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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

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Journal of Pharmaceutical Analysis 2021年第2期11卷 200-209页

作者： Xuguang Zhang Zhenrui Xie Xun Chen Junqiang Qiu Yinfeng Tan Xiaoliang Li Hailong Li Junqing Zhang Key Laboratory of Tropical Translation Medicine of Ministry of Education Hainan Provincial Key Laboratory for Research and Development of Tropical HerbsSchool of PharmacyHainan Medical UniversityHaikou571199China

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 ***, A. Officinarum might have a gastrointestinal protective effect through the interaction role with indomethacin based on the pharmacokinetics and excretion in rats.

关键词： Alpinia officinarum Hance Indomethacin herb-drug interaction Pharmacokinetics Tissue distribution Excretion

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herb-drug interaction:An Emerging Issue of Integrative Medicine

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Chinese Journal of Integrative Medicine 2010年第3期16卷 195-196页

作者：徐浩陈可冀 National Integrative Medicine Center for Cardiovascular Disease China-Japan Friendship Hospital

With the increasing enhancement of people＇s awareness of self-care,the voice for humans to return to nature is growing louder and *** 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,

关键词： In herb-drug interaction

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Potential herb-drug interaction in the Prevention of Cardiovascular Diseases during Integrated Traditional and Western Medicine Treatment

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Chinese Journal of Integrative Medicine 2015年第1期21卷 3-9页

作者：王肖龙 Cardiovascular Department Shanghai Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine

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.

关键词： integrated traditional and Western medicine herb-drug interaction cytochrome P450 transporter cardiovascular disease

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

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Acta Pharmaceutica Sinica B 2023年第9期13卷 3598-3637页

作者： Ling Ye Shicheng Fan Pengfei Zhao Chenghua Wu Menghua Liu Shuang Hu Peng Wang Hongyu Wang Huichang Bi NMPA Key Laboratory for Research and Evaluation of drug Metabolism&Guangdong Provincial Key Laboratory of New drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Guangdong Provincial Key Laboratory of New drug Design and Evaluation School of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhou 510006China

Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has spread *** treatments against COVID-19 remain urgently in need although vaccination significantly reduces the incidence,hospitalization,and *** present,antiviral drugs including Nirmatrelvir/Ritonavir(Paxlovid^(TM)),Remdesivir,and Molnupiravir have been authorized to treat COVID-19 and become more globally *** the other hand,traditional Chinese medicine(TCM)has been used for the treatment of epidemic diseases for a long ***,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 ***,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 *** well-characterized HDIs could provide useful information on clinical concomitant medicine use to maximize clinical outcomes and minimize adverse and toxic effects.

关键词： COVID-19 Antiviral drugs Anti-COVID-19 drugs Nirmatrelvir/Ritonavir(Paxlovid^(TM)) Remdesivir Molnupiravir Traditional Chinese medicine Pharmacokinetics herb-drug interaction

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interaction study between Ocimum sanctum and Glimepiride(sulfonylurea derivative) in diabetic rats

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Journal of Chinese Pharmaceutical Sciences 2015年第3期24卷 156-163页

作者： Mohd Fasih Ahmad Raj K.Keservani D J Mani Babu Department of Pharmacology V. L. College of Pharmacy School of Pharmaceutical Sciences Rajiv Gandhi Proudyogiki Vishwavidyalaya

The present study was intended to discover the interaction between Ocimum sanctum(O. sanctum) and Glimepiride, a sulfonylurea derivative used in the treatment of type-2 diabetes, in diabetic rats to suggest an alteration in the dose of Glimepiride in case of hypoglycaemia. LD50 studies for the aqueous extract of O. sanctum leaf were carried out in albino mice up to the dose level of 2000 mg/kg. O. sanctum at low, medium and high doses(100, 200 and 400 mg/kg, per oral), respectively and Glimepiride ?(half) therapeutic dose, therapeutic dose and 2 time therapeutic dose(0.036, 0.072 and 0.144 mg/200 g, per oral) were selected. After the treatment with O. sanctum and Glimepiride as single doses and in various combinations of these two drugs in streptozotocin-induced diabetic rats serum glucose levels in all the groups were analysed by the glucose oxidase-peroxidase method. When administered alone as single doses both aqueous extract of O. sanctum leaf and Glimepiride produced a significant anti-diabetic effect in diabetic rats. The anti-diabetic effect observed with combination of aqueous extract of O. sanctum leaf and Glimepiride was significant and more when compared to either of the drugs given alone. There was a definite interaction that necessitates dose readjustment of Glimepiride and further glucose levels are to be frequently monitored to avoid complication of hypoglycemic condition with aqueous extract of O. sanctum leaf and Glimepiride combination.

关键词： herb-drug interaction Ocimum sanctum Glimepiride Type-2 diabetes

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

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Journal of Traditional Chinese Medicine 2016年第3期36卷 392-408页

作者： Li Bo Zhao Baosheng Liu Yang Tang Mingmin Lǚe Beiran Luo Zhiqiang Zhai Huaqiang School of Chinese Materia Medica Beijing University of Chinese Medicine Beijing 100102 China Center of Scientific and Experiment Beijing niversity of Chinese Medicine Beijing 100029 China Beijing Key Laboratory of Protection and Utilization of Chinese Medicine Beijing Normal UniversityBeijing 100875 China

OBJECTIVE: To review the interactions between herbs and widely used drugs and summarize the associated experimental ***: 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 ***: 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 ***: 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.

关键词： herb-drug interaction Metabolism Cytochrome P-450 enzyme system P-glycoprotein Review

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Alterations of Gefitinib Pharmacokinetics by Co-administration of herbal Medications in Rats

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Chinese Journal of Integrative Medicine 2018年第6期24卷 460-466页

作者： Kwon-Yeon Weon Min Gi Kim Soyoung Shin Tae Hwan Kim Sang Hoon Joo Eunsook Ma Seok Won Jeong Sun Dong Yoo Yu Seok Youn Beom Soo Shin College of Pharmacy Catholic University of Daegu School of Pharmacy Sungkyunkwan University College of Pharmacy Wonkwang University

Objective： To evaluate the potential pharmacokinetic interactions of the anticancer agent gefitinib （Iressae） and the oriental medications Guipi Decoction （归脾汤, GPD, Guibi-tang in Korean） and Bawu Decoction （八物汤, BWD, Palmul-tang in Korean）. Methods： Methylceliulose （MC, control）, GPD （1,200 mg/kg）, or BWD （6,000 mg/kg） was orally administered to rats either as a single dose or multiple doses prior to gefitinib administration. To examine the effects of a single dose of the herbal medicines, gefitinib （10 mg/kg） was orally administered after 5 min or 1 h of MC or the herbal medicine pretreatments. To examine the effects of the multiple doses of the herbal medicines, gefltinib （10 mg/kg） was orally administered following 7 consecutive days of the administration of MC or each herbal medicine. The plasma concentrations of gefitinib were determined with liquid chromatography-tandem mass spectrometry assay. The plasma concentration-time profiles of gefitinib were analyzed with a noncompartmental analysis. Results： Gefitinib was rapidly absorbed and showed a mono- exponential decline with an elimination half-life of 3.7-4.1 h. The pharmacokinetics of gefitinib was not affected by GPD pretreatment. However, a significantly lower maximum plasma concentration （Crux, P〈0.05） and area under the curve （P〈0.05）, and a delayed time to reach Cmax （Tmax, P〈0.01） were observed in both single- and multiple- dose BWD-pretreated rats compared with the control rats. Conclusions： BWD and not GPD might delay and interfere with gefitinib absorption. Further evaluations of the clinical significance of these findings are needed.

关键词： herb-drug interaction pharmacokinetics gefitinib Guipi Decoction Bawu Decoction

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Nucleotide binding domain 1 pharmacophore modeling for visualization and analysis of P-glycoprotein-flavonoid molecular interactions

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Frontiers in Biology 2016年第5期11卷 391-395页

作者： Pathomwat Wongrattanakamon Vannajan Sanghiran Lee Piyarat Nimmanpipug Supat Jiranusomkul Laboratory for Molecular Design and Simulation (LMDS) Department of Pharmaceutical Sciences Faculty of Pharmacy Chiang Mai University Chiang Mai 50200 Thailand Department of Chemistry Faculty of Science University of Malaya Kuala Lumpur 50603 Malaysia Computational Simulation and Modelling Laboratory (CSML) Department of Chemistry Faculty of Science Chiang Mai University Chiang Mai 50200 Thailand

BACKGROUND： P-glycoprotein （P-gp） is a 170-kDa membrane protein. It provides a barrier function and help to excrete toxins from the body as a transporter. Some bioflavonoids have been shown to block P-gp activity. OBJECTIVE： To evaluate the important amino acid residues within nucleotide binding domain 1 （NBD l） of P-gp that play a key role in molecular interactions with flavonoids using structure-based pharmacophore model. METHODS： In the molecular docking with NBD 1 models, a putative binding site of flavonoids was proposed and compared with the site for ATP. The binding modes for ligands were achieved using LigandScout to generate the P-gp-flavonoid pharmacophore models. RESULTS： The binding pocket for flavonoids was investigated and found these inhibitors compete with the ATP for binding site in NBD1 including the NBD1 amino acid residues identified by the in silico techniques to be involved in the hydrogen bonding and van der Waals （hydrophobic） interactions with flavonoids. CONCLUSION： These flavonoids occupy with the same binding site of ATP in NBD1 proffering that they may act as an ATP competitive inhibitor.

关键词： P-glycoprotein Nucleotide-binding domain 1 pharmacophore model flavonoid competitive inhibition herb-drug interaction

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Isochlorogenic acid A affects P450 and UGT enzymes in vitro and in vivo

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Chinese Journal of Natural Medicines 2016年第11期14卷 865-870页

作者： WANG Jing WANG Hong PENG Ying WANG Guang-Ji HAO Hai-Ping Key Lab of drug Metabolism & Pharmacokinetics State Key Laboratory of Natural Medicines China Pharmaceutical University

Isochlorogenic acid A(ICQA), which has anti-inflammatory, hepatoprotective, and antiviral properties, is commonly presented in fruits, vegetables, coffee, plant-based food products, and herbal medicines. These herbal medicines are usually used in combination with other medicines in the clinic. However, little is known about the regulatory effects of ICQA on drug-metabolizing enzymes and the herb-drug interactions. In the present study, we evaluated the inhibitory potentials of ICQA on CYP1A2, CYP2C9,CYP2C19, CYP3A4, CYP2D6, and CYP2E1 in vitro based on a cocktail approach. The P450 and UGT activities in mice treated with ICQA for a prolonged period were also determined. Our results demonstrated that ICQA exhibited a weak inhibitory effect on CYP2C9 in human liver microsomes with IC_(50) being 57.25 μmol·L^(-1) and Ki being 26.77 μmol·L^(-1). In addition, ICQA inhibited UGT1A6 activity by 25%, in the mice treated with ICQA(i.p.) at 30 mg·kg^(-1)for 14 d, compared with the control group. Moreover, ICQA showed no mechanism-based inhibition on CYP2C9 or UGT1A6. In conclusion, our results further confirm a safe use of ICQA in clinical practice.

关键词： Isochlorogenic acid A P450 UGT herb-drug interaction

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Piper betle leaf extract enhances the cytotoxicity effect of 5-fluorouracil in inhibiting the growth of HT29 and HCT116 colon cancer cells

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2014年第8期15卷 692-700页

作者： Pek Leng NG Nor Fadilah RAJAB Sue Mian THEN Yasmin Anum MOHD YUSOF Wan Zurinah WAN NGAH Kar Yong PIN Mee Lee LOOI Department of Biomedical Sciences Faculty of Allied Health Universiti Kebangsaan Malaysia (UKM) Jalan Raja Muda Abdul Aziz50300 Kuala Lumpur Malaysia UKM Medical Molecular Biology Institute (UMBI) Universiti Kebangsaan Malaysia (UKM) Jalan Yaacob Latiff Bandar Tun Razak Cheras56000 Kuala Lumpur Malaysia School of Biomedical Science University of Nottingham Malaysia Campus43500 Semenyih Selangor Malaysia Department of Biochemistry Faculty of Medicine Universiti Kebangsaan Malaysia (UKM) Jalan Raja Muda Abdul Aziz50300 Kuala Lumpur Malaysia Forest Research Institute Malaysia (FRIM) 52109 Kuala Lumpur Kepong Malaysia School of Biosciences Taylor’s University Lakeside Campus47500 Subang Jaya Selangor Malaysia

Objective： The combination effect of Piperbetle （PB） and 5-fluorouracil （5-FU） in enhancing the cytotoxic potential of 5-FU in inhibiting the growth of colon cancer cells was investigated. Methods： HT29 and HCT116 cells were subjected to 5-FU or PB treatment. 5-FU and PB were then combined and their effects on both cell lines were observed after 24 h of treatment. PB-5-FU interaction was elucidated by isobologram analysis. Apoptosis features of the treated cells were revealed by annexin V/PI stain. High-performance liquid chromatography （HPLC） was performed to exclude any possible chemical interaction between the compounds. Results： In the presence of PB extract, the cytotoxicity of 5-FU was observed at a lower dose （IC^0 12.5 pmol/L） and a shorter time （24 h） in both cell lines. Both cell lines treated with 5-FU or PB alone induced a greater apoptosis effect compared with the combination treatment. Isobologram analysis indicated that PB and 5-FU interacted synergistically and antagonistically in inhibiting the growth of HT29 and HCT116 cells, respectively. Conclusions： In the presence of PB, a lower dosage of 5-FU is required to achieve the maximum drug effect in inhibiting the growth of HT29 cells. However, PB did not significantly reduce 5-FU dosage in HCT116 cells. Our result showed that this interaction may not solely contribute to the apoptosis pathway.

关键词： Piperaceae Piper beUe L. 5-Fiuorouracil Isobologram analysis herb-drug interaction

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