Effects of ephedra water decoction and cough tablets containing ephedra and liquorice on CYP1A2 and the pharmacokinetics of theophylline in rats

Ephedra water decoction (EWD) and cough tablets containing ephedra and liquorice (maxing cough tablets, MXCT) have been used widely in the treatment of asthma. In the clinic, EWD and MXCT may be prescribed with theophylline, one of the most popular antiasthmatic drugs and a typical substrate of cytochrome P450 (CYP) 1A2. So in the present study the potential effects of EWD and MXCT on CYP1A2 activity and the pharmacokinetics of theophylline in rats were evaluated. In the in vivo CYP1A2 activity research, the rats were given oral caffeine (10 mg/kg) after a 14 day pretreatment with EWD (18 g/kg) and MXCT (0.1, 0.2 or 0.4 g/kg). Then the CYP 1A2 activity was expressed by using the caffeine metabolic ratio (CMR). The results showed that the CMR increased markedly compared with the control groups. In the pharmacokinetics experiment, the rats were given oral theophylline (10 mg/kg) after a 14 day pretreatment with EWD (18 g/kg) and MXCT (0.2 g/kg). The results showed that the AUC_{0‐24 h} and C_max of theophylline were reduced markedly compared with the control groups. These results demonstrated that EWD or MXCT pretreatment obviously induced CYP1A2 activity, therefore, speeding up the metabolism of theophylline. The concomitant use of EWD or MXCT may decrease the effect of theophylline in rats. Copyright © 2011 John Wiley & Sons, Ltd.     

复方钩藤降压片对自发性高血压大鼠血压及炎症水平的影响

目的:试从干预高血压病炎症的角度,为复方钩藤降压片治疗高血压病及防治靶器官损害提供理论依据。方法:21只7周龄雄性自发性高血压大鼠(SHR)随机分为3组:模型组(SHR-S组)、复方钩藤降压片组(SHR-G组)、缬沙坦组(SHR-D组),另7只WKY大鼠为空白对照组(WKY组)。无创测压仪测量血压,连续干预6周,ELISA法测定血清CRP、TNF-α、IL-6的水平。结果:1对血压的影响:自第1周开始,SHR-G组血压均低于SHR-S组(P<0.01),而均较SHR-D组、WKY组高(P<0.01),一直持续到实验结束;实验前后血压值比较:SHR-S组治疗前较治疗后升高(P<0.01),SHR-G组与SHR-D组治疗前较治疗后减低(P<0.01);2对炎症因子的影响:SHR-G组及SHR-D组血清CRP、TNF-α、IL-6水平低于SHR-S组,与SHR-D组比较,SHR-G组除血清CRP水平高于SHR-D组(P<0.01),血清TNF-α、IL-6水平无明显差异(P>0.05)。结论:1SHR血压及炎症水平明显升高;2复方钩藤降压片具有较好的降压疗效;3复方钩藤降压片能有效降低高血压病炎症水平,可能是其有效降低血压及防治靶器官损害的机制,具体的抗炎机制还有待进一步研究。     

Pharmacokinetic and pharmacodynamic interaction of Danshen-Gegen extract with warfarin and aspirin

Ethnopharmacological relevance

Danshen–Gegen (DG) product has clinically been proven to be an effective agent for heart-tonic efficacy by our previous research. In the mean time, herb–drug interactions between DG product and its commonly co-administered drugs, such as aspirin or warfarin need to be explored to ensure its safe clinical usage.

Aim of the study

Current study aims to investigate whether DG extract interacts with warfarin or aspirin when administered concomitantly to ensure the safety and efficacy of their usage.

Material and methods

Five groups of SD rats (n=6/group) received DG alone (0.15 g/kg, human relevant dose), warfarin alone (0.2 mg/kg), warfarin (0.2 mg/kg) in combination with DG (0.15 g/kg), aspirin alone (10.3 mg/kg), or aspirin (10.3 mg/kg) in combination with DG (0.15 g/kg), respectively. DG product was given twice daily for 5 day. Warfain or aspirin were given once daily for 5 day. DG morning doses were given 2 h post that of warfarin/aspirin. Following first dosing on day 5, plasma samples were collected at different time points. For the pharmacodynamic measurement, whole blood was collected at 30 min after DG dosing or at 2.5 h after warfarin/aspirin dosing, and the prothrombin time assay was conducted.

Results

Co-administration of DG with warfarin could significantly decrease the C_max, AUC and the prothrombin time of warfarin (p<0.05). In the mean time, the C_max and AUC of danshensu, the active bioavailable component of DG were significantly increased (p<0.01) in presence of warfarin. Co-administration of DG with aspirin could significantly increase the C_max and AUC of both aspirin (p<0.01) and its metabolite salicylic acid (p<0.01) and significantly decrease the prothrombin time of aspirin (p<0.05). However, the pharmacokinetics parameters of danshensu were not significantly affected by aspirin.

Conclusion

Our animal study indicated that co-administration of DG with warfarin/aspirin can cause significant pharmacokinetic and pharmacodynamic herb–drug interactions in rat.     

Pharmacokinetic interactions between warfarin and kangen-karyu,a Chinese traditional herbal medicine,and their synergistic action

Kangen-Karyu (KGK), containing six herbs, is a formula created under the theory of Chinese traditional medicine (CTM) to invigorate the 'blood' and dispel 'blood stasis', which arises from poor blood circulation. The present study was conducted to evaluate the interactions between KGK and warfarin. Warfarin was administered orally or intravenously to KGK-treated rats, and plasma warfarin concentration and prothrombin time were measured. Although KGK did not influence the absorption or serum protein binding of warfarin, KGK significantly suppressed the metabolism and elimination of warfarin. This interaction depends on the dosage of KGK, and ten times the amount of the human daily dose of KGK did not exhibit pharmacokinetic interaction with warfarin, suggesting that KGK did not influence the effect of warfarin unless the daily dose was strictly maintained. Warfarin alone significantly prolonged mice tail-bleeding time, which was further prolonged significantly by KGK at a dose that did not exhibit pharmacokinetic interactions with warfarin, suggesting that KGK and warfarin might synergistically prevent thrombosis, and that combined use of these drugs could be therapeutically valuable. When physicians or pharmacists utilize combined therapy using warfarin and KGK, they must make a careful effort to check the coagulative status and regulate the dosage of each drug.     

Induction of liver cytochrome P450s by Danshen–Gegen formula is the leading cause for its pharmacokinetic interactions with warfarin

Ethnopharmacological relevance

Although the increased usage of herbal medicine leading to herb–drug interactions is well reported, the mechanism of such interactions between herbal medicines with conventionally prescribed drugs such as warfarin is not yet fully understood. Our previous rat in vivo study demonstrated that co-administration of Danshen–Gegen Formula (DGF), a Radix Salvia miltiorrhiza (Danshen) and Radix Puerariae lobatae (Gegen) containing Chinese medicine formula recently developed for the treatment of cardiovascular disease, with warfarin could cause significant herb–drug interactions. The current study aims to explore the pharmacokinetics-based mechanism of the DGF–warfarin interactions during absorption, distribution and metabolism processes.

Materials and methods

Caco-2 cell monolayer model and rat in situ intestinal perfusion model were used to study the DGF–warfarin interactions during the intestinal absorption processes. Male Sprague–Dawley rats were orally administered warfarin in presence and absence of DGF for consecutive 5 days. The microsomal activity and expression of the liver CYP isozymes were determined and compared among different treatment groups. Blood from the rats administered DGF was employed to evaluate effects of DGF on the plasma protein binding of warfarin.

Results

Absorption studies demonstrated that DGF could potentially increase the intestinal absorption of warfarin (32% and 75% increase of warfarin P_app in Caco-2 and intestinal perfusion models, respectively) via altering the regional pH environment in GI tract. DGF administration could lead to significant increase in liver microsomal activity and mRNA expression of CYP1A1 and CYP2B1, indicating the potential induction on the liver metabolism of warfarin by DGF. Moreover, it has been proven by ex vivo study that the single-dose administration of DGF could decrease the protein binding of warfarin in plasma by at least 11.6%.

Conclusion

Collectively, current study demonstrated that DGF could significantly induce the liver phase I metabolism of warfarin, and to a less extent, potentially increase the intestinal absorption and decrease the plasma protein binding of warfarin. The inductive effects of DGF on the liver phase I metabolism of warfarin may be dominantly responsible for the DGF–warfarin pharmacokinetics interactions.     

Effect of decursin on the pharmacokinetics of theophylline and its metabolites in rats

Ethnopharmacological relevance

Decursin is used as a traditional Asian medicine to treat various women's diseases.

Aim of the study

Herb–drug interaction has become a serious problem since herbal medicine is extensively used in the modern world. This study investigates effects of decursin, on the pharmacokinetics of theophylline, a typical substrate of cytochrome P450 1A2 enzyme, in rats.

Materials and methods

After decursin pretreatment for 3 days, on the fourth day rats were administered decursin and theophylline concomitantly. The blood theophylline and its major metabolites (1-methylxanthine (1-MX), 3-methylxanthine (3-MX), 1-methyluric acid (1-MU), and 1,3-dimethyluric acid (1,3-DMU)) levels were monitored with LC–MS/MS.

Results

The results indicated that the clearance, elimination rate constant (K_el) of theophylline was significantly decreased and area under concentration–time curve (AUC), C_max, half-life was increased in decursin (25 mg/kg) pretreatment when theophylline (10 mg/kg) was given. In the presence of decursin, the pharmacokinetic parameters of three metabolites (1-MX, 1,3-DMU, and 1-MU) were affected and the differences were statistically significant about AUC_24 h parameter.

Conclusion

Our results suggest that patients who want to use CYP1A2-metabolized drugs such as caffeine and theophylline should be advised of the potential herb–drug interaction, to reduce therapeutic failure or increased toxicity of conventional drug therapy.     

早产儿体内茶碱的药动学研究

 目的 研究早产儿血清茶碱的药动学,指导临床合理用药。 方法 11 例早产儿单次静脉滴注氨茶碱注射液 5 mg ·kg^-1 ,采用荧光偏振免疫法测定茶碱血药浓度,利用 DAS 软件拟合求得主要药动学参数。 结果 早产儿茶碱半衰期为（ 43.4 ± 33.2 ） h ,表观分布容积为（ 0.682 ± 0.113 ） L·kg^-1 , 清除率为（ 14 ± 6 ） mL · h ^-1 · kg ^-1 。与国内足月儿茶碱代谢数据比较均有显著差异,与国外早产儿茶碱药动学参数比较半衰期和清除率有显著差异,而表观分布容积无显著差异。 结论 早产儿茶碱药动学与足月儿有显著不同,且个体差异大,临床需根据血药浓度监测来调整用药。     

Piperine Decreases Binding of Drugs to Human Plasma and Increases Uptake by Brain Microvascular Endothelial Cells

We previously reported that piperine, an active alkaloidal principal of black and long peppers, enhances drug bioavailability by inhibiting drug metabolism. Another mechanism influencing drug availability/uptake is its free fraction. Since piperine is highly lipophilic, we hypothesize that it could also interact with drugs through binding displacement and influence their bioavailability. Accordingly, using equilibrium dialysis, we investigated whether piperine alters the binding of model drug ligands, that is flunitrazepam, diazepam, warfarin, salicylic acid, propranolol, lidocaine, and disopyramide to human plasma (n = 4). Since alterations in binding influence drug disposition, we also studied the effects of piperine on the uptake of plasma bound ³H‐propranolol and ¹⁴C‐warfarin by cultured bovine brain microvascular endothelial cells (BMECs). Piperine (1–1000 μM) increased the free fraction (fu) of both albumin and alpha‐acid glycoprotein bound drugs in a concentration‐dependent manner (p < 0.01). Moreover, piperine (10 μM) increased the uptake of ³H‐propranolol and ¹⁴C‐warfarin by BMECs (p < 0.01). In conclusion, our findings provide the first evidence that piperine displaces plasma bound drugs from both albumin and alpha‐acid glycoprotein and facilitates drug uptake across biological membranes (e.g. BMEC). Moreover, it is feasible that piperine may similarly facilitate the transport of drugs into tissues, in vivo, and alter both pharmacokinetics and pharmacodynamics of administered drugs. Copyright © 2017 John Wiley & Sons, Ltd.     

Evaluation of Food–drug Interaction of Guava Leaf Tea

Guava leaf tea (GLT) contains guava leaf polyphenol (Gvpp), which regulates the absorption of dietary carbohydrate from the intestines. Borderline diabetics, who are at high risk of development of diabetes, take GLT to suppress a rapid increase of blood sugar level after meals. However, patients with diabetes in whom diabetic drugs or warfarin as a blood thinner are prescribed also take GLT with the expectation of glycemic control. Therefore, we studied whether GLT had potential for inhibition or induction of cytochrome P450 (CYP) and an influence on the action of warfarin. Extract of guava leaf (GvEx) consists of carbohydrate and polyphenols, which are Gvpp, quercetin, and ellagic acid. These polyphenols, but not GvEx, showed a certain level of inhibition of human‐cDNA‐expressed CYPs. In a comparison of GLT and grapefruit juice, GLT showed weaker inhibition of CYP activities and of midazolam 1′‐hydroxylation than grapefruit juice. Furthermore, neither liver weight nor CYP3A expression in the liver was changed in rats that received GvEx for 90 days compared with the control group. When rats were concomitantly treated with GLT and warfarin, the prolongation of clotting time of blood by warfarin was not influenced. These data suggest that GLT is unlikely to interact with drugs. Copyright © 2012 John Wiley & Sons, Ltd.     

多索茶碱与莫西沙星在大鼠体内药动学的相互作用

 目的考察多索茶碱和莫西沙星在大鼠体内的药动学特性及合用时的相互作用。方法采用高效液相色谱法测定大鼠给药后不同时间的多索茶碱和莫西沙星的血浆浓度。血浆浓度 时间数据用非线性程序WINNONLIN拟合，求得药动学参数。结果两药合用与单独用药时的药-时曲线基本一致,多索茶碱呈一级吸收一级开放式模型，莫西沙星呈一级吸收二室开放式模型，药动学参数无统计学差异。但多索茶碱与莫西沙星合用时，多索茶碱的代谢产物之一茶碱的AUC约是单用多索茶碱时的2倍。结论两药合用药动学上无明显的相互作用, 但莫西沙星有减慢多索茶碱的代谢产物茶碱代谢的趋势，两药可以同时服用，但应注意监测茶碱的血药浓度。     

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??OBJECTIVE Blood tends to deposit in atrium to form thrombus in patients with atrial fibrillation. Patients with diabetes are in high coagulation state, for whom thrombosis is easy to occur. The number of diabetic patients with atrial fibrillation is large. Warfarin is one of the most widely used oral anticoagulants, which can cause major or fatal bleeding, so it is necessary to perform regular monitoring of international normalized ratio (INR) on all patients treated with warfarin. New kinds of antidiabetic drugs are widely used in clinic, among which a lot affect INR levels achieved with warfarin therapy. Clinical pharmacists should pay attention to drug interactions and monitor adverse drug reactions. As a new antidiabetic drug, exenatide has less reports of interaction with warfarin. The characteristic of the interaction between exenatide and warfarin was investigated, with the aim to optimize the rational and individualized medication. METHODS A case was introduced in which exenatide was administrated combined with warfarin, so that the possible mechanism of exenatide affecting to warfarin were analyzed. RESULTS INR declined from 2.13 to 1.57 after exenatide being added, and decreased further to 1.43 with concurrency of the increasing exenatide dose. On the contrary, INR was on rise as result of discontinuing exenatide. At last, INR returned to 1.78 when the patient discharged. CONCLUSION Exenatide inhibited the absorption of warfarin, which lead to INR decline attributed to its effect of slowing down the gastric emptying. When exenatide and warfarin are combined,the dose of warfarin must be adjusted based on INR under clinical monitoring.     

The effect of Compound Danshen Dripping Pills, a Chinese herb medicine, on the pharmacokinetics and pharmacodynamics of warfarin in rats

Aim of the study

Significant pharmacokinetic/pharmacodynamic (PK/PD) interactions between various herbal products and warfarin have recently been reported. The present study was conducted to determine whether Compound Danshen Dripping Pills (CDDP), a Chinese herb medicine used for the treatment of cardiovascular diseases, interacts with warfarin when administered concomitantly.

Materials and methods

Each day for 7 days two groups of rats were treated orally with CDDP (50 mg/kg and 250 mg/kg, twice daily), and the control group received similar treatment with appropriate volumes of water only. Sixty minutes after the final daily administration of CDDP or water, an aqueous solution of warfarin (0.2 mg/mL) was given to each rat at a dose of 1.0 mg/kg, and blood samples were collected at 0, 0.5, 1, 2, 4, 8, 12, 24, 36, and 48 h after warfarin-treatment. The concentration of warfarin in blood plasma was determined by high performance liquid chromatography (HPLC). Prothrombin time (PT) in blood plasma was measured using thromboplastin reagent.

Results

Excellent linearity was found between 0.05 and 10 μg/mL with a lower limit of quantitation (LLOQ) of 0.05 ng/mL (r > 0.999); moreover, all the validation data including accuracy and precision (intra- and inter-day), were within the required limits. No significant differences were found in PT_max and AUC_PT 0-∞ between the two CDDP-treated groups and the control. Besides, there was little alteration in any of the pharmacokinetic parameters of warfarin between the two CDDP-treated groups and the control.

Conclusion

The concomitant application of CDDP and warfarin did not give rise to significant effect on the pharmacodynamics of warfarin, and practically no effect on its pharmacokinetics. It was speculated that the PK/PD interactions between CDDP and warfarin was likely to be negligible as long as the patients took CDDP at a normal dose.     

立体选择性高效液相色谱法测定血浆中华法林对映体浓度

 目的：建立血浆中华法林对映体浓度的立体选择性高效液相色谱法。方法：血浆标本经碱洗、酸化和乙醚提后，与碳苄氧基-L-脯氨酸进行柱前衍生化为差向体。以正己烷-乙酸乙酯-乙酸-甲醇为流动相，经普通硅胶柱分离对映体和在紫外λ313 nm处检测。结果：对映体标准曲线范围0～4.0 mg/L,最低检出限＜0.1 mg/L,批内，批间平均RSD均＜7%,平均回收率100.22%，临床上常用药物对本法没有干扰。结论：本法简便可靠，可用于临床华法林对映体的药动学和药效学研究。     

茶碱治疗早产儿原发性呼吸暂停的药效学研究

 目的 研究茶碱治疗早产儿原发性呼吸暂停的药效学,指导临床合理用药。方法 21例诊断为原发性呼吸暂停的早产儿静脉滴注氨茶碱,（7±1d后采用荧光偏振免疫法测定茶碱血药浓度,记录呼吸暂停次数和给氧条件,观察不良反应。结果 测得65.8%（25/38茶碱血清浓度分布在3~6 mg·L^-1之间。呼吸暂停治疗有效率为81.0%。茶碱给药后呼吸暂停次数发作明显减少,给药前后对给氧条件无显著差异。其中有3例患儿出现窦性心动过速,7例患儿出现多尿。结论 需根据血药浓度和临床表现来共同判定茶碱剂量是否有效。临床需密切关注窦性心动过速和多尿的不良反应。     

中药缓释剂的药代动力学研究

本文从中药缓释剂的药代动力学研究在中药现代化中的作用出发，以肝苏缓释胶囊的药代动力学研究为例，对中药缓释剂药代动力学的方法进行分析和评价，总结各自的优缺点。并根据大量文献资料及作者在肝苏缓释胶囊药代动力学研究过程中的体会，对中药缓释剂动力学研究的难点及发展趋势进行分析和概括。中药缓释剂药代动力学的研究还处于探索阶段，其理论及技术体系的创新，必将随着科学技术的发展进一步规范和成熟。     

Pharmacokinetic changes of unbound theophylline are due to plasma protein binding displacement and CYP1A2 activity inhibition by baicalin in rats

Ethnopharmacological relevance

Baicalin is one of the major bioactive constituents of Scutellariae Radix, the root of Scutellariae baicalensis Georgi and possesses a wide variety of pharmacological properties.

Aim of the study

To elucidate the effect of baicalin on the pharmacokinetics of theophylline in rats, focusing on plasma protein binding displacement and inhibition effect on CYP1A2 in vivo and in vitro.

Materials and methods

The study was a randomized, three-period crossover design. Nine rats were given saline (control) or 450 mg/kg baicalin (dosage regimen A or B). Dosage regimen A was administered once at 0 h. Dosage regimen B was divided into three dosages (225,112.5, 112.5 mg/kg) and was given at 0, 2 and 4 h, respectively. Then theophylline (5 mg/kg, i.v.) was administered immediately. The effect of baicalin on CYP1A2 activity was determined by metabolism of phenacetin in vitro and plasma protein binding of theophylline was determined by ultrafiltration.

Results

C_max decreased from (12.4±1.6) to (8.7±0.9) and (8.6±2.0) mg/L, T_1/2 increased by 116 and 96%, V_d increased by 51 and 49% for total theophylline in rats treated with dosage regimen A and B of baicalin, respectively. C_max was significantly increased, V_d decreased by 43 and 29% for unbound theophylline in rats treated with dosage regimen A and B of baicalin, respectively (P<0.01). T_1/2 of unbound theophylline increased by 104% only in rats treated with dosage regimen B. No significant effects on the CL and AUC of both total and unbound theophylline were observed in the rats treated with dosage regimen A, but the CL decreased and AUC increased for total theophylline and CL decreased for unbound theophylline in the group treated with dosage regimen B (P<0.05). Correlation analysis showed that the mean unbound theophylline (%) and mean baicalin concentration was in good correlation (P<0.01). Baicalin decreased metabolism of phenacetin and exhibited a mixed-type inhibition in rat liver microsomes, with a K_i value of 88.1 μM in vitro. Moreover baicalin was a competitive displacer of theophylline from plasma protein in vitro.

Conclusions

The changes in C_max, T_1/2, CL and AUC of theophylline due to baicalin may be attributed to two mechanisms, plasma protein binding displacement and CYP1A2 activity inhibition.     

多糖放射性同位素标记及其体内药动学应用的研究进展

多糖具有良好的药理活性和较低的毒副作用,关于天然多糖药理活性的报道也是层出不穷。随着对多糖理化性质研究的进一步深入,多糖作为生物材料也逐渐用于新制剂的开发。但是相较于多糖药理活性和作为生物材料的研究,多糖体内药动学的研究十分匮乏,这严重限制了多糖进一步的开发应用。目前,体外放射性同位素标记成为了多糖体内药动学研究的重要手段,本研究总结了用于多糖标记的各种放射性同位素,并分析了不同放射性同位素在多糖体内药动学研究中的特点,以及影响多糖药动学的因素和基于多糖体内药动学特征的应用。对多糖体内药动学的深入研究,能够为多糖作为药品和生物材料的开发提供重要的指导。     

化学药及中药缓释制剂的药动学研究进展

目的综述化学药、中药缓释制剂的药动学研究进展,为开展中药缓释制剂设计提供参考。方法综述液相色谱法、离子选择电极法、气相色谱法、质谱联用技术以及串联质谱法等在化学药缓释制剂药动学中的应用;中药单体、中药有效部位、中药复方缓释制剂的药动学研究进展。结果化学药检测限越来越低;中药缓释制剂常应用血药浓度法和药理效应法进行药动学的研究。结论现代分析技术可以更加准确、稳定地测定化学药的血药浓度;血药浓度法和药理效应法对测定中药缓释制剂药动学具有针对性。化学药缓释制剂药动学文献资料可指导中药缓释制剂药动学研究。     

探针药物法评价柴胡生品及醋炙品对细胞色素P450酶的影响（英文）

目的：研究柴胡生品及醋炙品对细胞色素P450酶的影响。方法：采用多探针技术,应用高效液相色谱三重四级杆串联质谱（HPLC-MS/MS）测定连续给予7天柴胡生品或醋炙品前后大鼠血浆中相应的探针药物咪达唑仑、奥美拉唑、甲苯磺丁脲、氯唑沙宗、右美沙芬和咖啡因的浓度及其药代动力学参数。结果：连续7天给予柴胡生品或醋炙品后,咪达唑仑、氯唑沙宗和右美沙芬的血药浓度均显著下降,AUC和T1/2显著减小（P〈0.05）,清除率增大,而咖啡因的血药浓度无明显变化;连续7天给予柴胡生品后,奥美拉唑的消除明显加快,而连续7天给予柴胡醋炙品正常剂量后,奥美拉唑的代谢无明显变化;连续7天给予柴胡生品高剂量后,甲苯磺丁脲的代谢加快。结论：柴胡生品及醋炙品对CYP2E1、CYP2D6和CYP3A4均产生诱导作用,对CYP1A2不产生诱导作用;柴胡生品及醋炙品对CYP2C9和CYP2C19的影响存在差异,这种差异可能是柴胡经炮制后作用发生变化的原因。     

Relaxant effects of Rosa damascena on guinea pig tracheal chains and its possible mechanism(s)

Several therapeutic effects including hypnotic, antispasmodic, treatment of abdominal and chest pain and strengthening the heart have been described for the flowers of Rosa damascena. Therefore in the present study, the relaxant effects of ethanolic extract and essential oils of Rosa damascena on tracheal chains of guinea pigs were examined. The relaxant effects of four cumulative concentrations of ethanolic extract (0.25, 0.5, 0.75, and 1.0g%) and essential oils (0.25, 0.5, 0.75, and 1.0vol.%) in comparison with saline as negative control and four cumulative concentrations of theophylline (0.25, 0.5, 0.75, and 1.0mM) were examined by their relaxant effects on precontracted tracheal chains of guinea pig by 60mM KCl (group 1, n=5) and 10microM methacholine in two different conditions including: non-incubated tissues (group 2, n=8) and incubated tissues with 1microM propranolol and 1microM chlorpheniramine (group 3, n=5). In group 1 experiments two final concentrations of essential oil and theophylline and only final concentration of ethanolic extract showed relaxant effects compared to that of saline (p<0.01-0.001). In group 2 three higher concentrations of ethanolic extract and theophylline and all concentrations of essential oil showed concentration dependent relaxant effects compared to that of saline (p<0.05-0.001). In addition, the effect of 0.25 and 0.5g% of essential oils in group 2 was significantly higher than those of theophylline and ethanolic extract (p<0.01 for all cases). However, in group 3 experiments the extract and essential oil of Rosa damascena did not show any significant relaxant effect. There were significant correlations between the relaxant effects and concentrations for ethanolic extract and essential oil and theophylline in groups 1 and 2. These results showed a potent relaxant effect of Rosa damascena on tracheal chains of guinea pigs that was comparable to that of theophylline at concentrations used.