Pyrroloquinoline Quinone Chemistry, Biology, and Biosynthesis.

The widely distributed, essential redox factor pyrroloquinoline quinone (PQQ, methoxatin) (1) was discovered in the mid-1960s. The breadth and depth of its biological effects are steadily being revealed, and understanding its biosynthesis at the genomic level is a continuing process. In this review, aspects of the chemistry, biology, biosynthesis, and commercial production of 1 at the gene level, and some applications, are presented from discovery through to mid-2021.

Ergothioneine, Ovothiol A, and Selenoneine-Histidine-Derived, Biologically Significant, Trace Global Alkaloids.

The history, chemistry, biology, and biosynthesis of the globally occurring histidine-derived alkaloids ergothioneine (10), ovothiol A (11), and selenoneine (12) are reviewed comparatively and their significance to human well-being is discussed.

Biologically Significant and Recently Isolated Alkaloids from Endophytic Fungi.

A selection of the established and recently characterized alkaloids from the exploration of plant- and some marine-associated endophytic fungi is reviewed, with reference to alkaloids of biological significance.

Alkaloids in Contemporary Drug Discovery to Meet Global Disease Needs.

An overview is presented of the well-established role of alkaloids in drug discovery, the application of more sustainable chemicals, and biological approaches, and the implementation of information systems to address the current challenges faced in meeting global disease needs. The necessity for a new international paradigm for natural product discovery and development for the treatment of multidrug resistant organisms, and rare and neglected tropical diseases in the era of the Fourth Industrial Revolution and the Quintuple Helix is discussed.

Dental Applications of Carbon Nanotubes.

Glass ionomer cements and resin-based composites are promising materials in restorative dentistry. However, their limited mechanical properties and the risk of bulk/marginal fracture compromise their lifespan. Intensive research has been conducted to understand and develop new materials that can mimic the functional behavior of the oral cavity. Nanotechnological approaches have emerged to treat oral infections and become a part of scaffolds for tissue regeneration. Carbon nanotubes are promising materials to create multifunctional platforms for dental applications. This review provides a comprehensive survey of and information on the status of this state-of-the-art technology and describes the development of glass ionomers reinforced with carbon nanotubes possessing improved mechanical properties. The applications of carbon nanotubes in drug delivery and tissue engineering for healing infections and lesions of the oral cavity are also described. The review concludes with a summary of the current status and presents a vision of future applications of carbon nanotubes in the practice of dentistry.

Natural diterpene pyrones: chemistry and biology.

Diterpene pyrones (DTPs) are a group of well-known, mainly fungal, natural products, first isolated in 1966. As the name indicates, they are composed of two main structural features: a diterpenyl moiety and a pyrone ring. Various names have been given to this class of metabolites; however, biogenetic evidence indicates that they originate through the same metabolic pathway. Based on their biosynthesis, which leads to differences in their structural architecture, the DTPs can be classified into three main types. In addition to their intriguing chemistry, these compounds demonstrate a wide range of biological activities rendering them a desirable target for total synthesis. To date, sixty-seven DTPs have been isolated from various fungal species, with one example originating from the plant kingdom. This review aims at unifying the classification of these compounds, in addition to presenting a detailed description of their isolation, bioactivities, biosynthesis, and total synthesis.

Absolute Configuration of Alkaloids from Uncaria longiflora through Experimental and Computational Approaches.

The structure elucidation of three new alkaloids named isoformosaninol (1), formosaninol (2), and longiflorine (3), isolated from the leaves of Uncaria longiflora var. pteropoda (Miq.) Ridsdale, along with their biosynthetic pathways are discussed. Their absolute structures were determined through a combination of physical data interpretation and quantum chemical calculations using the time-dependent density functional theory (TDDFT) method.

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.

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.

Implication of coumarins towards central nervous system disorders.

Coumarins are widely distributed, plant-derived, 2H-1-benzopyran-2-one derivatives which have attracted intense interest in recent years as a result of their diverse and potent pharmacological properties. Particularly, their effects on the central nervous system (CNS) have been established. The present review discusses the most important pharmacological effects of natural and synthetic coumarins on the CNS, including their interactions with benzodiazepine receptors, their dopaminergic and serotonergic affinity, and their ability to inhibit cholinesterases and monoamine oxidases. The structure-activity relationships pertaining to these effects are also discussed. This review posits that natural or synthetic coumarins have the potential for development in the therapy of psychiatric and neurodegenerative disorders, including Alzheimer's and Parkinson's diseases, schizophrenia, anxiety, epilepsy, and depression.

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.

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.

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.

Nanofibrous ε-Polycaprolactone Matrices Containing Nano-Hydroxyapatite and Humulus lupulus L. Extract: Physicochemical and Biological Characterization for Oral Applications.

Oral bone defects occur as a result of trauma, cancer, infections, periodontal diseases, and caries. Autogenic and allogenic grafts are the gold standard used to treat and regenerate damaged or defective bone segments. However, these materials do not possess the antimicrobial properties necessary to inhibit the invasion of the numerous deleterious pathogens present in the oral microbiota. In the present study, poly(ε-caprolactone) (PCL), nano-hydroxyapatite (nHAp), and a commercial extract of Humulus lupulus L. (hops) were electrospun into polymeric matrices to assess their potential for drug delivery and bone regeneration. The fabricated matrices were analyzed using scanning electron microscopy (SEM), tensile analysis, thermogravimetric analysis (TGA), FTIR assay, and in vitro hydrolytic degradation. The antimicrobial properties were evaluated against the oral pathogens Streptococcus mutans, Porphyromonas gingivalis, and Aggregatibacter actinomycetemcomitans. The cytocompatibility was proved using the MTT assay. SEM analysis established the nanostructured matrices present in the three-dimensional interconnected network. The present research provides new information about the interaction of natural compounds with ceramic and polymeric biomaterials. The hop extract and other natural or synthetic medicinal agents can be effectively loaded into PCL fibers and have the potential to be used in oral applications.

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.

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.

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.

Evolving paradigms for natural-product drug discovery.

Natural products are an essential aspect of global human health. Integration of contemporary technologies based on the Fourth Industrial Revolution (4IR) and the Quintuple Helix is needed to discover additional metabolites to be developed sustainably for the broad and unmet range of human healthcare needs.

Drug-Eluting, Bioresorbable Cardiovascular Stents─Challenges and Perspectives.

Globally, the leading causes of natural death are attributed to coronary heart disease and type 1 and type 2 diabetes. High blood pressure levels, high cholesterol levels, smoking, and poor eating habits lead to the agglomeration of plaque in the arteries, reducing the blood flow. The implantation of devices used to unclog vessels, known as stents, sometimes results in a lack of irrigation due to the excessive proliferation of endothelial tissue within the blood vessels and is known as restenosis. The use of drug-eluting stents (DESs) to deliver antiproliferative drugs has led to the development of different encapsulation techniques. However, due to the potency of the drugs used in the initial stent designs, a chronic inflammatory reaction of the arterial wall known as thrombosis can cause a myocardial infarction (MI). One of the most promising drugs to reduce this risk is everolimus, which can be encapsulated in lipid systems for controlled release directly into the artery. This review aims to discuss the current status of stent design, fabrication, and functionalization. Variables such as the mechanical properties, metals and their alloys, drug encapsulation and controlled elution, and stent degradation are also addressed. Additionally, this review covers the use of polymeric surface coatings on stents and the recent advances in layer-by-layer coating and drug delivery. The advances in nanoencapsulation techniques such as liposomes and micro- and nanoemulsions and their functionalization in bioresorbable, drug-eluting stents are also highlighted.

COVID-19: the impact on oral health care.

The COVID-19 pandemic has highlighted the economic, social, and oral care health inequities in societies, especially in the developing world. Severe restrictions have been imposed on dental practices, limiting prophylactic and routine oral care health, allowing treatment only for emergencies. Since dental care includes procedures that generate aerosols, the risk of infection for dental personnel has increased significantly. In this review, a comprehensive and updated source of information about SARS-CoV-2/COVID-19 and the impacts it is having on oral health care is presented. The ongoing repercussions in dental practice and in dental education, including the opportunities for practice innovation that are evolving, are also indicated. Also, a discussion of the psychosocial factors that affect health and the quality of life of an individual, such as stress, depression, and anxiety, is provided. This pandemic may be an opportunity to promote the inclusion of well-established prevention measures, together with the use of teledentistry in academic dental curricula, encourage the implementation of new perspectives for the effective instruction and interactions with students, and foster the transition toward e-learning strategies in dental education.