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.

Pectin a multifaceted biopolymer in the management of cancer: A review.

This review article focuses on the multifaceted roles of pectin in cancer management, namely as an oncotherapeutic delivery vehicle and a pharmacological agent. Over the past decades, the potential of pectin as a novel therapeutical agent for the prevention and/or management of cancer has gained increasing interest. Pectin has been found to modulate different mechanisms involved in the onset and progression of carcinogenesis, such as galectin-3 inhibition, caspase-3-induced apoptosis, and autophagy. Elucidating the structure-activity relationship provides insight into the relationship between the structure of pectin and different mechanism/s. The bioactivity of pectin, with respect to its structure, was critically discussed to give a better insight of the relationship between the structure of the extracted pectin and the observed bioactive effects. The rhamnogalacturonan I part of the pectin chain was found to bind to galectin-3, associated with several cancer hallmarks. The anti-inflammatory and antioxidant potential of pectin were also described. The roles of pectin as a treatment enhancer and a drug delivery vehicle for oncotherapeutics were critically defined. The scientific findings presented in this paper are expected to highlight the potential and role of pectin recovered from various plant sources in preventing and managing cancer.

The functional potential of nine Allium species related to their untargeted phytochemical characterization, antioxidant capacity and enzyme inhibitory ability.

In this study, the aerial parts and bulbs of nine Allium species were investigated for their functional phytochemical profile, in vitro antioxidant activities, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-amylase, α-glucosidase, and tyrosinase inhibitory properties. Phenolics, alkaloids, glucosinolates and other sulfur-containing compounds were distinctively profiled in the different species. Maceration in methanol allowed recovering the highest cumulative phenolic content in A. scabrifolium (42.31 mg/g), followed by A. goekyigiti (33.15 mg/g) and A. atroviolaceum (28.35 mg/g). The aerial parts of all Allium species showed high in vitro antioxidant activity whereas methanolic extract of A. cappadocicum bulb showed the highest inhibition against AChE (2.44 mg galantamine equivalent/g) and the water extracts of A. isauricum aerial part were the best BChE inhibitors (4.31 mg galantamine equivalent/g). Bulbs were the richer source of oligosaccharides, and in vitro digestion determined an increase of oligosaccharides bioaccessibility. A promising nutraceutical potential could be highlighted in our understudied Allium species.

Conventional and Non-Conventional Targets of Natural Products in the Management of Diabetes Mellitus and Associated Complications.

BACKGROUND: Diabetes Mellitus (DM) is a severe endocrine metabolic disease coupled with various long-term complications. A plethora of targets have been identified, however, with possible adverse effects. Therefore, researchers are in the perpetual quest for safe and more effective therapeutics. Natural products, particularly derived from plants, have proven to exert anti-diabetic effects via diverse mechanisms. METHODS: An overview of DM pathogenesis and its associated micro- and macro-vascular complications is presented. Possible underlying mechanisms of herbal remedies in DM management are provided, highlighting some key therapeutic targets. The review also appraises the recent progress of herbal products in treating DM through regulating inflammation and gut microbiota. Finally, currently available pharmacological treatments are discussed. RESULTS: The results show that numerous plants have proven to be promising sources of insulin secreting agents, α-glucosidase and α-amylase inhibitors. Among the non- conventional targets, inhibition of key enzymes such as lipase, cholinesterases and angiotensin converting enzyme has been directly and/or indirectly linked to DM and DM complications. For instance, hypericin, pseudohypericin and I3,II8-biapigenin isolated from Hypericum perforatum L., and palmatine and columbamine isolated from Dichocarpum auriculatum (Franch.) W. T. Wang & P. K have been found to be powerful lipase and cholinesterase inhibitors, respectively. Moreover, a number of plant-derived compounds such as feruloylated oligosaccharides from maize bran, baicalein and berberine are reported to mediate anti-diabetic property via modulation of gut microbiota. CONCLUSION: The information amassed in this review is anticipated to provide useful scientific baseline information to support advanced research in natural antidiabetic drug development.

Exploring the Chemical Profiles and Biological Values of Two Spondias Species (S. dulcis and S. mombin): Valuable Sources of Bioactive Natural Products.

Spondias species have been used in traditional medicine for different human ailments. In this study, the effect of different solvents (ethyl acetate, methanol, and water) and extraction methods (infusion, maceration, and Soxhlet extraction) on the enzyme inhibitory activity against acetylcholinesterase, butyrylcholinesterase, tyrosinase, α-amylase, α-glucosidase, and antioxidant properties of S. mombin and S. dulcis leaves and stem bark were evaluated. Ultra-high-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) yield in the identification and/or annotation of 98 compounds showing that the main secondary metabolites of the plant are gallic and ellagic acids and their derivatives, ellagitannins, hydroxybenzoic, hydroxycinnamic, acylquinic acids and flavonols, flavanones, and flavanonols. The leaves infusion of both Spondias species showed highest inhibition against acetylcholinesterase (AChE) (10.10 and 10.45 mg galantamine equivalent (GALAE)/g, for S. dulcis and S. mombin, respectively). The ethyl acetate extracts of the stem bark of S. mombin and S. dulcis actively inhibited α-glucosidase. Methanolic extracts of the leaves and stem bark exhibited highest tyrosinase inhibitory action. Antioxidant activity and higher levels of phenolics were observed for the methanolic extracts of Spondias. The results suggested that the Spondias species could be considered as natural phyto-therapeutic agents in medicinal and cosmeceutical applications.

Chemical composition, biological properties and bioinformatics analysis of two Caesalpina species: A new light in the road from nature to pharmacy shelf.

Caesalpinia bonduc and C. decapeleta var. japonica have great importance in traditional medicine systems but scientific information's are still lacking for their potentials. To explore their bioactivity, we assessed the antioxidant, enzyme inhibitory abilities of the dichloromethane (DCM), ethyl acetate, methanol, and water extracts prepared from the leaves and bark. The cytotoxicity and anticancer properties of the extracts were also assessed in vitro. The water extract of C. decapeleta leaves possessed highest phenolic content (108.16 mg gallic acid equivalent (GAE)/g extract), while the highest flavonoid content was recorded for the C. bonduc leaf methanolic extract (27.89 mg rutin equivalent (RE)/g extract). In general, C. decapeleta extracts possessed higher radical scavenging potential compared to C. bonduc extracts. C. decapeleta DCM leaves extract (10.20 mg galantamine equivalent (GALAE)/g extract) showed highest inhibition against butyrylcholinesterase. The cytotoxicity of the most potent methanolic and aqueous extracts were assessed against four cell lines. The chemical profiles of both species appeared to be different. C. bonduc was abundant in organic and phenolic acids as well as their esters. Flavonoid glycosides, bonducellin and its derivatives and caesalminaxins were identified. Whereas, C. decalpetala possessed many galloylated compounds. The cytotoxicity of C. bonduc and C. decapetala extracts was tested using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) based assay on VERO (kidney of an adult African Green monkey cells), HeLa (human cervical adenocarcinoma cells), RKO (human colon carcinoma cells), FaDu (human hypopharyngeal squamous carcinoma cells) cell lines. C. bonduc bark water extract exhibited the highest cytotoxicity towards HeLa (50 % cytotoxic concentration (CC50): 28.5 µg/mL) cancer cell line, as compared to normal VERO cells (CC50:35.87 µg/mL). For C. decapetala, the highest cytotoxicity was found for bark methanol extract on the HeLa cells with CC50 of 46.08 µg/mL and selectivity index of 3.33. In the gene ontology analysis, prostate cancer, nuclear factor kappa B (NF-kappa B) signaling, proteoglycans in cancer pathways might support the results of the cytotoxic assays. These results showed that the tested Caesalpinia species, showing potent inhibitory action against butyrylcholinesterase, might represent novel phytotherapeutic avenues for the management of Alzheimer's disease.

Identification of bioactive compounds from Rhaponticoides iconiensis extracts and their bioactivities: An endemic plant to Turkey flora.

Rhaponticoides iconiensis (Hub.-Mor.) M.V.Agab. & Greuter. (Asteraceae) is an endemic species spread in several small populations in the province of Konya (Turkey). It is critically endangered with an extremely high risk of extinction. Recently, based on the molecular phylogenetic and eco geographical studies on Cardueae-Centaureinae, the genus Rhaponticoides Vaill. was separated from Centaurea L. Antioxidant properties and enzyme inhibition, as well as the phenolic and flavonoid contents, of the methanol (Soxhlet extraction and maceration) and water (infusion) extracts of R. iconiensis leaves, roots, and flower heads were determined. The methanol extracts of R. iconiensis leaves contained the highest amount of phenolic (52.37 and 54.37 mg gallic acid equivalent/g) and flavonoids (74.13 and 80.75 mg rutin equivalent/g). Accordingly, the leaves methanol extracts showed the highest antioxidant potential. Interestingly, the roots methanol extracts were the most potent acetylcholinesterase (4.75 mg galantamine equivalent/g) and butyrylcholinesterase inhibitors (5.26 and 5.14 mg galantamine equivalent/g). The leaves and roots methanol extracts exhibited high α-glucosidase (2.48-3.08 mmol acarbose equivalent/g) and α-amylase (0.17-0.70 mmol acarbose equivalent/g) inhibition. The highest tyrosinase inhibition was recorded for leaves methanol extracts (138.79 and 140.34 mg kojic acid equivalent/g). 87 natural products (including hydroxybenzoic, hydroxycinnamic and acylquinic acids, flavones, flavonols, flavanones and anthocyanins) were unambiguously identified or tentatively annotated in the studied extracts. Findings presented in the present study appraise the bioactivity of R. iconiensis, an understudied species.

Chemical Characterization and Bioactive Properties of Different Extracts from Fibigia clypeata, an Unexplored Plant Food.

Fibigia clypeata (L.) Medik. is a poorly studied plant species belonging to the Brassicaceae family, and usually used as cress in the salads. The current investigation aimed at assessing the antioxidant potential and inhibitory activity of ethyl acetate, methanol, and aqueous extracts of F. clypeata against key enzymes targeted in the management of type II diabetes (α-amylase and α-glucosidase), Alzheimer's disease (acetylcholinesterase and butyrylcholinesterase), and skin hyperpigmentation (tyrosinase). Cytotoxicity of the extracts was also determined using normal VERO and cancer FaDu and SCC-25 cell lines. Besides, LC-MS was employed to investigate the detailed phytochemical profiles of the extracts. The methanol extract showed potent enzyme inhibitory activity (4.87 mg galantamine equivalent/g, 3.52 mg galantamine equivalent/g, 126.80 mg kojic acid equivalent/g, and 24.68 mg acarbose equivalent/g, for acetylcholinesterase, butyrylcholinesterase, tyrosinase, and α-glucosidase, respectively) and antioxidant potential (96.52, 109.10, 154.02, and 104.85 mg trolox equivalent/g, for DPPH, ABTS, CUPRAC, and FRAP assays, respectively). Interestingly, caffeic acid-O-hexoside derivative, caffeyl alcohol O-glucopyranoside, and ferulic acid derivative were identified in all extracts. F. clypeata extracts showed no cytotoxicity towards VERO cell line and a weak cytotoxic potential against FaDu and SCC-25 cell lines. Interesting scientific evidence gathered from the present study support further investigation on F. clypeata in the view of designing and developing a novel therapeutic agent for the management of Alzheimer's disease, type II diabetes, skin hyperpigmentation problems, as well as cancer.

Metabolomics profiling and biological properties of root extracts from two Asphodelus species: A. albus and A. aestivus.

The pharmacological properties of Asphodelus species have been advocated previously. In this respect, the present study attempts to unravel the antioxidant and enzyme inhibitory activity of root extracts of two Asphodelus species, namely, A. albus and A. aestivus. Data gathered demonstrated that the dichloromethane (25.49, 51.30, 104.31, and 81.58 mg Trolox equivalents [TEs]/g, for 2,2-diphenyl-1-picrylhydrazyl [DPPH], 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) [ABTS], cupric ion reducing antioxidant capacity [CUPRAC], and ferric reducing antioxidant power[FRAP] assays respectively) and ethyl acetate (20.60, 41.86, 89.07, and 57.85 mg TEs/g, for DPPH, ABTS, CUPRAC, and FRAP assays respectively) extracts of A. albus roots showed highest radical scavenging and reducing potential. These findings were in accordance with total phenolic content observed which showed the highest phenolic content of A. albus dichloromethane (30.74 mg gallic acid equivalents [GAEs]/g) and ethyl acetate (23.41 mg GAEs/g) extracts. Interestingly, A. albus and A. aestivus root extracts were active inhibitors of tyrosinase and lipase, with values varying from 56.52 to 71.49 mg kojic acid equivalent/g and 34.88 to 86.32 mg orlistat equivalent/g, respectively. Flavonoids, anthraquinones, and phenolic acids were identified as main individual compounds in chemical profile analysis. This is the first report of the presence of aloin A, aloin B, and aloesin in species other than in Aloe. Scientific evidences gathered from this study claimed the biological activity of the studied Asphodelus species and provided rationale for further investigations which might lead to the development of novel pharmacophores to alleviate oxidative stress related complications, obesity, as well as, skin hyperpigmentation complications.

Chemical characterization, antioxidant, enzyme inhibitory and cytotoxic properties of two geophytes: Crocus pallasii and Cyclamen cilicium.

The Crocus and Cyclamen genus have been reported to possess diverse biological properties. In the present investigation, two geophytes from these genus, namely Crocus pallasi and Cyclamen cilicium have been studied. The in vitro antioxidant, enzyme inhibitory, and cytotoxic effects of the methanol extracts of Crocus pallasii and Cyclamen cilicium aerial and underground parts were investigated. Antioxidant abilities of the extracts were investigated via different antioxidant assays (metal chelating, radical quenching (ABTS and DPPH), reducing power (CUPRAC and FRAP) and phosphomolybdenum). Cholinesterases, amylase, tyrosinase, and glucosidase were used as target enzymes for detecting enzyme inhibitory abilities of the samples. Regarding the cytotoxic abilities, breast cancer cell lines (MDA-MB 231 and MCF-7) and prostate cancer cell lines (DU-145) were used. The flowers extracts of Crocus pallasii and C. cilicium possessed the highest flavonoid content. The highest phenolic content was recorded from C. cilicium root extract (47.62 mg gallic acid equivalent/g extract). Cyclamen cilicium root extract showed significantly (p < 0.05) high radical scavenging (94.28 and 139.60 mg trolox equivalent [TE]/g extract, against DPPH and ABTS radicals, respectively) and reducing potential (173.30 and 109.53 mg TE/g extract, against CUPRAC and FRAP, respectively). The best acetylcholinesterase, glucosidase and tyrosinase inhibition was observed in C. cilicium root (4.46 mg GALAE/g; 15.75 mmol ACAE/g; 136.99 mg KAE/g, respectively). Methanolic extracts of C. pallasii and C. cilicium showed toxicity against breast cancer cell lines. In light of the above findings, C. cilicium might be considered as an interesting candidate in the development of anti-cancer agent coupled with antioxidant properties.

Ricinodendronheudelotii(Baill.) Heckelstem barks and seed extracts, a native food plant from Africa: Characterization by NMR and HPLC-DAD-ESI-MSn.

Ricinodendron heudelotii (Baill.) Heckle is used as food ingredient and in the African traditional medicine. In the present study inhibitory activity on α-amylase, α-glucosidase, acetylcholinesterase, butyrylcholinesterase, and tyrosinase of ethyl acetate, methanol, and water extracts of R. heudelotii seeds and stem bark were assessed. Stem bark extracts exhibited significant antioxidant properties. Ethyl acetate extract of seed had great inhibitory potential against α-glucosidase, acetylcholinesterase, and butyrylcholinesterase. Nuclear magnetic resonance (NMR) and high-performance liquid chromatography with electrospray ionization mass spectrometry (HPLC-DAD-ESI-MSn) analysis revealed the presence of catechin and gallic acid derivatives in bark while fatty acid in seeds. Multivariate analysis of obtained data was performed showing a clear separation between seed and stem bark. Obtained results indicate R. heudelotii stem bark as new starting materials for the development of novel pharmaceutical formulations.

Evaluation of Pharmacological and Phytochemical Profiles Piptadeniastrum africanum (Hook.f.) Brenan Stem Bark Extracts.

The stem bark (SB) of Piptadeniastrum africanum (PA) has been extensively used in African traditional medicinal systems. However, there is a dearth of scientific information regarding its possible activity in the management of type II diabetes, Alzheimer's disease, and skin hyperpigmentation disorders. This study therefore attempted to elucidate the in vitro inhibitory action of ethyl acetate, methanol, and water extracts of P. africanum stem bark (PA-SB) on α-amylase, α-glucosidase, acetylcholinesterase, butyrylcholinesterase, and tyrosinase. Cell viability, catecholamine, and 3-hydroxykynurenine levels of hypothalamic HypoE22 cells exposed to PA-SB extracts were also investigated. The phytochemical profiles of the extracts were determined by high performance liquid chromatography (HPLC) and antioxidant properties were investigated. Saponin (867.42 mg quillaja equivalent/g) and tannin (33.81 mg catechin equivalent/g) contents were higher in the methanol extract. Multiple dihydroxy-trimethoxy(iso)flavone isomers, loliolide, eriodictyol, naringenin, luteolin, chrysoeriol, apigenin, and liquiritigenin, were characterized from PA-SB extracts using HPLC. The methanol extract of PA-SB showed highest inhibitory activity against acetylcholinesterase (4.88 mg galantamine equivalent (GALAE)/g extract), butyrylcholinesterase (5.37 mg GALAE/g extract), and tyrosinase (154.86 mg kojic acid equivalent/g extract) while α-glucosidase was effectively inhibited by the ethyl acetate extract (15.22 mmol acarbose equivalent/g extract). The methanol extract of PA-SB also showed potent antioxidant properties (493.87, 818.12, 953.07, and 732.19 mg Trolox equivalent/g extract, for 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS), cupric reducing antioxidant capacity (CUPRAC), and ferric reducing antioxidant power (FRAP) assays, respectively). PA-SB extracts exhibited antioxidant activity and promising inhibition against key enzymes related to type II diabetes, Alzheimer's disease, and skin hyperpigmentation disorders. Additionally, all extracts were able to contrast hydrogen peroxide-induced oxidative stress, in HypoE22 cells, thus restoring basal catecholamine and 3-hydroxykinurenine levels, whereas only methanol and water extracts stimulated basal dopamine release. Overall, data from the present study contribute to the biological assessment of P. africanum that appears to be a promising source of natural compounds with protective and neuromodulatory effects.

Biopotential of Bersama abyssinica Fresen Stem Bark Extracts: UHPLC Profiles, Antioxidant, Enzyme Inhibitory, and Antiproliferative Propensities.

In this study, ethyl acetate, methanol, and water extracts of Bersama abyssinica (Melianthaceae) stem bark were screened for enzyme inhibitory and antioxidant properties. The water extract possessed the highest concentration of phenols (230.83 mg gallic acid equivalent/g extract), while the methanol extract was rich in flavonoids (75.82 mg rutin equivalent/g extract), and the ethyl acetate extract possessed the highest amount of saponins (97.37 mg quillaja equivalent/g). The aim of this study was to investigate the antiproliferative effects against the human colon cancer HCT116 cell line challenged with serotonin (5-HT) as a stimulating-proliferation factor. The level of HCT116 cell-deriving pool of kynurenic acid (KA) was also assessed. The UHPLC results confirmed the presence of 58, 68, and 63 compounds in the ethyl acetate, methanol, and water extracts, respectively. Mangiferin, vitexin and its isomer isovitexin were tentatively identified in all extracts and KA (m/z 190.05042 [M-H]+) was also tentatively identified in the methanol and water extracts. The methanol extract (1464.08 mg Trolox equivalent [TE]/g extract) showed the highest activity in the CUPRAC assay, whereas the water extract (1063.70 mg TE/g extract) showed the highest activity with the FRAP technique. The ethyl acetate extract was the most active acetylcholinesterase (4.43 mg galantamine equivalent/g extract) and α-glucosidase (mmol acarbose equivalent /g extract) inhibitor. The water extract was able to inhibit 5-HT-stimulated viability of HCT116 cells, and blunt 5-HT-induced reduction of cell-deriving KA. The scientific data generated in this study provide baseline data regarding the biological properties of B. abyssinica stem bark, highlighting its potential use for the development of new pharmaceutic and cosmetic agents.

Bridelia speciosa Müll.Arg. Stem bark Extracts as a Potential Biomedicine: From Tropical Western Africa to the Pharmacy Shelf.

Bridelia species have been used in traditional African medicine for the management of diverse human ailments. In the current work, the detailed phytochemical profiles of the extracts of the stem bark of B. speciosa were evaluated and the antioxidant and enzyme inhibitory properties of the extracts were assessed. The anti-bacterial and anti-mycotic effects of the extracts were evaluated against selected pathogen strains. Additionally, the anti-proliferative effects were studied on the liver cancer HepG2 cell line. Finally, the putative protective effects were assessed on isolated rat liver that was challenged with lipopolysaccharide (LPS). The results revealed the presence of 36 compounds in the ethyl acetate extract, 44 in the methanol extract, and 38 in the water extract. Overall, the methanol extract showed the highest antioxidant activity, particularly in LPS-stimulated rat liver. Additionally, this extract exerted the highest antimycotic effect on C. albicans, whereas the water extract showed a promising anti-proliferative effect on liver cancer HepG2 cells. The methanol extract was also the most active as enzyme inhibitor, against acetylcholinesterase and butyrylcholinesterase. The current study appraises the antioxidant and enzyme inhibition properties of B. speciosa methanol extract and showed that this specie could be a promising source of biologically active phytochemicals, with potential health uses.