Biochemical and toxicity evaluation of Retama sphaerocarpa extracts and in-silico investigation of phenolic compounds as potential inhibitors against HPV16 E6 oncoprotein.

Cervical cancer is a type of cancer which affects the cervix cells. The conventional treatments for cervical cancer including surgery, chemotherapy, and radiotherapy are only effective in premature stages and less effective in late stages of this tumor. Therefore, the therapeutic strategies based on biologically active substances from plants are needed to develop for the treatment of cervical cancer. The aim of the present study was to assess in vivo toxicity, hematological and biochemical blood parameters in Wistar rats fed Retama sphaerocarpa aqueous leaf extract (RS-AE), as well as to perform in silico molecular docking studies and dynamic simulation of phenolic compounds against HPV16 oncoprotein E6 in order to identify potential inhibitors. RS-AE was found not to induce acute or sub-acute oral toxicity or significant alterations in hematological and biochemical blood parameters in Wistar rats. A total of 11 phenolic compounds were identified in RS-AE, including dihydrodaidzein glucuronide, chrysoperiol pentoside, genistin and vitexin, which turned out to have the highest binding affinity to HPV16 oncoprotein E6. Based on these results, these RS-AE phenolic compounds could be used as natural drugs against the HPV16 E6 oncoprotein.

Phenolic Compound, Antioxidant, Antibacterial, and In Silico Studies of Extracts from the Aerial Parts of Lactuca saligna L.

Medicinal plants are considered a major source for discovering novel effective drugs. To our knowledge, no studies have reported the chemical composition and biological activities of Moroccan Lactuca saligna extracts. In this context, this study aims to characterize the polyphenolic compounds distributed in hydro-methanolic extracts of L. saligna and evaluate their antioxidant and antibacterial activities; in addition, in silico analysis based on molecular docking and ADMET was performed to predict the antibacterial activity of the identified phenolic compounds. Our results showed the identification of 29 among 30 detected phenolic compounds with an abundance of dicaffeoyltartaric acid, luteolin 7-glucoronide, 3,5-di-O-caffeoylquinic acid, and 5-caffeoylquinic acid with 472.77, 224.30, 196.79, and 171.74 mg/kg of dried extract, respectively. Additionally, antioxidant activity assessed by DPPH scavenging activity, ferric reducing antioxidant power (FRAP) assay, and ferrous ion-chelating (FIC) assay showed interesting antioxidant activity. Moreover, the results showed remarkable antibacterial activity against Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus, and Listeria monocytogenes with minimum inhibitory concentrations between 1.30 ± 0.31 and 10.41 ± 0.23 mg/mL. Furthermore, in silico analysis identified three compounds, including Apigenin 7-O-glucuronide, Quercetin-3-O-glucuronide, and 3-p-Coumaroylquinic acid as potent candidates for developing new antibacterial agents with acceptable pharmacokinetic properties. Hence, L. saligna can be considered a source of phytochemical compounds with remarkable activities, while further in vitro and in vivo studies are required to explore the main biological activities of this plant.

Phytochemical profile, in vivo anti-inflammatory and wound healing activities of the aqueous extract from aerial parts of Cistus ladanifer L.

Cistus ladanifer L. is a Mediterranean shrub, well recognized for its many pharmacological properties. The present study aimed to investigate the phytochemical profile, the in vivo anti-inflammatory and the wound healing activities of the aqueous extract from its aerial parts (AECL). The in vivo anti-inflammatory and the wound healing properties were evaluated by carrageenan-induced paw edema (CAECL) and burn wound in rats, respectively. The results showed that six compounds belonging to flavonoids and tannins were identified in the AECL extract. Moreover, the AECL administrated orally at a dose of 500 mg/kg significantly reduced edema with a percentage of 72 % in terms of inflammation inhibition, using indomethacin as reference drug. On the other hand, when administrated topically, both doses of CAECL cream (5 % and 10 %) manifested a significant anti-inflammatory action using diclofenac as reference drug with a percentage reduction of inflammation that reached 85 % (CAECL-10). As far as wound healing is concerned, the CAECL showed higher effect at a dose of 10 % (CAECL-10) producing a wound contraction of 96 %, similar to that of the reference drug. The findings of the present study indicate that the aqueous extract from aerial parts of Cistus ladanifer L. display strongly anti-inflammatory and wound healing effects to be advantageously used for medical purposes.

Determination of the Phenolic Profile, and Evaluation of Biological Activities of Hydroethanolic Extract from Aerial Parts of Origanum compactum from Morocco.

Origanum compactum belonging to the family Lamiaceae is widely used in food and pharmaceutical fields due to its biologically active substances. We aimed to investigate the total phenol and flavonoid contents and the phenolic composition, and to evaluate the antioxidant and antibacterial properties of hydroethanolic extract from of Origanum compactum. Total phenol and flavonoid contents were evaluated using gallic acid and quercetin as standards, respectively, and the phenolic profile was characterized using high-performance liquid chromatography coupled to a photodiode array and electrospray ionization mass spectrometry (HPLC-PDA-ESI/MS). The antioxidant activity was determined by two methods: ferric reducing power (FRAP) assay and the phosphomolybdate method. The antibacterial effect was evaluated against four bacteria (Escherichia coli, Salmonella typhimurium, Staphylococcus aureus and Listeria monocytogenes) using the broth microdilution method. The findings show that the total phenolic and flavonoid contents were 107.789 ± 5.39 mg GAE/g dm and 14,977 ± 0.79 mg QE/g dm, respectively. A total of sixteen phenolic compounds belonging to phenolic acids and flavonoids were detected. Furthermore, the extract showed strong antioxidant activity, and displayed a bacteriostatic effect against Escherichia coli and Salmonella typhimuriumn, and a bactericidal effect against Staphylococcus aureus and Listeria monocytogenes. Therefore, this study reveals that Origanum compactum extracts display potential as antibacterial and natural antioxidant agents for fighting against pathogenic bacteria and preventing oxidative stress.

Phenolic compounds, in vivo anti-inflammatory, analgesic and antipyretic activities of the aqueous extracts from fresh and dry aerial parts of Brocchia cinerea (Vis.).

Aerial parts of Brocchia cinerea (Vis.) (Asteraceae family) are traditionally used for the treatment of pain, fever and inflammation. The present study aimed to investigate the phenolic profile, the acute oral toxicity, and anti-inflammatory, analgesic and antipyretic activities of the aqueous extracts from fresh (FBC) and dry (DBC) aerial parts of Brocchia cinerea (Vis.). Phenolic profile from FBC and DBC was characterized by HPLC-PDA/ESI-MS. The anti-inflammatory, analgesic and antipyretic of both FBC and DBC were evaluated by carrageenan induced paw edema, acetic acid induced writhing and brewer's yeast-induced pyrexia in Wistar rats, respectively. The results achieved showed that thirteen phenolic compounds were detected in the aqueous extracts obtained from the aerial parts of FBC and DBC, highlighting a quite different quantitative profile. The FBC and DBC administrated orally at a dose of 400 mg/kg significantly reduced edema, after 2 h of the injection of carrageenan (p < 0.001) with a percentage inhibition of 47.73% and 50.01% respectively. On the other hand the rats treated with DBC at the same dose significantly lowered the writhing induced by the injection of acetic acid (18.52 ± 0.38) with respect to the ones treated with FBC (20.47 ± 0.92). Moreover, a significant reduction in rectal temperature was observed in rats treated with FBC/DBC and at doses of 200 and 400 mg/kg. Furthermore, no acute toxicity symptoms were observed on oral administration of all doses of both FBC and DBC in Wistar rats. The results of the present study indicate that the aerial part of Brocchia cinerea extracts exhibit strongly anti-inflammatory, analgesic, and antipyretic properties and they can be potentially used in the treatment of inflammation, pain and fever.

Phenolic Compounds, Antioxidant and Antibacterial Activities of Extracts from Aerial Parts of Thymus zygis subsp. gracilis, Mentha suaveolens and Sideritis incana from Morocco.

Thymus zygis subsp. gracilis, Mentha suaveolens and Sideritis incana (Lamiaceae family) are well recognized for their medicinal, pharmaceutical and aromatic properties. The present study aimed to investigate for the first time the phenolic composition, the antioxidant and antibacterial properties of the extracts obtained from the aerial parts of these species collected from the Ifrane region of Morocco. The phenolic compounds were determined using high-performance liquid chromatography coupled to photodiode array and electrospray ionization mass spectrometry (HPLC-PDA-ESI/MS). The antioxidant activity was investigated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, reducing power and ferrous ion chelating assays. The antibacterial activity was evaluated against three Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa and Salmonella typhimurium) and three Gram-positive bacteria (Staphylococcus aureus, Enterococcus faecalis and Listeria monocytogenes). A total of thirty-three, sixteen and thirteen phenolic compounds were positively identified and characterized in T. zygis subsp. gracilis, M. suaveolens and S. incana extracts, respectively. Among the extracts, M. suaveolens exhibited the highest antioxidant activity, followed by S. incana and T. zygis subsp. gracilis in both DPPH and reducing power assays; all extracts showed the lowest activity in the chelating assay. In addition, all extracts demonstrated a bactericidal effect against Gram-positive bacteria and bacteriostatic effect against Gram-negative bacteria. Therefore, the aerial parts of Moroccan T. zygis subsp. gracilis, M. suaveolens and S. incana might be considered as a valuable source of natural antioxidant and antibacterial agents with potential application in food and pharmaceutical industries.

Flavonoid Composition and Antibacterial Properties of Crocus sativus L. Petal Extracts.

Saffron petals, which are the main by-products of Crocus sativus L. (Iridaceae family), are produced in large quantities and are known for their many beneficial properties. In this regard, this study aims to investigate the phenolic composition and antibacterial properties of hydroethanolic extracts from Crocus sativus L. petals collected from Serghina (province of Boulmane) in Morocco. The phenolic profiles were characterized using high-performance liquid chromatography coupled to a photodiode array and electrospray ionization mass spectrometry (HPLC-PDA-ESI/MS). The antibacterial potential was evaluated against four bacterial strains potentially causing food-borne disease (Staphylococcus aureus, Salmonella typhimurium, Escherichia coli, and Listeria monocytogenes) using disc diffusion and broth micro-dilution assays. Results showed that a total of 27 phenolic compounds was detected in the Crocus sativus L. petal extracts, which were assigned to flavonoids (kaempferol, quercetin, isorhamnetin, and myricetin derivatives). The most abundant compound was represented by kaempferol-sophoroside isomer (20.82 mg/g ± 0.152), followed by kaempferol-sophoroside-hexoside (2.63 mg/g ± 0.001). The hydroethanolic extracts of Crocus sativus L. petals demonstrated bactericidal effects against Staphylococcus aureus and Listeria monocetogenes and bacteriostatic effects against Escherichia coli and Salmonella typhimurium. Therefore, the by-product Crocus sativus L. petal extracts might be considered as valuable sources of natural antibacterial agents with potential applications in the food and pharmaceutical industries.

Salvia officinalis and Lippia triphylla: Chemical characterization and evaluation of antidepressant-like activity.

Salvia officinalis (Lamiaceae) and Lippia triphylla (Verbenaceae) are two plants known for their therapeutic effects in conventional medicine for the treatment of a wide extent of diseases, including the ones on the central nervous system. In the present study, the impact of aqueous extract from the leaves of these two herbs for the treatment of depression was examined. The phytochemical profile highlighted the presence of eighteen and ten polyphenolic compounds in Salvia officinalis and Lippia triphylla, respectively. The antidepressant effects of such extracts were assessed using two tests: the forced swimming test (FST) and tail suspension test (TST) in swiss albino mice. Five mice were partitioned into each group: control (distilled water), standard (Imipramine hydrochloride, 25 mg/kg) and three test ones treated with increased doses of aqueous extracts (250-500-1000 mg/kg), orally administered for two weeks. The acute treatment of the mice with aqueous extracts of Salvia officinalis and Lippia triphylla reduced significantly the time of immobility in the forced swimming test (p < 0.001) as compared to control group, and also decreased significantly the time of immobility of mice in the tail suspension test (p < 0.001). The findings attained in this work show how both plants possess potential anti-depressant-like effects; however, the translation from the results presented in this work to a potential use as therapeutic agents would require the acquisition of a stronger scientific evidence.