A hybrid silylene-Pd catalyst: efficient C-N cross-coupling of sterically bulky amines and chiral amines.

Herein, we report a catalytic system with N-heterocyclic silylene (NHSi)-phosphine-based hybrid bidentate ligands [PhC(NtBu)2SiN(PR2)(2,6-iPr2-C6H3)] and Pd(dba)2, which serves as an effective catalyst for C-N cross-coupling of a wide range of sterically bulky amines and optically active amines, which is challenging otherwise.

Telepsychiatry Current Practice and Implications for Future Trends: A 2023 American Psychiatric Association Member Survey.

Introduction: Although telehealth was a viable means of delivering psychiatric care even before the COVID-19 public health emergency, flexibilities at the federal and state levels during the pandemic prompted mass adoption in a short timeframe. Little is known about how psychiatrists plan to offer care going forward and to what degree services will be offered virtually, in-person, or in a hybrid format. Methods: We conducted a survey of American Psychiatric Association (APA) members regarding telepsychiatry practice and potential barriers. Results: The survey was completed by 1,660 APA members. Most survey respondents (94%) conduct at least some telepsychiatry. Most respondents indicate operating in a hybrid environment in which they maintain a physical practice location, while 16% indicate that they do not have a physical practice and only see patients remotely. Across all setting types, 82% of respondents deliver telehealth via all or mostly video; 11% report conducting telehealth visits via mostly audio-only modalities; and 7% report equal usage of both modalities. Barriers to telepsychiatry noted by respondents include limited reimbursement, state medical licensure, federal and state regulations regarding controlled substance prescribing via telehealth, and technical challenges. Conclusion: Results of this survey of APA members show that the majority conduct at least some telepsychiatry; operate in a hybrid environment; and deliver telehealth via all or mostly video. Reported barriers to telepsychiatry practice include legal, regulatory, reimbursement, and technical issues. The future of telepsychiatry may largely be determined by which legal, regulatory, and reimbursement flexibilities are ended, extended temporarily, or made permanent.

Silylene-Copper-Amide Emitters: From Thermally Activated Delayed Fluorescence to Dual Emission.

Herein, we report the inaugural instance of NHSi-coordinated copper amide emitters (2-5). These complexes exhibit thermally activated delayed fluorescence (TADF) and singlet-triplet dual emission in anaerobic conditions. The NHSi-Cu-diphenylamide (2) complex demonstrates TADF with a very small ΔEST gap (0.01 eV), an absolute quantum yield of 11%, a radiative rate of 2.55×105 s-1, and a short τTADF of 0.45 µs in the solid state. The dual emissive complexes (3-5) achieve an absolute quantum yield of up to 20% in the solid state with a kISC rate of 1.82×108 s-1 and exhibit room temperature phosphorescence (RTP) with lifetimes up to 9 ms. The gradual decrease in the intensity of the triplet state of complex 3 under controlled oxygen exposure demonstrates its potential for future oxygen-sensing applications. Complexes 2 and 3 have been further utilized to fabricate converted LEDs, paving the way for future OLED production using newly synthesized NHSi-Cu-amides.

Chitosan as a tool for tissue engineering and rehabilitation: Recent developments and future perspectives - A review.

Chitosan has established itself as a multifunctional and auspicious biomaterial within the domain of tissue engineering, presenting a decade of uninterrupted advancements and novel implementations. This article provides a comprehensive overview of the most recent developments in chitosan-based tissue engineering, focusing on significant progress made in the last ten years. An exploration is conducted of the various techniques utilized in the modification of chitosan and the production of scaffolds, with an analysis of their effects on cellular reactions and tissue regeneration. The investigation focuses on the integration of chitosan with other biomaterials and the addition of bioactive agents to improve their functionalities. Upon careful analysis of the in vitro and in vivo research, it becomes evident that chitosan effectively stimulates cell adhesion, proliferation, and differentiation. Furthermore, we offer valuable perspectives on the dynamic realm of chitosan-based approaches tailored to distinct tissue categories, including nerve, bone, cartilage, and skin. The review concludes with a discussion of prospective developments, with particular attention given to possible directions for additional study, translational implementations, and the utilization of chitosan to tackle existing obstacles in the field of tissue engineering. This extensive examination provides a significant amalgamation of the advancements achieved over the previous decade and directs scholars towards uncharted territories in chitosan-based tissue engineering.

Synthesis and catalytic application of a donor-free bismuthenium cation.

Herein, we report the synthesis and catalytic application of a new N,N'-dineopentyl-1,2-phenylenediamine-based bismuthenium cation (3). 3 has been synthesized via the treatment of chlorobismuthane LBiCl [L = 1,2-C6H4{N(CH2tBu)}2] (2) with AgSbF6, and was further used as a robust catalyst for the cyanosilylation of ketones under mild reaction conditions. Experimental studies and DFT calculations were performed to understand the mechanistic pathway.

Phytochemical analysis of Cichorium bottae root and anti-inflammatory potential assessment of isolates.

The Cichorium plants are particularly notable due to their remarkable therapeutic and medicinal properties, besides being used as food and conventional medication. Although Cichorium plants have been studied for their phytoconstituents and biological activities, there is limited knowledge about the constituents of the roots of C. bottae. A phytochemical study of the 90% MeOH extract of C. bottae roots resulted in the isolation of twelve compounds belonging to guaianolide sesquiterpene lactones, sesquiterpene lactone glucosides, and phenolic derivatives, of which two compounds designated as 9α-hydroxycrepediaside B (1) and cichobotinal (2) were previously undescribed. The isolated compounds were assessed for their anti-inflammatory potential through the inhibition of inducible nitric oxide synthase (iNOS) and resultant decrease in nitric oxide generation in LPS-induced macrophages. Among the isolates, compounds 2 and 11 (8-deoxylactucin) inhibited iNOS activity with IC50 values of 21.0 ± 4 and 6.8 ± 0.1 µM, respectively. The methanolic extract of C. bottae inhibited iNOS with an IC50 of 10.5 ± 0.5 µg/mL.

Immulina® mitigates the development of illness when administered during the prodromal period of influenza viral infection in mice (Part 2).

BACKGROUND: Immulina®, a dietary supplement derived from Limnospira (formerly Arthrospira), is being investigated as a potential agent to increase antiviral resilience. In our recently published manuscript, we described the effects of Immulina® on influenza when taken daily, beginning before infection (prophylaxis) or after the onset of clinical symptoms of viral illness (therapeutic). However, the benefit of Immulina® in infected individuals before the manifestation of any symptoms (prodromal) has not been investigated yet. PURPOSE: To evaluate Immulina®'s potential use to increase the host antiviral immune response using a prodromal therapy regime. STUDY DESIGN: The efficacy of Immulina® extract was evaluated in rodents using a prodromal protocol (test material administered prior to the emergence of viral illness symptoms). METHODS: Immulina® (25, 50 and 100 mg/kg body weight) was orally administered to both genders of mice, 2 h following influenza A viral infection, and continued daily for 14 days. RESULTS: Compared to the infected control mice, animals fed Immulina® exhibited statistically significant reduction in the emergence of various physical symptoms of viral-induced illness and decreased viral RNA levels. The effects are likely mediated through the host immune system since the level of various cytokines (IL-6 and IFN-γ) were significantly increased in lung tissue. CONCLUSION: This study, together with our previous paper, indicate that Immulina® was most effective at enhancing immune antiviral resilience if administered before or soon after initial infection. The data generated can be used to guide additional research using human subjects.

Prophylactic and therapeutic mouse models for evaluating immunologic resilience to infection with influenza virus by Immulina® (Part 1).

BACKGROUND: Illness resulting from influenza is a global health problem that has significant adverse socioeconomic impact. Although various strategies such as flu vaccination have beneficial effects, the risk of this illness has not been eliminated. The use of botanicals may provide a complementary approach by enhancement of the host antiviral immune response. PURPOSE: Generate preclinical data using rodent models to determine the most effective utility of a Limnospira (formerly Arthrospira)-derived oral supplement (Immulina®) for enhancing host immunity to improve antiviral resilience. STUDY DESIGN: Two non-lethal mouse models (prophylactic and therapeutic) were used to evaluate the impact of Immulina® on increasing host resilience against experimental influenza infection. METHODS: Mice were fed Immulina® only for the 2 weeks prior to viral infection (prophylactic regime) or starting 3 days post-viral infection (at the onset of symptoms, therapeutic design). Three doses of Immulina® were evaluated in each model using both female and male mice. RESULTS: Significant protective effect of Immulina® against viral illness was observed in the prophylactic model (improved clinical scores, less body weight loss, decreased lung/body weight ratio, lower lung viral load, and increased lung IFN-γ and IL-6). Substantially less (minimal) protective effect was observed in the therapeutic model. CONCLUSION: This study demonstrates that Immulina® exerts a protective effect against influenza illness when administered using a prophylactic regime and may not be effective if given after the onset of symptoms. The results will help to optimally design future clinical trials.

iso-Guttiferone J and Structure Revision of Guttiferone J from Garcinia gummi-gutta: A Combined Experimental and Integrated QM/NMR Approach.

Many polyprenylated acylphloroglucinols with fascinating chemical structures and intriguing biological activities have been identified as key to phytochemicals isolated from Garcinia, Hypericum, and related genera. In the present work, two chiral, tautomeric, highly-oxygenated polyprenylated acylphloroglucinols tethered with acyl and prenyl moieties on a bicyclo[3.3.1]nonanetrione core were isolated from the 95% ethanolic extract of Garcinia gummi-gutta fruit. The structures of both compounds were elucidated based on the NMR and MS data with ambiguity in the exact position of the enol and keto functions at C-1 and C-3 of the core structure. The structures of both polyprenylated acylphloroglucinols were established as a structurally revised guttiferone J and the new iso-guttiferone J with the aid of gauge-independent atomic orbital NMR calculations, CP3 probability analyses, specific rotation calculations, and electronic circular dichroism calculations in combination with the experimental data. The structures of both compounds resemble hyperforin, a potent activator of the human pregnane X receptor. As expected, both compounds showed strong pregnane X receptor activation at 10 µM [7.1-fold (guttiferone J) and 5.0-fold (iso-guttiferone J)], explained by a molecular docking study, necessitating further in-depth investigation to substantiate the herb-drug interaction potential of G. gummi-gutta upon co-administration with pharmaceutical drugs.

Assessment of coping capacity of public health facilities with health emergency situations during an event of flood in Mumbai.

BACKGROUND: Floods had been a repeated phenomenon in India, causing considerable losses to properties, life and infrastructure, and public utilities. Floods are found to be a common natural disaster occurring not only in developing countries but also in developed nations. Hospital preparedness against disaster could help in the management of the surge of patients in an effective manner. This study aims to assess the capacity of public health facilities for coping up with health emergency situations during an event of flood in Mumbai. MATERIALS AND METHODS: A cross-sectional study was conducted among 38 public health facilities in Mumbai. A purposive sampling technique was used for the selection of the health facilities. Administrative staff, medical officers, and pharmacy in charges were included in the study. RESULTS: The study revealed that surge capacities in hospitals were adequate as they had additional beds for monsoon-related diseases for the preceding flood situation. There was a triage policy, and the staff were trained on the same. Procurement of drugs was easy because of a good networking system between hospitals. Due to this networking system, patients were also transferred to the nearest healthcare facility in a short span of time. CONCLUSION: The response during an event of a flood in the health facilities of Mumbai city was good as they have regular training sessions to be prepared for the emergency situations during monsoon as they have repeated exposure to floods.

Applications of low-valent compounds with heavy group-14 elements.

Over the last two decades, the low-valent compounds of group-14 elements have received significant attention in several fields of chemistry owing to their unique electronic properties. The low-valent group-14 species include tetrylenes, tetryliumylidene, tetrylones, dimetallenes and dimetallynes. These low-valent group-14 species have shown applications in various areas such as organic transformations (hydroboration, cyanosilylation, N-functionalisation of amines, and hydroamination), small molecule activation (e.g. P4, As4, CO2, CO, H2, alkene, and alkyne) and materials. This review presents an in-depth discussion on low-valent group-14 species-catalyzed reactions, including polymerization of rac-lactide, L-lactide, DL-lactide, and caprolactone, followed by their photophysical properties (phosphorescence and fluorescence), thin film deposition (atomic layer deposition and vapor phase deposition), and medicinal applications. This review concisely summarizes current developments of low-valent heavier group-14 compounds, covering synthetic methodologies, structural aspects, and their applications in various fields of chemistry. Finally, their opportunities and challenges are examined and emphasized.

Diverse structural reactivity patterns of a POCOP ligand with coinage metals.

We have utilised the 4,6-di-tert-butyl resorcinol bis(diphenylphosphinite) (POCOP) ligand for exploring its coordination ability towards group 11 metal centres. The treatment of the bidentate ligand 1 with various coinage metal precursors afforded a wide range of structurally diverse complexes 2-12, depending upon the metal precursors used. This furnishes several multinuclear Cu(I) complexes with dimeric (2) and tetrameric cores (3, 4, and 5). The tetrameric stairstep complex 4 shows thermochromic behaviour, whereas the dimeric complex 2 and tetrameric complex 3 show luminescence properties at cryogenic temperatures. Interestingly, the halide substitution reaction of the dimeric complex 2 with KPPh2 produces a unique mixed phosphine-based tetrameric Cu(I) complex, 5. Treatment of the POCOP ligand with [CuBF4(CH3CN)4] in the presence of 2,2'-bipyridine afforded heteroleptic complex 6, consisting of tri- and tetra-coordinated cationic Cu(I) centres. Furthermore, we could also isolate cubane (8) and stairstep (9) complexes of Ag(I). The cationic Au(I) complex (12) was obtained from the dinuclear Au(I) complex of POCOP, 11. Complex 12 revealed the presence of a strong intramolecular aurophilic interaction with an Au⋯Au bond distance of 3.1143(9) Å. Subsequently, the photophysical properties of these complexes have been studied. All the complexes were characterised by single-crystal X-ray diffraction studies, routine NMR techniques, and mass spectroscopy.

Machine learning and traditional QSAR modeling methods: a case study of known PXR activators.

Pregnane X receptor (PXR), extensively expressed in human tissues related to digestion and metabolism, is responsible for recognizing and detoxifying diverse xenobiotics encountered by humans. To comprehend the promiscuous nature of PXR and its ability to bind a variety of ligands, computational approaches, viz., quantitative structure-activity relationship (QSAR) models, aid in the rapid dereplication of potential toxicological agents and mitigate the number of animals used to establish a meaningful regulatory decision. Recent advancements in machine learning techniques accommodating larger datasets are expected to aid in developing effective predictive models for complex mixtures (viz., dietary supplements) before undertaking in-depth experiments. Five hundred structurally diverse PXR ligands were used to develop traditional two-dimensional (2D) QSAR, machine-learning-based 2D-QSAR, field-based three-dimensional (3D) QSAR, and machine-learning-based 3D-QSAR models to establish the utility of predictive machine learning methods. Additionally, the applicability domain of the agonists was established to ensure the generation of robust QSAR models. A prediction set of dietary PXR agonists was used to externally-validate generated QSAR models. QSAR data analysis revealed that machine-learning 3D-QSAR techniques were more accurate in predicting the activity of external terpenes with an external validation squared correlation coefficient (R2) of 0.70 versus an R2 of 0.52 in machine-learning 2D-QSAR. Additionally, a visual summary of the binding pocket of PXR was assembled from the field 3D-QSAR models. By developing multiple QSAR models in this study, a robust groundwork for assessing PXR agonism from various chemical backbones has been established in anticipation of the identification of potential causative agents in complex mixtures.

Resource Document on Best Practices in Synchronous Videoconferencing-Based Telemental Health.

Background: This document represents an updated collaboration between the American Psychiatric Association (APA) and the American Telemedicine Association (ATA) to create a consolidated update of the previous APA and ATA official documents and resources in telemental health, to provide a single guide on clinical best practices for providing mental health services through synchronous videoconference. Methods: A joint writing committee drawn from the APA Committee on Telepsychiatry and the ATA TMH Special Interest Group (TMH SIG). was convened to draft and finalize the guidelines. This document draws directly from the 2018 APA/ATA guide and the ATA s previous guidelines, selecting from key statements/guidelines, consolidating them across documents, and then updating them where indicated. Guideline approval was provided following internal review by the APA, the ATA, the Board of Directors of the ATA, and the Joint Reference Committee of the APA. Results: The guidelines contain requirements, recommendations, and actions that are identified by text containing the keywords "shall," "should," or "may." Conclusions: Compliance with these recommendations will not guarantee accurate diagnoses or successful outcomes. The purpose of this guide is to assist providers in providing effective and safe medical care founded on expert consensus, research evidence, available resources, and patient needs.

Capsiate-Rich Fraction of Capsicum annuum Induces Muscular Glucose Uptake, Ameliorates Rosiglitazone-Induced Adipogenesis, and Exhibits Activation of NRs Regulating Multiple Signaling Pathways.

Capsiate is a key ingredient in the fruits of a nonpungent cultivar of Capsicum annuum. We investigated the effects of a C. annuum extract (CE) and a capsiate-rich fraction of CE (CR) on nuclear receptors involved in multiple signaling pathways, glucose uptake, and adipogenesis in comparison to pure capsiate (Ca). Similar to the effect of Ca (100 µM), CE (500 µg/mL) and CR (100 µg/mL) caused the activation of PPARα and PPARγ (>3-fold), while CR also activated LXR and NRF2 (>2 fold). CR (200 µg/mL) and Ca (100 µM) decreased lipid accumulation (22.6 ± 14.1 and 49.7 ± 7.3%, respectively) in adipocytes and increased glucose uptake (44.7 ± 6.2 and 30.1 ± 12.2%, respectively) in muscle cells and inhibited the adipogenic effect induced by rosiglitazone by 41.2 ± 5.6 and 13.9 ± 4.3%, respectively. This is the first report to reveal the agonistic action of CR and Ca on multiple nuclear receptors along with their enhanced glucose uptake and antiadipogenic effects. The results indicate the potential utility of the capsiate-rich fraction of C. annuum in alleviating the symptoms of metabolic syndrome and in preventing the undesired adipogenic effects of full PPARγ agonists such as rosiglitazone.

Prevalence and pattern of refractive errors among school-going children in district Baramulla, Kashmir: A cross sectional study.

PURPOSE: Uncorrected refractive error is one of the most important causes of visual impairment worldwide. Addressing childhood vision impairment (VI) is one of the main goals of the World Health Organization (WHO) to combat blindness strategies. OBJECTIVE: To ascertain the prevalence and pattern of refractive errors among children aged 10 to 16 years in Baramulla district, Kashmir. METHODS: A cross-sectional study was carried out among 680 school children during an eye camp under the school health program of the national program for control of blindness. The screening was conducted in four schools in Baramulla district, Kashmir. The schools were selected using the non-probability convenient sampling technique. RESULTS: A total of 680 school children from classes sixth to tenth aged 10-16 years participated in the study. Out of 680 students, 545 (80%) had normal vision, 97 (14%) had impaired visual acuity ranging between 6/9 and 6/24, and 38 (6%) had severe VI ranging from 6/36 to 6/60. Among the various types of refractive errors, myopia was the most prevalent affecting 54 children. Age distribution of refractive errors showed myopia to be more prevalent in the age group 13-14 years (16, 14 cases), hypermetropia was more prevalent in the age group 14-15 years (10, 8 cases), and astigmatism 5 cases in the age group 14-15 years. CONCLUSION: The study provides useful and baseline data about the refractive error amongst the school children of the Baramulla district. A larger study needs to be conducted in all schools of the state to get a clear picture of RE and other eye-related problems to detect vision problems earlier.

Chemical Profiles and Cytotoxic Activities of Essential Oils from Six Species of Baccharis Subgenus Coridifoliae (Asteraceae).

Several Baccharis species are popularly known in traditional medicine as "carquejas", "vassouras", "ervas-santas" and "mio-mios", and are used as anti-inflammatories, digestives, and diuretics. This study aimed to investigate the chemical compositions and cytotoxic activities of essential oils (EOs) of six Baccharis species belonging to subgenus Coridifoliae, namely B. albilanosa, B. coridifolia, B. erigeroides, B. napaea, B. ochracea, and B. pluricapitulata. GC/MS analyses of the EOs showed that the oxygenated sesquiterpenes spathulenol (7.32-38.22 %) and caryophyllene oxide (10.83-16.75 %) were the major components for all the species. The EOs of almost all species were cytotoxic against cancer (BT-549, KB, SK-MEL and SK-OV-3) and normal kidney (VERO and LLC-PK1) cell lines, whereas B. erigeroides EO showed cytotoxicity only against LLC-PK1. This article augments the current knowledge about the chemical-biological properties of Baccharis subgenus Coridifoliae and discusses the therapeutic potentials of these economically unexploited plants.

Juniper Berries Regulate Diabetes and Obesity Markers Through Modulating PPARα, PPARγ, and LXR: In Vitro and In Vivo Effects.

The berries of Juniperus communis have been traditionally used for therapeutic purposes. They have been reported to possess various pharmacological effects such as anti-inflammatory, hypoglycemic and hypolipidemic activities. In this study, a methanolic extract of J. communis berries (JB) was evaluated for its effects on peroxisome proliferator-activated receptors alpha and gamma (PPARα and PPARγ), liver X receptor (LXR), glucose uptake and lipid accumulation using various cellular systems. At a concentration of 25 µg/mL, JB caused 3.77-fold activation of PPARα, 10.90-fold activation of PPARγ, and 4.43-fold activation of LXR in hepatic cells. JB inhibited (11%) the adipogenic effect induced by rosiglitazone in adipocytes and increased glucose uptake (90%) in muscle cells. In high-fat diet (HFD) fed mice, JB at a dose of 25 mg/kg body weight exhibited a 21% decrease in body weight. Fasting glucose levels in mice treated with 12.5 mg/kg of JB were significantly decreased (39%) indicating its efficacy in regulating hyperglycemia and obesity induced by HFD thus ameliorating the symptoms of type 2 diabetes. A series of energy metabolic genes, including Sirt1 (2.00-fold) and RAF1 (2.04-fold), were upregulated by JB, while rosiglitazone regulated the hepatic PPARγ only. Phytochemical analysis of JB indicated presence of a number of flavonoids and biflavonoids which seem to be responsible for the observed activity. It was concluded that JB acted as a multiple agonist of PPARα, PPARγ and LXR without the undesired effect of adipogenesis and exhibited the property of enhancing glucose uptake. The regulation of PPARα, PPARγ and LXR seems to be through Sirt1 and RAF1. In vivo results confirmed the antidiabetic and antiobesity potential of JB and indicated its utility in metabolic disorder and type 2 diabetes.

Cannabinoid and Opioid Receptor Affinity and Modulation of Cancer-Related Signaling Pathways of Machaeriols and Machaeridiols from Machaerium Pers.

Machaeriols and machaeridiols are unique hexahydrodibenzopyran-type aralkyl phytocannabinoids isolated from Machaerium Pers. Earlier studies of machaeriol A (1) and B (2) did not show any affinity for cannabinoid receptor 1 (CB1 or CNR1), although they are structural analogs of psychoactive hexahydrocannabinol. This study comprehensively reports on the affinities of isolated Machaerium Pers. compounds, namely machaeriol A-D (1-4) and machaeridiol A-C (5-7), against cannabinoid (CB1 and CB2) and opioid (κ, δ and µ) receptors. Among the isolated compounds, machaeriol D (4) and machaeridiol A-C (5-7) showed some selective binding affinity for the CB2 receptor, using a radioligand binding assay, with Ki values of >1.3, >1.77, >2.18 and >1.1 µM, respectively. On the other hand, none of the compounds showed any binding to the CB1 receptor. Due to recent reports on the anticancer potential of the endocannabinoid system, compounds 1-7 were tested against a battery of luciferase reporter gene vectors that assess the activity of many cancer-related signaling pathways, including Stat3, Smad2/3, AP-1, NF-κB, E2F, Myc, Ets, Notch, FoxO, Wnt, Hedgehog and pTK in HeLa and T98G glioblastoma cells. Complete dose-response curves have been determined for each compound in both of these cell lines, which revealed that machaeridiol 6 displayed activities (IC50 in µM in HeLa and T98G cells) towards Stat3 (4.7, 1.4), Smad2/3 (1.2, 3.0), AP-1 (5.9, 4.2), NF-κB (0.5, 4.0), E2F (5.7, 0.7), Myc (5.3, 2.0), ETS (inactive, 5.9), Notch (5.3, 4.6), Wnt (4.2, inactive) and Hedgehog (inactive, 5.0). Furthermore, a combination study between machaeriol C (3) and machaeridiol B (6) displayed additive effects for E2F, ETS, Wnt and Hedgehog pathways, where these compounds individually were either minimally active or inactive. None of the compounds inhibited luciferase expression driven by the minimal thymidine kinase promoter (pTK), indicating the lack of general cytotoxicity for luciferase enzyme inhibition at the 50 µM concentration in both of these cell lines. The significance of the inhibition of these signaling pathways via machaeridiol 5-7 and their cross-talk potential has been discussed.

Evaluation of the Herb-Drug Interaction (HDI) Potential of Zingiber officinale and Its Major Phytoconstituents.

Ginger is currently one of the most popular herbs commonly added to diverse foods, beverages, and dietary supplements. We evaluated the ability of a well-characterized ginger extract, and several of its phytoconstituents, to activate select nuclear receptors as well as modulate the activity of various cytochrome P450s and ATP-binding cassette (ABC) transporters because phytochemical-mediated modulation of these proteins underlies many clinically relevant herb-drug interactions (HDI). Our results revealed ginger extract activated the aryl hydrocarbon receptor (AhR) in AhR-reporter cells and pregnane X receptor (PXR) in intestinal and hepatic cells. Among the phytochemicals investigated, (S)-6-gingerol, dehydro-6-gingerdione, and (6S,8S)-6-gingerdiol activated AhR, while 6-shogaol, 6-paradol, and dehydro-6-gingerdione activated PXR. Enzyme assays showed that ginger extract and its phytochemicals dramatically inhibited the catalytic activity of CYP3A4, 2C9, 1A2, and 2B6, and efflux transport capabilities of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). Dissolution studies with ginger extract conducted in biorelevant simulated intestinal fluid yielded (S)-6-gingerol and 6-shogaol concentrations that could conceivably exceed cytochrome P450 (CYP) IC50 values when consumed in recommended doses. In summary, overconsumption of ginger may disturb the normal homeostasis of CYPs and ABC transporters, which in turn, may elevate the risk for HDIs when consumed concomitantly with conventional medications.