Search

Redox imbalance is reported to play a pivotal role in tumorigenesis, cancer development, and drug resistance. Severe oxidative damage is a general consequence of cancer cell responses to treatment and may cause cancer cell death or severe adverse effects. To maintain their longevity, cancer cells can rescue redox balance and enter a state of resistance to anticancer drugs. Therefore, targeting redox signalling pathways has emerged as an attractive and prospective strategy for enhancing the efficacy of anticancer drugs and decreasing their adverse effects. Over the past few decades, natural products (NPs) have become an invaluable source for developing new anticancer drugs due to their high efficacy and low toxicity. Increasing evidence has demonstrated that many NPs exhibit remarkable antitumour effects, whether used alone or as adjuvants, and are emerging as effective approaches to enhance sensitivity and decrease the adverse effects of conventional cancer therapies by regulating redox balance. Among them are several novel anticancer drugs based on NPs that have entered clinical trials. In this review, we summarize the synergistic anticancer effects and related redox mechanisms of the combination of NPs with conventional anticancer drugs. We believe that NPs targeting redox regulation will represent promising novel candidates and provide prospects for cancer treatment in the future. Highlights: An abnormal redox microenvironment plays a critical role in the tumorigenesis, development, and drug resistance of cancer. NPs can selectively act as pro-oxidants, inducing cytotoxicity in cancer cells, while also serving as antioxidants and protectors in normal cells for detoxification. NPs play a dual role in increasing the sensitivity and reversing the drug resistance of cancer cells, primarily through pro-oxidant action and, in some cases, through antioxidant action. The heterogeneities in cellular and molecular biology provide the potential basis for the diverse regulation of NPs on the redox state. The advances in novel redox-sensitive materials and clinical applications of NPs offer promising prospects. [ABSTRACT FROM AUTHOR]

The article focuses on the emerging importance of managing food–drug interactions within pharmacovigilance systems. It highlights the complexities and risks associated with these interactions, including their impact on drug absorption, metabolism, and efficacy. It underscores the need for enhanced awareness among healthcare providers and the integration of this information into national and international pharmacovigilance frameworks.

Background: Combination therapy was associated with an increased risk of drug-drug interactions (DDIs) in patients with type 2 diabetes mellitus (T2DM). The present study aimed to investigate the epidemiology of potential DDIs (pDDIs), including potential chemical drug-drug interactions (pCDIs) and potential herb-drug interactions (pHDIs), and classify the influencing factors of pDDIs in these patients. Methods: A retrospective study of the epidemiology of pDDIs among T2DM hospitalized patients older than 18 years and treated with at least two drugs during hospitalization was conducted over a 12-month period in 2019. PDDIs were identified with C (monitor therapy), D (consider therapy modification), and X (avoid combination) risk ratings. Binary logistic regression was used to analyze the risk factors of pDDIs. Results: A total of 6796 pDDIs were identified from 737 T2DM hospitalized patients during hospitalization, with 0.87% classified as X risk rating, 13.39% as D risk rating. Additionally, 1753 pDDIs were identified after discharge, with 0.11% as X and 25.73% as D risk rating. The drug-drug association networks showed that the majority of pCDIs were associated with cardiovascular system drugs. Chlorphenamine-potassium chloride and danshen-warfarin were the most prevalent interacting pairs of pCDIs and pHDIs with X rating during hospitalization. Multivariate analysis indicated that the likelihood of developing over 4 pDDIs was significantly higher among T2DM patients who had received over 8 medications. The presence of pDDIs after discharge was strongly associated with the complications of T2DM and the number of discharge medications. Conclusions: T2DM patients were frequently exposed to pDDIs, including pCDIs and pHDIs, both during hospitalization and after discharge. Multi-drug combination was the primary risk factor for pDDIs. Strategies such as enhancing the monitoring and warning for pDDIs, increasing clinical pharmacological experience, as well as developing universally applicable clinical guidelines for pDDIs may be beneficial in reducing the incidence of potentially harmful drug-combinations. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is identified by lipid accumulation in the liver and liver injury due to obesity and metabolic syndrome. Herbs have been used in the treatment of various diseases, including liver disease. The present systematic review aimed to identify plants and the doses used in the management and prevention of NAFLD, as well as to assess the safety of these plants and determine their mechanisms of action, providing the preclinical evidence-based usage of herbs. Scientific databases, namely, Scopus, PubMed, Springer, NCBI, Google Scholar, Science Direct, and Web of Science were searched with key words, such as 'non-alcoholic fatty liver disease', 'non-alcoholic steatohepatitis', 'metabolic-associated fatty liver disease', 'medicinal plants', 'hyperlipidemia' and 'plant extracts' from January, 2016 to November, 2023. Manual screening, quality assessment, and data extraction of the search results were performed according to the inclusion and exclusion criteria. Herbs were identified which were able to ameliorate NAFLD symptoms in rodents through lipid metabolism, insulin resistance, inflammation and oxidative stress. These herbs were identified to lead to a reduction in steatosis in the histopathological assessment. The acute or chronic toxicity studies were not found to indicate any signs of toxicity. The present study provides information on the highest dose evaluated and which was effective against NAFLD, with safety assessment in studies using rats. Since chronic liver diseases progress over a long period of time with minimal or no symptoms, the consumption of herbs may provide alternative treatment strategies for the prevention of NAFLD. Further studies are warranted however, to identify their bioactive compounds for drug development or for the standardization of crude extracts. Drug-herb interactions also need to be further evaluated when used concurrently with drugs. [ABSTRACT FROM AUTHOR]

The interaction between herbal remedies and drugs is a fascinating phenomenon that might cause therapeutic complications in patients. Warfarin is an anticoagulant drug that provides anti-blood-clotting effects by inhibiting the formation of vitamin K-dependent coagulation factors, and warfarin interacts with the nuclear receptor PXR, subsequently modulating cytochrome P450 during the metabolism process. St. John's wort, an herbal medicine with antidepressant effects, can alter the pharmacokinetics of warfarin. Thymoquinone is one of the active compounds in N. sativa and has pharmacological activities such as anticoagulant, antidiabetic, diuretic, antidepressant, and anti-inflammatory effects. In this study, we investigated the compounds in Nigella sativa ( N. sativa) against pregnane X receptor (PXR) and evaluated the impact of thymoquinone (TQ) administration on PXR expression in HepG2 cells. The molecular docking analysis was conducted utilizing the Molecular Operating Environment (MOE) with the PXR (PDB ID: 7AXJ). At the same time, the PXR gene expression was measured using RT-PCR instruments. The RMSD value in docking represents the deviation criteria between the native ligand position and the redocking position result, indicating the capability of MOE and PDB qualification for performing molecular docking. The docking analysis showed that warfarin had the strongest binding energy (7AXJ -6.0507) by forming hydrogen binding type on Arg410. Despite TQ being the major component, it also displayed a high affinity for the two PDB IDs (7AXJ -4.5962). Furthermore, the concurrent administration of warfarin and TQ (19.27 μM) in HepG2 cells showed a significant reduction in the relative mRNA expression of the PXR gene. Given the above-mentioned findings, our study adequately enables us to predict the mechanism behind herb-drug interactions (HDIs) implicating N. sativa, specifically the TQ compound to warfarin metabolism via the activation of the PXR receptor. [ABSTRACT FROM AUTHOR]

\n Natural health products have emerged as a potential symptomatic therapeutic approach for people with Parkinson’s disease (PD).To determine the prevalence of natural health product use, interest in natural health products, awareness of potential herb-drug interactions, and consultation of healthcare professionals regarding natural health products use among people with PD.Cross-sectional 4-item survey embedded in the PRIME-NL study, which is a population-based cohort of PD.Of 367 people with PD, 36% reported having used natural health products to alleviate PD-related symptoms, with coffee, cannabis and turmeric being the most popular. Furthermore, 71% of people with PD were interested in learning more about natural health products. 39% of natural health products users were aware that these products could interact with PD medication and 39% had discussed their use with their healthcare professional.Natural health products are commonly used to alleviate symptoms by people with PD, but most users are unaware that these products can interact with PD medication and do not discuss their consumption with their healthcare professional.Parkinson’s disease is a complex neurodegenerative disorder for which current treatments are limited to symptomatic relief, and prescribed medication often causes side effects. In this context, there is an increasing interest in non-pharmacological interventions, and people living with Parkinson’s disease may want to explore natural health products to alleviate disease-associated symptoms. Examples of these products include cannabis, coffee, or velvet bean (as a natural source of Levodopa). However, it remains unclear how many people with Parkinson’s disease have ever used, or wish to use, natural health products to relieve disease-related symptoms. In addition, limited information is available to evaluate whether they are aware of possible interactions between these products and prescribed medication. Therefore, the aim of this study was to investigate these questions in a large representative group of people with Parkinson’s disease. A total of 367 people responded to the survey, and 36% reported that they had used natural health products to relieve Parkinson’s disease-related symptoms. Among the supplements listed in our survey, coffee (16%), cannabis (13%) and turmeric (10%) were the most popular. Additionally, 71% of participants were interested in learning more about natural health products, and we found that 39% of natural health product users were aware of possible interactions with prescribed Parkinson’s disease medication. However, it appeared that only 39% of users had discussed these supplements with their healthcare provider. These observations are important because a concern regarding the integration of natural health products into clinical practice is their potential interactions with prescribed medication. Therefore, these findings support the need for additional research efforts into the health benefits and safety of these products. We conclude that natural health products are used by people with Parkinson’s disease to provide symptomatic relief, and open discussions with their healthcare providers are encouraged to ensure efficacy and safety. [ABSTRACT FROM AUTHOR]

Objective: Patients with cancer often use complementary and alternative medication (CAM). This research aims to study the current attitude of healthcare professionals toward the use of CAM to improve current care. Methods: A questionnaire on both the current practice and opinions about CAM use was sent to healthcare professionals in Amsterdam UMC, who work for the department of hematology or oncology. Oncologists, hematologists, residents, (specialized) nurses, dieticians, (hospital)pharmacists, and pharmacy technicians were asked to participate in this study. Results: Among eligible healthcare professionals, 77 responded to the questionnaire (34%). Overall, 87% of healthcare professionals indicate it is important to be aware of their patient's CAM use, and all find the potential of drug–herb interactions important. However, more than half of the healthcare professionals inquire about the patient's CAM use infrequently. In addition, only 15% of the healthcare professionals stated they had sufficient knowledge of CAM to advise patients on their use of CAM. Conclusions: Healthcare professionals are aware of the potential risks of CAM use in combination with anti-cancer treatment. However, CAM use is not yet discussed with every patient. This may be due to healthcare professionals' lack of knowledge about CAM. [ABSTRACT FROM AUTHOR]

Aims: Health food products (HFPs) are foods and products related to maintaining and promoting health. HFPs may sometimes cause unforeseen adverse health effects by interacting with drugs. Considering the importance of information on the interactions between HFPs and drugs, this study aimed to establish a workflow to extract information on Drug‐HFP Interactions (DHIs) from open resources. Methods: First, Information on drugs, enzymes, their interactions, and known DHIs was collected from multiple public databases and literature sources. Next, a network consisted of enzymes, HFP, and drugs was constructed, assuming enzymes as candidates for hubs in Drug‐HFP interactions (Method 1). Furthermore, we developed methods to analyze the biomedical context of each drug and HFP to predict potential DHIs out of the DHIs obtained in Method 1 by applying BioWordVec, a widely used biomedical terminology quantifier (Method 2‐1 and 2‐2). Results: 44,965 DHIs (30% known) were identified in Method 1, including 38 metabolic enzymes, 157 HFPs, and 1256 drugs. Method 2‐1 selected 7401 DHIs (17% known) from the DHIs of Method 1, while Method 2‐2 chose 2819 DHIs (30% known). Based on the different assumptions in these methods where Method 2‐1 specifically selects HFPs interacting with specific enzymes and Method 2‐2 specifically selects HFPs with similar function with drugs, the propsed methods resulted in extracting a wide variety of DHIs. Conclusions: By integrating the results of language processing techniques with those of the network analysis, a workflow to efficiently extract unknown and known DHIs was constructed. [ABSTRACT FROM AUTHOR]

Introduction. Depression a.ects an estimated 350 million people worldwide and is implicated in up to 60% of suicides. Only about 60-70% of patients respond to antidepressant therapy. One of the factors causing patients to not attain therapeutic goals is herbdrug interactions. Objective. To investigate any potential herb-drug interaction that might exist between Xylopia aethiopica extract (XAE) or xylopic acid (XA) and selected conventional antidepressants (imipramine,

The utilization of traditional medicine (TM) is prevalent among the general population in Africa; however, its use among individuals with diabetes in the region remains underdocumented. This review aimed to synthesize the available literature to identify the prevalence and predictors of TM use among persons with diabetes in Africa. A systematic search was conducted across multiple databases, including MEDLINE, Embase, CINAHL, and AMED, covering studies published from 2000 to April 2023. Of 1560 records identified, 24 articles met the inclusion criteria. The prevalence of TM use varied significantly, ranging from 12.4% to 77.1%, with a median prevalence of 50%. TM was commonly used concurrently with conventional medicine (CM) (35.4–88.4%), with a majority (63.8–91.3%) not disclosing TM use to healthcare providers. Female gender, long diabetes duration, use of oral antiglycaemic medication and family history of diabetes emerged as the most common factors that predicted the use of TM. This review highlights the widespread use of TM among individuals with diabetes in Africa, often in conjunction with CM. The high prevalence of undisclosed TM use emphasizes the urgent need for healthcare providers to actively inquire about TM use during clinical consultations to address potential herb–drug interactions and adverse effects. [ABSTRACT FROM AUTHOR]

• There is a global need for treatment of symptoms associated with Covid-19. • 10 of the 23 plants showed no toxicity against human lung fibroblast (MRC-5) cells. • Anti-coagulation activity shown by F. vulgare Mill., M. africana L., P. latifolius (Thunb.) R.Br. ex Mirb. and R. tridentata (L.f.) Willd. & R.B. Drumm. • Varying levels of anti-inflammatory activity observed in lead samples. Millions of people have been negatively affected by the Covid-19 (SARS-CoV-2) pandemic worldwide. Multiple stages characterize Covid-19 infection, initial stages include common symptoms that are milder in nature (fever, dry coughs, fatigue) with later stages being characterized by more severe symptoms such as pneumonia, acute respiratory stress disorder (ARDS), inflammation, coagulation, potentially multiple organ failure and death. This study aimed to evaluate the ethanolic extracts of twenty-three medicinal plants for their cytotoxic effects and their anticoagulant and anti-inflammatory activities. Furthermore, bioactive extracts were evaluated for potential interactions with Cytochrome P450 enzymes, which play a role in drug metabolism. Ten plants, namely, Aspalathus linearis, Bulbine frutescens, Clausena anisata, Capparis tomentosa, Foeniculum vulgare, Myrsine africana, Podocarpus latifolius, Polygala virgata, Rhoicissus tridentata and Tylosema esculentum exhibited no cytotoxicity on human lung fibroblast cells (MRC-5) and were subsequently tested for anticoagulant activity. Four plants, namely, F. vulgare, M. africana, P. latifolius and R. tridentata showed anticoagulant activity and were further tested for drug-herb interactions. Interactions with CYP 1A2, CYP 2C9, CYP 2C19, CYP 2D6 and CYP 3A4 showed that 10 µg/ml of M. africana and R. tridentata increased the activity of all enzymes. F. vulgare exhibited a significant increase in activity of all CYP P450 enzymes tested except for CYP 2C9, while P. latifolius showed significant inhibition of both CYP 2C9 and CYP 2C19 and significant increases in CYP 1A2, CYP 2D6 and CYP 3A4 activity. The given herb-drug interactions suggest caution and further investigation as both inhibition and induction of CYP P450 enzymes may lead to adverse effects in drug interactions through bioaccumulation of the drug to toxic amounts or increased clearance. During the evaluation of anti-inflammatory activity of F. vulgare, M. africana, P. latifolius and R. tridentata ethanolic extracts, it was found that F. vulgare inhibited the production of IL-8, IL-12p70 and IL-6 at 100 µg/ml. The extract of M. africana inhibited IL-12p70, IL-8, TNF-α and IL-6 cytokines at 100 µg/ml. Both P. latifolius and R. tridentata showed inhibition of IL-12p70, IL-6 and IL-8 at 100 µg/ml. It can be concluded that F. vulgare, M. africana, P. latifolius and R. tridentata have been identified as possible leads against the selected targets associated with Covid-19 infection and should be investigated further for pre-clinical studies. [ABSTRACT FROM AUTHOR]

Using herbs in the Arab world is becoming increasingly common. Hence, there is a potential for pharmacokinetic and pharmacodynamic herb-drug interactions. Cytochrome P450 (CYP) enzymes and efflux transporter such as P-glycoprotein (P-gp) are vulnerable to modulation by the multiple active constituents of herbs. To examine the effects of some herbal plants on the gene expression of CYP1A1 metabolizing enzyme and P-glycoprotein. In vitro approach using human breast cancer cell line MCF7 and human colon adenocarcinoma Caco2 cell line were used to evaluate the effects of ten herbal plants Paronychia argentea lam., Achillea bibersteni L., Teucrium polium L., Achillea santolina L., Arbutus andrachne L., Ruta graveolens L. Chrysanthemum coronarium L., Iles paraguariensis A.st., Catha edulis Forsk., and Anthemis palastina Boiss on the mRNA expression of CYP1A1 and P-gp. The toxicities of these plants on the cell lines were evaluated with tetrazolium dye MTT test. Only Catha edulis had shown anti-proliferative activity against MCF7, but not against Caco2. Paronychia argentea, Ruta graveolens and Catha edulis on MCF7 and Paronychia argentea, Arbutus andrachne,Chrysanthenum coronarium and Anthemis palastina on Caco2 observed induction of CYP1A1 with dose dependant manner. Variation between induction and inhibition were noticed with plant effects on P-gp expression. Paronychia argentea has shown dose dependant induction effect, Anthemis palastina induced P-gp at high concentrations, Whereas both Teucrium polium and Catha edulis inhibit P-gp at 100µg/ml. The overall results indicate a potential food-drug interaction, which definitely should be investigated further on animal and human kinetic models. [ABSTRACT FROM AUTHOR]

Integrative therapy by combining conventional with herbal medicines is one of the choices for the community. However, there are opportunities for potential drug-herb interactions. Piperine, the primary alkaloid in the Piperaceae family, has been shown to change the pharmacokinetic profile of drugs and influence drug pharmacodynamics. This study aimed to determine the potential interactions between the combination of Piperaceae herb extract and conventional drugs based on their pharmacological activity in vivo. Black and Javanese long pepper extracts were prepared using the maceration method in ethanol. Then, the piperine level was determined using the TLCdensitometric method. Potential interactions were investigated through in vivo analgesic, anxiolytic, and anti-inflammatory activity studies. Piperine content in black and Javanese long pepper extract was 20.46% and 15.65%, respectively. Conventional drugs consumed with piperine or Piperaceae herbal extracts showed an increase in the latency time of mice on a hot-cold plate but a decrease in mice's survival time on the rotarod and oedema volume compared to single drug administration at various times. All combined treatments also enhance the percentage of analgesic (21.73% to 25.60%), anxiolytic (65% to =80%), and inflammation inhibitory (14.81% to =51.85%) activities of drugs. It concluded that piperine in black pepper or Javanese long pepper extracts has the potency to interact with drugs, especially with diclofenac sodium, alprazolam, and dexamethasone, based on the enhancement of their activity. Thus, further research is needed to determine its toxicity and pharmacokinetic profile to ensure the safety of these drug interactions. [ABSTRACT FROM AUTHOR]

The prevalence of stress- and anxiety-related disorders is increasing along with widespread demand for anxiolytics. Due to drug supply shortages and access restrictions, nonprescription remedies have gained popularity. In addition, the marketing of herbals and botanicals as low-cost and all-natural products with fewer access restrictions has increased their use. The current article explores the evidence to provide an overview of the current understanding of Ashwagandha (Withania somnifera), an anxiolytic and apoptogenic herb with therapeutic and health-promoting potentials to help the body reduce stress and maintain a homeostatic state. Due to poor quality controls and diversity of Ashwagandha products, clinical trials on Ashwagandha's effectiveness in anxiety-related conditions reveal conflicting results, although many show favorable findings. Furthermore, health care professionals, such as nurses, advanced practice nurses, physicians, physician assistants, and pharmacists, need to be aware of variability in Ashwagandha products, quality controls, reported evidence regarding use, safety profile, and clinical implications in stress reduction. [Journal of Psychosocial Nursing and Mental Health Services, 62(4), 33–40.] [ABSTRACT FROM AUTHOR]

Traditional Chinese Medicine has a long history in ophthalmology in China. Over 250 kinds of Traditional Chinese Medicine have been recorded in ancient books for the management of eye diseases, which may provide an alternative or supplement to current ocular therapies. However, the core holistic philosophy of Traditional Chinese Medicine that makes it attractive can also hinder its understanding from a scientific perspective – in particular, determining true cause and effect. This review focused on how Traditional Chinese Medicine could be applied to two prevalent ocular diseases, glaucoma, and cataract. The literature on preclinical and clinical studies in both English and Chinese on the use of Traditional Chinese Medicine to treat these two diseases was reviewed. The pharmacological effects, safety profile, and drug-herb interaction of selected herbal formulas were also investigated. Finally, key considerations for conducting future Traditional Chinese Medicine studies are discussed. [ABSTRACT FROM AUTHOR]

Objective: A remarkably sensitive, accurate, and efficient ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) approach was developed as a facile and expeditious method for measuring cilofexor concentration in beagle dogs, the herb-drug interactions between silybinin and cilofexor was explored based on pharmacokinetics. Methods: The plasma sample protein of the beagles were rapidly sedimented with acetonitrile, and cilofexor and tropifexor (internal standard, ISTD) were separated by gradient elution using a 0.1% formic acid aqueous solution and acetonitrile as the mobile phase. The concentrations were detected using positive ion multiple reaction monitoring (MRM) mode. Mass transfer pairs were m/z 587.91-267.91 for cilofexor and m/z 604.08228.03 for ISTD, respectively. A two-period self-controlled experimental design was adopted for the HDIs experiment. In the first period (Group A), six beagle dogs were orally administered cilofexor at a dose of 1 mg/kg. In the second period (Group B), silybinin (3 mg/kg) was orally administered to the six beagle dogs twice a day for seven consecutive days, after which cilofexor was orally administered. The cilofexor concentration in beagle dogs was determined, and HDIs were evaluated based on their pharmacokinetics. Results: The accuracy and precision of cilofexor were both less than 15%, and the recoveries, matrix effects, and stability met the relevant requirements. The Cmax of cilofexor in group B was 49.62% higher than that in group A, whereas the AUC(0-t) and AUC(0-8) of cilofexor in group B were 47.85% and 48.52% higher, respectively, than those in group A. Meanwhile, the t1/2 extended from 7.84 h to 9.45 h, CL and Vz decreased in Group B. Conclusion: A novel UPLC-MS/MS approach was successfully applied for the measurement of cilofexor in beagle dog plasma. Silybinin can alter the pharmacokinetics of cilofexor in beagle dogs, thereby increasing plasma exposure to cilofexor. [ABSTRACT FROM AUTHOR]

Background: Herb-drug interactions may result in increased adverse drug reactions or diminished drug efficacy, especially for drugs with a narrow therapeutic index such as warfarin. The current study investigates the effects of sodium ferulate for injection (SFI) on anticoagulation of warfarin from aspects of pharmacodynamics and pharmacokinetics in rats and predicts the risk of the combination use. Methods: Rats were randomly divided into different groups and administered single- or multiple-dose of warfarin (0.2 mg/kg) with or without SFI of low dose (8.93 mg/kg) or high dose (26.79 mg/kg). Prothrombin time (PT) and activated partial thromboplastin time (APTT) were detected by a blood coagulation analyzer, and international normalized ratio (INR) values were calculated. UPLC-MS/MS was conducted to measure concentrations of warfarin enantiomers and pharmacokinetic parameters were calculated by DAS2.0 software. Results: The single-dose study demonstrated that SFI alone had no effect on coagulation indices, but significantly decreased PT and INR values of warfarin when the two drugs were co-administered (P < 0.05 or P < 0.01), while APTT values unaffected (P > 0.05). Cmax and AUC of R/S-warfarin decreased but CL increased significantly in presence of SFI (P < 0.01). The multiple-dose study showed that PT, APTT, INR, and concentrations of R/S-warfarin decreased significantly when SFI was co-administered with warfarin (P < 0.01). Warfarin plasma protein binding rate was not significantly changed by SFI (P > 0.05). Conclusions: The present study implied that SFI could accelerate warfarin metabolism and weaken its anticoagulation intensity in rats. [ABSTRACT FROM AUTHOR]

Purpose: Herbal medicines are occasionally used in combination with conventional antidepressants to mitigate various depression-associated symptoms. However, there is limited information on herb–antidepressant interactions. In this study, we investigated the pharmacokinetic (PK) effects of four herbal medicines (Gami-soyosan, Banhasasim-tang, Ojeok-san, and Bojungikgi-tang) on escitalopram, a commonly used antidepressant. Patients and Methods: In this open-label, fixed-sequence, three-period, crossover study, 18 participants were enrolled and divided into two groups. Each group received a 10 mg oral dose of escitalopram in period 1. Participants took escitalopram once daily and their assigned herbal medicines thrice a day for 7 d in periods 2 (group 1: Gami-soyosan, group 2: Ojeok-san) and 3 (group 1: Banhasasim-tang; group 2: Bojungikgi-tang). The primary endpoints were Cmax,ss and AUCtau,ss of escitalopram. Cmax,ss and AUCtau,ss in period 1 were obtained using nonparametric superposition from single-dose data. The PK endpoints were classified according to the CYP2C19 phenotype. Results: Of 18 participants, 16 completed the study. Systemic exposure to escitalopram resulted in a minor increase in the presence of each herbal medicine. The geometric mean ratios (GMRs, combination with herbal medicines/escitalopram monotherapy) and their 90% confidence intervals (CIs) for Cmax,ss and AUCtau,ss were as follows: Gamisoyosan– 1.1454 (0.9201, 1.4258) and 1.0749 (0.8084, 1.4291), Banhasasim-tang– 1.0470 (0.7779, 1.4092) and 1.0465 (0.7035, 1.5568), Ojeok-san– 1.1204 (0.8744, 1.4357) and 1.1267 (0.8466, 1.4996), and Bojungikgi-tang– 1.1264 (0.8594, 1.4762) and 1.1400 (0.8515, 1.5261), respectively. Furthermore, no significant differences in the GMRs of Cmax,ss and AUCtau,ss were observed across different CYP2C19 phenotypes in any of the groups. Conclusion: The co-administration of escitalopram with Gami-soyosan, Banhasasim-tang, Ojeok-san, or Bojungikgi-tang did not exert significant PK effects on escitalopram. These findings provide valuable insights into the safe use of herbal medicines along with escitalopram. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is one of the chronic non-communicable diseases and has been rapidly increasing globally. Alpha glucosidase is an important enzyme that hydrolyzes polysaccharides into monosaccharides before being absorbed into the bloodstream. The alpha glucosidase inhibitors, such as acarbose are expensive and have several adverse effects. The use of herbal products to prevent or treatment of disease is becoming popular. There are many herbal products that can reduce blood sugar levels. However, taking herbal products with anti-DM medicines may cause herb-drug interactions that affect either the pharmacokinetics or pharmacodynamics of the drugs, leading to adverse effects or ineffective treatment. The aim of this study is to examine the effect of herbal extracts on alpha-glucosidase activity and the level of cytochrome P450 3A4 (CYP3A4) by using HepaRG as a model. Three herbs that reported blood glucose-lowering activity were selected including Moringa oleifera, Momordica charantia, and Morus alba. All herbs were extracted with 95% ethanol and tested for their in vitro alpha glucosidase inhibitory activity. The results showed that M. alba extract exhibits the highest activity (IC50= 83.75 µg/mL). Then, the extracts were evaluated for their cytotoxicity on the HepaRG cell line. All extracts showed no cytotoxicity at concentrations up to 250 µg/mL. The sub-cytotoxic concentration of each extract was selected to test for the effect on the CYP3A4 enzyme. The results showed that only M. alba extract elevated the level of CYP3A4, while the others slightly reduce the level of CYP3A4. However, this is a preliminary study that the major compounds of each extract must be isolated and evaluated in the future. [ABSTRACT FROM AUTHOR]

Background: Determination of batch-to-batch consistency of botanical drugs (BDs) has long been the bottleneck in quality evaluation primarily due to the chemical diversity inherent in BDs. This diversity presents an obstacle to achieving comprehensive standardization for BDs. Basically, a single detection mode likely leads to substandard analysis results as different classes of structures always possess distinct physicochemical properties. Whereas representing a workaround for multi-target standardization using multi-modal data, data processing for information from diverse sources is of great importance for the accuracy of classification. Methods: In this research, multi-modal data of 78 batches of Guhong injections (GHIs) consisting of 52 normal and 26 abnormal samples were acquired by employing HPLC-UV, -ELSD, and quantitative 1H NMR (q1HNMR), of which data obtained was then individually used for Pearson correlation coefficient (PCC) calculation and partial least square-discriminant analysis (PLS-DA). Then, a mid-level data fusion method with data containing qualitative and quantitative information to establish a support vector machine (SVM) model for evaluating the batch-to-batch consistency of GHIs. Results: The resulting outcomes showed that datasets from one detection mode (e.g., data from UV detectors only) are inadequate for accurately assessing the product's quality. The mid-level data fusion strategy for the quality evaluation enabled the classification of normal and abnormal batches of GHIs at 100% accuracy. Conclusions: A quality assessment strategy was successfully developed by leveraging a mid-level data fusion method for the batch-to-batch consistency evaluation of GHIs. This study highlights the promising utility of data from different detection modes for the quality evaluation of BDs. It also reminds manufacturers and researchers about the advantages of involving data fusion to handle multi-modal data. Especially when done jointly, this strategy can significantly increase the accuracy of product classification and serve as a capable tool for studies of other BDs. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the effect of blackseed oil (BSO) single dose on prednisolone pharmacokinetics via p-gp inhibition. Methods: Three groups of rats (n = 5) were orally administered the vehicle, verapamil (50 mg/kg) or BSO (5 ml/kg) 15 min prior to prednisolone (5 mg/kg) administration. Blood samples were collected over 24 h and quantified. Non-compartmental analysis was employed to calculate maximum plasma concentration (Cmax), area under the curve (AUC0-last), time to reach Cmax (Tmax), apparent clearance (CL/F), and half-life (t1/2). Statistical significance was considered at p<0.05. Results: Prednisolone Cmax and AUC0-last decreased by 65% and 25% in the BSO group compared to the negative control (P <.0001,.0029, respectively) while they increased by 1.75-folds and 8-folds in verapamil group (P <.0001). Tmax was achieved at 0.16, 0.5, and 0.25 h in the negative control, verapamil, and BSO-treated groups, respectively. CL/F in the treatment group was 1.3-fold and 10-fold higher compared to the negative and positive control, respectively, whereas the t1/2 remained comparable. Conclusion: Administration of BSO decreased prednisolone Cmax and AUC0-last in rats indicating that there is a herb-drug interaction; however, p-gp inhibition cannot be concluded. Patients relying on folk medicine in chronic illnesses treatment might need to avoid combining BSO with prednisolone. Graphical Abstract [ABSTRACT FROM AUTHOR]

Magnoliae Officinalis Cortex (MOC), an herbal drug, contains polyphenolic lignans mainly magnolol (MN) and honokiol (HK). Methotrexate (MTX), a critical drug for cancers and autoimmune deseases, is a substrate of multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP). This study investigated the effect of coadministration of MOC on the pharmacokinetics of MTX and relevant mechanisms. SpragueeDawley rats were orally administered MTX alone and with single dose (2.0 and 4.0 g/kg) and repeated seven doses of MOC (2.0 g/kg thrice daily for 2 days, the 7th dose given at 0.5 h before MTX). The serum concentrations of MTX were determined by a fluorescence polarization immunoassay. The results showed that a single dose of MOC at 2.0 g/kg significantly increased the AUC0-t and MRT of MTX by 352% and 308%, and a single dose at 4.0 g/kg significantly enhanced the AUC0-t and MRT by 362% and 291%, respectively. Likewise, repeated seven doses of MOC at 2.0 g/kg significantly increased the AUC0-t and MRT of MTX by 461% and 334%, respectively. Mechanism studies indicated that the function of MRP2 was significantly inhibited by MN, HK and the serum metabolites of MOC (MOCM), whereas BCRP was not inhibited by MOCM. In conclusion, coadministration of MOC markedly enhanced the systemic exposure and mean residence time of MTX through inhibiting the MRP2-mediated excretion of MTX. [ABSTRACT FROM AUTHOR]

A simple and rapid high-performance liquid chromatography (HPLC) was developed to determine the plasma level of nifedipine in rats after its single administration and combination with herbs. Nifedipine was extracted with acetonitrile to precipitate protein from plasma samples. The separation was implemented on a C18 column with a mobile phase of acetonitrile: water (63:37, v/v). The calibration curve displayed good linearity in the 30-1000 ng/mL range. The lower limit of quantification (LLOQ) was 30 ng/mL. The intraday and interday assay accuracy and precision met the criteria of validation and study sample analysis. The recovery was found to be 101.89%. Stability studies showed that nifedipine was stable after 12 h at room temperature and 21 days at -20 °C. No significant difference was examined between the pharmacokinetic parameters of nifedipine with or without Gynura procumbens leaf extract. The proposed method was helpful for the pharmacokinetic interaction study of nifedipine combined with herbal in rats. [ABSTRACT FROM AUTHOR]

Introduction: Kangai (KA) injection, a Chinese herbal injection, is often used in combination with irinotecan (CPT-11) to enhance the effectiveness of anticolorectal cancer treatment and alleviate side effects. However, the combined administration of this herb-drug pair remains controversial due to limited preclinical evidence and safety concerns. This study aimed to determine the preclinical herb-drug interactions between CPT-11 and KA injection to provide a reference for their clinical co-administration. Methods: In the pharmacological study, BALB/c mice with CT26 colorectal tumors were divided into four groups and treated with vehicle alone (0.9% saline), CPT-11 injection (100 mg/kg), KA injection (10 mL/kg), or a combination of CPT-11 and KA injection, respectively. The tumor volume of mice was monitored daily to evaluate the therapeutic effect. Daily body weight, survival rate, hematopoietic toxicity, immune organ indices, and gut toxicity were analyzed to study the adverse effects. Healthy Sprague-Dawley rats in the pharmacokinetic study were administered KA injection only (4 mL/kg), or a combination of CPT-11 injection (20 mg/kg) and KA injection, respectively. Six key components of KA injection (oxymatrine, matrine, ginsenoside Rb1, Rg1, Re, and astragaloside IV) in rat plasma samples collected within 24 h after administration were determined by LC-MS/MS. Results: The pharmacological study indicated that KA injection has the potential to enhance the anti-colorectal cancer efficacy of CPT-11 injection and alleviate the severe weight loss induced by CPT-11 injection in tumor-bearing mice. The pharmacokinetic study revealed that co-administration resulted in inhibition of oxymatrine metabolism in rats, evidenced by the significantly reduced Cmax and AUC0-t of its metabolite, matrine (p < 0.05), from 2.23 ± 0.24 to 1.38 ± 0.12 μg/mL and 8.29 ± 1.34 to 5.30 ± 0.79 μg h/mL, respectively. However, due to the similar efficacy of oxymatrine and matrine, this may not compromise the anti-cancer effect of this herb-drug pair. Discussion: This study clarified the pre-clinical pharmacology and pharmacokinetic benefits and risks of the CPT-11-KA combination and provided a reference for their clinical co-administration.c [ABSTRACT FROM AUTHOR]

Gegenqinlian decoction (GQD) is a classic prescription of traditional Chinese medicine (TCM), which originated from Shanghanlun. The combination of GQD and hypoglycemic drugs (saxagliptin, Sax, metformin) is often used to treat Type 2 diabetes mellitus (T2DM) in TCM clinics. However, the herb–drug interactions (HDIs) between GQD and hypoglycemic drugs are still unclear. In order to determine the safety of the combination, we assessed the influences of GQD on the pharmacokinetics and pharmacodynamics of Sax in T2DM rats. The plasma concentration of Sax (5 mg/kg) pretreated with GQD (freeze‐dried powder, 1.35 g/kg) or not was determined by high‐performance liquid chromatography (HPLC), and pharmacokinetics parameters were calculated. The influence of GQD on the pharmacodynamics of Sax was investigated by detecting the levels of weight, (see abbreviations list) OGTT, TC, TG, LDL‐C, HDL‐C, FBG, FINS, HOMA‐IR, QUICKI, AST, ALT, and the liver coefficient. The Cmax, AUC0‐t,and AUC0‐∞ of Sax increased significantly in the combination group whether in normal or T2DM rats. The results of pharmacodynamics showed that the weight of rats in each treatment group increased. FBG, TC, TG, LDL‐C, and HOMA‐IR decreased, HDL‐C, FINS, and QUICKI increased significantly (p < 0.05) compared with the model control group. The result showed that the combination of GQD and Sax could not only improve the hypoglycemic effect but also increase the plasma exposure of Sax. The potential HDIs between GQD and Sax should be taken into consideration in clinics. Moreover, for the complexity of the human compared with experimental animals, as well as genetic differences, the in‐depth study should be carried out to assess the uniformity of the pharmacokinetics and pharmacodynamics between rats and humans. [ABSTRACT FROM AUTHOR]

Danggui Buxue Decoction (DBD), a traditional Chinese medicine formula, has the potential to enhance the antitumor effect of gemcitabine in non-small cell lung cancer (NSCLC) treatment by increasing gemcitabine's active metabolites. However, whether gemcitabine affects the pharmacokinetics of DBD's major components remains unclear. This study evaluates the herb–drug interaction between DBD's major components and gemcitabine and validates the underlying pharmacokinetic mechanism. The pharmacokinetics of 3.6 g/kg DBD with and without a single-dose administration of 50 mg/kg gemcitabine was investigated in Sprague-Dawley rats. The effects of gemcitabine on intestinal permeability, hepatic microsomal enzymes in rat tissues, and CYP3A overexpressing HepG2 cells were determined using western blot analysis. The combination of gemcitabine significantly altered the pharmacokinetic profiles of DBD's major components in rats. The Cmax and AUC of calycosin-7-O-β-d-glucoside notably increased through sodium-glucose transporter 1 (SGLT-1) expression promotion. The AUC of ligustilide and ferulic acid was also significantly elevated with the elimination half-life (t1/2) prolonged by 2.4-fold and 7.8-fold, respectively, by down-regulating hepatic CYP3A, tight junction proteins zonula occludens-1 (ZO-1) and occludin expression. Gemcitabine could modulate the pharmacokinetics of DBD's major components by increasing intestinal permeability, enhancing transporter expression, and down-regulating CYP3A. These findings provide critical information for clinical research on DBD as an adjuvant for NSCLC with gemcitabine and help make potential dosage adjustments more scientifically and rationally. [ABSTRACT FROM AUTHOR]

Introduction: Numerous investigations on herbal medicine that have been undertaken in the past several years demonstrate the general acceptance of its safety. The Saudi Food and Drug Authority (SFDA) established the Herb–Drug Interaction (HDI) project to detect and assess potential HDIs to ensure safety. The aim is to detect safety signals and assess them based on available evidence. Methods: First, SFDA-registered herbal products (n = 30) were selected and prioritized based on commonly used herbs. Second, reported potential HDIs were retrieved from the World Health Organization global database of individual case safety reports (VigiBase), AdisInsight®, and the Natural Medicines database. We excluded drugs non-registered by SFDA and labeled interactions in the product information of SFDA, the US Food and Drug Administration (FDA), and the European Medicines Agency (EMA). Finally, a comprehensive evaluation of potential HDIs was carried out using several evidence sources: literature, global cases, local cases, and other relevant documents. The Drug Interaction Probability Scale (DIPS) scale was used to assess the probability of a causal relationship between the interacting herb and drug and the event. Results: The search yielded 566 potential signals, and 41 had published evidence and were referred for assessment. The assessment results using DIPS were: 22 possible (53.6 %), 7 probable (17%), and 12 doubtful (29.2%) interactions. The recommendation was to include probable HDIs in the product information, including turmeric–tacrolimus, etoposide–Echinacea, Ginkgo biloba–ibuprofen, green tea–warfarin, and licorice–thiazides interactions. Conclusion: The HDI project assessed the screening and identification of potential HDIs. The action plan of this project can be used in post-marketing activities to identify potential drug interactions. [ABSTRACT FROM AUTHOR]

Unlike conventional drug substances, herbal medicines are composed of a complex of biologically active compounds. Therefore, the potential occurrence of herb-drug interactions is even more probable than for drug-drug interactions. Interactions can occur on both the pharmacokinetic and pharmacodynamic level. Herbal medicines may affect the resulting efficacy of the concomitantly used (synthetic) drugs, mainly on the pharmacokinetic level, by changing their absorption, distribution, metabolism, and excretion. Studies on the pharmacodynamic interactions of herbal medicines and conventional drugs are still very limited. This interaction level is related to the mechanism of action of different plant constituents. Herb-drug interactions can cause changes in drug levels and activities and lead to therapeutic failure and/or side effects (sometimes toxicities, even fatal). This review aims to provide a summary of recent information on the potential drug interactions involving commonly used herbal medicines that affect the central nervous system (Camellia, Valeriana, Ginkgo, Hypericum, Humulus, Cannabis) and conventional drugs. The survey databases were used to identify primary scientific publications, case reports, and secondary databases on interactions were used later on as well. Search keywords were based on plant names (botanical genera), officinal herbal drugs, herbal drug preparations, herbal drug extracts. [ABSTRACT FROM AUTHOR]

Natural products, such as herbal medicinal products, food supplements, and functional food, are widely used to support well-being and for promoting health. In general, the effects of using these products are desired and beneficial, but unexpected adverse effects might also occur, especially when natural products are used with medication. Consumers do not often even know that they are exposed to bioactive compounds that might interact with the body and have effects on their well-being. One of the objectives of the World Health Organization is to promote herb-drug interaction monitoring, and it is important to know how marketed preparations and compounds from common foods interact when they are absorbed. In this review, we describe how a Caco-2 cell absorption model has been used to study how natural products, such as flaxseed, rapeseed, purple loosestrife, pine, echinacea, certain berries and herbs, anthranoid laxatives, and traditional medicinal plants, affect the absorption of co-administered drugs. We discuss the types of interactions and adverse effects that might occur and their possible reasons. Overall, we conclude that the Caco-2 cell absorption model is a useful tool for studying the absorption of natural products with drugs; and that to enable the safe use of natural products with medicines, concomitant use should be studied. [ABSTRACT FROM AUTHOR]

Suberosin is a natural phytoconstituent isolated from Citropsis articulata, especially employed for its anticoagulant properties. Although metabolic studies assessing suberosin have been conducted, it is possible interactions with drugs and food have not yet been investigated. In the present study, we analyzed the selective inhibitory effects of suberosin on cytochrome P450 (CYP) enzymes using a cocktail probe assay. Various concentrations of suberosin (0–50 μM) were incubated with isoform‐specific CYP probes in human liver microsomes (HLMs). We found that suberosin significantly inhibited CYP1A2‐catalyzed phenacetin O‐deethylation, exhibiting IC50 values of 9.39 ± 2.05 and 3.07 ± 0.45 μM with and without preincubation in the presence of β‐NADPH, respectively. Moreover, suberosin showed concentration‐dependent, but not time‐dependent, CYP1A2 inhibition in HLMs, indicating that suberosin acts as a substrate and reversible CYP1A2 inhibitor. Using a Lineweaver‐Burk plot, we found that suberosin competitively inhibited CYP1A2‐catalyzed phenacetin O‐deethylation. Furthermore, suberosin showed similar inhibitory effects on recombinant human CYP1A1 and 1A2. In conclusion, suberosin may elicit herb–drug interactions by selectively inhibiting CYP1A2 during the concurrent administration of drugs that act as CYP1A2 substrates. [ABSTRACT FROM AUTHOR]

Background: The clinical outcomes of antiretroviral drugs may be modified through drug interactions; thus, it is important to update the drug interactions in people living with HIV (PLHIV). Aim: To update clinically relevant drug interactions in PLHIV on antiretroviral therapy with novel drug interactions published from 2017 to 2022. Methods: A systematic review in Medline/PubMed database from July 2017 to December 2022 using the Mesh terms antiretroviral agents and drug interactions or herb–drug interactions or food–drug interactions. Publications with drug interactions in humans, in English or Spanish, and with full-text access were retrieved. The clinical relevance of drug interactions was grouped into five levels according to the gravity and probability of occurrence. Results: A total of 366 articles were identified, with 219 (including 87 citation lists) were included, which allowed for the identification of 471 drug interaction pairs; among them, 291 were systematically reported for the first time. In total 42 (14.4%) and 137 (47.1%) were level one and two, respectively, and 233 (80.1%) pairs were explained with the pharmacokinetic mechanism. Among these 291 pairs, protease inhibitors (PIs) and ritonavir/cobicistat-boosted PIs, as well as integrase strand transfer inhibitors (InSTIs), with 70 (24.1%) and 65 (22.3%) drug interaction pairs of levels one and two, respectively, were more frequent. Conclusions: In PLHIV on antiretroviral therapy, we identify 291 drug interaction pairs systematically reported for the first time, with 179 (61.5%) being assessed as clinically relevant (levels one and two). The pharmacokinetic mechanism was the most frequently identified. PIs, ritonavir/cobicistat-boosted PIs, and InSTIs were the antiretroviral groups with the highest number of clinically relevant drug interaction pairs (levels one and two). [ABSTRACT FROM AUTHOR]

Background: Erlotinib is a selective epidermal growth factor receptor inhibitor that is used for the treatment of non‐small cell lung cancer and pancreatic cancer. Its metabolism is mainly mediated by cytochrome P450 3A (CYP 3A). Resveratrol, a natural compound found in many plants and supplements, is known to inhibit CYP3A enzyme, therefore, it may act as an inhibitor for the metabolism of erlotinib. Objective: Development of a rapid high performance liquid chromatography with photodiode array detection (HPLC‐PDA) method for the quantification of erlotinib in liver microsomes and cancer cells and its application to study resveratrol effect on metabolism and cellular uptake of erlotinib. Methods: HPLC‐PDA was used to develop an efficient bioanalytical method with a 2.5‐min runtime preceded by a simple protein precipitation step. The method was validated according to the European Medicines Agency guidelines. Erlotinib metabolic stability and resveratrol effect on erlotinib metabolite formation were evaluated in rat liver microsomes. Furthermore, the method was used to measure the intracellular concentrations of erlotinib in cancer colorectal cells and investigating resveratrol effect on the cellular uptake of erlotinib. Results: A rapid HPLC‐PDA method was developed and validated for the first time to address potential drug interaction of erlotinib with resveratrol. Resveratrol was a strong inhibitor of erlotinib metabolism in vitro with IC50 = 4.03 μM. Resveratrol, however, had no effect on erlotinib cellular uptake after 1 h incubation in human colorectal cancer cells. Conclusion: The study suggests that resveratrol may produce a potential herb–drug interaction with erlotinib at the metabolism level and should be investigated in patients in the clinic. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 15-year-old male teenager experiencing severe hypotension possibly due to an interaction between guanfacine and eucalyptus oil from over-the-counter cough drops. Topics discussed include the mechanism of guanfacine, its adverse effects, and the importance of considering drug interactions in clinical practice.

Background: With the rapid increase in the prevalence of cancer worldwide, the utilization of complementary and alternative medicine (CAM) has increased among cancer patients. This review aimed to understand the perception, attitudes, and knowledge of healthcare professionals toward using CAM for cancer patients. Methods: A mixed‐methods systematic review was undertaken in four databases. Inclusion criteria were primary studies reporting perception, attitudes, and knowledge of healthcare professionals for using CAM for cancer patients were eligible. A mixed‐methods convergent synthesis was carried out, and the findings were subjected to a GRADE‐CERQual assessment of confidence. Results: Forty‐two studies were chosen. The majority of the studies were quantitative and had less than 100 participants. Most publications were from European countries, and oncology was the highest among the specialties. The review found the following themes: feasibility of having negative adverse effects, low expectations of using CAM among HCPs, potential positive effects of using CAM, specific CAM training may be helpful, no concrete regulations to promote CAM practice, and poor physician–patient communication. Conclusions: Nurses had more positive views than other professions; oncologists were concerned regarding herb–drug interactions; integration of CAM into the healthcare system was favorable; HCPs felt the need to participate in specific CAM training; and HCPs agreed that CAM education should be provided more regularly. Future studies should explore the studies views of cancer patients and details of in‐depth evidence of CAM in oncology settings. [ABSTRACT FROM AUTHOR]

The use of information and communication technologies (ICTs) has revolutionized the provision of health services, often referred to as eHealth, benefiting community pharmacies that can offer new services in innovative formats, namely through telepharmacy. This study aimed to explore the perceptions of pharmacy professionals (i.e., pharmacists and pharmacy technicians) on the provision of new services. The study consisted of administering an online questionnaire to pharmacy professionals nationwide. The questionnaire was developed by the research team, based on focus group methodology, from which an inductive analysis led to the categories that made up the dimensions of the survey. Participants were 95 pharmacy professionals with a mean age of 33.69 years old (SD = 10.75). Almost 79% were women. The results show overall receptivity to the development of new services in community pharmacies. Suggestions for the development of the new services, conditions necessary for their implementation, potential obstacles, and strategies to promote adherence to the new services, among others, are identified. The knowledge thus acquired will help community pharmacies to develop innovative solutions in counselling, pharmacotherapy monitoring, and pharmacovigilance, for example, of herb/dietary supplement–drug adverse reactions and interactions. Based on this information, new services can become more accessible, namely through the use of ICTs. [ABSTRACT FROM AUTHOR]

Most of the currently available drugs are derived from natural sources, but they are used only after extensive chemical modifications to improve their safety and efficacy. Natural products are used in health supplements and cosmetic preparations and have been used as auxiliary drugs or alternative medicines. When used in combination with conventional drugs, these herbal products are known to alter their pharmacokinetics and pharmacodynamics, reducing their therapeutic effects. Moreover, herb–drug interactions (HDIs) may have serious side effects, which is one of the major concerns in health practice. It is postulated that HDIs affect the pathways regulating cytochrome P450 enzymes (CYPs). Betanin, the chief pigment of red beetroot (Beta vulgaris L.), has various types of pharmacological activity, such as anti-inflammatory, antioxidant, and anticancer effects. However, the potential risk of HDIs for betanin has not yet been studied. Thus, we aimed to predict more specific HDIs by evaluating the effects of betanin on CYPs (CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4), the major phase I metabolic enzymes, using fluorescence-/luminescence-based assays. Our results showed that betanin inhibited CYP3A4 activity in a dose-dependent manner (IC50 = 20.97 µΜ). Moreover, betanin acted as a competitive inhibitor of CYP3A4, as confirmed by evaluating Lineweaver–Burk plots (Ki value = 19.48 µΜ). However, no significant inhibitory effects were observed on other CYPs. Furthermore, betanin had no significant effect on CYP1A2, CYP2B6, or CYP2C9 induction in HepG2 cells. In conclusion, betanin acted as a competitive inhibitor of CYP3A4, and thus it should be used cautiously with other drugs that require metabolic enzymes as substrates. Additional in vivo studies and clinical trials are needed to further elucidate the HDIs of betanin. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: Theophylline is a bronchodilator with a narrow therapeutic index and primarily metabolised by cytochrome P450 (CYP) 1A2. Xin-yi-san (XYS) is a herbal formula frequently used to ameliorate nasal inflammation. This study aimed to investigate the effects of XYS and its ingredient, imperatorin, on theophylline pharmacokinetics in rats. Methods: The kinetics of XYS- and imperatorin-mediated inhibition of theophylline oxidation were determined. Pharmacokinetics of theophylline were analysed. Comparisons were made with the CYP1A2 inhibitor, fluvoxamine. Key findings: XYS extract and its ingredient, imperatorin, non-competitively inhibited theophylline oxidation. Fluvoxamine (50 and 100 mg/kg) and XYS (0.5 and 0.9 g/kg) significantly prolonged the time to reach the maximum plasma concentration (tmax) of theophylline by 3–10 fold. In a dose-dependent manner, XYS and imperatorin (0.1–10 mg/kg) treatments significantly decreased theophylline clearance by 27–33% and 19–56%, respectively. XYS (0.9 g/kg) and imperatorin (10 mg/kg) significantly prolonged theophylline elimination half-life by 29% and 142%, respectively. Compared with the increase (51–112%) in the area under curve (AUC) of theophylline by fluvoxamine, the increase (27–57%) by XYS was moderate. Conclusions: XYS decreased theophylline clearance primarily through imperatorin-suppressed theophylline oxidation. Further human studies are essential for the dose adjustment in the co-medication regimen. [ABSTRACT FROM AUTHOR]

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

Herbal medicines (HMs) have been traditionally used for the prophylaxis/treatment of cardiovascular diseases (CVDs). Their use is steadily increasing and many patients with CVDs often combine HMs with prescribed cardiovascular medications. Interestingly, up to 70% of patients do not notify cardiologists/physicians the use of HMs and up to 90% of cardiologists/physicians may not routinely inquire them about the use of HMs. There is limited scientific evidence from well-designed clinical trials supporting the efficacy and safety of HMs and because they do not reduce morbidity and mortality are not recommended in clinical guidelines for the prophylaxis/treatment of CVDs. There is also a great deal of confusion about the identification, active constituents and mechanisms of action of HMs; the lack of standardization and quality control (contaminations, adulterations) represent other sources of concern. Furthermore, the widespread perception that unlike prescription drugs HMs are safe is misleading and some HMs can cause clinically relevant adverse events and interactions, particularly when used with narrow therapeutic index prescribed cardiovascular drugs (antiarrhythmics, antithrombotics, digoxin). Cardiologists/physicians can no longer ignore the problem. They must improve their knowledge about the HMs their patients consume to provide the best advice and prevent adverse reactions and drug interactions. This narrative review addresses the putative mechanisms of action, suggested clinical uses and safety of most commonly used HMs, the pivotal role of cardiologists/physicians to protect consumers and the main challenges and gaps in evidence related to the use of HMs in the prophylaxis and treatment of CVDs. Main concerns and challenges to be faced by cardiologists/physicians and patients with cardiovascular diseases that consume herbal medicines. Abbreviations. AE: adverse events. CPG: clinical practice guidelines. CTs: clinical trials. CV: cardiovascular. CVDs: cardiovascular diseases. EMA: European Medicines Agency. FDA: Food and Drug Administration. HDIs: herb-drug interactions. HMs: herbal medicines. RCTs: randomized clinical trials. [Display omitted] • Many patients with cardiovascular diseases (CVDs) combine herbal medicines (HMs) with prescription drugs. • Patients do not notify their use and physicians do not ask about this common practice. • The perception that HMs are safe is misleading as they can produce adverse events and interact with prescribed drugs. • Current scientific evidence does not support the use of HMs for the prevention/treatment of CVDs. • Physicians play a pivotal role in minimizing the risks of HMs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The tumor microenvironment (TME) plays an important role in the development of tumors. Immunoregulatory cells and cytokines facilitate cancer cells to avoid immune surveillance. Overexpression of immune checkpoint molecules such as CTLA-4 and PD-1/PD-L1 inhibits immune function and enables cancer cells to avoid clearance by the immune system. Thus, minimizing tumor immunosuppression could be an important strategy for cancer therapy. Currently, many immune checkpoint-targeted drugs, such as PD-1/PD-L1 inhibitors, have been approved for marketing and have shown unique advantages in the clinical treatment of cancers. The concept of "strengthening resistance to eliminate pathogenic factors" in traditional Chinese medicine (TCM) is consistent with the immunotherapy of cancer. According to previous studies, the role of TCM in tumor immunotherapy is mainly associated with the positive regulation of natural killer cells, CD8/CD4 T cells, dendritic cells, M2 macrophages, interleukin-2, tumor necrosis factor- α , and IFN- γ , as well as with the negative regulation of Tregs, myeloid-derived suppressor cells, cancer-associated fibroblasts, PD-1/PD-L1, transforming growth factor- β , and tumor necrosis factor- β. This paper summarizes the current research on the effect of TCM targeting the TME, and further introduces the research progress on studying the effects of TCM on immune checkpoints. Modern pharmacological studies have demonstrated that TCM can directly or indirectly affect the TME by inhibiting the overexpression of immune checkpoint molecules and enhancing the efficacy of tumor immunotherapy. TCM with immunomodulatory stimulation could be the key factor to achieve benefits from immunotherapy for patients with non-inflammatory, or "cold", tumors. [ABSTRACT FROM AUTHOR]

Catha edulis Forsk., commonly known as Khat, is a stimulant plant that is chewed in the Horn of Africa and the southern regions of the Arabian Peninsula. It is often used alongside conventional drugs, but there is a lack of research on its interactions with other drugs. In this study, our aim was to investigate the possibility of an herb–drug interaction between KT extract and metformin (MT) by exploring the effect of KT on the in vivo pharmacokinetics of MT in diabetic Wistar albino rats and monitoring blood glucose levels through time intervals, comparing when MT was given alone and co-administered with KT. Rats were given 500 mg/kg of KT extract and 300 mg/kg of MT daily for 7 days. The pharmacokinetic parameters of MT were analyzed using UPLC-MS/MS. The quantification was conducted using multiple reaction monitoring (MRM) in positive ion mode. The transitions used were (m/z) 130.006→59.939 for MT and 260.125→116.018 for propranolol as an internal standard (IS). An Acquity UPLC BEH HSS T3 C18 column was used with isocratic elution, and the mobile phase was formic acid (0.1%): acetonitrile (70:30 v/v) at a flow rate of 0.25 mL/min. In addition, the study delved into the in vitro impact of KT on the CYP3A4 enzyme, seeking to identify any potential disruptions in MT's metabolism that could alter its pharmacokinetics. The effect of KT extract on CYP3A4 enzyme activity was investigated using fluorescence-based enzyme assays and a CYP3A4 Inhibitor Screening Kit. The results indicated that the combined treatment showed increased systemic exposure to MT, with Cmax and AUC levels increasing by 33.42% and 45.23%, respectively. Additionally, the combination treatment led to significantly lower fasting blood glucose (FBG) levels compared to the groups treated with MT alone. It was found that at a concentration of 500 µg/mL, the CYP3A4 enzyme activity was maximally suppressed by approximately 57%, while at 250 µg/mL, it was inhibited by almost 50%. In comparison, the standard Ketoconazole only inhibited CYP3A4 activity by approximately 58%. Therefore, the in vitro results suggest that KT extract has the potential to affect CYP3A4 activity at high doses. In conclusion, the combination treatment resulted in a significant increase in MT's blood sugar-lowering effects. Therefore, it is important to be aware of this potential interaction and to monitor blood sugar levels closely when using KT alongside MT. [ABSTRACT FROM AUTHOR]

The emergence of diabetes as a silent epidemic and the failure of conventional medicines to provide a safe, effective, and affordable stance has rendered scientists to go back to the ancient literature on traditional plant-based therapies. Though many spices and herbs are used for usual culinary purposes, organized research on the beneficial effect of such herbs in regard to diabetes is less explored. Traditionally, ayurvedic phyto-based polyherbal formulations have been described to reduce blood glucose levels and ease allied complications related to diabetes. The present review amasses nine ethnomedicinal plants (cinnamon, fenugreek, bitter gourd, neem, Indian bael, black myrobalan, Indian gooseberry, turmeric, and giloy) of the Indian subcontinent frequently mentioned in a traditional setting. Systematic assessment of different extraction methods, computational, in vitro, in vivo, and human trials for diabetes involving plants, is presented. A list of some of the commercially available polyherbal formulations for diabetes, along with their key constituents, is discussed. Finally, considering the concomitant use of herbs along with conventional drugs, a brief perspective on the possible herb-drug interactions, limitations, and future directions is provided. This review sheds light on the bioactive components of pharmaceutically relevant plants mentioned in traditional settings for hypoglycemic control. Subsequently, wider acceptance of complementary therapy for efficient management of diabetes would improve the quality of life of patients across the globe. [ABSTRACT FROM AUTHOR]

As a promiscuous xenobiotic sensor, pregnane X receptor (PXR) plays a crucial role in drug metabolism. Since dietary phytochemicals exhibit the potential to modulate human PXR, this review aims to summarize the plant-derived PXR modulators, including agonists, partial agonists, and antagonists. The crystal structures of the apo and ligand-bound forms of PXR especially that of PXR complexed with binary mixtures are summarized, in order to provide the structural basis for PXR binding promiscuity and synergistic activation of PXR by composite ligands. Furthermore, this review summarizes the characterized agonists, partial agonists, and antagonists of human PXR from botanical source. Contrary to PXR agonists, there are only a few antagonists obtained from botanical source due to the promiscuity of PXR. it is worth noting that trans-resveratrol and a series of methylindoles have been identified as partial agonists of PXR, both in activating PXR function, but also inhibiting the effect of other PXR agonists. Since antagonizing PXR function plays a crucial role in the prevention of drug-drug interactions and improvement of therapeutic efficacy, further research is necessary to screen more plant-derived PXR antagonists in the future. in summary, this review may contribute to understanding the roles of phytochemicals in food-drug and herb-drug interactions. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic sparked the development of novel anti-viral drugs that have shown to be effective in reducing both fatality and hospitalization rates in patients with elevated risk for COVID-19 related morbidity or mortality. Currently, nirmatrelvir/ritonavir (Paxlovid™) fixed-dose combination is recommended by the World Health Organization for treatment of COVID-19. The ritonavir component is an inhibitor of cytochrome P450 (CYP) 3A, which is used in this combination to achieve needed therapeutic concentrations of nirmatrelvir. Because of the critical pharmacokinetic effect of this mechanism of action for Paxlovid™, co-administration with needed medications that inhibit or induce CYP3A is contraindicated, reflecting concern for interactions with the potential to alter the efficacy or safety of co-administered drugs that are also metabolized by CYP3A. Some herbal medicines are known to interact with drug metabolizing enzymes and transporters, including but not limited to inhibition or induction of CYP3A and P-glycoprotein. As access to these COVID-19 medications has increased in low- and middle-income countries (LMICs), understanding the potential for herb-drug interactions within these regions is important. Many studies have evaluated the utility of herbal medicines for COVID-19 treatments, yet information on potential herb-drug interactions involving Paxlovid™, specifically with herbal medicines commonly used in LMICs, is lacking. This review presents data on regionally-relevant herbal medicine use (particularly those promoted as treatments for COVID-19) and mechanism of action data on herbal medicines to highlight the potential for herbal medicine interaction Herb-drug interaction mediated by ritonavir-boosted antiviral protease inhibitors This work highlights potential areas for future experimental studies and data collection, identifies herbal medicines for inclusion in future listings of regionally diverse potential HDIs and underscores areas for LMIC-focused provider-patient communication. This overview is presented to support governments and health protection entities as they prepare for an increase of availability and use of Paxlovid™. [ABSTRACT FROM AUTHOR]

Throughout history, complementary and alternative therapies have been widely utilised. In recent years, there has been a surge in interest in the usage of herbal treatments all around the world. Various natural chemicals, such as those produced from plants, have been investigated as potential therapies for a myriad of ailments. The essence of this review was to methodically describe everything we know about Bacopa monnieri (L.) Pennell, a mysterious holistic Vedic herb belonging to the Plantaginaceae family, a well-known nootropic and effective memory enhancer, which has recently emerged as one of the most important medical herbs, widely used therapeutically in the Orient and growing in popularity around the world. Literature was gathered from sources such as Scopus, PubMed, Google Scholar, and ScienceDirect, and reviewed using the Prisma quality metacritic paradigm. It is now plainly obvious that current therapies fall short of meeting the demands of the vast majority of individuals with health problems, and traditional medicines are gaining appeal as a result of their reduced toxicity. Bacopa is a traditional herb used in Ayurvedic medicine to treat brain and nerve weariness, as well as in Siddha medicine to treat impaired memory. It's also used to cure brain and nerve exhaustion in Unani medicine. We improved Brahmi micropropagation and secondary metabolite biosynthesis by compiling pharmacobotanical and pharmacognostical descriptions, as well as ethnoarchaeological data and nanotechnology domination. This critique also highlights our contemporary information of pharmacological activity, preclinical and clinical investigations, significant bioactives, reported mechanisms of action, clinical effectiveness, safety, and the potential for herb-drug interactions. At the same time, the current incarnation of research at the plant is reviewed, as well as future research possibilities. Brahmi offers a lot of potential for treating a range of illnesses, including neuro-pharmacological, depression, inflammation, hepatoprotective, antidiabetic, and others. According to the presumptions of this review, further clinical trials and research are needed. While the impact of Brahmi as an anxiolytic and antidepressant has to be explored further, its potential as an anti-epileptic therapy and a treatment for antiepileptic drugs side effects is also being researched. Furthermore, Brahmi's antioxidant ability may explain, at least in part, the antistress, immunomodulatory, cognition-facilitating, anti-inflammatory, and anti-aging benefits documented in experimental animals and clinical circumstances, necessitating further study into its other therapeutic characteristics. [ABSTRACT FROM AUTHOR]