ROS; DNA topoisomerase; c-Jun

体外活性：发现小檗碱能够在脂肪细胞、肝细胞和肌管中缺乏胰岛素的情况下增加葡萄糖消耗和/或葡萄糖摄取。小檗碱增强糖代谢可能是由于糖酵解刺激，而这与抑制线粒体氧化有关。小檗碱也可能充当α-葡萄糖苷酶抑制剂。此外，小檗碱抑制双糖酶的活性并减少穿过肠上皮的葡萄糖转运。

在饮食诱导的肥胖大鼠中，小檗碱被发现可以降低胰岛素抵抗，类似于二甲双胍。小檗碱和二甲双胍改善胰岛素抵抗模型中的胰岛素抵抗和肝糖原水平，但对胰岛素、血糖、血脂水平和肌肉甘油三酯库没有影响

蛋白质印迹和OPTDI分析用于检测细胞周期蛋白[1]
收获LoVo细胞，在100°C的裂解缓冲液[50 mmol/L TrisCl（pH 6.8）、100 mmol/L DTT、2%SDS、0.1%溴酚蓝、10%甘油]中裂解10分钟，并在−20°C下储存。蛋白质浓度通过BCA测定法测定。将等量的蛋白质装载到SDS聚丙烯酰胺凝胶上，并将蛋白质电泳转移到PVDF膜上。使用细胞周期蛋白B1、cdc2和cdc25c的特异性一级抗体（1:200稀释）分析免疫印迹，并与辣根过氧化物酶偶联的二级抗体（1:1000稀释）孵育，并使用增强化学发光检测试剂盒观察蛋白质。通过自动图像分析系统对光密度积分（OPTDI）进行分析。将细胞周期蛋白B1、cdc2和cdc25c的表达标准化为内部对照（GAPDH）。结果以处理与对照相比的百分比表示

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DNA和蛋白质合成的测量[1]
通过3H-胸苷和L-[4,5-3H]-亮氨酸（分别为60 Ci/mg分子和0.5μCi/孔）的细胞掺入来评估DNA和蛋白质合成。将分离的细胞（每孔1×105个细胞）与含有一系列浓度的黄连素的培养基一起孵育。在24小时黄连素暴露前4小时，将放射性前体加入培养物中。在培养期结束时，将培养基移到一片滤膜上；用蒸馏水洗涤细胞三次。用液体闪烁光谱法测定3H-胸苷和L-[4,5-3H]-亮氨酸的掺入量。

细胞增殖测定[1]
细胞类型：四种结直肠癌细胞系 LoVo、HCT116、SW480 和 HT-29
测试浓度： 1.25、2.5 、5、10、20、40、80 和 160 μM
孵育时间：72 小时
实验结果：抑制四种细胞的增殖细胞系。 IC50 范围为 40.8±4.1 μM (LoVo) 至 98.6±2.9 μM (HCT116)。

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细胞增殖测定[1]
细胞类型：结直肠癌细胞系 LoVo
测试浓度： 1.25、2.5、5、10 、20、40、80 和 160 μM
孵育持续时间：24、48、72 小时
实验结果：诱导时间和细胞生长的剂量依赖性抑制。 72 小时时，160.0 μM 在 LoVo 细胞中诱导 71.1±1.9% 的生长抑制。

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细胞周期分析[1]
细胞类型： LoVo 细胞
测试浓度：0、10、20、40 或 80 μM
孵育持续时间：24 小时
实验结果：暴露于 40.0 μM 诱导 G2/M 期细胞周期停滞，细胞周期增加G2/M 期群体和 G1 期群体逐渐减少。

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蛋白质印迹分析[1]
细胞类型： LoVo 细胞
测试浓度： 10、20、40 或 80 μM
孵化持续时间： 24 小时
实验结果： 黄连素对细胞周期蛋白B1、cdc2和cdc25c的表达有抑制作用。

In vivo anti-tumor effect of berberine in human colorectal adenocarcinoma (LoVo)[1]
The in vivo antitumor efficacy of berberine was examined using human colorectal adenocarcinoma LoVo xenografts in a nude mouse model; 1 × 107 cells were implanted subcutaneous injection (s.c.) in the flanks of 5-week-old BALB/c nu/nu mice. After the tumors were grown up to about 1,000–1,500 mm3, the mice were sacrificed and the tumors were divided into equal fragments. Fragments (6–8 mm3) of colorectal adenocarcinoma were implanted s.c. in the flanks of 5-week-old BALB/c nu/nu mice. Tumors were allowed to develop for 2 weeks. Once tumors were established, the mice were divided randomly into five groups. The berberine-treated groups (ten mice each group) received 10, 30, or 50 mg kg−1 day−1 berberine by gastrointestinal gavage for 10 consecutive days. The 5-FU-treated group (10 mice) was given 30 mg kg−1 day−1 by intraperitoneal injection for 10 consecutive days. The control group (11 mice) was given sterile water. Measurements of body weights and tumor volumes were recorded every 1–3 days until the experimental endpoint, at which the tumors were debilitating to the mice. The long axis (L) and the short axis (S) were measured, and the tumor volume (V) was calculated using the following equation: V = S × S × L/2. Once the final measurement was taken, the mice were sacrificed by cervical dislocation. The inhibitory rates were determined by comparing the volume of the control group and the treatment group: (1 − V treatment/Vcontrol).

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Effect of the combination of berberine and 5-FU on the growth of human colorectal adenocarcinoma (HT-29) xenografts in nude mice[1]
The in vivo antitumor efficacy of the combination of berberine and 5-FU was examined using human colorectal adenocarcinoma HT-29 xenografts in a nude mouse model; 1 × 107 cells were implanted subcutaneous injection (s.c.) in the flanks of 5-week-old BALB/c nu/nu mice. After the tumors were grown up to about 1,000–1,500 mm3, the mice were sacrificed and the tumors were divided into equal fragments. Fragments (6–8 mm3) of colorectal adenocarcinoma were implanted s.c. in the flanks of 5-week-old BALB/c nu/nu mice. Tumors were allowed to develop for 3 weeks. Once tumors were established, the mice were divided randomly into four groups. The berberine-treated group (ten mice) received 50 mg kg−1 day−1 berberine by gastrointestinal gavage for 10 consecutive days. The 5-FU-treated group (10 mice) was given 30 mg kg−1 day−1 by intraperitoneal injection for 10 consecutive days. The combination group (10 mice) was given berberine and 5-FU. The control group (10 mice) was given sterile water. Measurements of body weights and tumor volumes were recorded every 3–4 days until the experimental endpoint, at which the tumors were debilitating to the mice. The long axis (L) and the short axis (S) were measured, and the tumor volume (V) was calculated using the following equation: V = S × S × L/2. Once the final measurement was taken, the mice were sacrificed by cervical dislocation. The inhibitory rates were determined by comparing the volume of the control group and the treatment group: (1 − V treatment/V control).

Hepatotoxicity
Berberine has not been linked to serum enzyme elevations during therapy, although there have been few prospective studies in humans that have reported on its effects on laboratory test results in any detail. In published trials, berberine has appeared to be well tolerated with only minor and few adverse effects which have been similar in frequency among persons receiving placebo. Despite wide scale use as an herbal supplement, berberine has not been linked to published instances of clinically apparent liver injury. The frequency of hypersensitivity reactions to berberine is also not known.
Likelihood score: E (unlikely cause of clinically apparent liver injury).
Other Names: Goldenseal, Oregon grape, Tree turmeric.
Drug Class: Herbal and Dietary Supplements

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Effects During Pregnancy and Lactation
◈ What is berberine?
Berberine is an ingredient found in many plant species, including goldthread, huang lian, Oregon grape, and barberry. It has been used to treat many conditions, such as diarrhea, diabetes, and high cholesterol. It has also been used for weight loss.Berberine is available as a supplement sold over the counter. In general, it is suggested to speak with your healthcare provider before taking any supplements. Many supplements are not recommended for use during pregnancy unless your healthcare provider has prescribed them to treat a medical condition. This is because they are not well-regulated or studied for use in pregnancy. For more detail on supplements, please see the fact sheet at https://mothertobaby.org/fact-sheets/herbal-products-pregnancy/.
◈ I take berberine. Can it make it harder for me to get pregnant?
It is not known if berberine can make it harder to get pregnant. There is some information to suggest berberine can increase fertility and pregnancy rates in females with polycystic ovary syndrome (PCOS).
◈ Does taking berberine increase the chance of miscarriage?
Miscarriage is common and can occur in any pregnancy for many different reasons. It is not known if berberine increases the chance for miscarriage. One study suggests that berberine may cause uterine contractions and miscarriage. However, information is very limited. As there can be many causes of miscarriage, it is hard to know if an exposure, the medical condition, or other factors are the cause of a miscarriage.
◈ Does taking berberine increase the chance of birth defects?
Every pregnancy starts out with a 3-5% chance of having a birth defect. This is called the background risk. One report looking at 218 pregnancies exposed to huang lian (which contains berberine) did not show an increased chance of birth defects above the background chance.
◈ Does taking berberine in pregnancy increase the chance of other pregnancy-related problems?
Studies have not been done to see if berberine increases the chance for pregnancy-related problems such as preterm delivery (birth before week 37) or low birth weight (weighing less than 5 pounds, 8 ounces [2500 grams] at birth).Berberine can change how bilirubin (a yellowish pigment that is made during the breakdown of red blood cells) binds to serum albumin (the main protein in blood plasma). This can cause a buildup of bilirubin in the brain, which can lead to brain damage and other issues. While information on this is very limited, one author suggests avoiding herbs and products that contain berberine during pregnancy.
◈ Does taking berberine in pregnancy affect future behavior or learning for the child?
Studies have not been done to see if berberine can cause behavior or learning issues for the child.
◈ Breastfeeding while taking berberine:
Berberine passes into breastmilk, but how much berberine gets into breastmilk is not known.. It is possible that berberine in breastmilk could cause a buildup of bilirubin in the infant brain, which can result in brain damage and other issues. This makes berberine exposure via breastmilk a concern, especially in newborns. Also, because berberine is a supplement, it is not recommended for use during breastfeeding unless your healthcare provider has prescribed it to treat a medical condition. Be sure to talk to your healthcare provider about all your breastfeeding questions.
◈ If a male takes berberine, could it affect fertility (ability to get partner pregnant) or increase the chance of birth defects?
Studies have not been done in humans to see if berberine could affect male fertility or increase the chance of birth defects above the background risk. In general, exposures that fathers or sperm donors have are unlikely to increase risks to a pregnancy. For more information, please see the MotherToBaby fact sheet Paternal Exposures at https://mothertobaby.org/fact-sheets/paternal-exposures-pregnancy/.

[1]. J Nat Med . 2014 Jan;68(1):53-62. doi: 10.1007/s11418-013-0766-z. Epub 2013 Apr 21.

[2]. Int J Obes (Lond) . 2013 May;37(5):712-7.

[3]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 1997 Mar;17(3):162-4.

Berberine is an organic heteropentacyclic compound, an alkaloid antibiotic, a botanical anti-fungal agent and a berberine alkaloid. It has a role as an antilipemic drug, a hypoglycemic agent, an antioxidant, a potassium channel blocker, an antineoplastic agent, an EC 1.1.1.21 (aldehyde reductase) inhibitor, an EC 1.1.1.141 [15-hydroxyprostaglandin dehydrogenase (NAD(+))] inhibitor, an EC 1.13.11.52 (indoleamine 2,3-dioxygenase) inhibitor, an EC 1.21.3.3 (reticuline oxidase) inhibitor, an EC 2.1.1.116 [3'-hydroxy-N-methyl-(S)-coclaurine 4'-O-methyltransferase] inhibitor, an EC 3.1.1.4 (phospholipase A2) inhibitor, an EC 3.4.21.26 (prolyl oligopeptidase) inhibitor, an EC 3.4.14.5 (dipeptidyl-peptidase IV) inhibitor, an EC 3.1.3.48 (protein-tyrosine-phosphatase) inhibitor, an EC 3.1.1.7 (acetylcholinesterase) inhibitor, an EC 3.1.1.8 (cholinesterase) inhibitor, an EC 2.7.11.10 (IkappaB kinase) inhibitor, an EC 2.1.1.122 [(S)-tetrahydroprotoberberine N-methyltransferase] inhibitor, a geroprotector and a metabolite.
An alkaloid from Hydrastis canadensis L., Berberidaceae. It is also found in many other plants. It is relatively toxic parenterally, but has been used orally for various parasitic and fungal infections and as antidiarrheal.
Berberine is a quaternary ammonia compound found in many botanical products, including goldenseal, barberry and Oregon grape, which is used for its purported antioxidant and antimicrobial properties for a host of conditions, including obesity, diabetes, hyperlipidemia, heart failure, H. pylori infection and colonic adenoma prevention. Berberine has not been linked to serum aminotransferase elevations during therapy nor to instances of clinically apparent liver injury.
Berberine has been reported in Stephania tetrandra, Coptis omeiensis, and other organisms with data available.
Berberine is a quaternary ammonium salt of an isoquinoline alkaloid and active component of various Chinese herbs, with potential antineoplastic, radiosensitizing, anti-inflammatory, anti-lipidemic and antidiabetic activities. Although the mechanisms of action through which berberine exerts its effects are not yet fully elucidated, upon administration this agent appears to suppress the activation of various proteins and/or modulate the expression of a variety of genes involved in tumorigenesis and inflammation, including, but not limited to transcription factor nuclear factor-kappa B (NF-kB), myeloid cell leukemia 1 (Mcl-1), B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xl), cyclooxygenase (COX)-2, tumor necrosis factor (TNF), interleukin (IL)-6, IL-12, inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), E-selectin, monocyte chemoattractant protein-1 (MCP-1), C-X-C motif chemokine 2 (CXCL2), cyclin D1, activator protein (AP-1), hypoxia-inducible factor 1 (HIF-1), signal transducer and activator of transcription 3 (STAT3), peroxisome proliferator-activated receptor (PPAR), arylamine N-acetyltransferase (NAT), and DNA topoisomerase I and II. The modulation of gene expression may induce cell cycle arrest and apoptosis, and inhibit cancer cell proliferation. In addition, berberine modulates lipid and glucose metabolism.
An alkaloid from Hydrastis canadensis L., Berberidaceae. It is also found in many other plants. It is relatively toxic parenterally, but has been used orally for various parasitic and fungal infections and as antidiarrheal.
See also: Goldenseal (part of); Berberis aristata stem (part of).

C20H18CLNO4

371.81

372.099

C, 64.61; H, 4.88; Cl, 9.53; N, 3.77; O, 17.21

633-65-8

1868138-66-2 (ursodeoxycholate); 2086-83-1; 2086-83-1 (cation); 633-66-9 (hydrosulfate); 316-41-6 (sulfate); 633-65-8 (chloride); 117-74-8 (hydroxide)

2353

Light yellow to yellow solid powder

1.654g/cm3

200ºC

0.1

40.8

0

4

2

25

488

0

[Cl-].O1C([H])([H])OC2=C1C([H])=C1C(=C2[H])C2C([H])=C3C([H])=C([H])C(=C(C3=C([H])[N+]=2C([H])([H])C1([H])[H])OC([H])([H])[H])OC([H])([H])[H]

VKJGBAJNNALVAV-UHFFFAOYSA-M

InChI=1S/C20H18NO4.ClH/c1-22-17-4-3-12-7-16-14-9-19-18(24-11-25-19)8-13(14)5-6-21(16)10-15(12)20(17)23-2;/h3-4,7-10H,5-6,11H2,1-2H3;1H/q+1;/p-1

16,17-dimethoxy-5,7-dioxa-13-azoniapentacyclo[11.8.0.02,10.04,8.015,20]henicosa-1(13),2,4(8),9,14,16,18,20-octaene;chloride

2934.99.03.00

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: ≥ 1.25 mg/mL (3.36 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 12.5 mg/mL澄清的DMSO储备液加入到400 μL PEG300中，混匀；再向上述溶液中加入50 μL Tween-80，混匀；然后加入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。

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配方 2 中的溶解度: ≥ 1.25 mg/mL (3.36 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 12.5 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。

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配方 3 中的溶解度: 10 mg/mL (26.90 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 悬浊液; 超声助溶。

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配方 4 中的溶解度: 11 mg/mL (29.59 mM) in 0.5% CMC-Na/saline water (这些助溶剂从左到右依次添加，逐一添加), 悬浊液; 超声助溶。
*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。

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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。