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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-G 1 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.

Background: Kratom ( Mitragyna speciosa ) consumption and associated health effects have raised debates in the United States. Although most people using this herb do not experience adverse health effects associated with kratom use, medical providers should be knowledgeable of emerging substances and concurrent, sequential, or simultaneous use of other drugs which may impact healthcare recommendations and prescribing practices., Methods: The objective of this narrative review was to elucidate selected health effects associated with using kratom-either alone or with other substances. Since scientifically controlled human subjects research on kratom use is still limited, relevant case reports were also described., Results: Cardiovascular, gastrointestinal, neurological, and psychiatric effects associated with kratom use were especially notable, and in-utero exposure accompanied concern regarding a neonate's risk for developing neonatal abstinence syndrome. Our ability to identify and understand the role of this herb in kratom-associated fatalities is complicated since kratom is not routinely screened for in standard forensic toxicology. If a screening is performed, it is usually for the major alkaloid, mitragynine, as a surrogate for kratom use. In addition to lacking a standard practice of screening decedents for kratom alkaloids, the association between mortality and kratom use may be confounded by polysubstance use, adulteration of kratom products, and drug-herb interactions., Conclusions: Increasing medical awareness of this herb is vital to ensuring prompt administration of best-practice medical advice or treatment for people seeking information related to kratom use or for patients experiencing an adverse health effect that may be associated with using or withdrawing from kratom. Knowledge gained from continued surveillance and study of kratom and its associated health effects may assist in guiding clinical decision-making and preventing development of adverse health effects among people using kratom., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Introduction: Acute pancreatitis associated with Pazopanib has been reported in the literature. Bitter Melon (Momordica Charantia) is traditionally used as a folk medicine in many regions. In this report, we describe a 65-year-old patient with a diagnosis of renal cell carcinoma, admitted to the hospital with symptoms of acute pancreatitis at the 8th year of pazopanib treatment., Case Report: The patient diagnosed with renal cell carcinoma was admitted to the hospital with the complaint of abdominal pain, nausea, and vomiting in the 8th year of Pazopanib treatment. It was noticed from the patient's history that he had received Bitter Melon extract for 4 days prior to the beginning of his complaints (100-150 ml/day). Levels of serum amylase and lipase were measured as 9163 U/L and 14,206 U/L, respectively., Management & Outcome: Pazopanib drug was held. The patient was treated for acute pancreatitis. Pazopanib treatment was started again after the clinical condition of the patient had improved and levels of serum amylase and lipase had returned to normal levels. Levels of serum amylase and lipase did not increase again after re-administration of pazopanib treatment., Discussion: It is thought that Bitter Melon extract and pazopanib interaction might have led to acute pancreatitis. To the best of our knowledge, this case is the first to highlight the interaction of Bitter Melon extract with pazopanib. The Drug Interaction Probability Scale indicates that there is a probable association between bitter melon and acute pancreatitis.

Phytotherapy is the main complementary medicine for which patients afflicted with cancer have recourse but the associated consumption of phytotherapy products gives rise to a risk of interaction with anticancer agents. The aim of this prospective study was to measure the prevalence of the consumption of phytotherapy products as well as their interactions with anticancer agents in a cohort of patients from January 2018 to August 2019. Patients hospitalized in the conventional hematology unit and outpatients who had their prescriptions for oral anticancer agents filled at the hospital pharmacy were questioned about consumption of phytotherapy products by pharmacy externs trained in pharmaceutical interviews. Among the 110 hospitalized patients who answered the questionnaire, 40% (n = 44) used phytotherapy and 5 of them continued to consume it during the cycles of injectable chemotherapy. As a result, 10 interactions were found between the plants and the anticancer agents (prevalence of 27%). Among the 59 outpatients, 17% (n = 10) consumed phytotherapy. Eight interactions were identified (prevalence of 80%). The potential consequences were an increase or a decrease in the concentration of the anticancer agents and an increase in the risk of bleeding, hepatoxicity, and hypokalemia. The consumption of phytotherapy was unknown by a health professional for 44% of hospitalized patients and 60% of the outpatients. The risk of interactions between plants and anticancer agents is not negligible and professionals should be cognizant of this in their daily practice. The availability of tools for training and detection of interactions is indispensable for managing patients undergoing onco-hematology treatments.

Introduction: Patients with cancer are increasingly using herbal supplements, unaware that supplements can interact with oncology treatment. Herb-drug interaction management is critical to ensure optimal treatment outcomes. Several screening tools exist to detect drug-drug interactions, but their performance to detect herb-drug interactions is not known. This study compared the performance of eight drug-drug interaction screening tools to detect herb-drug interaction with anti-cancer agents., Methods: The herb-drug interaction detection performance of four subscription (Micromedex, Lexicomp, PEPID, Facts & Comparisons) and free (Drugs.com, Medscape, WebMD, RxList) drug-drug interaction tools was assessed. Clinical relevance of each herb-drug interaction was determined using Natural Medicine and each drug-drug interaction tool. Descriptive statistics were used to calculate sensitivity, specificity, positive predictive value, and negative predictive value. Linear regression was used to compare performance between subscription and free tools., Results: All tools had poor sensitivity (<0.20) for detecting herb-drug interaction. Lexicomp had the highest positive predictive value (0.98) and best overall performance score (0.54), while Medscape was the best performing free tool (0.52). The worst subscription tools were as good as or better than the best free tools, and as a group subscription tools outperformed free tools on all metrics. Using an average subscription tool would detect one additional herb-drug interaction for every 10 herb-drug interactions screened by a free tool., Conclusion: Lexicomp is the best available tool for screening herb-drug interaction, and Medscape is the best free alternative; however, the sensitivity and performance for detecting herb-drug interaction was far lower than for drug-drug interactions, and overall quite poor. Further research is needed to improve herb-drug interaction screening performance.

Introduction: Dietary herbal products taken together with prescription medicines may have harmful effects. In this study, we evaluated the use of dietary herbal supplements and identified factors that predict the concomitant use of these supplements in patients taking drugs prescribed for chronic cardiovascular diseases., Methods: We performed a cross-sectional study with 343 patients with cardiovascular diseases. Data regarding the sociodemographic status, medical condition, number of prescription drugs, and use of herbal supplements were collected using a self-administered questionnaire., Results: Regular use of dietary herbal supplements was reported by 82.5% of patients. The most commonly consumed herbal supplement was garlic (71.2%), followed by onion (67.1%), and walnut (63.6%). Consumption of herbal supplements was commonly observed in patients with hypertension (53.6%). Among the patients in the study, 21.3% patients reported consumption of herbal supplements to the physician. Results of multivariable analysis showed that body mass index (odds ratio [OR] = 0.890, 95% confidence interval [CI] = 0.826-0.960), heart failure (OR = 0.325, 95% CI = 0.142-0.742), coronary artery disease (OR = 0.162, 95% CI = 0.069-0.379), smoking (OR = 3.852, 95% CI = 1.194-12.433), hypertension (OR = 10.584, 95% CI = 4.648-24.103), and dysrhythmia (OR = 9.339, 95% CI = 2.035-42.853) were associated with the use of dietary herbal supplements., Conclusions: Our results showed that dietary herbal supplements were commonly used by patients with chronic cardiovascular diseases. Therefore, understanding the interactions between the herbal supplements and drugs is necessary for minimizing adverse reactions.

Background: Although the use of complementary and alternative medicines is widespread in cancer patients, clinical evidence of their benefits is sparse. Furthermore, while they are often assumed to be safe with regard to concurrent use of anticancer therapies, few studies have been carried out to investigate possible interactions. Fucoidans are a group of sulfated carbohydrates, derived from marine brown algae, which have long been used as dietary supplements due to their reported medicinal properties, including anticancer activity. The aim of this study was to investigate the effect of co-administration of fucoidan, derived from Undaria pinnatifida, on the pharmacokinetics of 2 commonly used hormonal therapies, letrozole and tamoxifen, in patients with breast cancer., Methods: This was an open label non-crossover study in patients with active malignancy taking letrozole or tamoxifen (n = 10 for each group). Patients took oral fucoidan, given in the form of Maritech extract, for a 3-week period (500 mg twice daily). Trough plasma concentrations of letrozole, tamoxifen, 4-hydroxytamoxifen, and endoxifen were measured using HPLC-CAD (high-performance liquid chromatography charged aerosol detector), at baseline and after concomitant administration with fucoidan., Results: No significant changes in steady-state plasma concentrations of letrozole, tamoxifen, or tamoxifen metabolites were detected after co-administration with fucoidan. In addition, no adverse effects of fucoidan were reported, and toxicity monitoring showed no significant differences in all parameters measured over the study period., Conclusions: Administration of Undaria pinnatifida fucoidan had no significant effect on the steady-state trough concentrations of letrozole or tamoxifen and was well tolerated. These results suggest that fucoidan in the studied form and dosage could be taken concomitantly with letrozole and tamoxifen without the risk of clinically significant interactions.

Objective: The aim of this study was to investigate the possible herb-drug interactions between the traditional herbal formula Guibi-tang (GBT; Guipi-tang , Kihi-to ) and conventional drugs., Materials and Methods: GBT was orally administered to either male or female Sprague Dawley (SD) rats once daily at doses of 1000, 2000, or 5000 mg/kg/day for 13 weeks. The messenger ribonucleic acid (mRNA) expression of drug-metabolizing enzyme cytochrome P450 isozymes (cytochrome P450s; CYP1A1, 1A2, 2B1/2, 2C11, 2E1, 3A1, 3A2, and 4A1) was analyzed in hepatic tissues by reverse transcription-polymerase chain reaction., Results: Repeated oral administration of GBT did not significantly influence the mRNA expression of hepatic CYP1A1, 1A2, 2B1/2, 2C11, 2E1, 3A1, 3A2, and 4A1 in male rats. By contrast, in female rats, the mRNA expression of hepatic CYP1A2 and 2B1/2 was significantly increased by repeated GBT treatment., Conclusion: Our findings indicate that caution is required in females when GBT is taken concomitantly with conventional drugs metabolized by CYP1A2 or 2B1/2. Our results provide information regarding the safety and effectiveness of GBT for clinical use., Summary: Repeated oral administration of Guibi-tang (GBT) for 13 weeks did not affect the messenger ribonucleic acid (mRNA) expression of hepatic CYP1A1, 1A2, 2B1/2, 2C11, 2E1, 3A1, 3A2, and 4A1 in male ratsRepeated oral administration of GBT for 13 weeks induced mRNA expression of hepatic CYP1A2 and 2B1/2 but not for CYP1A1, 2C11, 2E1, 3A1, 3A2, and 4A1 in female rats. Abbreviations used: CYP450: Cytochrome P450s, GBT: Guibi-tang , SD: Sprague Dawley, HPLC: High-performance liquid chromatography, OECD: Organization for Economic Cooperation and Development, RNA: Ribonucleic acid, RT-PCR: Reverse transcription-polymerase chain reaction, GADPH: Glyceraldehyde-3-phosphate dehydrogenase., Competing Interests: There are no conflicts of interest.

Drug interactions are key reasons for adverse drug reactions and attrition from market. Major infectious diseases causing morbidity/mortality in Ghana are malaria, tuberculosis, and HIV/AIDS. In this study, plant medicines commonly used to treat/manage these diseases in Ghana were investigated for their potential to modulate rat cytochrome P450 enzyme activities. Fluorescence and high-performance liquid chromatography-based assays were used to assess effects of antimalarial plant medicines, Fever (FEV), Mal-TF (MAL), and Kantinka terric (KT); anti-TB medicines, Chestico (CHES), CA + ST Pains + HWNT (TF), and Kantinka herbatic (KHB); and anti-HIV/AIDS medicines, Wabco (WAB), AD + T/AD (LIV) and Kantinka BA (KBA) on rat liver microsomal cytochrome P450 enzyme activities. Effects of medicines on rat biochemical and hematological parameters were also assessed. Generally, the medicines altered microsomal CYP1A1/1A2, CYP2B1/2B2, CYP2C9, and CYP2D6 activities. Only KBA elicited an increase (80%) in CYP1A1/1A2 activity. FEV, MAL, CHES, WAB, and LIV strongly inhibited the enzyme activity. All the medicines significantly inhibited CYP2C9 (24%-80%) activity. CYP2D6 activity increased after treatment with MAL, KBA, LIV, and TF. Also, MAL, WAB, LIV, KHB, and CHES increased CYP2B1/2B2 activity, while KT decrease the activity. Generally, the medicines altered liver function in the rats. Cholesterol levels declined after KBA treatment only. White and red blood cell counts, hemoglobin and hematocrit levels were significantly reduced in KT- and KBA-treated rats. Our results suggest that use of the medicines could have implications for drug interactions and safety, particularly if the medicines are administered over prolonged periods. Further investigations are imperative to establish clinical relevance of these results.

Background: Quercetin (QR) and thymoquinone (TQ) are herbal remedies that are currently extensively used by the general population to prevent and treat various chronic conditions. Therefore, investigating the potential of pharmacokinetic interactions caused by the concomitant use of these herbal remedies and conventional medicine is warranted to ensure patient safety., Purpose of the Study: This study was conducted to determine the inhibitory effect of QR and TQ, two commonly used remedies, on the activities of selected cytochrome P450 (CYP) enzymes that play an important role in drug metabolism and/or toxicology., Materials and Methods: The in vitro studies were conducted using fluorescence-based high throughput assays using human c-DNA baculovirus expressed CYP enzymes. For measuring CYP2E1 activity, a validated High-performance liquid chromatography (HPLC) assay was utilized to measure the formation of 6-hydroxychlorzoxazone., Results: The obtained half-maximum inhibitory concentration values with known positive control inhibitors of this study were comparable to the published values indicating accurate experimental techniques. Although QR did not show any significant effect on CYP1A2 and CYP2E1, it exhibited a strong inhibitory effect against CYP2D6 and a moderate effect against CYP2C19 and CYP3A4. On the other hand, TQ demonstrated a strong and a moderate inhibitory effect against CYP3A4 and CYP2C19, respectively., Conclusions: The findings of this study may indicate that consumption of QR or TQ, in the form of food or dietary supplements, with drugs that are metabolized by CYP2C19, CYP2D6, or CYP3A4 may cause significant herb-drug interactions., Summary: Neither QR nor TQ has any significant inhibitory effect on the activity of CYP1A2 or CYP2E1 enzymesBoth QR and TQ have a moderate to strong inhibitory effect on CYP3A4 activityQR has a moderate inhibitory effect on CYP2C19 and a strong inhibitory effect on CYP2D6Both QR and TQ are moderate inhibitors of the CYP2C9 activity. Abbreviations used: ABT: Aminobenztriazole, BZF: 7,8 Benzoflavone, CYP: Cytochrome P450, GB: Gingko Biloba, IC 50 : Half-maximum inhibitory concentration, KTZ: Ketoconazole, QND: Quinidine, QR: Quercetin, TCP: Tranylcypromine, TQ: Thymoquinone., Competing Interests: There are no conflicts of interest.

Background: The cardioprotective effects of Persea americana extract was investigated on biochemical activities of high salt-fed adult Wistar rats in this study., Method: Forty healthy Wistar rats of both sexes weighing 120 to 150 g were randomly assigned into 8 groups of 5 rats each (groups A, B, C, D, E, F, G, and H). Rats in groups A, F, G, and H were fed with standard laboratory pellets, while groups B, C, D, and E were fed on the high-salt diet for 4 weeks. Concomitantly, daily administration of 50, 100, and 150 mg/kg of the P americana extract were given orally to groups C and F, D and G, and E and H, respectively, while rats in groups A and B were administered distilled water. Blood samples were taken by cardiac puncture; concentration of sodium ion, potassium ion, nitric oxide, and activity of lactate dehydrogenase were determined. One-way analysis of variance was used to analyze data, followed by Student-Newman-Keuls (SNK) test for multiple comparison., Results: Results revealed that concentration of potassium ion and nitric oxide was significantly lower ( P < .05) in high salt-fed groups. Sodium ion concentration and activity of lactate dehydrogenase were higher in high salt-fed group while P americana prevented biochemical perturbations in other experimental groups., Conclusion: In conclusion, high salt-diet induced biochemical alterations which were significantly protected by oral administration of P americana extract.

Extracts of Desmodium adscendens (Sw) DC are used for the treatment of various diseases but limited toxicological evaluations have been done on the medicinal plant. This study investigates toxicity effects of the leave extract of D adscendens, and the possibility of drug-drug interaction of the plant extract when co-administered with other drugs. Oral administrations of leaf extract of D adscendens to white Wistar rats in an acute toxicity studies allowed the estimation of an LD 50 (median lethal dose) value of 1122 mg/kg body weight. In a subchronic toxicity studies, the plant extract caused a decrease in zoxazolamine paralysis time and prevented thiopentone from causing sleep in test animals compared to controls. Overall, the results are consistent with the plant extract being safe at the doses administered in humans. However, the induction of the CYP enzymes is an indication of a possible drug interaction when the plant extract is co-administered with other drugs.

Background: Hovenia dulcis (Rhamnaceae) fruits are popularly used as herbal medicines or dietary supplements in Asian countries due to functions such as liver protection and detoxification from alcohol poisoning. Accordingly, it is very likely for dietary supplemental products, including H. dulcis fruit extracts, to be taken with prescription drugs., Objective: In this study, possible food-drug interactions involving H. dulcis fruit extracts were evaluated based on the inhibition of cytochrome P450 (CYP) enzyme activity., Material and Methods: The water extract of H. dulcis fruit extracts was incubated in human liver microsomes with CYP-specific substrates. The formation of the CYP-specific metabolites was measured using liquid chromatography-tandem mass spectrometry., Results: H. dulcis fruit extracts showed negligible effects on seven CYP isozyme activities at all concentrations tested., Conclusion: This result suggests that H. dulcis fruit extracts may have minimal pharmacokinetic interactions with coadministered drugs through the modulation of CYP enzymes., Summary: Food-drug interactions involving H. dulcis fruit extracts were evaluated.The inhibition of CYPs by H. dulcis extracts was tested. H. dulcis extracts showed negligible effects on CYP activities. H. dulcis extracts may have minimal pharmacokinetic interactions with co-administered drugs. Abbreviations Used: CYP: cytochrome P450 enzymes, HPLC: High performance liquid chromatography, LC-MS/MS : liquid chromatography-tandem mass spectrometry, MRM: multiple-reaction monitoring., Competing Interests: There are no conflicts of interest.

The use of alternative medicines, including herbs, is common among HIV-positive patients, even in those on antiretroviral treatment. Equisetum arvense, known as "horsetail," is mainly used for its diuretic properties. There are limited data about the pharmacological properties of this compound and the potential drug-herb interactions. The authors report 2 cases in which a possible drug-herb interaction may have led to virological breakthrough in patients who were maintained on the same regimen for many years, including lamivudine (3TC)/zidovudine (ZDV)/efavirenz (EFV) and emtricitabine (FTC)/tenofovir (TDF)/EFV, respectively. Therefore, a drug-herb interaction may be expected when these agents are taken concurrently. Until additional data are available, the authors advise clinicians to avoid this combination when possible.

This study investigated the anticonvulsant activity of Citrullus colocynthis fruit extract used traditionally in the treatment of convulsion. Albino mice were pretreated with extract in different doses (10, 25, 50, and 100 mg/kg), prior to injection of pentylenetetrazole. Animals received pretreatments with naloxone and flumazenil to further clarify the mechanisms of anticonvulsant action. The total flavonoid content of Citrullus colocynthis extract was also determined. Citrullus colocynthis hydroalcoholic extract with doses 25 and 50 mg/kg prolonged the onset of seizures and decreased the duration compared with control group. Pretreatment by flumazenil could inhibit the effect of Citrullus colocynthis on latency of seizure to some extent and administration of naloxone significantly inhibited changes in latency and duration of seizure produced by Citrullus colocynthis This study showed that Citrullus colocynthis has significant anticonvulsant effect in pentylenetetrazole-induced seizures in mice, and these effects may be related to its effect on γ-aminobutyric acid-ergic and opioid systems. These results confirmed the traditional use of Citrullus colocynthis in Iranian traditional medicine., (© The Author(s) 2015.)

Objective: The aim of this study was to assess the influence of traditional herbal formulas, including Bangpungtongseong-san (BPTSS; Fangfengtongsheng-san , Bofu-tsusho-san ), Ojeok-san ( OJS; Wuji-san , Goshaku-san ), and Oyaksungi-san (OYSGS; Wuyaoshungi-san , Uyakujyunki-san ), on the activities of the human cytochrome P450s (CYP450s) and UDP-glucuronosyltransferases (UGTs), which are drug-metabolizing enzymes., Materials and Methods: The activities of the major human CYP450 isozymes (CYP1A2, CYP3A4, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP2E1) and UGTs (UGT1A1, UGT1A4, and UGT2B7) were investigated using in vitro fluorescence-based and luminescence-based enzyme assays, respectively. The inhibitory effects of the herbal formulas were characterized, and their IC 50 values were determined., Results: BPTSS inhibited the activities of CYP1A2, CYP2C19, CYP2E1, and UGT1A1 while it exerted relatively weak inhibition on CYP2B6, CYP2C9, CYP2D6, and CYP3A4. BPTSS also negligibly inhibited the activities of UGT1A4 and UGT2B7, with IC 50 values in the excess of 1000 μg/mL. OJS and OYSGS inhibited the activity of CYP2D6, whereas they exhibited no inhibition of the UGT1A4 activity at doses <1000 μg/mL. In addition, OJS inhibited the CYP1A2 activity but exerted a relatively weak inhibition on the activities of CYP2C9, CYP2C19, CYP2E1, and CYP3A4. Conversely, OJS negligibly inhibited the activities of CYP2B6, UGT1A1, and UGT2B7 with IC 50 values in excess of 1000 μg/mL. OYSGS weakly inhibited the activities of CYP1A2, CYP2C19, CYP2E1, CYP3A4, and UGT1A1, with a negligible inhibition on the activities of CYP2B6, CYP2C9, and UGT2B7, with IC 50 values in excess of 1000 μg/mL., Conclusions: These results provide information regarding the safety and effectiveness of BPTSS, OJS, and OYSGS when combined with conventional drugs., Summary: Bangpungtongseong-san inhibited the activities of human microsomal CYP1A2, CYP2C19, CYP2E1, and UGT1A1, with a negligibly inhibition on the activities of CYP2B6, CYP2C9, CYP2D6, CYP3A4, UGT1A4, and UGT2B7 Ojeok-san (OJS) inhibited the CYP1A2 and CYP2D6 mediated metabolism while showing a comparatively weak inhibition against CYP2B6, CYP2C9, CYP2C19, CYP2E1, CYP3A4, and UGT1A1 in human microsomes Oyaksungi-san (OYSGS) inhibited the activities of human microsomal CYP2D6, with a relatively weak inhibition on the activities of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2E1, CYP3A4, UGT1A1, and UGT2B7OJS showed no inhibition on the activities of human microsomal UGT1A4 and UGT2B7, and OYSGS did not affect the human microsomal UGT1A4 activity. Abbreviations used: BPTSS: Bangpungtongseong-san , OJS: Ojeok-san , OYSGS: Oyaksungi-san , CYP450s: cytochrome P450s, UGTs: UDP-glucuronosyltransferases, MSDs: Musculoskeletal disorders, NSAIDs: nonsteroidal anti-inflammatory drugs, EOMCC: 7-ethoxy-methyloxy-3-cyanocoumarin, DBOMF: di(benzyloxymethoxy)fluorescein, BOMCC: 7-benzyloxy-4-trifluoromethylcoumarin, HPLC: High-performance liquid chromatography, PDA: photo diode array, SEM: standard error of the mean, UDPGA: uridine 5'-diphosphoglucuronic acid.

Objective: The purpose of this study was to investigate the potential influences of Socheongryong-tang (SCRT) on the messenger ribonucleic acid (mRNA) and protein expression of cytochrome P450 (CYP450) in vivo., Materials and Methods: SCRT was orally administered to either male or female Sprague-Dawley rats once daily at doses of 0, 1000, 2000, or 5000 mg/kg/day for 13 weeks. The mRNA expression of CYP450s (CYP1A1, 1A2, 2B1/2, 2C11, 2E1, 3A1, 3A2, and 4A1) in liver tissues was measured by reverse transcription polymerase chain reaction. And then, the protein expression of CYP1A1 and CYP2B1/2 in liver tissues was analyzed by the Western blot., Results: We found no significant influence in the mRNA expression of hepatic CYP1A2, 2C11, 2E1, 3A1, 3A2, and 4A1 after repeated administration of SCRT for 13 weeks. By contrast, the mRNA and protein expression of hepatic CYP1A1 was increased by repeated SCRT treatment in male rats, but not in female rats. The mRNA and protein expression of hepatic CYP2B1/2 in both genders was increased by administration of SCRT., Conclusion: A caution is needed when SCRT is co-administered with substrates of CYP2B1/2 for clinical usage. In case of male, an attention is also required when SCRT and drugs metabolized by CYP1A1 are taken together. Our findings provide information regarding the safety and effectiveness of SCRT when combined with conventional drugs., Summary: Oral administration of Socheongryong-tang for 13 weeks did not affect the mRNA expression of hepatic CYP1A2, 2C11, 2E1, 3A1, 3A2, and 4A1In male rats, oral administration of Socheongryong-tang for 13 weeks induced the mRNA and protein expression of hepatic CYP1A1 and CYP2B1/2In female rats, oral administration of Socheongryong-tang for 13 weeks induced the mRNA and protein expression of hepatic CYP2B1/2. Abbreviations used: SCRT: Socheongryong-tang, CYP450: Cytochrome P450, HPLC: High performance liquid chromatography,, Rt-Pcr: Reverse transcription polymerase chain reaction.

Background: Cassia auriculata L. (CA) leaf extract might increase the body's production of insulin thereby suppressing the elevated blood glucose and lipid levels in diabetic rats. CA has been used as dietary supplement in India from ancient times., Objective: The present study was to elucidate the synergistic pharmacodynamic (PD) and pharmacokinetic (PK) interaction of metformin (MT) with CA., Materials and Methods: A simple, precise reverse phase high performance liquid chromatography - UV detection mode method was developed to quantify MT in rat plasma. In PD interaction, streptozotocin (45mg/kg, intraperitoneally) induced diabetic Wistar rats weighing 180-250 g of either sex were randomized to receive MT (90 mg/kg, MT-HD), CA (500 mg/kg) separately and in combination of MT (90 mg/kg, MT-HD) + CA (500 mg/kg), and MT (45 mg/kg, MT-LD) + CA (500 mg/kg) (all oral) along with normal and diabetic control groups for 21 days. PK of MT was carried out in normal rats with preadministration of CA (500 mg/kg) for 14 days., Results: PD data showed reasonable blood glucose lowering effect of CA. The reduction of MT dose with combination of CA achieved a similar blood glucose lowering effect of MT alone. PK data showed enhanced time taken to achieve maximum plasma concentration (Cmax), area under the curve (AUC0-t), and Cmax in combination group of MT (90mg/kg) and CA (500mg/kg), and reduction of MT dose in Group III had a reduced Cmax and AUC0-t compared to MT alone treated groups., Conclusion: Co-administration of CA with MT at varying dose showed a synergistic herb-drug interaction. Thus using the synergistic herb-drug interaction, the dose level of MT may be reduced to produce the same therapeutic effect as when taken alone., Summary: Elucidating the synergistic pharmacodynamic (PD) and pharmacokinetic (PK) interaction of metformin (MT) with Cassia auriculata L. (CA)PD data showed reasonable blood glucose lowering effect of CA. The reduction of MT dose with combination of CA achieved a similar blood glucose lowering effect of MT alonePK data showed enhanced time taken to achieve maximum plasma concentration (Cmax), area under the curve (AUC0-t), and Cmax in combination group of MT and CA, and reduction of MT dose had a reduced Cmax and AUC0-t compared to MT alone treated groupsCo-administration of CA with MT at varying dose showed a synergistic herb-drug interaction. Thus using the synergistic herb-drug interaction, the dose level of MT may be reduced to produce the same therapeutic effect as when taken alone. Abbreviations used: CA: Cassia auriculata L., PD: Pharmacodynamic, PK: Pharmacokinetic, MT: Metformin, RP-HPLC-UV: Reverse phase High Performance Liquid Chromatography-UV detection mode, Tmax: Time taken to achieve maximum plasma concentration, AUC0-t: Area under the curve, Cmax: Maximum plasma concentration.

Background: Polysaccharide K, also known as PSK or Krestin, is derived from the Coriolus versicolor mushroom and is widely used in Japan as an adjuvant immunotherapy for a variety of cancer including lung cancer. Despite reported benefits, there has been no English language synthesis of PSK for lung cancer. To address this knowledge gap, we conducted a systematic review of PSK for the treatment of lung cancer., Methods: We searched PubMed, EMBASE, CINAHL, the Cochrane Library, AltHealth Watch, and the Library of Science and Technology from inception to August 2014 for clinical and preclinical evidence pertaining to the safety and efficacy of PSK or other Coriolus versicolor extracts for lung cancer., Results: Thirty-one reports of 28 studies were included for full review and analysis. Six studies were randomized controlled trials, 5 were nonrandomized controlled trials, and 17 were preclinical studies. Nine of the reports were Japanese language publications. Fifteen of 17 preclinical studies supported anticancer effects for PSK through immunomodulation and potentiation of immune surveillance, as well as through direct tumor inhibiting actions in vivo that resulted in reduced tumor growth and antimetastatic effects. Nonrandomized controlled trials showed improvement of various survival measures including median survival and 1-, 2-, and 5-year survival. Randomized controlled trials showed benefits on a range of endpoints, including immune parameters and hematological function, performance status and body weight, tumor-related symptoms such as fatigue and anorexia, as well as survival. Although there were conflicting results for impact on some of the tumor-related symptoms and median survival, overall most randomized controlled trials supported a positive impact for PSK on these endpoints. PSK was safely administered following and in conjunction with standard radiation and chemotherapy., Conclusions: PSK may improve immune function, reduce tumor-associated symptoms, and extend survival in lung cancer patients. Larger, more rigorous randomized controlled trials for PSK in lung cancer patients are warranted., (© The Author(s) 2015.)

As constituents of Averrhoa bilimbi leaves we identified three new compounds (1-3) together with 12 known ones (4-15); their inhibitory activities on cytochrome P450 3A4 (CYP3A4) and 2D6 (CYP2D6) were examined. Among the isolated compounds, the mixture of 1 and 2, and compounds 4 and 9 showed strong inhibition on CYP3A4, but mild or no inhibition on CYP2D6. These compounds revealed the characteristics of 1) time- and concentration-dependent inhibition, 2) requirement of NADPH for the inhibition, 3) no protection by nucleophiles, and 4) suppression of the inhibition by competitive inhibitor. Thus, they are suggested to be mechanism-based inactivators of CYP3A4 and CYP2D6. The kinetic parameters for the inactivation (k(inact) and K(I)) were 0.19 min(-1) and 36.7 μM for the mixture of 1 and 2, 0.126 min(-1) and 10.5 μM for 4, and 0.29 min(-1) and 23.4 μM for 9.

Recognition of the adverse effects of medicinal herbs is not routine and the reports on such effects are even less frequent in clinical practice. Potential herb-drug interactions are of a major safety concern, especially for drugs with narrow therapeutic indices like warfarin, which can lead to severe adverse reactions that are sometimes life-threatening. The interactions between warfarin and medicinal herbs described in the literature have been summarized in this paper relying on Medline database (via PubMed) using the key words: warfarin, herbal supplements and interactions. The references on the analyzed literature have been investigated in order to collect the existing data. The case reports with severe adverse effects such as spontaneous postoperative bleeding, formation of hematomas, hematemesis, melena, thrombosis, subarachnoid hemorrhage and/or subdural hematomas after concomitant use of warfarin and the medicinal herbs: Panax ginseng, Hypericum perforatum, Salvia milthiorizza, Gingko biloba, Serenoa repens, Angelica sinensis, Vaccinium species, Allium sativum, Zingiber officinale, Tanacetum parthenium, Lucium barbarum, Matricaria chamomilla, Boswellia serrata and Camellia sinensis have been estimated. Some of the interactions between warfarin and medicinal herbs have been well assessed proving that they are closely-dependent. The interactions between warfarin and medicinal herbs, not generally reported in previous reviews, are presented in our review. The health professionals who are involved in treating the patients are expected to be fully informed about the interactions between warfarin and medicinal herbs in order to minimize the health risks of the patients.

Introduction: There is epidemiological evidence that Jia-Wei-Xiao-Yao-San (JWXYS) is the most common Chinese medicine decoction coprescribed with tamoxifen (Tam) when breast cancer is treated by hormonal therapy. However, whether there is interaction between JWXYS and Tam remains to be clarified. The aim of this study was to investigate the in vitro and in vivo effects of JWXYS on human breast cancer MCF-7 cells treated with Tam., Methods: In vitro cultured MCF-7 cells were cotreated with JWXYS and Tam. This was followed by MTT ([4,5-cimethylthiazol-2-yl]- 2,5-diphenyl tetrazolium bromide) assays and cell cycle analysis to assess cell proliferation; Western blot analysis was used to analyze the expression of various proteins involved in growth-related signal pathways. In addition, immunohistochemistry was used to detect autophagy among the cancer cells. In vivo analysis used female athymic nude mice implanted with MCF-7 cells; these mice were randomly assigned to 6 groups. All mice were killed humanely after 21 days of treatment; body weight, tumor volume, and tumor weight were then measured., Results: JWXYS was not cytotoxic to MCF-7 cells, based on the fact that there were no statistically significant changes between the JWXYS + Tam groups and the Tam-alone group in cell numbers, cell cycle progression, and cell proliferation signals, the latter including the expression levels of AKT, ERK, P38, p27(Kip1), and light chain (LC3)-I, II. Furthermore, using the MCF-7 xenograft mouse model, there were no significant changes between the JWXYS (1.3-3.9 gm/kg) + Tam groups and the Tam-alone group in terms of tumor weight and the protein expression levels of AKT, ERK, P38, and p27 (Kip1). However, there was a significant decrease in LC3-II protein expression with the low-dose JWXYS + Tam group but not with the middle- or high-dose JWXYS + Tam groups compared with the Tam-alone group., Conclusion: Based on in vitro studies and in vivo functional studies, there is no obvious interaction between JWXYS and Tam. However, the presence of interference at the molecular level in relation to LC3-II expression provides important information and may affect treatment strategies when physicians have patients with estrogen receptor-α(+) or progesterone receptor(+) breast cancers., (© The Author(s) 2014.)

Purpose: Many botanical immunomodulators are used as adjuvants along with cancer chemotherapy. However, information on the impact of concurrent administration of such botanicals on pharmacokinetics of chemotherapy agents is inadequate. This study investigates inhibitory activities of 3 popular botanical adjuvants: ASPARAGUS RACEMOSU: (root aqueous extract; ARE), WITHANIA SOMNIFER: (root aqueous extract; WSE), and TINOSPORA CORDIFOLI: (stem aqueous extract, TCE) on human CYP3A4 isoenzyme, responsible for metabolism of several chemotherapy agents., Experimental Desig: . Testosterone 6-β hydroxylation was monitored using high-performance liquid chromatography as an indicator of CYP3A4 catalytic activities. Ketoconazole (positive control) and extracts were studied at their in vivo-relevant concentrations., Results: TCE showed mild inhibition while no significant inhibitory activities were observed in WSE and ARE. TCE was further fractionated to obtain polar and nonpolar fractions. The nonpolar fraction showed significant CYP3A4 inhibition with IC50 13.06 ± 1.38 µg/mL. Major constituents of nonpolar fraction were identified using HPLC-DAD-MS profiling as berberine, jatrorrhizine, and palmatine, which showed IC50 values as 6.25 ± 0.30, 15.18 ± 1.59, and 15.53 ± 1.89 µg/mL, respectively., Conclusion: Our findings suggest that constituents of TCE extract especially protoberberine alkaloids have the potential to interact with cancer chemotherapy agents that are metabolized by CYP3A4 in vivo.

Background: Many women use black cohosh as a natural treatment for menopausal symptoms. However, controversy exists around safety in breast cancer, because of its purported estrogenic activity. We conducted a systematic review of black cohosh use in women with or at risk of breast cancer., Methods: We searched MEDLINE, Embase, the Cochrane Library, and AMED from inception to July 2012 and October 2012 for human interventional or observational data pertaining to the safety and efficacy of black cohosh in patients with or at risk of breast cancer, including an assessment of the effect of black cohosh on estrogen responsive tissues., Results: Of 450 records, we included 26 articles: 14 randomized controlled trials, 7 uncontrolled trials, and 5 observational studies.The evidence on efficacy for ho t flashes is divided, with some benefits seen when compared with baseline, but not when compared with placebo. Two observational studies found no association between black cohosh and risk of breast cancer, whereas 2 studies reported significant reductions in risk of primary breast cancer among postmenopausal women (adjusted odds ratio = 0.47, 95% confidence interval = 0.27-0.82), and risk of recurrence (adjusted hazard ratio = 0.75, 95% confidence interval = 0.63-0.89). Seventeen trials showed no significant impact on circulating hormone levels or proliferation in estrogen responsive tissues., Conclusions: Current evidence does not support an association between black cohosh and increased risk of breast cancer. There is a lack of evidence supporting the efficacy of black cohosh for reduction of hot flashes in breast cancer patients. Given conflicting but promising results, and apparent safety, further research is warranted.

Background: Green tea is a beverage widely used by lung cancer patients and the public for its purported anticancer properties. The authors conducted a systematic review of green tea for the treatment and prevention of lung cancer., Methodology: Six electronic databases were searched from inception until November 2011 for human interventional and preclinical evidence pertaining to the safety and efficacy of green tea for lung cancer., Results: A total of 84 articles met inclusion criteria: two Phase I trials, three reports of one surrogate study, and 79 preclinical studies. There is a lack of controlled trials investigating green tea for lung cancer. Two Phase I studies showed no objective tumor responses at the maximum tolerated dose, ranging from 3 to 4.2 g/m(2) green tea extract (GTE) per day. Four cups of green tea daily decreased DNA damage (8OH-dG) in smokers. Human studies indicate that 800mg of green tea catechins daily does not alter activity of the CYP2D6, CYP1A2, CYP3A4 and CYP2C9 enzymes, however in vitro evidence suggests that green tea may bind to and reduce the effectiveness of bortezomib. Green tea applied topically may improve the healing time of radiation burns., Conclusions: Although some evidence suggests that chemopreventative benefits can be accrued from green tea, there is currently insufficient evidence to support green tea as a treatment or preventative agent for lung cancer. Green tea should not be used by patients on bortezomib therapy. Further research is warranted to explore this natural agent for lung cancer treatment and prevention.

The use of herbal preparations for staunching blood flow and reducing the risk of vascular thrombosis is common worldwide. In this study, aqueous and methanolic extracts of plants used to treat blood-associated complaints were investigated to determine their effects on red blood cell haemolysis and coagulation. The extent of haemolysis was determined spectrophotometrically. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) as indicators of coagulation rate were determined using a coagulatometer. All of the plant extracts tested had a significant effect on coagulation time, prolonging the aPTT. Cassia petersiana had the greatest prolonging effect on PT compared to the control, phosphate buffered saline (PBS). As all of the herbal extracts tested had a delaying effect on coagulation, patients using herbal/plant therapies should be cautioned to stop their medication before surgery.