Protective effect of saffron (Crocus sativus L.) aqueous extract against genetic damage induced by anti-tumor agents in mice

The genotoxic potential of anti-tumor drugs limits their efficacy in the treatment of cancers. Since ancient times, saffron (dried stigmas of Crocus sativus L.) has been used as a spice and medicinal herb. Saffron is a rich source of carotenoids and is known for its anti-cancer and anti-tumor properties. The present study was designed to ascertain the chemoprotective potential of saffron against the genotoxicity of three well-known anti-tumor drugs-cisplatin (CIS), cyclophosphamide (CPH) and mitomycin-C (MMC)--using comet assay. Three doses of saffron (20, 40 and 80 mg/kg b.w.) were orally administered to mice for five consecutive days prior to the administration of anti-tumor drugs under investigation. Pre-treatment with saffron significantly inhibited anti-tumor drugs induced cellular DNA damage (strand breaks) as revealed by decreased comet tail length, tail moment and percent DNA in the tail. These findings, together with our previous results, suggest a potential role for saffron as an anti-genotoxic, anti-oxidant and chemopreventive agent and could be used as an adjuvant in chemotherapeutic applications.     

Investigation of the neuroprotective action of saffron (Crocus sativus L.) in aluminum-exposed adult mice through behavioral and neurobiochemical assessment

In the present study, the possible reversal effects of saffron against established aluminum (Al)-toxicity in adult mice, were investigated. Control, Al-treated (50 mg AlCl₃/kg/day diluted in the drinking water for 5 weeks) and Al + saffron (Al-treatment as previously plus 60 mg saffron extract/kg/day intraperitoneally for the last 6 days), groups of male Balb-c mice were used. We assessed learning/memory, the activity of acetylcholinesterase [AChE, salt-(SS)/detergent-soluble(DS) isoforms], butyrylcholinesterase (BuChE, SS/DS isoforms), monoamine oxidase (MAO-A, MAO-B), the levels of lipid peroxidation (MDA) and reduced glutathione (GSH), in whole brain and cerebellum. Brain Al was determined by atomic absorption spectrometry, while, for the first time, crocetin, the main active metabolite of saffron, was determined in brain after intraperitoneal saffron administration by HPLC. Al intake caused memory impairment, significant decrease of AChE and BuChE activity, activation of brain MAO isoforms but inhibition of cerebellar MAO-B, significant elevation of brain MDA and significant reduction of GSH content. Although saffron extract co-administration had no effect on cognitive performance of mice, it reversed significantly the Al-induced changes in MAO activity and the levels of MDA and GSH. AChE activity was further significantly decreased in cerebral tissues of Al + saffron group. The biochemical changes support the neuroprotective potential of saffron under toxicity.     

The safety assessment of saffron (Crocus sativus L.) on sympathovagal balance and heart rate variability; a comparison with amiodarone

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Use of in vitro assays to assess the potential antigenotoxic and cytotoxic effects of saffron (Crocus sativus L.).

Saffron is harvested from the dried, dark red stigmas of Crocus sativus L. flowers. It is used as a spice for flavoring and coloring food and as a perfume. It is often used for treating several diseases. We assessed the antimutagenic, comutagenic and cytotoxic effects of saffron and its main ingredients using the Ames/Salmonella test system, two well known mutagens (BP, 2AA), the in vitro colony formation assay and four different cultured human normal (CCD-18Lu) and malignant (HeLa, A-204 and HepG2) cells. When only using the TA98 strain in the Ames/Salmonella test system, saffron showed non-mutagenic, as well as non-antimutagenic activity against BP-induced mutagenicity, and demonstrated a dose-dependent co-mutagenic effect on 2-AA-induced mutagenicity. The saffron component responsible for this unusual comutagenic effect was safranal. In the in vitro colony formation test system, saffron displayed a dose-dependent inhibitory effect only against human malignant cells. All isolated carotenoid ingredients of saffron demonstrated cytotoxic activity against in vitro tumor cells. Saffron crocin derivatives possessed a stronger inhibitory effect on tumor cell colony formation. Overall, these results suggest that saffron itself, as well as its carotenoid components might be used as potential cancer chemopreventive agents.     

气相色谱法用于西红花的真伪鉴别研究

目的利用气相色谱法鉴别西红花真品与掺假品、伪品。方法采用气相色谱（GC）法测定了11个不同产地的21个西红花样品。采用HP-5毛细管色谱柱（30.0 m×0.32 mm×0.25 m）,程序升温,氢火焰离子化检测器（FID）。结果气相色谱图特征显著,西红花真品和伪品的色谱图明显不同;真品和掺假品色谱图也有明显的区别,特征性成分的保留时间一致,只是含量有较大差别。结论本研究可为西红花真伪鉴别及质量控制提供一定的参考依据。     

Bacillus subtilis FZB24 affects flower quantity and quality of saffron (Crocus sativus)

The effect of Bacillus subtilis FZB24 on saffron ( Crocus sativus L.) was studied using saffron corms from Spain and the powdered form of B. SUBTILIS FZB24(R). Corms were soaked in water or in B. subtilis FZB24 spore solution for 15 min before sowing. Some corms were further soil drenched with the spore solution 6, 10 or 14 weeks after sowing. Growth and saffron stigma chemical composition were measured. Compared to untreated controls, application of B. subtilis FZB24 significantly increased leaf length, flowers per corm, weight of the first flower stigma, total stigma biomass; microbe addition also significantly decreased the time required for corms to sprout and the number of shoot sprouts. Compared to the controls, picrocrocin, crocetin and safranal compounds were significantly increased when the plants were soil drenched with the spore solution 14 weeks after sowing; in contrast crocin was highest in untreated controls. Results of this study suggest that application of B. subtilis FZB24 may provide some benefit to saffron growers by speeding corm growth (earlier shoot emergence) and increasing stigma biomass yield by 12 %. While some treatment conditions also increased saffron chemical composition, these were generally not the same treatments that simultaneously improved growth yields and thus, more study is required.     

Relaxant effect of Crocus sativus (saffron) on guinea-pig tracheal chains and its possible mechanisms

As indicated in ancient Iranian medical books, Crocus sativus has therapeutic effects on respiratory diseases. The relaxant effect of this plant has been observed also on smooth muscles in previous studies. Therefore, in this study the relaxant effects of aqueous-ethanolic extracts of C. sativus and one of its main constituents, safranal, were examined on guinea-pig tracheal chains. The relaxant effects of four cumulative concentrations of aqueous-ethanolic extract (0.15, 0.3, 0.45, and 0.60 g %) and safranal (0.15, 0.30, 0.45, and 0.60 mL 0.2 mg mL(-1) solution) in comparison with saline, as negative control, and four cumulative concentrations of theophylline (0.15, 0.30, 0.45, and 0.60 mM), as positive control, were examined using guinea-pig precontracted tracheal chains. The tracheal chains had been precontracted by three different methods. Group 1 had been precontracted using 10 microM methacholine. The other two groups had been precontracted using 60 mM KCl at two different conditions: non-incubated tissues (group 2) and tissues incubated with 1 microM propranolol, 1 microM chlorpheniramine and 1 microM atropine (group 3) (for each group, n = 6). In group 1 all concentrations of theophylline, extract and safranal showed significant relaxant effects compared with saline (P < 0.05 to P < 0.001). In group 2 theophylline, extract and safranal showed concentration-dependent relaxant effects also compared with saline (P < 0.05 to P < 0.001 for different concentrations except two low concentrations of safranal). However, in group 3 the extracts of C. sativus showed a weak relaxant effect (P < 0.05 only for the highest concentration). The effects of the last concentration of safranal (0.60 mL 0.2 mg mL(-1) solution) in group 1, and all its concentrations in group 2 were significantly lower than those of theophylline (P < 0.05 to P < 0.001). In addition, the effects of safranal 0.45 and 0.60 mL 0.2 mg mL(-1) solution in groups 1 and 2 were significantly lower than that of C. sativus extract. There were significant correlations between the relaxant effects and concentrations for extract, safranal and theophylline in all experimental groups (P < 0.001 for all cases). These results showed a potent relaxant effect of C. sativus on tracheal chains of guinea-pigs that was comparable to or even higher than that of theophylline at the concentrations used. The results indicated that safranal was, at least in part, responsible for the relaxant effect of C. sativus.     

Protective effects of saffron (Crocus sativus) against lethal ventricular arrhythmias induced by heart reperfusion in rat: A potential anti-arrhythmic agent

Abstract

Context: Saffron (Crocus sativus L.) has been used as a cuisine spice in eastern and western societies for thousands of years. In traditional medicine, saffron is recommended for the treatment of various kinds of disorders including heart palpitations.

Objective: We investigated the hypothesis of the protective effect of saffron on lethal cardiac arrhythmias induced by heart ischemia-reperfusion in rat.

Materials and methods: Animals were divided into a control (CTL) group that received tap water, Saf50, Saf100 and Saf200 groups that were orally treated with aqueous extracts of saffron, at dosages of 50, 100 and 200?mg/kg/day, respectively, and amiodarone (Amio) group that orally received 30?mg/kg/day for seven days. On day 8, heart ischemia-reperfusion was induced by ligation and releasing of the left anterior descending coronary artery.

Results: During reperfusion, the numbers and durations of ventricular fibrillation (VF) decreased in all groups compared to the CTL group (p?<?0.05). Ventricular tachycardia (VT)/VF numbers (3.2?±?1.2), durations (4.9?±?2.6) and also arrhythmia severity (1.9?±?0.35) were decreased significantly in the Saf100 group versus CTL group values (18.4?±?11.6, 52?±?31 and 3.3?±?0.3, respectively). The PR and QTcn intervals of ECG were significantly longer in the Saf200 group (p?<?0.001 versus CTL). The other doses of saffron only significantly prolonged the QTcn interval.

Conclusion: The results suggest that pretreatment with saffron, especially at the dosage of 100?mg/kg/day, attenuates the susceptibility and incidence of fatal ventricular arrhythmia during the reperfusion period in the rat. This protective effect is apparently mediated through reduction of electrical conductivity and prolonging the action potential duration.     

西红花花瓣化学成分研究

采用硅胶、制备HPLC等柱色谱方法对鸢尾科植物西红花(Crocus sativus L.)花瓣的化学成分进行分离,通过NMR、MS等波谱技术鉴定化合物结构,分离鉴定了9个化合物,分别为:苯乙醇-O-β-D-吡喃葡萄糖苷(1),苄醇-1-O-[6′-O-(S)-3′′-羟基-3′′-甲基戊二酸单酯]-β-D-吡喃葡萄糖苷(2),苯乙醇-1-O-[6′-O-(S)-3′′-羟基-3′′-甲基戊二酸单酯]-β-D-吡喃葡萄糖苷(3),4-羟基苯甲酸-4-O-α-L-吡喃鼠李糖-1-O-β-D-吡喃葡萄糖酯苷(4),4-羟基苯甲酸-4-O-β-D-吡喃葡萄糖苷(5),菠甾醇-3-O-β-D-吡喃葡萄糖苷(6),山柰酚(7),山柰酚-3-O-β-D-吡喃葡萄糖苷(8),山柰酚-7-O-β-D-吡喃葡萄糖苷(9).其中,化合物4为新化合物,化合物1～3,5～6均为首次从该植物中分离得到.体外活性初步评价了化合物1～9对皮质酮诱导PC12细胞损伤的保护作用,化合物2～5具有中等神经保护作用.     

The cytolytic effect of a glycoconjugate extracted from corms of saffron plant (Crocus sativus) on human cell lines in culture

Corms of Crocus sativus L. (Iridaceae) contain a glycoconjugate that shows cytotoxic activity on tumoral cells in culture. Studies of intracellular calcium fluctuations, and release of lactate dehydrogenase in human cervical epitheloid carcinoma cells, showed that this compound caused plasma membrane damage, allowing movements of both calcium and macromolecules, and leading to cell lysis. Analysis of DNA fragmentation showed that cell death was not mediated by apoptosis. This molecule is active against human tumoral cells derived from fibrosarcoma, cervical epithelioid carcinoma and breast carcinoma, with IC50 values of 7, 9 and 22 micrograms/ml, respectively. The proteoglycan is about 8 times more cytotoxic for malignant cells than for their normal counterparts. In addition, 100 micrograms/ml of proteoglycan produced 50% in vitro lysis of normal human erythrocytes, whereas 320 micrograms/ml induced about 60% cell death on cultured human hair follicles. Altogether, these results suggests a distinctive cytotoxic activity of this molecule on different human cell types.     

西红花组织培养研究进展

西红花是一种名贵的中草药,其传统方法繁殖不能满足市场需求,近年来研究者们尝试以西红花作为外植体,探索其组织培养方法。该文从外植体、培养基、培养条件等不同方面论述西红花国内外研究进展,以期系统了解并科学指导该领域的研究。     

反相高效液相色谱法对不同来源西红花药材中西红花苷-1、苷-2的定量分析

目的 :测定西红花药材中西红花苷 1、苷 2的含量。方法 :采用反相高效液相色谱 ,以Nova PakC18( 4 μm ,150mm×3 .9mm)柱为色谱柱 ,甲醇 水 ( 55∶45)为流动相 ,测定波长为 ( 4 4 0± 1)nm。结果 :西红花苷 1的平均回收率为 99.53 % ,日内、日间RSD分别为 1.0 % ,1.6 % ;西红花苷 2的平均回收率为 99.43 % ,日内、日间RSD分别为 1.3 % ,1.8%。进口西红花商品药材中有 2种未测出或只有痕量 ,3种含量较低 (西红花苷 1为 80 .9～ 10 2 .0mg·g- 1生药 ,西红花苷 2为 44.5～ 62 .3mg·g- 1生药 ) ,而国产西红花商品药材中含量最高 (西红花苷 1为 176 .2mg·g- 1生药 ,西红花苷 2为 10 8.5mg·g- 1生药 )。结论 :建立的RP HPLC法测定不同来源西红花药材中西红花苷 1、苷 -2的含量 ,操作简便 ,结果准确。     

西红花酸药理作用的研究进展

西红花的化学成分包括类胡萝卜素类及其糖苷类、黄酮苷类、氨基酸等.西红花酸是主要有效成分之一,本文对西红花酸的药理作用进行了较全面的综述,为合理开发利用西红花提供参考.     

Inhibition of in vivo genotoxicity by coffee

The possible role of coffee in modulating the in vivo genotoxicity of the well established genotoxic chemicals, mitomycin C, cyclophosphamide, procarbazine and adriamycin, was evaluated. Coffee was administered orally to mice that received the genotoxic chemicals ip. Genotoxicity was assessed in the bone-marrow micronucleus test. Doses of coffee in the range 225 to 1125 mg (dry weight)/kg body weight caused significant reductions in the in vivo genotoxicity of mitomycin C, cyclophosphamide and procarbazine but not adriamycin. The inhibitory effect was significant when the coffee was given about 2 hr before the genotoxin; there was a lesser effect when coffee was given together with the genotoxin but there was no inhibition when coffee was given 2–4 hr after the genotoxin. An experiment with mitomycin C demonstrated that the reduction in genotoxicity was dependent on the coffee dose. The inhibition of genotoxicity by coffee was observed in bone-marrow cells sampled 24, 48 or 68 hr after injecting cyclophosphamide. Freshly brewed coffee extract, standard instant coffee, decaffeinated instant coffee and freeze-dried home-brew coffee all exerted inhibitory effects.