In Silico Study Approach on a Series of 50 Polyphenolic Compounds in Plants; A Comparison on the Bioavailability and Bioactivity Data.

Fifty (50) phytocompounds from several subclasses of polyphenols, chosen based on their abundance in the plant world, were analyzed through density functional methods, using computational tools to evaluate their oral availability and particular bioactivity on several cell modulators; key descriptors and molecular features related to the electron density and electrostatic potential for the lowest energy conformers of the investigated molecules were computed. An analysis of the bioactivity scores towards six cell modulators (GPCR ligand, ion channel modulator, kinase inhibitor, nuclear receptor ligand, protease inhibitor and enzyme inhibitor) was also achieved, in the context of investigating their potential side effects on the human digestive processes. Summarizing, computational results confirmed in vivo and in vitro data regarding the high bioavailability of soy isoflavones and better bioavailability of free aglycones in comparison with their esterified and glycosylated forms. However, by a computational approach analyzing Lipinski's rule, apigenin and apigenin-7-O-rhamnoside, naringenin, hesperetin, genistein, daidzin, biochanin A and formonetin in the flavonoid series and all hydroxycinnamic acids and all hydroxybenzoic acids excepting ellagic acid were proved to have the best bioavailability data; rhamnoside derivatives, the predominant glycosides in green plants, which were reported to have the lowest bioavailability values by in vivo studies, were revealed to have the best bioavailability data among the studied flavonoids in the computational approach. Results of in silico screening on the phenolic derivatives series also revealed their real inhibitory potency on the six parameters studied, showing a remarkable similitude between the flavonoid series, while flavonoids were more powerful natural cell modulators than the phenyl carboxylic acids tested. Thus, it can be concluded that there is a need for supplementation with digestive enzymes, mainly in the case of individuals with low digestive efficiency, to obtain the best health benefits of polyphenols in humans.

Research Progress in the Pharmacological Activities, Toxicities, and Pharmacokinetics of Sophoridine and Its Derivatives.

Sophoridine is a natural quinolizidine alkaloid and a bioactive ingredient that can be isolated and identified from certain herbs, including Sophora flavescens Alt, Sophora alopecuroides L, and Sophora viciifolia Hance. In recent years, this quinolizidine alkaloid has gained widespread attention because of its unique structure and minimal side effects. Modern pharmacological investigations have uncovered sophoridine's multiple wide range biological activities, such as anti-cancer, anti-inflammatory, anti-viral, anti-arrhythmia, and analgesic functions, among others. These pharmacological activities and beneficial effects point to sophoridine as a strong potential therapeutic candidate for the treatment of various diseases, including several cancer types, hepatitis B virus, enterovirus 71, coxsackievirus B3, cerebral edema, cancer pain, heart failure, acute myocardial ischemia, arrhythmia, inflammation, acute lung injury, and osteoporosis. The data showed that sophoridine had adverse reactions, including hepatotoxicity and neurotoxicity. Additionally, analyses of sophoridine's safety, bioavailability, and pharmacokinetic parameters in animal models of research have been limited, especially in the clinic, as have been investigations on its structure-activity relationship. In this article, we comprehensively summarize the biological activities, toxicity, and pharmacokinetic characteristics of sophoridine and its derivatives, as currently reported in publications, as we attempt to provide an overall perspective on sophoridine analogs and the prospects of its application clinically.

Preliminary screening of the potential active ingredients in traditional Chinese medicines using the Ussing chamber model combined with HPLC-PDA-MS.

An in vitro intestinal absorption model combined with high-performance liquid chromatography-photo diode array-tandem mass spectrometry (HPLC-PDA-MS) was used for preliminary screening of potential active ingredients from complex multi-component traditional Chinese medicine (TCM) system. Oral administration is one of the main administration methods for TCMs. Only the ingredients that could be absorbed have the opportunity to play a role. Thus, these were defined as potential active ingredients. Studying of intestinal absorption can provide a theoretical basis for the mechanism of TCMs. The Caco-2 cell model, the everted rat gut sac model, and the Ussing chamber model were established for TCMs. The degree of anastomosis between the in vitro intestinal model and the actual intestinal absorption of TCMs were evaluated by the gavage method in rats. The Ussing chamber model was best fit for oral experiments in rats and was selected as the research means to preliminarily screen potential active ingredients from eight TCMs, including Salvia miltiorrhiza Bunge, Astragalus propinquus Schischkin, Plantago asiatica L, Fallopia multiflora (Thunb.) Harald, Epimedium brevicornu Maxim, Moutan Cortex, Citrus reticulata Blanco, and Panax notoginseng (Burkill) F. H. Chen ex C. H. Chow. A total of 44 components were absorbed and screened as the potential active ingredients from the 80 components identified in eight TCMs by HPLC-PDA-MS.

Toward the next-generation phyto-nanomedicines: cell-derived nanovesicles (CDNs) for natural product delivery.

Phytochemicals are plant-derived bioactive compounds, which have been widely used for therapeutic purposes. Due to the poor water-solubility, low bioavailability and non-specific targeting characteristic, diverse classes of nanocarriers are utilized for encapsulation and delivery of bio-effective agents. Cell-derived nanovesicles (CDNs), known for exosomes or extracellular vesicles (EVs), are biological nanoparticles with multiple functions. Compared to the artificial counterpart, CDNs hold great potential in drug delivery given the higher stability, superior biocompatibility and the lager capability of encapsulating bioactive molecules. Here, we provide a bench-to-bedside review of CDNs-based nanoplatform, including the bio-origin, preparation, characterization and functionalization. Beyond that, the focus is laid on the therapeutic effect of CDNs-mediated drug delivery for natural products. The state-of-art development as well as some pre-clinical applications of using CDNs for disease treatment is also summarized. It is highly expected that the continuing development of CDNs-based delivery systems will further promote the clinical utilization and translation of phyto-nanomedicines.

A comprehensive review of ethnopharmacology, phytochemistry, pharmacology, and pharmacokinetics of Schisandra chinensis (Turcz.) Baill. and Schisandra sphenanthera Rehd. et Wils.

ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis (called bei-wuweizi in Chinese, S. chinensis) and Schisandra sphenanthera (called nan-wuweizi in Chinese, S. sphenanthera) are two highly similar plants in the Magnoliaceae family. Their dried ripe fruits are commonly used as traditional Chinese medicine in the treatment of coughs, palpitation, spermatorrhea, and insomnia. They also are traditionally used as tonics in Russia, Japan, and Korea. AIM OF THE REVIEW: S. chinensis and S. sphenanthera are similar in appearance, traditional applications, ingredient compositions, and therapeutic effects. This review, therefore, aims to provide a systematic insight into the botanical background, ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics, quality control, and toxicology of S. chinensis and S. sphenanthera, and to explore and present the similarities and differences between S. chinensis and S. sphenanthera. MATERIALS AND METHODS: A comprehensive literature search regarding S. chinensis and S. sphenanthera was collected by using electronic databases including PubMed, SciFinder, Science Direct, Web of Science, CNKI, and the online ethnobotanical database. RESULTS: In the 2020 Edition of Chinese Pharmacopoeia (ChP), there were 100 prescriptions containing S. chinensis, while only 11 contained S. sphenanthera. Totally, 306 and 238 compounds have been isolated and identified from S. chinensis and S. sphenanthera, respectively. Among these compounds, lignans, triterpenoids, essential oils, phenolic acid, flavonoids, phytosterols are the major composition. Through investigation of pharmacological activities, S. chinensis and S. sphenanthera have similar therapeutic effects including hepatoprotection, neuroprotection, cardioprotection, anticancer, antioxidation, anti-inflammation, and hypoglycemic effect. Besides, S. chinensis turns out to have more effects including reproductive regulation and immunomodulatory, antimicrobial, antitussive and antiasthmatic, anti-fatigue, antiarthritic, and bone remodeling effects. Both S. chinensis and S. sphenanthera have inhibitory effects on CYP3A and P-gp, which can mediate metabolism or efflux of substrates, and therefore interact with many drugs. CONCLUSIONS: S. chinensis and S. sphenanthera have great similarities. Dibenzocyclooctadiene lignans are regarded to contribute to most of the bioactivities. Schisandrin A-C, schisandrol A-B, and schisantherin A, existing in both S. chinensis and S. sphenanthera but differing in the amount, are the main active components, which may contribute to the similarities and differences. Study corresponding to the traditional use is needed to reveal the deep connotation of the use of S. chinensis and S. sphenanthera as traditional Chinese medicine. In addition, a joint study of S. chinensis and S. sphenanthera can better show the difference between them, which can provide a reference for clinical application. It is worth mentioning that the inhibition of S. chinensis and S. sphenanthera on CYP3A and P-gp may lead to undesirable drug-drug interactions.

Clopidogrel-herb Interactions: A Pharmacokinetic and Pharmacodynamic Assessment in a Rat Model.

BACKGROUND: Herbs usually contain a mixture of biologically active constituents, which can interact with numerous prescribed drugs and alter their safety profiles. OBJECTIVES: The current investigation was aimed to evaluate the effect of commonly used herbal products including black seed (Nigella sativa), garden cress (Lepidium sativum), and fenugreek (Trigonella foenum-graecum) on the pharmacokinetics and pharmacodynamics of clopidogrel using a Wistar rat model. METHODS: A GC-MS analysis revealed the presence of several phytoconstitutents (polyphenols) in the extracts of black seed, garden cress, and fenugreek. These polyphenols have the potential to interfere with clopidogrel effect. Plasma concentrations of clopidogrel were measured at different time points in the absence and presence of the concurrent use of tested herbal products and the pharmacokinetic parameters were calculated. Bleeding time was measured in various groups as a measure of the antiplatelet effect of clopidogrel. RESULTS: Area under the plasma concentration-time curves (AUC0-∞) of clopidogrel were 35.53 ±0.89 µg/ml*h (p<0.05), 26.01 ±0.90 µg/ml*h (p>0.05) and 32.80 ±2.51 µg/ml*h (p<0.05) in the black seed, garden cress and fenugreek group, respectively, compared with that of the control group (27.02 ±0.42 µg/ml*h). Treatment with black seed also caused an increase in clopidogrel Cmax by 31.52% (p<0.05) and with fenugreek by 21.42% (p<0.05); Cmax, did not changed with garden cress treatment (6.48 ±0.15 µg/ml versus 6.12 ±0.21 µg/ml, p>0.05). The pharmacodynamic evaluation of the antiplatelet effect of clopidogrel in the presence of herbal products treatment showed a significant prolongation in the bleeding time from a control baseline by ~22-26%, and by added ~8-12% in reference to clopidogrel therapeutic effect (p<0.05). CONCLUSION: The concurrent use of black seed, fenugreek, or garden cress can alter the pharmacokinetics and pharmacodynamics of clopidogrel to varying degrees due to the presence of various bioactive polyphenols. This is probably due to changes in drug disposition and its antiplatelet action. Further confirmation can determine the clinical relevance of these observations and identify the exact constituents responsible for such activities.

In Vitro Evidence on Bioaccessibility of Flavonols and Cinnamoyl Derivatives of Cruciferous Sprouts.

Cruciferous sprouts are rising in popularity as a hallmark of healthy diets, partially because of their phytochemical composition, characterized by the presence of flavonols and cinnamates. However, to shed light on their biological activity, the ability to assimilate (poly)phenols from sprouts (bioaccessible fraction) during gastrointestinal digestion needs to be studied. In this frame, the present work studies the effect of the physicochemical and enzymatic characteristics of gastrointestinal digestion on flavonols and cinnamoyl derivatives, by a simulated static in vitro model, on different cruciferous (red radish, red cabbage, broccoli, and white mustard) sprouts. The results indicate that, although the initial concentrations of phenolic acids in red radish (64.25 mg/g fresh weight (fw)) are lower than in the other sprouts studied, their bioaccessibility after digestion is higher (90.40 mg/g fw), followed by red cabbage (72.52 mg/g fw), white mustard (58.72 mg/g fw), and broccoli (35.59 mg/g fw). These results indicate that the bioaccessibility of (poly)phenols is not exclusively associated with the initial concentration in the raw material, but that the physico-chemical properties of the food matrix, the presence of other additional molecules, and the specific characteristics of digestion are relevant factors in their assimilation.

Diterpenes/Diterpenoids and Their Derivatives as Potential Bioactive Leads against Dengue Virus: A Computational and Network Pharmacology Study.

Dengue fever is a dangerous infectious endemic disease that affects over 100 nations worldwide, from Africa to the Western Pacific, and is caused by the dengue virus, which is transmitted to humans by an insect bite of Aedes aegypti. Millions of citizens have died as a result of dengue fever and dengue hemorrhagic fever across the globe. Envelope (E), serine protease (NS3), RNA-directed RNA polymerase (NS5), and non-structural protein 1 (NS1) are mostly required for cell proliferation and survival. Some of the diterpenoids and their derivatives produced by nature possess anti-dengue viral properties. The goal of the computational study was to scrutinize the effectiveness of diterpenoids and their derivatives against dengue viral proteins through in silico study. Methods: molecular docking was performed to analyze the binding affinity of compounds against four viral proteins: the envelope (E) protein, the NS1 protein, the NS3 protein, and the NS5 protein. Results: among the selected drug candidates, triptolide, stevioside, alepterolic acid, sphaeropsidin A, methyl dodovisate A, andrographolide, caesalacetal, and pyrimethamine have demonstrated moderate to good binding affinities (-8.0 to -9.4 kcal/mol) toward the selected proteins: E protein, NS3, NS5, and NS1 whereas pyrimethamine exerts -7.5, -6.3, -7.8, and -6.6 kcal/mol with viral proteins, respectively. Interestingly, the binding affinities of these lead compounds were better than those of an FDA-approved anti-viral medication (pyrimethamine), which is underused in dengue fever. Conclusion: we can conclude that diterpenoids can be considered as a possible anti-dengue medication option. However, in vivo investigation is recommended to back up the conclusions of this study.

Characterization of Metabolites of α-mangostin in Bio-samples from SD Rats by UHPLC-Q-exactive Orbitrap MS.

BACKGROUND: α-mangostin, a typical xanthone, often exists in Garcinia mangostana L. (Clusiaceae). α-mangostin was found to have a wide range of pharmacological properties. However, its specific metabolic route in vivo remains unclear, while these metabolites may accumulate to exert pharmacological effects, too. OBJECTIVE: This study aimed to clarify the metabolic pathways of α-mangostin after oral administration to the rats. METHODS: Here, an UHPLC-Q-Exactive Orbitrap MS was used for the detection of potential metabolites formed in vivo. A new strategy for the identification of unknown metabolites based on typical fragmentation routes was implemented. RESULTS: A total of 42 metabolites were detected, and their structures were tentatively identified in this study. The results showed that major in vivo metabolic pathways of α-mangostin in rats included methylation, demethylation, methoxylation, hydrogenation, dehydrogenation, hydroxylation, dehydroxylation, glucuronidation, and sulfation. CONCLUSIONS: This study is significant to expand our knowledge of the in vivo metabolism of α-mangostin and to understand the mechanism of action of α-mangostin in rats in vivo.

Identification and pharmacokinetics of bioavailable anti-resorptive phytochemicals after oral administration of Psoralea corylifolia L.

Osteoporosis and resulting bone fractures are the major health issues associated with morbidity in the aging population; however, there is no effective treatment that does not cause severe side effects. In East Asia, dried seeds of Psoralea corylifolia L. (PC) have traditionally been used as an herbal medicine to manage urinary tract, cutaneous, and gastrointestinal disorders, as well as bone health. However, the mechanism of action and active biocomponents of PC are unclear. Here, we adopted a pharmacokinetic (PK) study aiming to identify the bioavailable phytochemicals in aqueous and ethanolic extracts of PC (APC) and (EPC), respectively. In addition, we aimed to determine anti-resorptive constituents of PC, which accounted for its beneficial effects on bone health. To this end, we used ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). A rapid, sensitive, and reliable UPLC-MS/MS method was developed and determined the 17 PC ingredients. In the PK study, nine components (two chalcones, two coumarins, one coumestan, two flavonoids, and two isoflavonoids) were observed between 36 and 48 h after oral administration of APC or EPC. Among the bioavailable ingredients, four PC constituents (psoralidin, isobavachin, corylifol A, and neobavaisoflavone) inhibited M-CSF-and RANKL-induced osteoclast differentiation in bone marrow-derived macrophages. In addition, two chalcones and two isoflavonoids markedly inhibited cathepsin K activity, and their binding modes to cathepsin K were determined by molecular docking. In summary, our data suggest that bioavailable multicomponents of PC could contribute to the management of bone health.

Resveratrol (RV): A pharmacological review and call for further research.

Resveratrol (RV) is a well-known polyphenolic compound in various plants, including grape, peanut, and berry fruits, which is quite famous for its association with several health benefits such as anti-obesity, cardioprotective neuroprotective, antitumor, antidiabetic, antioxidants, anti-age effects, and glucose metabolism. Significantly, promising therapeutic properties have been reported in various cancer, neurodegeneration, and atherosclerosis and are regulated by several synergistic pathways that control oxidative stress, cell death, and inflammation. Similarly, RV possesses a strong anti-adipogenic effect by inhibiting fat accumulation processes and activating oxidative and lipolytic pathways, exhibiting their cardioprotective effects by inhibiting platelet aggregation. The RV also shows significant antibacterial effects against various food-borne pathogens (Listeria, Campylobacter, Staphylococcus aureus, and E. coli) by inhibiting an electron transport chain (ETC) and F0F1-ATPase, which decreases the production of cellular energy that leads to the spread of pathogens. After collecting and analyzing scientific literature, it may be concluded that RV is well tolerated and favorably affects cardiovascular, neurological, and diabetic disorders. As such, it is possible that RV can be considered the best nutritional additive and a complementary drug, especially a therapeutic candidate. Therefore, this review would increase knowledge about the blend of RV as well as inspire researchers around the world to consider RV as a pharmaceutical drug to combat future health crises against various inhumane diseases. In the future, this article will be aware of discoveries about the potential of this promising natural compound as the best nutraceuticals and therapeutic drugs in medicine.

Epiphytic Acampe ochracea orchid relieves paracetamol-induced hepatotoxicity by inhibiting oxidative stress and upregulating antioxidant genes in in vivo and virtual screening.

Orchids are basically ornamental, and biological functions are seldom evaluated. This research investigated the effects of Acampe ochracea methanol extract (AOME) in ameliorating the paracetamol (PCM) induced liver injury in Wistar albino rats, evaluating its phytochemical status through UPLC-qTOF-MS analysis. With molecular docking and network pharmacology, virtual screening verified the inevitable interactions between the UPLC-qTOF-MS-characterized compounds and hepatoprotective drug receptors. The AOME has explicit a dose-dependent decrease of liver enzymes acid phosphatase (ACP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), total bilirubin, as well as an increase of serum total protein and antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GSH) with a virtual normalization (p < 0.05-p < 0.001) and the values were almost equivalent to the reference drug silymarin. After pretreatment with AOME, PCM-induced malondialdehyde (MDA) levels were considerably decreased (p < 0.001). Histopathological examinations corroborated the functional and biochemical findings. The AOME upregulated the genes involved in antioxidative (CAT, SOD, ß-actin, PON1, and PFK1) and hepatoprotective mechanisms in PCM intoxicated rats. An array of 103 compounds has been identified from AOME through UPLC-qTOF-MS analysis. The detected compounds were substantially related to the targets of several liver proteins and antioxidative enzymes, according to an in silico study. Virtual prediction by SwissADME and admetSAR showed that AOME has drug-like, non-toxic, and potential pharmacological activities in hepatic damage. Furthermore, VEGFA, CYP19A1, MAPK14, ESR1, and PPARG genes interact with target compounds impacting the significant biological actions to recover PCM-induced liver damage.

Lamiophlomis herba: A comprehensive overview of its chemical constituents, pharmacology, clinical applications, and quality control.

Lamiophlomis rotata (Benth.) Kudo (LR) is an extensively used Chinese herbal medicine. It contains a variety of chemical constituents with significant biological activities that were first recorded in the classical masterpiece of Tibetan Medicine, Somaratsa. In this review, we summarize the information regarding the traditional uses, chemical constituents, pharmacological effects, clinical applications, quality control, toxicology, and pharmacokinetics of LR. At least 223 chemical constituents have been isolated from LR, including phenylethanoid glycosides, flavonoids, iridoids, volatile oils, et al. Their various physiological activities have been demonstrated as analgesic, hemostatic, anti-inflammatory, anti-tumor, marrow-supplementing, anti-bacterial, and immunity-strengthening. The clinical applications of LR and quality control are also discussed, as well as some existing problems. This article aims to provide more comprehensive information on the chemical composition, pharmacological activity, and clinical application of LR, so as to provide a theoretical basis for the further reasonable development of LR in clinical practice and of new drugs.

Impact of Phytochemicals on Viability and Cereulide Toxin Synthesis in Bacillus cereus Revealed by a Novel High-Throughput Method, Coupling an AlamarBlue-Based Assay with UPLC-MS/MS.

Due to its food-poisoning potential, Bacillus cereus has attracted the attention of the food industry. The cereulide-toxin-producing subgroup is of particular concern, as cereulide toxin is implicated in broadscale food-borne outbreaks and occasionally causes fatalities. The health risks associated with long-term cereulide exposure at low doses remain largely unexplored. Natural substances, such as plant-based secondary metabolites, are widely known for their effective antibacterial potential, which makes them promising as ingredients in food and also as a surrogate for antibiotics. In this work, we tested a range of structurally related phytochemicals, including benzene derivatives, monoterpenes, hydroxycinnamic acid derivatives and vitamins, for their inhibitory effects on the growth of B. cereus and the production of cereulide toxin. For this purpose, we developed a high-throughput, small-scale method which allowed us to analyze B. cereus survival and cereulide production simultaneously in one workflow by coupling an AlamarBlue-based viability assay with ultraperformance liquid chromatography-mass spectrometry (UPLC-MS/MS). This combinatory method allowed us to identify not only phytochemicals with high antibacterial potential, but also ones specifically eradicating cereulide biosynthesis already at very low concentrations, such as gingerol and curcumin.

Metabolite profiling, anti-inflammatory, analgesic potentials of edible herb Colocasia gigantea and molecular docking study against COX-II enzyme.

ETHNOPHARMACOLOGICAL RELEVANCE: Consumable herbs play a basic part in sustenance and human health. Traditionally, Colocasia gigantea Hook (Araceae) is used to treat fever, infection, wounds healing, drowsiness, tuberculosis, stomach problems etc. AIM OF THE STUDY: The study aspired to identify bioactive compounds, to evaluate anti-inflammatory and analgesic potentials of edible herb C. gigantea, and to molecular docking study against anti-inflammatory enzyme Cyclooxygenase-2 (COX-2). MATERIALS AND METHODS: Chemical components of C. gigantea were discerned by HPLC and GCMS assays. In vitro anti-inflammatory activity was appraised by heat-induced, hypotonicity, and hydrogen peroxide-induced hemolysis assays and in vivo by formalin-induced paw edema assay. In vivo analgesic activity was evaluated by acetic acid-induced pain modulation assay. Also, molecular docking of the identified compounds was explored against the anti-inflammatory enzyme cyclooxygenase-2. RESULTS: HPLC-DAD analysis divulged the presence of trans-cinnamic acid along with (-)-epicatechin as a prime component. Also, 9, 12-Octadecadienoic acid (37.86%) and n-Hexadecanoic acid (25.89%) as the major as well as 24 other compounds were confirmed through GCMS in the extract. In in vitro anti-inflammatory study, C. gigantea extract indicated prominent erythrocyte membrane stabilization activity with good percentage aegis in all experimental assays. In addition to, formalin-induced in vivo anti-inflammatory assay revealed the maximum (42.37% and 48.72%) suppression of edema at the fourth hour at 250 and 500 mg/kg body weight, respectively. Moreover, an in-vivo pain modulation assay exposed significant (p < 0.05) activity at experimental doses. Furthermore, in the docking study, (-)-epicatechin was more active rather than other identified compounds with strong binding affinity to COX-2 protein. CONCLUSIONS: The extract evinced remarkable anti-inflammatory and analgesic activities. Identified bioactive components along with other components of the extract might play a pivotal role in the observed bioactivity and the results vindicate the use of edible herb C. gigantea in ancestral medicine.

Identification of 3-Methoxycarpachromene and Masticadienonic Acid as New Target Inhibitors against Trypanothione Reductase from Leishmania Infantum Using Molecular Docking and ADMET Prediction.

Polyphenolic and Terpenoids are potent natural antiparasitic compounds. This study aimed to identify new drug against Leishmania parasites, leishmaniasis's causal agent. A new in silico analysis was accomplished using molecular docking, with the Autodock vina program, to find the binding affinity of two important phytochemical compounds, Masticadienonic acid and the 3-Methoxycarpachromene, towards the trypanothione reductase as target drugs, responsible for the defense mechanism against oxidative stress and virulence of these parasites. There were exciting and new positive results: the molecular docking results show as elective binding profile for ligands inside the active site of this crucial enzyme. The ADMET study suggests that the 3-Methoxycarpachromene has the highest probability of human intestinal absorption. Through this work, 3-Methoxycarpachromene and Masticadienonic acid are shown to be potentially significant in drug discovery, especially in treating leishmaniasis. Hence, drug development should be completed with promising results.

Colloidal and vesicular delivery system for herbal bioactive constituents.

OBJECTIVES: The main objective of the present review is to explore and examine the effectiveness of currently developed novel techniques to resolve the issues which are associated with the herbal constituents/extract. METHODS: A systematic thorough search and collection of reviewed information from Science direct, PubMed and Google Scholar databases based on various sets of key phrases have been performed. All the findings from these data have been studied and briefed based on their relevant and irrelevant information. RESULT: Herbal drugs are gaining more popularity in the modern world due to their applications in curing various ailments with minimum toxic effects, side effect or adverse effect. However, various challenges exist with herbal extracts/plant actives such as poor solubility (water/lipid), poor permeation, lack of targeting specificity, instability in highly acidic pH, and liver metabolism, etc. Nowadays with the expansion in the technology, novel drug delivery system provides avenues and newer opportunity towards the delivery of herbal drugs with improved physical chemical properties, pharmacokinetic and pharmacodynamic. Developing nano-strategies like Polymeric nanoparticles, Liposomes, Niosomes, Microspheres, Phytosomes, Nanoemulsion and Self Nano Emulsifying Drug Delivery System, etc. imparts benefits for delivery of phyto formulation and herbal bioactives. Nano formulation of phytoconstituents/ herbal extract could lead to enhancement of aqueous solubility, dissolution, bioavailability, stability, reduce toxicity, permeation, sustained delivery, protection from enzymatic degradation, etc. CONCLUSION: Based on the above findings, the conclusion can be drawn that the nano sized novel drug delivery systems of herbal and herbal bioactives have a potential future for upgrading the pharmacological action and defeating or overcoming the issues related with these constituents. The aims of the present review was to summarize and critically analyze the recent development of nano sized strategies for promising phytochemicals delivery systems along with their therapeutic applications supported by experimental evidence and discussing the opportunities for further aspects.

Herb-drug interactions and toxicity: Underscoring potential mechanisms and forecasting clinically relevant interactions induced by common phytoconstituents via data mining and computational approaches.

Herbals in the form of medicine are employed extensively around the world. Herbal and conventional medicine combination is a potentially dangerous practice mainly in comorbid, hepato insufficient and frail patients leading to perilous herb-drug interactions (HDI) and toxicity. This study features potential HDI of 15 globally famous plant species through data mining and computational methods. Several plant species were found to mimic warfarin. Phytochemicals from M. charantia induced hypoglycemica. M. chamomila and G. biloba possessed anticoagulant activities. S. hispanica reduces postprandial glycemia. R. officinalis has been reported to inhibit the efflux of anticancer substrates while A. sativum can boost the clearance of anticancer agents. P. ginseng can alter blood coagulation. A cross link of the biological and in silico data revealed that a plethora of herbal metabolites such as ursolic and rosmarinic acid among others are possible/probable inhibitors of specific CYP450 enzymes. Consequently, plant species/metabolites with a given pharmacological property/metabolizing enzyme should not be mixed with drugs having the same pharmacological property/metabolizing enzyme. Even if combined with drugs, herbal medicines must be used at low doses for a short period of time and under the supervision of a healthcare professional to avoid potential adverse and toxic effects.

Evaluation of Microwave-Assisted Extraction Method for Preparation and Assessment of Thai Herbal Medicine Oral Tablets With Enriched Phytochemical Compounds.

In developing countries, populations have employed herbal medicines for primary health care because they are believed to be more appropriate to the human body and have less side effects than chemically synthesized drugs. The present study aimed to develop and evaluate herbal tablets incorporated with a Thai traditional medicinal extract, U-pa-ri-waat (URW), using microwave-assisted extraction (MAE). The extraction efficiency for URW using MAE and traditional solvent extraction was compared based on the percent yield after spray drying. URW tablets were prepared using the dry granulation method. The optimized products were assessed using standard characterization methods based on the United States and British Pharmacopeias. DPPH and ABTS radical scavenging assays were performed to analyze the antioxidant capacity of the microwave-assisted extracts. The results revealed that the flowability of the dry granule with added maltodextrin was improved compared to a granule without additives, as indicated by an angle of repose of 33.69 ± 2.0°, a compressibility index of 15.38 ± 0.66, and a Hausner's ratio of 1.18 ± 0.06. The resulting formulation produced flat tablets with uniform weight variation, hardness, thickness, friability, and optimum disintegration time. The URW extracts showed antioxidant activity and MAE with maltodextrin carrier displayed the strongest DPPH and ABTS radical activities with IC50 values of 1.60 ± 0.02 µg/mL and 4.02 ± 0.24 µg/mL, respectively. The URW tablet formulation passed the quality control tests. Storage of the formulation tablets for 90 days under accelerated conditions had minimal effects on tablet characteristics.

Oleuropein-Induced Acceleration of Cytochrome P450-Catalyzed Drug Metabolism: Central Role for Nuclear Receptor Peroxisome Proliferator-Activated Receptor α.

Oleuropein (OLE), the main constituent of Olea europaea, displays pleiotropic beneficial effects in health and disease, which are mainly attributed to its anti-inflammatory and cardioprotective properties. Several food supplements and herbal medicines contain OLE and are available without a prescription. This study investigated the effects of OLE on the main cytochrome P450s (P450s) catalyzing the metabolism of many prescribed drugs. Emphasis was given to the role of peroxisome proliferator-activated receptor α (PPARα), a nuclear transcription factor regulating numerous genes including P450s. 129/Sv wild-type and Ppara-null mice were treated with OLE for 6 weeks. OLE induced Cyp1a1, Cyp1a2, Cyp1b1, Cyp3a14, Cyp3a25, Cyp2c29, Cyp2c44, Cyp2d22, and Cyp2e1 mRNAs in liver of wild-type mice, whereas no similar effects were observed in Ppara-null mice, indicating that the OLE-induced effect on these P450s is mediated by PPARα. Activation of the pathways related to phosphoinositide 3-kinase/protein kinase B (AKT)/forkhead box protein O1, c-Jun N-terminal kinase, AKT/p70, and extracellular signal-regulated kinase participates in P450 induction by OLE. These data indicate that consumption of herbal medicines and food supplements containing OLE could accelerate the metabolism of drug substrates of the above-mentioned P450s, thus reducing their efficacy and the outcome of pharmacotherapy. Therefore, OLE-induced activation of PPARα could modify the effects of drugs due to their increased metabolism and clearance, which should be taken into account when consuming OLE-containing products with certain drugs, in particular those of narrow therapeutic window. SIGNIFICANCE STATEMENT: This study indicated that oleuropein, which belongs to the main constituents of the leaves and olive drupes of Olea europaea, induces the synthesis of the major cytochrome P450s (P450s) metabolizing the majority of prescribed drugs via activation of peroxisome proliferator-activated receptor α. This effect could modify the pharmacokinetic profile of co-administered drug substrates of the P450s, thus altering their therapeutic efficacy and toxicity.