Citronellol biosynthesis in pelargonium is a multistep pathway involving progesterone 5ß-reductase and/or iridoid synthase-like enzymes.

Citronellol is a pleasant-smelling compound produced in rose (Rosa spp.) flowers and in the leaves of many aromatic plants, including pelargoniums (Pelargonium spp.). Although geraniol production has been well studied in several plants, citronellol biosynthesis has been documented only in crab-lipped spider orchid (Caladenia plicata) and its mechanism remains open to question in other species. We therefore profiled 10 pelargonium accessions using RNA sequencing and gas chromatography-MS analysis. Three enzymes from the progesterone 5ß-reductase and/or iridoid synthase-like enzymes (PRISE) family were characterized in vitroand subsequently identified as citral reductases (named PhCIRs). Transgenic RNAi lines supported a role for PhCIRs in the biosynthesis of citronellol as well as in the production of mint-scented terpenes. Despite their high amino acid sequence identity, the 3 enzymes showed contrasting stereoselectivity, either producing mainly (S)-citronellal or a racemate of both (R)- and (S)-citronellal. Using site-directed mutagenesis, we identified a single amino acid substitution as being primarily responsible for the enzyme's enantioselectivity. Phylogenetic analysis of pelargonium PRISEs revealed 3 clades and 7 groups of orthologs. PRISEs from different groups exhibited differential affinities toward substrates (citral and progesterone) and cofactors (NADH/NADPH), but most were able to reduce both substrates, prompting hypotheses regarding the evolutionary history of PhCIRs. Our results demonstrate that pelargoniums evolved citronellol biosynthesis independently through a 3-step pathway involving PRISE homologs and both citral and citronellal as intermediates. In addition, these enzymes control the enantiomeric ratio of citronellol thanks to small alterations of the catalytic site.

Bridging fungal resistance and plant growth through constitutive overexpression of Thchit42 gene in Pelargonium graveolens.

KEY MESSAGE: Thchit42 constitutive expression for fungal resistance showed synchronisation with leaf augmentation and transcriptome analysis revealed the Longifolia and Zinc finger RICESLEEPER gene is responsible for plant growth and development. Pelargonium graveolens essential oil possesses significant attributes, known for perfumery and aromatherapy. However, optimal yield and propagation are predominantly hindered by biotic stress. All biotechnological approaches have yet to prove effective in addressing fungal resistance. The current study developed transgenic geranium bridging molecular mechanism of fungal resistance and plant growth by introducing cassette 35S::Thchit42. Furthermore, 120 independently putative transformed explants were regenerated on kanamycin fortified medium. Primarily transgenic lines were demonstrated peak pathogenicity and antifungal activity against formidable Colletotrichum gloeosporioides and Fusarium oxysporum. Additionally, phenotypic analysis revealed ~ 2fold increase in leaf size and ~ 2.1fold enhanced oil content. To elucidate the molecular mechanisms for genotypic cause, de novo transcriptional profiles were analyzed to indicate that the auxin-regulated longifolia gene is accountable for augmentation in leaf size, and zinc finger (ZF) RICESLEEPER attributes growth upregulation. Collectively, data provides valuable insights into unravelling the mechanism of Thchit42-mediated crosstalk between morphological and chemical alteration in transgenic plants. This knowledge might create novel opportunities to cultivate fungal-resistant geranium throughout all seasons to fulfil demand.

UHPLC-ESI-QTOF-MS metabolite profiles of different extracts from Pelargonium endlicherianum parts and their biological properties based on network pharmacological approaches.

In the present study, we aimed to investigate the chemical profiles and biological activities of different extracts (ethyl acetate, dichloromethane, ethanol, and water) of Pelargonium endlicherianum parts (aerial parts and roots). Free radical scavenging, reducing power, phosphomolybdenum, and metal chelating were assayed for antioxidant properties. To detect enzyme inhibitory properties, cholinesterase, amylase, glucosidase, and tyrosinase were chosen as target enzymes. The ethanol extract of the aerial parts contained higher amounts of total bioactive compounds (120.53 mg GAE/g-24.46 mg RE/g). The ethanol and water extracts of these parts were tentatively characterized by UHPLC-ESI-QTOF-MS and 95 compounds were annotated. In addition, the highest acetylcholiesterase (3.74 mg GALAE/g) and butyrylcholinesterase (3.92 mg GALAE/g) abilities were observed by the ethanol extract of roots. The water extract from aerial parts exhibited the most pronounced inhibitory effects on multiple cancer cell lines, especially A549 (IC50: 23.2 µg/mL) and HT-29 (IC50: 27.43 µg/mL) cells. Using network pharmacology, P. endlicherianum compounds were studied against cancer, revealing well-connected targets such as epidermal growth factor receptor (EGFR), phosphoinositide-3-kinase (PI3K), AKT, receptor tyrosine-protein kinase erbB-2, and growth factor receptor bound protein 2 (GRB2) with significant impact on cancer-related pathways. The results could open a new path from natural treasure to functional applications with P. endlicherianum and highlight a new study on other uninvestigated Pelargonium species.

UV-A and UV-B combined with photosynthetically active radiation change plant growth, antioxidant capacity and essential oil composition of Pelargonium graveolens.

BACKGROUND: The different wavelengths of solar radiation incident on earth [herein: Photosynthetically Active Radiation (PAR) , Ultra Violet-A (UV-A) and Ultra Violet-B (UV-B)] and their spectral balance not only have an impact on plants' growth, morphology and physiology, but also are important for the quality and quantity of plant secondary metabolites. MATERIAL AND METHODS: In an outdoor study we addressed the effects of PAR intensity and UV-A and UV-B on the growth, yield, phenolic and flavonoid content, antioxidant activity and essential oil composition of Pelargonium graveolens L'Hér. The experiment was performed with split plots in a randomized complete block design with three replications. During the growth, two PAR intensities (ambient PAR and reduced PAR) and four UV treatments (ambient UV, enhanced UV-A, enhanced UV-B and enhanced UVA + B) were applied. RESULTS: High PAR intensity decreased the length and width of leaf, the height of plant and fresh weight of aerial parts, and increased the dry weight of aerial parts. Enhanced UV-B irradiation was associated with reduced plant height, leaf expansion and fresh and dry weight of aerial parts. Interestingly, the negative effect of UV-B radiation on morphology and growth of plant was largely alleviated by high PAR intensity. The amount of total phenols and flavonoids, antioxidant activity and essential oil production of P. graveolens strongly increased with the increase of UV-B irradiation and PAR. On the other hand, UV-A radiation did not significantly influence total phenol and flavonoid content, antioxidant activity and essential oil composition. Moreover, the combination of high PAR intensity and UV-B led to further increases in total flavonoid content and antioxidant capacity. Both high PAR intensity and enhanced UV-B increased the percentage of geraniol in essential oil, leading to a slight reduction of citronellol/geraniol ratio which is a marker of quality for rose geranium essential oil. CONCLUSIONS: Overall, we conclude that UV-B irradiation was associated to reduction of plant growth and yield, while, the adverse effect of UV-B irradiation on the plant was mitigated by high PAR intensity. On the other hand, both high PAR and enhanced UV-B boosted the production of phenols, flavonoids and essential oil. Considering that the lower citronellol/geraniol ratio is the most important indicator for the economic value of rose geranium essential oil, reducing citronellol/geraniol ratio under enhanced UV-B radiation and/or high PAR is likely to be favorable.

Chronobiological Efficacy of Combined Therapy of Pelargonium Sidoides and Melatonin in Acute and Persistent Cases of COVID-19: A Hypothetical Approach.

Since the outbreak of the first SARS-CoV-2 epidemic in China, pharmacists have rapidly engaged and developed strategies for pharmaceutical care and supply. According to the guidelines of the International Pharmaceutical Federation (FIP), clinical pharmacists/hospital pharmacists, as members of care teams, play one of the most important roles in the pharmaceutical care of patients with COVID-19. During this pandemic, many immuno-enhancing adjuvant agents have become critical in addition to antivirals and vaccines in order to overcome the disease more easily. The liquid extract obtained from the Pelargonium sidoides plant is used for many indications such as colds, coughs, upper respiratory tract infections, sore throat, and acute bronchitis. The extract obtained from the roots of the plant has been observed to have antiviral and immunomodulatory activity. In addition to its anti-inflammatory and antioxidant effects, melatonin plays a role in suppressing the cytokine storm that can develop during COVID-19 infection. Knowing that the severity and duration of COVID-19 symptoms vary within 24 hours and/or in different time periods indicates that COVID-19 requires a chronotherapeutic approach. Our goal in the management of acute and long COVID is to synchronize the medication regimen with the patient's biological rhythm. This chapter provides a comprehensive review of the existing and emerging literature on the chronobiological use of Pelargonium sidoides and melatonin during acute and prolonged COVID-19 episodes.

Contrasting Metabolisms in Green and White Leaf Sectors of Variegated Pelargonium zonale-An Integrative Transcriptomic and Metabolomic Study.

The photosynthetically active green leaf (GL) and non-active white leaf (WL) tissues of variegated Pelargonium zonale provide an excellent model system for studying processes associated with photosynthesis and sink-source interactions, enabling the same microenvironmental conditions. By combining differential transcriptomics and metabolomics, we identified the main differences between these two metabolically contrasting tissues. Genes related to photosynthesis and associated pigments, the Calvin-Benson cycle, fermentation, and glycolysis were strongly repressed in WL. On the other hand, genes related to nitrogen and protein metabolism, defence, cytoskeletal components (motor proteins), cell division, DNA replication, repair and recombination, chromatin remodelling, and histone modifications were upregulated in WL. A content of soluble sugars, TCA intermediates, ascorbate, and hydroxybenzoic acids was lower, while the concentration of free amino acids (AAs), hydroxycinnamic acids, and several quercetin and kaempferol glycosides was higher in WL than in GL. Therefore, WL presents a carbon sink and depends on photosynthetic and energy-generating processes in GL. Furthermore, the upregulated nitrogen metabolism in WL compensates for the insufficient energy from carbon metabolism by providing alternative respiratory substrates. At the same time, WL serves as nitrogen storage. Overall, our study provides a new genetic data resource for the use of this excellent model system and for ornamental pelargonium breeding and contributes to uncovering molecular mechanisms underlying variegation and its adaptive ecological value.

Odor Perception and Descriptions of Rose-Scented Geranium Pelargonium graveolens 'Dr. Westerlund'-Sensory and Chemical Analyses.

A recent study found that the natural scent from the rose-scented geranium Pelargonium graveolens 'Dr. Westerlund' had positive effects on stress reduction. Essential oils from many pelargonium species are known to have phytochemical properties and pharmacological activities. No study has, so far, explored and identified the chemical compounds and the sensory perception of these compounds in 'Dr. Westerlund' plants. Such knowledge would be an important contribution to an increased understanding of the effects of plants' chemical odor properties on human well-being, and link this to the expressed perceived scents. This study aimed to identify the sensory profile and suggest responsible chemical compounds of Pelargonium graveolens 'Dr. Westerlund'. The sensory and chemical analysis results revealed sensory profiles of Pelargonium graveolens 'Dr. Westerlund's and provided suggestions for the chemical compounds attributed to the sensory profiles. Further studies are recommended to investigate the correlation between volatile compounds and possible stress reduction in humans.

Chemical Composition, Analgesic and Anti-Inflammatory Activity of Pelargonium peltatum Essential Oils from Eastern Cape, South Africa.

Pelargonium species are native to South Africa, and they have a long history in medicinal use. This study aimed to extract essential oils from different parts of P. peltatum, determine the chemical composition of the essential oils, and assess the essential oils' biological potential as analgesic and anti-inflammatory agents. The essential oils were obtained by hydro-distilling different parts of P. peltatum, and the essential profile was determined by GC-FID and GC-MS. The analgesic activity of the essential oil was determined by using a tail immersion in hot water method in rats, whereas the anti-inflammatory activity of the essential oils was assessed according to right hind paw oedema induced by egg albumin; the three doses selected for each experiment were 100, 200, and 400 mg/kg. According to the GC-FID and GC-MS analysis, camphene (3.6-33.4%), α-terpineol (4.8-19.1%), α-thujone (1.5-15.6%), piperitone (0.9-12.2%), linalool (1.6-11.7%), myrcene (5.2-10.7%), germacrene D (3.7-10.4%), ß-caryophyllene (1.2-9.5%), ß-cadinene (3.4-6.7%), and ß-bourbonene (4.2-6.2%) were some of the major compounds identified in the oil. P. peltatum essential oils demonstrated analgesic activity by increasing pain latency in hot water; furthermore, in an inflammation test, the essential oil reduced the egg-albumin-induced paw oedema in both the first and second phases. Therefore, the current findings suggest that P. peltatum essential oils have analgesic and anti-inflammatory properties.

Cinnamomum sp. and Pelargonium odoratissimum as the Main Contributors to the Antibacterial Activity of the Medicinal Drink Horchata: A Study Based on the Antibacterial and Chemical Analysis of 21 Plants.

Horchata, a herbal infusion drink from Ecuador containing a mixture of medicinal plants, has been reported to exhibit anti-inflammatory, analgesic, diuretic, and antioxidant activity. The antibacterial activity of each of the plants contained in the horchata mixture has not been fully evaluated. Thus, in this study, we analysed the antibacterial activity of 21 plants used in horchata, collected from the Ecuadorian Andes region, against bacterial strains of clinical importance. The methanolic extract of Cinnamomum sp. showed minimal inhibitory concentration (MIC) values of 250 µg/mL against Staphylococcus aureus ATCC25923 and Methicillin-resistant S. aureus (MRSA), while Pelargonium odoratissimum exhibited a MIC value of 500 µg/mL towards S. aureus ATCC25923. The high-performance liquid chromatography-diode array detector-tandem mass spectrometry (HPLC-DAD-MS/MS) analyses identified in Cinnamomum sp. epicatechin tannins, cinnamaldehyde, and prehelminthosporol molecules, whereas in P. odoratissimum, gallocatechin and epigallocatechin tannins, some flavonoids, and gallic acid and derivatives were identified. Finally, Cinnamomum sp. and P. odoratissimum showed partial inhibition of biofilm formation of S. aureus ATCC25923 and MRSA. Overall, our findings revealed which of the plants used in horchata are responsible for the antibacterial activity attributed to this herbal drink and exhibit the potential for Cinnamomum sp. and P. odoratissimum secondary metabolites to be explored as scaffolds in drug development.

Cytosolic geraniol and citronellol biosynthesis require a Nudix hydrolase in rose-scented geranium (Pelargonium graveolens).

Geraniol, citronellol and their esters are high-value acyclic monoterpenes used in food technology, perfumery and cosmetics. A major source of these compounds is the essential oil of rose-scented geraniums of the genus Pelargonium. We provide evidence that their biosynthesis mainly takes place in the cytosol of glandular trichomes via geranyl monophosphate (GP) through the action of a Nudix hydrolase. Protein preparations could convert geranyl diphosphate (GDP) to geraniol in in vitro assays, a process which could be blocked by inorganic phosphatase inhibitors, suggesting a two-step conversion of GDP to geraniol. Pelargonium graveolens chemotypes enriched in either geraniol or (-)-citronellol accumulate GP or citronellyl monophosphate (CP), respectively, the presumed precursors to their monoterpenoid end products. Geranyl monophosphate was highly enriched in isolated glandular trichomes of lines producing high amounts of geraniol. In contrast, (-)-isomenthone-rich lines are depleted in these prenyl monophosphates and monoterpene alcohols and instead feature high levels of GDP, the precursor to plastidic p-menthane biosynthesis. A Nudix hydrolase cDNA from Pelargonium glandular trichomes, dubbed PgNdx1, encoded a cytosolic protein capable of hydrolyzing GDP to GP with a KM of about 750 nm but is only weakly active towards farnesyl diphosphate. In citronellol-rich lines, GDP, GP and CP were detected in nearly equimolar amounts, while citronellyl diphosphate was absent, suggesting that citronellol biosynthesis may proceed by reduction of GP to CP in this species. These findings highlight the cytosol as a compartment that supports monoterpene biosynthesis and expands the roles of Nudix hydrolases in the biosynthesis of plant volatiles.

GC-MS Profiling and Antineoplastic Activity of Pelargonium Inquinans Ait Leaves on Acute Leukaemia Cell Lines U937 and Jurkat.

We investigated the antineoplastic activities of extracts of Pelargonium inquinans leaves, a plant native to South Africa on acute leukemia cell lines, U937 and Jurkat and the inflammatory effect (nitric oxide and cyclo-oxygenase-2) on RAW 264.7 cells. The extracts of Pelargonium inquinans have significant cytotoxicity especially on U937 cells and pro-inflammatory release of nitric oxide on RAW 264.7 macrophages. The GC-MS study of the essential oil showed it had more than a hundred compounds. This study showed that Pelargonium inquinans have antineoplastic and anti-inflammatory activities which can be further explored in In Vivo studies.

Anti-mosquito properties of Pelargonium roseum (Geraniaceae) and Juniperus virginiana (Cupressaceae) essential oils against dominant malaria vectors in Africa.

BACKGROUND: More than 90% of malaria cases occur in Africa where the disease is transmitted by Anopheles gambiae and Anopheles arabiensis. This study evaluated the anti-mosquito properties of Juniperus virginiana (JVO) and Pelargonium roseum (PRO) essential oils (EOs) against larvae and adults of An. gambiae sensu lato (s.l.) from East Africa in laboratory and semi-field conditions. METHODS: EOs was extracted from the aerial green parts of Asian herbs by hydrodistillation. Their constituents were characterized by gas chromatography-mass spectrometry (GC-MS). Larvicidal activities of JVO, PRO, and PRO components [citronellol (CO), linalool (LO), and geraniol (GO)] were investigated against An. gambiae sensu stricto (s.s.). The percentage of knockdown effects and mortality rates of all oils were also evaluated in the adults of susceptible An. gambiae s.s. and permethrin-resistant An. arabiensis. RESULTS: GC-MS analyses identified major constituents of JVO (sabinene, dl-limonene, ß-myrcene, bornyl acetate, and terpinen-4-ol) and PRO (citronellol, citronellyl formate, L-menthone, linalool, and geraniol). Oils showed higher larvicidal activity in the laboratory than semi-field trials. The LC50 values for JVO/PRO were computed as 10.82-2.89/7.13-0.9 ppm and 10.75-9.06/13.63-8.98 ppm in laboratory and semi-field environments, respectively at exposure time of 24-72 h. The percentage of knockdown effects of the oils were also greater in An. gambiae s.s. than in An. arabiensis. Filter papers impregnated with JVO (100 ppm) and PRO (25 ppm) displayed 100% mortality rates for An. gambiae s.s. and 3.75% and 90% mortality rates, for An. arabiensis populations, respectively. Each component of CO, LO, and GO exhibited 98.13%, 97.81%, and 87.5%, respectively, and a mixture of the PRO components indicated 94.69% adult mortality to permethrin-resistant An. arabiensis. CONCLUSIONS: The findings of this study show that PRO and its main constituents, compared to JVO, have higher anti-mosquito properties in terms of larvicidal, knockdown, and mortality when applied against susceptible laboratory and resistant wild populations of An. gambiae s.l. Consequently, these oils have the potential for the development of new, efficient, safe, and affordable agents for mosquito control.

Chemical characterisation of Pelargonium sidoides root based on LC-QToF-MS non-target screening strategies.

INTRODUCTION: Pelargonium sidoides is a member of the Geraniaceae family and it originates from the coastal regions of South Africa. In the last decades, Pelargonium sidoides root has been subjected to several surveys due to the assertion of its health benefits, such as the relief of symptoms of acute bronchitis, common cold and acute rhinosinusitis. Many studies have been conducted to reveal its naturally occurring bioactive chemicals, yet no wide-scope chemical characterisation strategies have been done using mass spectrometry. OBJECTIVE: This research aimed to comprehensively characterise the chemical profile of Pelargonium sidoides root via high-resolution mass spectrometry. METHODOLOGY: The Pelargonium sidoides root was extracted by a mixture of methanol: water in the proportion of 80:20. The extraction procedure included vortexing, shaking as well as the use of an ultrasound sonication bath under 40°C. After centrifugation, the supernatant was evaporated to dryness. The dry residue was reconstituted with a mixture of methanol/water (50:50, v/v), filtered and injected into an ultra-high-pressure liquid chromatography-quadruple time-of-flight mass spectrometer. RESULTS: Overall, 33 compounds were identified in the root using suspect and non-target screening. These compounds were originated from different classes of compounds such as amino acids, phenolic acids, α-hydroxy-acids, vitamins, polyphenols, flavonoids, coumarins, coumarins glucosides, coumarin sulphates and nucleotides. Quantitative results were provided for the identified compounds, where their reference standards were available. CONCLUSION: Some important compounds were elucidated, belonging to different classes of compounds such as antioxidants (coumarins and phenolic compounds), amino acids, nucleotides and vitamins revealing the importance of the bioactive content of this root.

Effects of High Pressure Processing and Thermal Treatment on the Interaction between α-Lactalbumin and Pelargonium-3-Glucoside.

In this study, high pressure processing (HPP) and thermal treatment were comparatively evaluated by examining their impacts on the binding behavior and interaction between α-lactalbumin (α-La) and pelargonium-3-glucoside (P3G) under pH values of 6.0, 7.4, and 8.0. The methods of circular dichroism spectroscopy, fluorescence quenching, dynamic light scattering, and molecular simulation were used to characterize the effects of processing-induced changes in protein structure, size distribution, binding site conformation, and residue charges on their binding characteristics between them. The results indicated that the thermal treatments significantly increased the quenching constants of the complex at pH 7.4/8.0 and 60/80 °C, as well as the accessible fraction of protein at pH 8.0/80 °C. Both HPP and thermal treatments increased the random coil content and showed limited effects on the α-helix and ß-sheet contents of α-La and caused the aggregation of the complex to varying degrees. Molecular dynamic simulation and docking analyses revealed that the binding site of the complex did not change under different processing conditions, but the solvent-accessible surface area varied under different conditions.

Laser Light Treatment Improves the Mineral Composition, Essential Oil Production and Antimicrobial Activity of Mycorrhizal Treated Pelargoniumgraveolens.

Pelargonium graveolens, rose-scented geranium, is commonly used in the perfume industry. P. graveolens is enriched with essential oils, phenolics, flavonoids, which account for its tremendous biological activities. Laser light treatment and arbuscular mycorrhizal fungi (AMF) inoculation can further enhance the phytochemical content in a significant manner. In this study, we aimed to explore the synergistic impact of these two factors on P. graveolens. For this, we used four groups of surface-sterilized seeds: (1) control group1 (non-irradiated; non-colonized group); (2) control group2 (mycorrhizal colonized group); (3) helium-neon (He-Ne) laser-irradiated group; (4) mycorrhizal colonization coupled with He-Ne laser-irradiation group. Treated seeds were growing in artificial soil inculcated with Rhizophagus irregularis MUCL 41833, in a climate-controlled chamber. After 6 weeks, P. graveolens plants were checked for their phytochemical content and antibacterial potential. Laser light application improved the mycorrhizal colonization in P. graveolens plants which subsequently increased biomass accumulation, minerals uptake, and biological value of P. graveolens. The increase in the biological value was evident by the increase in the essential oils production. The concomitant application of laser light and mycorrhizal colonization also boosted the antimicrobial activity of P. graveolens. These results suggest that AMF co-treatment with laser light could be used as a promising approach to enhance the metabolic content and yield of P. graveolens for industrial and pharmaceutical use.

Chemical Markers and Pharmacological Characters of Pelargonium graveolens Essential Oil from Palestine.

Pelargonium graveolens leaves are widely used in traditional medicine for relieving some cardiovascular, dental, gastrointestinal, and respiratory disorders. They are also used as food and tea additives in Palestine and many other countries. Consequently, this investigation aimed to describe the chemical markers, cytotoxic, antioxidant, antimicrobial, metabolic, and cyclooxygenase (COX) enzymes inhibitory characteristics of P. graveolens essential oil (PGEO) from Palestine utilizing reference methods. There were 70 chemicals found in the GCMS analysis, and oxygenated terpenoids were the most abundant group of the total PGEO. Citronellol (24.44%), citronellyl formate (15.63%), γ-eudesmol (7.60%), and iso-menthone (7.66%) were the dominant chemical markers. The EO displayed strong antioxidant activity (IC50 = 3.88 ± 0.45 µg/mL) and weak lipase and α-amylase suppressant effects. Notably, the PGEO displayed high α-glucosidase inhibitory efficacy compared with Acarbose, with IC50 doses of 52.44 ± 0.29 and 37.15 ± 0.33 µg/mL, respectively. PGEO remarkably repressed the growth of methicillin-resistant Staphylococcus aureus (MRSA), even more than Ampicillin and Ciprofloxacin, and strongly inhibited Candida albicans compared with Fluconazole. The highest cytotoxic effect of the PGEO was noticed against MCF-7, followed by Hep3B and HeLa cancer cells, with IC50 doses of 32.71 ± 1.25, 40.71 ± 1.89, and 315.19 ± 20.5 µg/mL, respectively, compared with doxorubicin. Moreover, the screened EO demonstrated selective inhibitory activity against COX-1 (IC50 = 14.03 µg/mL). Additionally, PGEO showed a weak suppressant effect on COX-2 (IC50 = 275.97 µg/mL). The current research can be considered the most comprehensive investigation of the chemical and pharmacological characterization of the PGEO. The results obtained in this study demonstrate, without doubt, that this plant represents a rich source of bioactive substances that can be further investigated and authenticated for their medicinal potential.

GC/MS Analysis, Antioxidant Activity, and Antimicrobial Effect of Pelargonium peltatum (Geraniaceae).

In recent years, the increase in antibiotic resistance demands searching for new compounds with antimicrobial activity. Phytochemicals found in plants offer an alternative to this problem. The genus Pelargonium contains several species; some have commercial use in traditional medicine such as P. sinoides, and others such as P. peltatum are little studied but have promising potential for various applications such as phytopharmaceuticals. In this work, we characterized the freeze-dried extracts (FDEs) of five tissues (root, stem, leaf, and two types of flowers) and the ethyl acetate fractions from leaf (Lf-EtOAc) and flower (Fwr-EtOAc) of P. peltatum through the analysis by thin-layer chromatography (T.L.C.), gas chromatography coupled to mass spectrometry (GC-MS), phytochemicals quantification, antioxidant capacity, and antimicrobial activity. After the first round of analysis, it was observed that the FDE-Leaf and FDE-Flower showed higher antioxidant and antimicrobial activities compared to the other FDEs, for which FDE-Leaf and FDE-Flower were fractionated and analyzed in a second round. The antioxidant activity determined by ABTS showed that Lf-EtOAc and Fwr-EtOAc had the lowest IC50 values with 27.15 ± 1.04 and 28.11 ± 1.3 µg/mL, respectively. The content of total polyphenols was 264.57 ± 7.73 for Lf-EtOAc and 105.39 ± 4.04 mg G.A./g FDE for Fwr-EtOAc. Regarding the content of flavonoid, Lf-EtOAc and Fw-EtOAc had the highest concentration with 34.4 ± 1.06 and 29.45 ± 1.09 mg Q.E./g FDE. In addition, the minimum inhibitory concentration (M.I.C.) of antimicrobial activity was evaluated: Lf-EtOAc and Fwr-EtOAc were effective at 31.2 µg/mL for Staphylococcus aureus and 62.5 µg/mL for Salmonella enterica, while for the Enterococcus feacalis strain, Fwr-EtOAc presented 31.2 µg/mL of M.I.C. According to the GC-MS analysis, the main compounds were 1,2,3-Benzenetriol (Pyrogallol), with 77.38% of relative abundance in the Lf-EtOAc and 71.24% in the Fwr-EtOAc, followed by ethyl gallate (13.10%) in the Fwr-EtOAc and (Z)-9-Octadecenamide (13.63% and 6.75%) in both Lf-EtOAc and Fwr-EtOAc, respectively.

The Biosynthesized Zinc Oxide Nanoparticles' Antiviral Activity in Combination with Pelargonium zonale Extract against the Human Corona 229E Virus.

Almost one-third of all infectious diseases are caused by viruses, and these diseases account for nearly 20% of all deaths globally. It is becoming increasingly clear that highly contagious viral infections pose a significant threat to global health and economy around the world. The need for innovative, affordable, and safe antiviral therapies is a must. Zinc oxide nanoparticles are novel materials of low toxicity and low cost and are known for their antiviral activity. The genus Pelargonium was previously reported for its antiviral and antimicrobial activity. In this work, Pelargonium zonale leaf extract chemical profile was studied via high-performance liquid chromatography (HPLC) and was used for the biosynthesis of zinc oxide nanoparticles. Furthermore, the antiviral activity of the combination of P. zonale extract and the biosynthesized nanoparticles of ZnO against the human corona 229E virus was investigated. Results revealed that ZnONPs had been biosynthesized with an average particle size of about 5.5 nm and characterized with UV, FTIR, TEM, XRD, and SEM. The antiviral activity showed significant activity and differences among the tested samples in favor of the combination of P. zonale extract and ZnONPs (ZnONPs/Ex). The lowest IC50, 2.028 µg/mL, and the highest SI, 68.4 of ZnONPs/Ex, assert the highest antiviral activity of the combination against human coronavirus (229E).

Anti-Quorum Sensing and Anti-Biofilm Activity of Pelargonium × hortorum Root Extract against Pseudomonas aeruginosa: Combinatorial Effect of Catechin and Gallic Acid.

HPLC-UV was used to compare the major constituents of two Pelargonium × hortorum cultivars and Pelargonium sidoides root extract. It revealed the presence of catechin and gallic acid in high concentrations and the absence of umckalin in P. × hortorum root extracts. The antibacterial activity of these extracts was screened against 19 Pseudomonas aeruginosa clinical isolates. P. × hortorum root extracts showed the lowest MIC values (512-1024 µg/mL). This activity was concluded to be attributable to the high concentrations of catechin and gallic acid. The anti-biofilm activity of catechin, gallic acid, and their combination was examined by a crystal violet assay. The combination reduced the percentage of strong and moderate biofilm-forming isolates from 52.63% to 5.26%. The impact on lasI and lasR genes expression using qRT-PCR and simultaneous docking against LasR protein was explored. The combination downregulated lasI and lasR gene expression in eight and six P. aeruginosa isolates, respectively, and showed the greatest docking score. Additionally, the in vivo protection capability of this combination in infected mice showed enhancement in the survival rate. Our study revealed the potential biofilm and quorum-sensing-inhibitory activity of the catechin and gallic acid combination as a novel alternative to inhibit bacterial pathogenicity.

[Rose-scented geranium essential oil from Algeria (Pelargonium graveolens L'Hérit.): Assessment of antioxidant, anti-inflammatory and anticancer properties against different metastatic cancer cell lines]. / Essence aromatique du Géranium Odorant (Pelargonium graveolens L'Hérit.) d'Algérie : exploration des propriétés antioxydante, anti-inflammatoire et anticancéreuse (anti-angiogénique et cytotoxique), in vitro et in ovo, vis-à-vis de différentes lignées cellulaires cancéreuses métastasiques.

INTRODUCTION: The study of natural products is one of the strategies implemented for the discovery of new compounds that can be used in cancer therapy. Aromatic herbs and medicinal plants found in Algeria and their anti-angiogenesis and cytotoxic potentials against cancer have not been much explored. OBJECTIVES: Our work aimed to evaluate the antioxidant, anti-inflammatory and anticancer properties of the essential oil (EO) extracted from rose-scented geranium (Pelargonium graveolens) and its major (citronellol) and characteristic (linalool) constituents. RESULTS: The chemical composition of EO was determined with chromatographic analysis and revealed the presence of citronellol as the major compound (25.84%). A strong chelating power of terpene alcohols (IC50=1.58±0.23mg/mL for citronellol) was found, with a significant difference (P<0.05) compared with the standard antioxidants used (L-ascorbic acid and butylated hydroxyanisole). The EO is distinguished by an interesting anti-inflammatory effect with the lowest IC50 (4.63±0.3mg/mL), and it constitutes a good stabilizer of the erythrocyte membrane. Citronellol also exhibited the best anti-inflammatory effect (IC50=0.74±0.09mg/mL). We also assessed the anticancer effect of EO on two main pathways involved in cancer development, angiogenesis and cell proliferation, using in ovo bioassays with a chorio-allantoic membrane (CAM) of chicken eggs and in vitro assays of its cytotoxicity on different metastatic breast cancer (MDA-MB-231), gastric (AGS) and melanoma (MV3) cell lines. In the CAM model, the density of micro-vessels is 75±10 in the group supplemented with EO compared to 140±9 for the control group (b-FGF). In addition, the EO significantly reduced the number of newly formed vessels. The cytotoxicity was evaluated using the cell proliferation inhibition method and cell viability was measured using the MTT test. Results revealed that the treatment of cancer lines with different concentrations of EO reduces the rate of cell viability in a dose-dependent manner. EO showed the greatest cytotoxicity on the AGS line with an inhibition rate of 92.87±0.13% at the highest dose (4µL/mL), followed by the MV3 line (88.76±0.96%). CONCLUSION AND PROSPECTS: Data demonstrated that rose-scented geranium EO has an antitumor potential on metastatic cancer cell lines. It is distinguished by its antiproliferative, anti-angiogenic, and anti-inflammatory activities. Medicinal plants might contain new molecules, with new structures, which could become lead candidate among future anticancer drugs.