Potential Herb-drug Interactions Research Articles

In vitro inhibitory effects of major bioactive constituents of Andrographis paniculata, Curcuma longa and Silybum marianum on human liver microsomal morphine glucuronidation: A prediction of potential herb-drug interactions arising from andrographolide, curcumin and silybin inhibition in humans

This study aimed to investigate the liver microsomal inhibitory effects of silybin, silychristin, andrographolide, and curcumin by using morphine as an in vitro UGT2B7 probe substrate, and predict the magnitude of the herb-drug interaction arising from these herbal constituents' inhibition in vivo. Studies were performed in the incubation with and without bovine serum albumin (BSA). Andrographolide and curcumin showed a marked inhibition on morphine 3- and 6-glucuronidation with IC50 of 50&87 and 96&111 μM, respectively. In the presence of 2%BSA, andrographolide also showed a strong inhibition on morphine 3- and 6-glucuronidation (IC50 4.4&21.6 μM) whereas curcumin showed moderate inhibition (IC50 338&333 μM). In the absence and presence of 2%BSA, morphine 3- and 6-glucuronidation was moderately inhibited by silybin (IC50 583&862 and 1252&1421 μM, respectively), however was weakly inhibited by silychristin (IC50 3527&3504 and 1124&1530 μM, respectively). The Ki of andrographolide, curcumin and silybin on morphine 3- and 6-glucuronidation were 7.1&9.5, 72.7&65.2, and 224.5&159.7 μM, respectively, while the respective values generated from the system containing 2%BSA were 2.4&3.1, 96.4&108.8, and 366.3&394.5 μM. Using the in vitro and in vivo extrapolation approach, andrographolide was herbal component that may have had a potential interaction in vivo when it was co-administered with morphine.

The impact of sesquiterpenes β-caryophyllene oxide and trans-nerolidol on xenobiotic-metabolizing enzymes in mice in vivo

1. Sesquiterpenes, constituents of plant essential oil, are popular bioactive compounds due to the positive effect on human health, but their potential toxicity and possible herb-drug interactions are often omitted. In our in vivo study, we followed up the effect of p.o. administration of two sesquiterpenes β-caryophyllene oxide (CAO) and trans-nerolidol (NER) on various xenobiotic-metabolizing enzymes in mice liver and small intestine.2. To spot the early effect of studied compounds, enzymatic activity and mRNA levels were assessed 6 and 24 h after single dose.3. CAO and NER markedly increased cytochromes P450 (CYP2B, 3A, 2C) activity and mRNA levels in both tissues. Liver also showed elevated activity of aldo-ketoreductase 1C and carbonyl reductase after treatment. Contrary, sesquiterpenes decreased NAD(P)H:quinone oxidoreductase 1 activity in small intestine. Among conjugation enzymes, only liver sulfotransferase activity was increased by sesquiterpenes.4. Our results document that single dose of sesquiterpenes modulate activities and expression of several xenobiotic-metabolizing enzymes.

PXR mediated induction of CYP3A4, CYP1A2, and P-gp by Mitragyna speciosa and its alkaloids.

Kratom (Mitragyna speciosa), a native herb of Southeast Asia, is widely known for its psychoactive properties. Recent increase in the use of kratom as a recreational drug has increased the risk of its interaction with conventional drugs if taken concomitantly. A few reports are available related to the effects of kratom on the activity of cytochrome P450 enzymes (CYPs), but there are no reports of its effects on pregnane X receptor (PXR), a transcription factor that regulates the expression of CYPs and P-glycoprotein (P-gp). This study was carried out to evaluate the effects of a methanolic extract of kratom leaves, an alkaloid rich fraction and its 5 indole and 4 oxindole alkaloids on PXR activation and the resulting changes in the mRNA expression of PXR target genes (CYP3A4, CYP1A2, and P-gp). A significant activation of PXR was observed by the extract (3-fold), alkaloidal fraction (4-fold) and all 9 alkaloids (4- to 6-fold) that was associated with an increased mRNA expression which resulted into an increase in the activity of CYP3A4, CYP1A2, and P-gp. These results indicate that high consumption of Mitragyna speciosa extract along with the conventional drugs may lead to potential herb-drug interactions due to its effects on PXR.

High hepatic exposure of furanocoumarins in Radix Angelica dahuricae is associated with transporter mediated active uptake

Ethnopharmacological relevanceRadix Angelica dahuricae (RAD), the roots of Angelica dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Sav, is a well-known traditional Chinese medicine (TCM) and has been used for centuries to treat headaches, toothaches, nose congestion, abscesses, furunculoses, and acne. This herb is also one of frequently reported TCMs showing the herb-drug interaction potential. Furanocoumarins are main bioactive components of RAD. Aim of the studyThis study is designed to characterize the tissue distribution profiles of furanocoumarins after oral administration of RAD extract in rats and to explore the mechanism underlying the high hepatic exposure of the major furanocoumarins. Materials and methodsThe tissue distribution of nine furanocoumarins was determined in rats after an oral dose of 0.46g/kg RAD extract using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Unbound fractions (ƒu) of major furanocoumarins, including imperatorin (IM), isoimperatorin (IIM), bergapten (BER) and oxypeucedanin hydrate (OXYH), were measured in rat plasma and selected tissue homogenates (liver, kidney, lung and brain) with Rapid Equilibrium Dialysis (RED) method. The temperature dependent hepatic uptake of IM, IIM, BER and OXYH were evaluated in suspended rat primary hepatocytes at 4°C or 37°C by the oil-spin method. The uptake kinetics was conducted in the cells over a wide concentration range. The furanocoumarins were co-incubated with a panel of transporter inhibitors to investigate the involvement of uptake transporters in the hepatic uptake. The transcellular transport characteristics of IM, IIM, BER and OXYH were further assessed using Caco-2 cell monolayer model. ResultsIM, IIM, BER and OXYH were found to be the major bioactive furanocoumarins in rat plasma and tissues, representing more than 90% exposure for all the detected furanocoumarins. The most concentrative organ of major furanocoumarins was the liver, with liver-to-plasma exposure ratio (Kp,AUC) of 5.1, 6.5 and 4.7 for IM, IIM and BER, and 2.3 for OXYH, respectively. IM, IIM and BER also showed higher concentrations in the kidney with Kp above 2.2. The higher protein binding of the furanocoumarins partially contributed to their higher tissue exposure. In suspended rat primary hepatocyte, the hepatic uptake of IM, IIM, BER and OXYH was temperature-dependent, with considerably higher uptake at 37°C than at 4°C. Uptake kinetics indicated that the hepatic uptake of IM, IIM, BER and OXYH involved both active transport and passive diffusion processes. For IM, IIM and BER, the contribution of the active transport was greater than the passive process, with the CLactive/CLuptake > 72%. Ritonavir (RTN) and cyclosporine A (CsA), the known inhibitors of organic anion transporting polypeptide (Oatp) significantly inhibited the hepatic uptake of IM and BER, while the inhibitor of the organic anion transporters (Oat) probenecid (PBC) remarkably reduced IIM uptake. In the Caco-2 cell model, the furanocoumarins were highly permeable in the apical to basolateral direction without notable active efflux. ConclusionThe furanocoumarins rapidly and widely distributed into various tissues after oral dose of the RAD extract. IM, IIM, BER and OXYH were the major components detected in both plasma and tissues. Liver was the most distributed tissue of the total and free furanocoumarins. Non-specific protein binding contributed partially to the higher tissue exposures of these bioactive components. The Oatp and Oat mediated active uptake played the primal role in the high hepatic exposure of the furanocoumarins.

The Undisclosed Usage of Dietary Supplements in Chinese Elderly Patients

The use of dietary herbal supplements in patients taking prescribed or over-the-counter medications may not be appropriate due to potential herb-drug interactions. The case report of an 81-year-old Chinese American woman taking nonprescribed, over-the-counter, dietary herbal supplements is presented to demonstrate the risk of undisclosed use of supplements. This article emphasizes the need for registered dietitian nutritionists and other health care professionals to encourage patients disclose their use of dietary supplements and conduct evaluations on potential adverse herb-drug interactions. Recommendations should be provided to patients regarding the use of dietary supplements as part of the comprehensive patient care.

Chinese Herbal Medicine for Hyperlipidaemia: A Review Based on Data Mining from 1990 to 2016.

Many studies have shown that the reduction of low density lipoprotein (LDLC) levels provides cardiovascular protection; therefore LDL-C is considered to be a core therapeutic target in anti-hyperlipidaemia treatment. However, the LDL-C goal attainment is often not satisfied in China with conventional lipid-lowering agents. Many patients seek help from Chinese Herbal Medicine (CHM). To further understand the current use of CHM in hyperlipidaemia, we conducted a review based on a systematic literature search and data mining. We comprehensively searched MEDLINE, EBSCO, Cochrane Library, EMBASE, Chinese Biomedical Literature Database (CBM), Chinese Scientific Journal Database (VIP), China National Knowledge Infrastructure (CNKI) and Wanfang database to identify potentially relevant articles. We included literatures that met the following criteria: (1) randomized or non-randomized controlled trials; (2) observational clinical trials; (3) case series or case reports. In order to enrich the systematic literature searching and provide the quantitative relationship between relative items and the treatment of hyperlipidaemia, the data mining was also conducted by filtering the biomedical literature on hyperlipidaemia in SinoMed and other available databases like VIP and CNKI. In summary, 282 records of CHM on hyperlipidaemia were captured and analysed. The top used single herb was Radix Salviae Miltiorrhizae. The most frequently used formula was Xuefuzhuyu Decoction. The most used herbs in clinical practice have some pharmacological evidences. The mechanisms are different, but could be classified into three categories: inhibiting synthesis, increasing decomposition and reducing absorption. CHM shows positive effect in the treatment of hyperlipidaemia and has the potential to be used in combination with conventional drugs. However, their use should be demonstrated in highquality clinical trials and clinicians should pay attention to potential herb-drug interactions.

Concealed use of herbal and dietary supplements among Thai patients with type 2 diabetes mellitus

BackgroundDiabetes mellitus (DM) has been one of the most common chronic diseases that create great impacts on both morbidities and mortalities. Many patients who suffering from this disease seek for complementary and alternative medicine. The aim of this study was to determine the prevalence and related factors of herbal and dietary supplement (HDS) use in patients with DM type 2 at a single university hospital in Thailand.MethodsA cross-sectional study was performed in 200 type 2 DM patients via face-to-face structured interviews using developed questionnaires comprised of demographic data, diabetes-specific information, details on HDS use, and medical adherence.ResultsFrom the endocrinology clinic, 61% of total patients reported HDS exposure and 28% were currently consuming. More than two-thirds of HDS users did not notify their physicians, mainly because of a lack of doctor concern; 73% of cases had no awareness of potential drug-herb interaction. The use of drumstick tree, turmeric and bitter gourd and holy mushroom were most frequently reported. The main reasons for HDS use were friend and relative suggestions and social media. Comparisons of demographic characteristics, medical adherence, and hemoglobin A1c among these non-HDS users, as well as current and former users, were not statistically significantly different.ConclusionsThis study revealed a great number of DM patients interested in HDS use. The use of HDS for glycemic control is an emerging public health concern given the potential adverse effects, drug interactions and benefits associated with its use. Health care professionals should aware of HDS use and hence incorporate this aspect into the clinical practice.

The potential of Epimedium koreanum Nakai for herb-drug interaction.

This study aims to investigate potential herb-drug interactions (HDI) of Epimedium koreanum Nakai. Human liver microsomes (HLMs) were used to determine the enzyme kinetics of the major human cytochrome P450s (CYPs). Inducible potential of E.koreanum on CYP1A2, 2B6, 2C19 and 3A4 activities of human primary hepatocytes was also examined. Ethanol extract of E.koreanum showed direct inhibitory potency for CYP1A2 (IC50 =121.8μg/ml, Ki =110.7±36.8μg/ml) and CYP2B6 (IC50 =59.5μg/ml, Ki =18.1±2.9μg/ml). For CYP2C9, 2C19, 2D6, 2E1 and 3A4, only negligible effect was observed. Time-dependent (irreversible) inhibition by E.koreanum was observed for CYP1A2 (KI =32.9±18.4μg/ml, kinact =0.031±0.006min-1 ). However, ethanol extract of E.koreanum (1.5-150μg/ml) did not change the activity or mRNA expressions for CYP3A4, 1A2, 2C19 and 2B6. The ethanol extract of E.koreanum is not likely to cause HDI via inducing the major human CYPs. But the potential for interactions between E.koreanum extract and substrates of CYP1A2 or 2B6 cannot be overlooked.

Potential Drug-Drug and Herb-Drug Interactions in Patients With Cancer: A Prospective Study of Medication Surveillance.

Patients with cancer frequently use herbal supplements and concomitant medications along with antineoplastic agents. These patients are at high risk of herb-drug interactions (HDIs) and drug-drug interactions (DDIs). We aimed to determine clinically relevant DDIs and HDIs leading to pharmaceutical intervention. Patients starting a new anticancer therapy were asked to complete a questionnaire to identify concomitant use of any over-the-counter drug or herbal supplement. Potential DDIs and HDIs were identified using two different databases. If a potentially clinically relevant DDI was recognized by the clinical pharmacist, a notification was sent to the prescribing oncologist, who decided whether to carry out a suggested intervention. Regression analyses were performed to identify variables associated with clinically relevant DDIs. A total of 149 patients were included in this study, with 36 potentially clinically relevant DDIs identified in 26 patients (17.4%; 95% CI, 11.3% to 23.5%), all of them leading to therapy modifications. In total, four patients (2.7%; 95% CI, 0.1% to 5.3%) had experienced clinical consequences from DDIs at the time of pharmacist notification. Additionally, 84 patients (56.4%; 95% CI, 48.4% to 64.4%) reported using concurrent herbal supplements, and 122 possible HDIs were detected. Concomitant use of two or more drugs was independently associated with high risk of a clinically significant DDI (odds ratio, 2.53; 95% CI, 1.08 to 5.91; P = .03). Potentially clinically relevant DDIs and possible HDIs were frequently detected in this prospective study. A multidisciplinary approach is required to identify and avoid potentially harmful combinations with anticancer therapy.

The effect of tripterygium glucoside tablet on pharmacokinetics of losartan and its metabolite EXP3174 in rats.

Losartan and tripterygium glucoside tablet (TGT) are often simultaneously used for reducing urine protein excretion in clinic. However, it is unknown whether there is potential herb-drug interaction between losartan and TGT. The aim of this study was to investigate their potential herb-drug interaction, and clarify the mechanism of the effect of TGT on the pharmacokinetics of losartan and its metabolite EXP3174 in rats. The plasma concentrations of losartan and EXP3174 were determined by LC-MS, and the main pharmacokinetic parameters were calculated. The Cmax , t1/2 and AUC(0-t) of losartan became larger after co-administration, while the Cmax and AUC(0-t) of EXP3174 became smaller, suggesting that TGT could influence the pharmacokinetics of losartan and EXP3174. The effects of TGT and its main components on the metabolic rate of losartan were further investigated in rat liver microsomes. Results indicated that TGT and its two main ingredients could decrease the metabolic rate of losartan. Therefore, it was speculated that TGT might increase the plasma concentration of losartan and decrease the concentration of EXP3174 by inhibiting the metabolism of losartan. The results could provide references for clinical medication guidance of losartan and TGT to avoid the occurrence of adverse reactions.

Multiple Oral Dosing Pharmacokinetics of Standardized Extract of Centella asiatica ECa 233 and Its Inductive Effect on Efflux Transporters in Rats

AbstractECa 233 is a standardized extract of Centella asiatica, characterized as a white powder containing triterpenoid glycosides not less than 80% with a ratio of madecassoside to asiaticoside of 1.5±0.5:1. Although pharmacological and toxicological profiles of ECa 233 have been successively reported, the pharmacokinetic data needed for further therapeutic development are not fully elucidated. This study aimed to investigate the pharmacokinetics of multiple oral dosing of ECa 233 at 100 mg/kg/day for 7 days in rats. Plasma, tissues, urine, and feces were collected from 0 to 24 h after dosing on days 1 and 7. The concentrations of asiaticoside, madecassoside, asiatic acid, and madecassic acid were simultaneously analyzed by liquid chromatography-tandem mass spectrometry. No significant change was observed in physical and blood biochemical parameters of the animals treated with ECa 233 for 7 days. The maximum plasma concentration and area under the curve at day 7 of madecassoside and asiaticoside decreased by 70–80% from day 1. However, both triterpenoid glycosides were extensively distributed and accumulated, resulting in significantly higher concentrations at pharmacologically relevant organs. Madecasssic acid and asiatic acid are major metabolites mainly found in and excreted via feces. Moreover, multiple dosing of ECa 233 increased mRNA expression of Abcb1a and Abcc2 in the small intestine by approximately 2- to 3-fold. This is the first study to identify an inductive effect of a standardized extract of C. asiatica after multiple oral dosing in rats. Potential drug-herb interactions when ECa 233 is coadministered with Abcb1a and Abcc2 substrates calls for further investigations.

Inhibition of human CYP3A4 and CYP3A5 enzymes by gomisin C and gomisin G, two lignan analogs derived from Schisandra chinensis

Gomisin C (GC) and gomisin G (GG) are two lignan analogs isolated from the Traditional Chinese Medicine Schisandra chinensis which possesses multiple pharmacological activities. However, the potential herb-drug interactions (HDI) between these lignans and other drugs through inhibiting human cytochrome P450 3A4 (CYP3A4) and CYP3A5 remains unclear. In the present study, the inhibitory action of GC and GG on CYP3A4 and CYP3A5 were investigated. The results demonstrated that both GC and GG strongly inhibited CYP3A-mediated midazolam 1′-hydroxylation, nifedipine oxidation and testosterone 6β-hydroxylation. Notably, the inhibitory intensity of GC towards CYP3A4 was stronger than CYP3A5 when using midazolam and nifedipine as substrates. While inhibition of GC towards CYP3A5 was weaker than CYP3A4 when using testosterone as substrate. In contrast, GG showed a stronger inhibitory activity on CYP3A5 than CYP3A4 without substrate-dependent behavior. In addition, docking simulations indicated that the π–π interaction between CYP3A4 and GC, and hydrogen-bond interaction between CYP3A5 and GG might result in their different inhibitory actions. Furthermore, the AUC of drugs metabolized by CYP3A was estimated to increase by 8%–321% and 2%–3190% in the presence of GC and GG, respectively. These findings strongly suggested that GC and GG showed high HDI potentials, and the position of methylenedioxy group determined their different inhibitory effect towards CYP3A4 and CYP3A5, which are of significance for the application of Schisandra chinensis-containing herbs.

Effects of Angelica gigas extract on the oral pharmacokinetics of gefitinib in rats

This study was performed to evaluate the potential drug–herb interaction between the conventional anti-cancer drug, gefitinib, and the herbal medication, Angelica gigas (AG) extract. One group of rats received a single intravenous (IV) dose of gefitinib (10 mg/kg) to determine its basic pharmacokinetics. Another group received a single oral dose of gefitinib (10 mg/kg) after pretreatment with saline or AG extract (500 mg/kg). The third group received an oral dose of gefitinib after pretreatment with saline or AG extract daily for 7 days. In addition, fecal and urinary recovery of gefitinib after IV and oral administration was evaluated. Gefitinib concentrations were determined using liquid chromatography–tandem mass spectrometry (LC–MS/MS) and the pharmacokinetic parameters were estimated by non-compartmental analysis. In addition, inhibition by AG of CYP3A4, the primary enzyme responsible for the metabolism of gefitinib, was evaluated. The results indicated that the pharmacokinetic parameters of gefitinib following single and multiple doses were not significantly affected by pretreatment with AG extract. Fecal and urinary recovery of gefitinib was not significantly different between groups, and AG extract did not inhibit CYP3A4 activity until the concentration reached 600 μg/mL. Therefore, the data indicated that gefitinib was not significantly affected by co-treatment with AG extract.

Herb-Drug Interactions of Commonly Used Chinese Medicinal Herbs.

With more and more popular use of traditional herbal medicines, in particular Chinese herbal medicines, herb-drug interactions have become a more and more important safety issue in the clinical applications of the conventional drugs. Researches in this area are increasing very rapidly. Herb-drug interactions are complicated due to the fact that multiple chemical components are involved, and these compounds may possess diverse pharmacological activities. Interactions can be in both pharmacokinetics and pharmacodynamics. Abundant studies focused on pharmacokinetic interactions of herbs and drugs. Herbs may affect the behavior of the concomitantly used drugs by changing their absorption, distribution, metabolism, and excretion. Studies on pharmacodynamics interactions of herbs and drugs are still very limited. Herb-drug interactions are potentially causing changes in drug levels and drug activities and leading to either therapeutic failure or toxicities. Sometime it can be fatal. The exposures to drugs, lacking of knowledge in the potential adverse herb-drug interactions, will put big risk to patients' safety in medical services. On the contrary, some interactions may be therapeutically beneficial. It may be used to help develop new therapeutic strategies in the future. This chapter is trying to review the development in the area of herb-drug interactions based on the recently published research findings. Information on the potential interactions among the commonly used Chinese medicinal herbs and conventional drugs is summarized in this chapter.

Therapeutic Risk and Benefits of Concomitantly Using Herbal Medicines and Conventional Medicines: From the Perspectives of Evidence Based on Randomized Controlled Trials and Clinical Risk Management.

Despite increased awareness of the potential of herb-drug interactions (HDIs), the lack of rigorous clinical evidence regarding the significance provides a challenge for clinicians and consumers to make rational decisions about the safe combination of herbal and conventional medicines. This review addressed HDIs based on evidence from randomized controlled trials (RCTs). Literature was identified by performing a PubMed search till January 2017. Risk description and clinical risk management were described. Among 74 finally included RCTs, 17 RCTs (22.97%) simply addressed pharmacodynamic HDIs. Fifty-seven RCTs (77.03%) investigated pharmacokinetic HDIs and twenty-eight of them showed potential or actual clinical relevance. The extent of an HDI may be associated with the factors such as pharmacogenomics, dose of active ingredients in herbs, time course of interaction, characteristics of the object drugs (e.g., administration routes and pharmacokinetic profiles), modification of herbal prescription compositions, and coexistence of inducers and inhibitors. Clinical professionals should enhance risk management on HDIs such as increasing awareness of potential changes in therapeutic risk and benefits, inquiring patients about all currently used conventional medicines and herbal medicines and supplements, automatically detecting highly substantial significant HDI by computerized reminder system, selecting the alternatives, adjusting dose, reviewing the appropriateness of physician orders, educating patients to monitor for drug-interaction symptoms, and paying attention to follow-up visit and consultation.

Herb–drug interaction potential of Berberis aristata through cytochrome P450 inhibition assay

Abstract Herbal medicines have been used from ancient times for the management of several disease and ailments along with prescribed medicine without consulting the physicians. Berberis aristata DC. has been widely used in management of diabetes as alternative therapy in India and other Asian countries. An approach has been made to evaluate the possible cytochrome P450 (CYP450) enzyme inhibition potential with the bark of the anti-diabetic herb Berberis aristata DC. along with combination of oral hypoglycaemic agents like glimepiride and gliclazide. Bioactive compound was quantified through RP-HPLC, in order to standardize the plant extract and interaction potential of standardized extract and bioactive compound with oral hypoglycaemic drugs were evaluated. Herb–drug interaction potential of the test samples were evaluated by CYP450-carbonmonoxide complex (CYP450-CO) assay with pooled rat liver microsome. Influence on individual recombinant human CYP450 isoforms such as CYP3A4, CYP2D6, CYP2C9 and CYP1A2 isozymes were analyzed through fluorescence microplate screening assay. The combination index (CI)—isobologram method was applied for the prediction of combination effects. Plant extract showed significantly higher IC50 value than respective positive control against CYP3A4, 2D6, 2C9 and 1A2. Combination of the test extract and the phytoconstituent present therein along with oral hypoglycemic drugs also showed significantly less (P

Mulberroside A suppresses PXR‐mediated transactivation and gene expression of P‐gp in LS174T cells

Mulberroside A (Mul A) is the main bioactive constituents of Sangbaipi, which is officially listed in the Chinese Pharmacopoeia. The pregnane X receptor (PXR) has been recognized as the critical mediator of human P-glycoprotein (P-gp) gene transactivation. In this study, the effect of Mul A on PXR-mediated transactivation and gene expression of P-gp was investigated. It was found that Mul A significantly suppressed PXR-mediated P-gp luciferase activity induced by rifampicin (Rif). Furthermore, Rif induced an elevation of P-gp expression and transport activity, which was apparently suppressed by Mul A. However, Mul A did not suppress the P-gp luciferase activity, P-gp expression, and function in the absence of Rif. These findings suggest that Mul A suppresses PXR-mediated transactivation and P-gp expression induced by Rif. This should be taken into consideration to predict any potential herb-drug interactions when Mul A or Sangbaipi are co-administered with Rif or other PXR agonist drugs.

Inhibitory Interactions of Aspalathus linearis (Rooibos) Extracts and Compounds, Aspalathin and Z-2-(β-d-Glucopyranosyloxy)-3-phenylpropenoic Acid, on Cytochromes Metabolizing Hypoglycemic and Hypolipidemic Drugs.

Rooibos extract, due to its glucose and lipid lowering effects, has potential as a nutraceutical for improvement of metabolic dysfunction. Potential herb-drug interactions as a result of the use of natural products are of increasing concern. Cytochrome P450 enzymes, CYP2C8, CYP2C9, and CYP3A4, are important in the metabolism of hypoglycemic drugs, such as thiazolidinediones (TZDs) and sulfonylureas, and hypocholesterolemic drugs, such as atorvastatin. This study investigated the effects of rooibos extracts, prepared from “unfermented” and “fermented” rooibos plant material and two of the major bioactive compounds, Z-2-(β-d-glucopyranosyloxy)-3-phenylpropenoic acid (PPAG) and aspalathin (ASP), on Vivid® recombinant CYP450 enzymes. Unfermented (GRT) and fermented (FRE) rooibos extracts inhibited the activity of CYP2C8 (7.69 ± 8.85 µg/mL and 8.93 ± 8.88 µg/mL, respectively) and CYP3A4 (31.33 ± 4.69 µg/mL and 51.44 ± 4.31 µg/mL, respectively) based on their respective IC50 concentrations. Both extracts dose- and time-dependently inhibited CYP2C8 activity, but only time-dependently inhibited CYP2C9. CYP3A4 showed concentration-dependent inhibition by ASP, GRT, and FRE at 25, 50, and 100 µg/mL concentrations. ASP, GRT, and FRE time-dependently inhibited CYP3A4 activity with GRT and FRE showing a more potent time-dependent inhibition, comparable to erythromycin. These findings suggest that herb-drug interactions may occur when nutraceuticals containing rooibos extracts are co-administered with hypoglycemic drugs such as TZDs, sulfonylureas, and dyslipidemic drug, atorvastatin.

Assessment of Potential Herb-Drug Interactions among Nigerian Adults with Type-2 Diabetes.

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.

Decreased absorption of midazolam in the stomach due to low pH induced by co-administration of Banha-sasim-tang.

ObjectivesBanha-sasim-tang (BST), which consists of seven different herbs, is one of the most popular herbal formulae for treating gastrointestinal disorders in Eastern Asia. The commonly used herbal medicine is often co-administered with other therapeutic drugs, which raises the possibility of herb–drug interactions and may modify the clinical safety profile of therapeutic drugs.MethodsWe investigated the potential herb–drug interactions between BST extract and midazolam (MDZ) in mice. The area under the plasma concentration-time curve (AUC) of MDZ and 1ʹ-hydroxymidazolam (1ʹ-OH-MDZ) was evaluated for both oral and intraperitoneal administration of MDZ, following oral administration of BST (0.5 and 1 g/kg).ResultsIt was found that the AUC of MDZ and 1ʹ-OH-MDZ was lower in case of oral administration of MDZ. Administration of BST extract was not associated with hepatic cytochrome P450 activity. BST extract induced a strong reduction in pH and it has been reported that oral mucosal absorption of MDZ is lower at low pH. The decreased absorption rate of MDZ might be caused by the ingredients of BST and may not be related to other factors such as increased excretion of MDZ by P-glycoprotein.ConclusionsThe altered pharmacokinetics of midazolam caused by co-administration with BST in vivo could be attributed to a decrease in pH and subsequent reduction of MDZ absorption rate.