Isoliquiritigenin,a natural anti‐oxidant,selectively inhibits the proliferation of prostate cancer cells

1. Isoliquiritigenin (ISL) is a simple chalcone‐type flavonoid derived from liquorice compounds. It has been reported to have anti‐oxidative and antitumour activities. The aim of the present study was to investigate the antitumour effect of ISL on prostate cancer cells and to explore the possible signalling mechanisms involved. 2. Cell viability was assessed using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. The fluorescent probe 2′,7′‐dichlorofluorescein diacetate (H₂DCF‐DA) was used to measure intracellular levels of reactive oxygen species (ROS). Mitochondrial membrane potential (Ψ_m) was measured using the mitochondrial probe 5,5′,6,6′‐tetrachloro‐1,1′,3,3′‐tetraethyl‐benzimidazolylcarbocyanine iodide (JC‐1). 3. Isoliquiritigenin treatment (10–100 μmol/L for 24 h) markedly inhibited the proliferation of both C4‐2 and LNCaP prostate cancer cells in a dose‐dependent manner. Intriguingly, ISL treatment (10–100 μmol/L for 24 h) had no effect on the viability of IEC‐6 normal epithelial cells. Treatment of C4‐2 and IEC‐6 cells with 87.0 μmol/L ISL significantly decreased ROS levels and the Ψ_m of C4‐2 cells, but had no effect on either parameter in IEC‐6 cells. Furthermore, AMP‐activated protein kinase (AMPK) and extracellular‐signal regulated kinase (ERK) levels were three to fourfold higher in IEC‐6 cells than in C4‐2 cells (P < 0.05). 4. The results of the present study suggest that ISL, a natural anti‐oxidant, selectively inhibits the proliferation of prostate cancer C4‐2 cells, which may be attributed, in part, to defective AMPK and ERK signalling pathways in C4‐2 compared with IEC‐6 cells.     

VC银翘片中异甘草素二糖苷的1HNMR和13CNMR法鉴定分析

目的：对Vc银翘片有效成分异甘草素二糖苷的存在进行鉴定分析。方法：运用色谱技术进行分离；运用^1HNMR和^13CNMR方法进行鉴定分析。结果：Vc银翘片中含有异甘草素二糖苷。结论：Vc银翘片中含有银翘散的有效抗流感病毒成分，其处方保留了银翘散的主要功效。     

Isoliquiritigenin,a flavonoid from licorice,blocks M2 macrophage polarization in colitis-associated tumorigenesis through downregulating PGE2 and IL-6

M2 macrophage polarization is implicated in colorectal cancer development. Isoliquiritigenin (ISL), a flavonoid from licorice, has been reported to prevent azoxymethane (AOM) induced colon carcinogenesis in animal models. Here, in a mouse model of colitis-associated tumorigenesis induced by AOM/dextran sodium sulfate (DSS), we investigated the chemopreventive effects of ISL and its mechanisms of action. Mice were treated with AOM/DSS and randomized to receive either vehicle or ISL (3, 15 and 75 mg/kg). Tumor load, histology, immunohistochemistry, and gene and protein expressions were determined. Intragastric administration of ISL for 12 weeks significantly decreased colon cancer incidence, multiplicity and tumor size by 60%, 55.4% and 42.6%, respectively. Moreover, ISL inhibited M2 macrophage polarization. Such changes were accompanied by downregulation of PGE₂ and IL-6 signaling. Importantly, depletion of macrophages by clodronate (Clod) or zoledronic acid (ZA) reversed the effects of ISL. In parallel, in vitro studies also demonstrated that ISL limited the M2 polarization of RAW264.7 cells and mouse peritoneal macrophages with concomitant inactivation of PGE₂/PPARδ and IL-6/STAT3 signaling. Conversely, exogenous addition of PGE₂ or IL-6, or overexpression of constitutively active STAT3 reversed ISL-mediated inhibition of M2 macrophage polarization. In summary, dietary flavonoid ISL effectively inhibits colitis-associated tumorigenesis through hampering M2 macrophage polarization mediated by the interplay between PGE₂ and IL-6. Thus, inhibition of M2 macrophage polarization is likely to represent a promising strategy for chemoprevention of colorectal cancer.     

双波长切换HPLC同时测定桂枝甘草汤中4种成分的含量

目的建立桂枝甘草汤中4种成分同时含量测定的方法。方法采用高效液相色谱法,KromasilC18柱（4．6mm×250mm,5um）,以乙腈-0．1％甲酸水溶液为流动相进行梯度洗脱,流速：1．0mL·min-1,双波长切换时间序列采样：0～29．5 min为276nm;29．5～32．0min为370nm。结果甘草苷、肉桂酸、桂皮醛、异甘草素分别在10．0～160,2．50～40．0,16．0～256,0．050～0．8ug·mL-1内,线性关系良好。结论该方法准确、简便、专属性好,可用于桂枝甘草汤中甘草苷、肉桂酸、桂皮醛和异甘草素4种成分的含量测定,为桂枝甘草汤的质量控制提供依据。     

不同药性成分对OAT4、URAT1抑制作用及对急性高尿酸血症小鼠血尿酸水平的影响

目的研究不同药性中药成分对尿酸重吸收转运体尿酸转运蛋白1(URAT1)和有机阴离子转运蛋白4(OAT4)的抑制作用及对急性高尿酸血症小鼠尿酸水平的影响。方法应用OAT4、URAT1过表达单克隆细胞株(MDCK-hOAT4、HEK293-hURAT1),检测各药性中药单体对OAT4、URAT1的抑制作用及半数抑制浓度(IC50);运用黄嘌呤联合氧嗪酸钾制备急性高尿酸血症小鼠模型,研究原儿茶酸、甘草素、异甘草素对急性高尿酸血症小鼠血清尿酸的影响。结果苦味药中的川陈皮素,甘味药中的甘草素、异甘草素、甘草查耳酮A对OAT4抑制作用较强,IC50分别是0.556、18.40、6.831、6.825μmol/L。酸味药中的原儿茶酸、甘味药中的甘草素对URAT1具有较强的抑制作用,IC50分别是7.709、14.540μmol/L。甘草素能显著降低急性高尿酸血症小鼠的血尿酸水平,增加尿酸排泄量,降低血清肌酐、尿素氮的含量。结论川陈皮素、甘草素、异甘草素、甘草查耳酮A对OAT4具有较强的抑制作用,原儿茶酸、甘草素对URAT1具有较强抑制作用。甘草素能显著降低急性高尿酸血症小鼠血尿酸水平,其作用机制可能是抑制OAT4、URAT1对尿酸的重吸收,并具有一定的肾脏保护作用。     

不同品种甘草化学成分、药理作用的研究进展及质量标志物（Q-Marker）预测分析

甘草为多年生草本植物,为我国传统常用中药材。《中国药典》2020年版中收载甘草为乌拉尔甘草Glycyrrhiza uralensis、光果甘草G.glabra、胀果甘草G.inflata 3个品种。不同品种甘草在某些化学成分上不仅存在含量上的差异,也存在种属特异性,药理活性也不尽相同。对不同品种甘草化学成分、药理作用的研究进展进行综述,并对其质量标志物（quality marker,Q-Marker）进行预测分析,建议将黄酮类化合物甘草苷、异甘草苷、甘草素、异甘草素和三萜类化合物甘草酸、甘草次酸作为3种甘草的Q-Marker。另外考虑到不同品种之间成分的特有性和各自的优势生物活性,建议可以将光甘草定作为光果甘草的Q-Marker,将查耳酮A作为胀果甘草的Q-Marker,以期为明确不同品种甘草Q-Marker及不同品种甘草药材质量标准建立及合理开发利用提供理论依据。     

酸水解法提取甘草中异甘草素工艺研究

 目的以甘草粉末为原料,研究了酸水解法提取异甘草素的工艺。方法采用正交实验考察盐酸浓度、水解时间、水解温度、料液比(甘草重量:盐酸体积)4个因素对异甘草素提取率的影响,确定酸水解法提取异甘草素的最佳工艺。结果酸水解法提取异甘草素的最佳工艺参数为盐酸浓度1mol·L^-1,水解作用时间2h,水解温度90℃,料液比1∶5。水解后碱中和pH为7,过滤后用体积分数80%乙醇提取滤渣,料液比1∶10,超声20min,提取2次;乙酸乙酯萃取滤液,液液比1∶1,萃取2次。结论酸水解法提取异甘草素的提取率为2.47‰,浸膏中异甘草素含量为3.01%,其提取率和含量分别是索氏提取的8.82和10.03倍,是乙醇超声提取的9.88和9.41倍。     

甘草中异甘草素和甘草素含量测定方法研究

目的 建立同时测定甘草中异甘草素和甘草素含量的方法。方法 采用高效液相色谱（HPLC）等度洗脱和检测波长时间序列采样的方法,流动相为甲醇-水=（45∶55）,检测波长0~25min时为276nm,25~70min时为360mn,流速为0.8mL/min,同时测定甘草中异甘草素和甘草素的含量。结果 异甘草素和甘草素进样量线性范围分别为0.028~0.28μg和0.064~0.64μg,平均加样回收率分别为97.92%和98.27%,RSD分别为1.29%和1.67%。结论 该方法准确、灵敏度高、重现性好、操作简单,可为甘草药材的质量评价提供参考。     

Isoliquiritigenin inhibits microglia-mediated neuroinflammation in models of Parkinson's disease via JNK/AKT/NFκB signaling pathway

Isoliquiritigenin (ISL) is a flavonoid with numerous pharmacological properties, including anti-inflammation, yet its role in Parkinson's disease (PD) with microglia-mediated neuroinflammation remains unknown. In this study, the effects of ISL on inhibiting microglia-mediated neuroinflammation in PD were evaluated in the 1-methyl-4-phenylpyridinium (MPTP)-induced mouse model of PD and in lipopolysaccharide (LPS)-stimulated BV-2 microglia. Our results showed that ISL prevented behavioral deficits and excessive microglial activation in MPTP-treated mice. Moreover, ISL was found to prevent the elevation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and mitigate the phosphorylation of c-Jun N-terminal protein kinase (JNK), protein kinase B (AKT), nuclear factor kappa light-chain enhancer of activated B cells (NFκB), and inhibitor of NFκB protein ɑ (IκBɑ) in the substantia nigra and striatum of MPTP-treated mice and LPS-stimulated BV-2 cells. Meanwhile, in LPS-stimulated BV-2 cells, ISL inhibited the production of inflammatory mediators such as interleukin (IL)-1β, IL-6 and tumor necrosis factor alpha (TNF-α). In addition, the agonist of JNK partly abolished the inhibitory effects of ISL in LPS-treated BV-2 cells. Our results demonstrated that ISL inhibits microglia-mediated neuroinflammation in PD models probably through deactivating JNK/AKT/NFκB signaling pathways. The novel findings suggest the therapeutic potential of ISL for microglia-mediated neuroinflammation in PD.     

异甘草素对豚鼠离体气管平滑肌收缩功能的影响

异甘草素(isoliquiritigenin,ISL)是从甘草中提取出的一种黄酮类化合物.本文观察了ISL对豚鼠离体气管条张力的影响,旨在为其治疗支气管哮喘等呼吸道疾病提供实验依据.