Comparison of the protective effects of curcumin and caffeic acid phenethyl ester against doxorubicin-induced testicular toxicity

Whether testicular toxicity is mediated by matrix metalloproteinases (MMPs) is an important question that has not been examined. This study investigated the suppressive effect of curcumin and caffeic acid phenethyl ester (CAPE) on oxidative stress, apoptosis, and whether MMPs mediate doxorubicin (DOX)-induced testicular injury. Male rats were randomly divided into eight groups (n = 8 per group). The groups were as follows: sham, dimethyl sulphoxide (100 µL), DOX (3 mg/kg), CAPE (2.68 mg/kg), curcumin (30 mg/kg), DOX+CAPE (3 mg/kg DOX and 2.68 mg/kg CAPE), DOX+curcumin (3 mg/kg DOX and 30 mg/kg curcumin) and DOX+CAPE+curcumin (3 mg/kg DOX, 2.68 mg/kg CAPE and 30 mg/kg curcumin). Injections were administered daily for 21 days. The oxidative stress, MMPs, proinflammatory cytokines and apoptotic markers in the DOX group were higher than the sham group (p < .05); these measures were lower in the groups treated with CAPE and curcumin together with DOX compared with the DOX group (p < .05). The results showed that MMPs mediated DOX-induced testicular injury, but CAPE and especially curcumin suppressed testis injury and cell apoptosis by suppressing DOX-induced increases in MMPs, oxidative stress and proinflammatory cytokines. However, curcumin exhibited more pronounced effects than CAPE in terms of all studied parameters.     

狗牙花属植物生物碱类成分及生物活性的研究进展

夹竹桃科(Apocynaceae)狗牙花属(Ervatamia Stapf)植物中的化学成分以及其生物活性一直是研究热点。其在全世界有约120种,主要分布在印度、中国西南地区,东南亚、大洋洲、北美洲、南美洲部分地区以及各海岛;在我国主要有15种和5变种,主要分布在华南地区及西南地区和台湾。我国傣族将云南狗牙花茎用于治疗产后体虚、头晕目眩、恶露淋漓等症状。据《中国植物志》中记载,产于亚洲热带与亚热带地区的单瓣狗牙花,其叶有降低血压功效,常用于治眼病、疮疥、乳疮、咬伤等;根可治头痛和骨折等。生物碱是狗牙花属植物中的主要化学成分,具有新颖的化学结构。现代药理学研究发现,狗牙花属植物中生物碱类成分具有抗肿瘤和抗乙酰胆碱脂酶等生物活性,其中抗肿瘤活性最为显著。因此狗牙花属植物具有很好的开发价值。但是,科研人员对狗牙花属植物生物碱类成分的研究仅限于发现与生物活性的测定,临床功效的研究较少。笔者结合近20年来的国内外文献对该属植物中149个生物碱进行总结,为进一步研究具有显著活性的生物碱类化学成分,合理充分利用狗牙花属植物的药用资源提供有价值的参考。     

The co-expression characteristics of LAG3 and PD-1 on the T cells of patients with breast cancer reveal a new therapeutic strategy

Many studies have shown a special interaction between LAG3 and PD-1 in T cell inhibition, while the co-expression and effect of LAG3 and PD-1 on T cells in breast cancer patients are still not very clear. Here, with strict exclusion criteria, 88 patients with breast cancer and 18 healthy controls were enrolled. The percentages of LAG3⁺PD-1⁺ T cells in their peripheral blood (PBL) and tumor infiltrating T cells (TIL) were analyzed by flow cytometry, which showed an increase in TILs but no difference in PBLs and presented differences in TILs in different molecular subtypes (P < 0.05). In triple-negative breast cancer (TNBC), the highest percentages were observed, while in ER+/PR+ breast cancer, the lowest percentages were observed; however, these percentages were not different in different clinical stages (P > 0.05). Immunohistochemical staining showed that the expression of their ligands, PD-L1, MHC class II molecular and FGL1, was inconsistent in different molecular subtypes and clinical stages. Analysis of the functions of T cells with different phenotypes showed that the proliferation and secretion capacity of LAG3⁺PD-1⁺ T cells was obviously exhausted, with more than a two-fold of decrease compared with the groups of single positive LAG3 or PD-1 (P < 0.05). Finally, in a mouse model of TNBC, the dual blockade of LAG3 and PD-1 was indicated to achieve a better anti-tumour effect than either one alone (P < 0.05), which may provide a new strategy for the immunoregulatory treatment of patients with TNBC in the future.     

Interactions of polar lipids with cholesteryl ester multilayers elucidate tear film lipid layer structure

PurposeThe tear film lipid layer (TFLL) covers the tear film, stabilizing it and providing a protective barrier against the environment. The TFLL is divided into polar and non-polar sublayers, but the interplay between lipid classes in these sublayers and the structure-function relationship of the TFLL remains poorly characterized. This study aims to provide insight into TFLL function by elucidating the interactions between polar and non-polar TFLL lipids at the molecular level.MethodsMixed films of polar O-acyl-ω-hydroxy fatty acids (OAHFA) or phospholipids and non-polar cholesteryl esters (CE) were used as a model of the TFLL. The organization of the films was studied by using a combination of Brewster angle and fluorescence microscopy in a Langmuir trough system. In addition, the evaporation resistance of the lipid films was evaluated.ResultsPhospholipids and OAHFAs induced the formation of a stable multilamellar CE film. The formation of this film was driven by the interdigitation of acyl chains between the monolayer of polar lipids and the CE multilayer lamellae. Surprisingly, the multilayer structure was destabilized by both low and high concentrations of polar lipids. In addition, the CE multilayer was no more effective in resisting the evaporation of water than a polar lipid monolayer.ConclusionsFormation of multilamellar films by major tear film lipids suggest that the TFLL may have a similar structure. Moreover, in contrast to the current understanding, polar TFLL lipids may not mainly act by stabilizing the non-polar TFLL sublayer, but through a direct evaporation resistant effect.     

Palmatine: A review of pharmacological properties and pharmacokinetics

The aim of this review is to collect together the results of the numerous studies over the last two decades on the pharmacological properties of palmatine published in scientific databases like Scopus and PubMed, which are scattered across different publications. Palmatine, an isoquinoline alkaloid from the class of protoberberines, is a yellow compound present in the extracts from different representatives of Berberidaceae, Papaveraceae, Ranunculaceae, and Menispermaceae. It has been extensively used in traditional medicine of Asia in the treatment of jaundice, liver‐related diseases, hypertension, inflammation, and dysentery. New findings describe its possible applications in the treatment of civilization diseases like central nervous system‐related problems. This review intends to let this alkaloid come out from the shade of a more frequently described alkaloid: berberine. The toxicity, pharmacokinetics, and biological activities of this protoberberine alkaloid will be developed in this work.     

麦芽4个化学部位通过多巴胺D2受体对产后缺乳模型大鼠催乳作用研究

目的基于多巴胺D2受体(DRD2),考察小剂量麦芽4个化学部位的催乳作用,初步探讨小剂量麦芽生物碱对产后缺乳模型大鼠泌乳素(PRL)分泌的调节机制。方法采用ig甲磺酸溴隐亭方法制备缺乳大鼠模型,造模成功后,各给药组均ig给予相应的药物,应用ELISA法检测各组大鼠血清PRL、雌二醇(E_2)、孕酮(P)水平;HE染色观察各组大鼠乳腺组织病理改变;采用实时荧光定量PCR(qRT-PCR)法检测各组大鼠脑垂体中泌乳素受体及DRD2 mRNA表达。结果与对照组比较,模型组大鼠血清中PRL、P及E_2水平、脑垂体PRL mRNA表达水平显著降低;脑垂体DRD2 mRNA表达水平显著升高。与模型组比较,麦芽总生物碱组大鼠乳腺小叶体积明显增加,导管明显扩张,且导管及腺泡内含有大量乳汁。麦芽总生物碱明显增加模型大鼠血清中PRL、P、E_2水平及脑垂体PRL mRNA表达水平,降低脑垂体DRD2 mRNA表达水平。结论麦芽催乳的主要药效物质为总生物碱,其作用机制可能与促进PRL分泌,增加脑垂体PRL受体、降低DRD2 mRNA表达水平有关。     

基于UPLC-LTQ-Orbitrap高分辨质谱的葛根芩连汤的化学成分分析

目的基于超高效液相色谱-离子阱-静电场轨道阱质谱(UPLC-LTQ-Orbitrap-MS)的分析方法鉴定葛根芩连汤中化学成分。方法采用色谱柱Dikma Endeavorsil C18(100 mm×2.1 mm,1.8μm),流动相为0.1%甲酸水(A)-乙腈(B),体积流量0.3 mL/min,梯度洗脱。质谱采用ESI源,正负离子模式分别采集一级、二级质谱数据。结果通过对照品指认、软件预测分析,结合文献报道,从葛根芩连汤中鉴定出67个化合物,包括黄酮类36个、生物碱类12个、三萜类及三萜皂苷类4个及其他15个。结论利用UPLC-LTQ-Orbitrap-MS系统阐明葛根芩连汤中化学成分,并初步归纳其各类主要化学成分的质谱裂解特点,为葛根芩根芩连汤的质量控制和作用机制研究提供了参考依据。     

吴茱萸化学成分和药理作用及质量标志物(Q-marker)的预测分析

吴茱萸是我国常用的大宗中药材,资源丰富且分布较广,具有广阔的开发利用前景。吴茱萸中化学成分类型丰富,包括生物碱、苦味素、挥发油、黄酮等类成分,传统认为生物碱和苦味素为其主要药效成分。对其化学成分、药理作用综述的基础上,根据中药质量标志物(Q-marker)理论,从生源途径、化学成分与传统功效、传统药性、新的临床用途、毒性、可测成分、入血成分及不同配伍环境几方面对吴茱萸Q-marker成分进行预测分析,为明确吴茱萸Q-marker和制定科学的质量标准提供基础。     

Caffeic acid phenethyl ester,a propolis polyphenolic,attenuates potentially cadmium-induced testicular dysfunction in mice

Abstract

Cadmium (Cd) as environmental pollutant can induce severe damage, particularly to the testis. This study investigated the effects of Caffeic acid phenethyl ester (CAPE) on testicular dysfunction induced by Cd. Adult mice were intraperitoneally injected with cadmium chloride (CdCl₂) with different doses of CAPE pretreatment. After CdCl₂ injection, body/testis weight ratio decreased, Cd levels accumulated and zinc levels decreased in testis. Furthermore, Cd intoxication caused a significant increase of oxidative stress levels, antioxidant enzymes activities, and glutathione levels. Interestingly, significant improvements were observed after the administration of CAPE. Our results demonstrated the protective effect of CAPE, linking Cd testicular dysfunction to oxidative stress.