Zorić Nataša, Kosalec Ivan, Tomić Siniša, Bobnjarić Ivan, Jug Mario, Vlainić Toni, Vlainić Josipa
Agency for Medicinal Products and Medical Devices of Croatia, Ksaverska cesta 4, 10000, Zagreb, HR, Croatia.
University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, Croatia.
BMC Complement Altern Med. 2017 May 17;17(1):268. doi: 10.1186/s12906-017-1773-5.
We investigated the mechanisms of anti-Candida action of isoquinoline alkaloid berberine, active constituent of medically important plants of Barberry species.
The effects on membrane, morphological transition, synthesis of ergosterol and the consequent changes in membrane permeability have been studied. Polarization and lipid peroxidation level of the membrane following berberine treatment have been addressed.
Minimal inhibitory concentration (MIC) of berberine against C. albicans was 17.75 μg/mL. Cytotoxic effect of berberine was concentration dependent, and in sub-MIC concentrations inhibit morphological transition of C. albicans cells to its filamentous form. Results showed that berberine affects synthesis of membrane ergosterol dose-dependently and induces increased membrane permeability causing loss of intracellular material to the outer space (DNA/protein leakage). Berberine also caused membrane depolarization and lipid peroxidation of membrane constituents indicating its direct effect on the membrane. Moreover, ROS levels were also increased following berberine treatment indicating further the possibility of membrane damage.
Based on the obtained results it seems that berberine achieves its anti-Candida activity by affecting the cell membrane.
我们研究了异喹啉生物碱黄连素（小檗碱）的抗念珠菌作用机制，黄连素是小檗属重要药用植物的活性成分。
研究了黄连素对细胞膜、形态转变、麦角固醇合成以及随之而来的膜通透性变化的影响。探讨了黄连素处理后细胞膜的极化和脂质过氧化水平。
黄连素对白色念珠菌的最低抑菌浓度（MIC）为17.75μg/mL。黄连素的细胞毒性作用呈浓度依赖性，在亚MIC浓度下可抑制白色念珠菌细胞向丝状形态的转变。结果表明，黄连素剂量依赖性地影响膜麦角固醇的合成，并诱导膜通透性增加，导致细胞内物质泄漏到细胞外空间（DNA/蛋白质泄漏）。黄连素还引起细胞膜去极化和膜成分的脂质过氧化，表明其对细胞膜有直接作用。此外，黄连素处理后活性氧水平也升高，进一步表明存在膜损伤的可能性。
根据所得结果，黄连素似乎通过影响细胞膜来实现其抗念珠菌活性。
