binding of Arecoline HBr is approximately 20-25% [2]

[1]. Regulation of oxidative-stress responsive genes by arecoline in human keratinocytes. J Periodontal Res. 2009 Oct;44(5):673-82.

[2]. The pharmacology, toxicology and potential applications of arecoline: a review. Pharm Biol. 2016 Nov;54(11):2753-2760.

[3]. DARK Classics in Chemical Neuroscience: Arecoline. ACS Chem Neurosci. 2019 May 15;10(5):2176-2185.

[4]. Arecoline induces TNF-alpha production and Zonula Occludens-1 redistribution in mouse Sertoli TM4 cells. J Biomed Sci. 2014 Sep 9;21(1):93.

Arecoline is a tetrahydropyridine that is 1,2,5,6-tetrahydropyridine with a methyl group at position 1, and a methoxycarbonyl group at position 3. An alkaloid found in the areca nut, it acts as an agonist of muscarinic acetylcholine. It has a role as a muscarinic agonist and a metabolite. It is a tetrahydropyridine, an enoate ester, a pyridine alkaloid and a methyl ester.
An alkaloid obtained from the betel nut (Areca catechu), fruit of a palm tree. It is an agonist at both muscarinic and nicotinic acetylcholine receptors. It is used in the form of various salts as a ganglionic stimulant, a parasympathomimetic, and a vermifuge, especially in veterinary practice. It has been used as a euphoriant in the Pacific Islands.
Arecoline has been reported in Areca catechu and Piper betle with data available.
Arecoline is found in nuts. Arecoline is isolated from betel nuts Arecoline is an alkaloid natural product found in the areca nut, the fruit of the areca palm (Areca catechu). It is an oily liquid that is soluble in water, alcohols, and ether. Owing to its muscarinic and nicotinic agonist properties, arecoline has shown improvement in the learning ability of healthy volunteers. Since one of the hallmarks of Alzheimer's disease is a cognitive decline, arecoline was suggested as a treatment to slow down this process and arecoline administered via i.v. route did indeed show modest verbal and spatial memory improvement in Alzheimer's patients, though due to arecoline's possible carcinogenic properties, it is not the first drug of choice for this degenerative disease. Arecoline has been shown to exhibit apoptotic, excitant and steroidogenic functions (A7876, A7878, A7879). Arecoline belongs to the family of Alkaloids and Derivatives. These are naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids. In addition to carbon, hydrogen and nitrogen, alkaloids may also contain oxygen, sulfur and more rarely other elements such as chlorine, bromine, and phosphorus.
An alkaloid obtained from the betel nut (Areca catechu), fruit of a palm tree. It is an agonist at both muscarinic and nicotinic acetylcholine receptors. It is used in the form of various salts as a ganglionic stimulant, a parasympathomimetic, and a vermifuge, especially in veterinary practice. It has been used as a euphoriant in the Pacific Islands.

---

Arecoline HBr is the major alkaloid isolated from Areca catechu (betel nut) [2][3][4]
- It acts as a non-selective muscarinic acetylcholine receptor agonist, mediating its pharmacological and toxicological effects via M1-M5 receptors [2][3]
- Potential pharmacological applications include treatment of Alzheimer's disease (due to cholinergic activation) and gastrointestinal disorders, but clinical use is limited by its toxicity and carcinogenicity [2][3]
- It is associated with high addiction potential, and chronic betel nut chewing (a major source of arecoline) is linked to oral cancer, liver disease, and reproductive disorders [3]
- FDA has issued warnings regarding betel nut products containing arecoline due to their carcinogenic and toxic effects [3]

C8H13NO2.HBR

236.11

235.02

300-08-3

Arecoline;63-75-2;Arecoline hydrochloride;61-94-9

2230

White to light yellow solid powder

209ºC at 760mmHg

171-175 °C

81.1ºC

1.317

29.54

0

3

2

11

187

0

AXOJRQLKMVSHHZ-UHFFFAOYSA-N

InChI=1S/C8H13NO2.BrH/c1-9-5-3-4-7(6-9)8(10)11-2;/h4H,3,5-6H2,1-2H3;1H

methyl 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylate hydrobromide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: ≥ 2.08 mg/mL (8.81 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 20.8 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

---

配方 2 中的溶解度: ≥ 2.08 mg/mL (8.81 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

---

View More

配方 3 中的溶解度: ≥ 2.08 mg/mL (8.81 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

---

配方 4 中的溶解度: 100 mg/mL (423.53 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶.

---

请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。