Berberis Vulgaris and Berberine: An Update Review

Berberine is an isoquinoline alkaloid present in several plants, including Coptis sp. and Berberis sp. Berberine is a customary component in Chinese medicine, and is characterized by a diversity of pharmacological effects. An extensive search in electronic databases (PubMed, Scopus, Ovid, Wiley, ProQuest, ISI, and Science Direct) were used to identify the pharmacological and clinical studies on Berberis vulgaris and berberine, during 2008 to 2015, using ‘berberine’ and ‘Berberis vulgaris’ as search words. We found more than 1200 new article studying the properties and clinical uses of berberine and B. vulgaris, for treating tumor, diabetes, cardiovascular disease, hyperlipidemia, inflammation, bacterial and viral infections, cerebral ischemia trauma, mental disease, Alzheimer disease, osteoporosis, and so on. In this article, we have updated the pharmacological effects of B. vulgaris and its active constituent, berberine. Copyright © 2016 John Wiley & Sons, Ltd.     

Berberine and barberry (Berberis vulgaris): A clinical review

Barberry (Berberis vulgaris L.) has different medicinal applications in folk medicine of Iran. Berberine, an alkaloid constituent of this plant, is present in the roots, rhizomes, stem, and bark of B. vulgaris and many other plants. There have been many clinical trials conducted that suggested a wide range of therapeutic applications. Here, we investigated the clinical uses of berberine and B. vulgaris in the treatment of different diseases in humans. An extensive search in electronic databases (PubMed, Scopus, Embase, Web of Sciences and Science Direct) was used to identify the clinical trials on B. vulgaris and berberine. Lipid‐lowering and insulin‐resistance improving actions are the most studied properties of berberine in numerous randomized clinical trials. There are also clinical trials regarding cardiovascular, anticancer, gastrointestinal, CNS, endocrine, and so on. Berberine has very low toxicity in usual doses and reveals clinical benefits without major side effects. Only mild gastrointestinal reactions may occur in some patients. The purpose of this review is to provide a summary concerning the clinical trials conducted on berberine to improve the clinical application of this nutraceutical in different diseases. In this review article, we used 77 clinical studies on human subjects.     

Antioxidant and cytoprotective compounds from Berberis vulgaris (barberry)

Activity-guided fractionation of an EtOAc-soluble partition of the MeOH extract from the root bark of Berberis vulgaris L. (barberry), using a hydroxyl radical-scavenging assay, led to the isolation and identification of three phenolic compounds of a previously known structure, N-(p-trans-coumaroyl)tyramine, cannabisin G and (+/-)-lyoniresinol. Of these, cannabisin G and (+/-)-lyoniresinol exhibited antioxidant activity in this bioassay. Furthermore, it was found that cannabisin G showed cytoprotective activity in cultured MCF-7 cells modulated by hydrogen peroxide.     

Comparison of the antidiabetic activity of Berberis lyceum root extract and berberine in alloxan-induced diabetic rats

Berberine has been shown to have hypoglycaemic activity in several in vitro and in vivo models, although the mechanism of action is not fully known. Berberis lyceum Royle root produces high concentrations of berberine, and in traditional medicine, the whole extract of this plant is used widely to treat diabetes. The antidiabetic activity of the ethanol root extract of Berberis lyceum was compared with pure berberine in normal and alloxan-diabetic rats using similar doses of each. The concentration of berberine in the extract was determined to be 80% dry weight with only trace amounts of other alkaloids present. The purpose of the study was to investigate the effects of berberine and a whole extract of Berberis lyceum on blood glucose and other parameters associated with diabetes, to compare the effects of the crude extract with those of pure berberine and thus validate its use as a therapeutic agent, and finally to identify any contribution of the other components of the extract to these effects. Oral administration of 50 mg/kg of Berberis extract and berberine to normal and experimental diabetic rats produced a significant (p < 0.05) reduction in blood glucose levels from days 3-7 days of treatment. Significant effects were also observed on the glucose tolerance, glycosylated haemoglobin, serum lipid profiles and body weight of experimental animals. Berberis extract and berberine demonstrated similar effects on all parameters measured, and although the extract was comparable in efficacy to berberine, it did not produce any effects additional to those shown by pure berberine. The results support the use of the extract in traditional medicine, and demonstrate that apart from being a highly cost-effective means of treating with berberine, the total extract does not appear to confer any additional benefits or disadvantages compared with the pure compound.     

The antihypertensive and vasodilator effects of aqueous extract from Berberis vulgaris fruit on hypertensive rats

The aqueous extract from Berberis vulgaris fruit (B.V.) was tested to evaluate its antihypertensive effects on DOCA-induced hypertension in the rats. Hypertension was induced in male Sprague-Dawley rats (200-250 g) by DOCA-salt injection (20 mg/kg, twice weekly, for 5 weeks, s.c.) plus NaCl (1%) which was added to the animals' drinking water. Then 5 weeks later, the rats were anaesthetized with thiopental (30 mg/kg, i.p.) and the arterial blood pressure was measured. The mean arterial blood pressure and heart rate were 231 +/- 6.4 (mmHg) and 506 +/- 12 (beats/min), respectively. Administration of B.V. extracts significantly reduced the rat arterial blood pressure. In in vitro studies, rings of descending aorta were cut and mounted for isometric tension recording in an organ chamber containing Krebs solution. Mesenteric beds were also removed and perfused with Krebs solution. After 1 h of stabilization, preparations (aortic rings or mesenteric beds) were precontracted with phenylephrine (10(-5) M), then different concentrations of B.V. (0.4, 2 and 4 mg/mL) were added which caused a relaxation in these vessels. To investigate the mechanism of action of the extract, the tissues were incubated with either L-NAME (10(-5) M) or indomethacin (10(-5) M) for 20 min. In the aortic rings L-NAME pretreatment could only reduce the vasodilatory effects of a low concentration of B.V. (0.4 mg/mL), but indomethacin was without effect. In isolated perfused mesenteric beds preincubation with either L-NAME or indomethacin did not modify the vasodilator effects of the aqueous extract from B.V. fruit. The present results suggest that the antihypertensive and vasodilatory effects of B.V. fruit extract are mainly endothelial-independent and it may be used to treat hypertension, a status with endothelial dysfunction.     

Berberis vulgaris root bark extract prevents hyperoxaluria induced urolithiasis in rats

Berberis vulgaris is a widely used plant for the treatment of urolithiasis. To evaluate its antiurolithic potential, the crude aqueous‐methanol extract of Berberis vulgaris root bark (Bv.Cr) was tested in an animal model of urolithiasis, developed in male Wistar rats by adding 0.75% ethylene glycol in drinking water. Bv.Cr (50 mg/kg) inhibited CaOx crystal deposition in renal tubules and protected against associated changes including polyuria, weight loss, impaired renal function and the development of oxidative stress in kidneys. Activity‐guided fractionation revealed the concentration of antiurolithic constituent(s) mainly in the aqueous fraction. These data, indicating the presence of antiurolithic activity in Berberis vulgaris root bark, rationalize its medicinal use for the treatment of urolithiasis. Copyright © 2010 John Wiley & Sons, Ltd.     

6省13个产地细叶小檗中盐酸小檗碱测定与相关性分析

目的 测定6省13个产地细叶小檗Berberis poiretii Schneid.中盐酸小檗碱含量并分析其相关性.方法 细叶小檗甲醇提取物采用YMC-Pack Polymer C18色谱柱(4.6 mmx250 mm,5 μm);流动相乙腈-0.02 mol/L磷酸二氢钾溶液;体积流量1.0 mL/min;检测波长2...     

Effect of berberine and Berberis aetnensis C. Presl. alkaloid extract on glutamate-evoked tissue transglutaminase up-regulation in astroglial cell cultures

Berberis aetnensis C. Presl. is a bushy-spiny shrub common on Mount Etna (Sicily, Italy), containing various alkaloids with several pharmacological properties. This study assessed the effect of berberine and of the alkaloid extract of B. aetnensis roots on the glutamate-evoked tissue transglutaminase (TG2) up-regulation in rat astrocyte primary cultures, used as an in vitro model of excitotoxicity. The findings show that the alkaloid extract of B. aetnensis roots consists mainly of berberine. Furthermore, berberine and the alkaloid extract of B. aetnensis roots were able to restore the oxidative status modified by glutamate and the levels of TG2 to control values. It was found that berberine or the alkaloid extract of B. aetnensis roots are able to ameliorate the excessive production of glutamate, protein misfolding and aggregation, mitochondrial fragmentation, and neurodegeneration. Thus, it is suggested that berberine and the alkaloid extract of B. aetnensis roots, may represent a natural therapeutic strategy in the neuropathological conditions associated with excitotoxicity.     

夏枯草提取物的药理作用和研究进展

夏枯草为临床常用中药,具有清火明目、软坚散结的功效。夏枯草常用提取物为水提取物、醇提取物、乙酸乙酯提取物,3种提取物具有抗肿瘤、抗菌消炎、免疫调节、清除自由基及抗氧化、抑制病毒生长等多种药理作用。现综合近年来国内外文献报道,对夏枯草提取物的药理作用进行综述,为其研究和临床应用提供参考。     

HPLC测定复方黄连素注射液中黄连素和甲氧苄氨嘧啶含量

 用高效液相色谱法测定复方黄连素注射液中硫酸氢黄连素和甲氧苄氨嘧定的含量。方法简便，结果准确．采用ＯＤＳ－Ｃ＿（１８）柱，流动相为甲醇－１ｍｏｌ／Ｌ醋酸铵溶液（ｐＨ５．５，８０：２０），流速１ｍｌ／ｍｉｎ，以非那西丁为内标，检测波长２６５ｎｍ。结果：硫酸氢黄连素线性范围０．１０～０．３０ｍｇ／ｍｌ，回收率为１０１．６６％，ＲＳＤ＝１．６％（ｎ＝６）；甲氧苄氨嘧啶线性范围０．２３～１．２５ｍｇ／ｍｌ，回收率为１０１．４２％，ＲＳＤ＝１．１９％（ｎ＝６）。     

主动载药法制备盐酸小檗碱脂质体

 目的　采用主动载药法制备盐酸小檗碱脂质体,并考察其包封率的影响因素。方法　以阳离子交换树脂法分离脂质体,于347nm处测定吸光度,计算包封率;考察加药顺序、孵化时间、孵化温度、外水相pH值及粒径对包封率的影响。 结果　被动载药法得到的包封率仅有13.3%,主动载药法的包封率最高可达84.6%。主动载药法中,加药顺序不同,得到的包封率亦有不同;包封率随着孵化温度的升高和孵化时间的增加有提高的趋势;外水相最佳pH值为6.8;粒径小,包封率高。 结论　主动载药法适于制备盐酸小檗碱脂质体。     

Preventive and curative effects of Berberis aristata Fruit extract on paracetamol- and CCl4-induced hepatotoxicity

The effect of an aqueous-methanol extract of Berberis aristata fruits (Berberidaceae) was investigated against paracetamol- and CCl₄-induced hepatic damage. Paracetamol produced 100% mortality at a dose of 1 g/kg in mice while pre-treatment of animals with crude extract (500 mg/kg) reduced the death rate to 10%. Pre-treatment of rats with fruit extract (500 mg/kg, orally twice daily for 2 days) prevented (p<0.05) the paracetamol (640 mg/kg) as well as CCl₄ (1.5 mL/kg)-induced rise in serum transaminases (GOT and GPT). Post-treatment with three successive doses of extract (500 mg/kg, 6h) restricted the hepatic damage induced by acetaminophen (p<0.01) but CCl₄-induced hepatotoxicity was not altered (p>0.05). Plant extract (500 mg/kg) caused significant prolongation (p<0.01) in pentobarbital (75 mg/kg)-induced sleep as well as increased strychnine-induced lethality in mice suggestive of inhibitory effect on microsomal drug metabolizing enzymes (MDME). These results indicate that the crude extract of Berberis aristata fruits exhibits hepatoprotective action partly through MDME inhibitory action.     

黄芩苷、小檗碱和葛根素体外胰岛素抵抗细胞差异化降糖作用研究

探讨中药成分黄芩苷、小檗碱、葛根素和甘草苷对肝胰岛素抵抗(insulin resistance,IR)细胞糖代谢的改善作用。采用胰岛素和地塞米松联合诱导建立IR-HepG2细胞模型,给药24 h测定不同剂量黄芩苷、小檗碱、葛根素和甘草苷对葡萄糖消耗量、糖原含量和细胞活性的影响。结果显示,与IR模型组相比,除甘草苷和1μmol·L-1黄芩苷组外,各给药组均显著升高葡萄糖消耗量;黄芩苷组(10,20,50μmol·L-1)、小檗碱组(5,10,20,50μmol·L-1)和葛根素组(40,80,160μmol·L-1)显著增加细胞内肝糖原含量;而甘草苷降糖作用不明显。在此基础上,重点研究黄芩苷、小檗碱和葛根素对IR-HepG2细胞葡萄糖转运蛋白(GLUTs)表达水平的影响。q PCR结果显示IR-HepG2细胞GLUT1和GLUT4基因mRNA表达比正常组低。5,20μmol·L-1小檗碱下调IR-HepG2细胞GLUT1基因mRNA水平;20,40,80μmol·L-1葛根素上调GLUT1基因mRNA水平。10,20,50μmol·L-1黄芩苷和20μmol·L-1小檗碱上调GLUT4基因mRNA水平,40,80μmol·L-1葛根素下调GLUT4基因mRNA水平。Western blot法检测结果显示,与正常组相比,IR-HepG2细胞GLUT1和GLUT4蛋白表达降低,GLUT2表达升高。10,20,50μmol·L-1黄芩苷上调GLUT2和GLUT4蛋白表达;20μmol·L-1小檗碱升高GLUT2蛋白表达,10,20μmol·L-1小檗碱增加GLUT4蛋白表达;20,40,80μmol·L-1葛根素上调GLUT1和GLUT2蛋白表达。以上成分体外差异化影响GLUT1/2/4表达,可以有效调节葡萄糖转运的瞬时响应和长期响应。降糖途径分析显示黄芩苷和葛根素与油酸诱导IR-HepG2细胞降糖作用途径环节及效应强弱存在一定程度差异,而小檗碱和甘草苷在2种不同诱因的IR-HepG2细胞中无明显差异。体外研究初步表明黄芩苷、小檗碱和葛根素具有体外差异化降糖作用,可加速糖转运增加糖原合成调节糖代谢改善肝IR。     

小檗碱对多柔比星的增效减毒作用及其机制研究进展

多柔比星是临床治疗中有效的抗肿瘤药,但其严重的心脏、肝脏毒性使其临床应用受到了极大限制。小檗碱是从黄连属植物分得的生物碱,具有多种生物活性和药理作用,对痢疾、真菌感染、糖尿病、肿瘤等都有治疗作用。研究发现小檗碱不仅可以通过诱导肿瘤细胞的凋亡来增强多柔比星的抗肿瘤活性;还可以通过改变多柔比星引起心肌病的相关指标来降低多柔比星引起的心肌细胞的损伤;另外,小檗碱对多柔比星引起的肝脏损伤也有一定的保护作用。综述了小檗碱对多柔比星的增效减毒作用及其机制的研究进展,这种发现提供了一种新颖的治疗方法,对多柔比星临床治疗的发展具有重要的意义。     

小檗碱对实验性大鼠结肠癌的防治作用与环氧化酶2关系的研究

目的:观察小檗碱对实验性结肠癌的防治作用及其与环氧酶-2表达的关系。方法:以二甲肼(1-2 dimethyl-hydrazine,DMH)40 mg.kg-1皮下注射+1%葡聚糖硫酸钠(dextran sodium sulfate,DSS)水溶液饮用诱导形成大鼠结肠癌模型。观察小檗碱(100 mg.kg-1.d-1,1周5 d)和美洛昔康(1.35 mg.kg-1.d-1,1周5天)灌服,连续16周对大鼠体重、异常隐窝灶(abrrant crypt foci,ACF)和结肠癌发生率的影响。采用四甲基谷氮蓝法(MTT)研究小檗碱和美洛昔康抑制培养的人结肠癌lovo细胞增殖的量-效和时-效关系;用RT-PCR和Western blot法检测各组细胞COX-2 mRNA和蛋白表达水平。结果:与模型组相比,小檗碱明显改善DMH+DSS诱癌过程中大鼠的恶液质状态并阻遏体重减轻,显著减少实验第10周大鼠结肠ACF数和明显降低结肠癌的发生率;其作用与美洛昔康组相似。小檗碱呈浓度和时间依赖性明显抑制lovo细胞增殖,其作用6,12,24 h的IC50均显著小于美洛昔康。小檗碱也呈浓度依赖性降低lovo细胞中COX-2 mNRA和蛋白表达。结论:小檗碱能抑制DMH和DSS联合使用诱导大鼠早期ACF的形成和结肠癌发生,其作用途径可能至少与细胞抑制COX-2表达有关。     

药代动力学和核磁共振代谢组学方法评价小檗碱和黄连对脓毒症的治疗效果

目的：脓毒症是由感染引起的系统性炎症反应，经常会导致器官功能障碍。尽管其死亡率和发病率很高，但其病理生理学仍然知之甚少。黄连及其主要活性成分小檗碱（生物碱类化合物）已经在临床上用作抗菌和抗炎药物。本研究的目的是为了研究小檗碱和黄连在大鼠体内的吸收与分布，以及对脓毒症的治疗效果。 方法：对黄连及其主要活性成分小檗碱进行药代动力学和代谢组学研究。 结果：盲肠结扎穿孔诱导的脓毒症大鼠的能量代谢和氨基酸代谢明显被扰乱，而黄连和小檗碱治疗之后能让代谢物的扰乱向正常大鼠回归。 结论：小檗碱与黄连在脓毒症的治疗上，具有相当甚至更好的药效。     

Protective effects of berberine in an experimental rat osteoarthritis model

Berberine shows anticancer, antibacterial, antiinflammatory and antioxidant effects and may be useful in many clinical applications. The effects of berberine on articular cartilage metabolism remain unknown, so this study was performed to evaluate these effects in vitro and in vivo. For the in vitro work, rat articular chondrocytes were cultured in a monolayer and matrix metalloproteinase-1 (MMP-1), -3, -13 and tissue inhibitor of metalloproteinase (TIMP-1) expression was evaluated by real-time quantitative PCR. Nitric oxide (NO) levels were determined using the Griess reaction, and glycosaminoglycan (GAG) release was measured using the dimethylmethylene blue method. For the in vivo work, berberine was administered by intraarticular injection, and the effects on MMPs and TIMP-1 were examined at the gene and protein levels. Berberine was found to inhibit the expression of MMP-1, -3 and -13, and increased the level of TIMP-1 at the mRNA level in a dose-dependent manner. In IL-1β-induced rat articular chondrocytes, berberine decreased IL-1β-induced GAG release and NO production. Meanwhile, high-dose berberine exhibited an anticatabolic effect in an IL-1β-induced rat osteoarthritis (OA) model. These findings suggest that berberine may play a protective role in the development of OA and may be useful in the treatment of OA.     

The therapeutic potential of berberine chloride against SARM1-dependent axon degeneration in acrylamide-induced neuropathy

Chronic acrylamide (ACR) intoxication causes typical pathology of axon degeneration. Moreover, sterile-α and toll/interleukin 1 receptor motif-containing protein 1 (SARM1), the central executioner of the programmed axonal destruction process under various insults, is up-regulated in ACR neuropathy. However, it remains unclear whether inhibitors targeting SARM1 are effective or not. Among all the pharmacological antagonists, berberine chloride (BBE), a natural phytochemical and the first identified non-competitive inhibitor of SARM1, attracts tremendous attention. Here, we observed the protection of 100 μM BBE against ACR-induced neurites injury (2 mM ACR, 24 hr) in vitro, and further evaluated the neuroprotective effect of BBE (100 mg/kg p.o. three times a week for 4 weeks) in ACR-intoxicated rats (40 mg/kg i.p. three times a week for 4 weeks). The expression of SARM1 was also detected. BBE intervention significantly inhibited the overexpression of SARM1, ameliorated axonal degeneration, alleviated pathological changes in the sciatic nerve and spinal cord, and improved neurobehavioral symptoms in ACR-poisoned rats. Thus, BBE exhibits a strong neuroprotective effect against the SARM1-dependent axon destruction in ACR neuropathy. Meanwhile, our study underscores the need for appropriate inhibitor selection in diverse situations that would benefit from blocking the SARM1-dependent axonal destruction pathway.     

黄连素对外源胰岛素抵抗的2型糖尿病患者血糖的短期影响

目的: 观察黄连素对存在外源胰岛素抵抗的2型糖尿病患者血糖的影响,并探索其机制。 方法: 对外源性胰岛素抵抗的患者加用黄连素,监测空腹、餐后2 h血糖,调整药物用量,35 d后测定空腹胰岛素水平,用HOMA公式计算胰岛素抵抗指数。 结果: 黄连素对全部患者黄连素均有效,14 d起效,21 d达最佳效果,35 d可减将胰岛素减少30%。 结论: 黄连素可能通过增加胰岛素的敏感性,而改善外源性胰岛素抵抗。     

小檗碱、莲心碱和甲基莲心碱对HERG通道表达的影响

目的:利用免疫荧光化学染色法和Western blot法分别定性、定量地检测不同浓度的小檗碱、莲心碱和甲基莲心碱对稳定转染在HEK-293细胞中HERG钾通道表达的影响,以及不同浓度的小檗碱对大鼠心肌组织Ikr通道蛋白表达的影响,探讨小檗碱、莲心碱和甲基莲心碱的抗心律失常机制.方法:Western blot法检测HERG-HEK细胞上HERG通道蛋白的表达;免疫荧光化学染色法并利用共聚焦显微镜定性测定不同浓度的小檗碱、莲心碱和甲基莲心碱对HERG通道蛋白表达的影响;Western blot法定量检测不同浓度的小檗碱对大鼠心肌组织Ikr通道蛋白表达的影响以及小檗碱、莲心碱和甲基莲心碱对稳定转染在HEK-293细胞中HERG钾通道蛋白表达的影响.结果:Western blot法检测稳定转染有HERG基因的HEK293细胞能高水平的表达HERG通道蛋白.10,30μmol· L-1的小檗碱明显抑制HERG-HEK细胞中HERG通道蛋白的表达(P＜0.0l).10,20 mg·kg-1的小檗碱抑制大鼠心肌组织Ikr通道蛋白的表达(P＜0.05).3,10,30μmol·L-1的莲心碱促进HERG-HEK细胞中HERG通道蛋白的表达(P＜0.05).甲基莲心碱不影响HERG-HEK细胞中HERG通道蛋白的表达.结论:稳定转染的HERG-HEK细胞能高水平的表达HERG通道蛋白;小檗碱对体外HERG-HEK细胞和大鼠心肌组织Ikr通道的蛋白表达均有抑制作用;莲心碱促进HERG-HEK细胞中HERG通道蛋白的表达;甲基莲心碱对HERG通道蛋白表达无影响.