Therapeutic Effect of an Ursolic Acid-Based Nutraceutical on Neuronal Regeneration after Sciatic Nerve Injury.

Peripheral nerve injuries lead to severe functional impairments and long recovery times, with limited effectiveness and accessibility of current treatments. This has increased interest in natural bioactive compounds, such as ursolic acid (UA). Our study evaluated the effect of an oleolyte rich in UA from white grape pomace (WGPO) on neuronal regeneration in mice with induced sciatic nerve resection, administered concurrently with the induced damage (the WGPO group) and 10 days prior (the PRE-WGPO group). The experiment was monitored at two-time points (4 and 10 days) after injury. After 10 days, the WGPO group demonstrated a reduction in muscle atrophy, evidenced by an increased number and diameter of muscle fibers and a decreased Atrogin-1 and Murf-1 expression relative to the denervated control. It was also observed that 85.7% of neuromuscular junctions (NMJs) were fully innervated, as indicated by the colocalization of α-bungarotoxin and synaptophysin, along with the significant modulation of Oct-6 and S-100. The PRE-WGPO group showed a more beneficial effect on nerve fiber reformation, with a significant increase in myelin protein zero and 95.2% fully innervated NMJs, and a pro-hypertrophic effect in resting non-denervated muscles. Our findings suggest WGPO as a potential treatment for various conditions that require the repair of nerve and muscle injuries.

Chemical exploration of different extracts from Phytolacca americana leaves and their potential utilization for global health problems: in silico and network pharmacology validation.

Phytolacca americana L. is of great interest as a traditional additive in various folk remedies in several countries, including Turkey. We aimed to determine the chemical profile (assisted by high-Performance liquid chromatography-electrospray ionization-tandem mass apectrometry (HPLC-ESI-MS/MS) experiments of three extracts obtained by different polarity solvents viz. ethyl acetate (to extract semipolar compounds), methanol and water (to extract highly polar metabolites) from P. americana leaves. Their anti-diabetic effects were investigated in vitro by assessing their inhibition toα-amylase and α-glucosidase. Assessment of the neuroprotective potential of the three extracts was carried out against acetyl-(AChE) and butyryl-(BChE) cholinesterase enzymes. HPLC-ESI-MS/MS experiments showed a total of 17 chromatographic peaks primarily classified to six flavonoids, two saponins, and six fatty acids. Antioxidant assays revealed remarkable activity for the ethyl acetate and methanol extracts. The BChE inhibition was considerably more significant (4.08 mg galantamine equivalent (GALAE)/g) for the ethyl acetate extract, whereas the methanol extract had good inhibitory efficacy for AChE (2.05 mg GALAE/g). Through network pharmacology, the compounds' mechanism of action of targeted key gene in their associated diseases were identified. The hubb gene signal transducer and activator of transcription 3 (STAT3) and tumour necrosis factor (TNFα) where the P. americana compound's site of action in inflammation bowel disease. The results offer possibilities for the prospective application of P. americana in metabolic regulation, blood glucose control, and as a source of bioactive compounds with cholinesterase enzyme inhibitory characteristics which could be of relevance in the cosmetic or pharmaceutical industry for combating melanogenesis.Communicated by Ramaswamy H. Sarma.

Understanding the Chemical Composition and Biological Activities of Different Extracts of Secamone afzelii Leaves: A Potential Source of Bioactive Compounds for the Food Industry.

Secamone afzelii (Roem. & Schult.) K. Schum (family Asclepiadaceae) is a creeping woody climber used to treat ailments in many traditional medicine systems. The present study aims to examine the antioxidant and enzyme inhibition activities of S. afzelii leaf using different compositions of methanol-water mixture as an extraction solvent. The extracts were characterized by HPLC-ESI-MSn in terms of chemical compounds. The in silico results show that compound 23 (quercitrin) has the higher docking scores among the selected substances and the MD simulation revealed that the interactions with the enzymatic pocket are stable over the simulation time and strongly involve the tyrosinase catalytic Cu atoms. All together the results showed that both 80% and 100% methanolic extracts contained significantly (p < 0.05) the highest total phenolics content while the highest content of total flavonoids was significantly (p < 0.05) extracted by 100% methanol. About 26 compounds were tentatively identified by HPLC-ESI-MSn and 6 of them were quantified using standards. Results showed that the extracts were rich in flavonoids with a relatively high abundance of two kaempferol glycosides comprising 60% of quantified compounds. The 100% and 80% methanol extracts recorded significantly (p < 0.05) the highest total antioxidant, DPPH and ABTS activity as well as tyrosinase and ⍺-amylase inhibitory activities. The best significant (p < 0.05) cholinesterase inhibitory activity and reducing capacity of Fe+++ and Cu++ was recorded from the 80% methanolic extract while 100% ethanolic extract gave the highest significant (p < 0.05) butyrylcholinesterase inhibitory activity. The best glucosidase activity was observed in the 50% and 80% methanolic extracts. Although the water extract displayed the least total phenolics and flavonoids content and consequently the lowest antioxidant and enzyme inhibition activity, it displayed significantly (p < 0.05) the highest chelating power. In conclusion, these results demonstrated the richness of S. afzelii leaf as a potential source of bioactive compounds for the food industry, for the preparation of food supplements and functional foods.

A Study on Chemical Characterization and Biological Abilities of Alstonia boonei Extracts Obtained by Different Techniques.

In the quest for novel therapeutic agents from plants, the choice of extraction solvent and technique plays a key role. In this study, the possible differences in the phytochemical profile and bioactivity (antioxidant and enzyme inhibitory activity) of the Alstonia boonei leaves and stem bark extracted using water, ethyl acetate and methanol, and different techniques, namely infusion, maceration and Soxhlet extraction, were investigated. Data collected showed that methanol extracts of both A. boonei leaves (48.34-53.08 mg gallic acid equivalent [GAE]/g dry extract) and stem bark (37.08-45.72 mg GAE/g dry extract) possessed higher phenolic content compared to the ethyl acetate extracts (leaves: 30.64-40.19 mg GAE/g; stem bark: 34.25-35.64 mg GAE/g). The methanol extracts of A. boonei leaves showed higher radical scavenging and reducing capacity, and these findings were in accordance with phenolic content results. In general, water extracts of A. boonei leaves and stem bark obtained by infusion were poor inhibitors of acetylcholinesterase, α-amylase, α-glucosidase, and tyrosinase, except for butyrylcholinesterase. The chemical profiles of the extracts were determined by UHPLC-MS and the presence of several compounds, such as phenolic acids (caffeic, chlorogenic and ferulic acids, etc.), flavonoids (rutin and isoquercetin) and flavonolignans (Cinchonain isomers). Cell viability was tested using the human peripheral blood monocytic cell line (THP-1), and the extracts were safe up to 25 µg/mL. In addition, anti-inflammatory effects were investigated with the releasing of IL-6 TNF-α and IL-1ß. In particular, stem bark extracts exhibited significant anti-inflammatory effects. Data presented in this study highlight the key role of solvent choice in the extraction of bioactive secondary metabolites from plants. In addition, this study appraises the antioxidant and enzyme inhibitory action of A. boonei leaves and stem bark, which are extensively used in traditional medicine.

Calceolarioside A, a Phenylpropanoid Glycoside from Calceolaria spp., Displays Antinociceptive and Anti-Inflammatory Properties.

Phenylpropanoid glycosides are a class of natural substances of plant origin with interesting biological activities and pharmacological properties. This study reports the antinociceptive and anti-inflammatory effects of calceolarioside A, a phenylpropanoid glycoside previously isolated from various Calceolaria species. In models of acute nociception induced by thermal stimuli, such as the hot plate and tail flick test, calceolarioside administered at doses of 1, 5, and 10 µg in the left cerebral ventricles did not modify the behavioral response of mice. In an inflammatory based persistent pain model as the formalin test, calceolarioside A at the high dose tested (100 µg/paw) reduced the licking activity induced by formalin by 35% in the first phase and by 75% in the second phase of the test. In carrageenan-induced thermal hyperalgesia, calceolarioside A (50 and 100 µg/paw) was able to significantly reverse thermal hyperalgesia induced by carrageenan. The anti-inflammatory activity of calceolarioside A was then assessed using the zymosan-induced paw edema model. Calceolarioside A (50 and 100 µg/paw) induced a significant reduction in the edema from 1 to 4 h after zymosan administration. Measuring IL-6, TNFα, and IL-1ß pro-inflammatory cytokines released from LPS-stimulated THP-1 cells, calceolarioside A in a concentration-dependent manner reduced the release of these cytokines from THP-1 cells. Taken together, our results highlight, for the first time, the potential and selective anti-inflammatory properties of this natural-derived compound, prompting its rationale use for further investigations.

Tribulus terrestris and female reproductive system health: A comprehensive review.

BACKGROUND: Tribulus terrestris L. (T. terrestris) positive performance on the male sexual system has been confirmed, but little is known about its effects on the female reproductive system. PURPOSE: This review discussed in detail the beneficial impact of T. terrestris and its secondary metabolites on the female reproductive system. STUDY DESIGN AND METHODS: In this review, the scientific Databases of Science direct, Pubmed, Web of Science, Google, Google Scholar, Researchgate, EMBASE, Scientific Information (SID), and Elsevier were searched profoundly. Studies about the pharmacological activities of T. terrestris on the female reproductive system in each aspect of investigations: human, in vivo, and in vitro studies, in the period from 1998 to 2020 were admitted. Our study was not limited by the language of publications. RESULTS: 23 articles about the effects of T. terrestris on the female reproductive system were found. These studies approved the T. terrestris efficacy on improvements in histological features of the ovary and uterus of polycystic ovary syndrome patients as well as the well-working of normal ovaries, enhancements in the sexual desire of postmenopausal syndrome, improve ovarian and breast cancers. CONCLUSION: These studies showed that the positive effect of T. terrestris on the female reproductive system was due to the presence of a secondary metabolite called protodioscin; a steroidal saponin compound, as the dominant active component of this plant.

A comparative study of the HPLC-MS profiles and biological efficiency of different solvent leaf extracts of two African plants: Bersama abyssinica and Scoparia dulcis.

In the present study, two medicinal plants from Africa, namely Bersama abyssinica Fresen. and Scoparia dulcis L., were extracted using ethyl acetate, methanol, and water. The antioxidant, enzyme (α-amylase, α-glucosidase, acetyl- and butyrylcholinesterase, lipase, and tyrosinase) inhibitory action, and phytochemical profiles of extracts of Bersama abyssinica and Scoparia dulcis were determined. The aqueous (180.62 and 61.81 mg gallic acid equivalent/g extract, for B. abyssinica and S. dulcis respectively) and methanol (75.21 and 57.81 mg rutin equivalent/g extract, for B. abyssinica and S. dulcis, respectively) extracts contained high concentrations of phenolic and flavonoids, respectively. The ethyl acetate extracts of both plants were potent inhibitors of α-glucosidase and tyrosinase. Several phytochemical groups were determined by HPLC-MS/MS. The study tend to suggest that B. abyssinica and S. dulcis are potential candidates for the development of novel therapeutical agents.

Cucumeropsis mannii reverses high-fat diet induced metabolic derangement and oxidative stress.

Cucumeropsis mannii (CM) belongs to the melon family and is native to West Africa. There is a paucity of information on its medicinal or nutraceutical potential. Here, we examined the impact of CM in mice that were treated with a normal or a high fat diet (HFD). The CM extracts had a high levels of phenols, flavonoids, ascorbic acid and significant antioxidant activity. Treatment of mice with a HFD diet, led to the memory impairment. However, mice on HFD and received CM, despite increased food intake, showed a decrease in the body weight, locomotion, rearing, grooming, acetylcholinesterase activity and ?-amino butyric acid levels and anxiolysis. Also CM induced a reversal of HFD-induced changes in glucose levels, lipid peroxidation and super-oxide dismutase activity. These data show that CM leads to variable behavioural, biochemical and metabolic effects depending on the diet of animals.

Corylus avellana L. modulates neurobehaviour and brain chemistry following high-fat diet.

Consumption of a high-fat diet has adverse impacts on metabolism, neurobehavioral, and neurochemical homeostasis in both humans and experimental animals. Here, we examined the effects of two different cultivars of Corylus avellana L. in a mouse model of metabolic syndrome. Corylus avellana L. reduced weight gain in mice that were treated with a high-fat diet, improved their behavioral parameters as exemplified by locomotion and rearing, working-memory, and reduced grooming and anxiety indices. Both Corylus avellana L. varieties reduced blood glucose levels and lipid peroxidation, improved lipid profile, and antioxidant status in mice placed on a high fat diet. Finally, brain acetylcholinesterase activity was also reduced, dopamine level was increased, while caspase-3 level in the brain was reduced. Thus, the Corylus avellana L. cultivars improve metabolic, behavioral, and neurochemical homeostasis in a diet with a high-fat content.

Viscum album L. homogenizer-assisted and ultrasound-assisted extracts as potential sources of bioactive compounds.

Viscum album L. (Mistletoe) is one of the most famous plants in many countries utilized for several purposes. The current study aimed to describe chemical profiles and biological activities of homogenizer-assisted extract (HAE) and ultrasound-assisted extract (UAE)) of V. album parts (leaf, fruits, and seeds). Antioxidant (radical scavenging, reducing power, metal chelation, and phosphomolybdenum assays) and enzyme inhibitory properties (cholinesterases, amylase, glucosidase, and tyrosinase) were selected for biological evaluation. Chemical profiles were studied by HPLC-MS/MS and 32 compounds were identified in the extracts; caffeoylquinic acids and its derivatives, dimethylated flavonoids were the most significant compounds. Generally, the leaf extracts exhibited the best antioxidant and enzyme inhibitory effects in our tests. Multivariate analysis was performed to obtain more information for these data, then strong correlations between total bioactive compounds and tested parameters were observed. The present findings encourage us to further investigate V. album as a potential candidate for pharmaceutical and nutraceutical applications. PRACTICAL APPLICATIONS: Viscum album L. commonly called European mistletoe is a woody perennial shrub growing on coniferous trees with lathery leaves, small flowers, and white berries. It belongs to the Santalaceae R. Br. family from Europe and western/southern Asia. Traditional medicine recognizes mistletoe as a folk remedy to manage inflammation, hypertension, ulcers, and other diseases due to the presence of different bioactive compounds, among them mistletoe lectins and viscotoxins. Recent studies documented the possible therapeutic applications of Viscum extracts in association with cancer's therapy leading to improvements in health and patient's quality of life. Thus, this work gives novel data regarding the phytochemical characterizations and antioxidant/enzymatic inhibitor activities of different types of extracts from seeds, leaves, and fruits of Viscum L. obtained by homogenizer-assisted and ultrasound-assisted techniques, in order to increase the data set of potential applications in medicine.

Discovery of Kynurenines Containing Oligopeptides as Potent Opioid Receptor Agonists.

Kynurenine (kyn) and kynurenic acid (kyna) are well-defined metabolites of tryptophan catabolism collectively known as "kynurenines", which exert regulatory functions in host-microbiome signaling, immune cell response, and neuronal excitability. Kynurenine containing peptides endowed with opioid receptor activity have been isolated from natural organisms; thus, in this work, novel opioid peptide analogs incorporating L-kynurenine (L-kyn) and kynurenic acid (kyna) in place of native amino acids have been designed and synthesized with the aim to investigate the biological effect of these modifications. The kyna-containing peptide (KA1) binds selectively the m-opioid receptor with a Ki = 1.08 ± 0.26 (selectivity ratio m/d/k = 1:514:10000), while the L-kyn-containing peptide (K6) shows a mixed binding affinity for m, d, and k-opioid receptors, with efficacy and potency (Emax = 209.7 + 3.4%; LogEC50 = -5.984 + 0.054) higher than those of the reference compound DAMGO. This novel oligopeptide exhibits a strong antinociceptive effect after i.c.v. and s.c. administrations in in vivo tests, according to good stability in human plasma (t1/2 = 47 min).

Multi-targeted potential of Pittosporum senacia Putt.: HPLC-ESI-MSn analysis, in silico docking, DNA protection, antimicrobial, enzyme inhibition, anti-cancer and apoptotic activity.

Pittosporum senacia (PS) Putt. (Pittosporaceae), indigenous to the Mascarene Islands, is a common ingredient in traditional medicines. However, there is currently a dearth of studies to validate some of these traditional claims. Given the broad traditional uses of PS against several diseases, we aimed to provide a comprehensive insight into the biological and chemical profile of P. senacia. The antioxidant, enzyme inhibitory activity, anticancer, and phytochemical composition of the methanolic extract of P. senacia leaf extracts were studied. The possible interaction and binding mode of the most abundant phytochemicals were studied via in silico docking experiments on tyrosinase and α-glucosidase. The mechanism behind the cytotoxic property of P. senacia extract for MDA-MB-231 was also examined using different methods including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability test checking apoptosis-associated genes, and wound healing assays. Twenty-six compounds were identified, of which caffeoylquinic acid derivatives, ferulic acid derivative, cinnamoylquinic acid derivative and two other polyphenols (oleuropeine and isoramnetin glucoside) being abundant, have been tested using in silico studies, against α-glucosidase and tyrosinase. The extract (IC50 = 118.8 µg/ml) exhibited time and dose dependent anti-proliferative effect on human breast cancer cell line, MDA-MB-231. According to the expression profile of apoptosis inhibitors and apoptosis promoters genes, expression of Bax and Bak genes were significantly increased compared to Bcl-2 and Birc5 genes. Based on wound healing analysis, cell migration was inhibited after the application of the plant extract. The present findings suggested that PS might be a good candidate as sources of bioactive compounds for designing functional applications.

Nanoformulations of natural products for management of metabolic syndrome.

Metabolic syndrome is a common metabolic disorder which has become a public health challenge worldwide. There has been growing interest in medications including natural products as complementary or alternative choices for common chemical therapeutics regarding their limited side effects and ease of access. Nanosizing these compounds may help to increase their solubility, bioavailability, and promisingly enhance their efficacy. This study, for the first time, provides a comprehensive overview of the application of natural-products-based nanoformulations in the management of metabolic syndrome. Different phytochemicals including curcumin, berberine, Capsicum oleoresin, naringenin, emodin, gymnemic acid, resveratrol, quercetin, scutellarin, stevioside, silybin, baicalin, and others have been nanosized hitherto, and their nanosizing method and effect in treatment and alleviating metabolic syndrome have been reviewed and discussed in this study. It has been discovered that there are several pathways or molecular targets relevant to metabolic disorders which are affected by these compounds. Various natural-based nanoformulations have shown promising effect in treatment of metabolic syndrome, and therefore can be considered as future candidates instead of or in conjunction with pharmaceutical drugs if they pass clinical trials successfully.

Chemical profiling, antioxidant, enzyme inhibitory and molecular modelling studies on the leaves and stem bark extracts of three African medicinal plants.

Africa is famous for its floral biodiversity, exploited by local people for therapeutic purposes. However, such plants need to be scrutinised scientifically for the presence of bioactive compounds and possible biological properties. This study attempts for the first time to highlight the pharmacological and phytochemical profile of extracts prepared from leaves and stem barks of three African plants (Macaranga hurifolia Beille, Sterculia tragacantha Lindl. and Zanthoxylum gilletii (De Wild.) P. G. Waterman. The extracts were tested for antioxidant and enzyme inhibitory effects. Free radical scavenging, metal chelator, reducing power and phosphomolybdenum assays were performed to evaluate antioxidant effects. To identify enzyme inhibitory effects, cholinesterases (acetylcholinesterase (AChE) and butrylcholinesterase (BChE)), tyrosinase, α-amylase and α-glucosidase were selected as target enzymes. High performance liquid chromatography-Electrospray tandem mass spectrometry (HPLC-ESI-MS) technique was also used for chemical profiling. ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) and DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging assays showed that the stem barks of all three African plants were better scavenger than leaf extracts. Sterculia tragacantha was found to be a better metal chelator (64.10 ±â€¯4.66 mg EDTAE/g) among the studied plants. All extracts exhibited good clinical enzyme inhibitory activities. The stem bark of S. tragacantha exhibited the best acetylcholinesterase activity compared to the other plants. HPLC-ESI-MS characterization showed that the most abundant compounds in stem bark were flavonoids in M. hurifolia (4.2 ±â€¯0.2 mg/g DE), proanthocyanidins in S. tragacantha (42 ±â€¯1 mg/g DE) and similar concentrations of phenolic acids and flavonoids in Z. gilletii (2.8-3.1 mg/g DE). Based on the biological activity, the most abundant and relevant bioactive compounds in the extracts were studied using molecular modelling approach against tyrosinase. The studied African plants showed good antioxidant and enzymatic propensities and thus can be considered as potential bioresources for future development of nutraceuticals and/or for pharmaceutical applications.

Pharmacological, phytochemical and in-vivo toxicological perspectives of a xero-halophyte medicinal plant: Zaleya pentandra (L.) Jeffrey.

This study endeavours to investigate the phytochemical composition, biological properties and in vivo toxicity of methanol and dichloromethane extracts of Zaleya pentandra (L.) Jeffrey. Total bioactive contents, antioxidant (phosphomolybdenum and metal chelating, DPPH, ABTS, FRAP and CUPRAC) and enzyme inhibition (cholinesterases, tyrosinase α-amylase, and α-glucosidase) potential were assessed utilizing in vitro bioassays. UHPLC-MS phytochemical profiling was carried out to identify the essential compounds. The methanol extract was found to contain highest phenolic (22.60 mg GAE/g) and flavonoid (31.49 mg QE/g) contents which correlate with its most significant radical scavenging, reducing potential and tyrosinase inhibition. The dichloromethane extract was most potent for phosphomolybdenum, ferrous chelation, α-amylase, α-glucosidase, and cholinesterase inhibition assays. UHPLC-MS analysis of methanol extract unveiled to identify 11 secondary metabolites belonging to five sub-groups, i.e., phenolic, alkaloid, carbohydrate, terpenoid, and fatty acid derivatives. Additionally, in vivo toxicity was conducted for 21 days and the methanol extract at different doses (150, 200, 250 and 300 mg/kg) was administered in experimental chicks divided into five groups each containing five individuals. Different physical, haematological and biochemical parameters along with the absolute and relative weight of visceral body organs were studied. Overall, no toxic effect was noted for the extract at tested doses.

Pharmacological and polyphenolic profiles of Phyllanthus phillyreifolius var. commersonii Müll. Arg: An unexplored endemic species from Mauritius.

Phyllanthus phillyreifolius var. commersonii Müll. Arg is an endemic plant of Mauritius. To date, no study has been performed concerning its polyphenolic profile and pharmacological properties. In this study, a decoction (water), ethyl acetate and methanol extracts of the aerial parts of P. phillyreifolius, obtained from different extraction procedures (maceration and Soxhlet), were studied for antibacterial, antioxidant, anticancer, and enzyme inhibitory properties along with their polyphenolic profile. The ethyl acetate macerated extract showed high antibacterial activity against B. cereus (MIC = 0.293 mg/mL) and E. coli (MIC = 0.417 mg/mL) while S. epidermidis was most susceptible to the ethyl acetate-Soxhlet extract (MIC = 0.521 mg/mL). The methanol-Soxhlet extract displayed the most potent cupric and ferric reducing power, and metal chelating effect, while the macerated methanolic extract was the most effective DPPH and ABTS scavenger, and BChE inhibitor. Only the ethyl acetate-Soxhlet extract exhibited α-glucosidase inhibition. All extracts exhibited a strong anti-tyrosinase activity, which was further investigated by molecular docking and molecular dynamic. After 48 h exposure to the extracts for HeLa cell lines, the ethyl acetate-Soxhlet extract showed the highest inhibition (IC50 = 533.1 µg/mL) while the decoction extract was more cytotoxic to MDA-MB-231 cells (IC50 = 337.4 µg/mL). Treatment of cancer cell lines with all P. phillyreifolius extracts resulted in a time-dependent reduction of cell viability for HeLa and dose-and time-dependent reduction for MDA-MB-231. Gene expression ratio of Bcl-2 to Bax was higher for all Soxhlet-extracts. Total phenolics (TPC) and flavonoids (TFC) content were highest in the decoction and methanol-Soxhlet extract, respectively (122.43 mg GAE/g extract and 31.28 mg RE/g extract, respectively). The extracts were abundant in ellagitannins, although phenolic acids and flavonoids were also detected. Granatin B was detected for the first time in Phyllanthus species. Overall, the aerial parts of P. phillyreifolius exemplify a potent reservoir of bioactive phytochemicals for therapeutic applications.

Biologically active compounds from two members of the Asteraceae family: Tragopogon dubius Scop. and Tussilago farfara L.

Tragopogon dubius and Tussilago farfara are consumed as vegetables and used in folk medicine to manage common diseases. Herein, the chemical compositions and biological activities of different leaf extracts (ethyl acetate, methanol, and water) of T. dubius and T. farfara were evaluated. The antibacterial, antifungal, and antioxidant abilities of the extracts were tested using different assays including free radical scavenging, reducing power, phosphomolybdenum, and metal chelating assays. Enzyme inhibitory potentials were evaluated against cholinesterases, tyrosinase, α-amylase and α-glucosidase. Complexes of bioactive compounds (chlorogenic and rosmarinic acid) were docked into the enzymatic cavity of α-glucosidase and subjected to molecular dynamic calculation, enzyme conformational stability, and flexibility analysis. T. dubius and T. farfara extracts showed remarkable antioxidant potentials. Ethyl acetate extracts of T. dubius and T. farfara were the most potent inhibitors of acetylcholinesterase and butyrylcholinesterase. T. dubius ethyl acetate extract and T. farfara methanolic extract showed noteworthy activity against α-glucosidase. High performance liquid chromatography analysis revealed the abundance of some phenolic compounds including chlorogenic and rosmarinic acids. Ethyl acetate extract of T. dubius showed notable antifungal activity against all strains. Docking studies showed best pose for chlorogenic acid was stabilized by a network of hydrogen bonds with residues Asp1157, Asp1279, whereas rosmarinic acid showed several hydrogen bonds with Asp1157, Asp1420, Asp1526, Lys1460 and Trp1369. This study further validates the use of T. dubius and T. farfara in traditional medicine, as well as act as a stimulus for further studies for future biomedicine development. Communicated by Ramaswamy H. Sarma.

Multifunctional approaches to provide potential pharmacophores for the pharmacy shelf: Heracleum sphondylium L. subsp. ternatum (Velen.) Brummitt.

Heracleum sphondylium L. subsp. ternatum (Velen.) Brummitt. commonly known as "hogweed" is traditionally used to manage several human ailments. This investigation assessed, for the first time, the enzyme inhibitory properties, antioxidant activity, phytochemical profile, antimutagenic, and antimicrobial potential of the ethyl acetate, methanol, and water extracts of H. sphondylium. We also established the possible interactions of identified phenolic compounds with cholinesterases, amylase, glucosidase, and tyrosinase using in silico docking studies. Chlorogenic acid was found in high amounts in the methanol extract of H. sphondylium. The methanol extract was an effective inhibitor of acetylcholinesterase (1.70 mg galantamine equivalent (GALAE)/g extract) while the ethyl acetate extract showed pronounced inhibitory action against butyrylcholinesterase (1.77 mg GALAE/g extract). The extracts exhibited low inhibition against amylase (0.12-0.84 mmol acarbose equivalent (ACAE)/g extract) and a more pronounced inhibition against glucosidase (2.29-3.65 mmol ACAE/g extract). In silico results showed that rutin and quercetin (-70.4 and -72.2 Kcal/mol, for rutin and quercetin respectively) docked to the enzymatic cavity of acetylcholinesterase but these phenolic compounds showed less affinity with butyrylcholinesterase (-15.0 and -5.2 Kcal/mol, for rutin and quercetin respectively). The extracts did not induce any mutations on the bacterial strains, while they have excellent antimutagenic capacity against well-known mutagens (inhibition values 98%, 97% and 96%). The methanol extract (0.78 mg/ml) showed moderate antifungal activity while the ethyl acetate extract (0.78-3.12 mg/ml) showed weak to moderate antimicrobial activity. This study provides valuable baseline data which might serve for the development of future pharmacophores for the management of human ailments.

Scrophularia lucida L. as a valuable source of bioactive compounds for pharmaceutical applications: In vitro antioxidant, anti-inflammatory, enzyme inhibitory properties, in silico studies, and HPLC profiles.

The genus Scrophularia has received much interest with regards to its traditional uses against eczema, psoriasis, and mastitis. Yet, the medicinal properties of some species still need to be scientifically validated. The present study was designed to investigate into the biological properties of various solvent extracts (ethyl acetate, methanol, and aqueous) of the roots and aerial parts of Scrophularia lucida based on its antioxidant, anti-inflammatory, and enzyme inhibitory activities together with phytochemical screening. Our results revealed that the solvent extracts differed in their biological effectiveness. The root ethyl acetate extract showed the highest ABTS scavenging, FRAP, CUPRAC, and inhibitory activity against AChE and α-glucosidase. The ethyl acetate extract of the aerial parts displayed the highest BChE and α-amylase inhibition and antioxidant effect in the phosphomolybdenum assay, while the methanol extracts of both parts were the most effective DPPH• scavengers and tyrosinase inhibitors. The methanol extracts of the root and aerial parts also inhibited NO production in lipopolysaccharide (LPS)-stimulated murine leukemic monocyte-macrophage cell (4.99% and 10.77%, respectively), at 31.25 µg/mL concentration. The highest TPC (34.98 mg GAE/g extract) and TFC (48.33 mg RE/g extract) were observed in the ethyl acetate extract of the root and aerial parts, respectively. The most abundant compounds in the root ethyl acetate extract were luteolin (852 µg/g extract), rosmarinic acid (522 µg/g extract), and hesperidin (394 µg/g extract) while kaempferol was most abundant in the ethyl acetate extract of the aerial parts (628 µg/g extract). In silico experiments were conducted on tyrosinase and the higher docking values were observed for rosmarinic acid and hesperidin. The present findings provide base line information which tend to support the potential use of S. lucida in the management of several chronic diseases, including Alzheimer's disease and diabetes mellitus.