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Diabetes is a complex disease that affects a large percentage of the world's population, and it is associated with several risk factors. Self-management poses a significant challenge, but natural sources have shown great potential in providing effective glucose reducing solutions. Flavonoids, a class of bioactive substances found in different natural sources including medicinal plants, have emerged as promising candidates in this regard. Indeed, several flavonoids, including apigenin, arbutin, catechins, and cyanidin, have demonstrated remarkable anti-diabetic properties. The clinical effectiveness of these flavonoids is linked to their potential to decrease blood glucose concentration and increase insulin concentration. Thus, the regulation of certain metabolic pathways such as glycolysis and neoglycogenesis has also been demonstrated. In vitro and in vivo investigations revealed different mechanisms of action related to flavonoid compounds at subcellular, cellular, and molecular levels. The main actions reside in the activation of glycolytic signaling pathways and the inhibition of signaling that promotes glucose synthesis and storage. In this review, we highlight the clinical efficiency of natural flavonoids as well as the molecular mechanisms underlying this effectiveness.

Objective: To investigate the Pinus halepensis extracts and determine its healing and antibacterial effects, and to evaluate the treatment of skin burns. Methods: Aqueous and ethanolic extracts and topical based on Aleppo pine plant extracts were prepared. Thirty male and female Wistar rats were used to study the cutaneous toxicity of extracts from the bark of P. halepensis . The extracts’ healing potential for burn wounds were also assessed by evaluating the clinical and macroscopic aspects of the wounds. The antibacterial activity of crude extracts of P. halepensis as well as its wound healing abilities was verified in this investigation. Results: In animals with acute dermal toxicity, there were no signs of treatment-related toxicity or death. The extracts of these plants could be transformed into phytomedicines for the treatment of infected wounds. The results demonstrated that formulated ointments are successful in treating second-degree burns in rats and may be suitable for the short-term therapeutic treatment of second-degree burns. Conclusion: This study successfully answered our problem, regarding the efficacy of our extract for treating second-degree burns in rats. Further studies are needed to confirm these results by identifying the molecules responsible for these activities and examining their mechanism of action.

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.

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.

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.

Although people with human leukocyte antigens (HLA) DQ2 and/or DQ8 are more likely to develop celiac disease (CD), the condition cannot be fully explained by this genetic predisposition alone. Multiple, as yet unidentified, factors contribute to the genesis of CD, including genetics, the environment, and the immune system. In order to provide insight into a prospective possibility and an expanded screening technique, we aim to undertake a comprehensive and meta-analytical study of the assessment and distribution of HLA class II (HLA-DQ2/DQ8) in adult CD patients. A systematic review was conducted using an electronic search of databases (PubMed, Google Scholar, Embase, and Direct Science) from January 2004 to February 2022. DQ2/DQ2 homozygotes have the highest risk of developing CD. DQ2/DQ8 typing is an effective test to exclude CD from the differential diagnosis of a patient with CD symptoms. Although other non-HLA genes have been associated with CD, they are rarely considered at diagnosis because they account for only a small proportion of the heritability of CD. This finding, together with the information gathered previously, may be useful in considering widely available and economically feasible screening options for celiac disease in young people.

Chalcones are among the leading bioactive flavonoids with a therapeutic potential implicated to an array of bioactivities investigated by a series of preclinical and clinical studies. In this article, different scientific databases were searched to retrieve studies depicting the biological activities of chalcones and their derivatives. This review comprehensively describes preclinical studies on chalcones and their derivatives describing their immense significance as antidiabetic, anticancer, anti-inflammatory, antimicrobial, antioxidant, antiparasitic, psychoactive, and neuroprotective agents. Besides, clinical trials revealed their use in the treatment of chronic venous insufficiency, skin conditions, and cancer. Bioavailability studies on chalcones and derivatives indicate possible hindrance and improvement in relation to its nutraceutical and pharmaceutical applications. Multifaceted and complex underlying mechanisms of chalcone actions demonstrated their ability to modulate a number of cancer cell lines, to inhibit a number of pathological microorganisms and parasites, and to control a number of signaling molecules and cascades related to disease modification. Clinical studies on chalcones revealed general absence of adverse effects besides reducing the clinical signs and symptoms with decent bioavailability. Further studies are needed to elucidate their structure activity, toxicity concerns, cellular basis of mode of action, and interactions with other molecules.

Berry-derived polyphenols are bioactive compounds synthesized and secreted by several berry fruits. These polyphenols feature a diversity of chemical compounds, including phenolic acids and flavonoids. Here, we report the beneficial health effects of berry-derived polyphenols and their therapeutical application on gut-microbiota-related diseases, including inflammation and cancer. Pharmacokinetic investigations have confirmed the absorption, availability, and metabolism of berry-derived polyphenols. In vitro and in vivo tests, as well as clinical trials, showed that berry-derived polyphenols can positively modulate the gut microbiota, inhibiting inflammation and cancer development. Indeed, these compounds inhibit the growth of pathogenic bacteria and also promote beneficial bacteria. Moreover, berry-derived polyphenols exhibit therapeutic effects against different gut-microbiota-related disorders such as inflammation, cancer, and metabolic disorders. Moreover, these polyphenols can manage the inflammation via various mechanisms, in particular the inhibition of the transcriptional factor Nf-κB. Berry-derived polyphenols have also shown remarkable effects on different types of cancer, including colorectal, breast, esophageal, and prostate cancer. Moreover, certain metabolic disorders such as diabetes and atherosclerosis were also managed by berry-derived polyphenols through different mechanisms. These data showed that polyphenols from berries are a promising source of bioactive compounds capable of modulating the intestinal microbiota, and therefore managing cancer and associated metabolic diseases. However, further investigations should be carried out to determine the mechanisms of action of berry-derived polyphenol bioactive compounds to validate their safety and examinate their clinical uses.

Background. Human leishmaniasis, both visceral and cutaneous, has been reported in Morocco for centuries and constitutes a serious public health problem. However, the evolution of this pathology depends on several factors such as ecological, socioeconomic, and climatic conditions. The risk study of the affected foci is of great value for the control and surveillance of this endemic disease, especially in the provinces where Leishmania infantum predominates. Methods. This study concerned nine provinces located in the extreme and central north of Morocco (Taounate, Taza, Chefchaouen, Al Hoceima, Larache, Tétouane, Tanger-Assilah, M’diq-Fnideq, and Fahs-Anjra Provinces). In this work, leishmaniasis cases (VL and CL) were subjected to an epidemiological study which was performed using a linear regression model to identify the impact as well as the interaction between all predictor variables on the distribution of leishmaniasis in this region. Results. During the period 1997–2018, a total of 6 128 cases of VL and CL were recorded in the study area. Our results showed that among demographic factors studied, urbanization showed significance for both cutaneous and visceral forms (P

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.

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.

Carvone is a monoterpene ketone contained in the essential oils of several aromatic and medicinal plants of the Lamiaceae and Asteraceae families. From aromatic plants, this monoterpene is secreted at different concentrations depending on the species, the parts used, and the extraction methods. Currently, pharmacological investigations showed that carvone exhibits multiple pharmacological properties such as antibacterial, antifungal, antiparasitic, antineuraminidase, antioxidant, anti-inflammatory, and anticancer activities. These studies were carried out in vitro and in vivo and involved a great deal of knowledge on the mechanisms of action. Indeed, the antimicrobial effects are related to the action of carvone on the cell membrane and to ultrastructural changes, while the anti-inflammatory, antidiabetic, and anticancer effects involve the action on cellular and molecular targets such as inducing of apoptosis, autophagy, and senescence. With its multiple mechanisms, carvone can be considered as natural compounds to develop therapeutic drugs. However, other investigations regarding its precise mechanisms of action as well as its acute and chronic toxicities are needed to validate its applications. Therefore, this review discusses the principal studies investigating the pharmacological properties of carvone, and the mechanism of action underlying some of these properties. Moreover, further investigations of major pharmacodynamic and pharmacokinetic studies were also suggested.

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.

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.

Abstract Background After alleged stop of transmission of schistosomiasis and further down the line in post elimination settings, sensitive tools are required to monitor infection status to prevent potential re-emergence. In Rahala, where transmission cycle of Schistosoma haematobium is interrupted since 2004 but where 30% of snails are still infected by S. bovis, potential human S. bovis infection can’t be excluded. As methods based on egg-counts do not provide the required sensitivity, antibody or antigen assays are envisaged as the most appropriate tools for this type of monitoring. Methods In this pilot study, the performances of three assays were compared: two commercially available antibody tests (ELISA and haemagglutination format) indicating exposure, and an antigen test (lateral flow strip format) demonstrating active infection. All 37 recruited study participants resided in Rahala (Akka, province Tata, Morocco). Participants had been diagnosed and cured from schistosomiasis in the period between 1983 and 2003. In 2015 these asymptomatic participants provided fresh clinical samples (blood and urine) for analysis with the aforementioned diagnostics tests. Results No eggs were identified in the urine of the 37 participants. The haemagglutination test indicated 6 antibody positives whereas the ELISA indicated 28 antibody positives, one indecisive and one false positive. ELISA and haemagglutination results matched for 18 individuals, amongst which 5 out of 6 haemagglutination positives. With the antigen test (performed on paired serum and urine samples), serum from two participants (cured 21 and 32 years ago) indicated the presence of low levels of the highly specific Schistosoma circulating anodic antigen (CAA), demonstrating low worm level infections (less than 5 pg/ml corresponding to probably single worm pair). One tested also CAA positive with urine. ELISA indicated the presence of human anti-Schistosoma antibodies in these two CAA positive cases, haemagglutination results were negative. Conclusions To prevent reemergence of schistosomiasis in Morocco current monitoring programs require specific protocols that include testing of antibody positives for active infection by the UCP-LF CAA test, the appropriate diagnostic tool to identify Schistosoma low grade infections in travelers, immigrants and assumed cured cases. The test is genus specific will also identify infections related to S. bovis.

Cancer is a heterogeneous disease and one of the major issues of health concern, especially for the public health system globally. Nature is a source of anticancer drugs with abundant pool of diverse chemicals and pharmacologically active compounds. In recent decade, some natural products and synthetic analogs have been investigated for the cancer treatment. This article presents the utilization of natural products as a source of antitumor drugs.