Browsing by Author "Kharbach, Mourad"
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Item Bioassay-guided isolation of anti-inflammatory and antinociceptive metabolites among three Moroccan Juniperus leaves extract supported with in vitro enzyme inhibitory assays(Elsevier Ireland Ltd, 2024-05) El Jemli, Meryem; Ezzat, Shahira M; Kharbach, Mourad; Mostafa, Eman Sherien; Radwan, Rasha Ali; El Jemli, Yousra; El-Guourrami, Otman; Ahid, Samir; Cherrah, Yahia; Zayed, Ahmed; Alaoui, KatimEthnopharmacological relevance: Herbs of the genus Juniperus (family Cupressaceae) have been commonly used in ancestral folk medicine known as “Al’Araar” for treatment of rheumatism, diabetes, inflammation, pain, and fever. Bioassay-guided isolation of bioactives from medicinal plants is recognized as a potential approach for the discovery of novel drug candidates. In particular, non-addictive painkillers are of special interest among herbal phytochemicals. Aim of the study: The current study aimed to assess the safety of J. thurifera, J. phoenicea, and J. oxycedrus aqueous extracts in oral treatments; validating the traditionally reported anti-inflammatory and analgesic effects. Further phytochemical investigations, especially for the most bioactive species, may lead to isolation of bioactive metabolites responsible for such bioactivities supported with in vitro enzyme inhibition assays. Materials and methods: Firstly, the acute toxicity study was investigated following the OECD Guidelines. Then, the antinociceptive, and anti-inflammatory bioactivities were evaluated based on chemical and mechanical trauma assays and investigated their underlying mechanisms. The most active J. thurifera n-butanol fraction was subjected to chromatographic studies for isolating the major anti-inflammatory metabolites. Moreover, several enzymatic inhibition assays (e.g., 5-lipoxygenase, protease, elastase, collagenase, and tyrosinase) were assessed for the crude extracts and isolated compounds. Results: The results showed that acute oral administration of the extracts (300–500 mg/kg, p. o.) inhibited both mechanically and chemically triggered inflammatory edema in mice (up to 70% in case of J. thurifera) with a dose-dependent antinociceptive (tail flick) and anti-inflammatory pain (formalin assay) activities. This effect was partially mediated by naloxone inhibition of the opioid receptor (2 mg/kg, i. p.). In addition, 3-methoxy gallic acid (1), quercetin (2), kaempferol (3), and ellagic acid (4) were successfully identified being involved most likely in J. thurifera extract bioactivities. Nevertheless, quercetin was found to be the most potent against 5-LOX, tyrosinase, and protease with IC50 of 1.52 ± 0.01, 192.90 ± 6.20, and 399 ± 9.05 μM, respectively. Conclusion: J. thurifera extract with its major metabolites are prospective drug candidates for inflammatory pain supported with inhibition of inflammatory enzymes. Interestingly, antagonism of opioid and non-opioid receptors is potentially involved.Item The food plant Silybum marianum (L.) Gaertn.: Phytochemistry, Ethnopharmacology and clinical evidence(Elsevier Ireland Ltd, 1/30/2020) Marmouzia, Ilias; Bouyahya, Abdelhakim; Ezzat, Shahira M; El Jemli, Meryem; Kharbach, MouradEthnopharmacological relevance: Silybum marianum (L.) Gaertn. or Milk thistle is a medicinal plant native to Northern Africa, Southern Europe, Southern Russia and Anatolia. It also grows in South Australia, North and South America. In traditional knowledge, people have used S. marianum for liver disorders such as hepatitis, liver cirrhosis and gallbladder diseases. The main active compound of the plant seeds is silymarin, which is the most commonly used herbal supplement in the United States for liver problems. Nowadays, S. marianum products are available as capsules, powders, and extracts. Aim of study: The aim of our study is to draw a more comprehensive overview of the traditional heritage, pharmacological benefits and chemical fingerprint of S. marianum extracts and metabolites; as well as their metabolism and bioavailability. Materials and methods: An extensive literature search has been conducted using relavant keywords and papers with rationale methodology and robust data were selected and discussed. Studies involving S. marianum or its main active ingredients with regards to hepatoprotective, antidiabetic, cardiovascular protection, anticancer and antimicrobial activities as well as the clinical trials performed on the plant, were discussed here. Results: S. marianum was subjected to thousands of ethnopharmacological, experimental and clinical investigations. Although, the plant is available for use as a dietary supplement, the FDA did not yet approve its use for cancer therapy. Nowadays, clinical investigations are in progress where a global evidence of its real efficiency is needed. Conclusion: S. marianum is a worldwide used herb with unlimited number of investigations focusing on its benefits and properties, however, little is known about its clinical efficiency. Moreover, few studies have discussed its metabolism, pharmacokinetics and bioavailability, so that all future studies on S. marianum should focus on such areas. © 2020 Elsevier B.V.Item Thymelaea genus: Ethnopharmacology, Chemodiversity, and Bioactivities(Elsevier, 6/14/2021) Marmouzi, Ilias; Bouchmaa, Najat; Kharbach, Mourad; Ezzat, Shahira M; Merghany, Rana M; Berkiksh, Inssaf; El Jemli, MeryemThymelaea (F. Thymelaeaceae) is a large genus comprising around 30 species of evergreen and flowering plants. Most of them are native to the Mediterranean area. Despite its interesting chemical diversity and potent activities, there is still a lack of information about the characterization of its chemistry and mecha- nisms of action. This review aims to highlight the chemical and biological profiles of different Thymelaea spe- cies along with their Ethnopharmacology. In general, Thymelaea species possess potent anti-inflammatory, neuroprotective, antidiabetic, antihypertensive, and antioxidant activities. The pharmacology of the different plants is due to their remarkable active ingredients that vary from daphnane diterpenes, lignans, flavonoids, and phenolic acids to volatile oils. From ethnopharmacology to preclinical evidence, Thymelaea species dem- onstrated a unique chemical profile with potent bioactivities. However, until now, there is a lack of informa- tion about their toxicological and clinical controlled trials, and so this review may give attention to more clinical trials to be proceeded on Thymelaea species.