The extrapituitary prolactin promoter polymorphism is associated with rheumatoid arthritis and anti-CCP antibodies in Mexican population

Prolactin (PRL) is a hormone–cytokine that has been involved in autoimmunity due to its immunoregulatory and lymphoproliferative effects. It is produced by various extrapituitary sites including immune cells, under control of a superdistal promoter that contains a single nucleotide polymorphism − 1149 G/T previously associated with rheumatoid arthritis (RA) susceptibility in European population. The aim of this study was to investigate the association of the extrapituitary PRL − 1149 G/T promoter polymorphism with clinical parameters, clinical activity and disability indices in RA patients from Western Mexico and to analyze the PRL mRNA expression according to the PRL − 1149 G/T promoter polymorphism in total leucocytes from RA patients and controls. We conducted a case–control study that included 258 RA patients and 333 control subjects (CS). The DNA samples were genotyped using the PCR–RFLP method and the PRL mRNA expression was determined by quantitative real time PCR. PRL serum levels and antibodies to cyclic citrullinated peptides (anti-CCP) were measured with ELISA. We found significant differences in the genotype (p = 0.022) and allelic (p = 0.046) distribution of the polymorphism between RA patients and control subjects. According to the dominant genetic model, there is an association between the T allele (GT + TT genotypes) and decreased RA susceptibility in comparison to the G allele carriers (GG genotype) (OR 0.64, 95% CI 0.45–0.92; p = 0.011). The T allele carriers (GT + TT genotypes) had lower titers of anti-CCP antibodies in comparison to the G allele carriers (GG genotype) (median, 66 U/mL vs. 125 U/mL; p = 0.03). Furthermore, the GG homozygotes had higher PRL mRNA expression in comparison to the GT heterozygotes, and this latter with respect to the TT homozygotes, in both groups (RA: 1 > 0.72 > 0.19; CS: 1 > 0.54 > 0.28). However, PRL serum levels were similar in both groups. Our results suggest that the PRL − 1149 T allele is a genetic marker for decreased RA susceptibility and is associated with lower titers of anti-CCP antibodies in Mexican population. We also suggest influence of genotype upon PRL mRNA expression.     

蒺藜总皂苷灌胃大鼠体内海柯皂苷元的代谢与分布

采用HPLC-UV和LC-MS方法相结合测定分析了海柯皂苷元在蒺藜总皂苷灌胃Sprague-Dawley(SD)大鼠体内不同器官组织分布动态变化。结果表明在大鼠胃肠中蒺藜总皂苷中有部分海柯皂苷水解为海柯皂苷元;在从6到32 h灌胃蒺藜总皂苷的大鼠肝脏中可检测到海柯皂苷元的存在,证明有一定量海柯皂苷元从大鼠胃肠道吸收进入体内;对于海柯皂苷元检测,API-MS检测方法较UV方法有更高的灵敏度,且有好的专属性。     

New triterpene saponins from the seed cake of Camellia Oleifera and their cytotoxic activity

Two new oleanane-type triterpene saponins, identified as 16α-hydroxy-22-O-angeloyl-23-formyl-28,31-dihydroxymethylene-olean-12-ene-3β-O-{β-d-galactopyranosyl-(1 → 2)[β-d-xylopyranosyl-(1 → 2)-α-l-arabinopyranosyl(1 → 3)]-β-d-glucopyranosiduronic acid} (oleiferasaponin B₁, 1) and 22-O-hydrocinnamoyl-23-formyl-28-dihydroxymethylene-olean-12-ene-3β-O-{β-d-glucopyranosyl-(1 → 2)[β-d-xylopyranosyl-(1 → 2)-α-l-arabinopyranosyl(1 → 3)]-β-d-glucopyranosiduronic acid} (oleiferasaponin B₂, 2), were isolated from the seed cake of Camellia oleifera Abel. Their structures were established by extensive 1D- and 2D-NMR experiments along with TOF-MS analysis and acid hydrolysis. The cytotoxicity of the isolated compounds was evaluated in four human carcinoma cell lines: A 549, SK-OV-3, SK-MEL-2 and HCT15. Both compounds 1 and 2 exhibited significantly cytotoxic activity with IC₅₀ values of 18.5 μM (A549), 11.3 μM (SK-OV-3), 13.9 μM (SK-MEL-2) and 1.6 μM (HCT15) for 1 and IC₅₀ values of 8.4 μM (A549), 6.3 μM (SK-OV-3), 9.2 μM (SK-MEL-2) and 0.8 μM (HCT15) for 2. In addition, compound 2 showed more effective cytotoxic activity than compound 1.     

大孔吸附树脂富集穿龙薯蓣水溶性皂苷工艺研究

以穿龙薯蓣水溶性皂苷的洗脱率、精制度为指标,考察大孔吸附树脂对穿龙薯蓣水溶性皂苷的吸附性能和洗脱参数。实验结果表明:经ZTC澄清剂澄清后的穿龙薯蓣水溶性皂苷提取液40 mL(6.57 mg/mL)上大孔树脂柱(R25 mm×H100 mm,干重6.0 g),用蒸馏水80 mL、50%乙醇100 mL依次洗脱。穿龙薯蓣水溶性皂苷富集于50%乙醇洗脱液部位,洗脱率达80%以上,干燥后总固物中穿龙薯蓣水溶性皂苷纯度可达26.1%,达到较好的纯化目的。     

三七总皂苷联合顺铂对胃癌大鼠肾损伤的改善作用及机制分析

摘要 目的：探讨三七总皂苷联合顺铂对胃癌大鼠肾损伤的改善作用并分析潜在机制。方法：选择60只健康SD雄性大鼠分为对照组、胃癌模型组、顺铂组及三七总皂苷组,各15只。除对照组外,其余组大鼠采用皮下接种胃癌BGC823细胞悬液法建立胃癌模型。建模成功后,给予对照组和胃癌模型组大鼠生理盐水腹腔注射和灌胃,给予顺铂组大鼠腹腔注射25 mg/kg顺铂注射液并灌胃生理盐水,给予三七总皂苷组大鼠腹腔注射25 mg/kg顺铂注射液并灌胃30 mg/kg三七总皂苷。分别于建模成功时、药物处理28 d时采用酶联免疫吸附法检测血清肌酐（SCr）、尿素氮（BUN）和尿液β-N-乙酰氨基葡萄糖苷酶（NAG）、肾损伤分子1（KIM-1）水平。处死大鼠后取肾脏,分别测定肾脏组织匀浆中超氧化物歧化酶（SOD）、丙二醛（MDA）、过氧化氢酶（CAT）、谷胱甘肽（GSH）水平,制备肾脏组织石蜡切片并行苏木精-伊红染色后观察大鼠肾组织的病理学变化。采用TUNEL染色法检测肾脏组织细胞凋亡情况,采用Western Blotting法检测肾脏组织中LC3、HIF-1α和Beclin1 蛋白表达情况。结果：顺铂组和三七总皂苷组大鼠血清SCr、BUN和尿液NAG、KIM-1水平均显著高于对照组和模型组（P<0.05）,三七总皂苷组大鼠血清SCr、BUN和尿液NAG、KIM-1水平显著高于顺铂组（P<0.05）。三七总皂苷组大鼠肾脏组织SOD、GSH水平显著低于模型组但显著高于顺铂组,MDA显著高于模型组但显著低于顺铂组（P＜0.05）,CAT与模型组无显著差异（P＜0.05）,但显著高于顺铂组（P>0.05）。顺铂组大鼠肾小管明显扩张、管腔狭窄,基底层上皮细胞水肿、坏死并形成空泡,肾小管。三七总皂苷组大鼠肾脏病理学改变程度显著轻于顺铂组。顺铂组和三七总皂苷组大鼠肾脏组织细胞凋亡指数显著增加,三七总皂苷组大鼠肾脏组织细胞凋亡指数显著低于顺铂组（P＜0.05）。顺铂组大鼠肾脏组织中LC3、HIF-1α和Beclin1蛋白水平均显著高于模型组,但显著低于三七总皂苷组（P＜0.05）。结论：三七总皂苷可能通过减轻过氧自由基和过氧化水平、增强线粒体自噬水平减少肾组织细胞凋亡,减轻顺铂引起的胃癌大鼠肾损伤。     

Triterpene Saponins from Polygalaceae

The aim of this review is to give updated results on the chemistry and biological activities of Polygalaceae saponins from literature data and from authors’ studies. During the last decade the improvement of isolation and structure elucidation techniques allowed the characterization of about 150 complex triterpene saponins from Polygalaceae having mainly preatroxigenin, medicagenic acid and presenegenin as aglycone. The sequence 3-O-(β-d-glucopyranosyl)-presenegenin 28-[O-α-L-rhamnopyranosyl-(1→2)-β-d-fucopyranosyl] ester with additional acylations with p-methoxy-, di- or trimethoxycinnamoyl groups at the position 4 of the fucopyranosyl moiety often encountered in the genera Polygala, Muraltia, Carpolobia, and Securidaca may represent a chemotaxonomic marker for the Polygalaceae family. The biological and pharmacological properties of some Polygalaceae species such as in vitro activity on the central nervous system, the hypoglycemic, cytotoxic, immunomodulatory activities and in vivo immunoadjuvant properties are highlighted.     

A spirostanol glycoside from Agave cantala

A new steroidal saponin has been isolated from the ethanolic extract of the roots of Agave cantata and shown to be 3-O-[β-d-glucopyranosyl]-6O-[β-d-glucopyranosyl]-(25R)-5α-22α-O- spirostan-3β, 6α-diol.     

Aculeamine,a solanocapsine-type steroidal alkaloid from Solanum aculeatum

A new solanocapsine-type alkaloid named aculeamine has been isolated from roots of Solanum aculeatum and its structure elucidated by physical methods including X-ray analysis as 22,26-epimino-22β-methoxy- 16α,23-epoxy-5α,22αH,25βH-cholestane-3β-ol. The corresponding 23β-ethoxy compound was also isolated as an artefact.     

Sitosterol 3-O-α-riburonofuranoside from Bauhinia candicans

From the aerial parts of Bauhinia candicans a novel steroidal glycoside was isolated and identified as sitosterol 3-O-α-D-riburonofuranoside.     

C21 steroidal glycosides with cytotoxic activities from Cynanchum otophyllum

Eight new C21 steroidal glycosides, namely cynanotins A–H (1–8), together with fifteen known analogues, were isolated from the roots of Cynanchum otophyllum. Their structures were elucidated by spectroscopic analysis and chemical methods. In this study, all of isolates were tested for their vitro inhibitory activities against five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7 and SW480). Compounds 3–15 showed moderate cytotoxic activities against HL-60 cell lines with IC₅₀ values ranging from 11.4 to 37.9?µM. Compounds 5, 9, and 10 showed marked or moderate cytotoxic activities against five human tumor cell lines with IC₅₀ values ranging from 11.4 to 36.7?µM. Compound 11 displayed moderate cytotoxic activities against HL-60, SMMC-7721, MCF-7 and SW480 cell lines with IC₅₀ values of 12.2–30.8?µM. Compared to the positive control (IC₅₀: 35.0?µM), compounds 5, 9–11 exhibited more potential inhibitory activity against MCF-7 cells (IC₅₀: 16.1–25.6?µM).