Herb-Drug Interactions: Worlds Intersect with the Patient at the Center.
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ABSTRACT:
SUBMITTER: Babos MB
PROVIDER: S-EPMC8401017 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Human cytochrome P450 3A4 (hCYP3A4) is a predominant enzyme to trigger clinically relevant drug/herb-drug interactions (DDIs or HDIs). Although a number of herbal medicines have been found with strong anti-hCYP3A4 effects in vitro, the in vivo modulatory effects of herbal medicines on hCYP3A4 and their potential risks to trigger HDIs are rarely investigated. Herein, we demonstrate a case study to efficiently find the herbal medicine(s) with potent hCYP3A4 inhibition in vitro and to accurately assess the potential HDIs risk in vivo. Following screening over 100 herbal medicines, the Chinese herb Styrax was found with the most potent hCYP3A4 inhibition in HLMs. In vitro assays demonstrated that Styrax could potently inhibit mammalian CYP3A in liver and intestinal microsomes from both humans and rats. In vivo pharmacokinetic assays showed that Styrax (i.g., 100 mg/kg) significantly elevated the plasma exposure of two CYP3A-substrate drugs (midazolam and felodipine) when midazolam or felodipine was administered orally. By contrast, the plasma exposure of either midazolam or felodipine was hardly affected by Styrax (i.g.) when the victim drug was administered intravenously. Further investigations demonstrated that seven pentacyclic triterpenoid acids (PTAs) in Styrax were key substances responsible for CYP3A inhibition, while these PTAs could be exposed to intestinal tract at relatively high exposure levels but their exposure levels in rat plasma and liver were extremely low. These findings well explained why Styrax (i.g.) could elevate the plasma exposure of victim drugs only when these agents were orally administrated. Collectively, our findings demonstrate that Styrax can modulate the pharmacokinetic behavior of CYP3A-substrate drugs via inhibiting intestinal CYP3A, which is very helpful for the clinical pharmacologists to better assess the HDIs triggered by Styrax or Styrax-related herbal products.
| S-EPMC9469097 | biostudies-literature
Project description:The worldwide using of herb products and the increasing potential herb-drug interaction issue has raised enthusiasm on discovering the underlying mechanisms. Previous review indicated that the interactions may be mediated by metabolism enzymes and transporters in pharmacokinetic pathways. On the other hand, an increasing number of studies found that genetic variations showed some influence on herb-drug interaction effects whereas these genetic factors did not draw much attention in history. We highlight that pharmacogenomics may involve the pharmacokinetic or pharmacodynamic pathways to affect herb-drug interaction. We are here to make an updated review focused on some common herb-drug interactions in association with genetic variations, with the aim to help safe use of herbal medicines in different individuals in the clinic.
| S-EPMC4363646 | biostudies-literature
Project description:A plethora of active compounds found in herbal medicines can serve as substrate for enzymes involved in the metabolism of xenobiotics. When a medicinal plant is co-administered with a conventional drug and little or no information is known about the pharmacokinetics of the plant metabolites, there is an increased risk of potential herb-drug interactions. Moreover, genetic polymorphisms in a population may act to predispose individuals to adverse reactions. The use of herbal medicines is rapidly increasing in many countries, particularly Brazil where the vast biodiversity is a potential source of new and more affordable treatments for numerous conditions. Accordingly, the Brazilian Unified Public Health System (SUS) produced a list of 71 plant species of interest, which could be made available to the population in the near future. Physicians at SUS prescribe a number of essential drugs and should herbal medicines be added to this system the chance of herb-drug interactions further increases. A review of the effects of these medicinal plants on Phase 1 and Phase 2 metabolic mechanisms and the transporter P-glycoprotein was conducted. The results have shown that approximately half of these medicinal plants lack any pharmacokinetic data. Moreover, most of the studies carried out are in vitro. Only a few reports on herb-drug interactions with essential drugs prescribed by SUS were found, suggesting that very little attention is being given to the safety of herbal medicines. Here we have taken this information to discuss the potential interactions between herbal medicines and essential drugs prescribed to Brazilian patients whilst taking into account the most common polymorphisms present in the Brazilian population. A number of theoretical interactions are pinpointed but more pharmacokinetic studies and pharmacovigilance data are needed to ascertain their clinical significance.
| S-EPMC4087670 | biostudies-literature
Project description:Late-life mild cognitive impairment and dementia represent a significant burden on healthcare systems and a unique challenge to medicine due to the currently limited treatment options. Plant phytochemicals have been considered in alternative, or complementary, prevention and treatment strategies. Herbals are consumed as such, or as food supplements, whose consumption has recently increased. However, these products are not exempt from adverse effects and pharmacological interactions, presenting a special risk in aged, polymedicated individuals. Understanding pharmacokinetic and pharmacodynamic interactions is warranted to avoid undesirable adverse drug reactions, which may result in unwanted side-effects or therapeutic failure. The present study reviews the potential interactions between selected bioactive compounds (170) used by seniors for cognitive enhancement and representative drugs of 10 pharmacotherapeutic classes commonly prescribed to the middle-aged adults, often multimorbid and polymedicated, to anticipate and prevent risks arising from their co-administration. A literature review was conducted to identify mutual targets affected (inhibition/induction/substrate), the frequency of which was taken as a measure of potential interaction. Although a limited number of drugs were studied, from this work, interaction with other drugs affecting the same targets may be anticipated and prevented, constituting a valuable tool for healthcare professionals in clinical practice.
| S-EPMC7835864 | biostudies-literature
Project description:More than half of Thai patients with cancer take herbal preparations while receiving anticancer therapy. There is no systematic or scoping review on interactions between anticancer drugs and Thai herbs, although several research articles have that Thai herbs inhibit cytochrome P450 (CYP) or efflux transporter. Therefore, we gathered and integrated information related to the interactions between anticancer drugs and Thai herbs. Fifty-two anticancer drugs from the 2020 Thailand National List of Essential Medicines and 75 herbs from the 2020 Thai Herbal Pharmacopoeia were selected to determine potential anticancer drug-herb interactions. The pharmacological profiles of the selected anticancer drugs were reviewed and matched with the herbal pharmacological activities to determine possible interactions. A large number of potential anticancer drug-herb interactions were found; the majority involved CYP inhibition. Efflux transporter inhibition and enzyme induction were also found, which could interfere with the pharmacokinetic profiles of anticancer drugs. However, there is limited knowledge on the pharmacodynamic interactions between anticancer drugs and Thai herbs. Therefore, further research is warranted. Information regarding interactions between anticancer drugs and Thai herbs should provide as a useful resource to healthcare professionals in daily practice. It could enable the prediction of possible anticancer drug-herb interactions and could be used to optimize cancer therapy outcomes.
| S-EPMC8880589 | biostudies-literature
Project description:BackgroundSince OpenAI released ChatGPT, with its strong capability in handling natural tasks and its user-friendly interface, it has garnered significant attention.ObjectiveA prospective analysis is required to evaluate the accuracy and appropriateness of medication consultation responses generated by ChatGPT.MethodsA prospective cross-sectional study was conducted by the pharmacy department of a medical center in Taiwan. The test data set comprised retrospective medication consultation questions collected from February 1, 2023, to February 28, 2023, along with common questions about drug-herb interactions. Two distinct sets of questions were tested: real-world medication consultation questions and common questions about interactions between traditional Chinese and Western medicines. We used the conventional double-review mechanism. The appropriateness of each response from ChatGPT was assessed by 2 experienced pharmacists. In the event of a discrepancy between the assessments, a third pharmacist stepped in to make the final decision.ResultsOf 293 real-world medication consultation questions, a random selection of 80 was used to evaluate ChatGPT's performance. ChatGPT exhibited a higher appropriateness rate in responding to public medication consultation questions compared to those asked by health care providers in a hospital setting (31/51, 61% vs 20/51, 39%; P=.01).ConclusionsThe findings from this study suggest that ChatGPT could potentially be used for answering basic medication consultation questions. Our analysis of the erroneous information allowed us to identify potential medical risks associated with certain questions; this problem deserves our close attention.
| S-EPMC10477918 | biostudies-literature
Project description:Jingyin granules, a marketed antiviral herbal medicine, have been recommended for treating H1N1 influenza A virus infection and Coronavirus disease 2019 (COVID-19) in China. To fight viral diseases in a more efficient way, Jingyin granules are frequently co-administered in clinical settings with a variety of therapeutic agents, including antiviral drugs, anti-inflammatory drugs, and other Western medicines. However, it is unclear whether Jingyin granules modulate the pharmacokinetics of Western drugs or trigger clinically significant herb-drug interactions. This study aims to assess the inhibitory potency of the herbal extract of Jingyin granules (HEJG) against human drug-metabolizing enzymes and to clarify whether HEJG can modulate the pharmacokinetic profiles of Western drug(s) in vivo. The results clearly demonstrated that HEJG dose-dependently inhibited human CES1A, CES2A, CYPs1A, 2A6, 2C8, 2C9, 2D6, and 2E1; this herbal medicine also time- and NADPH-dependently inhibited human CYP2C19 and CYP3A. In vivo tests showed that HEJG significantly increased the plasma exposure of lopinavir (a CYP3A-substrate drug) by 2.43-fold and strongly prolonged its half-life by 1.91-fold when HEJG (3 g/kg) was co-administered with lopinavir to rats. Further investigation revealed licochalcone A, licochalcone B, licochalcone C and echinatin in Radix Glycyrrhizae, as well as quercetin and kaempferol in Folium Llicis Purpureae, to be time-dependent CYP3A inhibitors. Collectively, our findings reveal that HEJG modulates the pharmacokinetics of CYP substrate-drug(s) by inactivating CYP3A, providing key information for both clinicians and patients to use herb-drug combinations for antiviral therapy in a scientific and reasonable way.
| S-EPMC8237038 | biostudies-literature
Project description:BackgroundThe identification of chemical-target interaction is key to pharmaceutical research and development, but the unclear materials basis and complex mechanisms of traditional medicine (TM) make it difficult, especially for low-content chemicals which are hard to test in experiments. In this research, we aim to apply the node2vec algorithm in the context of drug-herb interactions for expanding potential targets and taking advantage of molecular docking and experiments for verification.MethodsRegarding the widely reported risks between cardiovascular drugs and herbs, Salvia miltiorrhiza (Danshen, DS) and Ligusticum chuanxiong (Chuanxiong, CX), which are widely used in the treatment of cardiovascular disease (CVD), and approved drugs for CVD form the new dataset as an example. Three data groups DS-drug, CX-drug, and DS-CX-drug were applied to serve as the context of drug-herb interactions for link prediction. Three types of datasets were set under three groups, containing information from chemical-target connection (CTC), chemical-chemical connection (CCC) and protein-protein interaction (PPI) in increasing steps. Five algorithms, including node2vec, were applied as comparisons. Molecular docking and pharmacological experiments were used for verification.ResultsNode2vec represented the best performance with average AUROC and AP values of 0.91 on the datasets "CTC, CCC, PPI". Targets of 32 herbal chemicals were identified within 43 predicted edges of herbal chemicals and drug targets. Among them, 11 potential chemical-drug target interactions showed better binding affinity by molecular docking. Further pharmacological experiments indicated caffeic acid increased the thermal stability of the protein GGT1 and ligustilide and low-content chemical neocryptotanshinone induced mRNA change of FGF2 and MTNR1A, respectively.ConclusionsThe analytical framework and methods established in the study provide an important reference for researchers in discovering herb-drug interactions, alerting clinical risks, and understanding complex mechanisms of TM.
| S-EPMC10233865 | biostudies-literature
Project description:It is becoming increasingly evident that patients with diabetes do not rely only on prescription drugs for their disease management. The use of herbal medicines is one of the self-management practices adopted by these patients, often without the knowledge of their healthcare practitioners. This study assessed the potential for pharmacokinetic herb-drug interactions (HDIs) amongst Nigerian adult diabetic patients. This was done through a literature analysis of the pharmacokinetic profile of their herbal medicines and prescription drugs, based on information obtained from 112 patients with type-2 diabetes attending two secondary health care facilities in Nigeria. Fifty percent of the informants used herbal medicines alongside their prescription drugs. Worryingly, 60% of the patients taking herbal medicines did not know their identity, thus increasing the risk of unidentified HDIs. By comparing the pharmacokinetic profile of eight identified herbs taken by the patients for the management of diabetes against those of the prescription drugs, several scenarios of potential HDIs were identified and their clinical relevance is discussed. The lack of clinical predictors points toward cultural factors as the influence for herb use, making it more difficult to identify these patients and in turn monitor potential HDIs. In identifying these possible interactions, we have highlighted the need for healthcare professionals to promote a proactive monitoring of patients' use of herbal medicines.
| S-EPMC4978708 | biostudies-literature
Project description:Corona Virus Disease 2019 (COVID-19) has spread all over the world and brings significantly negative effects on human health. To fight against COVID-19 in a more efficient way, drug-drug or drug-herb combinations are frequently used in clinical settings. The concomitant use of multiple medications may trigger clinically relevant drug/herb-drug interactions. This study aims to assay the inhibitory potentials of Qingfei Paidu decoction (QPD, a Chinese medicine compound formula recommended for combating COVID-19 in China) against human drug-metabolizing enzymes and to assess the pharmacokinetic interactions in vivo. The results demonstrated that QPD dose-dependently inhibited CYPs1A, 2A6, 2C8, 2C9, 2C19, 2D6 and 2E1 but inhibited CYP3A in a time- and NADPH-dependent manner. In vivo test showed that QPD prolonged the half-life of lopinavir (a CYP3A substrate-drug) by 1.40-fold and increased the AUC of lopinavir by 2.04-fold, when QPD (6 g/kg) was co-administrated with lopinavir (160 mg/kg) to rats. Further investigation revealed that Fructus Aurantii Immaturus (Zhishi) in QPD caused significant loss of CYP3A activity in NADPH-generating system. Collectively, our findings revealed that QPD potently inactivated CYP3A and significantly modulated the pharmacokinetics of CYP3A substrate-drugs, which would be very helpful for the patients and clinicians to avoid potential drug-interaction risks in COVID-19 treatment.
| S-EPMC7816587 | biostudies-literature