Potential Herb-drug Interactions Research Articles

Evaluation potential effects of Picroside II on cytochrome P450 enzymes in vitro and in vivo

Ethnopharmacology relevancePicrorhiza scrophulariiflora Pennell, a well-known Chinese herb, has been traditionally utilized as an antioxidant and anti-inflammatory agent. One of its main bioactive components is Picroside II, a glycoside derivative. However, there is limited information on the effects of Picroside II on the activity of cytochrome P450 (CYP) enzymes nor on potential herb-drug interactions are rarely studied. Aim of the studyThe purpose of the study was to investigate the effects of Picroside II on the activity of cytochrome P450 enzymes in vitro and in vivo and its potential herb-drug interactions. Materials and methodsSpecific probe substrates were employed to assess the effect of Picroside II on the activity of P450 enzymes. The inhibitory effects of Picroside II on CYP enzymes were assayed both in human (i.e., 1A, 2C9, 2C19, 2D6, 2E1, and 3A) and rat (i.e., 1A, 2C6/11, 2D1, 2E1, and 3A) liver microsomes in vitro. The inductive effects were investigated in rats following oral gavage of 2.5 mg/kg and 10 mg/kg Picroside II. A specific Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS) method was developed to determine the formation of specific metabolites. ResultsEnzyme inhibition results showed that Picroside II (0.5–200 μM) had no evident inhibitory effects on rat and human liver microsomes in vitro. Interestingly, the administration of multiple doses of 10 mg/kg Picroside II inhibited the activity of CYP2C6/11 by reducing the rate of formation of 4-hydroxydiclofenac and 4-hydroxymephenytoin, while Picroside II at 2.5 mg/kg increased the activity of CYP3A by promoting the formation of 1-hydroxymidazolam and 6-hydroxychlorzoxazone in rats. In addition, there were negligible effects on CYP1A, CYP2D1, and CYP2E1 in rats. ConclusionsThe results indicated that Picroside II modulated the activities of CYP enzymes and was involved in CYP2C and CYP3A medicated herb-drug interactions. Therefore, careful monitoring is necessary when Picroside II is used in combination with related conventional drugs.

In Vitro Hepatic Models to Assess Herb-Drug Interactions: Approaches and Challenges.

A newfound appreciation for the benefits of herbal treatments has emerged in recent decades. However, herbal medication production still needs to establish standardized protocols that adhere to strict guidelines for quality assurance and risk minimization. Although the therapeutic effects of herbal medicines are extensive, the risk of herb-drug interactions remains a serious concern, limiting their use. Therefore, a robust, well-established liver model that can fully represent the liver tissue is required to study potential herb-drug interactions to ensure herbal medicines' safe and effective use. In light of this, this mini review investigates the existing in vitro liver models applicable to detecting herbal medicines' toxicity and other pharmacological targets. This article analyzes the benefits and drawbacks of existing in vitro liver cell models. To maintain relevance and effectively express the offered research, a systematic strategy was employed to search for and include all discussed studies. In brief, from 1985 to December 2022, the phrases "liver models", "herb-drug interaction", "herbal medicine", "cytochrome P450", "drug transporters pharmacokinetics", and "pharmacodynamics" were combined to search the electronic databases PubMed, ScienceDirect, and the Cochrane Library.

Identification of PXR Activators from Uncaria Rhynchophylla (Gou Teng) and Uncaria Tomentosa (Cat's Claw).

Uncaria rhynchophylla (Gou Teng) and Uncaria tomentosa (cat's claw) are frequently used herbal supplements in Asia and America, respectively. Despite their common usage, information is limited regarding potential herb-drug interactions associated with Gou Teng and cat's claw. The pregnane X receptor (PXR) is a ligand-dependent transcription factor that regulates cytochrome P450 3A4 (CYP3A4) expression and contributes to some known herb-drug interactions. A recent study found that Gou Teng induces CYP3A4 expression, but its mechanism is unknown. Cat's claw has been determined as a PXR-activating herb, but the PXR activators in cat's claw have not been identified. Using a genetically engineered PXR cell line, we found that the extracts of Gou Teng and cat's claw can dose-dependently activate PXR and induce CYP3A4 expression. We next used a metabolomic approach to profile the chemical components in the extracts of Gou Teng and cat's claw followed by screening for PXR activators. Four compounds, isocorynoxeine, rhynchophylline, isorhynchophylline, and corynoxeine, were identified as PXR activators from both Gou Teng and cat's claw extracts. In addition, three more PXR activators were identified from the extracts of cat's claw, including isopteropodine, pteropodine, and mitraphylline. All seven of these compounds showed the half-maximal effective concentration <10 µM for PXR activation. In summary, our work determined Gou Teng as a PXR-activating herb and discovered novel PXR activators from Gou Teng as well as cat's claw. SIGNIFICANCE STATEMENT: This study's data can be used to guide the safe use of Gou Teng and cat's claw by avoiding PXR-mediated herb-drug interactions.

Inhibitory effect of Selaginella doederleinii hieron on human cytochrome P450.

Introduction: Selaginella doederleinii Hieron is a traditional Chinese herbal medicine, the ethyl acetate extract from Selaginella doederleinii (SDEA) showed favorable anticancer potentials. However, the effect of SDEA on human cytochrome P450 enzymes (CYP450) remains unclear. To predict the herb-drug interaction (HDI) and lay the groundwork for further clinical trials, the inhibitory effect of SDEA and its four constituents (Amentoflavone, Palmatine, Apigenin, Delicaflavone) on seven CYP450 isoforms were investigated by using the established CYP450 cocktail assay based on LC-MS/MS. Methods: Appropriate substrates for seven tested CYP450 isoforms were selected to establish a reliable cocktail CYP450 assay based on LC-MS/MS. The contents of four constituents (Amentoflavone, Palmatine, Apigenin, Delicaflavone) in SDEA were determined as well. Then, the validated CYP450 cocktail assay was applied to test the inhibitory potential of SDEA and four constituents on CYP450 isoforms. Results: SDEA showed strong inhibitory effect on CYP2C9 and CYP2C8 (IC50 ≈ 1μg/ml), moderate inhibitory effect against CYP2C19, CYP2E1 and CYP3A (IC50 < 10μg/ml). Among the four constituents, Amentoflavone had the highest content in the extract (13.65%) and strongest inhibitory effect (IC50 < 5μM), especially for CYP2C9, CYP2C8 and CYP3A. Amentoflavone also showed time-dependent inhibition on CYP2C19 and CYP2D6. Apigenin and Palmatine both showed concentration-dependent inhibition. Apigenin inhibited CYP1A2, CYP2C8, CYP2C9, CYP2E1 and CYP3A. Palmatine inhibited CYP3A and had a weak inhibitory effect on CYP2E1. As for Delicaflavone, which has the potential to develop as an anti-cancer agent, showed no obvious inhibitory effect on CYP450 enzymes. Conclusion: Amentoflavone may be one of the main reasons for the inhibition of SDEA on CYP450 enzymes, the potential HDI should be considered when SDEA or Amentoflavone were used with other clinical drugs. On the contrast, Delicaflavone is more suitable to develop as a drug for clinical use, considering the low level of CYP450 metabolic inhibition.

Phytochemical Comparison of Medicinal Cannabis Extracts and Study of Their CYP-Mediated Interactions with Coumarinic Oral Anticoagulants

Introduction: Treatment with cannabis extracts for a variety of diseases has gained popularity. However, differences in herb-drug interaction potential of extracts from different plant sources are poorly understood. In this study, we provide a characterization of cannabis extracts prepared from four cannabis chemotypes and an in vitro assessment of their Cytochrome P450 (CYP)-mediated herb-drug interaction profiles. Methods: Plant extracts were either commercially obtained or prepared using ethanol as solvent, followed by overnight decarboxylation in a reflux condenser system. The extracts were characterized for their cannabinoid content using NMR and HPLC-PDA-ELSD-ESIMS. CYP inhibition studies with the cannabis extracts and pure cannabinoids (tetrahydrocannabinol [THC] and cannabidiol [CBD]) were performed using pooled, mixed gender human liver microsomes. Tolbutamide and testosterone were used as specific substrates to assess the inhibitory potential of the extracts on CYP2C9 and CYP3A4, and the coumarinic oral anticoagulants warfarin, phenprocoumon, and acenocoumarol were studied as model compounds since in vivo herb-drug interactions have previously been reported for this compound class. Results: In accordance with the plant chemotypes, two extracts were rich in THC and CBD (at different proportions); one extract contained mostly CBD and the other mostly cannabigerol (CBG). Residual amounts of the corresponding acids were found in all extracts. The extracts with a single major cannabinoid (CBD or CBG) inhibited CYP2C9- and CYP3A4-mediated metabolism stronger than the extracts containing both major cannabinoids (THC and CBD). The inhibition of CYP3A4 and CYP2C9 by the extract containing mostly CBD was comparable to their inhibition by pure CBD. In contrast, the inhibitory potency of extracts containing both THC and CBD did not correspond to the combined inhibitory potency of pure THC and CBD. Although being structural analogs, the three coumarin derivatives displayed major differences in their herb-drug interaction profiles with the cannabis extracts and the pure cannabinoids. Conclusion: Despite the fact that cannabinoids are the major components in ethanolic, decarboxylated cannabis extracts, it is difficult to foresee their herb-drug interaction profiles. Our in vitro data and the literature-based evidence on in vivo interactions indicate that cannabis extracts should be used cautiously when co-administered with drugs exhibiting a narrow therapeutic window, such as coumarinic anticoagulants, regardless of the cannabis chemotype used for extract preparation.

The prevalence and predictors of herb-drug interactions among Iranian cancer patients during chemotherapy courses

BackgroundThe concurrent usage of herbal medicines with conventional therapies is an important concern in cancer treatment which can lead to unexpected consequences like herb-drug interactions. This study aimed to determine the prevalence of potential herb-drug interactions and to predict factors associated with herb-drug interactions for cancer patients.MethodsThis cross-sectional study was conducted among a convenience sample of 315 cancer patients referring to the oncology clinics of Kerman city in 2018. Data were collected via comprehensive face-to-face interviews and medical chart reviews. A drug interaction checker was used to determine herb-drug interactions. The information of patients was compared based on herb-drug interactions using bivariable logistic regression models, and predictors were determined by the multivariable logistic regression model. All analyses were performed by Stata software version 16.ResultsOf 262 patients (83.2% of the patients) who used herbal medicines, 209 patients [79.8% (95% Confidence Intervals (CI): 75.2 – 85.1)] had potential herb-drug interactions. Chamomile was the most popular herbal medicine (n = 163, 78.0%), and minor and moderate herb-drug interactions were caused by green tea (n = 34, 16.3%) and peppermint (n = 78, 37.5%). The number of chemotherapeutic agents (OR: 1.92, 95% CI: 1.43–2.58; P-value < 0.0001) and the experienced of pain during chemotherapy courses (OR = 2.22, 95%CI:1.00–4.94; P-value = 0.04) were some of the predictors of herb-drug interactions among cancer patients.ConclusionHerbal medicine use during chemotherapy was found prevalent among cancer patients; of them, the experience of potential herb-drug interactions was highly frequent. Oncologists and clinical pharmacologists are recommended to take into account challenges associated with herb-drug interactions in their routine practices, particularly during chemotherapy among these patients.

In Vitro Metabolism and CYP-Modulating Activity of Lavender Oil and Its Major Constituents

The application of essential oils has historically been limited to topical (massage therapy) and inhalational (aromatherapy) routes of administration. More recently, however, evaluation of the therapeutic effects of essential oils has expanded to include the oral route of administration, which increases the herb-drug interaction potential. The purpose of this study was to evaluate the herb-drug interaction potential of lavender essential oil and two of its primary phytoactive constituents, namely linalool and linalyl acetate. The metabolic stability of linalool and linalyl acetate was determined in human liver microsomes (HLM) and S9 fractions by quantitative analysis using UPLC-MS/MS system. Linalool was metabolically unstable in HLM and S9 fractions with an intrinsic clearance of 31.28 mL·min-1·kg-1, and 7.64 mL·min-1·kg-1, respectively. Interestingly, it was observed that linalyl acetate converted to linalool both in HLM and S9 fractions. Lavender oil showed weak inhibitory effect on the catalytic activity of CYP3A4 and CYP1A2 enzymes (IC50 12.0 and 21.5 µg/mL). Linalyl acetate inhibited CYP3A4 (IC50 4.75 µg/mL) while linalool did not show any inhibitory effect on any of the enzymes. The lavender oil and its constituents did not activate PXR to a considerable extent, and no activation of AhR was observed, suggesting a lack of potential to modify the pharmacokinetic and pharmacodynamic properties of conventional medications if used concurrently.

Antiproliferative and Anti-Inflammatory Activities of Deprungsith Formulation and Its Bioactive Compounds Against Mild Psoriasis and Potential of Metabolic Herb-Drug Interactions.

Psoriasis is an incurable, chronic and auto-immune skin disorder with a global prevalence rate of approximately 2-3%. The study investigated the antipsoriasis activities of Deprungsith formulation and its bioactive components and their potential for inhibitory activities on human cytochrome P450 (CYP450). HaCaT and peripheral blood mononuclear cells (PBMCs) from healthy volunteers (n = 9) and psoriasis patients (n = 10) were exposed to Deprungsith formulation (Thai traditional medicine for psoriasis consisting of 16 plants), ethyl p-methoxycinnamate (EPMC), ligustilide and cyclosporin for 24 and 48 h. The antiproliferative, cell apoptosis and cell cycle arrest activities were evaluated using MTT assay and flow cytometry, respectively. The pro-inflammatory cytokine mRNA expression levels were measured using real-time polymerase chain reaction (RT-PCR). The CYP450 inhibitory effect was investigated using a bioluminescent-based CYP450 assay. Deprungsith formulation and the bioactive compounds inhibited HaCaT cells and PBMCs with weak to moderate potencies. EPMC and ligustilide combination produced an additive effect. Most substances arrested cell transition at sub-G1 and S phases, leading to early and late apoptosis induction. With prolonged exposure (48 h), all test substances decreased PBMCs necrosis. The mRNA expression of all pro-inflammatory cytokines was downregulated. Deprungsith formulation, EPMC, ligustilide and ferulic acid inhibited CYP1A2, CYP2C9, CYP2D6 and CYP3A4 activities with weak to moderate potencies. Deprungsith formulation and bioactive components induced cell apoptosis by inhibiting cell transition at specific cell cycle phases, which was correlated with the mRNA downregulation of interleukin (IL-6, IL-12p19, IL-23) and tumor necrosis factor (TNF-α). There is a low risk of potential adverse drug reactions and toxicity due to CYP450 interaction when Deprungsith formulation is concurrently administered with modern medicines.

Этические аспекты фитотерапии

The review is devoted to safety issues of herbal medicinal products. Apart from the most known adverse effects such as allergic reactions and irritation ofmucous membranes, use of a number of herbal medicines results in hormonal disturbances, organotoxic reactions and CNS disturbances. The problem of intoxication is pressing in case of uncontrolled administration of herbal remedies, which is often accompanied by a carefree attitude towards them as natural and thus safe agents. This assurance is developed in the result of non-ethical advertising of dietary supplements in mass media. Finally, an important factor of safe therapy is comprehensive accounting of potential herb-herb and herb-drug interactions. The purpose of the article is to attract attention to a weighted attitude towards phytotherapy concerning its safety both in administration of traditional herbal medicinal products by doctors and during self-treatment bypatients.

Chemical basis of pregnane X receptor activators in the herbal supplement Gancao (licorice)

Background and aimsThe herbal supplement Gancao, also known as licorice, belongs to the genus Glycyrrhiza and has been used worldwide for its hepatoprotective effect. Recent studies have raised concerns about potential herb-drug interactions associated with Gancao via pregnane X receptor (PXR)-mediated induction of hepatic cytochrome P450 3A4 (CYP3A4). The current work aimed to determine the phytochemicals in Gancao that activate PXR and induce CYP3A4. MethodsDPX2 cells were used for cell-based PXR reporter assays. The phytochemicals in Gancao extract were identified using a metabolomics approach. The effects of PXR activators identified from in vitro studies were further investigated in PXR- and CYP3A4-humanized mouse models. ResultsGancao was verified to be a PXR-activating herb. Two major phytochemicals in Gancao, glycyrrhizin (GZ) and glycyrrhetinic acid (GA), did not activate PXR in the cell-based reporter assays. However, glabridin was shown to activate PXR in a dose-dependent manner. In vivo studies confirmed that GZ is not a PXR activator and glabridin is a weak PXR activator. Although GA did not active PXR in vitro, it induced CYP3A4 expression in a PXR-dependent manner in the PXR- and CYP3A4-humanized mice. ConclusionsGZ is not a PXR activator. GA could not activate PXR in cell-based reporter assays but it could activate PXR in vivo. Glabridin is a weak PXR activator. This work provides novel insights into the underlying mechanisms of Gancao-related herb-drug interactions via PXR.

Use of Cheminformatics to Determine Potential Drug Interactions between Popular Barbadian Botanical Medicines and Antihypertensive Drugs.

Barbados has a rich traditional use of medicinal plants, especially among the older population who may have a chronic noncommunicable disease. This study aims to identify possible drug-herb interactions between popular herbal remedies used to manage elevated blood pressure and conventional antihypertensive drugs. In this study, in silico molecular docking experiments with AutoDock Vina (Scripps Research Institute, La Jolla, CA), a part of Yasara Structure software, version 20.12.24, were used to screen 30 potential phytochemicals for drug interactions from 11 popular plants in Barbados that are used for high blood pressure and could influence the pharmacology of the most prescribed antihypertensive drugs in Barbados. Thiazide and thiazide-like diuretics, calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACE-I), and angiotensin receptor blockers (ARBs) are the most prescribed antihypertensive drugs. Twenty-seven phytochemicals show dissociation constants (K d) < 10 μM with pharmacological drug targets. Catharanthus roseus (L.) G. Don, Phyllanthus niruri L., Petroselinum crispum (Mill.) Fuss, and Lantana involucrata L. contain various compounds that show high binding affinities in all experiments. Possible interactions could affect renal excretion (thiazide-like diuretics), CYP metabolism (CCBs), absorption (ACE-I), hepatic CYP, and phase II metabolism (ARB). Oleanolic acid shows high binding affinities to almost all protein targets. This study also reveals potential candidates for the drug targets: T-type Cav3.3 (psychiatric diseases), PEPT1/2 (influencing bioavailability), and BK channel (epilepsy). Twenty-seven of 30 phytochemicals from C. roseus (L.) G. Don (Madagascar periwinkle), P. niruri L. (Seed under leaf), P. crispum Mill. Fuss (Parsley), and L. involucrata L. (Rock sage) have potential binding affinities with pharmacological targets of frequently prescribed antihypertensive drugs in Barbados and are likely to cause drug interactions. Compounds that are similar to naringin (e.g., astragalin, rutin, and quercitrin) and compounds that bind to OATP1, PEPT1/2, and enzymes involved in the metabolism of CCBs may be clinically relevant for further research. There should be greater awareness of potential drug-herb interactions, and further in vitro and in vivo studies are needed to unravel the exact effects on the pharmacology.

Prevalence, Perception and Predictors of Concomitant Herbal Medicine Use among HIV/AIDS and Tuberculosis Patients in Metekel Zone, Northwest Ethiopia: A Cross-Sectional Study.

The use of herbal medicine is common in Ethiopia. However, evidence on the extent and predictors of concomitant use of herbal medicine with conventional treatment among HIV/AIDS and tuberculosis patients is limited. To assess the extent of concomitant use of herbal medicine with conventional therapy and associated factors among HIV/AIDS and tuberculosis patients in Metekel Zone, Northwest Ethiopia. A cross-sectional study was conducted from January to March 2020. HIV/AIDS and tuberculosis patients who visited the health facilities during the study were interviewed face-to-face using a structured and pretested questionnaire. The descriptive statistics and univariate and multivariate logistic regression analyses were conducted using SPSS version 25. A P-value of <0.05 was considered significant. 412 patients on conventional treatment were included in this study; 355 (86.2%) were HIV patients, and 57 (13.8%) were TB patients. More than half, 217 (52.7%) participants reported using herbal medicine while on conventional therapy. Among those who claimed to have used herbal medicines, 32 (14.7%) received herbal medicine from traditional healers. About four of five herbal users did not disclose their use to their healthcare providers. The type of health facility on follow-up (P=0.03), disease status (P=0.01), occupation (P=0.02), discontinuing ART (P=0.03), and encountering side (P=0.04) were the determinant factors for the use of herbal medicine among our study participants. In the Metekel Zone, concomitant consumption of herbal medication is common among HIV/AIDS and tuberculosis patients. Furthermore, most patients did not disclose the healthcare practitioners about their herbal use. Therefore, healthcare practitioners must assess and counsel patients regarding the potential adverse effects and herb-drug interaction to optimize therapy.

Atractylodes lancea for cholangiocarcinoma: Modulatory effects on CYP1A2 and CYP3A1 and pharmacokinetics in rats and biodistribution in mice.

Atractylodes lancea (Thunb.) DC. (A. lancea: AL) is a promising candidate for the treatment of cholangiocarcinoma (bile duct cancer). The study investigated (i) the propensity of capsule formulation of the standardized extract of AL (formulated AL) to modulate mRNA and protein expression and activities of CYP1A2 and CYP3A1 in rats after long- and short-term exposure, (ii) the pharmacokinetics of atractylodin (ATD: active constituent) after long-term administration of formulated AL, and (iii) the biodistribution of atractylodin-loaded polylactic-co-glycolic acid (ATD-PLGA-NPs) in mice. To investigate CYP1A2 and CYP3A1 modulatory activities following long-term exposure, rats of both genders received oral doses of the formulated AL at 1,000 (low dose), 3,000 (medium dose), and 5,000 (high dose) mg/kg body weight daily for 12 months. For short-term effects, male rats were orally administered the formulated AL at the dose of 5,000 mg/kg body weight daily for 1, 7, 14 and 21 days. The pharmacokinetic study was conducted in male rats after administration of the formulated AL at the dose of 5,000 mg/kg body weight daily for 9 months. The biodistribution study was conducted in a male mouse receiving ATD-PLGA-NPs at the equivalent dose to ATD of 100 mg/kg body weight. The high dose of formulated AL produced an inducing effect on CYP1A2 but an inhibitory effect on CYP3A1 activities in male rats. The low dose, however, did not inhibit or induce the activities of both enzymes in male and female rats. ATD reached maximum plasma concentration (Cmax) of 359.73 ng/mL at 3 h (tmax). Mean residence time (MRT) and terminal phase elimination half-life (t1/2z) were 3.03 and 0.56 h, respectively. The extent of biodistribution of ATD in mouse livers receiving ATD-PLGA-NPs was 5-fold of that receiving free ATD. Clinical use of low-dose AL should be considered to avoid potential herb-drug interactions after long-term use. ATD-PLGA-NPs is a potential drug delivery system for cholangiocarcinoma treatment.

Inhibition of UGT1A1*1 and UGT1A1*6 catalyzed glucuronidation of SN-38 by silybins

UGT1A1 is the main enzyme that catalyzes the metabolic elimination and detoxification of SN-38, the active form of the drug irinotecan. Milk thistle products have been used widely to protect the liver from injury associated with the use of chemotherapeutic agents. To evaluate whether SN-38 metabolism can be affected by milk thistle products, the inhibitory effects of silybins on UGT1A1*1 and UGT1A1*6 were evaluated in the present investigation. Both silybin A and silybin B potently inhibited SN-38 glucuronidation catalyzed by UGT1A1*1 or UGT1A1*6. It was noteworthy that silybin A and silybin B showed synergistic effect in UGT1A1*1 microsomes at concentration around IC50, while additive effect in UGT1A1*6. According to the predicted AUCi/AUC ratios (the ratio of the area under the plasma concentration–time curve of SN-38 in the presence and absence of silybins), the coadministration of irinotecan and several milk thistle products, including silybin-phosphatidylcholine complex, two Legalon capsules, four Silymarin tablets or four Liverman capsules, may lead to clinically significant herb-drug interactions (HDI) via UGT1A1 inhibition. Meanwhile, Rgut values were much higher than 11 in all the groups, indicating potential HDI due to intestinal UGT1A1 inhibition.

Pharmacy practitioners' practice, awareness and knowledge about herbal products and their potential interactions with cardiovascular drugs.

Background: Herbal medicine use is widespread among patients, as community pharmacies may provide such products. Therefore, pharmacy practitioners should be aware of potential herbal products' adverse effects and herb-drug interactions, particularly with medications for comorbid diseases, such as cardiovascular drugs, in which pharmacy practitioners need to have good knowledge to provide patients with relevant advice to get optimal and safe therapeutic outcomes. Accordingly, the study is designed to assess the knowledge and awareness of pharmacy practitioners regarding herbal product dispensing and cardiovascular drug interaction in Jordan and view their role in patients' counselling to set up safe and effective drug use. Methods: A cross-sectional study was conducted in Jordan using an online formatted questionnaire distributed to pharmacy practitioners working in community pharmacies. Descriptive and analytical statistics were performed for the responses using the Statistical Package for the Social Sciences (SPSS) software, version 26. Results: Out of 508 participants, 41.7% had medium knowledge of herbal products pertaining mainly to university education (68.1%); 55.1% of participants dispensed herbal products without prescriptions for obesity and weight reduction (72.8%) and gastrointestinal problems (70.9%); this is because respondents agreed that herbal remedies are safe (28.5%) and effective (38.4%). Whilst the knowledge level of respondents about herbal medicine interaction with cardiovascular medication was medium, with a mean of 1.94, as this interaction may result in potentially serious consequences, 40.7% of respondents strongly agreed to gain more knowledge about the side effects of herbal products and medicine interactions through educational courses. Conclusions: The pharmacy practitioners had medium knowledge of herbal products; however, more attention should be paid to herb-drug interactions in the pharmacy educational curriculum. Additionally, pharmacy practitioners need to refresh their knowledge by attending periodic educational courses and by using reliable resources for information about herbal products in order to provide effective and competent pharmaceutical care.

Factors Affecting the Uptake of Combination Therapy for the Treatment of COVID-19

Aims: To analyze factors affecting the use of a combination of herbs and medication or supplements for COVID-19 treatment among self-isolation patients.&#x0D; Methodology: A cross-sectional study was conducted to 268 COVID-19 patients with home self-isolation in Indonesia. Data were collected by using a google form questionnaire, consisting of closed-formatted and open-ended questions, from October 9th to December 9th, 2021. A multivariate analysis was performed using a logistic regression test.&#x0D; Results: The proportion of COVID-19 patients who used a combination of herbs and medication or supplements was 78.4%. Vitamin C, vitamin D, and paracetamol were the medication and supplements most frequently taken by patients. The most commonly consumed herbs were honey (70.7%), ginger (50.18%), and saffron (26.74%). The multivariate analysis results showed that the duration of infection, sunbathing activities, and marital status were factors significantly associated with the use of a combination of herbs and medication or supplements (P&lt;0.05).&#x0D; Conclusion: This study highlighted that most COVID-19 patients used herbs in combination with medication or supplements for their treatment. Therefore, there is a necessity for education, especially for patients and health professionals about the potential herb-drug interactions.

Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2

In this study, hydroethanolic extracts of 30 top-selling botanicals (herbs) commonly used as ingredients of herbal dietary supplements in the US were screened for their potential to activate the human pregnane X receptor (hPXR) and human aryl hydrocarbon receptor (hAhR) and to increase the activities of hPXR- and hAhR-regulated drug metabolizing cytochrome P450 enzymes (i.e., CYP3A4 and CYP1A2, respectively). Of the 30 botanicals tested, 21 induced PXR and 29 induced AhR transcriptional activities. Out of the 21 botanicals that induced hPXR transcriptional activity, 14 yielded >50% induction in CYP3A4 activity at concentrations ranging from 6 to 60 µg/mL and 16 out of the 29 botanicals that activated hAhR yielded >50% induction in CYP1A2 activity at concentrations ranging from 3 to 30 µg/mL. Moreover, eight botanicals (G. gummi-gutta [garcinia], Hemp [low and high CBD content], H. perforatum [St. John’s wort], M. vulgare [horehound], M. oleifera [moringa], O. vulgare [oregano], P. johimbe [yohimbe] and W. somnifera [ashwagandha]) yielded >50% induction in both CYP3A4 and CYP1A2 activity. Herbal products are mixtures of phytoconstituents, any of which could modulate drug metabolism. Our data reveals that several top-selling botanicals may pose herb-drug interaction (HDI) risks via CYP450 induction. While in vitro experiments can provide useful guidance in assessing a botanical’s HDI potential, their clinical relevance needs to be investigated in vivo. Botanicals whose effects on hPXR/CYP3A4, and hAhR/CYP1A2 activity were most pronounced will be slated for further clinical investigation.

Herb-drug interaction resources: The PHYDGI database

BackgroundAccording to the WHO, about 60% of the world's population currently uses traditional herbal remedies as complementary or alternative medicine and 80% of the population in developing countries depends almost totally on them for their primary health-care requirements. Due to a lack of knowledge on the action mechanisms of plant compounds or mixture, concerns regarding the safety of potential Herb-Drug Interactions (HDIs) have been raised. Over the past two decades and by 2018, 124 WHO Member States had implemented regulations on herbal medicines. However, databases of interactions between plants and modern allopathic drugs are still limited. MethodsThis study aims to build a database containing the information required for the proper concomitant use of chemical drugs and plant remedies. To develop the HDI database, scientific research articles were searched online using Medline, Scopus and Google scholar databases. Specific key-words, including plant names and “herb” “drug” “interactions” were questioned. Articles were then selected on the availability of required information including the fine identification of the plant extracts. Peculiar attention was paid on data reliability, and redundancies in interaction data increased their credibility. To inform about this reliability, a specific grade was applied. Besides, a grade based on the strength of pharmacokinetic changes was also given. ResultsAs of February 2022, the PHYDGI database allows health care professionals, researchers and manufacturers of plant-based remedies and dietary supplements to search an entity amongst 58 plants and its potential interactions with a given drug amongst 114 commonly used medical substances. ConclusionThe PHYDGI database integrates scientific data on HDI in well-structured forms including reference to the scientific sources. It provides herbal entities and their interactions as well as the level of strength for the pharmacokinetic interactions. This database which will be available for health practitioners, for phyto-drugs and food supplement manufacturers should help reducing potential HDI and developing safe use of plant-based remedies or supplements.

Evaluation of Pharmacodynamic interaction between Tinospora Cordifolia Alcoholic extract and Gliclazide : An herb-drug interaction study

Many diabetic people today consume herbs or herbal formulations along with prescription and non-prescription medications which may result in the herb-drug interaction Tinospora Cordifolia, with berberine being one of the most abundant active phytoconstituent widely used as an antidiabetic While Gliclazide is indicated to treat type 2 diabetes mellitus whichacts asan insulin secretagogue .T. Cordifolia is a potent inhibitor of CYP2C9 and Gliclazide is known to be metabolized by this enzyme. Potential Pharmacodynamic herb drug interaction might be possible in case of co administration of both. The pharmacodynamic interaction between TCE and Gliclazide was evaluated on hypoglycemic activity in normal and streptozotocinnicotinamide-induced diabetic rats. The study was conducted in 2 parts viz. acute study and sub-acute study in both normal and diabetic animals. The serum triglyceride level and histopathology of pancreawas performed to assess effect on glucose metabolism and pancreas.FTIR Analysis was also carried out to evaluate the interaction between functional groups. The combination showed pharmacodynamic interaction as reduction the time of onset of action and increasing the duration of action of gliclazide when administered in combination with T. cardiofolia. In FTIR studies of combination showed no physical interaction betweenfunctional groups suggesting both drugs might be acting on the different receptors. The study concludes that the combination of Gliclazide with TCE showed an increase in the hypoglycemic effect as compared to the gliclazide alone in STZ-NIC induced diabetic rats. This might be utilized clinically as a beneficial drug interaction in patients after thorough investigations in clinical studies

Herbal supplements in Jordan: a cross-sectional survey of pharmacists’ perspectives and knowledge

ObjectivesPharmacists are ideal partners for engaging with the needs and expectations of patients. They can play a vital role by providing information and supplying herbal medicines. In some community settings,...