Ultra-High-Performance Liquid Chromatography with Photodiode Array and High-Resolution Time-of-Flight Mass Spectrometry Detectors (UHPLC-PDA-ESI-ToF/HRMS) for the Tentative Structural Characterization of Bioactive Compounds of Salvia verbenaca Extracts in Relation to Their Biological Activities.

BACKGROUND: Salvia verbenaca of the Lamiaceae family is a Mediterranean plant widely used in the Moroccan traditional folk medicine. The aim of this work was to explore the phytochemical composition of Salvia verbenaca extracts and its antioxidant activity. METHODS: Separation and identification of the major phytochemicals present in the two hexane and ethyl acetate explored extracts have been achieved through ultra-high-performance liquid chromatography separation technique coupled to photodiode array and high-resolution time-of-flight mass spectrometry detectors. Antioxidant activity of the obtained extracts was evaluated through DPPH• (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azinobis(3-ethylbenzothiazoline6-sulfonic acid) diammonium salt) assays and the obtained results were compared to TROLOX (6-hydroxy2,5,7,8-tetramethylchroman-2-carboxylic acid). RESULTS: Using the analysis technique indicated above, eighteen phytochemicals belonging to phenolic acids, phenolic diterpenes and flavonoids have been characterized on the basis of the obtained UV and mass spectroscopic properties and on the subsequent fragmentations. The antioxidant activity of the explored extracts showed potential scavenging activities compared to TROLOX. A detailed discussion of the attained results has been presented considering the activities observed of each extract. CONCLUSIONS: The research herein presented an analysis technique allowing to screen Salvia verbenaca phytochemicals. The explored plant could be considered as a source of functional phenolic compounds. These could be useful for further pharmacological studies such as new drugs design after clinic and its safety evaluation. It is thus hoped that the information presented here might prompt further studies that will possibly lead to development of therapeutic agents from this plant.

Health Benefits and Pharmacological Aspects of Chrysoeriol.

A flavone, chrysoeriol is synthetized in several plant species. It comes from several natural sources, especially medicinal plants. The identification and isolation of this compound has been carried out and verified by several research teams using different spectral methods. It seems that the concentration of this molecule is variable and fluctuating depending on the source, the part extracted, the region, and the methods of extraction and characterization. The aim of this paper is to highlight the in vitro and in vivo pharmacological properties of chrysoeriol and to provide insight into its pharmacokinetics. Anticancer, anti-inflammatory, antibacterial, antifungal, anti-osteoporosis, anti-insecticide, and neuroprotective actions have been shown in a number of studies on this chemical. Different mechanisms in theses pharmacological effects include subcellular, cellular, and molecular targets. In vivo pharmacokinetic analysis has proved the good stability of this molecule, showing its promising potential to prevent or treat diseases including cancer, diabetes, inflammation, osteoporosis, Parkinson's disease, and cardiovascular diseases.

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 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.

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.

Plant-microbial interaction: The mechanism and the application of microbial elicitor induced secondary metabolites biosynthesis in medicinal plants.

Plants and microbes interact with each other via different chemical signaling pathways. At the risophere level, the microbes can secrete molecules, called elicitors, which act on their receptors located in plant cells. The so-called elicitor molecules as well as their actions differ according to the mcirobes and induce different bilogical responses in plants such as the synthesis of secondary metabolites. Microbial compounds induced phenotype changes in plants are known as elicitors and signaling pathways which integrate elicitor's signals in plants are called elicitation. In this review, the impact of microbial elicitors on the synthesis and the secretion of secondary metabolites in plants was highlighted. Moreover, biological properties of these bioactive compounds were also highlighted and discussed. Indeed, several bacteria, fungi, and viruses release elicitors which bind to plant cell receptors and mediate signaling pathways involved in secondary metabolites synthesis. Different phytochemical classes such as terpenoids, phenolic acids and flavonoids were synthesized and/or increased in medicinal plants via the action of microbial elicitors. Moreover, these compounds compounds exhibit numerous biological activities and can therefore be explored in drugs discovery.

Phytochemistry, Toxicology, and Pharmacological Properties of Origanum elongatum.

Origanum elongatum L. is an endemic aromatic and medicinal plant. This work reports previous studies on O. elongatum concerning its taxonomy, botanical description, geographical distribution, bioactive compounds, toxicology, and biological effects. Chemical analyses showed that O. elongatum contains different chemical compounds, in particular volatile compounds. Pharmacological investigations showed that volatile compounds and extracts from O. elongatum exhibit different pharmacological properties, such as antibacterial, antifungal, antiviral, antioxidant, vasodilator, corrosion inhibitor, and hepatoprotective effects. Moreover, toxicological reports revealed the safety of this species. The pharmacological effects of O. elongatum could be correlated with the main compounds, which exhibit different pharmacological properties with numerous mechanism insights.

Phytochemical properties, biological activities and medicinal use of Centaurium erythraea Rafn.

ETHNOPHARMACOLOGICAL RELEVANCE: Centaurium erythraea is an important medicinal plant in many countries, e.g. Morocco, Algeria, Italy, Spain, Portugal, and countries of Balkan Peninsula. It is used in folk medicine to treat various illnesses. It is also used as an antiapoplectic, anticoagulant, anticholagogue, antipneumonic, hematocathartic, and as a hypotensive agent. AIM OF THE REVIEW: In this review, previous reports on the taxonomy, botanical description, geographic distribution, ethnomedicinal applications, phytochemistry, pharmacological properties, and toxicity of Centaurium erythraea were critically summarized. MATERIALS AND METHODS: Scientific search engines including PubMed, ScienceDirect, SpringerLink, Web of Science, Scopus, Wiley Online, SciFinder, and Google Scholar were consulted to collect data on C. erythraea. The data presented in this work summarized the main reports on C. erythraea phytochemical compounds, ethnomedicinal uses, and pharmacological activities. RESULTS: C. erythraea is used in traditional medicine to treat various diseases such as diabetes, fever, rhinitis, stomach ailments, urinary tract infections, dyspeptic complaints, loss of appetite, and hemorrhoids, and as diuretic. The essential oils and extracts of C. erythraea exhibited numerous biological properties such as antibacterial, antioxidant, antifungal, antileishmanial, anticancer, antidiabetic, anti-inflammatory, insecticidal, diuretic, gastroprotective, hepatoprotective, dermatoprotective, neuroprotective, and inhibitory agent for larval development. Phytochemical characterization of C. erythraea revealed the presence of several classes of secondary metabolites such as xanthonoids, terpenoids, flavonoids, phenolic acids, and fatty acids. CONCLUSIONS: Ethnomedicinal studies demonstrated the use of C. erythraea for the treatment of various disorders. Pharmacological reports showed that C. erythraea especially its aerial parts and roots exhibited potent, and beneficial activities. These findings confirmed the link between the traditional medicinal use and the results of the scientific biological experiments. Considering these results, further investigation using diverse in vivo pharmacological assays are strongly recommended to validate the results of its traditional use. Toxicological tests and pharmacokinetic studies are also required to validate the safety and efficacy of C. erythraea and its bioactive contents.

Ethnomedicinal use, phytochemistry, pharmacology, and toxicology of Daphne gnidium: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Daphne gnidium L., (Lazaz or Metnan) is a perennial plant that grows around the Mediterranean basin, in Southern Europe, North Africa and the Middle East. It is used in different countries for hair care and to treat several diseases including skin cancer, diabetes, nervous breakdowns, sinusitis, poisoning, rheumatic disorders, odontalgia, muscular pain, and gastrointestinal infections. It is also used as anti-inflammatory, insecticide, and anti-parasitic remedy. AIM OF THE REVIEW: In this review, previous studies on D. gnidium including its botanical description, taxonomy, geographical distribution, medicinal use, phytochemistry, and pharmacological properties were critically highlighted and discussed for suggesting the exploration of this specie and its bioactive compounds in medical applications. MATERIALS AND METHODS: Data on D. gnidium were gathered from Scientific search engines including PubMed, ScienceDirect, SpringerLink, Web of Science, Scopus, Wiley Online, SciFinder, and Google Scholar. Reports on D. gnidium written in English published before September 2020 were summarized. RESULTS: In traditional medicine, D. gnidium is used to treat diabetes, gastrointestinal infections, skin cancer, nervous breakdowns, and sinusitis. The extracts and essential oil of D. gnidium exhibited several biological properties such as antibacterial, antifungal, antiviral, antigenotoxic, hemolytic, anti-inflammatory, immunomodulatory, neuroprotective, allelopathic, and insecticidal effects. Phytochemical investigations identified several chemical classes of secondary metabolites in D. gnidium essential oil and extracts including terpenoids, coumarins, flavonoids, fatty acids, and alkanes. CONCLUSIONS: The findings presented in this study showed a link between the traditional medicinal use and scientific biological results about D. gnidium. However, further investigations should be carried out to support medical and cosmetic applications of this species. Indeed, D. gnidium and its main compounds should be confirmed concerning their safety and their bioavailability. Moreover, pharmacodynamic studies should be conducted to support their efficacy in medical applications.

Traditional use, phytochemistry, toxicology, and pharmacology of Origanum majorana L.

ETHNOPHARMACOLOGICAL RELEVANCE: Origanum majorana L., is an aromatic and medicinal plant distributed in different parts of Mediterranean countries. This species is widely used in traditional medicine for the treatment of many diseases such as allergies, hypertension, respiratory infections, diabetes, stomach pain, and intestinal antispasmodic. AIM OF THE REVIEW: This work reports previous studies on O. majorana concerning its taxonomy, botanical description, geographical distribution, traditional use, bioactive compounds, toxicology, and biological effects. MATERIALS AND METHODS: Different scientific data bases such as Web of Science, Scopus, Wiley Online, SciFinder, Google Scholar, PubMed, ScienceDirect, and SpringerLink were consulted to collect data about O. majorana. The presented data emphasis bioactive compounds, traditional uses, toxicological investigations, and biological activities of O. majorana. RESULTS: The findings of this work marked an important correlation between the traditional use of O. majorana as an anti-allergic, antihypertensive, anti-diabetic agent, and its biological effects. Indeed, pharmacological investigations showed that essential oils and extracts from O. majorana exhibit different biological properties, particularly; antibacterial, antifungal, antioxidant, antiparasitic, antidiabetic, anticancer, nephrotoxicity protective, anti-inflammatory, analgesic and anti-pyretic, hepatoprotective, and antimutagenic effects. Toxicological evaluation confirmed the safety and innocuity of this species and supported its medicinal uses. Several bioactive compounds belonging to different chemical family such as terpenoids, flavonoids, and phenolic acids were also identified in O. majorana. CONCLUSIONS: The results suggest that the pharmacological properties of O. majorana confirm its traditional uses. Indeed, O. majorana essential oils showed remarkable antimicrobial, antioxidant, anticancer, anti-inflammatory, antimutagenic, nephroprotective, and hepatoprotective activities. However, further investigations regarding the evaluation of molecular mechanisms of identified compounds against human cancer cell lines, inflammatory process, and microbial infections are needed to validate pharmacodynamic targets. The toxicological investigation of O. Majorana confirmed its safety and therefore encouraged pharmacokinetic evaluation tests to validate its bioavailability.

Ethnomedicinal use, phytochemistry, pharmacology, and toxicology of Ajuga iva (L.,) schreb.

ETHNOPHARMACOLOGICAL RELEVANCE: Ajuga iva (L.,) Schreb (A. iva). is a medicinal plant commonly used in Africa to treat several diseases such as diabetes, rheumatism, allergy, cancer, renal, metabolic disorders, cardiovascular disorders, digestive, and respiratory disorders. AIM OF THE REVIEW: We highlighted previous reports on A. iva including its ethnopharmacological uses, the chemistry of its secondary metabolites, in vitro and in vivo pharmacological properties, and toxicological evidence. MATERIALS AND METHODS: The data on A. iva were gathered using scientific research databases such as ScienceDirect, PubMed, SpringerLink, Web of Science, Scopus Wiley Online, and Google Scholar. In this review, studies focused on A. iva and its phytopharmacological activities were explored. RESULTS: A. iva is used by many North African folk medicine practitioners especially against diabetes and immunological diseases. Our analysis of the previous reports confirmed the scientific evidence of A. iva ethnomedicinal uses, especially the antidiabetic and anti-hypercholesterolemia activity. However, there was no clear correlation between previous pharmacological reports on A. iva and its other ethnomedicinal uses in the treatment of rheumatism, allergy, metabolic, digestive, and respiratory disorders. The extracts and isolated compounds from A. iva exhibited numerous in vitro and in vivo pharmacological activities such as antidiabetic, antioxidant, antimicrobial, anti-hypercholesterolemia, insecticide, and litholitic effects. Chemical characterization using GC-MS, HPLC, and NMR revealed the presence of many chemical compounds such as 20-hydroxyecdysone, cyasterone, ajugasterone, apigenin dihexoside, apigenin, carvacrol, ecdysterone, palmitic acid in different parts of A. iva. These compounds belong to different classes of chemical compounds such as steroids, flavonoids, fatty acids, and terpenoids. CONCLUSIONS: A. iva extracts especially from the leaves showed significant antidiabetic, antioxidant, anti-hypercholesterolemia, and analgesic effects. Future studies are required to validate the results of clinical trials on A. iva antidiabetic, anti-hypercholesterolemia, antioxidant/anti-inflammatory, antimicrobial, and analgesic properties. Toxicological validation and pharmacokinetics investigation are necessary to validate the efficacy and safety A. iva extracts and its secondary metabolites. An in-depth investigation is needed to reveal the biological activity of A. iva active compounds in preventing the development of cancer and neurodegenerative disorders such as Alzheimer's and Parkinson's diseases.

Ethnomedicinal use, phytochemistry, pharmacology, and food benefits of Thymus capitatus.

ETHNOPHARMACOLOGICAL RELEVANCE: Thymus capitatusHoffm. et Link. is an endemic medicinal plant to the Mediterranean region. It is used in folk medicine to treat various diseases including diabetes, flu, cough, flatulence, dermatitis, indigestion, respiratory disorders, asthma, rheumatic, diarrhea, and influenza. It is also used as antiseptic, analgesic, stimulant, and sedative. AIM OF THE REVIEW: In this review, previous reports on T. capitatusconcerningits taxonomy, botanical description, geographical distribution, ethnomedicinal use, phytochemistry, pharmacological properties, and food benefits were critically summarized. MATERIALS AND METHODS: Scientificsearch engines including PubMed, ScienceDirect, SpringerLink, Web of Science, Scopus, Wiley Online, Scifnder, and Google Scholar were consulted to gather data on T. capitatus. The data presented in this work summarize T. capitatus phytochemical compounds, ethnomedicinaluses, pharmacological properties, and food value. RESULTS: In traditional medicine, T. capitatusis used to treat various illnesses including diabetes, dermatitis, and diarrhea. The essential oils and extracts of T. capitatus exhibited several biological properties such as antibacterial, antioxidant, antifungal, antiparasitic, hypoglycemic, anticancer, antiviral, and hepatoprotective effects. T. capitatus possesses high nutritional value and its essential oil showed promising activity in food preservation. Phytochemical characterization of T. capitatus revealed the presence of several classes of secondary metabolites such as terpenoids, flavonoids, and phenolic acids. CONCLUSIONS: Ethnomedicinal surveys indicated the use of T. capitatus for the treatment of various disorders. Pharmacological reports showed that T. capitatus especially its essential oils, exhibited potent antimicrobial, antioxidant, antidiabetic and hepatoprotective effects. These findings confirmed the link between traditional medicinal use and scientific biological results. Moreover, T. capitatus exhibited a potent food preservative effect which justifies its use in traditional medicine as a food additive. In light of these findings, further studies to validate the industrial applications of T. capitatus essential oils as a food additive are required. Further investigations on the in vivo pharmacological properties of T. capitatus are strongly recommended to validate the results of its clinical uses as an antimicrobial, hepatoprotective, and antiviral agent. Toxicological tests and pharmacokinetic investigations are also needed to validate the safety and efficacy ofT. capitatus and its bioactive compounds.

Structural characterization of bioactive compounds in Cotula cinerea extracts by ultra-high-performance liquid chromatography with photodiode array and high-resolution time-of-flight mass spectrometry detectors.

RATIONALE: Cotula cinerea of the Asteraceae family is a traditional Moroccan plant with various biological activities such as analgesic, cytotoxic and antioxidant effects which are often related to the presence of secondary metabolites. The present work aims to screen and identify the main phytochemicals compounds of Cotula cinerea extracts. METHODS: A method was developed that coupled a rapid and simple ultra-high-performance liquid chromatography system with both photodiode array and high-resolution time-of-flight mass spectrometry detectors (UHPLC-PDA/TOF-HRMS) for the identification of the main secondary metabolites of three investigated extracts (hexane, AcOEt and n-BuOH). RESULTS: A total of 30 phytocomponents pertaining to phenolic compounds and terpenoids have been detected, identified and quantified. Among these were previously reported free and conjugated coumaric and caffeic acids along with free and conjugated flavones and flavonols with kaempferol, quercetin, luteolin and apigenin aglycones. In addition, sulfated flavonoids were identified in the investigated extracts and are reported in this work for the first time in Cotula cinerea. The obtained results have been discussed in relation to the biological activities of the corresponding extracts. CONCLUSIONS: This study proposed a practical strategy for rapidly screening and identifying secondary metabolites of Cotula cinerea and provided new information on the phytochemicals of this Saharan plant. This work has therefore provided useful results for further pharmacological studies and the design of new drugs based on this species and will facilitate the utilization of Cotula cinerea in the clinic and its safety evaluation. It is also hoped that the information presented here might stimulate further studies that will possibly lead to development of therapeutic agents from this plant.

Cytotoxicological Investigation of the Essential Oil and the Extracts of Cotula cinerea and Salvia verbenaca from Morocco.

The objective of this work was to investigate the cytotoxicological effect of the extracts (hexane, ethyl acetate, and n-butanol) of Cotula cinerea and Salvia verbenaca in addition to the essential oil of Cotula cinerea. These plants are widely used in the Moroccan traditional folk medicine. The cytotoxic effect was explored against two cancer cell lines, Vero and RD, using the colorimetric MTT assay. The obtained results showed that the cytotoxicity differed according to the used extract with an efficient effect of Cotula cinerea extracts compared to Salvia verbenaca. A potent cytotoxicity was thus observed for the Cotula cinerea hexane extract which inhibited the growth of RD cell line at the lowest IC50 value (57.21±3.43 µg/mL). This was followed by the ethyl acetate extract and the essential oil with moderate effects against RD cell line and showed IC50 values of 187.52±6.27 µg/mL and 173.05±4.46 µg/mL, respectively. On the other hand, different results were obtained and Cotula cinerea essential oil was the most cytotoxic with the lowest IC50 value (72.72±2.18 µg/mL) against Vero cell line. In the same conditions, higher concentrations were needed in the case of Salvia verbenaca extracts. The results of this study showed thus that Cotula cinerea essential oil and hexane extract showed significant cytotoxic effects against RD and Vero cell lines, respectively, and could be considered as novel source of antitumor agents. This study is expected to be beneficial for clinical and traditional applications for Cotula cinerea as a remedy against cancer and opens new perspectives for further investigations on other types of cancer cell lines.