Anti-inflammatory and anti-hyperalgesic effects induced by an aqueous aged black garlic extract in rodent models of ulcerative colitis and colitis-associated visceral pain.

Inflammatory bowel disease (IBD) is a morbid condition characterized by relapsing-remitting inflammation of the colon, accompanied by persistent gut dysmotility and abdominal pain. Different reports demonstrated biological activities of aged black garlic (ABG), including anti-inflammatory and antioxidant effects. We aimed to investigate beneficial effects exerted by ABGE on colon inflammation by using ex vivo and in vivo experimental models. We investigated the anti-inflammatory effects of an ABG water extract (ABGE) on rat colon specimens exposed to E. coli lipopolysaccharide (LPS), a known ex vivo experimental model of ulcerative colitis. We determined gene expression of various biomarkers involved in inflammation, including interleukin (IL)-1ß, IL-6, nuclear factor-kB (NF-kB), tumor necrosis factor (TNF)-α. Moreover, we studied the acute effects of ABGE on visceral pain associated with colitis induced by 2,4-di-nitrobenzene sulfonic acid (DNBS) injection in rats. ABGE suppressed LPS-induced gene expression of IL-1ß, IL-6, NF-kB, and TNF-α. In addition, the acute administration of ABGE (0.03-1 g kg-1) dose-dependently relieved post-inflammatory visceral pain, with the higher dose (1 g kg-1) able to significantly reduce both the behavioral nociceptive response and the entity of abdominal contraction (assessed by electromyography) in response to colorectal distension after the acute administration in DNBS-treated rats. Present findings showed that ABGE could represent a potential strategy for treatment of colitis-associated inflammatory process and visceral pain. The beneficial effects induced by the extract could be related to the pattern of polyphenolic composition, with particular regard to gallic acid and catechin.

Combining the Pharmaceutical and Toxicological Properties of Selected Essential Oils with their Chemical Components by GC-MS Analysis.

In the current investigation, a comprehensive analysis was carried out on essential oils (EOs) extracted from six aromatic plant species, namely Rosmarinus officinalis, Pelargonium graveolens, Thymus vulgaris, Origanum vulgare, Laurus nobilis, and Aloysia citrodora. An exploration was conducted into the chemical composition using Gas Chromatography-Mass Spectrometry (GC/MS), antioxidant properties assessed through DPPH, ABTS, CUPRAC, FRAP, MCA, and PBD assays, ecotoxicological impacts evaluated via allelopathy and the Daphnia magna heartbeat test, as well as bio-pharmacological effects including anticancer activity and gene expression analysis. Results revealed strong antioxidant activity in all essential oils, with T. vulgaris EO (2748.00 mg TE/g) and O. vulgare EO (2609.29 mg TE/g) leading in CUPRAC assay. R. officinalis EO showed the highest α-amylase inhibition at 1.58 mmol ACAE/g, while O. vulgare EO excelled in α-glucosidase inhibition at 1.57 mmol ACAE/g. Additionally, cytotoxic effects were evaluated on human colorectal cancer (HCT116) cells. A. citrodora, O. vulgare, and R. officinalis EOs were found the most potent anticancer, as also witnessed by their higher modulatory effects on the gene expression of BAX and Bcl-2. Collectively, the present data highlight the importance to implement the knowledge and to valorize the supply chain of aromatic plants.

Neuromodulatory Effects Induced by the Association of Moringa oleifera Lam., Tribulus terrestris L., Rhodiola rosea Lam., and Undaria pinnatidifida Extracts in the Hypothalamus.

The present study investigated the role of a commercial formulation constituted by herbal extracts from Rhodiola rosea, Undaria pinnatifida, Tribulus terrestris, and Moringa oleifera. The formulation was analysed for determining the content in total phenols and flavonoids and scavenging/reducing properties. The formulation was also tested on isolated mouse hypothalamus in order to investigate effects on serotonin, dopamine, neuropeptide Y (NPY), and orexin A. The gene expression of gonadrotopin releasing hormone (GnRH) was also assayed. The formulation was able to reduce dopamine and serotonin turnover, and this could be related, albeit partially, to the capability of different phytochemicals, among which hyperoside and catechin to inhibit monoaminooxidases activity. In parallel, the formulation was effective in reducing the gene expression of NPY and orexin-A and to improve the gene expression of GnRH. In this context, the increased GnRH gene expression induced by the formulation may contribute not only to improve the resistance towards the stress related to ageing, but also to prevent the reduction of libido that could be related with a stimulation of the serotoninergic pathway. According to the in silico analysis, hyperoside could play a pivotal role in modulating the gene expression of GnRH. Regarding NPY and orexin A gene expression, no direct interactions between the formulation phytochemicals and these neuropeptides were anticipated; thus, suggesting that the pattern of gene expression observed following exposure of the hypothalamus to the formulation may be secondary to inhibitory effects of dopamine and serotonin turnover. Concluding, the present study demonstrated the efficacy of the formulation in exerting neuromodulatory effects at the hypothalamic level; thus, suggesting the potential to contrast stress and fatigue.

Chemical Characterization of Different Extracts from Artemisia annua and Their Antioxidant, Enzyme Inhibitory and Anti-Inflammatory Properties.

Artemisia annua L. (Asteraceae Family) is an important plant in Asia that has been used for treating different diseases, including fever due to malaria, wounds, tubercolisis, scabues, pain, convulsions, diabetes, and inflammation. In this study we aimed to evaluate the effects of different polarity extracts (hexane, dichloromethane, ethyl acetate, ethanol, ethanol/water (70 %) and water) from A. annua against the burden of inflammation and oxidative stress occurring in colon tissue exposed to LPS. In parallel, chemical composition, antiradical, and enzyme inhibition effects against α-amylase, α-glucosidase, tyrosinase, and cholinesterases were evaluated. The water extract contained the highest content of the total phenolic with 34.59 mg gallic acid equivalent (GAE)/g extract, while the hexane had the highest content of the total flavonoid (20.06 mg rutin equivalent (RE)/g extract). In antioxidant assays, the polar extracts (ethanol, ethanol/water and water) exhibited stronger radical scavenging and reducing power abilities when compared to non-polar extracts. The hexane extract showed the best AChE, tyrosinase and glucosidase inhibitory effects. All extracts revealed effective anti-inflammatory agents, as demonstrated by the blunting effects on COX-2 and TNFα gene expression. These effects seemed to be not related to the only phenolic content. However, it is worthy of interest to highlight how the higher potency against LPS-induced gene expression was shown by the water extract ; thus suggesting a potential phytotherapy application in the management of clinical symptoms related to inflammatory colon diseases, although future in vivo studies are needed to confirm such in vitro and ex vivo observations.

Evaluating Phytochemical Profiles, Cytotoxicity, Antiviral Activity, Antioxidant Potential, and Enzyme Inhibition of Vepris boiviniana Extracts.

In the present study, we performed comprehensive LC-MS chemical profiling and biological tests of Vepris boiviniana leaves and stem bark extracts of different polarities. In total, 60 bioactive compounds were tentatively identified in all extracts. The 80% ethanolic stem bark extract exhibited the highest activity in the ABTS assay, equal to 551.82 mg TE/g. The infusion extract of stem bark consistently demonstrated elevated antioxidant activity in all assays, with values ranging from 137.39 mg TE/g to 218.46 mg TE/g. Regarding the enzyme inhibitory assay, aqueous extracts from both bark and leaves exhibited substantial inhibition of AChE, with EC50 values of 2.41 mg GALAE/g and 2.25 mg GALAE/g, respectively. The 80% ethanolic leaf extract exhibited the lowest cytotoxicity in VERO cells (CC50: 613.27 µg/mL) and demonstrated selective cytotoxicity against cancer cells, particularly against H1HeLa cells, indicating potential therapeutic specificity. The 80% ethanolic bark extract exhibited elevated toxicity in VERO cells but had reduced anticancer selectivity. The n-hexane extracts, notably the leaves' n-hexane extract, displayed the highest toxicity towards non-cancerous cells with selectivity towards H1HeLa and RKO cells. In viral load assessment, all extracts reduced HHV-1 load by 0.14-0.54 log and HRV-14 viral load by 0.13-0.72 log, indicating limited antiviral activity. In conclusion, our research underscores the diverse bioactive properties of Vepris boiviniana extracts, exhibiting potent antioxidant, enzyme inhibitory, and cytotoxicity potential against cancer cells.

Beyond the Psychoactive Effects of Ayahuasca: Cultural and Pharmacological Relevance of Its Emetic and Purging Properties.

The herbal preparation ayahuasca has been an important part of ritual and healing practices, deployed to access invisible worlds in several indigenous groups in the Amazon basin and among mestizo populations of South America. The preparation is usually known to be composed of two main plants, Banisteriopsis caapi and Psychotria viridis, which produce both hallucinogenic and potent purging and emetic effects; currently, these are considered its major pharmacological activities. In recent decades, the psychoactive and visionary effect of ayahuasca has been highly sought after by the shamanic tourism community, which led to the popularization of ayahuasca use globally and to a cultural distancing from its traditional cosmological meanings, including that of purging and emesis. Further, the field of ethnobotany and ethnopharmacology has also produced relatively limited data linking the phytochemical diversity of ayahuasca with the different degrees of its purging and emetic versus psychoactive effects. Similarly, scientific interest has also principally addressed the psychological and mental health effects of ayahuasca, overlooking the cultural and pharmacological importance of the purging and emetic activity. The aim of this review is therefore to shed light on the understudied purging and emetic effect of ayahuasca herbal preparation. It firstly focuses on reviewing the cultural relevance of emesis and purging in the context of Amazonian traditions. Secondly, on the basis of the main known phytochemicals described in the ayahuasca formula, a comprehensive pharmacological evaluation of their emetic and purging properties is presented.

Biological investigation of N-methyl thiosemicarbazones as antimicrobial agents and bacterial carbonic anhydrases inhibitors.

The enormous burden of the COVID-19 pandemic in economic and healthcare terms has cast a shadow on the serious threat of antimicrobial resistance, increasing the inappropriate use of antibiotics and shifting the focus of drug discovery programmes from antibacterial and antifungal fields. Thus, there is a pressing need for new antimicrobials involving innovative modes of action (MoAs) to avoid cross-resistance rise. Thiosemicarbazones (TSCs) stand out due to their easy preparation and polypharmacological application, also in infectious diseases. Recently, we reported a small library of TSCs (1-9) that emerged for their non-cytotoxic behaviour. Inspired by their multifaceted activity, we investigated the antibacterial, antifungal, and antidermatophytal profiles of derivatives 1-9, highlighting a new promising research line. Furthermore, the ability of these compounds to inhibit selected microbial and human carbonic anhydrases (CAs) was assessed, revealing their possible involvement in the MoA and a good selectivity index for some derivatives.

A grape (Vitis vinifera L.) pomace water extract modulates inflammatory and immune response in SW-480 cells and isolated mouse colon.

Grape (Vitis vinifera L.) pomace is a residue derived from the winemaking process, which contains bioactive compounds displaying noteworthy health-promoting properties. The aim of the present study was to investigate the phenolic composition and protective effects of a water extract of grape pomace (WEGP) in colorectal cancer cell line SW480 and in isolated mouse colon exposed to Escherichia coli lipopolysaccharide (LPS). The extract decreased SW-480 cell viability, as well as vascular endothelial factor A (VEGFA), hypoxia-induced factor 1α (HIF1α), and transient receptor potential M8 (TRPM8) LPS-induced gene expression. Moreover, the extract inhibited mRNA levels of nuclear factor kB (NFkB), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)α, interleukin (IL)-6, IL-1ß, IL-10, inducible nitric oxide synthase (iNOS), and interferon (IFN)γ, in isolated colon. Conversely, WEGP increased the gene expression of antioxidant catalase (CAT) and superoxide dismutase (SOD), in the same model. The modulatory effects exerted by WEGP could be related, at least in part, to the phenolic composition, with particular regards to the catechin level. Docking calculations also predicted the interactions of catechin toward TRPM8 receptor, deeply involved in colon cancer; thus further suggesting the grape pomace as a valuable source of bioactive extracts and phytochemicals with protective effects in the colon.

Protective Effects of PollenAid Plus Soft Gel Capsules' Hydroalcoholic Extract in Isolated Prostates and Ovaries Exposed to Lipopolysaccharide.

Pollen extract represents an innovative approach for the management of the clinical symptoms related to prostatitis and pelvic inflammatory disease (PID). In this context, the aims of the present work were to analyze the phenolic composition of a hydroalcoholic extract of PollenAid Plus soft gel capsules, and to evaluate the extract's cytotoxic effects, in human prostate cancer PC3 cells and human ovary cancer OVCAR-3 cells. Additionally, protective effects were investigated in isolated prostate and ovary specimens exposed to lipopolysaccharide (LPS). The phytochemical investigation identified catechin, chlorogenic acid, gentisic acid, and 3-hydroxytyrosol as the prominent phenolics. The extract did not exert a relevant cytotoxic effect on PC3 and OVCAR-3 cells. However, the extract showed a dose-dependent inhibition of pro-inflammatory IL-6 and TNF-α gene expression in prostate and ovary specimens, and the extract was effective in preventing the LPS-induced upregulation of CAT and SOD gene expression, which are deeply involved in tissue antioxidant defense systems. Finally, a docking approach suggested the capability of catechin and chlorogenic acid to interact with the TRPV1 receptor, playing a master role in prostate inflammation. Overall, the present findings demonstrated anti-inflammatory and antioxidant effects of this formulation; thus, suggesting its capability in the management of the clinical symptoms related to prostatitis and PID.

Characterization of the Phytochemical Composition and Bioactivities of Anacyclus maroccanus Ball. and Anacyclus radiatus Loisel Aerial Parts: Preliminary Evidence for the Possible Development of Moroccan Plants.

In the present study, the phytochemical composition and bioactivities of A. maroccanus (AM) and A. radiatus (AR), two ecotypes collected in the Demnate road and Essaouira regions, respectively, were studied to highlight a pharmacological interest and to enable possible pharmaceutical development. To this end, methanolic and ethyl acetate extracts were prepared for each ecotype by fractionation; next, their phytochemical composition was evaluated by spectrophotometric and chromatographic analysis. Moreover, in line with the available evidence for Anacyclus spp. and their traditional use, a screening of bioactivities, including antioxidant, hypoglycemic, antiglycative, chelating, and antibacterial activities, was performed. The extracts were characterized by high amounts of polyphenols, tannins, and flavonoids, especially in the methanolic extracts; these samples were also enriched in carotenoids despite a lower chlorophyll content. Chlorogenic acid and rutin were the major identified compounds. The extracts also showed interesting hypoglycemic, antiglycative, and antibacterial properties, although with differences in efficacy and potency. Present results provide more scientific basis to the ethnopharmacological uses of Anacyclus spp. and suggest a further interest in AM and AR ecotypes as natural sources of bioactive compounds and/or phytocomplexes for possible pharmaceutical and nutraceutical developments.

New Biological and Chemical Evidences of Two Lamiaceae Species (Thymbra capitata and Thymus sipyleus subsp. rosulans): In Vitro, In Silico and Ex Vivo Approaches.

In this study, the methanolic and infusion extracts of two species, Thymbra capitata and Thymus sipyleus subsp. rosulans, were tested for their chemical composition and biological abilities (antioxidant, enzyme inhibitory and anti-inflammatory effects). The extracts yielded total phenolic and flavonoid contents in the range of 83.43-127.52 mg GAE/g and 9.41-46.34 mg RE/g, respectively. HPLC analysis revealed rosmarinic acid to be a major component of the studied extracts (15.85-26.43%). The best ABTS radical scavenging ability was observed in the methanol extract of T. capitata with 379.11 mg TE/g, followed by in the methanol extract of T. sipylus (360.93 mg TE/g). In the CUPRAC assay, the highest reducing ability was also found in the methanol extract of T. capitata with 802.22 mg TE/g. The phosphomolybdenum ability ranged from 2.39 to 3.61 mmol TE/g. In terms of tyrosinase inhibitory effects, the tested methanol extracts (83.18-89.66 mg KAE/g) were higher than the tested water extracts (18.74-19.11 mg KAE/g). Regarding the BChE inhibitory effects, the methanol extracts were active on the enzyme while the water extracts showed no inhibitory effect on it. Overall, the methanolic extracts showed better enzyme inhibition compared to the infusion extracts. Molecular docking also showed the selected exhibited potential binding affinities with all enzymes, with a preference for cholinesterases. Additionally, the extracts were effective in attenuating the LPS-induced increase in COX-2 and IL-6 gene expression in isolated colon, thus indicating promising anti-inflammatory effects. The preliminary results of this study suggest that these species are good natural sources of antioxidants and also provide some scope as enzyme inhibitors, most likely due to their bioactive contents such as phenolic acids, and thus can be exploited for different applications related to health promotion and disease prevention.

1H-NMR Metabolic Profiling and Antioxidant Activity of Saffron (Crocus sativus) Cultivated in Lebanon.

Despite the beneficial health properties shown by Lebanese saffron, its qualitative and quantitative composition has never been investigated before. In the present study, NMR spectroscopy, together with antioxidant activity assays, were applied to evaluate the chemical composition of saffron samples of different geographical origins (Lebanon, Italy, Iran, and India) and to categorize the Lebanese saffron for the first time. The distinction between Lebanese saffron and that produced in other countries was attributed to its higher linolenic and linoleic fatty acids, glucose and picrocrocin contents. Moreover, spices produced in three different regions of the Lebanese territory have been clearly differentiated. Saffron cultivated in the Qaa region displayed a high glucose, fatty acids and polyphenols content, whereas Hermel saffron exhibited the largest rate of picrocrocin and glycosylated carotenoids. Finally, samples from Baalbeck showed lower rates for the majority of metabolites. Moreover, Lebanese saffron showed a high antioxidant activity in ABTS and DPPH assays. A low dose of saffron extract (10 µg/mL) inhibited the growth of human lung adenocarcinoma cells, probably due to the high polyphenolic content. This study highlights the quality and peculiarity of Lebanese saffron cultivated in Northern Beqaa district and allows for a good discrimination between spices produced in relatively close territory.

Phenolic Characterization and Neuroprotective Properties of Grape Pomace Extracts.

Vitis vinifera (grape) contains various compounds with acknowledged phytochemical and pharmacological properties. Among the different parts of the plant, pomace is of particular interest as a winemaking industry by-product. A characterization of the water extract from grape pomace from Montepulciano d'Abruzzo variety (Villamagna doc) was conducted, and the bioactive phenolic compounds were quantified through HPLC-DAD-MS analysis. HypoE22, a hypothalamic cell line, was challenged with an oxidative stimulus and exposed to different concentrations (1 µg/mL-1 mg/mL) of the pomace extract for 24, 48, and 72 h. In the same conditions, cells were exposed to the sole catechin, in a concentration range (5-500 ng/mL) consistent with the catechin level in the extract. Cell proliferation was investigated by MTT assay, dopamine release through HPLC-EC method, PGE2 amount by an ELISA kit, and expressions of neurotrophin brain-derived neurotrophic factor (BDNF) and of cyclooxygenase-2 (COX-2) by RT-PCR. The extract reverted the cytotoxicity exerted by the oxidative stimulus at all the experimental times in a dose-dependent manner, whereas the catechin was able to revert the oxidative stress-induced depletion of dopamine 48 h and 72 h after the stimulus. The extract and the catechin were also effective in preventing the downregulation of BDNF and the concomitant upregulation of COX-2 gene expression. In accordance, PGE2 release was augmented by the oxidative stress conditions and reverted by the administration of the water extract from grace pomace and catechin, which were equally effective. These results suggest that the neuroprotection induced by the extract could be ascribed, albeit partially, to its catechin content.

Unravelling the Phytochemical Composition and the Pharmacological Properties of an Optimized Extract from the Fruit from Prunus mahaleb L.: From Traditional Liqueur Market to the Pharmacy Shelf.

Prunus mahaleb L. fruit has long been used in the production of traditional liqueurs. The fruit also displayed scavenging and reducing activity, in vitro. The present study focused on unravelling peripheral and central protective effects, antimicrobial but also anti-COVID-19 properties exerted by the water extract of P. mahaleb. Anti-inflammatory effects were studied in isolated mouse colons exposed to lipopolysaccharide. Neuroprotection, measured as a blunting effect on hydrogen-peroxide-induced dopamine turnover, was investigated in hypothalamic HypoE22 cells. Antimicrobial effects were tested against different Gram+ and Gram- bacterial strains. Whereas anti-COVID-19 activity was studied in lung adenocarcinoma H1299 cells, where the gene expression of ACE2 and TMPRSS2 was measured after extract treatment. The bacteriostatic effects induced on Gram+ and Gram- strains, together with the inhibition of COX-2, TNFα, HIF1α, and VEGFA in the colon, suggest the potential of P. mahaleb water extract in contrasting the clinical symptoms related to ulcerative colitis. The inhibition of the hydrogen peroxide-induced DOPAC/DA ratio indicates promising neuroprotective effects. Finally, the downregulation of the gene expression of ACE2 and TMPRSS2 in H1299 cells, suggests the potential to inhibit SARS-CoV-2 virus entry in the human host. Overall, the results support the valorization of the local cultivation of P. mahaleb.

Antioxidant and Neuroprotective Effects Induced by Cannabidiol and Cannabigerol in Rat CTX-TNA2 Astrocytes and Isolated Cortexes.

Cannabidiol (CBD) and cannabigerol (CBG) are Cannabis sativa terpenophenols. Although CBD's effectiveness against neurological diseases has already been demonstrated, nothing is known about CBG. Therefore, a comparison of the effects of these compounds was performed in two experimental models mimicking the oxidative stress and neurotoxicity occurring in neurological diseases. Rat astrocytes were exposed to hydrogen peroxide and cell viability, reactive oxygen species production and apoptosis occurrence were investigated. Cortexes were exposed to K+ 60 mM depolarizing stimulus and serotonin (5-HT) turnover, 3-hydroxykinurenine and kynurenic acid levels were measured. A proteomic analysis and bioinformatics and docking studies were performed. Both compounds exerted antioxidant effects in astrocytes and restored the cortex level of 5-HT depleted by neurotoxic stimuli, whereas sole CBD restored the basal levels of 3-hydroxykinurenine and kynurenic acid. CBG was less effective than CBD in restoring the levels of proteins involved in neurotransmitter exocytosis. Docking analyses predicted the inhibitory effects of these compounds towards the neurokinin B receptor. Conclusion: The results in the in vitro system suggest brain non-neuronal cells as a target in the treatment of oxidative conditions, whereas findings in the ex vivo system and docking analyses imply the potential roles of CBD and CBG as neuroprotective agents.

Reconsidering Hydrosols as Main Products of Aromatic Plants Manufactory: The Lavandin (Lavandula intermedia) Case Study in Tuscany.

: The present work evaluates for the first time two Lavandin (Lavandula × intermedia Emeric ex Loisel.) aromatic waters obtained from different plant organs, the flowers and the stems. Both extracts were analysed by GC-MS, which indicates semi-quantitative differences between the major metabolites including linalool, 1,8-cineole, camphor, linalyl acetate and 4-terpineol. 1H-NMR and LC-MS investigation confirmed the presence of these compounds. Moreover, behavioural tests with the food insect pest Tribolium confusum (Coleoptera Tenebrionidae) showed a good repellency for both hydrosols extracts with RD50 values of 3.6 and 3.3 µL cm-2 for the flowers and stems, respectively; at the higher concentrations, however, the hydrosol extract from the flowers is expected to be more effective than the one from the stems. The effect of the flowers and stems aromatic water of Lavandin on seed germination of Raphanus sativus was also evaluated. Results showed that seed germination was completely inhibited by flowers hydrolate, having a possible application as natural herbicide. The overall experience with these Lavandin extracts indicates the potential of improved hydrolates to become the main distillation products, rather than by-products, of the aromatic plants manufacturing; this stimulates further discussions about the potential positive impacts that such a shift could have in the context of ecopharmacognosy.

Phytocomplex Characterization and Biological Evaluation of Powdered Fruits and Leaves from Elaeagnus angustifolia.

Fully ripe fruits and mature leaves of Elaeagnus angustifolia were harvested and analyzed by means of analytical and biological tests to better comprehend the chemical composition and therapeutic/nutraceutical potential of this plant. Fruits and leaves were dried and the obtained powders were analyzed to study their color character and (via headspace gas chromatography) describe the chemical profile. Subsequently, they were submitted to a chloroform-methanol extraction, to a hydroalcoholic extraction procedure assisted or not by microwaves, and to an extraction with supercritical CO2, assisted or not by ethanol as the co-solvent, to detect the polyphenolic and the volatile content. The resulting extracts were evaluated in terms of chlorophyll and carotenoid content, polyphenolic content, volatile fraction, total phenolic content, total flavonoid content, antioxidant activity, radical scavenging activity, and enzymatic inhibition activity. The results confirmed the correlation between the chemical composition and the high antioxidant potential of leaf extracts compared to the fruit extracts in terms of the phenolic and pigment content. A promising effect against tyrosinase emerged for all the extracts, suggesting a therapeutic/nutraceutical use for this plant. Conversely, the volatile content from both natural matrices was similar.

Anti-Inflammatory and Neuromodulatory Effects Induced by Tanacetum parthenium Water Extract: Results from In Silico, In Vitro and Ex Vivo Studies.

Tanacetum parthenium (feverfew) has traditionally been employed as a phytotherapeutic remedy in the treatment of migraine. In this study, a commercial T. parthenium water extract was investigated to explore its anti-inflammatory and neuromodulatory effects. Isolated mouse cortexes were exposed to a K+ 60 mM Krebs-Ringer buffer and treated with T. parthenium water extract. The prostaglandin E2 (PGE2) level, brain-derived neurotrophic factor (BDNF), interleukin-10 (IL-10), and IL-1ß gene expression were evaluated in the cortex. The effects on dopamine (DA) release and dopamine transporter (DAT) gene expression were assayed in hypothalamic HypoE22 cells. A bioinformatics analysis was conducted to further investigate the mechanism of action. The extract was effective in reducing cortex PGE2 release and IL-1ß gene expression. In the same experimental system, IL-10 and BDNF gene expressions increased, and in HypoE22 cells, the extract decreased the extracellular dopamine level and increased the DAT gene expression due to the direct interaction of parthenolide with the DAT. Overall, the present findings highlight the efficacy of T. parthenium water extract in controlling the inflammatory pathways that occur during cortical-spreading depression. Additionally, the inhibition of the hypothalamic DA release observed in this study further supports the role of dopaminergic pathways as key targets for novel pharmacological approaches in the management of migraine attacks.

Qualitative Phytochemical Fingerprint and Network Pharmacology Investigation of Achyranthes aspera Linn. Extracts.

Achyranthes aspera Linn. (Amaranthaceae), commonly known as the Prickly Chaff flower, is used as herbal medicine in the Ivorian's culture, Africa. Nonetheless, there is currently a paucity of scientific information on A. aspera from the Ivory Coast. Herein, the antioxidant activity of A. aspera extracts (methanol, dichloromethane, ethyl acetate and infusion) as well as the enzymatic inhibitory potentials towards key enzymes in human diseases, namely Alzheimer's disease, (cholinesterases: AchE and BChE), type 2 diabetes (α-glucosidase and α-amylase) and hyperpigmentation (tyrosinase) were assessed. The total phenolic (TPC) and flavonoid (TFC) content was determined using colorimetric methods and the individual compounds were characterized using ultra-high performance liquid chromatography coupled with hybrid quadrupole-Orbitrap high resolution mass spectrometry (UHPLC-HRMS). Furthermore, a network pharmacology analysis was conducted to predict putative targets of identified phenolic compounds. The highest TPC was observed in the infused extract (28.86 ± 0.12 mg GAE/g), while the dichloromethane extract (38.48 ± 1.48 mg RE/g) showed the highest level of TFC. UHPLC-HRMS analysis has revealed an abundance of fatty acids, flavonoids, phenols and acylquinic acids. Among tested extracts, the infused extract displayed the highest free radical quenching, reducing and metal-chelating ability. The extracts (except infusion) were effective as enzyme inhibitors against AChE, while only methanolic and infused extracts showed noteworthy anti-BChE effects. The methanolic extract showed a remarkable antityrosinase effect (56.24 ± 5.05 mg KAE/g), as well. Modest to moderate inhibitory activity was observed against α-amylase (all extracts) and α-glucosidase (only dichloromethane extract). Finally, the network pharmacology analysis suggested the carbonic anhydrase II enzyme as a putative target for explaining, at least in part, the traditional use of A. aspera preparations as diuretic and blood clotting agent. Data amassed herein tend to validate the use of A. aspera in traditional medicine, as well as act as a stepping stone for further studies in the quest for novel phytopharmaceuticals. In this context, it is desirable that this study will contribute to the validation of the traditional uses of this plant in the African herbal medicine, and to the valorization of the whole chain production of A. aspera, as a local and sustainable botanical resource.

Phytochemical Analysis, Network Pharmacology and in Silico Investigations on Anacamptis pyramidalis Tuber Extracts.

Anacamptis pyramidalis (L.) Rich. forms part of the Orchidaceae family that is highlyvalued for its horticultural as well as therapeutic benefits. The present study set out to investigatethe inhibitory activity of A. pyramidalis tubers against key biological targets for the management oftype 2 diabetes, Alzheimer disease, and skin hyperpigmentation. In addition, the antioxidantpotential of the extracts was also assessed using multiple methods. The detailed phytochemicalprofiles of the extracts were determined using high-performance liquid chromatography. Based onqualitative phytochemical fingerprint, a network pharmacology analysis was conducted as well.Parishin was identified from the water extract only, whereas gastrodin and caffeic acid derivativeswere present in the methanol extract. The methanol extract exhibited high inhibitory activityagainst tyrosinase (69.69 mg kojic acid equivalent/g extract), α-amylase (15.76 mg acarboseequivalent/g extract), and α-glucosidase (20.07 mg acarbose equivalent/g extract). Similarly, themethanol extract showed highest antioxidant potential (22.12, 44.23, 45.56, and 29.38 mg Troloxequivalent/g extract, for 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), CUPric Reducing Antioxidant Capacity (CUPRAC),and Ferric Reducing Antioxidant Power (FRAP) assays, respectively). Finally, the results ofnetwork pharmacology analysis, besides corroborating traditional uses of plant extracts in themanagement of cold and flu, confirmed a direct involvement of identified phytochemicals in theobserved enzyme inhibitory effects, especially against tyrosinase, α-amylase, and α-glucosidase.Furthermore, based on the results of both colorimetric assays and network pharmacology analysis related to the activity of A. pyramidalis extracts and identified phytocompounds on enzymesinvolved in type 2 diabetes, a docking study was conducted in order to investigate the putativeinteractions of oxo-dihydroxy octadecenoic acid trihydroxy octadecenoic acid against aldosereductase, peroxisome proliferator-activated receptor (PPAR)-α, dipeptidyl peptidase (DPP)-IV,and α-glucosidase. Docking analysis suggested the inhibitory activity of these compounds againstthe aforementioned enzymes, with a better inhibitory profile shown by oxo-dihydroxyoctadecenoic acid. Overall, the present findings supported the rationale for the use of A.pyramidalis as source of bioactive metabolites and highlight, today more than ever, for the strongnecessity of linkage strategy between wild resource valorization and conservation policy.