Chemical composition and potential antioxidant, anti-inflammatory, and analgesic efficacy of Cistus albidus L.

This study aims to assess the chemical composition of the aqueous extract of Cistus albidus L. leaves, as well as the potential of aqueous and hydroethanol extracts of the leaves and seeds as analgesic, anti--inflammatory, and antioxidant agents. The contents of phenolics and inorganic constituents were determined in C. albidus seeds and leaves; antioxidant capacity was assessed by 3 complementary and diverse tests. The carrageenan-induced paw edema technique was used to investigate the anti-inflammatory effect in vivo, and albumin denaturation to evaluate the anti-inflammatory effect in vitro. The acetic acid-induced contortion test, the tail-flick test, and the plantar test were used to assess the analgesic effi cacy in vivo. Chemical analysis was performed by UPLC-MS/MS to quantify several phenolic compounds including catechin (1,627.6 mg kg-1), quercitrin (1,235.8 mg kg-1) and gallic acid (628. 2 mg kg-1). The ICP analysis revealed that potassium and calcium were the main inorganic components in the seeds and leaves of C. albidus. The hydroethanolic extract of the leaves showed the highest content of polyphenols/flavonoids, whereas the highest value of proantho cyanidins was detected in the aqueous extract of the seeds. All extracts showed potent antioxidant activity related to different phenolic compounds (quercetin, gallic acid, astragalin, catechin, and rutin). The aqueous extract of the leaves strongly inhibited paw edema (76.1 %) after 6 h of treatment and showed maximal inhibition of protein denaturation (191.0 µg mL-1 for 50 % inhibition) and analgesic activity in different nociceptive models. The presented data reveal that C. albidus extracts potentially show antioxidant, anti-inflammatory, and analgesic activities that could confirm the traditional use of this plant.

Study of the Analgesic Potential of the Ethanolic Extract of Moroccan Cistus ladanifer L.

AIMS: The study aimed to analyze the analgesic activity of Cistus ladanifer L. BACKGROUND: Cistus ladanifer L. is a fragrant shrub of the Cistaceae family widespread in the Mediterranean basin, it has various biological activities, including antidiabetic and antihypertensive effects. OBJECTIVES: The objective of this work was to study the phytochemical profile, the acute toxicity and the analgesic power of the ethanolic extract of the species Cistus ladanifer L. (C. ladanifer) collected in Northern Morocco. METHODS: The evaluation of antinociceptive activity in mice was performed using two validated models, the formalin-induced paw-licking model and the acetic acid-provoked writhing test. RESULTS: According to the results, five phenolic compounds were identified in the ethanolic extract by HPLC-MS/MS. As regards the acute toxicity study, the results showed no mortality or clinical symptoms in mice treated to compare the control group at doses up to 5,000 mg/kg BW. Regarding the analgesic effect, the ethanolic extract at the doses of 400 and 800 mg/kg, BW showed a statistically significant (p <0.05) and dose-dependent analgesic effect in two nociceptive tests. On the other hand, in the syrup of ethanolic extract at the dose of 800 mg/kg, BW expressed the most superior pain-inhibiting effect in both tests, producing an analgesic effect equivalent to that of the reference drug (indomethacin). CONCLUSION: These findings provide pharmacological justification that might aid in the development of a natural anti-nociceptive medication as an alternative to chemical analgesic drugs.

Impact of Pretreatment and Drying Factors on Chemical and Biochemical Attributes of Moroccan Thompson Seedless Grapes.

Drying is a common technique in the agrifood industry, but insufficient control in the drying process can result in changes to the fruit's appearance due to physiological damage during processing. The aim of this study was to investigate the impact of pretreatment and drying process parameters on Moroccan raisins' quality and safety. The experimental levels of pretreatment factors (blanching, browning agents) and drying temperature were defined at the beginning. Subsequently, a 24-factorial design was employed to provide a simple and reliable model capable of relating directly the response factor (drying time, color intensity change (E∗), chromaticity (C∗), and browning rate) to the variables (NaOH concentration, antibrowning agent concentration, temperature, and relative humidity). All four parameters had a statistically considerable effect on studied responses. Blanching for 5 minutes at 1% of NaOH solution, using an appropriate concentration of antibrowning agent (5% Na2S2O5), and drying at 70°C with 30% of relative moisture can lead to better preservation of grapes' appearance and quality (chromaticity (C∗) and color change (E∗)). Also, in these conditions, a lower browning rate (14.48%), a lower 5-hydroxymethylfurfural content (12.40 mg/100 g DW), and a higher level of polyphenols (135.79 ± 13.17 mg GAE/100 g DW) and flavonoid content (57.81 ± 3.08 mg Qeq/100 g DW) have been recorded while meeting international standards for SO2 content and microbial quality.

Effect of Cannabidiol in LPS-Induced Toxicity in Astrocytes: Possible Role for Cannabinoid Type-1 Receptors.

Cerebral metabolic abnormalities are common in neurodegenerative diseases. Previous studies have shown that mitochondrial damage alters ATP production and increases reactive oxygen species (ROS) release which may contribute to neurodegeneration. In the present study, we investigated the neuroprotective effects of cannabidiol (CBD), a non-psychoactive component derived from marijuana (Cannabis sativa L.), on astrocytic bioenergetic balance in a primary cell culture model of lipopolysaccharide (LPS)-induced neurotoxicity. Astrocytic metabolic profiling using an extracellular flux analyzer demonstrated that CBD decreases mitochondrial proton leak, increased spare respiratory capacity and coupling efficiency in LPS-stimulated astrocytes. Simultaneously, CBD increased astrocytic glycolytic capacity and glycolysis reserve in a cannabinoid receptor type 1 (CB1)-dependent manner. CBD-restored metabolic changes were correlated with a significant decrease in the pro-inflammatory cytokines tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) concentration and reduction of ROS production in LPS-stimulated astrocytes. These results suggest that CBD may inhibit LPS-induced metabolic impairments and inflammation by enhancing astrocytic metabolic glycolysis versus oxidative phosphorylation through its action on CB1 receptors. The present findings suggest CBD as a potential anti-inflammatory treatment in metabolic pathologies and highlight a possible role for the cannabinoidergic system in the modulation of mitochondrial oxidative stress. CBD enhances mitochondrial bioenergetic profile, attenuates proinflammatory cytokines release, and ROS overproduction of astrocytes stimulated by LPS. These effects are not mediated directly by CB1 receptors, while these receptors seem to have a key role in the anti-inflammatory response of the endocannabinoid system on astrocytes, as their specific inhibition by SR141716A led to increased pro-inflammatory cytokines release and ROS production. The graphical abstract is created with BioRender.com.

An Update on Tamoxifen and the Chemo-Preventive Potential of Vitamin E in Breast Cancer Management.

Breast cancer (BC) is the most common female cancer in terms of incidence and mortality worldwide. Tamoxifen (Nolvadex) is a widely prescribed, oral anti-estrogen drug for the hormonal treatment of estrogen-receptor-positive BC, which represents 70% of all BC subtypes. This review assesses the current knowledge on the molecular pharmacology of tamoxifen in terms of its anticancer and chemo-preventive actions. Due to the importance of vitamin E compounds, which are widely taken as a supplementary dietary component, the review focuses only on the potential importance of vitamin E in BC chemo-prevention. The chemo-preventive and onco-protective effects of tamoxifen combined with the potential effects of vitamin E can alter the anticancer actions of tamoxifen. Therefore, methods involving an individually designed, nutritional intervention for patients with BC warrant further consideration. These data are of great importance for tamoxifen chemo-prevention strategies in future epidemiological studies.

Thymus atlanticus: A Source of Nutrients with Numerous Health Benefits and Important Therapeutic Potential for Age-Related Diseases.

Thymus atlanticus (Lamiaceae) is a plant endemic to the Mediterranean basin that is found in significant quantities in the arid regions of Morocco. Thymus atlanticus is used in traditional medicine to treat infectious and non-infectious diseases. It is also used for the isolation of essential oils and for the seasoning of many dishes in the Mediterranean diet. The major constituents of Thymus atlanticus are saponins, flavonoids, tannins, alkaloids, various simple and hydroxycinnamic phenolic compounds, and terpene compounds. Several of these compounds act on signaling pathways of oxidative stress, inflammation, and blood sugar, which are parameters often dysregulated during aging. Due to its physiochemical characteristics and biological activities, Thymus atlanticus could be used for the prevention and/or treatment of age-related diseases. These different aspects are treated in the present review, and we focused on phytochemistry and major age-related diseases: dyslipidemia, cardiovascular diseases, and type 2 diabetes.

Ionomic analysis, polyphenols characterization, analgesic, antiinflammatory and antioxidant capacities of Cistus laurifolius leaves: in vitro, in vivo, and in silico investigations.

This study aims to investigate the chemical and mineral composition, antioxidant, analgesic, and anti-inflammatory effects of the aqueous extract of Cistus laurifolius var. atlanticus Pit. (Cistaceae). Additionally, molecular docking interactions of various ligands with antioxidant protein target urate oxidase (1R4U) and anti-inflammatory protein target cyclooxygenase-2 (3LN1), revealing potential dual activities and highlighting specific residue interactions. The chemical characterization focused at first glance on the mineral composition which showed that C. laurifolius extract is a mineral-rich source of potassium (K), magnesium (Mg), manganese (Mn), sodium (Na), phosphorus (P), and zinc (Zn). We next performed, ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis, the latter showed various polyphenols in C. laurifolius extract including Gallic acid as the predominant polyphenol. Isoquercetin, Taxifolin and Astragalin were also among the major flavonoids detected. The antioxidant capacity of C. laurifolius leaves was tested using 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1- picrylhydrazyl (DPPH) and reducing power (RP) assays. In vitro analysis of the anti-inflammatory property of C. laurifolius leaves was conducted by the albumin denaturation test and the in vivo was assessed in the sequel by carrageenan-induced paw edema test. The analgesic activity was evaluated in vivo using tail flick, acetic acid-induced contortion, and plantar tests. The findings showed that the leave extract had a powerful antioxidant activity with an IC50 values of 2.92 ± 0.03 µg/mL (DPPH) and 2.59 ± 0.09 µg/mL (in RP test). The studied extract strongly abolished the induced inflammation (82%). Albumin denaturation test recorded an IC50 value of 210 µg/mL. Importantly, the oral administration of C. laurifolius extract considerably reduced the nociceptive effect of acetic acid in rats, showing a significant analgesic effect in a dose-related manner. Altogether, our results showed that C. laurifolius can be a promising source of phytochemicals for drug development potential.

Seasonal Patterns of Zoonotic Cutaneous Leishmaniasis Caused by L. major and Transmitted by Phlebotomus papatasi in the North Africa Region, a Systematic Review and a Meta-Analysis

BACKGROUND: In North African countries, zoonotic cutaneous leishmaniasis (ZCL) is a seasonal disease linked to Phlebotomus papatasi, Scopoli, 1786, the primary proven vector of L. major dynamics. Even if the disease is of public health importance, studies of P. papatasi seasonal dynamics are often local and dispersed in space and time. Therefore, a detailed picture of the biology and behavior of the vector linked with climatic factors and the framework of ZCL outbreaks is still lacking at the North African countries' level. Our study aims to fill this gap via a systematic review and meta-analysis of the seasonal incidence of ZCL and the activity of P. papatasi in North African countries. We address the relationship between the seasonal number of declared ZCL cases, the seasonal dynamic of P. papatasi, and climatic variables at the North African region scale. METHODS: We selected 585 publications, dissertations, and archives data published from 1990 to July 2022. The monthly incidence data of ZCL were extracted from 15 documents and those on the seasonal dynamic of P. papatasi from 11 publications from four North African countries. RESULTS: Our analysis disclosed that for most studied sites, the highest ZCL incidence is recorded from October to February (the hibernal season of the vector), while the P. papatasi density peaks primarily during the hot season of June to September. Overall, at the North African region scale, two to four months laps are present before the apparition of the scars reminiscent of infection by L. major. CONCLUSIONS: Such analysis is of interest to regional decision-makers for planning control of ZCL in North African countries. They can also be a rationale on which future field studies combining ZCL disease incidence, vector activity, and climatic data can be built.

A systematic review and global analysis of the seasonal activity of Phlebotomus (Paraphlebotomus) sergenti, the primary vectors of L. tropica.

BACKGROUND: Phlebotomus (Paraphlebotomus) sergenti is a widespread proven vector of Leishmania pathogens causing anthroponotic cutaneous leishmaniasis (ACL), due to L. tropica, in the old world. The activity of P. (Par.) sergenti is seasonal and sensitive to general variations in climate. Phenological data sets can thus provide a baseline for continuing investigations on P. (Par.) sergenti population dynamics that may impact future leishmaniasis transmission and control scenarios. METHODS/PRINCIPAL FINDING: A systematic review of the seasonality of P. (Par.) sergenti was undertaken globally. Six hundred eight scientific papers were identified, and data were extracted from 35 ones, with informative data on sand fly seasonal dynamics on trapping performed from 1992 to December 2021 on 63 sites from 12 countries. Morocco, Saudi Arabia, Iraq, Iran, Pakistan, Palestine, Turkey, Spain, Portugal, Italy, Cyprus, and Georgia. The data extracted from the literature survey were further normalized. Our analysis recorded that the highest P.(Par.) sergenti activity occurs during the hot and dry seasons, primarily in July and August, whatever the location studied. We noticed a relationship between the latitude of sites and sand fly presence (from early April to June) and the type of density trend, varying from a single peak to multiple peaks. On a geographical scale, P. (Par.) sergenti concentrates between 32-37° in latitude in a large interval following the longitude and the highest number of sites with high P. (Par.) sergenti activity is located at the latitude 32°. We also quoted a similar seasonal dynamic and geographic distribution with Phlebotomus (Phlebotomus) papatasi, a proven vector of L. major that causes cutaneous infection. No apparent risk for ACL occurred from December to March, at least in the years and geographic areas considered in this survey. Altogether, knowing that high P. (Par.) sergenti activity would be linked with an increased risk of leishmaniasis transmission, and our study provides information that can be used for control programs on ACL transmission. CONCLUSIONS: Despite variations, we found a relatively homogeneous pattern of P. (Par.) sergenti potential behavior in sites whose data are published. A higher risk for L. tropica transmission was identified in the June-October period. Still, such risk was not equally distributed throughout the area since density waves of adults occurred earlier and were more frequent in some territories, like Saudi Arabia.

Exploring the genetic and phenotypic diversity within and between onion (Allium cepa L.) ecotypes in Morocco.

BACKGROUND: Gaining insight into crop diversity, both at the genetic and phenotypic levels, is of prime importance for onion breeding with an enhanced yield and quality in combination with improved resistance to biotic and abiotic stresses. In the current study, 192 different onion plants, representing 16 ecotypes, were characterized using ISSR markers. RESULTS: Based on the ISSR marker profile, there was a clear grouping of the plants into 16 different ecotypes. Though the 16 populations originated from the same geographic region in Morocco, a significant genetic diversity was detected. After a genomic characterization, field trials in three different environments in Morocco were laid out. The phenotypic characterization showed that there were always significant differences between ecotypes, and for most traits, there was also a significant environmental effect and a significant interaction between environment and ecotype. The broad-sense heritability (H2) for the phenotypic traits associated with color (L*, a*, and b*) was the largest (84.2%, 80.6%, 79.2%), demonstrating that color is conditioned primarily by genetic factors. In contrast, the H2 for yield was the lowest (41.8%), indicating that the environment has a substantial effect on yield. In addition, there was a significant association between the presence/absence of certain bands and various phenotypic traits. CONCLUSION: ISSR markers are a powerful tool in distinguishing onion ecotypes. In addition, significant associations between marker scores and phenotypic traits could be detected, representing particular importance for future breeding programs.

A conceptual model for understanding the zoonotic cutaneous leishmaniasis transmission risk in the Moroccan pre-Saharan area.

Leishmanioses are of public health concern in Morocco, mainly the Zoonotic Cutaneous Leishmaniasis (ZCL) endemic in the Moroccan pre-Saharian area. Transmission of this disease depends on eco-epidemiological and socio-economic conditions. Therefore, a multivariable approach is required to delineate the risk and intensity of transmission. This will help outline main disease risk factors and understand interactions between all underlying factors acting on disease transmission at a local and regional scale. In this context, we propose a new conceptual model, the Biophysical-Drivers-Response-Zoonotic Cutaneous Leishmaniasis (BDRZCL), adapted to the Pre-Saharian area. The proposed model highlights how the physical and human drivers affect the environment and human health. The incidence of ZCL is linked to human activity and biophysical changes or by their interactions. The human response added to risk drivers are the main components that influence the biophysical part. This model improves our understanding of the cause-effect interactions and helps decision-makers and stakeholders react appropriately.

Characterization of the Biochemical Potential of Moroccan Onions (Allium cepa L.).

Allium cepa L. remains the most cultivated Allium species in Morocco and around the world. With the purpose of making the first biochemical characterization of Moroccan onions, several biochemical components have been measured in eleven onion ecotypes. Onions were collected as seeds from different geographical origins and cultivated in the same environment, to eliminate the influence of the environment on biochemical expression. Moisture, total phenols, flavonoids, antioxidant activity, total and reducing sugars, and sulfur dioxide were the biochemical properties of interest. Except for moisture, the eleven onion ecotypes revealed a highly significant variation in terms of the studied biochemical characters. The total phenol and flavonoid content ranged from 5.94 to 11.22 mg equivalent gallic acid/g dry weight and 0.67 to 1.52 mg equivalent quercetin/g dry weight, respectively. The antioxidant activity of the studied onions showed a strong correlation with the polyphenols (R 2 = 0.7189), especially with the flavonoids (R 2 = 0.8063). The sulfur dioxide content parted from 85.60 to 30.43 ppm when measured using the Monier-Williams distillation method. The current results show that there is no correlation between total sugars and reducing sugars. In conclusion, these findings present a clear biochemical profile of Moroccan onion ecotypes, as well as confirm, for the first time, the presence of a clear variation between the biochemical profiles of Moroccan onion ecotypes, which could be useful for future valorization programs.

Organic Honey from the Middle Atlas of Morocco: Physicochemical Parameters, Antioxidant Properties, Pollen Spectra, and Sugar Profiles.

This work aimed to characterize and compare the physicochemical, ascorbic acid, phenolic, and flavonoid compounds, as well as the antioxidant properties, pollen spectra, and sugar profiles of twenty-three organic honeys produced in the Middle Atlas of Morocco. As results, the pollen analysis showed 22 taxa and revealed the dominance of Ziziphus lotus pollens for all monofloral honeys. The moisture content ranged from 15.9 to 19.0%, pH values werebetween 3.9 and 4.8, electrical conductivity varied from 100 to 581 µs/cm, ash content varied from 0.1 to 2.4%, and the invertase activity ranged from 3.5 to 36 U/kg. Moreover, hydroxymethylfurfural(HMF) varied from 1.2 to 13.5 mg/kg, which confirmed the freshness of our honey samples. For the sugar profiles, there were no significant differences between the examined groups of honeys (p > 0.05) for both fructose and glucose. Additionally, our study showed good antioxidant properties (total antioxidant activity ranged from 34.18 to 131.20 mg AAE/g; DPPH IC50 values ranged from 8.14 to 45.20 mg/mL; ABTS IC50 values ranged from 8.19 to 32.76 mg/mL) and high amounts of phenolic compounds ranging between 20.92 ± 0.03 and 155.89 ± 0.03 mg GAE/100 g, respectively; flavonoid compounds ranged from 5.52 to 20.69 mg QE/100 g, and ascorbic acid ranged from 8.01 to 23.26 mg/100 g. Overall, the proximate composition and the general characterization of organic monofloral and polyfloral honeys as sustainable and health-promising functional products may increase their commercial values, promote their marketability, and might have a significant impact on the basic circular/sustainable economy as a solid lever for solidarity economic development, especially in the rural/poor Moroccan communities. The investigated features may allow and support the incorporation of Moroccan organic honeys and their biovaluable ingredients in the nutraceutical and food industries for multiple purposes.

Geographic distribution of Meriones shawi,Psammomys obesus, and Phlebotomus papatasi the main reservoirs and principal vector of zoonotic cutaneous leishmaniasis in the Middle East and North Africa.

Rodents play a significant role in the balance of a terrestrial ecosystem; they are considered prey for many predators like owls and snakes. However, they present a high risk to agriculture (damaging crops) and health. These rodents are the main reservoirs of some vector-borne diseases like leishmaniasis. Meriones shawi (MS) and Psammomys obesus (PO) are the primary Zoonotic cutaneous leishmaniasis (ZCL) reservoirs in the Middle East and North Africa (MENA). A review on the MS and PO at the MENA scale was explored. A database of about 1500 papers was used. 38 sites were investigated as foci for MS and 36 sites for PO, and 83 sites of Phlebotomus papatasi (Pp) in the studied region. An updated map at the regional scale and the trend of the reservoir distribution was carried out using a performing proper density analysis. In this paper, climatic conditions and habitat characteristics of these two reservoirs were reviewed. The association of rodent density with some climatic variables is another aspect explored in a case study from Tunisia in the period 2009-2015 using Pearson correlation. Lastly, the protection and control measures of the reservoir were analyzed. The high concentration of the MS, PO, and Pp can be used as an indicator to identify the high-risk area of leishmaniasis infection.

Eco-epidemiological aspects of Zoonotic cutaneous leishmaniasis in Ouarzazate Province, Morocco.

Some epidemiological and ecological aspects of Zoonotic cutaneous leishmaniasis (ZCL) in Ouarzazate province, southern Morocco, were explored with the objective of analyzing ZCL distribution and associated ecological factors. Information on cutaneous leishmaniasis patients attending the local health centers of Ouarzazate during the period 2002-2009 was gathered and compiled. Urban, peri-urban, rural origin, precipitation, wind speed, temperature, water irrigation, dam volume, and altitude were studied. The findings show that the disease affected 5405 person during this period; the major part was found in the municipalities near both oases (desert oasis) and water resources, with a high concentration of cases in the peri-urban area. The highest percentage of cases was recorded mainly in September. Considerable associations were found between relative humidity and wind speed with ZCL occurrence. A large number of cases were recorded in areas with altitude ranging from 800 to 2000 m.a.s.l. and spatial precipitation from 15 to 150 mm. The statistical analysis showed a strong association between water storage volume and water irrigation with the annual ZCL occurrence recorded in the downstream area (Zagora province). The results will lead us to understand ZCL risk areas for effective control. Further work is needed mainly for gathering these variables in one single and simplest model.

Antidiabetic plants improving insulin sensitivity.

BACKGROUND: Globally, the prevalence of diabetes mellitus is increasing at an alarming rate. This chronic pathology gravely troubled the human health and quality of life. Both insulin deficiency and insulin resistance are involved in the pathophysiology of diabetes mellitus. Moreover, insulin resistance is being diagnosed nowadays in a growing population of diabetic and obese patients, especially in industrialized societies. There are lots of conventional agents available to control and to treat diabetes, but total recovery from this disorder has not been reported up to this date. Plants provided a potential source of hypoglycemic drugs and are widely used in several traditional systems of medicine to prevent diabetes. A few reviews with less attention paid to mechanisms of action have been published on antidiabetic plants. OBJECTIVES: The present review focuses on the various plants that have been reported to be effective in improving insulin sensitivity associated with diabetes. KEY FINDINGS: In this work, an updated systematic review of the published literature has been conducted to review the antidiabetic plants improving insulin sensitivity and 111 medicinal plants have been reported to have a beneficial effect on insulin sensitivity using several in-vitro and in-vivo animal models of diabetes. CONCLUSION: The different metabolic and cellular effects of the antidiabetic plants improving insulin sensitivity are reported indicating the important role of medicinal plants as potential alternative or complementary use in controlling insulin resistance associated with diabetes mellitus.