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Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopamine-producing cells in the Substantia nigra region of the brain. Complementary and alternative medicine approaches have been utilized as adjuncts to conventional therapies for managing the symptoms and progression of PD. Natural compounds have gained attention for their potential neuroprotective effects and ability to target various pathways involved in the pathogenesis of PD. This comprehensive review aims to provide an in-depth analysis of the molecular targets and mechanisms of natural compounds in various experimental models of PD. This review will also explore the structure-activity relationship (SAR) of these compounds and assess the clinical studies investigating the impact of these natural compounds on individuals with PD. The insights shared in this review have the potential to pave the way for the development of innovative therapeutic strategies and interventions for PD., (© 2024. The Author(s).)

Several Pelargonium species are cultivated mainly to produce essential oils used in perfume industry and for ornamental purposes. Although the chemical composition and biological activities of their essential oils were extensively investigated, there is limited information about the chemical composition of their non-volatile constituents. In this study, we report an Ultra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS)-based metabolomics approach for the annotation and analysis of various metabolites in three species; P. graveolens, P. denticulatum, and P. fragrans utilizing The Global Natural Product Social Molecular Networking (GNPS) and multivariate data analyses for clustering of the metabolites. A total of 154 metabolites belonging to different classes were annotated. The three species are good sources of coumarins, benzoic acid derivatives, organic acids, fatty acids, and phospholipids. However, the highest level of flavonols (mono- and di-O-glycosides) and cinnamic acid derivatives was found in P. graveolens and P. denticulatum, whereas tannins and flavone C-glycosides were abundant in P. fragrans. The metabolic profiles clarified here provide comprehensive information on the non-volatile constituents of the three Pelargonium species and can be employed for their authentication and possible therapeutic applications., (© 2024. The Author(s).)

Ethnopharmacological Relevance: Herbs of the genus Juniperus (family Cupressaceae) have been commonly used in ancestral folk medicine known as "Al'Araar" for treatment of rheumatism, diabetes, inflammation, pain, and fever. Bioassay-guided isolation of bioactives from medicinal plants is recognized as a potential approach for the discovery of novel drug candidates. In particular, non-addictive painkillers are of special interest among herbal phytochemicals., Aim of the Study: The current study aimed to assess the safety of J. thurifera, J. phoenicea, and J. oxycedrus aqueous extracts in oral treatments; validating the traditionally reported anti-inflammatory and analgesic effects. Further phytochemical investigations, especially for the most bioactive species, may lead to isolation of bioactive metabolites responsible for such bioactivities supported with in vitro enzyme inhibition assays., Materials and Methods: Firstly, the acute toxicity study was investigated following the OECD Guidelines. Then, the antinociceptive, and anti-inflammatory bioactivities were evaluated based on chemical and mechanical trauma assays and investigated their underlying mechanisms. The most active J. thurifera n-butanol fraction was subjected to chromatographic studies for isolating the major anti-inflammatory metabolites. Moreover, several enzymatic inhibition assays (e.g., 5-lipoxygenase, protease, elastase, collagenase, and tyrosinase) were assessed for the crude extracts and isolated compounds., Results: The results showed that acute oral administration of the extracts (300-500 mg/kg, p. o.) inhibited both mechanically and chemically triggered inflammatory edema in mice (up to 70% in case of J. thurifera) with a dose-dependent antinociceptive (tail flick) and anti-inflammatory pain (formalin assay) activities. This effect was partially mediated by naloxone inhibition of the opioid receptor (2 mg/kg, i. p.). In addition, 3-methoxy gallic acid (1), quercetin (2), kaempferol (3), and ellagic acid (4) were successfully identified being involved most likely in J. thurifera extract bioactivities. Nevertheless, quercetin was found to be the most potent against 5-LOX, tyrosinase, and protease with IC 50 of 1.52 ± 0.01, 192.90 ± 6.20, and 399 ± 9.05 μM, respectively., Conclusion: J. thurifera extract with its major metabolites are prospective drug candidates for inflammatory pain supported with inhibition of inflammatory enzymes. Interestingly, antagonism of opioid and non-opioid receptors is potentially involved., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Stress, obesity, hormonal changes, and aging have been connected to cellulite aggravation resulting in skin dimpled appearance, a very common painless skin disorder with a female preponderance. Several Apiaceae plants have been traditionally used for cosmetic applications. However, their screening for anti-cellulite potential has not been deeply investigated. In this work, UPLC-HRMS/MS coupled with molecular networking was employed to glean a holistic overview of the chemodiversity of the metabolome of nine Apiaceae fruits. Additionally, the extracts were screened for in vitro antioxidant and anti-cellulite activities. Apium graveolens and Petroselinum crispum revealed excellent free radical scavenging activity, remarkably increased lipolysis, and decreased adipogenesis. Furthermore, apigenin and its glycosides were identified to be the major components in both extracts, which might be responsible for the antioxidant activity and anti-cellulite potential. Conclusively, these results signify the potent antioxidant and anti-cellulite properties of A. graveolens and P. crispum fruit extracts, holding potential for the development of plant derived products for cellulite management., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

This review aims to provide an in-depth analysis of the pharmacological properties of mangiferin, focusing primarily on its bioavailability and mechanisms of action, and its potential therapeutic applications, especially in the context of chronic diseases. We conducted a comprehensive examination of in vitro and in vivo studies, as well as clinical trials involving mangiferin or plant extracts containing mangiferin. The primary source of mangiferin is Mangifera indica, but it's also found in other plant species from the families Anacardiaceae, Gentianaceae, and Iridaceae. Mangiferin has exhibited a myriad of therapeutic properties, presenting itself as a promising candidate for treating various chronic conditions including neurodegenerative disorders, cardiovascular diseases, renal and pulmonary diseases, diabetes, and obesity. Despite the promising results showcased in many in vitro studies and certain animal studies, the application of mangiferin has been limited due to its poor solubility, absorption, and overall bioavailability. Mangiferin offers significant therapeutic potential in treating a spectrum of chronic diseases, as evidenced by both in vitro and clinical trials. However, the challenges concerning its bioavailability necessitate further research, particularly in optimizing its delivery and absorption, to harness its full medicinal potential. This review serves as a comprehensive update on the health-promoting and therapeutic activities of mangiferin., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Ferulic acid (FA) has powerful antioxidant and antitumor activities, but it has low bioavailability owing to its poor water solubility. Our aim is to formulate polymeric mixed micelles loaded with FA to overcome its poor solubility and investigate its potential anticancer activity via miRNA-221/TP53INP1 axis-mediated autophagy in colon cancer. A D-optimal design with three factors was used for the optimization of polymeric mixed micelles by studying the effects of each of total Pluronics mixture (mg), Pluronic P123 percentage (%w/w), and drug amount (mg) on both entrapment efficiency (EE%) and particle size. The anticancer activity of FA and Tocopheryl polyethylene glycol 1000 succinate (TPGS) mixed micelles formula (O2) was assessed by MTT and flow cytometry. O2 showed an EE% of 99.89%, a particle size of 13.86 nm, and a zeta potential of - 6.02 mv. In-vitro drug release studies showed a notable increase in the release rate of FA from O2, as compared to the free FA. The (IC 50 ) values for FA from O2 and free FA were calculated against different cell lines showing a prominent IC 50 against Caco-2 (17.1 µg/ml, 191 µg/ml respectively). Flow cytometry showed that FA caused cell cycle arrest at the G2/M phase in Caco-2. RT-PCR showed that O2 significantly increased the mRNA expression level of Bax and CASP-3 (4.72 ± 0.17, 3.67 ± 0.14), respectively when compared to free FA (2.59 ± 0.13, 2.14 ± 0.15), while miRNA 221 levels were decreased by the treatment with O2 (0.58 ± 0.02) when compared to free FA treatment (0.79 ± 0.03). The gene expression of TP53INP1 was increased by the treatment with O2 compared to FA at P < 0.0001. FA-loaded TPGS mixed micelles showed promising results for enhancing the anticancer effect of FA against colorectal cancer, probably due to its enhanced solubility. Thus, FA-loaded TPGS mixed micelles could be a potential therapeutic agent for colorectal cancer by targeting miRNA-221/TP53INP1 axis-mediated autophagy., (© 2024. The Author(s).)

Leukemia is a group of malignant disorders which affect the blood and blood-forming tissues in the bone marrow, lymphatic system, and spleen. Many types of leukemia exist; thus, their diagnosis and treatment are somewhat complicated. The use of conventional strategies for treatment such as chemotherapy and radiotherapy may develop many side effects and toxicity. Hence, modern research is concerned with the development of specific nano-formulations for targeted delivery of anti-leukemic drugs avoiding toxic effects on normal cells. Nanostructures can be applied not only in treatment but also in diagnosis. In this article, types of leukemia, its causes, diagnosis as well as conventional treatment of leukemia shall be reviewed. Then, the use of nanoparticles in diagnosis of leukemia and synthesis of nanocarriers for efficient delivery of anti-leukemia drugs being investigated in in vivo and clinical studies. Therefore, it may contribute to the discovery of novel and emerging nanoparticles for targeted treatment of leukemia with less side effects and toxicities., (© 2023. The Author(s).)

Non-small-cell lung carcinoma (NSCLC) is a type of epithelial lung cancer accounting for about 85% of all lung cancers. In our research, a novel lupene derivative namely acetoxy-lup-5(6), 20(29)-diene (ALUP), as well as two known triterpenes; lupeol (LUP) and betulinic acid (BA) were isolated through the chromatographic purification of the 95% ethanolic extract of Thymus capitatus. Identification of the compounds was carried out by physicochemical properties as well as spectral 1D and 2D NMR analysis. The anti-cancer activity of the three triterpenes was assessed on non-small cell lung cancer cell line; A549 using MTT assay and cell cycle analysis using annexin V/propidium iodide. The molecular mechanism underlying anti-apoptotic effects was determined by analyzing Let-7 miRNA and miRNA-21 expression, the mRNA gene expression level of Bax, CASP-8, CD95, Bcl2, KRAS, VEGF, Cyclin D1 using qRT-PCR. Our results revealed that the three isolated compounds ALUP, LUP, and BA caused cell cycle arrest at the G2/M phase with an increase in the apoptosis which may be attributed to their significant effect on raising Bax, CASP-8, and CD95 and reducing the mRNA expression levels of Bcl-2, KRAS, VEGF, and Cyclin D1 compared to control cells. RT-PCR results showed that the ALUP, LUP, and BA significantly downregulated miRNA-21 expression. Meanwhile, the three compounds caused significant overexpression of Let-7 miRNA. This is the first report on the anti-cancer activity of acetoxy-lup-5(6), 20(29)-diene (ALUP) in reducing the proliferation and differentiation of the A549 cell line through inducing apoptosis. Finally, by targeting the Let-7 miRNA/Cyclin D1/VEGF cascade, acetoxy-lup-5(6), 20(29)-diene could be a potential therapeutic agent for lung cancer., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The aim of the present study is to explore the potential anticancer effect of the cardenolide; acovenoside A against non-small cell lung cancer (NSCLC), understand its molecular mechanism in inducing apoptosis and show the effect of its combination with carboplatin and taxol. MTT assay showed that the combination of acovenoside A with taxol and carboplatin caused 78.9% cytotoxicity reflecting the synergistic effect. The triple combination showed the best growth inhibition efficiency where the number of cells at the G2/M phase was decreased and boosted up apoptotic and necrotic activity. The combination also showed the most remarkable increase in gene expression of Bax and p53 and the least level of Bcl2. The gene expression of miRNA181a and miRNA630 was significantly upregulated in cell lines treated with the combination. The present study has proven that the underlying mechanism of acovenoside A is partially attributed to the upregulation of miR-630 and miR-181a gene expressions which in turn targets the intrinsic apoptosis genes as p53, Bax and Bcl2 as well as caspase 3. The present study is the first to address the valuable effect of using acovenoside A together with carboplatin and taxol in the treatment of NSCLC via exerting apoptotic, antiproliferative, and cytotoxic effects.., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Agri-food wastes, produced following industrial food processing, are mostly discarded, leading to environmental hazards and losing the nutritional and medicinal values associated with their bioactive constituents. In this study, we performed a comprehensive analytical and biological evaluation of selected vegetable by-products (potato, onion, and garlic peels). The phytochemical analysis included UHPLC-ESI-qTOF-MS/MS in combination with molecular networking and determination of the total flavonoid and phenolic contents. Further, the antimicrobial, anti-osteoarthritis and wound healing potentials were also evaluated. In total, 47 compounds were identified, belonging to phenolic acids, flavonoids, saponins, and alkaloids as representative chemical classes. Onion peel extract (OPE) showed the higher polyphenolic contents, the promising antioxidant activity, the potential anti-osteoarthritis activity, and promising antimicrobial activity, especially against methicillin-resistant Staphylococcus aureus (MRSA). Furthermore, OPE revealed to have promising in vivo wound healing activity, restoring tissue physiology and integrity, mainly through the activation of AP-1 signaling pathway. Lastly, when OPE was loaded with nanocapsule based hydrogel, the nano-formulation revealed enhanced cellular viability. The affinities of the OPE major metabolites were evaluated against both p65 and ATF-2 targets using two different molecular docking processes revealing quercetin-3,4'-O-diglucoside, alliospiroside C, and alliospiroside D as the most promising entities with superior binding scores. These results demonstrate that vegetable by-products, particularly, those derived from onion peels can be incorporated as natural by-product for future evaluation against wounds and osteoarthritis., (© 2023. Springer Nature Limited.)

White, green, and oolong teas are produced from the tea plant ( Camellia sinensis (L.) Kuntze) and are reported to have anti-obesity and hypolipidemic effects. The current study aims to investigate the anti-obesity effects of a tea mixture nano-formulation by targeting the AMPK/Sirt-1/GLUT-4 axis in rats. In vitro lipase and α -amylase inhibition assays were used to determine the active sample, which was then incorporated into a nanoparticle formulation subjected to in vivo anti-obesity testing in rats by measuring the expression level of different genes implicated in adipogenesis and inflammation using qRT-PCR. Moreover, metabolomic analysis was performed for each tea extract using LC/ESI MS/MS coupled to chemometrics in an attempt to find a correlation between the constituents of the extracts and their biological activity. The in vitro pancreatic lipase and α -amylase inhibition assays demonstrated more effective activity in the tea mixture than the standards, orlistat and acarbose, respectively, and each tea alone. Thus, the herbal tea mixture and its nanoparticle formulation were evaluated for their in vivo anti-obesity activity. Intriguingly, the tea mixture significantly decreased the serum levels of glucose and triglycerides and increased the mRNA expression of GLUT-4, P-AMPK, Sirt-1, and PPAR-γ, which induce lipolysis while also decreasing the mRNA expression of TNF-α and ADD1/SREBP-1c, thereby inhibiting the inflammation associated with obesity. Our study suggests that the tea mixture nano-formulation is a promising therapeutic agent in the treatment of obesity and may also be beneficial in other metabolic disorders by targeting the AMPK/Sirt-1/Glut-4 pathway.

Eurycoma longifolia Jack is one of traditional herbal medicines in South-East Asia. This study evaluated the anticancer, cell-cycle arrest, and apoptotic induction potentials of eurycomanone (EONE) and eurycomanol (EOL), highly oxygenated quassinoids previously isolated from its roots, against large (H460) and small (A549) lung cancer cells. EOL and EONE exhibited IC 50 of 386 and 424 µg/mL on normal human lung cell line. EONE exhibited higher anticancer activity with an IC 50 of 1.78 µg/mL and 20.66 μg/mL than EOL which exhibited an IC 50 of 3.22 µg/mL and 38.05 µg/mL against H460 and A549, respectively. Both reduced the viability of H460 and A549 and arrested G0/G1 phase. The increase in the apoptotic rates was mainly in the percentage of late apoptosis. Moreover, they inhibited A549 by inducing the accumulation of S and G2/M phases. This study revealed EOL and EONE potential as novel leads exhibiting cell-cycle arrest and apoptosis induction potentials.

Mycophenolic acid (MPA) is the active ingredient in the most important immunosuppressive pharmaceuticals. It has antifungal, antibacterial, antiviral, anti-psoriasis, and antitumor activities. Therefore, its overproduction in addition to gene expression analysis was our main target. Through this study, we isolated a novel potent mycophenolic acid (MPA) producer strain of the genus Penicillium from the refrigerated Mozzarella cheese and it was identified with the molecular marker ITS and benA genes as P. arizonenseHEWt1. Three MPA overproducer mutants were isolated by exposing the wild type to different doses of gamma-rays, and the fermentation conditions for the highest production of MPA were optimized. The results indicated that MPA amounts produced by the mutants MT1, MT2, and MT3 were increased by 2.1, 1.7, and 1.6-fold, respectively, compared with the wild-type. The growth of both mutant and wild-type strains on PD broth, adjusted to pH 6 and incubated at 25 °C for 15 d, were the best conditions for maximum production of MPA. In a silico study, five orthologs genes of MPA biosynthesizing gene clusters in P. brevicompactum were predicted from the genome of P. arizonense. Sequencing and bioinformatic analyses proved the presence of five putative genes namely mpaA, mpaC, mpaF, mpaG, and mpaH in the P. arizonense HEWt1 genome. Gene expression analysis by qRT-PCR indicated an increase in the transcription value of all annotated genes in the three mutants over the wild type. A highly significant increase in the gene expression of mpaC, mpaF, and mpaH was observed in P. arizonense-MT1 compared with wild-type. These results confirmed the positive correlation of these genes in MPA biosynthesis and are the first report regarding the production of MPA by P. arizonense.Kew word.Mycophenolic acid, Penicillium arizonense, mutagenesis, gene expression., (© 2023. The Author(s).)

This systematic review identified various bioactive compounds which have the potential to serve as novel drugs or leads against acute myeloid leukemia. Acute myeloid leukemia (AML) is a heterogeneous hematopoietic malignancy that arises from the dysregulation of cell differentiation, proliferation, and cell death. The risk factors associated with the onset of AML include long-term exposure to radiation and chemicals such as benzene, smoking, genetic disorders, blood disorders, advancement in age, and others. Although novel strategies to manage AML, including a refinement of the conventional chemotherapy regimens, hypomethylating agents, and molecular targeted drugs, have been developed in recent years, resistance and relapse remain the main clinical problems. In this study, three databases, PubMed/MEDLINE, ScienceDirect, and Google Scholar, were systematically searched to identify various bioactive compounds with antileukemic properties. A total of 518 articles were identified, out of which 59 were viewed as eligible for the current report. From the data extracted, over 60 bioactive compounds were identified and divided into five major groups: flavonoids, alkaloids, organosulfur compounds, terpenes, and terpenoids, and other known and emerging bioactive compounds. The mechanism of actions of the analyzed individual bioactive molecules differs remarkably and includes disrupting chromatin structure, upregulating the synthesis of certain DNA repair proteins, inducing cell cycle arrest and apoptosis, and inhibiting/regulating Hsp90 activities, DNA methyltransferase 1, and histone deacetylase 1., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

The glycoprotein (GP) IIb/IIIa receptor is found integrin present in platelet aggregations. GP IIb/IIIa antagonists interfere with platelet cross-linking and platelet-derived thrombus formation through the competition with fibrinogen and von Willebrand factor. Currently, three parenteral GP IIb/IIIa competitors (tirofiban, eptifibatide, and abciximab) are approved for clinical use in patients affected by percutaneous coronary interventions (PCI) in the location of acute coronary syndrome (ACS). GP IIb/IIIa antagonists have their mechanism of action in platelet aggregation prevention, distal thromboembolism, and thrombus formation, whereas the initial platelet binding to damage vascular areas is preserved. This work is aimed to provide a comprehensive review of the significance of GP IIb/IIIa inhibitors as a sort of antiplatelet agent. Their mechanism of action is based on factors that affect their efficacy. On the other hand, drugs that inhibit GP IIb/IIIa already approved by the FDA were reviewed in detail. Results from major clinical trials and regulatory practices and guidelines to deal with GP IIb/IIIa inhibitors were deeply investigated. The cardiovascular pathology and neuro-interventional surgical application of GP IIb/IIIa inhibitors as a class of antiplatelet agents were developed in detail. The therapeutic risk/benefit balance of currently available GP IIb/IIa receptor antagonists is not yet well elucidated in patients with ACS who are not clinically evaluated regularly for early cardiovascular revascularization. On the other hand, in patients who have benefited from PCI, the antiplatelet therapy intensification by the addition of a GP IIb/IIIa receptor antagonist (intravenously) may be an appropriate therapeutic strategy in reducing the occurrence of risks of thrombotic complications related to the intervention. Development of GP IIb/IIIa inhibitors with oral administration has the potential to include short-term antiplatelet benefits compared with intravenous GP IIb/IIIa inhibitors for long-term secondary preventive therapy in cardiovascular disease. But studies showed that long-term oral administration of GP IIb/IIIa receptor inhibitors has been ineffective in preventing ischemic events. Paradoxically, they have been linked to a high risk of side effects by producing prothrombotic and pro-inflammatory events., (© 2023. Italian Society of Hypertension.)

Plant resins are rich in bioactive compounds with high medicinal values. However, the chemistry and anti-inflammatory activity of the resins produced by trees of the genus Eucalyptus were scarcely investigated. The inflammatory targets cyclooxygenase-1 (COX-1), COX-2, TNF-, NF-B, and NO were significantly inhibited by the methanolic extract of Eucalyptus maculata kino resin (EME) and its CH 2 Cl 2 soluble fraction (MCF). Sakuranetin (C1), (E)-cinnamic acid (C2), kaempferol 7- methyl ether (C3), 7-O-methyl aromadendrin (C4), and 1,6- dicinnamoyl-O-α-D-glucopyranoside (C5) were isolated from MCF. Three compounds (C1, C2, and C4) showed potent in vitro COX-1 inhibition, while C5 inhibited COX-2, TNF-α, NF-κB, and NO significantly. An in-silico study revealed that C5 had the highest binding affinity to the active site in COX-2 with binding energy score (S) of -14.85 kcal/mol, better than celecoxib (COX-2 inhibitor). In conclusion, 1,6-dicinnamoyl-O-α-D-glucopyranoside (C5) could be investigated further in the search for anti-inflammatory agents., (© 2023. The Author(s).)

Vector-borne diseases (VBDs) are a worldwide critical concern accounting for 17% of the estimated global burden of all infectious diseases in 2020. Despite the various medicines available for the management, the deadliest VBD malaria, caused by Plasmodium sp., has resulted in hundreds of thousands of deaths in sub-Saharan Africa only. This finding may be explained by the progressive loss of antimalarial medication efficacy, inherent toxicity, the rise of drug resistance, or a lack of treatment adherence. As a result, new drug discoveries from uncommon sources are desperately needed, especially against multi-drug resistant strains. Marine organisms have been investigated, including sponges, soft corals, algae, and cyanobacteria. They have been shown to produce many bioactive compounds that potentially affect the causative organism at different stages of its life cycle, including the chloroquine (CQ)-resistant strains of P. falciparum . These compounds also showed diverse chemical structures belonging to various phytochemical classes, including alkaloids, terpenoids, polyketides, macrolides, and others. The current article presents a comprehensive review of marine-derived natural products with antimalarial activity as potential candidates for targeting different stages and species of Plasmodium in both in vitro and in vivo and in comparison with the commercially available and terrestrial plant-derived products, i.e. , quinine and artemisinin., Competing Interests: Authors declare that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (This journal is © The Royal Society of Chemistry.)

Nigella sativa L. seeds (NS) are known as one of the most traditional immunomodulatory and nutritive food additives. NS can, furthermore, be roasted to give curries, breads, and other dishes a smoky, nutty flavor. This study evaluated the effect of roasting NS on the metabolic profile and immunomodulatory activity. Non-targeted metabolomics analysis was conducted using several analytical platforms, including GC-MS and UPLC-MS. A total of 197 metabolites were identified, belonging to different classes such as saponins, alkaloids, flavonoids, and lipids. In vitro immunomodulatory activity on the differentiated monocytic cell line THP-1 was assessed, revealing that the roasted seeds showed significantly-decreased immunomodulatory activity. Furthermore, a molecular docking study, which was carried out against immunomodulation-related pathway protein (iNOS), revealed that compounds which showed the best binding scores were severely decreased by roasting. Conclusively, our results demonstrate that the roasting of NS results in severe losses in their bioactive metabolites and immunomodulatory activity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Alzheimer's disease (AD) is an increasingly common neurodegenerative disease that attracts the attention of researchers and medical community in order to develop new, safe and more effective drugs. Currently available drugs could only slow the AD progression and relieve the symptoms, in addition to being linked to moderate-to-severe side effects. N-methyl D-aspartate (NMDA) receptors antagonists were reported to have the ability to block the glutamate-mediated excitotoxic activity being good therapeutic targets for several neurodegenerative diseases, including AD. Based on data obtained so far, this review provides an overview over the use of NMDA antagonists for AD treatment, starting with a key emphasis on present features and future aspects regarding the use of NMDA antagonists for AD, and lastly a key focus is also given on its use in precision medicine., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Cuphea ignea A. DC. is an ornamental tropical plant belonging to the family Lythraceae. The aim of this study is to verify the in vivo antihypertensive potential of C. ignea A. DC. and to explore its metabolic profile using a UHPLC-Orbitrap-HRMS technique. The results revealed that the ethanolic extract of the leaves in two doses (250 and 500 mg/kg b.wt.) significantly normalized the elevated systolic blood pressure in N(G)-nitro-l-arginine-methyl ester-induced hypertension in rats. An angiotensin-converting enzyme (ACE) concentration was significantly decreased by the high dose extract compared to lisinopril. Nitric oxide (NO) level was significantly restored by both doses. Concerning the oxidative stress parameters, both doses displayed significant reduction in malondialdehyde (MDA) level while the high dose restored elevated glutathione level. These biochemical results were clearly supported by the histopathological examination of the isolated heart and aorta. A UHPLC-Orbitrap-HRMS study was represented by a detailed metabolic profile of leaves and flowers of C. ignea A. DC., where 53 compounds were identified among which flavonoids, fatty acids, and hydrolysable tannins were the major identified classes. This study established scientific evidence for the use of C. ignea A. DC., a member of genus Cuphea as a complementary treatment in the management of hypertension., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Enterococci are a common cause of urinary tract infections. The severity of enterococcal infections is associated with their ability to form biofilms. Morus leaves are known as a natural antibacterial, however, their antibiofilm activity against Enterococcus remains unveiled. This study aimed to evaluate the ability of four polyphenol-rich Morus leaves extracts (Morus nigra, M. rubra, M. macroura, and M. alba) to inhibit biofilm formed by enterococcal clinical isolates in relation to their metabolic profiling. Results revealed that 48% of the isolates formed strong biofilm, 28% formed moderate biofilm, 20% formed weak biofilm, and only 4% did not form a biofilm. The strong biofilm-forming isolates were E. faecalis, and hence were chosen for this study. The antibiofilm activity of the four polyphenol-rich Morus leaves extracts revealed that the M. nigra extract exhibited the highest percentage of biofilm inhibition followed by M. rubra then M. macroura and the least inhibition was detected in M. alba, and these results were in accordance with the phenolic and flavonoid contents of each extract. UPLC-ESI-MS/MS identified 61 polyphenolic compounds in the four extracts. Further, multivariate analysis confirmed clear segregation of M. nigra from the other species suggesting disparity in its metabolome, with accumulation of flavonoids, anthocyanidins, phenolic acids and coumarin derivatives. Quercetin and kaempferol glycosides were found to be positively and significantly correlated to the antibiofilm activity. In conclusion, M. nigra ethanolic extracts showed the highest phenolic content and antibiofilm activity and they could be developed as a complementary treatment for the development of antimicrobial agents., (© 2022. The Author(s).)

A crucial target in drug research is magnifying efficacy and decreasing toxicity. Therefore, using natural active constituents as precursors will enhance both safety and biological activities. Despite having many pharmacological activities, caffeic and ferulic acids showed limited clinical usage due to their poor bioavailability and fast elimination. Therefore, semisynthetic compounds from these two acids were prepared and screened as anticancer agents. In this study, CA and FA showed very potent anticancer activity against Caco-2 cells. Consequently, eighteen derivatives were tested against the same cell line. Four potent candidates were selected for determination of the selectivity index, where compound 10 revealed a high safety margin. Compound 10 represented a new scaffold and showed significant cytotoxic activity against Caco-2. Cell-cycle analysis and evaluation of apoptosis showed that derivatives 10 , 7 , 11 , 15 and 14 showed the highest proportion of cells in a late apoptotic stage.

Artemisia plants are traditional and ethnopharmacologically used to treat several diseases and in addition in food, spices, and beverages. The genus is widely distributed in all continents except the Antarctica, and traditional medicine has been used as antimalarial, antioxidant, anticancer, antinociceptive, anti-inflammatory, and antiviral agents. This review is aimed at systematizing scientific data on the geographical distribution, chemical composition, and pharmacological and toxicological profiles of the Artemisia genus. Data from the literature on Artemisia plants were taken using electronic databases such as PubMed/MEDLINE, Scopus, and Web of Science. Selected papers for this updated study included data about phytochemicals, preclinical pharmacological experimental studies with molecular mechanisms included, clinical studies, and toxicological and safety data. In addition, ancient texts and books were consulted. The essential oils and phytochemicals of the Artemisia genus have reported important biological activities, among them the artemisinin, a sesquiterpene lactone, with antimalarial activity. Artemisia absinthium L. is one of the most famous Artemisia spp. due to its use in the production of the absinthe drink which is restricted in most countries because of neurotoxicity. The analyzed studies confirmed that Artemisia plants have many traditional and pharmacological applications. However, scientific data are limited to clinical and toxicological research. Therefore, further research is needed on these aspects to understand the full therapeutic potential and molecular pharmacological mechanisms of this medicinal species., Competing Interests: The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties., (Copyright © 2022 Javad Sharifi-Rad et al.)

Stratified random sampling is an effective sampling technique for estimating the population characteristics. The determination of strata boundaries and the allocation of sample size to the strata are two of the most critical factors in maximizing the precision of the estimates. Most surveys are conducted in an environment of severe budget constraints and a specific time is required to finish the survey. So cost and time are two important objectives that are taken under consideration in most surveys. The study suggested Mathematical goal programming model for determining optimum stratum boundaries for an exponential study variable under multiple objectives model when cost and time are under consideration. Compared to other techniques, Goal programming has many advantages in resources planning. Determining the required resources to satisfy the desired goals and the effectiveness of the available resources as well as providing best solutions under different amounts of resources are examples of the advantages of Goal programming. In addition the paper used data on Covid-19 to evaluate the performance of the suggested model for the exponential distribution. The study divided the number of new cases diseases into small, medium and high numbers. It also compared the results with the findings in the reports of the World Health Organization. The suggested mathematical goal programming revealed that Egypt was exposed to three waves of infection during the interval (5/3/2020 to 12/8/2021). These results are identical to the actual reality of covid-19 waves in Egypt., Competing Interests: The authors have declared that no competing interests exist.

Biodegradation is a sustainable green strategy that gives the opportunity for remediation of water contaminated with petroleum products. In this study, 12 bacterial isolates were recovered from River Nile, Egypt and screened for their potential to degrade a mixture of paraffinic petroleum crude oil. The most promising isolate was identified according to 16S rRNA sequencing as Janibacter terrae strain S1N1 (GenBank accession No. KX570955.1). In order to boost the biodegradation efficiency, the bacterial suspension was photostimulated by exposure to different irradiation doses using a low-power helium-neon (He-Ne) laser (λ = 632.8 nm). Maximum biodegradation was achieved after 4 min of exposure (134.07 J cm -2 ) at optimized pH value (6) and temperature (35 °C). The gas chromatography-mass spectrometry (GC-MS) analysis revealed the biodegradation of 96.5% of the substrate after only 48 h of incubation. The n-C 17 /Pr and n-C 18 /Ph ratios indicated a preferential biodegradation of iso-paraffines over normal ones. Meanwhile, pristane/phytane (Pr/Ph) ratios were indicative of selective biodegradation for pristane. The carbon preference index (CPI) was nearly around unity indicating the ability of Janibacter terrae to attack the odd and even n -alkanes simultaneously. These results support the superiority of irradiated bacteria in optimizing the biodegradation efficiency and shortening the time of treatment, thus proposing an eco-friendly technique in water bioremediation programs., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Aims: Contamination with heavy metal (HM) is a severe environmental issue. Therefore, there is a pressing need to create environmentally safe and cost-effective HM bioremediation approaches., Methods and Results: Three iron-tolerant fungal strains were isolated from sewage-irrigated soils, molecularly identified and deposited in the GenBank as Aspergillus flavus MT639638, A. terreus MT605370 and Fusarium oxysporum MT605399. The fungal growth, minimum inhibitory concentration (MIC), tolerance index (TI), removal efficiency, bioaccumulation, and enzymatic and non-enzymatic antioxidants were determined. Based on MIC values, A. flavus MT639638 was the most resistant strain. F. oxysporum displayed the highest percent removal efficiency (93.65% at 4000 mg L -1 ) followed by A. flavus (92.92%, at 11,000 mg L -1 ), and A. terreus (91.18% at 3000 mg L -1 ). F. oxysporum was selected based on its highly sensitivity for further characterization of its response to Fe(II) stress using TEM, SEM and EDX, in addition to HPLC analysis of organic acids. These analyses demonstrated the localization of bioaccumulated Fe(II) and ultrastructural changes induced by iron and indicated induction release of organic acids., Conclusions: Our fungal strains showed an effective capacity for removal of Fe(II) via bioaccumulation and biosorption mechanisms which were supported by instrumental analyses. The iron tolerance potentiality was mediated by induction of selected antioxidative enzymes and biomolecules., Significance and Impact of the Study: This study depicts a potential utilization of the three fungal strains for the bioremediation of iron-contaminated soils., (© 2021 The Society for Applied Microbiology.)

The immune system is a potent army that defends our body against various infections and diseases through innate and adaptive immunity. Herbal medicine is one of the essential sources for enhancing immunity because of affordability, availability, minor side effects, and consumers' preferences. Hazelnuts, walnuts, almonds, and peanuts are among the most widespread edible nuts that are rich in phenolics, fats, fibers, vitamins, proteins, and minerals. The potential of nut shells in phytoremediation has attracted increasing attention as a sustainable solution for waste recycling. Here, we determined the in vitro immune-modulatory activity as well as the metabolite profile of the four nut shell extracts. The addition of the extracts to LPS-stimulated macrophages, especially peanut and walnut shells, has downregulated the gene expression of AP-1, TNF-α, IL-8, iNOS, and COX-2 expression levels. Significant antioxidant capabilities and immune-modulatory effects have been traced for peanut shells. UPLC-MS metabolic profiling of the four nut shell extracts allowed the detection of a relatively high level of phenolic compounds in peanut shells. Intriguingly, a significant correlation between the antioxidant capacity and the total phenolic content was found, indicating the contribution of the phenolic compounds to the antioxidant properties and hence the immune-modulatory activity. Furthermore, molecular docking and structure-activity relationship (SAR) studies revealed kaempferol rutinoside and proanthocyanidin A5' as potential iNOS inhibitors.

Urtica dioica belongs to the Urticaceae family and is found in many countries around the world. This plant contains a broad range of phytochemicals, such as phenolic compounds, sterols, fatty acids, alkaloids, terpenoids, flavonoids, and lignans, that have been widely reported for their excellent pharmacological activities, including antiviral, antimicrobial, antihelmintic, anticancer, nephroprotective, hepatoprotective, cardioprotective, antiarthritis, antidiabetic, antiendometriosis, antioxidant, anti-inflammatory, and antiaging effects. In this regard, this review highlights fresh insight into the medicinal use, chemical composition, pharmacological properties, and safety profile of U. dioica to guide future works to thoroughly estimate their clinical value., Competing Interests: The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties., (Copyright © 2022 Yasaman Taheri et al.)

Ethnopharmacological relevance: Since ancient times, Hibiscus sabdariffa L. calyces have been used as a folk remedy for the treatment of hypertension. However, it is questionable as to whether there is a difference in the antihypertensive activity of the hot or cold aqueous extracts. Aim of the study: We designed this study to specify the best method for water extraction of the antihypertensive metabolites of H . sabdariffa and to confirm their in vivo antihypertensive capabilities . Materials and methods: The powdered dried calyces of H. sabdariffa were independently extracted with cold and hot water. A comparative study was performed between the cold and hot aqueous extracts of H . sabdariffa based on evaluation of the in vitro renin and angiotensin-converting enzyme (ACE) inhibition activities. Additionally, both extracts were subjected to an in vivo study for the evaluation of their antihypertensive activities in L-N w -Nitro arginine methyl ester (L-NAME)-induced hypertensive rats. Further, a metabolomics study was also performed for both extracts to identify their chemical constituents. Results: The cold and hot extracts significantly reduced the angiotensin II, ACE, and aldosterone levels in the plasma. Furthermore, in the myocardium and aorta, decreased iNOS (inducible nitric oxide synthase) levels and elevated eNOS (endothelial nitric oxide synthase), as well as the rise in plasma NO levels, were reported with both extracts, but better results were displayed with the hot extract, leading to a potential antihypertensive effect. Additionally, the cold and hot Hibiscus extracts induced a cardioprotective effect through reducing necrosis, inflammation, and vacuolization that results from the induction of hypertension, an effect that was more prominent with the hot extract. Moreover, a comprehensive metabolomics approach using ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) was able to trace the metabolites in each extraction. Conclusion: The extracts showed different anthocyanin and phenolic compounds, but the hot extract showed higher contents of specific phenolics to which the superior antihypertensive and cardioprotective activities could be related., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Salem, Ezzat, Ahmed, Alseekh, Fernie and Essam.)

Crocus species are mainly distributed in North Africa, Southern and Central Europe, and Western Asia, used in gardens and parks as ornamental plants, while Crocus sativus L. (saffron) is the only species that is cultivated for edible purpose. The use of saffron is very ancient; besides the use as a spice, saffron has long been known also for its medical and coloring qualities. Due to its distinctive flavor and color, it is used as a spice, which imparts food preservative activity owing to its antimicrobial and antioxidant activity. This updated review discusses the biological properties of Crocus sativus L. and its phytoconstituents, their pharmacological activities, signaling pathways, and molecular targets, therefore highlighting it as a potential herbal medicine. Clinical studies regarding its pharmacologic potential in clinical therapeutics and toxicity studies were also reviewed. For this updated review, a search was performed in the PubMed, Science, and Google Scholar databases using keywords related to Crocus sativus L. and the biological properties of its phytoconstituents. From this search, only the relevant works were selected. The phytochemistry of the most important bioactive compounds in Crocus sativus L. such as crocin, crocetin, picrocrocin, and safranal and also dozens of other compounds was studied and identified by various physicochemical methods. Isolated compounds and various extracts have proven their pharmacological efficacy at the molecular level and signaling pathways both in vitro and in vivo . In addition, toxicity studies and clinical trials were analyzed. The research results highlighted the various pharmacological potentials such as antimicrobial, antioxidant, cytotoxic, cardioprotective, neuroprotective, antidepressant, hypolipidemic, and antihyperglycemic properties and protector of retinal lesions. Due to its antioxidant and antimicrobial properties, saffron has proven effective as a natural food preservative. Starting from the traditional uses for the treatment of several diseases, the bioactive compounds of Crocus sativus L. have proven their effectiveness in modern pharmacological research. However, pharmacological studies are needed in the future to identify new mechanisms of action, pharmacokinetic studies, new pharmaceutical formulations for target transport, and possible interaction with allopathic drugs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Monica Butnariu et al.)

Green beans (Phaseolus vulgaris L.) are consumed as pods or mature seeds (common beans). The pods were extracted with 95% ethanol and processed to prepare non-polar and polar fractions. Comparing the antihyperglycemic activity of both fractions, non-polar fraction (NPF, 200 mg kg -1  day -1 ) lowered blood glucose in streptozotocin diabetic rats by 65% compared to 57% for the polar fraction at the same dose. When NPF treatment was combined with injection of mesenchymal stem cells (MSC) a 4.4-fold increase in serum insulin and a 73.6% reduction in blood glucose were observed compared to untreated control. Additionally, a significant decrease in malondialdehyde (76.2%), nitric oxide (68.2%), cholesterol (76.1%), and triglycerides (69.5%) and a 1.75-fold increase in HDL concentrations were observed in the group treated with this combination compared to diabetic animals. Interestingly, NPF increased homing of MSC in pancreas potentiating their antidiabetic activity. Finally, 26 compounds were identified in NPF using LC/MS analysis and four were isolated in pure form. The isolated compounds namely calotroproceryl acetate, fridelin, calotroproceryl A, and stigmasterol showed good inhibitory activity against pancreatic lipase with IC 50 at 1.93, 1.07, 1.34 and 1.44-1 μg/ml, respectively. Additionally, these compounds inhibited α-amylase, albeit at higher concentration, with IC 50 at 248, 212, 254, and 155 μg/ml for calotroproceryl acetate, fridelin, calotroproceryl A, and stigmasterol, respectively. Our results suggest that green beans extract can potentiate effect of MSC in diabetes directly due to its own antidiabetic effect and indirectly by increasing MSC homing in pancreatic tissues. PRACTICAL APPLICATIONS: It has been suggested in this study that green beans can improve hyperglycemia, oxidative balance in diabetes, so green beans can be promoted as a healthy nutrient for diabetic patients. Green beans also can enhance homing and differentiation of mesnchymal stem cells in the pancreas for future stem cell therapy of type I diabetes., (© 2022 Wiley Periodicals LLC.)

Flavonoids are common in the plant kingdom and many of them have shown a wide spectrum of bioactive properties. Hesperetin (Hst), the aglycone form of hesperidin, is a great example, and is the most abundant flavonoid found in Citrus plants. This review aims to provide an overview on the in vitro, in vivo and clinical studies reporting the Hst pharmacological effects and to discuss the bioavailability-related issues. Preclinical studies have shown promising effects on cancer, cardiovascular diseases, carbohydrate dysregulation, bone health, and other pathologies. Clinical studies have supported the Hst promissory effects as cardioprotective and neuroprotective agent. However, further well-designed clinical trials are needed to address the other Hst effects observed in preclinical trials, as well as to a more in-depth understanding of its safety profile.

The outbreak of coronavirus disease-2019, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a worldwide emerging crisis. Polyphenols are a class of herbal metabolites with a broad-spectrum antiviral activity. However, most polyphenols encounter limited efficacy due to their poor solubility and degradation in neutral and basic environments. Thus, the effectiveness of their pharmaceutical application is critically dependent on the delivery systems to overcome the aforementioned drawbacks. Herein, Polyphenols-rich Cuphea ignea extract was prepared and its constituents were identified and quantified. Molecular docking was conducted for 15 compounds in the extract against SARS-CoV-2 main protease, among which rutin, myricetin-3- O -rhamnoside and rosmarinic acid depicted the most promising antiviral activity. Further, a self-nanoemulsifying formulation, composed of 10% oleic acid, 40% tween 20 and propylene glycol 50%, was prepared to improve the solubility of the extract components and enable its concurrent delivery permitting combined potency. Upon dilution with aqueous phases, the formulation rapidly Formsnanoemulsion of good stability and excellent dissolution profile in acidic pH when compared to the crude extract. It inhibited SARS-CoV-2 completely in vitro at a concentration as low as 5.87 μg/mL presenting a promising antiviral remedy for SARS-CoV-2, which may be attributed to the possible synergism between the extract components., Competing Interests: This work has been submitted for patent application to patent office Academy of Scientific Research and Technology, Egypt under number 2020/1698., (© 2021 Elsevier B.V. All rights reserved.)

Aims: Calcium carbonate is a biomineral whose precipitation could be mediated by ureolytic bacteria and contributes in strengthening of sandy soils. The type of bacteria and grade of reagents have significant influence on microbially induced calcite precipitation (MICP). In the present study, factorial experiments based on these two factors were designed to determine their potential on MICP process, taking into consideration the economic advantages while giving quality results as well., Methods and Results: For the first time, Alkalibacterium iburiense strain EE1 (GenBank accession no. MF355369.1) is reported for its biogrouting activity. Optimum growth conditions for MICP treatments were pH (9·56 ± 0·021), EC (44·7 ± 0·057 mS cm -1 ), OD 600 (2·04 ± 0·015), NH 4 + concentration (487·06 ± 1·021 mmol l -1 ), and urease activity (20·0 ± 0·75 mmol l -1 urea hydrolysed min -1 ) after 72-h incubation. Statistical analysis comparing the growth in technical-grade medium prepared in tap water and analytical-grade medium prepared in deionized water showed no significant differences (P = 1·0) in biomass and urease activity. In contrast to previous studies, the current approach could reduce the bacterial culture and cementation solution ratio by about 50%, using a simple surface percolation method with staged injection instead of parallel injection to treat different sand columns. Using fixation solution could immobilize the bacteria over the full length of columns for better strength improvement. The unconfined compressive strength ranged between 0·64 to 2·11 kg cm -2 , and the corresponding CaCO 3 contents 5·7-38·5%. The scanning electron microscope images indicated that the precipitated CaCO 3 by bacteria was stable calcite., Conclusions: Alkalibacterium iburiense and technical-grade reagents under nonsterile conditions are satisfactory consolidating agents for sandy soils., Significance and Impact of the Study: This approach is considered eco-friendly and cost-effective for future scale-up applications in various geotechnical engineering., (© 2021 The Society for Applied Microbiology.)

The objective of our study was to evaluate the effect of Physalis peruviana L. fruits in the management of diabetes and diabetic nephropathy in relation to its metabolic profile. In-vitro α-amylase, β-glucosidase, and lipase inhibition activities were assessed for the ethanolic extract (EtOH) and its subfractions. Ethyl acetate (EtOAc) fraction showed the highest α-amylase, β-glucosidase, and lipase inhibition effect. In vivo antihyperglycemic testing of EtOAc in streptozotocin (STZ)-induced diabetic rats showed that it decreased the blood glucose level, prevented the reduction in body weight, improved serum indicators of kidney injury (urea, uric acid, creatinine), and function (albumin and total protein). EtOAc increased autophagic parameters (LC3B, AMPK) and depressed mTOR contents. Histopathology revealed that EtOAc ameliorated the pathological features and decreased the glycogen content induced by STZ. The immunohistochemical analysis showed that EtOAc reduced P53 expression as compared to the STZ-diabetic group. UPLC-ESI-MS/MS metabolite profiling of EtOAc allowed the identification of several phenolic compounds. Among the isolated compounds, gallic acid, its methylated dimer and the glycosides of quercetin had promising α-amylase and β-glucosidase inhibition activity. The results suggest that the phenolic-rich fraction has a protective effects against diabetic nephropathy presumably via enhancing autophagy (AMPK/mTOR pathway) and prevention of apoptosis (P53 suppression)., (Copyright © 2021. Published by Elsevier Masson SAS.)

Nanoparticles are of great importance in development and research because of their application in industries and biomedicine. The development of nanoparticles requires proper knowledge of their fabrication, interaction, release, distribution, target, compatibility, and functions. This review presents a comprehensive update on nanoparticles' toxic effects, the factors underlying their toxicity, and the mechanisms by which toxicity is induced. Recent studies have found that nanoparticles may cause serious health effects when exposed to the body through ingestion, inhalation, and skin contact without caution. The extent to which toxicity is induced depends on some properties, including the nature and size of the nanoparticle, the surface area, shape, aspect ratio, surface coating, crystallinity, dissolution, and agglomeration. In all, the general mechanisms by which it causes toxicity lie on its capability to initiate the formation of reactive species, cytotoxicity, genotoxicity, and neurotoxicity, among others., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Chukwuebuka Egbuna et al.)

Emerging pollutants represent a group of synthetic or naturally occurring compounds that are not normally monitored within the environment but can enter into the environment and cause different adverse ecological and health effects. This systematic review identified the various emerging pollutants in Nigeria. The following databases, ScienceDirect, PubMed, Google Scholar, and African Journals OnLine (AJOL) were searched to identify studies on pollutants of emerging concerns in Nigeria. A total of 933 articles were identified out of which 30 articles were selected to be eligible for the study. Over 250 emerging pollutants were identified and divided into 9 major groups which are personal care products, pharmaceuticals, industrial chemicals, polycyclic aromatic hydrocarbons, volatile organic compounds, pesticides, mycotoxins, radionuclides and electromagnetic radiations (Gamma radiation) and other pollutants of emerging concerns such as microbes, microplastics, and particulate matter. These pollutants are found in water bodies and underground waters, soils and sediments, biological systems, and ambient air at different concentrations with seasonal variations. Some of these pollutants act as endocrine disruptors, β-adrenergic receptors agonist blockers, oxidative stress inducers and can cause genetic alterations in DNA and epigenetic reprogramming through global DNA methylation, gene-specific CpG methylation and microRNA expression. Emerging pollutants of public health concern in Nigeria are on the increase and are threat to both ecological and human health., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Flaxseed is considered an indispensable generally recognized as safe (GRAS) source of polyphenolic lignans, polyunsaturated fatty acids (PUFA), fibers as well as minerals and vitamins. The metabolite content of flaxseed reflects its nutritional and medicinal value. Therefore, the selection of flaxseed variety for food industry is dependent on its metabolome. A metabolomics approach based on liquid or gas chromatography coupled to mass spectrometry has been applied to discriminate different flaxseed cultivars that are commercially available in Egypt. The available Sakha cultivars were subjected to a comprehensive metabolomics and lipidomics approach for investigation of their metabolomes. Our results showed that among the screened cultivars, Sakha 6, with its yellow-colored testa, showed marked metabolic discrimination. This yellow cultivar showed high accumulation of essential amino acids. Additionally, the oil of this cultivar accumulated the highest content of the two essential PUFA: alpha-linolenic acid (an ω-3 fatty acid) and linoleic acid (an ω-6 fatty acid). Interestingly, the content of the main antinutritional cyanogenic glycosides such as linustatin and neolinustatin was lower, while, the content of medicinally-important secondary metabolites was higher in Sakha 6 cultivar. These results support the use of this cultivar for human consumption owing to its high nutritional and medicinal value.

Aging of the skin is a complicated bioprocess that is affected by constant exposure to ultraviolet irradiation. The application of herbal-based anti-aging creams is still the best choice for treatment. In the present study, Citrus sinensis L. fruit peels ethanolic extract (CSPE) was formulated into lipid nanoparticles (LNPs) anti-aging cream. Eight different formulations of CSEP-LNPs were prepared and optimized using 2 3 full factorial designs. In vivo antiaging effect of the best formula was tested in Swiss albino mice where photo-aging was induced by exposure to UV radiation. HPLC-QToF-MS/MS metabolic profiling of CSPE led to the identification of twenty-nine metabolites. CSPE was standardized to a hesperidin content of 15.53 ± 0.152 mg% using RP-HPLC. It was suggested that the optimized formulation (F7) had (245 nm) particle size, (91.065%) EE, and (91.385%) occlusive effect with a spherical and smooth surface. The visible appearance of UV-induced photoaging in mice was significantly improved after topical application on CSPE-NLC cream for 5 weeks, levels of collagen and SOD were significantly increased in CSPE- NLC group, while levels of PGE2, COX2, JNK, MDA, and elastin was reduced. Finally, The prepared anti-aging CSPE-NLC cream represents a safe, convenient, and promising skincare cosmetic product., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The Red Sea is one of the most biodiverse aquatic ecosystems. Notably, seagrasses possess a crucial ecological significance. Among them are the two taxa Halophila stipulacea (Forsk.) Aschers., and Thalassia hemprichii (Ehrenb. ex Solms) Asch., which were formally ranked together with the genus Enhalus in three separate families. Nevertheless, they have been recently classified as three subfamilies within Hydrocharitaceae. The interest of this study is to explore their metabolic profiles through ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS/MS) analysis in synergism with molecular networking and to assess their chemosystematics relationship. A total of 144 metabolites were annotated, encompassing phenolic acids, flavonoids, terpenoids, and lipids. Furthermore, three new phenolic acids; methoxy benzoic acid- O -sulphate ( 16 ), O -caffeoyl- O -hydroxyl dimethoxy benzoyl tartaric acid ( 26 ), dimethoxy benzoic acid- O -sulphate ( 30 ), a new flavanone glycoside; hexahydroxy-monomethoxy flavanone- O -glucoside ( 28 ), and a new steviol glycoside; rebaudioside- O -acetate ( 96 ) were tentatively described. Additionally, the evaluation of the antidiabetic potential of both taxa displayed an inherited higher activity of H. stipulaceae in alleviating the oxidative stress and dyslipidemia associated with diabetes. Hence, the current research significantly suggested Halophila , Thalassia , and Enhalus categorization in three different taxonomic ranks based on their intergeneric and interspecific relationship among them and supported the consideration of seagrasses in natural antidiabetic studies.

Morinda citrifolia L. is a plant of the family Rubiaceae and is known as Indian mulberry or Noni in India. It is a perennial herb native to Southeast Asia and has been used over the years as a food supplement and medicinal plant. Noni fruits are reported to possess anticancer, fungicidal, antiviral and antiarthritic effects. The objective of our study is the screening of the immunomodulatory activity of the total extract, fractions, and isolated compounds of Noni fruits to identify their bioactive compounds. To achieve our goal, an ethanol extract (EE) was prepared from Noni fruits. Fractionation and purification of the EE were accomplished. The cell-mediated immune (CMI) response in prednisolone-induced immunosuppression rats was evaluated. The toxicity of the EE, fractions and isolated compounds on the differentiated THP-1 macrophage was assessed using the MTT viability assay. Moreover, the inflammation-related immune responses in lipopolysaccharide (LPS)-induced THP-1 macrophage activation were evaluated. Fractionation of the EE gave three fractions, dichloromethane (DCMF), water (WF) and methanol (MF). Purification of DCMF yielded stigmast-7-ene-3-ol (M1), 28-hydroxy-3β-acetoxy-9-dehydrogramisterol (M2), 3β-acetoxy-taraxast-20(30)-ene-21-ol (M3), 22-dehydroclerosterol (M4) and 22-dehydroclerosterol-3-O-β-d-glucopyranoside (M5), while purification of MF yielded quercetin (M6), hesperidin (M7), naringin (M9) and gallic acid (M8). The results revealed that DCMF elicited an increase in paw edema to the extent of 35.8%. All the tested samples had no cytotoxic effect on THP-1 macrophages. Co-treatment of the LPS-induced macrophages with DCMF, M2, M3, and M6 decreased the production of TNF-α, IL-1β, and IL-6/IL-10. The expression of iNOS, COX-2, and NF-κB decreased to 0.14 ± 0.02, 0.15 ± 0.02, and 0.17 ± 0.03, respectively, after co-treatment with LPS and DCMF. M2 attenuated the expression of iNOS and NF-κB to 0.18 ± 0.03 and 0.17 ± 0.03, respectively. Additionally, M3 attenuated the expression of iNOS to 0.18 ± 0.03, and after co-treatment with M6 and LPS, the expression of COX-2 and NF-κB was down-regulated to 0.2 ± 0.03. Our study proves the immunomodulatory effect of Noni fruits and specifies for the first time the compounds responsible for their activity.

Estrogen signaling is crucial for breast cancer initiation and progression. Endocrine-based therapies comprising estrogen receptor (ER) modulators and aromatase inhibitors remain the mainstay of treatment. This study aimed at investigating the antitumor potential of the most potent compounds in citrus peels on breast cancer by exploring their anti-estrogenic and anti-aromatase activities. The ethanolic extract of different varieties of citrus peels along with eight isolated flavonoids were screened against estrogen-dependent breast cancer cell lines besides normal cells for evaluating their safety profile. Naringenin, naringin and quercetin demonstrated the lowest IC 50s and were therefore selected for further assays. In silico molecular modeling against ER and aromatase was performed for the three compounds. In vivo estrogenic and anti-estrogenic assays confirmed an anti-estrogenic activity for the isolates. Moreover, naringenin, naringin and quercetin demonstrated in vitro inhibitory potential against aromatase enzyme along with anticancer potential in vivo, as evidenced by decreased tumor volumes. Reduction in aromatase levels in solid tumors was also observed in treated groups. Overall, this study suggests an antitumor potential for naringenin, naringin and quercetin isolated from citrus peels in breast cancer via possible modulation of estrogen signaling and aromatase inhibition suggesting their use in pre- and post-menopausal breast cancer patients, respectively.

Ethnopharmacological Relevance: Silybum marianum (L.) Gaertn. or Milk thistle is a medicinal plant native to Northern Africa, Southern Europe, Southern Russia and Anatolia. It also grows in South Australia, North and South America. In traditional knowledge, people have used S. marianum for liver disorders such as hepatitis, liver cirrhosis and gallbladder diseases. The main active compound of the plant seeds is silymarin, which is the most commonly used herbal supplement in the United States for liver problems. Nowadays, S. marianum products are available as capsules, powders, and extracts., Aim of Study: The aim of our study is to draw a more comprehensive overview of the traditional heritage, pharmacological benefits and chemical fingerprint of S. marianum extracts and metabolites; as well as their metabolism and bioavailability., Materials and Methods: An extensive literature search has been conducted using relavant keywords and papers with rationale methodology and robust data were selected and discussed. Studies involving S. marianum or its main active ingredients with regards to hepatoprotective, antidiabetic, cardiovascular protection, anticancer and antimicrobial activities as well as the clinical trials performed on the plant, were discussed here., Results: S. marianum was subjected to thousands of ethnopharmacological, experimental and clinical investigations. Although, the plant is available for use as a dietary supplement, the FDA did not yet approve its use for cancer therapy. Nowadays, clinical investigations are in progress where a global evidence of its real efficiency is needed., Conclusion: S. marianum is a worldwide used herb with unlimited number of investigations focusing on its benefits and properties, however, little is known about its clinical efficiency. Moreover, few studies have discussed its metabolism, pharmacokinetics and bioavailability, so that all future studies on S. marianum should focus on such areas., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The spore laccase enzyme production by B. amyloliquefaciens was optimized. It was characterized and tested for its textile dye decolorization potential. LB medium was found to be the most promising growth medium with addition of glucose (1-2%), yeast extract (0.1%), FeCl 3 (0.01 mM) and MnCl 2 (0.001 mM). The optimum spore laccase production was at pH 8, 30 °C, 1:5 medium to air ratio, 2% inoculum size and 7 days incubation. The characterization study of the enzyme showed the maximum activity at 60 °C and pH 6-7.5. It was induced by Ca +2 , Mg +2 , Fe +3 , Zn +2 , Cu +2 and Na + at 1 mM concentration. Also, it was stable in the presence of methanol, ethanol, acetone and chloroform. In addition, it enhanced about 34% by 5 mM H 2 O 2 and it was nearly stable at 10-20 mM H 2 O 2 . Furthermore, mediators such as ABTS, syrengaldazine and 2, 6 dimethyl phenol enhanced the spore laccase activity. The spore laccase enzyme efficiently decolorized direct red 81 and acid black 24 after 24 h. Phytotoxicity of the direct red 81 solution after decolorization by tested spore laccase was lower than that of the untreated dye solution. Finally, this study added a promising spore laccase candidate for ecofriendly and cost-effective dye wastewater bio-decolorization.

Mushrooms have a significant role in human diet as functional food and as a nutraceutical resource. The combination of its umami flavor, protein, vitamins, minerals and carbohydrates has meant that mushrooms could be considered a cheap food source for a long time in many countries. Moreover, mushrooms contain an excellent variety of bioactive metabolites that can be successful in both prevention and treatment of various human health hazards. In addition, extracts from medicinal mushrooms and their metabolites have been verified for wound treating with contribution to different mechanisms of the healing process. This review summarizes the nutritional value and composition of mushrooms, ethnobiology and ethnopharmacology, and wound healing potential., (Copyright © 2020 Sharifi-Rad, Butnariu, Ezzat, Adetunji, Imran, Sobhani, Tufail, Hosseinabadi, Ramírez-Alarcón, Martorell, Maroyi and Martins.)

Aging is an unavoidable fate that afflicts all life, during this process in mammals reactive oxygen species (ROS) are generated which stimulate tyrosinase, elastase and collagenase activities that actively participate in skin aging. Therefore, the maintenance of antioxidant homeostasis is an important anti-aging strategy for skin. Nature has excellent anti-aging remedies that act externally as well as internally to delay the visual signs of aging. In view of this fact, the present study investigates the in vitro anti-aging activity of five medicinal plants belonging to phenolic rich families namely Rosmarinus officinalis , Lavandula officinalis , Matricaria chamomilla , Camellia sinensis and Pelargonium graveolens . The selected plants are those most frequently used in the preparation of ethnomedicinal recipes for the prevention or treatment of aging. The inhibitory effects of the ethanolic and aqueous extracts of the five selected plants on the activity of tyrosinase, elastase, and collagenase enzymes were investigated. Furthermore, the chemical composition of the plants and the antioxidant capacity of their extracts were assessed. The results showed that R. officinalis had the highest total phenolics content which was correlated with its potent antioxidant and anti-aging activities. To pinpoint the active metabolites in the tested extracts, we evaluated the metabolite variations using ultra-performance liquid chromatography coupled with high resolution electrospray ionization-tandem mass spectrometry (UPLC-HR-ESI-MS/MS). Multivariate data analysis (MVDA) revealed that R. officinalis significantly accumulated metabolites from the aromatic diterpenoid, flavonoid and phenolic acid classes. These results indicate that rosemary can be used for further development of topical preparations with anti-aging properties., Competing Interests: No conflict to declare., (This journal is © The Royal Society of Chemistry.)

Rosmarinus species are aromatic plants that mainly grow in the Mediterranean region. They are widely used in folk medicine, food, and flavor industries and represent a valuable source of biologically active compounds (e.g., terpenoids, flavonoids, and phenolic acids). The extraction of rosemary essential oil is being done using three main methods: carbon dioxide supercritical extraction, steam distillation, and hydrodistillation. Furthermore, interesting antioxidant, antibacterial, antifungal, antileishmanial, anthelmintic, anticancer, anti-inflammatory, antidepressant, and antiamnesic effects have also been broadly recognized for rosemary plant extracts. Thus the present review summarized data on economically important Rosmarinus officinalis species, including isolation, extraction techniques, chemical composition, pharmaceutical, and food applications., (© 2020 John Wiley & Sons, Ltd.)

Hibiscus species (Malvaceae) have been long used as an antihypertensive folk remedy. The aim of our study was to specify the optimum solvent for extraction of the angiotensin-converting enzyme inhibiting (ACEI) constituents from Hibiscus sabdariffa L. The 80% methanol extract (H2) showed the highest ACEI activity, which exceeds that of the standard captopril (IC50 0.01255 ± 0.00343 and 0.210 ± 0.005 µg/mL, respectively). Additionally, in a comprehensive metabolomics approach, an ultra-performance liquid chromatography (UPLC) coupled to the high resolution tandem mass spectrometry (HRMS) method was used to trace the metabolites from each extraction method. Interestingly, our comprehensive analysis showed that the 80% methanol extract was predominated with secondary metabolites from all classes including flavonoids, anthocyanins, phenolic and organic acids. Among the detected metabolites, phenolic acids such as ferulic and chlorogenic acids, organic acids such as citrate derivatives and flavonoids such as kaempferol have been positively correlated to the antihypertensive potential. These results indicates that these compounds may significantly contribute synergistically to the ACE inhibitory activity of the 80% methanol extract.