Molecular networking-based mass spectral identification of Brucea javanica (L.) Merr. metabolites and their selective binding affinities for dengue virus enzymes.

Brucea javanica, a valued traditional medicinal plant in Malaysia, known for its fever-treating properties yet remains underexplored for its potential antiviral properties against dengue. This study aims to simultaneously identify chemical classes and metabolites within B. javanica using molecular networking (MN), by Global Natural Product Social (GNPS), and SIRIUS in silico annotation. Liquid chromatography-mass spectrometry (LC-MS2)-based MN explores chemical diversity across four plant parts (leaves, roots, fruits, and stem bark), revealing diverse metabolites such as tryptophan-derived alkaloids, terpenoids, and octadecadenoids. Simultaneous LC-MS2 and MN analyses reveal a discriminative capacity for individual plant components, with roots accumulating tryptophan alkaloids, fruits concentrating quassinoids, leaves containing fusidanes, and stem bark primarily characterised by simple indoles. Subsequently, extracts were evaluated for dengue antiviral activity using adenosine triphosphate (ATP) and plaque assays, indicates potent efficacy in the dichloromethane (DCM) extract from roots (EC50 = 0.3 µg/mL, SI = 10). Molecular docking analysis of two major compounds; canthin-6-one (264) and 1-hydroxy-11-methoxycanthin-6-one (275) showed potential binding interactions with active sites of NS5 RNA-dependent RNA polymerase (RdRp) of dengue virus (DENV) protein. Subsequent in vitro evaluation revealed compounds 264 and 275 had a promising dengue antiviral activity with SI value of 63 and 1.85. These identified metabolites emerge as potential candidates for further evaluation in dengue antiviral activities.

The contemporary nexus of medicines security and bioprospecting: a future perspective for prioritizing the patient.

Reacting to the challenges presented by the evolving nexus of environmental change, defossilization, and diversified natural product bioprospecting is vitally important for advancing global healthcare and placing patient benefit as the most important consideration. This overview emphasizes the importance of natural and synthetic medicines security and proposes areas for global research action to enhance the quality, safety, and effectiveness of sustainable natural medicines. Following a discussion of some contemporary factors influencing natural products, a rethinking of the paradigms in natural products research is presented in the interwoven contexts of the Fourth and Fifth Industrial Revolutions and based on the optimization of the valuable assets of Earth. Following COP28, bioprospecting is necessary to seek new classes of bioactive metabolites and enzymes for chemoenzymatic synthesis. Focus is placed on those performance and practice modifications which, in a sustainable manner, establish the patient, and the maintenance of their prophylactic and treatment needs, as the priority. Forty initiatives for natural products in healthcare are offered for the patient and the practitioner promoting global action to address issues of sustainability, environmental change, defossilization, quality control, product consistency, and neglected diseases to assure that quality natural medicinal agents will be accessible for future generations.

Maslinic acid exerts anticancer effects by targeting cancer hallmarks.

BACKGROUND: Natural products have long been regarded as a source of anticancer compounds with low toxicity. Evidence revealed that maslinic acid (MA), a widely distributed pentacyclic triterpene in common foodstuffs, exhibited pronounced inhibitory effects against various cancer cell lines. Most cancer cells thrive by acquiring cancer hallmarks, as coined by Hanahan and Weinberg in 2000 and 2011. PURPOSE: This represents the first systematic review concerning the anticancer properties of MA as these cancer hallmarks are targeted. It aims to summarize the antineoplastic activities of MA, discuss the diverse mechanisms of action based on the effects of MA exerted on each hallmark. METHODS: A comprehensive literature search was conducted using the search terms "maslinic," "cancer," "tumor," and "neoplasm," to retrieve articles from the databases MEDLINE, EMBASE, Web of Science, and Scopus published up to September 2022. Study selection was conducted by three reviewers independently from title and abstract screening until full-text evaluation. Data extraction was done by one reviewer and counterchecked by the second reviewer. RESULTS: Of the 330 articles assessed, 40 papers met the inclusion criteria and revealed that MA inhibited 16 different cancer cell types. MA impacted every cancer hallmark by targeting multiple pathways. CONCLUSION: This review provides insights regarding the inhibitory effects of MA against various cancers and its remarkable biological properties as a pleiotropic bioactive compound, which encourage further investigations.

Cyberecoethnopharmacolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Development of a new term which describes the contemporary, composite, constituent sciences of ethnopharmacology. AIM OF THE STUDY: To discuss the polysyllabic term cyberecoethnopharmacolomics in the context of the future of ethnopharmacology in global health care. MATERIALS AND METHODS: Literature background and assessment from the prior literature, diverse databases, and personal discussions. RESULTS: The profiles and literature background with contemporary and future thoughts regarding the concepts and practices of cyber-, eco-, ethno-, pharmacol-, and -omics, and their impact in ethnopharmacology for the future are presented in the context of integrated health care systems. CONCLUSIONS: Ethnopharmacology has a major role to play in global health care if the relevant sciences and cutting-edge technologies can coalesce synergistically as a responsive, evidence-based health care practice.

Goniolanceolatins A-H, Cytotoxic Bis-styryllactones from Goniothalamus lanceolatus.

Eight new bis-styryllactones, goniolanceolatins A-H (1-8), possessing a rare α,ß-unsaturated δ-lactone moiety with a (6S)-configuration, were isolated from the CH2Cl2 extract of the stembark and roots of Goniothalamus lanceolatus Miq., a plant endemic to Malaysia. Absolute structures were established through extensive 1D- and 2D-NMR data analysis, in combination with electronic dichroism (ECD) data. All of the isolates were evaluated for their cytotoxicity against human lung and colorectal cancer cell lines. Compounds 2 and 4 showed cytotoxicity, with IC50 values ranging from 2.3 to 4.2 µM, and were inactive toward human noncancerous lung and colorectal cells. Compounds 1, 3, 6, 7, and 8 showed moderate to weak cytotoxicity. Docking studies of compounds 2 and 4 showed that they bind with EGFR tyrosine kinase and cyclin-dependent kinase 2 through hydrogen bonding interactions with the important amino acids, including Lys721, Met769, Asn818, Arg157, Ile10, and Glu12.

Pharmacognosy in the digital era: shifting to contextualized metabolomics.

Humans have co-evolved alongside numerous other organisms, some having a profound effect on health and nutrition. As the earliest pharmaceutical subject, pharmacognosy has evolved into a meta-discipline devoted to natural biomedical agents and their functional properties. While the acquisition of expanding data volumes is ongoing, contextualization is lagging. Thus, we assert that the establishment of an integrated and open databases ecosystem will nurture the discipline. After proposing an epistemological framework of knowledge acquisition in pharmacognosy, this study focuses on recent computational and analytical approaches. It then elaborates on the flux of research data, where good practices could foster the implementation of more integrated systems, which will in turn help shaping the future of pharmacognosy and determine its constitutional societal relevance.

Effects of a Peganum harmala (Zygophyllaceae) preparation for root canal disinfection.

The aim of this study was to determine the antimicrobial capacity, minimum inhibitory concentration (MIC), and cytotoxic effects of a Peganum harmala seed extract in comparison to 5.25% sodium hypochlorite (NaOCl). The oral pathogen Enterococcus faecalis was used to evaluate the antimicrobial capacity, and the MIC values were determined through serial dilution. Inhibition zones were measured in millimeter, and the data were analyzed statistically by analysis of variance and the Tukey HSD test. For cytotoxicity testing, P. harmala seed extract and 5.25% NaOCl solution were incubated with L929 fibroblast cells. After 1, 24, and 72 hr of incubation, cells were stained and the optical density determined with an enzyme-linked immunosorbent assay (ELISA) reader. Data were analyzed with Chi-Square statistical test. The significance level was set at p < .05. There was no significant difference between the antimicrobial capacity of 5.25% NaOCl and the P. harmala extract (p > .05; MIC 4 µg/ml). The Microculture Tetrazolium (MTT) assay test showed that the cytotoxic effects of the P. harmala extract were significantly lower than 5.25% NaOCl (p < .05). The results show that 5.25% NaOCl and P. harmala seed extract have similar antimicrobial activity against Enterococcus faecalis; but P. harmala, which shows reduced cytotoxicity, should be considered for further investigation as a safe, phytotherapeutic, intracanal irrigant.

Slimming and Appetite-Suppressing Effects of Caraway Aqueous Extract as a Natural Therapy in Physically Active Women.

Following the current 'Globesity' trend, there is an increasing demand for alternative natural therapies for weight management. Numerous phytoconstituents reduce body weight through suppressing appetite and reducing food intake. Caraway (Carum carvi L.) is one of the medicinal plants that is traditionally used for weight loss. In this study, the appetite-suppressing effects of caraway aqueous extract (CAE) on 70 aerobically trained, overweight, and obese women were examined in a triple-blind, placebo-controlled, clinical study. Subjects were randomly allocated into placebo and experimental groups and consumed either 30 mL/day of CAE or placebo without changing their diet or physical activity over a period of 90 days. Calorie and macronutrient intake and anthropometric indices were measured before and after the intervention. In addition, appetite changes were assessed through a visual analog scale and an ad libitum pizza test. After the intervention, the results showed a significant reduction in appetite levels and carbohydrate intake of the experimental group compared with the placebo group. All of the anthropometric indices were reduced significantly in CAE compared with placebo group (p < 0.01). These preliminary outcomes suggest that a dietary CAE might be effective in weight management of physically active, adult females, reducing their body size and hunger level. Copyright © 2016 John Wiley & Sons, Ltd.

Molecular Docking and Binding Mode Analysis of Plant Alkaloids as in vitro and in silico Inhibitors of Trypanothione Reductase from Trypanosoma cruzi.

Trypanothione reductase (TryR) is a key enzyme in the metabolism of Trypanosoma cruzi, the parasite responsible for Chagas disease. The available repertoire of TryR inhibitors relies heavily on synthetic substrates of limited structural diversity, and less on plant-derived natural products. In this study, a molecular docking procedure using a Lamarckian Genetic Algorithm was implemented to examine the protein-ligand binding interactions of strong in vitro inhibitors for which no X-ray data is available. In addition, a small, skeletally diverse, set of natural alkaloids was assessed computationally against T. cruzi TryR in search of new scaffolds for lead development. The preferential binding mode (low number of clusters, high cluster population), together with the deduced binding interactions were used to discriminate among the virtual inhibitors. This study confirms the prior in vitro data and proposes quebrachamine, cephalotaxine, cryptolepine, (22S,25S)-tomatidine, (22R,25S)-solanidine, and (22R,25R)-solasodine as new alkaloid scaffold leads in the search for more potent and selective TryR inhibitors.

Alice, Benzene, and Coffee: The ABCs of Ecopharmacognosy.

The sesquicentennial celebrations of the publication of "Alice's Adventures in Wonderland" and the structure of benzene offer a unique opportunity to develop a contemporary interpretation of aspects of Alice's adventures, illuminate the symbolism of benzene, and contextualize both with the globalization of coffee, transitioning to how the philosophy and sustainable practices of ecopharmacognosy may be applied to modulating approaches to the quality, safety, efficacy, and consistency (QSEC) of traditional medicines and dietary supplements through technology integration, thereby improving patient-centered health care.

Preliminary safety evaluation and biochemical efficacy of a Carum carvi extract: results from a randomized, triple-blind, and placebo-controlled clinical trial.

Carum carvi L. (Apiaceae) is known as caraway, and its derivatives find wide medicinal use for health purposes, including for gastrointestinal problems and obesity. Since there is inconsistency among the reports on the safety of this plant in humans, this research was aimed at assessing the safety of a characterized caraway aqueous extract (CAE) in a randomized, triple-blind, placebo-controlled study. Seventy, overweight and obese, healthy women were randomly assigned into placebo (n = 35) and plant extract (n = 35) groups. Participants received either 30 ml/day of CAE or placebo. Subjects were examined at baseline and after 12 weeks for changes in heart rate, blood pressure, urine test, 25-item blood chemistries, and general health status. No significant changes of blood pressure, heart rate, urine specific gravity, and serum blood tests were observed between the two groups before and after treatment. However, in the complete blood count test, red blood cell levels were significantly (p < 0.01) increased, and platelet distribution width was significantly decreased after the dietary CAE treatment, as compared with placebo. No negative changes were observed in the general health status of the two groups. This preliminary study suggests that the oral intake of CAE appears to be without any adverse effects at a dosage of 30 ml daily for a period of 12 weeks.

Antiobesity effect of caraway extract on overweight and obese women: a randomized, triple-blind, placebo-controlled clinical trial.

Caraway (Carum carvi L.), a potent medicinal plant, is traditionally used for treating obesity. This study investigates the weight-lowering effects of caraway extract (CE) on physically active, overweight and obese women through a randomized, triple-blind, placebo-controlled clinical trial. Seventy overweight and obese, healthy, aerobic-trained, adult females were randomly assigned to two groups (n = 35 per group). Participants received either 30 mL/day of CE or placebo without changing their diet or physical activity. Subjects were examined at baseline and after 90 days for changes in body composition, anthropometric indices, and clinical and paraclinical variables. The treatment group, compared with placebo, showed a significant reduction of weight, body mass index, body fat percentage, and waist-to-hip ratio. No changes were observed in lipid profile, urine-specific gravity, and blood pressure of subjects. The results suggest that a dietary CE with no restriction in food intake, when combined with exercise, is of value in the management of obesity in women wishing to lower their weight, BMI, body fat percentage, and body size, with no clinical side effects. In conclusion, results of this study suggest a possible phytotherapeutic approach for caraway extract in the management of obesity. This trial is registered with NCT01833377.

Natural products and traditional medicine: turning on a paradigm.

Paradigm shifts in the strategies and the sciences that would enhance the quality, safety, and efficacy of traditional medicines and dietary supplements in global health care are discussed. Some of the challenges facing traditional medicine in health care are described, and the importance of defining clear goals and directions for the information systems, botany, chemistry, and biology related to plants and health care, including for drug discovery and quality control, is indicated.

Mycobacterium tuberculosis and cholinesterase inhibitors from Voacanga globosa.

Globospiramine (1), a new spirobisindole alkaloid possessing an Aspidosperma-Aspidosperma skeleton, together with deoxyvobtusine (2), deoxyvobtusine lactone (3), vobtusine lactone (4) and lupeol (5), were isolated and identified from Voacanga globosa through a bioassay-guided purification. The gross structure and absolute stereochemistry of 1 were established by circular dichroism spectroscopy, HR-MS and unambiguous NMR spectroscopic experiments. In addition, a new biogenetic pathway for the formation of the spiro-Aspidosperma-Aspidosperma skeleton is proposed. Alkaloid 1 showed potent antituberculosis activity against Mycobacterium tuberculosis H(37)Rv as evidenced in microplate Alamar blue assay (MIC = 4 µg/mL) and low-oxygen recovery assay (LORA (MIC = 5.2 µg/mL). The bisindole alkaloids also exhibited promising activity against acetylcholinesterase and, especially butyrylcholinesterase, with deoxyvobtusine (2) (IC(50) = 6.2 µM) as the most strongly inhibiting compound. This study extends the variety of alkaloid structural platforms which exhibit antimycobacterial and anticholinesterase activity.

Sustainable medicines and global health care.

The global population has now exceeded 7 billion, and forests and other resources around the world are being irreversibly depleted for energy, food, shelter, material goods, and drugs to accommodate population needs. For most of the world's population, plants, based on many well-established systems of medicine, in either crude or extract form, represent the foundation of primary health care for the foreseeable future. Contemporary harvesting methods for medicinal plants are severely depleting these critical indigenous resources. However, maintaining and enhancing the availability of quality medicinal agents on a sustainable basis is an unappreciated public health care concept. To accomplish these goals for future health care, and restore the health of the Earth, a profound paradigm shift is necessary: ALL medicinal agents should be regarded as a sustainable commodity, irrespective of their source. Several approaches to enhancing the availability of safe and efficacious plant-based medicinal agents will be presented including integrated strategies to manifest the four pillars (information, botany, chemistry, and biology) for medicinal plant quality control. These integrated initiatives involve information systems, DNA barcoding, metabolomics, biotechnology, nanotechnology, in-field analysis of medicinal plants, and the application of new detection techniques for the development of medicinal plants with enhanced levels of safe and reproducible biological agents.

Molecular modeling, NOESY NMR, and the structure of nicandrenone isolated from Nicandra physalodes (Solanaceae).

The configuration and conformation of nicandrenone, isolated from Nicandra physalodes, are described using molecular modeling and NMR NOESY techniques. Amsterdam Density Functional (ADF) software was used, and the structures were those reduced to minimum energy molecular models, utilizing B3LYP executions and Density Functional Theory (DFT). The first spectral proof that this withanolide has a 22-R configuration is also provided. This method may be adaptable to other natural products.

Pharmaceuticals and the strategic national stockpile program.

This article discusses current stockpile practices after exploring a history of the use of biologic agents as weapons, the preventive measures that the federal government has used in the past, and the establishment of a Strategic National Stockpile Program in 2003. The article also describes the additional medical supplies from the managed inventory and the federal medical stations. The issues (financial burden, personnel, and materiel selection) for local asset development are also discussed. Critical is the cost to local communities of the development and maintenance of a therapeutic agent stockpile and the need for personnel to staff clinics and medical stations. Finally, the important role of the dental profession for dispensing medication and providing mass immunization in the event of a disaster is described.

Cytotoxic constituents from the fruiting branches of Callicarpa americana collected in southern Florida.

Bioassay-guided fractionation of the combined fruits, leaves, and twigs (fruiting branches) of Callicarpa americana, collected from a plot in a forested area in southern Florida, led to the isolation of six new clerodane diterpenes (1-6) and eight known compounds. The structures of 1-6 [12(S),16xi-dihydroxycleroda-3,13-dien-15,16-olide (1), 12(S)-hydroxy-16xi-methoxycleroda-3,13-dien-15,16-olide (2), 12(S)-hydroxycleroda-3,13-dien-15,16-olide (3), 16xi-hydroxycleroda-3,11(E),13-trien-15,16-olide (4), 3beta,12(S)-dihydroxycleroda-4(18),13-dien-15,16-olide (5), and 12(S)-hydroxycleroda-3,13-dien-16,15-olide (6)] were elucidated by interpretation of spectroscopic data and chemical methods. The absolute configuration at C-12 in 1 and 3 was ascertained using the Mosher ester technique. The cytotoxicity of all isolates was tested against a panel of human cancer cell lines, and compounds 1, 4, and 6, and the known compounds genkwanin, 16xi-hydroxycleroda-3,13-dien-15,16-olide, and 2-formyl-16xi-hydroxy-3-A-norcleroda-2,13-dien-15,16-olide were active (ED50 <5 microg/mL). However, 1 was found to be inactive against human cancer cells implanted in mice using a hollow-fiber tumor model.

Cytotoxic flavaglines and bisamides from Aglaia edulis.

Two new cyclopenta[b]benzofurans, aglaroxin A 1-O-acetate (2) and 3'-methoxyaglaroxin A 1-O-acetate (3), a new benzo[b]oxepine, 19,20-dehydroedulisone A (4), and five new cyclopenta[bc]benzopyrans, edulirin A (5), edulirin A 10-O-acetate (6), 19,20-dehydroedulirin A (7), isoedulirin A (8), and edulirin B (9), were isolated from the bark of Aglaia edulis, along with one known cyclopenta[b]benzofuran, aglaroxin A (1). Additionally, four new amides, aglamides A-D (10-13), as well as three known compounds, aglalactone, scopoletin, and 5-hydroxy-3,6,7,4'-tetramethoxyflavone, were isolated from the leaves and/or twigs of this species. The structures of the new compounds (2-13) were elucidated by interpretation of their spectroscopic data. All isolates obtained in this study were evaluated for cytotoxicity against both several human cancer cell lines (Lu1, LNCaP, and MCF-7) and a nontumorigenic (HUVEC) cell line. Among these isolates, the cyclopenta[b]benzofurans (1-3) exhibited potent in vitro cytotoxic activity (ED50 range 0.001 to 0.8 microg/mL). Aglaroxin A 1-O-acetate (2) was further evaluated in the in vivo P388 lymphocytic leukemia model, by intraperitoneal injection, but found to be inactive in this model.

Survey of medical ethnobotanicals for dental and oral medicine conditions and pathologies.

Ethnomedical questionnaires were distributed in Chicago, Costa Rica, and Colombia to identify the most common over-the-counter (OTC) plant or plant-based products advocated for treating oral pain, ulcerative conditions, and cancer within these locations. Over 100 plants or plant-based herbal preparations and commercial products, purchased from local botanical markets and pharmacies, were advocated for the treatment of oral medicine conditions. Locally familiar and common language names were attributed to the plant products at the time of purchase. Plant products or plant-based commercial products containing plant-based essential oils, anesthetic constituents, and or chemical compounds recommended as OTC oral medicine preparations were systematized, tabulated, and correlated with the published phytotherapeutic literature. Though pharmacognostic research is available for some of the species collected, further ethnographic research is needed to correlate common names with the accurate taxonomic identification for each plant species. Furthermore, epidemiological research is needed to verify the use and standardized dosage for OTC ethnomedicine preparations for oral medicine conditions. Pharmacognostic research and clinical trails which can verify taxonomy, dose, safety, active principles, and efficacy of these OTC oral medicine products must be enhanced in order to verify the claimed validity in contemporary, global, oral medicine practice.