Fenchone and camphor: Main natural compounds from Lavandula stoechas L., expediting multiple in vitro biological activities.

Lavandula stoechas, a Mediterranean plant, renowned in traditional medicine for its health benefits, is also arousing strong interest associated with its essential oils (EOs) with promising therapeutic properties. The aim of this study was to analyze the chemical composition of the plant, as well as to study its major activities, including antioxidant, anti-diabetic, dermatoprotective, anti-inflammatory, and antibacterial effects, focusing on its major molecules. Using the GC-MS method, the main compounds identified in L. stoechas EO (LSEO) were fenchone (31.81 %) and camphor (29.60 %), followed by terpineol (13.14 %) and menthone (8.96 %). To assess their antioxidant activity, three in vitro methods were used (DPPH, FRAP, and ABTS). The results revealed that LSEO exhibited the best antiradical property (54 ± 62 µg/mL) according to the DPPH test, while fenchone demonstrated the highest antioxidant capacity (87 ± 92 µg/mL) in the FRAP test, and camphor displayed the highest antioxidant capacity (96 ± 32 µg/mL) in the ABTS test. However, these results were lower than those obtained by Trolox used as a reference. In addition, study also explored the anti-diabetic potential of LSEO and its major compounds by evaluating their inhibitory activity towards two digestive enzymes, α-glucosidase and α-amylase. Camphor (76.92 ± 2.43 µg/mL) and fenchone (69.03 ± 2.31 µg/mL) exhibited the best inhibitory activities for α-amylase and α-glucosidase assays, respectively. Interestingly, all elements of the study exerted activities superior to those of acarbose, regardless of the test performed. In contrast, the evaluation of the dermatoprotective potential was carried out in vitro by targeting two enzymes involved in cutaneous processes, tyrosinase and elastase. In this light, fenchone (53.14 ± 3.06 µg/mL) and camphor (48.39 ± 1.92 µg/mL) were the most active against tyrosinase and elastase, respectively. It should be noted that the effect of both molecules, as well as that of LSEO, ranged between 53.14 ± 3.06 and 97.45 ± 5.22 µg/mL, which was significantly lower than the standard, quercetin (IC50 of 246.90 ± 2 0.54 µg/mL) against tyrosinase. Furthermore, the anti-inflammatory potential of these elements has been studied by evaluating their ability to inhibit lipooxygenase (LOX), a class of enzymes involved in the inflammatory process in the human body. As a result, the LSEO demonstrated a remarkable effect with an IC50 of 6.34 ± 1.29 µg/mL, which was almost comparable to the standard, quercetin (IC50 = 3.93 ± 0.45 µg/mL). Concerning the antibacterial potential, we carried out a quantitative analysis of the various products tested, revealing a bactericidal activity of the LSEO against the strain L. monocytogenes ATCC 13932 at a minimum effective concentration (MIC = CMB = 0.25). Overall, LSEOs offer significant potential as a source of natural antioxidants, and antidiabetic and anti-inflammatory agents, as well as dermatoprotective and antibacterial compounds. Its major molecules, fenchone and camphor, showed promising activity in these areas of study, making it a valuable candidate for future research and development in the field of natural medicine.

Phytosterols activating nuclear receptors are involving in steroid hormone-dependent cancers: Myth or fact?

Nuclear receptors (NRs) represent intracellular proteins that function as a signaling network of transcriptional factors to control genes in response to a variety of environmental, dietary, and hormonal stimulations or serve as orphan receptors lacking a recognized ligand. They also play an essential role in normal development, metabolism, cell growth, cell division, physiology, reproduction, and homeostasis and function as biological markers for tumor subclassification and as targets for hormone therapy. NRs, including steroid hormone receptors (SHRs), have been studied as tools to examine the fundamentals of transcriptional regulation within the development of mammals and human physiology, in addition to their links to disturbances. In this regard, it is widely recognized that aberrant NR signaling is responsible for the pathological growth of hormone-dependent tumors in response to SHRs dysregulation and consequently represents a potential therapeutic candidate in a range of diseases, as in the case of prostate cancer and breast cancer. On the other hand, phytosterols are a group of plant-derived compounds that act directly as ligands for NRs and have proven their efficacy in the management of diabetes, heart diseases, and cancers. However, these plants are not suggested in cases of hormone-dependent cancer since a certain group of plants contains molecules with a chemical structure similar to that of estrogens, which are known as phytoestrogens or estrogen-like compounds, such as lignans, coumestans, and isoflavones. Therefore, it remains an open and controversial debate regarding whether consuming a phytosterol-rich diet and adopting a vegetarian lifestyle like the Mediterranean diet may increase the risk of developing steroid hormone-dependent cancers by constitutively activating SHRs and thereby leading to tumor transformation. Overall, the purpose of this review is to better understand the relevant mechanistic pathways and explore epidemiological investigations in order to establish that phytosterols may contribute to the activation of NRs as cancer drivers in hormone-dependent cancers.

Traditional Uses, Bioactive Compounds, and Pharmacological Investigations of Calendula arvensis L.: A Comprehensive Review.

Calendula arvensis L. (Asteraceae) is a famous ornamental and medicinal plant widely distributed in Mediterranean countries and the southern region of Europe. This reputed species is widely used in traditional medicine in the treatment of many disorders and has various bioactivities, especially anti-inflammatory, antiviral, antimutagenic, antimicrobial, insecticidal, antioxidant, and immunomodulatory activities. The present review was conducted to provide a critical review of the comprehensive and current knowledge regarding C. arvensis species, in particular, its taxonomy and geographical distribution, botanical description, medicinal uses, phytochemical compounds, pharmacological properties, and toxicity investigations. The data collected on C. arvensis were obtained using different scientific research databases such as PubMed, SciFinder, SpringerLink, Web of Science, Science Direct, Google Scholar, Wiley Online, and Scopus. Phytochemical screening of different C. arvensis extracts and essential oils showed their richness in bioactive compounds, particularly in fatty acids, sterols, phenolics, flavonoids, saponins, tannins, alkaloids, and terpenoid compounds. The findings of this review showed that the pharmacological activities of C. arvensis confirm its importance and diversity as a traditional remedy for many diseases. This plant presents a wide range of bioactivities, namely, anti-inflammatory, antimicrobial, antitrypanosomial, antitumoral, antimutagenic, and immunomodulatory activities, as well as hemolytic properties and wound treatment. Nevertheless, pharmacokinetic validation and toxicological examinations are required to detect any possible toxicity for future clinical trials.

Dietary Phenolic Compounds as Anticancer Natural Drugs: Recent Update on Molecular Mechanisms and Clinical Trials.

Given the stochastic complexity of cancer diseases, the development of chemotherapeutic drugs is almost limited by problems of selectivity and side effects. Furthermore, an increasing number of protective approaches have been recently considered as the main way to limit these pathologies. Natural bioactive compounds, and particularly dietary phenolic compounds, showed major protective and therapeutic effects against different types of human cancers. Indeed, phenolic substances have functional groups that allow them to exert several anti-cancer mechanisms, such as the induction of apoptosis, autophagy, cell cycle arrest at different stages, and the inhibition of telomerase. In addition, in vivo studies show that these phenolic compounds also have anti-angiogenic effects via the inhibition of invasion and angiogenesis. Moreover, clinical studies have already highlighted certain phenolic compounds producing clinical effects alone, or in combination with drugs used in chemotherapy. In the present work, we present a major advance in research concerning the mechanisms of action of the different phenolic compounds that are contained in food medicinal plants, as well as evidence from the clinical trials that focus on them.

The Current State of Knowledge in Biological Properties of Cirsimaritin.

The search for natural plant-based products as new pharmacological alternatives to treat various human pathologies has taken on great importance for researchers and research laboratories. In this context, research has intensified to extract and identify natural molecules endowed with biological effects. The objective of this study is to review the source and pharmacological properties of cirsimaritin. The identification and isolation of this flavonoid from various natural sources, including medicinal plants such as Artemisia judaica, Cirsium japonicum, Lithocarpus dealbatus, Microtea debilis, and Ocimum sanctum, has been carried out and verified using different spectral techniques. Biological effect investigations are carried out with a wide variety of experimental models in vitro and in vivo and laboratory techniques. The results of these research works showed the biological properties of cirsimaritin including anticancer, antimicrobial, antidiabetic, antiparasitic, antioxidant, and anti-inflammatory effects. The mechanisms involved in the multiple activities of this molecule are diverse and include sub-cellular, cellular, and molecular levels. Indeed, this bioactive induces anti-inflammatory and antiproliferative effects by inhibiting cell membrane receptors, interference with signaling pathways, and inhibiting transcriptional factors such as Nf-κB involved in cell promotion and proliferation. In the light of these results, cirsimaritin appears as a promising and viable alternative natural bioactive drug to treat many pathological conditions.

Pharmacological insights into the multifaceted biological properties of quinic acid.

Quinic acid is a cyclohexanecarboxylic acid contained in the extracts of several parts of medicinal plants including Haematocarpus validus, Hypericum empetrifolium, Achillea pseudoaleppica, Rumex nepalensis, Phagnalon saxatile subsp. saxatile, Coffea arabica, Ziziphus lotus L, and Artemisia annua L … etc. Currently, in vitro and in vivo pharmacological studies showed that quinic acid exhibits various biological activities, such as antioxidant, antidiabetic, anticancer activity, antimicrobial, antiviral, aging, protective, anti-nociceptive and analgesic effects. Indeed, QA possesses an important antibacterial effect which could be explained by the fact that this molecule modules the functions of ribosomes and the synthesis of aminoacyl-tRNAs, modifications the levels of glycerophospholipids and fatty acids and disruption of the oxidative phosphorylation pathway thereby causing interference with membrane fluidity. The antidiabetic activity of AQ is achieved by stimulation of insulin secretion via the mobilization of Ca2+ from intracellular reserves and the increase in the NAD(P)H/NAD(P)+ ratio. Its anticancer effect is through the promotion of apoptosis, inhibition of activator protein 1 (AP-1) and signaling pathways involving protein kinase C (PKC) and certain mitogen-activated protein kinases (MAPKs), resulting in the downregulation of matrix metallopeptidase 9 (MMP-9) expression. Therefore, this review describes the main research work carried out on the biological properties of AQ and the mechanism of action underlying some of these effects, as well as the investigations of the main pharmacokinetic studies.

Chemical Analysis and Investigation of Biological Effects of Salvia officinalis Essential Oils at Three Phenological Stages.

Salvia officinalis is a medicinal plant used to treat some diseases, including microbial infections and diabetes. Different studies showed the biological and pharmacological properties of this species. The aim of this study was the determination of the chemical compounds of S. officinalis essential oils and the investigation of their antimicrobial, antioxidant, antidiabetic, and anti-inflammatory properties. The chemical compounds of S. officinalis were determined by GC-MS analysis. The antioxidant activity was assessed by DPPH, ABTS, H2O2, and FRAP assays. The in vitro antidiabetic effect was evaluated by the inhibition of α-amylase, α-glucosidase, and lipase activities, and the anti-inflammatory effect was evaluated using the 5-lipoxygenase assay. Moreover, antibacterial activity was assessed against six bacterial strains using agar well diffusion assay and microdilution method. The main compounds in essential oils of S. officinalis at three phenological stages were naphthalenone, camphor, 1.8-cineole, and α-thujone. The full flowering stage essential oil showed the best antioxidant activity with different IC50 values according to the used tests. This oil also exhibited important inhibitory effects at the full flowering stage against α-amylase (IC50 = 69.23 ± 0.1 µg/mL), α-glucosidase (IC50 = 22.24 ± 0.07 µg/mL), and lipase (IC50 = 37.3 ± 0.03 µg/mL). The 5-lipoxygenase inhibitory effect was the best at the full flowering stage (IC50 = 9.24 ± 0.03 µg/mL). The results of the antibacterial evaluation revealed that, at three seasonal periods, S. officinalis essential oil demonstrated strong antibacterial activity. Although the full flowering stage had the best antibacterial activity, there were no significant differences between the three stages. Additionally, the essential oils showed bactericidal effects on Listeria monocytogenes, Staphylococcus aureus, Bacillus subtilis, Proteus mirabilis, Escherichia coli, and Salmonella typhimurium, respectively. The findings of this work showed remarkably that S. officinalis synthesizes essential oils according to different developmental stages. Moreover, it has exhibited interesting biological and pharmacological properties justifying its medicinal effects and suggesting it as a very important source of natural drugs.

Inflammatory auto-immune diseases of the intestine and their management by natural bioactive compounds.

Autoimmune diseases are caused by the overactivity of the immune system towards self-constituents. Risk factors of autoimmune diseases are multiple and include genetic, epigenetic, environmental, and psychological. Autoimmune chronic inflammatory bowel diseases, including celiac and inflammatory diseases (Crohn's disease and ulcerative colitis), constitute a significant health problem worldwide. Besides the complexity of the symptoms of these diseases, their treatments have only been palliative. Numerous investigations showed that natural phytochemicals could be promising strategies to fight against these autoimmune diseases. In this respect, plant-derived natural compounds such as flavonoids, phenolic acids, and terpenoids exhibited significant effects against three autoimmune diseases affecting the intestine, particularly bowel diseases. This review focuses on the role of natural compounds obtained from medicinal plants in modulating inflammatory auto-immune diseases of the intestine. It covers the most recent literature related to the effect of these natural compounds in the treatment and prevention of auto-immune diseases of the intestine.

Determination of Volatile Compounds of Mentha piperita and Lavandula multifida and Investigation of Their Antibacterial, Antioxidant, and Antidiabetic Properties.

Mentha piperita and Lavandula multifida are widely used in Moroccan traditional medicine for the treatment of diabetes and infectious diseases. The aims of this work were the determination of the chemical composition of Mentha piperita (MPEO) and Lavandula multifida (LMEO) essential oils and the evaluation of their antibacterial, antioxidant, and antidiabetic activities. The chemical composition was determined by GC-MS analysis. The antibacterial effects were evaluated against several bacterial strains using disc diffusion, MIC, and MBC methods. The antioxidant activity was evaluated in vitro using DPPH, H2O2, and xanthine oxidase, and the antidiabetic activity was estimated by the inhibitory effects of α-amylase, α-glucosidase, and lipase activities. GC-MS results showed that the main compounds of MPEO were menthone (29.24%), levomenthol (38.73%), and eucalyptol (6.75%). However, eucalyptol (28.11%), 2-bornanone (11.57%), endo-borneol (7.82%), and linalyl acetate (5.22%) are the major compounds of LMEO. The results exhibited important inhibitory effects against some bacterial strains with MIC = MBC = 0.39 mg/mL for MPEO against Staphylococcus aureus ATCC. However, LMEO exhibited remarkable antioxidant and antidiabetic activities compared to MPEO. Indeed, LMEO inhibited DPPH, H2O2, and xanthine oxidase with concentrations of 15.23, 21.52, and 8.89 µg/mL, respectively. Moreover, LMEO exhibited α-amylase and α-glucosidase at IC50 = 85.34 and IC50 = 59.36 µg/mL, respectively. The findings showed that both MPEO and LMEO exhibit promising biological properties. However, the application of these species or their main bioactive compounds requires further investigation.

Anti-inflammatory and analgesic properties of Moroccan medicinal plants: Phytochemistry, in vitro and in vivo investigations, mechanism insights, clinical evidences and perspectives.

Moroccan medicinal plants exhibit several pharmacological properties such as antimicrobial, anticancer, antidiabetic, analgesic, and anti-inflammatory effects, which are related to the presence of numerous bioactive compounds, including phenolic acids, flavonoids, and terpenoids. In the present review, we systematically evaluate previously published reports on the anti-inflammatory and analgesic effects of Moroccan medicinal plants. The in vitro investigations revealed that Moroccan medicinal plants inhibit several enzymes related to inflammatory processes, whereas in vivo studies noted significant anti-inflammatory and analgesic effects as demonstrated using different experimental models. Various bioactive compounds exhibiting in vitro and in vivo anti-inflammatory and analgesic effects, with diverse mechanisms of action, have been identified. Some plants and their bioactive compounds reveal specific secondary metabolites that possess important anti-inflammatory effects in clinical investigations. Our review proposes the potential applications of Moroccan medicinal plants as sources of anti-inflammatory and analgesic agents.

Natural Bioactive Compounds Targeting Histone Deacetylases in Human Cancers: Recent Updates.

Cancer is a complex pathology that causes a large number of deaths worldwide. Several risk factors are involved in tumor transformation, including epigenetic factors. These factors are a set of changes that do not affect the DNA sequence, while modifying the gene's expression. Histone modification is an essential mark in maintaining cellular memory and, therefore, loss of this mark can lead to tumor transformation. As these epigenetic changes are reversible, the use of molecules that can restore the functions of the enzymes responsible for the changes is therapeutically necessary. Natural molecules, mainly those isolated from medicinal plants, have demonstrated significant inhibitory properties against enzymes related to histone modifications, particularly histone deacetylases (HDACs). Flavonoids, terpenoids, phenolic acids, and alkaloids exert significant inhibitory effects against HDAC and exhibit promising epi-drug properties. This suggests that epi-drugs against HDAC could prevent and treat various human cancers. Accordingly, the present study aimed to evaluate the pharmacodynamic action of different natural compounds extracted from medicinal plants against the enzymatic activity of HDAC.

Medicinal Uses, Phytochemistry, Pharmacology, and Toxicology of Mentha spicata.

Mentha spicata, also called Mentha viridis, is a medicinal plant of the Lamiaceae family characterized by its potency to synthesize and secret secondary metabolites, essentially essential oils. Different populations use the aerial parts of this plant for tea preparation, and this tisane has shown several effects, according to ethnopharmacological surveys carried out in different areas around the world. These effects are attributed to different compounds of M. spicata, in which their biological effects were recently proved experimentally. Pharmacological properties of M. spicata extracts and essential oils were investigated for different health benefits such as antioxidant, anticancer, antiparasitic, antimicrobial, and antidiabetic effects. In vitro and in vivo studies showed positives effects that could be certainly related to different bioactive compounds identified in M. spicata. Indeed, volatile compounds seem to be efficient in inhibiting different microbial agents such as bacteria, fungi, and parasites through several mechanisms. Moreover, M. spicata exhibited, according to some studies, promising antioxidant, antidiabetic, anti-inflammatory, and anticancer effects, which show its potential to be used as a source for identifying natural drugs against cellular oxidative stress and its related diseases. Importantly, toxicological investigations of M. spicata show the safety of this species at different doses and several periods of use which justify its use in traditional medicines as tisane with tea. Here, we report, explore, and highlight the data published on M. spicata concerning its botanical description and geographical distribution, its phytochemical compounds, its pharmacological properties, and its toxicological investigations of M. spicata.

Genetic diversity, antimicrobial, nutritional, and phytochemical properties of Chenopodium album: A comprehensive review.

Chenopodium album L., is a medicinal plant widely cultivated in Europe, North America, Iran, South Africa, Australia, South America, and Asia. This species is commonly used in folk medicine to treat many diseases such as cancer, viral infections, parasitic diseases, gastrointestinal disorders, as well as bacterial and fungal infections. The present review was carried out to highlight previous studies on C. album, including its botanical description, geographical distribution, genetic diversity, ecological variability, ethnomedicinal use, bioactive compounds, pharmacological properties, and toxicology. The data collected on C. album was generated using various scientific research databases such as SciFinder, PubMed, Google Scholar, SpringerLink, ScienceDirect, Web of Science, Scopus, and Wiley Online. In this review, the data presented focus on C. album to elucidate its ethnomedicinal use, pharmacological activities, and chemical composition in order to investigate the possible therapeutic pathways of the plant. Analysis of the findings showed that C. album has a capital power in various therapeutic uses such as antibacterial, antifungal, antiviral, antiparasitic, antipruritic, anticancer, antiulcer, antirheumatic, antidiabetic, antihyperlipidemic, antioxidant, and anti-inflammatory as well as other biological functions. Indeed, data on the chemical composition of the extracts and essential oils of this plant revealed its richness in secondary metabolites. The results of this paper prove that the pharmacological properties of C. album confirm its traditional importance in the international traditional pharmacopeia. This species notably exhibits various biological activities; antibacterial, antifungal, and antioxidant effects. However, toxicological investigations and pharmacokinetic validation are necessary in order to identify a possible toxicity of this plant for future clinical trials and to validate its bioavailability.

The Role of Epigenetic Modifications in Human Cancers and the Use of Natural Compounds as Epidrugs: Mechanistic Pathways and Pharmacodynamic Actions.

Cancer is a complex disease resulting from the genetic and epigenetic disruption of normal cells. The mechanistic understanding of the pathways involved in tumor transformation has implicated a priori predominance of epigenetic perturbations and a posteriori genetic instability. In this work, we aimed to explain the mechanistic involvement of epigenetic pathways in the cancer process, as well as the abilities of natural bioactive compounds isolated from medicinal plants (flavonoids, phenolic acids, stilbenes, and ketones) to specifically target the epigenome of tumor cells. The molecular events leading to transformation, angiogenesis, and dissemination are often complex, stochastic, and take turns. On the other hand, the decisive advances in genomics, epigenomics, transcriptomics, and proteomics have allowed, in recent years, for the mechanistic decryption of the molecular pathways of the cancerization process. This could explain the possibility of specifically targeting this or that mechanism leading to cancerization. With the plasticity and flexibility of epigenetic modifications, some studies have started the pharmacological screening of natural substances against different epigenetic pathways (DNA methylation, histone acetylation, histone methylation, and chromatin remodeling) to restore the cellular memory lost during tumor transformation. These substances can inhibit DNMTs, modify chromatin remodeling, and adjust histone modifications in favor of pre-established cell identity by the differentiation program. Epidrugs are molecules that target the epigenome program and can therefore restore cell memory in cancerous diseases. Natural products isolated from medicinal plants such as flavonoids and phenolic acids have shown their ability to exhibit several actions on epigenetic modifiers, such as the inhibition of DNMT, HMT, and HAT. The mechanisms of these substances are specific and pleiotropic and can sometimes be stochastic, and their use as anticancer epidrugs is currently a remarkable avenue in the fight against human cancers.

Mechanisms, Anti-Quorum-Sensing Actions, and Clinical Trials of Medicinal Plant Bioactive Compounds against Bacteria: A Comprehensive Review.

Bacterial strains have developed an ability to resist antibiotics via numerous mechanisms. Recently, researchers conducted several studies to identify natural bioactive compounds, particularly secondary metabolites of medicinal plants, such as terpenoids, flavonoids, and phenolic acids, as antibacterial agents. These molecules exert several mechanisms of action at different structural, cellular, and molecular levels, which could make them candidates or lead compounds for developing natural antibiotics. Research findings revealed that these bioactive compounds can inhibit the synthesis of DNA and proteins, block oxidative respiration, increase membrane permeability, and decrease membrane integrity. Furthermore, recent investigations showed that some bacterial strains resist these different mechanisms of antibacterial agents. Researchers demonstrated that this resistance to antibiotics is linked to a microbial cell-to-cell communication system called quorum sensing (QS). Consequently, inhibition of QS or quorum quenching is a promising strategy to not only overcome the resistance problems but also to treat infections. In this respect, various bioactive molecules, including terpenoids, flavonoids, and phenolic acids, exhibit numerous anti-QS mechanisms via the inhibition of auto-inducer releases, sequestration of QS-mediated molecules, and deregulation of QS gene expression. However, clinical applications of these molecules have not been fully covered, which limits their use against infectious diseases. Accordingly, the aim of the present work was to discuss the role of the QS system in bacteria and its involvement in virulence and resistance to antibiotics. In addition, the present review summarizes the most recent and relevant literature pertaining to the anti-quorum sensing of secondary metabolites and its relationship to antibacterial activity.

Ethnobotany, Phytochemistry, Biological Activities, and Health-Promoting Effects of the Genus Bulbophyllum.

The genus Bulbophyllum is of scientific interest due to the phytochemical components and diverse biological activities found across species of the genus. Most Bulbophyllum species are epiphytic and located in habitats that range from subtropical dry forests to wet montane cloud forests. In many cultures, the genus Bulbophyllum has a religious, protective, ornamenting, cosmetic, and medicinal role. Detailed investigations into the molecular pharmacological mechanisms and numerous biological effects of Bulbophyllum spp. remain ambiguous. The review focuses on an in-depth discussion of studies containing data on phytochemistry and preclinical pharmacology. Thus, the purpose of this review was to summarize the therapeutic potential of Bulbophyllum spp. biocompounds. Data were collected from several scientific databases such as PubMed and ScienceDirect, other professional websites, and traditional medicine books to obtain the necessary information. Evidence from pharmacological studies has shown that various phytoconstituents in some Bulbophyllum species have different biological health-promoting activities such as antimicrobial, antifungal, antioxidant, anti-inflammatory, anticancer, and neuroprotective. No toxicological effects have been reported to date. Future clinical trials are needed for the clinical confirmation of biological activities proven in preclinical studies. Although orchid species are cultivated for ornamental purposes and have a wide traditional use, the novelty of this review is a summary of biological actions from preclinical studies, thus supporting ethnopharmacological data.

Natural Bioactive Compounds from Medicinal Plants as Antibacterial Drugs: Mechanism Insights and Clinical Perspectives.

The coevolution in microbes has generated major functional consequences leading bacteria to develop resistance to antibiotics. Indeed, bacterial strains have been able to develop and adapt to the action of antibiotics via several resistance mechanisms. In this context, researchers are currently conducting many studies to screen natural antibacterial substances such as secondary metabolites of medicinal plants. Indeed, the potential of many plants used in traditional medicine in the treatment of infectious diseases was confirmed experimentally, namely Anethum graveolens, Elettaria cardamomum, Foeniculum vulgare, Trachyspermum ammi, Viola odorata, Dioscorea dregeana, Cheilanthes viridis, Vernonia colorata, etc. Bioactive molecules from different medicinal plants include terpenoids, flavonoids, and phenolic acids, which were shown to have significant anti- bacterial effects. The mechanisms of action of these molecules are different and can include structural, cellular, and molecular levels, which suggests them as real candidates for the development of natural antibiotics. However, the clinical trials of these molecules have not been very well studied which limits their clinical use against infectious diseases of bacterial origin.

Pharmacological Effects of Grifolin: Focusing on Anticancer Mechanisms.

Grifolin is a volatile compound contained in essential oils of several medicinal plants. Several studies show that this substance has been the subject of numerous pharmacological investigations, which have yielded interesting results. Grifolin demonstrated beneficial effects for health via its multiple pharmacological activities. It has anti-microbial properties against bacteria, fungi, and parasites. In addition, grifolin exhibited remarkable anti-cancer effects on different human cancer cells. The anticancer action of this molecule is related to its ability to act at cellular and molecular levels on different checkpoints controlling the signaling pathways of human cancer cell lines. Grifolin can induce apoptosis, cell cycle arrest, autophagy, and senescence in these cells. Despite its major pharmacological properties, grifolin has only been investigated in vitro and in vivo. Therefore, further investigations concerning pharmacodynamic and pharmacokinetic tests are required for any possible pharmaceutical application of this substance. Moreover, toxicological tests and other investigations involving humans as a study model are required to validate the safety and clinical applications of grifolin.

Natural Bioactive Compounds Targeting Epigenetic Pathways in Cancer: A Review on Alkaloids, Terpenoids, Quinones, and Isothiocyanates.

Cancer is one of the most complex and systemic diseases affecting the health of mankind, causing major deaths with a significant increase. This pathology is caused by several risk factors, of which genetic disturbances constitute the major elements, which not only initiate tumor transformation but also epigenetic disturbances which are linked to it and which can induce transcriptional instability. Indeed, the involvement of epigenetic disturbances in cancer has been the subject of correlations today, in addition to the use of drugs that operate specifically on different epigenetic pathways. Natural molecules, especially those isolated from medicinal plants, have shown anticancer effects linked to mechanisms of action. The objective of this review is to explore the anticancer effects of alkaloids, terpenoids, quinones, and isothiocyanates.

Preclinical and Clinical Antioxidant Effects of Natural Compounds against Oxidative Stress-Induced Epigenetic Instability in Tumor Cells.

ROS (reactive oxygen species) are produced via the noncomplete reduction in molecular oxygen in the mitochondria of higher organisms. The produced ROS are placed in various cell compartments, such as the mitochondria, cytoplasm, and endoplasmic reticulum. In general, there is an equilibrium between the synthesis of ROS and their reduction by the natural antioxidant defense system, called the redox system. Therefore, when this balance is upset, the excess ROS production can affect different macromolecules, such as proteins, lipids, nucleic acids, and sugars, which can lead to an electronic imbalance than oxidation of these macromolecules. Recently, it has also been shown that ROS produced at the cellular level can affect different signaling pathways that participate in the stimulation of transcription factors linked to cell proliferation and, consequently, to the carcinogenesis process. Indeed, ROS can activate the pathway of tyrosine kinase, MAP kinase, IKK, NF-KB, phosphoinositol 3 phosphate, and hypoxia-inducible factor (HIF). The activation of these signaling pathways directly contributes to the accelerated proliferation process and, as a result, the appearance of cancer. In addition, the use of antioxidants, especially natural ones, is now a major issue in the approach to cancer prevention. Some natural molecules, especially phytochemicals isolated from medicinal plants, have now shown interesting preclinical and clinical results.