Herb-drug interaction in the protective effect of Alpinia officinarum against gastric injury induced by indomethacin based on pharmacokinetic, tissue distribution and excretion studies in rats

Alpinia officinarum Hance of the Chinese traditional herb for the treatment of emesis, abdominal pain and diarrhea has been used to counteract gastric disease induced by indomethacin in rats without obvious side effects. However, the role of herb-drug interaction between indomethacin and A. officinarum based on pharmacokinetic, tissue distribution and excretion still remains unknown. In this study, an ultra-fast liquid-tandem mass spectrometry(UFLC-MS/MS) method was developed for simultaneous determination of indomethacin and its three metabolites, O-desmethylindomethacin(ODI), deschlorobenzoylindomethacin(NDI) and indomethacin acyl-b-D-glucuronide(IDAbG) by oral administration of indomethacin solution with and without the ethanolic extract of A. officinarum and applied to comparative pharmacokinetic, tissue distribution and excretion studies. Our results clarified that oral administration of A. officinarum produced significant alterations in the pharmacokinetic parameters of indomethacin. And the pharmacokinetic interaction between indomethacin and A. officinarum reduced the systemic exposure of indomethacin and increased its elimination. Tissue distribution results demonstrated that co-administration of A. Officinarum could not reduce the accumulation of indomethacin in the target tissue of the stomach, but could accelerate the excretions of indomethacin and its three metabolites including ODI, NDI and IDAb G in the bile and feces of rats in the excretion study.Therefore, A. Officinarum might have a gastrointestinal protective effect through the interaction role with indomethacin based on the pharmacokinetics and excretion in rats.

Potential Mechanism of Herb-Drug Interaction Mediated by Angelica dahurica: Inhibition on CYP3A Enzymes in Rats

Angelica dahurica is commonly referred to as ‘Baizhi’ in China and has been noted for its therapeutic significance. The major active ingredients of Angelica dahurica is coumarin, which is reported as a kind of potent inhibitor of cytochrome P450 enzymes (CYP450s). The aim of this study was to investigate the inhibition of CYP3A enzymes by total coumarin extract (TCE) obtained from dried root of Angelica dahurica by using in situ single pass intestinal perfusion (SPIP) and in situ liver perfusion in rats. When midazolam (MDZ) which is a substrate of CYP3A co-perfused with TCE (198 μg/mL) from Baizhi in duodenum and ileum segments, the Peff of MDZ has increased significantly compared with the MDZ single perfused group (p 0.05) (n = 6). During in situ liver perfusion study, the results demonstrated that, 3 days oral administration of TCE obtained from Baizhi could significantly reduce the elimination rate of MDZ in the perfusate (p Angelica dahurica extract co-administrated with drugs which are the substrates of CYP3A, much more attention should be paid rather than that of other CYP450 enzymes. These findings may facilitate in predicting possible herb-drug interactions (HDIs) when Angelica dahurica is used in combination with other drugs, and decrease the incidence of the CYP450-mediated HDIs.

Carboxylesterases mediated herb-drug interactions:a systematic review

Esterases participate in the metabolism of^10%of the clinical drugs that contain ester or amide bonds,but the esterases mediated drug/herb-drug interactions(DDIs or HDIs)have not been reviewed in depth.Carboxylesterases(CEs),the most abundant esterases expressed in the metabolic organ of mammals,play a pivotal role in hydrolysis of a variety of endogenous and xenobiotic esters.In the human body,two predominant carboxylesterases including hCE1 and hCE2 have been identified and extensively studied over the past decade.These two enzymes have been found with hydrolytic activity towards a variety of endogenous esters and ester-containing drugs.Recent studies have demonstrated that strong inhibition on hCEs may slow down the hydrolysis of CEs substrates,which may affect their pharmacokinetic properties and thus trigger potential DDIs or HDIs.Over the past decade,many herbal extracts and herbal constitutes have been found with strong inhibitory effects against CEs,and their potential risks on herb-drug interactions(HDIs)have also attracted much attention.This review focused on recent progress in hCEs mediated herb-drug interactions.The roles of hCEs in drug metabolism,the inhibitory capacities and inhibition mechanism of a variety of herbal extract and herbal constitutes against hCEs have been well summarized.Furthermore,the challenges and future perspectives in this field are highlighted by the authors.All information and knowledge presented in this review will be very helpful for the pharmacologists to deeper understand the metabolic interactions between herbal constituents and hCEs,as well as for clinical clinicians to reasonable use herbal medicines for alleviating hCEs-associated drug toxicity or avoiding the occurrence of clinically relevant hCEs-mediated HDIs.

Potential herb-drug interactions between anti-COVID-19 drugs and traditional Chinese medicine

Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has spread worldwide.Effective treatments against COVID-19 remain urgently in need although vaccination significantly reduces the incidence,hospitalization,and mortality.At present,antiviral drugs including Nirmatrelvir/Ritonavir(Paxlovid^(TM)),Remdesivir,and Molnupiravir have been authorized to treat COVID-19 and become more globally available.On the other hand,traditional Chinese medicine(TCM)has been used for the treatment of epidemic diseases for a long history.Currently,various TCM formulae against COVID-19 such as Qingfei Paidu decoction,Xuanfei Baidu granule,Huashi Baidu granule,Jinhua Qinggan granule,Lianhua Qingwen capsule,and Xuebijing injection have been widely used in clinical practice in China,which may cause potential herb-drug interactions(HDIs)in patients under treatment with antiviral drugs and affect the efficacy and safety of medicines.However,information on potential HDIs between the above anti-COVID-19 drugs and TCM formulae is lacking,and thus this work seeks to summarize and highlight potential HDIs between antiviral drugs and TCM formulae against COVID-19,and especially pharmacokinetic HDIs mediated by metabolizing enzymes and/or transporters.These well-characterized HDIs could provide useful information on clinical concomitant medicine use to maximize clinical outcomes and minimize adverse and toxic effects.

7576张含丹参-当归药对的门诊中药饮片处方回顾性分析

目的:了解江苏省中西医结合医院南部院区/南京市溧水区中医院(以下简称“该院”)含丹参-当归药对的门诊中药饮片处方情况,探究该药对的临床配伍应用规律,为该药对的合理使用提供参考。方法:采用回顾性分析方法,统计2020—2022年该院使用丹参-当归药对的7576张门诊中药饮片处方,对患者的性别、年龄、处方药味数、金额、疗程、涉及科室及病症、使用剂量、常用的配伍比例及配伍饮片等相关内容进行统计分析。结果:7576张含丹参-当归药对的门诊中药饮片处方中,女性患者处方数约为男性患者处方数的3.21倍(5776张vs.1800张),>30~40岁患者居多。单张处方的中药饮片味数多集中在16~20味,开具的疗程均<30 d。丹参的使用剂量为《中华人民共和国药典》规定的10~15 g的处方有6490张,占85.67%;当归的使用剂量为《中华人民共和国药典》规定的6~12 g的处方有6608张,占87.22%。处方数排序居前3位的科室依次为国医堂、妇科及脑病科,治疗的病证以冲任失调、心脾两虚及气滞血瘀证为主。单张处方中丹参用量大于等于当归用量,丹参与当归的配伍比例以1∶1为多,高频配伍饮片为茯苓、川芎、炒白芍。结论:基于处方用药分析,该院含丹参-当归药对的门诊中药饮片处方基本合理,为丹参-当归药对的使用剂量范围及配伍规律研究提供了数据支持,有利于促进临床合理用药。

基于中药特色技术传承概述广东芸香科道地药材

基于中药传统特色技术,文章通过现场观摩调研与文献检索,概述在十大广药中占有1/3的芸香科药物的药用历史、产地采收加工、性状鉴别特点。芸香科药物多含挥发油,具有芳香气,大部分具有宽中理气的功效,临床应用广泛。据考证,柚类橘红始自清代,此前使用橘类橘红;广陈皮主产区在新会地区,也称新会陈皮,药用时间至今约有600年;广佛手以肇庆高要地区产量多且质优,“佛手柑”的记载最早见于元朝。化橘红的传统加工方法是将化州柚的外层果皮切成角状,加工成7角的毛橘红药材,称为“毛七爪”;新会陈皮需在新会地区内陈化三年,方可称为“新会陈皮”。化橘红鉴别特点为表面密被柔软毡状细绒毛,有油点,气清香;新会陈皮“鬃眼”明显,对光照视呈半透明状,香气浓郁。广佛手切面的外皮呈黄色,肉呈白色,俗称“金边白肉”。文章基于中药传统理论、技术对广东地区芸香科道地药材进行概述,以期守正创新,使中药的传统特色技术得到传承发展。

Potential Herb-Drug Interaction in the Prevention of Cardiovascular Diseases during Integrated Traditional and Western Medicine Treatment

The combination of herbs and drugs is one of the most important approaches in the prevention and treatment of diseases in the integrated traditional and Western medicine （ITWM）. While most medical practices have proved that the combination of herbs and drugs led to a clinical efficacy that was often superior to merely using only one of them; results from some studies have triggered adverse reactions to such an approach. Since few herb-drug interaction studies were carried out during treatments combining herbs and drugs, it really restricts the development of treatment and treatment theory of the combination of herbs and drugs. Given that herb-drug interactions may occur through the main pathway of cytochrome P450 enzymes and transporters; then to exhaustively study the role and impact of herbs in drug metabolism, as well as to establish a corresponding database, is of greatsignificance for guiding the rational combination of herbs and drugs. When the herb-drug interaction information platform is implemented, we would get at ease a reasonable herb-drug prescription to achieve a better outcome, reduce dosage of some expensive drugs preserving the same efficacy, or even reduce some side effects of particular drugs; which might also promote the dynamic combination of Chinese and Western medicine, and accelerate the theory development of ITWM.

Herb-drug Interaction:An Emerging Issue of Integrative Medicine

With the increasing enhancement of people＇s awareness of self-care,the voice for humans to return to nature is growing louder and louder.Drugs with natural plants as raw materials are increasingly favored by people all over the world for their unique advantages in preventing and curing diseases, rehabilitation and health care,especially in Europe,

4种单一中草药及其配伍用药对动物肠道益生菌乳杆菌的促进作用

试验旨在探究4种单一中草药五味子、山楂、木香、白术及其配伍用药对益生菌乳杆菌的激活增殖作用。试验测定添加不同单一和联合配伍中草药前后乳杆菌培养液OD值、菌落数变化情况,探究其激活益生菌乳杆菌增殖的最佳剂量浓度。建立阿莫西林型肠道菌群失衡模型,考察单一中草药及联合配伍中草药对小鼠肠道内乳杆菌的影响。结果显示,五味子、山楂和白术对乳杆菌的最佳激活增殖浓度均为0.250 g/mL,木香最佳激活增殖浓度为0.500 g/mL;五味子+山楂、五味子+白术、五味子+木香的最佳激活增殖浓度均为0.125 g/mL;白术+山楂、木香+山楂的最佳激活增殖浓度均为0.250 g/mL;白术+木香的最佳激活增殖浓度为0.450 g/mL。研究表明,在畜牧生产中,建议添加五味子与山楂水提液的最佳浓度为0.250 g/mL,五味子+山楂、五味子+白术、五味子+木香的最佳添加浓度均为0.125 g/mL,能够最大限度地发挥中草药对动物肠道乳杆菌的促进作用。

荭草苷对UGT1A1代谢伊立替康的抑制作用

目的探究荭草苷对野生型尿苷二磷酸葡萄糖醛酸转移酶1A1(UGT1A1)及其常见突变体UGT1A1*6酶活性的影响,定量预测含有荭草苷的中草药与伊立替康同时服用时发生草药-药物相互作用的风险。方法建立体外孵育体系,将系列浓度的荭草苷与SN-38共同孵育,用超高效液相色谱-串联质谱法(UPLC-MS/MS)测定SN-38代谢产物SN-38葡萄糖醛酸酯(SN-38G)的生成速率,考察荭草苷对SN-38葡萄糖醛酸化的影响。结果荭草苷对UGT1A1*1和UGT1A1*6的半抑制浓度(IC50)分别为19.04、34.35μmol/L,计算得到的Ki值分别为9.32、19.63μmol/L。利用体外-体内外推法(IVIVE)定量预测表明口服含有荭草苷的中草药与伊立替康联合使用时,会导致SN-38的血浆浓度-时间曲线下面积(AUC)至少增加87%。结论荭草苷有可能抑制UGT1A1的活性而引发伊立替康的不良反应,为合理使用含荭草苷的中草药与伊立替康提供了理论指导。

从单味中药的剂量选择探讨随证施量与临床用药安全

“随证施量”是“辨证论治”之后重要的一环,考虑患者体质、年龄、病程等个体化差异,是中医个体化治疗的体现。总结现代医家关于附子、大黄、水蛭、天花粉、淫羊藿五味常用中药在“随证施量”过程中超剂量用药情况,不同剂量针对疾病的轻重程度和相关指标的改善情况,希望能够拓宽药物临床剂量使用范围,为临床提供理论依据。

Herb-drug enzyme-mediated interactions and the associated experimental methods： a review

OBJECTIVE: To review the interactions between herbs and widely used drugs and summarize the associated experimental methods.METHODS: Definite herb-drug interactions were obtained by searching Pub Med, other large overseas databases and summarizing new researches from China. We summarize some methods to assess the interaction between herbs and drugs involving microsomal, cell culture and animal experiments, and clinical trials, classifying this method as single ingredient herbs, crude herb extracts, andherbal formulae.RESULTS: Many herbs interact with drugs through a complex cytochrome P450 and/or P-glycoprotein mechanism. Herb-induced enzyme inhibition and/or induction may result in enhanced and / or decreased plasma, tissue, urine and bile drug concentrations, leading to a change in a drug's pharmacokinetic parameters and resulting in the improper treatment of patients and potentially severe side effects. Use of an appropriate method for comprehensively assessing herb-drug interactions can minimize clinical risks. Different methods were used by researchers to assess the pharmacological changes of drugs in vivo and in vitro and the mechanisms of the interactions from microsomal, cell culture and animal experiments, and clinical trials are discussed in this review.CONCLUSION: Co-medication with herbs can result in changes in pharmacological effects of many drugs. This review describes the assessment of single-ingredient herbs, crude herb extracts, and herbal formulae. When choosing a research method to investigate herb-drug interactions, the properties of the drugs and herbs should be considered.

腹泻奶牛源大肠杆菌的分离鉴定及中药的体外抑菌效果

为了研究贵州毕节某奶牛场荷斯坦奶牛发生腹泻的原因,从该奶牛场采集50份新鲜粪便样本,通过平板划线法对大肠杆菌进行分离纯化和PCR鉴定,采用K-B纸片法进行药物敏感试验,并对多种耐药基因进行PCR检测。针对多重耐药菌,选取虎耳草和杜鹃花2种中草药进行体外抑菌效果研究。结果显示:从腹泻奶牛粪便中分离出31株细菌,其菌落形态和生化特性与大肠杆菌相符;16S rRNA基因测序比对发现该牛场分离的菌株与NCBI数据库中大肠杆菌参考菌株的同源性达到99.65%~99.86%,确定该奶牛场的腹泻病原为大肠杆菌;药敏试验发现该牛场来源的大肠杆菌对多种抗生素(强力霉素、红霉素、青霉素G和四环素)耐药,而对磺胺异恶唑、头孢曲松、环丙沙星、庆大霉素、多黏菌素B、磷霉素等10种抗生素敏感;PCR扩增相关耐药基因发现,导致该牛场腹泻的大肠杆菌携带2种β-内酰胺类(blaCTX-M、blaTEM),4种四环素类(TetD、TetB、TetK、TetD、TetA),2种氨基糖苷类(ant(3″)-Ia、rmtB)和3种喹诺酮类(qnrS、qepA、oqxA)耐药基因。体外抑菌研究发现,杜鹃花(3.125 mg/mL)的水提物有显著的抑菌效果。试验结果可为该奶牛场防治大肠杆菌性腹泻提供用药指导,同时为开发替抗中草药产品提供了依据。

矿物药琥珀的本草考证

琥珀为我国传统常用药材,距今已有1400余年的药用历史。历代本草关于琥珀来源说法不一,多有关于琥珀真伪鉴别的记载,目前市售琥珀品质亦存在质量参差不齐等问题。经考证,古代本草大多将琥珀列入寓木部或寓木类,然本品实为松脂化石,而产地、品质、采收、加工、炮制及功效等方面古今差异不大。通过本草文献学研究方法,对矿物药琥珀进行系统的本草考证,明确了历代本草中药用琥珀的正品来源及产地,以期规范琥珀药材的流通及应用,合理开发和利用琥珀药材资源。

特应性皮炎治疗的新进展

特应性皮炎(AD)是一种与遗传过敏素质有关的慢性、复发性、炎症性、瘙痒性皮肤病。传统治疗以修复皮肤屏障、外用糖皮质激素及钙调磷酸酶抑制剂、系统治疗、光疗等为主,通常难以达到临床治愈,故有一定局限性。近年来基于AD的病因与发病机制研究,生物制剂和小分子靶向药物已应用于AD的临床治疗,但因价格昂贵而受众面小,故学者亦在尝试探索其他治疗方法如中药提取物、变应原免疫治疗和微生态调节等。本文综述AD治疗的新进展。

Cocktail探针药物法评价玄参对大鼠细胞色素P450酶的影响

采用Cocktail探针药物法研究玄参对大鼠4种细胞色素P450(CYP3A4、CYP2D6、CYP2C9和CYP1A2)活性的影响.24只健康雄性SD大鼠(Sprague-Dawley rat)随机分为三组:A组为多剂量组,连续7 d给予150 mg/kg玄参.B组为单剂量组,第7 d给予150 mg/kg玄参.C组为对照组.第7 d,各组在给予玄参30 min后,再给予4种探针药物的混合溶液,其中咪达唑仑3 mg/kg、美托洛尔20 mg/kg、氯沙坦5 mg/kg、非那西汀5 mg/kg,分别用以评价CYP3A4、CYP2D6、CYP2C9和CYP1A2的活性.根据设定的时间点收集大鼠血浆样品,处理后的样品采用超高效液相色谱-串联质谱(UHPLC-MS/MS)法测定样品中4种探针药物的浓度.结果可见,玄参对大鼠体内氯沙坦和非那西汀的药代动力学参数无显著影响.单剂量的玄参导致咪达唑仑代谢减慢,多剂量给予的玄参显著诱导美托洛尔代谢.玄参对CYP2C9和CYP1A2的酶活性无明显影响,可以抑制CYP3A4或诱导CYP2D6的酶活性.

基于德尔菲法的中草药肝毒性评估量表研制

目的构建中草药肝毒性评估量表,对中草药及其相关制剂的肝毒性进行综合性证据评估。方法通过文献荟萃分析法结合专家访谈法收集国内外含有中草药肝毒性有效信息的数据库并进行遴选。制作专家咨询德尔菲问卷,采用德尔菲法进行2轮专家咨询,分析专家权威系数、意见集中度及一致性。根据专家意见进行修改和调整后计算指标条目权重,结合综合评价模型构建中草药肝毒性评估量表,并进行信效度测试。使用ROC曲线确定最佳诊断阈值。结果研究小组初步整理出9个相关因素,共涉及12个相关指标。经2轮咨询后,各指标条目咨询的专家共识度均不低于70%。第一、二轮咨询中Kendall协调系数W分别为0.162(χ^(2)=68.88,P<0.001)、0.246(χ^(2)=27.50,P<0.001)。最终形成包含8个条目的中草药肝毒性评估量表。量表的内容效度指数(I-CVI)>0.78,平均内容效度指数(S-CVI/Ave)=0.84,K^(*)=0.83,Cronbach’α系数为0.656。诊断模型ROC曲线下面积为0.906,Youden指数确定最佳阈值为0.99,灵敏度为95%,特异度为75%。根据四分位数法确定评分≥1.44(P75)者为高风险药物。结论初步建立了适合中草药肝毒性评估的工具量表,可用于评估中草药潜在的肝毒性,优化现有毒性药材评价体系,及时发现“高风险”“高警戒”中草药,为临床安全用药提供参考依据。

药食同源中药联合抑菌作用及抑菌喷雾剂的研制

探讨7味药食同源中药水提取物及其联用对大肠杆菌、金黄色葡萄球菌、白色念珠菌的体外抑菌效果,并将其应用于抑菌喷雾剂。采用水提法提取药液,用纸片扩散法测得单药最低抑菌浓度(MIC)及最小杀菌浓度(MBC),同时以“棋盘法+中药互配”筛选对上述致病菌具有较强协同抑制作用的药物组合,并确定适宜的药物配伍制备抑菌喷雾剂。结果显示,7味药食同源中药对3种供试病原菌均具有不同程度的抑菌效果,五味子、金银花、牡丹皮、肉桂、白芍和山楂的抑菌作用较强,其对大肠杆菌的抑菌圈直径为12.50~26.50 mm,最低抑菌浓度(MIC)<250.00 mg/mL,最小杀菌浓度(MBC)<500.00 mg/mL;其中,五味子的抑菌作用最显著,对大肠杆菌、金黄色葡萄球菌、白色念珠菌的MIC分别为31.25 mg/mL、15.62 mg/mL、250.00 mg/mL。互配试验结果表明,10种不同的药物组合对3种供试菌的联合抑菌作用各不相同,牡丹皮和肉桂的配伍组合对大肠杆菌以及肉桂和五味子的配伍组合对金黄色葡萄球菌的联合抑菌指数(FICI)均≤0.50,表现为协同作用,其中肉桂和白芍、牡丹皮和白芍的配伍组合对致病菌也有协同或相加作用。因此,选择牡丹皮、肉桂、五味子、白芍4味药食同源中药制备抑菌喷雾剂。同时初步确定药食同源中药抑菌喷雾制剂的制备工艺流程为在40℃水浴中,向中药提取液中依次搅拌加入0.2%苯甲酸、1.0%吐温-80和5.0%1,2-丙二醇。多种药食同源中药具有抗菌作用,且合理的配伍可以产生协同增效的效果,为无毒副作用抗菌喷雾剂的开发奠定了基础。

数据可视化技术在药品监管中的应用探索——以我所近三年中药材及中药饮片重金属监测为例

目的:通过对我所近三年中药材及饮片重金属监测数据进行可视化分析,展示应用数据可视化技术可为药品监管部门提供决策支持。方法:采用Power BI软件,对我所近三年中药材及中药饮片重金属检测数据进行多维度可视化分析,挖掘并发现中药材及中药饮片在重金属污染上存在的问题。结果:依托Power BI的可视化图表呈现,可使药品监管部门快速直观地发现中药材及中药饮片重金属污染问题及其规律,助力监管部门制定监管方案。结论:基于Power BI的数据分析和可视化展示,可为药品监管机构智慧监管、科学监管、精准监管提供高水平技术支撑。

马蔺子本草考证

目的:对马蔺子进行系统本草考证,为该药材质量标准的制订提供参考,也为进一步挖掘其新的药用功效提供线索。方法:查阅历代本草及中医典籍,比较马蔺子在16个地方标准中质量标准的差异,从其名称、产地、形态、药性及功用等方面进行本草考证。结果:马蔺子以“蠡实”之名始载于《神农本草经》,且别名众多,清代以后均以马蔺子作为药名;植物形态描述及绘图表明,马蔺子无混淆品,且与《中华本草》记述基本一致;古代本草记载产地以河北冀县最为道地,且清代以后全国各地均有出产;药性方面主要为性温、平,味甘,无毒,归肝、脾、胃、肺经,有清热利湿、解毒消肿、止血的功效。可治疗小便不利、寒痹湿滞、便血、寒疝、血崩、白带、痈肿等,其外敷还可治疗虫蛇咬伤。结论:通过对马蔺子进行本草考证,可为国家制定该药材的中药质量标准提供科学依据,为进一步开发其新功效提供重要参考。