Antifungal Mechanism of Ruta graveolens Essential Oil: A Colombian Traditional Alternative against Anthracnose Caused by Colletotrichum gloeosporioides.

Here, we report for the first time on the mechanisms of action of the essential oil of Ruta graveolens (REO) against the plant pathogen Colletotrichum gloeosporioides. In particular, the presence of REO drastically affected the morphology of hyphae by inducing changes in the cytoplasmic membrane, such as depolarization and changes in the fatty acid profile where straight-chain fatty acids (SCFAs) increased by up to 92.1%. In addition, REO induced changes in fungal metabolism and triggered apoptosis-like responses to cell death, such as DNA fragmentation and the accumulation of reactive oxygen species (ROS). The production of essential enzymes involved in fungal metabolism, such as acid phosphatase, ß-galactosidase, ß-glucosidase, and N-acetyl-ß-glucosaminidase, was significantly reduced in the presence of REO. In addition, C. gloeosporioides activated naphthol-As-BI phosphohydrolase as a mechanism of response to REO stress. The data obtained here have shown that the essential oil of Ruta graveolens has a strong antifungal effect on C. gloeosporioides. Therefore, it has the potential to be used as a surface disinfectant and as a viable replacement for fungicides commonly used to treat anthracnose in the postharvest testing phase.

Chemical Composition, Antioxidant, and Antibacterial Activity of Ruta chalepensis L. Ethanolic Extract.

Ruta chalepensis L. is a versatile herb used in culinary arts and traditional medicine. The study aimed to determine the chemical composition of an ethanolic extract from R. chalepensis and the total phenolic and flavonoid content. Additionally, the extracts' antimicrobial and antioxidant activities were tested. The disc diffusion method and minimum inhibitory concentration (MIC) were used to test the antibacterial properties on four types of bacteria: Escherichia coli, Proteus penneri, Bacillus cereus, and Staphylococcus aureus. A colorimetric assay was used to evaluate the total phenolic and flavonoid content, and the DPPH method was used to assess the antioxidant activity. The phytochemical constituents were determined using LC-MS/MS. The results indicated that R. chalepensis ethanolic extract had 34 compounds, and the predominant compounds were quercetin (9.2 %), myricetin (8.8 %), and camphene (8.0 %). Moreover, the extract had a good level of polyphenols and flavonoids, as demonstrated by inhibiting free radicals (DPPH) (IC50 was 41.2±0.1). Also, the extract exhibited robust antimicrobial activity against P. penneri and S. aureus with an MIC of 12.5 and 25.0 µg/mL, respectively. In conclusion, the results suggest that the R. chalepensis ethanolic extract has good antioxidant and antibacterial properties that could be utilized to develop new antibacterial agents.

Studies on the Accumulation of Secondary Metabolites and Evaluation of Biological Activity of In Vitro Cultures of Ruta montana L. in Temporary Immersion Bioreactors.

The present work focuses on in vitro cultures of Ruta montana L. in temporary immersion PlantformTM bioreactors. The main aim of the study was to evaluate the effects of cultivation time (5 and 6 weeks) and different concentrations (0.1-1.0 mg/L) of plant growth and development regulators (NAA and BAP) on the increase in biomass and the accumulation of secondary metabolites. Consequently, the antioxidant, antibacterial, and antibiofilm potentials of methanol extracts obtained from the in vitro-cultured biomass of R. montana were evaluated. High-performance liquid chromatography analysis was performed to characterize furanocoumarins, furoquinoline alkaloids, phenolic acids, and catechins. The major secondary metabolites in R. montana cultures were coumarins (maximum total content of 1824.3 mg/100 g DM), and the dominant compounds among them were xanthotoxin and bergapten. The maximum content of alkaloids was 561.7 mg/100 g DM. Concerning the antioxidant activity, the extract obtained from the biomass grown on the 0.1/0.1 LS medium variant, with an IC50 0.90 ± 0.03 mg/mL, showed the best chelating ability among the extracts, while the 0.1/0.1 and 0.5/1.0 LS media variants showed the best antibacterial (MIC range 125-500 µg/mL) and antibiofilm activity against resistant Staphylococcus aureus strains.

(+)-/(-)-Rutabenzofuran A and (+)-/(-)- Rutabenzofuran B: Two unprecedented pairs of Z/E isomeric benzofuran enantiomers from the aerial part of Ruta graveolens L.

Two pairs of Z/E isomeric benzofuran enantiomers possessing unprecedented carbon skeletons featuring ring cleavage and addition reactions in the α-pyrone ring of furocoumarin, named rutabenzofuran A [(+)-1 and (-)-1], and rutabenzofuran B [(+)-2 and (-)-2], respectively, were isolated as minor compounds from the water extract of the aerial part of Ruta graveolens L. Their structures were determined by extensive spectroscopic data analysis. The absolute configurations were assigned by comparing the optical rotation with previous research and the experimental circular dichroism (CD) spectra with the calculated electronic CD (ECD) spectra. (-)-1, (+)-2, and (-)-2 were evaluated for antibacterial, anticoagulant, anticancer, and acetylcholinesterase (AChE) inhibitory activities. No anticancer or anticoagulant activities were observed, yet (-)-2 exhibited weak antibacterial activity against Salmonella enterica subsp. Enterica. At the same time, (-)-1, (+)-2, and (-)-2 displayed weak inhibitory activity on AChE.

Headspace Solid Phase Micro-Extraction of Volatile Constituents Produced from Saudi Ruta chalepensis and Molecular Docking Study of Potential Antioxidant Activity.

Ruta chalepensis L., commonly known as Shazab in Saudi Arabia, is one of the famous culinary plants belonging to the Rutaceae family. It is commonly used in ethnomedicine in treating numerous diseases. This study was performed to characterize the essential oil isolated from Saudi species using a relatively new advanced headspace solid-phase microextraction technique. Following that, the antioxidant activity of the extracted oil was assessed using in vitro techniques such as the DPPH and nitric oxide scavenging tests, as well as the reducing power FRAP study and the molecular docking tool. The essential oil yield of the dried plant was 0.83% (v/w). Gas chromatography joined with a mass spectrometer was used to determine the chemical composition of the pale-yellow essential oil. Sixty-eight constituents were detected, representing 97.70% of the total oil content. The major constituents were aliphatic ketones dominated by 2-undecanone (37.30%) and 2-nonanone (20.00%), with minor constituents of mono and sesquiterpenoids chemical classes. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is one of the major causes of many contemporary diseases due to its ability to create a reactive oxygen species (ROS). Thus, molecular docking was used to confirm that some oil phytoconstituents have good docking scores compared to the standard antioxidant drug (Vitamin C), indicating great binding compatibility between the (NADPH) oxidase receptor site and the ligand. In conclusion, our findings suggest that the oil could be used safely and as a cost-effective remedy in treating various modern diseases caused by free radical formation.

Potential Protective Effects of Ruta Chalepensis L. Extracts Against Gentamicin-Induced Nephrotoxicity via Reduction on Apoptotic, DNA Damage and Oxidative Stress Markers in Mice.

In this study, the protective effects of Ruta chalepensis L. extracts on the extent of tissue damage in gentamicin-induced nephrotoxicity have been investigated. Ruta chalepensis L. extracts were prepared by subcritical water and ultrasound-assisted organic solvent extraction methods. Protective activity of Ruta chalepensis L. extracts on Gentamicin-induced nephrotoxicity is investigated by apoptotic, DNA damage, oxidative stress markers and evaluating histopathological in kidney tissue of mice. Gentamicin significantly increased Caspase-3 and -8 activities, NO levels, serum creatinine and BUN, while 8-OHdG and MDA levels were significantly decreased with Ruta chalepensis L. extract treatment. In addition, Ruta chalepensis L. extracts treatment significantly increased CAT and SOD activities. Histopathological alterations in Gentamicin group were significantly diminished by application of Ruta chalepensis L. extracts. These results suggest that treatment with Ruta chalepensis L. extracts may ameliorate renal dysfunction and structural damage through the reduction of oxidative stress and apoptosis in the kidney.

Antifungal, Repellency, and Insecticidal Activities of Cymbopogon distans and Ruta graveolens Essential Oils and Their Main Chemical Constituents.

Essential oils produced by Cymbopogon distans and Ruta graveolens with a similar Chinese name could be explained as book fragrance in the Chinese idiom 'shu xiang men di', namely, a wealthy intellectual family according to ancient Chinese. Therefore, volatile oils from these two plants and their main compounds were tested to explore their antifungal, repellent, and insecticide actions. In this study, the essential olis (EO) of C. distans exhibited significant antifungal activity against Rhizopus stolonifera (97 %), Mucor racemosus (97 %), and Trichoderma viride (84 %); its main compounds exhibit interesting activity, such as methyleugenol (87 %) and elemicine (85 %) against T. viride and butyl hydroxytoluene against M. racemosus (90 %) and R. stolonifera (95 %). The EO of R. graveolens and other major chemical constituents showed weak inhibitory effects against other fungi (Aspergillus flavus and Fusarium oxysporum). Then, EO (C. distans and R. graveolens) and its main compounds exhibited obvious repellent activity (more than 85 %) at a concentration of 16 nL/cm2 , which was consistent with the repellency of the positive control (DEET). In terms of insecticidal activity, the mortality of C. distans volatile oil against R. padi (56.4 %) was lower than that of R. graveolens volatile oil (92.4 %), and all compounds showed weak lethal effects. These results provide a natural substance for controlling fungi and insects when storing books and that can be used as a biological pesticide for industrial production. Through our study, the book fragrance in the Chinese idiom 'shu xiang men di' was speculated to be the EO odor of C. distans.

Phenolic Content and in Vitro Antioxidant, Anti-Inflammatory and antimicrobial Evaluation of Algerian Ruta graveolens L.

Plants constitute a valuable source of natural antioxidants such as polyphenols and are responsible for exhibiting many biologically significant functions. Ruta species including Ruta chalepensis L. and Ruta graveolens L. are widespread species in Algeria and are used as medicinal plants to treat various diseases; however, so far, most of the conducted studies focused on analyzing alkaloids and essential oils mostly on R. chalepensis. The aim of the present research is to investigate the phenolic profile of the aerial parts of Ruta graveolens L. from Algeria and assess its in vitro antioxidant, anti-inflammatory and antimicrobial properties. The total polyphenols and flavonoids were assessed using colorimetric methods, and the individual polyphenols were identified and quantified using HPLC-DAD-ESI-MS. The antioxidant activity was evaluated with DPPH and ß-carotene tests, and the anti-inflammatory activity with inhibition of bovine serum albumin denaturation and HRBC membrane stabilization methods. The results showed that Ruta graveolens extract is rich in phenolic compounds with a total phenol and flavonoid contents of 41.63±0.394 mg GAE/gE and 13.97±0.33 mg EQ/gE, respectively. Nine phenolic compounds were determined, including three phenolic acids and six flavonoids. Rutin was the major phenolic compound in Ruta graveolens (464.95 µg/g), followed by syringic acid (179.74 µg/g), and naringenin (109.78 µg/g). R. graveolens phenolic extract also showed good antioxidant activity with values of 0.77 mM TE/g DW and 0.37 mM ß-CE/g DW with DPPH and ß-carotene tests, respectively. For the anti-inflammatory activity, the highest tested concentration (200 µg/mL) gave 50.61 % of inhibition of the denaturation of albumin and 44.12 % of membrane stabilization. With regards to antimicrobial results, Staphylococcus aureus was the most sensitive bacteria with an inhibition zone of 14.37 mm and MIC value of 0.625 mg/mL, followed by Listeria monocytogenes (11.75 mm and MIC=1.25 mg/mL), and Escherichia coli (10.25 mm and MIC=1.25 mg/mL).

Ruta graveolens, Peganum harmala, and Citrullus colocynthis methanolic extracts have in vitro protoscolocidal effects and act against bacteria isolated from echinococcal hydatid cyst fluid.

Echinococcosis is a common and endemic disease that affects both humans and animals. In this study, the in vitro activities of methanolic extracts of Ruta graveolens, Peganum harmala aerial parts, and Citrullus colocynthis seeds against protoscolosis and isolated bacterial strains from hydatid cysts were assessed using disc diffusion methods and Minimum Inhibitory Concentration (MIC). The chemical composition of three methanolic extracts was studied using LC-MS. After 3 h of exposure to 40 mg/mL R. graveolens extract, a tenfold protoscolocidal effect was seen when compared to the convintional medication (ABZ) for the same duration (P < 0.05). The bacteria listed below were isolated from hydatid cyst fluid collected from a variety of sick locations, including the lung and liver. Micrococcus spp., E. coli, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter amnigenus, Pseudomonas aeruginosa, Staphylococcus xylosus, and Achromobacter xylosoxidans are among the bacteria that have been identified. The most effective extract was R. graveolens, followed by P. harmala and C. colocynthis, according to the results of antibacterial activity using the disc diffusion method. R. graveolens extract had the lowest MIC values (less than 2 mg/mL) against all microorganisms tested. This shows that the R. graveolens extract has additional properties, such as the ability to be both scolocidal and bactericidal. Because these bacteria are among the most prevalent pathogenic bacteria that increase the risk of secondary infection during hydatid cysts, the results of inhibitory zones and MICs of the R. graveolens methanol extract are considered highly promising.

Chemical constituents of Ruta graveolens L. and their melanogenic effects and action mechanism.

Ruta graveolens L. has been widely used to treat various skin ailments, especially vitiligo. In this study, we isolated a new furanocoumarin named Rutagrarin (1) along with 14 known compounds (2-15) from the aerial parts of R. graveolens and elucidated their chemical structures via various spectroscopy. We found that compound 5 promoted melanogenesis and tyrosinase activity in B16 cells. Further investigation on underlying mechanisms revealed that compound 5 activated the transcription of microtia-related transcription factors and promoted the production of melanin in B16 cells via the Akt/GSK-3ß/ß-catenin pathway. Therefore, we confirmed the traditional efficacy of R. graveolens and speculated that compound 5 could be used as a natural drug to treat vitiligo.

Ruta Essential Oils: Composition and Bioactivities.

Ruta L. is a typical genus of the citrus family, Rutaceae Juss. and comprises ca. 40 different species, mainly distributed in the Mediterranean region. Ruta species have long been used in traditional medicines as an abortifacient and emmenagogue and for the treatment of lung diseases and microbial infections. The genus Ruta is rich in essential oils, which predominantly contain aliphatic ketones, e.g., 2-undecanone and 2-nonanone, but lack any significant amounts of terpenes. Three Ruta species, Ruta chalepensis L., Ruta graveolens L., and Ruta montana L., have been extensively studied for the composition of their essential oils and several bioactivities, revealing their potential medicinal and agrochemical applications. This review provides a systematic evaluation and critical appraisal of publications available in the literature on the composition and bioactivities of the essential oils obtained from Ruta species and includes a brief outlook of the potential applications of nanotechnology and chitosan-based products of Ruta essential oils.

Phytochemical and antioxidant analysis of medicinal and food plants towards bioactive food and pharmaceutical resources.

Plants with medicinal properties play an increasingly important role in food and pharmaceutical industries for their functions on disease prevention and treatment. This study characterizes the phenolic composition and antioxidant activity of seven medicinal and food plants, including the leaves of Salvia officinalis L., Rosmarinus officinalis L., Olea europaea L., and Punica granatum L., as well as the leaves and young stems of Ruta graveolens L., Mentha piperita L., and Petroselinum crispum, Mill., by using colorimetric, chromatographic, and spectrophotometric assays. Results revealed that the hydro-methanolic leaf extracts of P. granatum (pomegranate) displayed the highest content of total phenols (199.26 mg gallic acid per gram of plant dry weight), ortho-diphenols (391.76 mg gallic acid per gram of plant dry weight), and tannins (99.20 mg epicatechin per gram of plant dry weight), besides a higher content of flavonoids (24 mg catechin per gram of plant dry weight). The highest antioxidant capacity measured by ABTS, DPPH, and FRAP (2.14, 2.27, and 2.33 mM Trolox per gram of plant dry weight, respectively) methods was also obtained in pomegranate leaf extracts, being 4-200 times higher than the other species. Such potent antioxidant activity of pomegranate leaves can be ascribed to the presence of different types of phenolic compounds and the high content in tannins, whilst phenolic acids and flavonoids were found to be the dominant phenolic classes of the other six plants. Consequently, despite the well-known antioxidant properties of these plant species, our study suggests pomegranate leaf can stand out as a relatively more valuable plant source of natural bioactive molecules for developing novel functional food-pharma ingredients, with potential for not only promoting human health but also improving bio-valorization and environment.

Chalepin and Chalepensin: Occurrence, Biosynthesis and Therapeutic Potential.

Dihydrofuranocoumarin, chalepin (1) and furanocoumarin, chalepensin (2) are 3-prenylated bioactive coumarins, first isolated from the well-known medicinal plant Ruta chalepensis L. (Fam: Rutaceae) but also distributed in various species of the genera Boenminghausenia, Clausena and Ruta. The distribution of these compounds appears to be restricted to the plants of the family Rutaceae. To date, there have been a considerable number of bioactivity studies performed on coumarins 1 and 2, which include their anticancer, antidiabetic, antifertility, antimicrobial, antiplatelet aggregation, antiprotozoal, antiviral and calcium antagonistic properties. This review article presents a critical appraisal of publications on bioactivity of these 3-prenylated coumarins in the light of their feasibility as novel therapeutic agents and investigate their natural distribution in the plant kingdom, as well as a plausible biosynthetic route.

Anti-MRSA Constituents from Ruta chalepensis (Rutaceae) Grown in Iraq, and In Silico Studies on Two of Most Active Compounds, Chalepensin and 6-Hydroxy-rutin 3',7-Dimethyl ether.

Ruta chalepensis L. (Rutaceae), a perennial herb with wild and cultivated habitats, is well known for its traditional uses as an anti-inflammatory, analgesic, antipyretic agent, and in the treatment of rheumatism, nerve diseases, neuralgia, dropsy, convulsions and mental disorders. The antimicrobial activities of the crude extracts from the fruits, leaves, stem and roots of R. chalepensis were initially evaluated against two Gram-positive and two Gram-negative bacterial strains and a strain of the fungus Candida albicans. Phytochemical investigation afforded 19 compounds, including alkaloids, coumarins, flavonoid glycosides, a cinnamic acid derivative and a long-chain alkane. These compounds were tested against a panel of methicillin-resistant Staphylococcus aureus (MRSA) strains, i.e., ATCC 25923, SA-1199B, XU212, MRSA-274819 and EMRSA-15. The MIC values of the active compounds, chalepin (9), chalepensin (10), rutamarin (11), rutin 3'-methyl ether (14), rutin 7,4'-dimethyl ether (15), 6-hydroxy-rutin 3',7-dimethyl ether (16) and arborinine (18) were in the range of 32-128 µg/mL against the tested MRSA strains. Compounds 10 and 16 were the most active compounds from R. chalepensis, and were active against four out of six tested MRSA strains, and in silico studies were performed on these compounds. The anti-MRSA activity of compound 16 was comparable to that of the positive control norfloxacin (MICs 32 vs 16 µg/mL, respectively) against the MRSA strain XU212, which is a Kuwaiti hospital isolate that possesses the TetK tetracycline efflux pump. This is the first report on the anti-MRSA property of compounds isolated from R. chalepensis and relevant in silico studies on the most active compounds.

Packham's Triumph Pears (Pyrus communis L.) Post-Harvest Treatment during Cold Storage Based on Chitosan and Rue Essential Oil.

Pears (Pyrus communis L.) cv. Packham's Triumph are very traditional for human consumption, but pear is a highly perishable climacteric fruit with a short shelf-life affected by several diseases with a microbial origin. In this study, a protective effect on the quality properties of pears was evidenced after the surface application of chitosan-Ruta graveolens essential oil coatings (CS + RGEO) in four different concentrations (0, 0.5, 1.0 and 1.5 %, v/v) during 21 days of storage under 18 °C. After 21 days of treatment, a weight loss reduction of 10% (from 40.2 ± 5.3 to 20.3 ± 3.9) compared to the uncoated pears was evident with CS + RGEO 0.5%. All the fruits' physical-chemical properties evidenced a protective effect of the coatings. The maturity index increased for all the treatments. However, the pears with CS + RGEO 1.5% were lower (70.21) than the uncoated fruits (98.96). The loss of firmness for the uncoated samples was higher compared to the coated samples. The pears' most excellent mechanical resistance was obtained with CS + RGEO 0.5% after 21 days of storage, both for compression resistance (7.42 kPa) and force (22.7 N). Microbiological studies demonstrated the protective power of the coatings. Aerobic mesophilic bacteria and molds were significantly reduced (in 3 Log CFU/g compared to control) using 15 µL/mL of RGEO, without affecting consumer perception. The results presented in this study showed that CS + RGEO coatings are promising in the post-harvest treatment of pears.

Pharmacological and toxicological effects of Ruta chalepensis L. on experimentally induced seizures and electroencephalographic spectral power in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Ruta chalepensis L. (Rutaceae) is used in traditional medicine to treat a wide variety of disorders such as rheumatism, fever, mental disorders, dropsy, neuralgia, menstrual problems, anxiety, and epilepsy. AIM OF THE STUDY: To evaluate and compare the anticonvulsant properties of an aqueous extract and ethyl acetate (AcOEt) fraction of R. chalepensis on pentylenetetrazole (PTZ)-induced seizures and maximal electroshock (MES) test in mice, by analyzing behavior and electroencephalogram (EEG), as well as GABAA receptors involvement. METHODS: The effect of an acute administration of different dosage of the aqueous extract (300 or 500 mg/kg) or AcOEt fraction (100, 300, 500 or 1000 mg/kg) of R. chalepensis was explored on two different models of acute seizure induction in mice, the PTZ and maximal electroshock (MES) tests. Behavioral and electrographic effects were quantified. Additionally, the possible involvement of the GABAA receptors was explored in the presence of picrotoxin (a non-competitive antagonist of the GABAA receptor). RESULTS: AcOEt fraction of R. chalepensis was more efficient than aqueous extract to reduce the incidence of tonic-clonic seizures and mortality in a significant and dose-dependent manner in both the PTZ and MES tests. This anticonvulsant effect was not abolished in the presence of picrotoxin. The EEG spectral power analysis revealed that aqueous extract decreased alpha and beta power, while AcOEt fraction decreased alpha and gamma power confirming previous findings of its depressant effect in the central nervous system. It is important to mention that the highest dosage of the AcOEt (1000 mg/kg) produced a severe suppression or isoelectric EEG activity (EEG flattening), recognized as a comatose state, suggesting a neurotoxic effect at this dosage. CONCLUSION: Our data reinforce that depressant and anticonvulsant effects of R. chalepensis depend in part on the presence of constituents from medium polarity. We also found that anticonvulsant effect is not mediated by GABAA receptors. In addition, cautious is emphasized when high doses of this natural product are used in traditional medicine since it might produce neurotoxic effects.

Synergistic Effect of Biosynthesized Silver Nanoparticles and Natural Phenolic Compounds against Drug-Resistant Fish Pathogens and Their Cytotoxicity: An In Vitro Study.

Fish pathogens causing disease outbreaks represent a major threat to aquaculture industry and food security. The aim of the presented study is to develop safe and effective bioactive agents against two bacterial isolates: Aeromonas hydrophila and Pseudomonas fluorescens. We employed a broth microdilution method to investigate the antibacterial effect of biosynthesized silver nanoparticles (AgNPs); rutin, a natural flavonoid extracted from Ruta graveneoles; and heliomycin, a secondary metabolite produced by marine actinomycetes AB5, as monotherapeutic agents. Moreover, AgNPs in combination with rutin (AgNP + R) and heliomycin (AgNPs + H) were examined for their synergistic effect. The cytotoxic effect of individual bioactive compounds and in combination with AgNPs was investigated on epithelioma papulosum cyprini (EPC) fish cell lines. Individual treatment of AgNPs, rutin, and heliomycin exhibited a dose-dependent antimicrobial activity against A. hydrophila and P. fluorescens. Rutin minimum inhibitory concentration (MIC) showed the lowest cytotoxicity when tested on EPC cell lines, while heliomycin MIC was highly cytotoxic. Combined subtherapeutic doses of AgNPs + R and AgNPs + H displayed additive and synergistic effects against A. hydrophila and P. fluorescens, respectively, with improved results and relative safety profile. The study findings demonstrate that a combination of AgNPs and natural bioactive compounds may represent novel therapeutics fighting fish pathogens potentially affecting the fish farming industry.

Rutamarin: Efficient Liquid-Liquid Chromatographic Isolation from Ruta graveolens L. and Evaluation of Its In Vitro and In Silico MAO-B Inhibitory Activity.

Naturally occurring coumarins are a group of compounds with many documented central nervous system (CNS) activities. However, dihydrofuranocoumarins have been infrequently investigated for their bioactivities at CNS level. Within the frame of this study, an efficient liquid-liquid chromatography method was developed to rapidly isolate rutamarin from Ruta graveolens L. (Rutaceae) dichloromethane extract (DCM). The crude DCM (9.78 mg/mL) and rutamarin (6.17 M) were found to be effective inhibitors of human monoamine oxidase B (hMAO-B) with inhibition percentages of 89.98% and 95.26%, respectively. The inhibitory activity against human monoamine oxidase A (hMAO-A) for the DCM extract was almost the same (88.22%). However, for rutamarin, it significantly dropped to 25.15%. To examine the molecular interaction of rutamarin with hMAO- B, an in silico evaluation was implemented. A docking study was performed for the two enantiomers (R)-rutamarin and (S)-rutamarin. The (S)-rutamarin was found to bind stronger to the hMAO-B binging cavity.

Genus Ruta: A natural source of high value products with biological and pharmacological properties.

ETHNOPHARMACOLOGICAL RELEVANCE: Ruta genus is constituted by ten species, of which the most commonly described are R. chalepensis and R. graveolens. Ruta plants are perennial shrubs belonging to the family Rutaceae, which are traditionally used in folk medicine, since ancient times mostly for the treatment of various ailments of the womb. AIM OF THE STUDY: To provide a review of the different uses of Ruta species in traditional medicine, as well as, on their multifactorial biological and pharmacological properties. MATERIAL AND METHODS: A search of the literature on genus Ruta and Ruta species was performed using various scientific databases and search engines and the information of articles were reviewed and compiled. RESULTS: Different parts of the plants belonging to Ruta genus are used in folk medicine to treat a wide range of different diseases. The principal use of these is in gynaecological field, but the treatment of pain, fever, nausea, inflammation, infections, nervous disorders, among others, are also described. These plants have been used to fertility regulation, as anti-fertility agent, to control menstrual flux and bleedings, as abortifacient and as contraceptive. The phytochemical composition of these plants consists mainly in essential oil (EO), but phenolic compounds were also reported, like coumarins and flavonoids, as well as alkaloids. Ruta species products like extracts and EOs have shown broad pharmacological activities, such as antimicrobial and antifungal activities, as well as, antiviral and antiparasitic. Moreover, Ruta plants products present antioxidant, neuroprotective, anti-inflammatory, anti-cancer and anti-diabetic activities and demonstrated contraceptive and abortifacient effects. These plants were also tested to be used for non-therapeutic approaches, as bio-insecticides in the control of different insect pests showing to be able to reduce infestation. CONCLUSIONS: Ruta species could be a potential source of natural products with biological activities. Ruta extracts, essential oils and isolated compounds have shown a diverse potential for use in the treatment of different diseases, as well as, for pests control, contributing to the valorisation of these plants. Nonetheless, this review indicates that more studies are needed to demonstrate the full potential of Ruta species, and to further explore the toxicology and safety of these plants.

Synthesis, Characterization, and Histological Evaluation of Chitosan-Ruta Graveolens Essential Oil Films.

The development of new biocompatible materials for application in the replacement of deteriorated tissues (due to accidents and diseases) has gained a lot of attention due to the high demand around the world. Tissue engineering offers multiple options from biocompatible materials with easy resorption. Chitosan (CS) is a biopolymer derived from chitin, the second most abundant polysaccharide in nature, which has been highly used for cell regeneration applications. In this work, CS films and Ruta graveolens essential oil (RGEO) were incorporated to obtain porous and resorbable materials, which did not generate allergic reactions. An oil-free formulation (F1: CS) and three different formulations containing R. graveolens essential oil were prepared (F2: CS-RGEO 0.5%; F3: CS+RGEO 1.0%; and F4: CS+RGEO 1.5%) to evaluate the effect of the RGEO incorporation in the mechanical and thermal stability of the films. Infrared spectroscopy (FTIR) analyses demonstrated the presence of RGEO. In contrast, X-ray diffraction (XRD) and differential scanning calorimetry (DSC) analysis showed that the crystalline structure and percentage of CS were slightly affected by the RGEO incorporation. Interesting saturation phenomena were observed for mechanical and water permeability tests when RGEO was incorporated at higher than 0.5% (v/v). The results of subdermal implantation after 30 days in Wistar rats showed that increasing the amount of RGEO resulted in greater resorption of the material, but also more significant inflammation of the tissue surrounding the materials. On the other hand, the thermal analysis showed that the RGEO incorporation almost did not affect thermal degradation. However, mechanical properties demonstrated an understandable loss of tensile strength and Young's modulus for F3 and F4. However, given the volatility of the RGEO, it was possible to generate a slightly porous structure, as can be seen in the microstructure analysis of the surface and the cross-section of the films. The cytotoxicity analysis of the CS+RGEO compositions by the hemolysis technique agreed with in vivo results of the low toxicity observed. All these results demonstrate that films including crude essential oil have great application potential in the biomedical field.