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The study aimed to evaluate the anticancer potential of hinokitiol in treating oral cancer by using in vitro models and examining its interaction with the Pim-1 protein through in silico methods. Hinokitiol was applied to KB-1 oral squamous carcinoma cells, where the half-maximal inhibitory concentrations (IC 50 ) was determined. Morphologic changes in treated cells were observed using phase contrast microscopy, while acridine orange/ethidium bromide (AO/EB) staining was used to assess nuclear changes and apoptosis. Flow cytometry was employed to analyze the cell-cycle progression. Given the high expression of Pim-1 in oral squamous carcinoma cells, molecular docking and simulation were performed to evaluate hinokitiol's binding affinity and stability with the Pim-1 protein. To compare its effects, hinokitiol was also tested on non-cancerous pre-adipocytes (3T3-L1), providing insights into its selective cytotoxicity between healthy and cancerous cells. Hinokitiol treatment resulted in cytotoxic effects on KB-1 oral squamous carcinoma cells, with an IC 50 of 30 µg/mL after 24 and 48 hs of exposure. Morphologic studies showed reduced cell population and density. In contrast, hinokitiol exhibited lower toxicity and caused fewer morphological changes in non-cancerous 3T3-L1 pre-adipocytes. Apoptosis was confirmed through acridine orange/ethidium bromide staining, while flow cytometry revealed cell-cycle arrest in the Synthesis phase (S) and Gap 2 phase/ Mitosis Phase (G2/M) phases. Molecular docking showed strong binding of hinokitiol to Pim-1, and simulations confirmed the interaction's stability. These findings suggest hinokitiol selectively targets cancer cells and effectively inhibit Pim-1, supporting its potential as an oral cancer treatment., Competing Interests: Declarations Conflict of interest No conflict of interest was declared by the authors., (© 2024. The Author(s), under exclusive licence to The Society of The Nippon Dental University.)

Enzymes are biologically active complex protein molecules that catalyze most chemical reactions in living organisms, and their inhibitors accelerate biological processes. This review emphasizes medicinal food plants and their isolated chemicals inhibiting clinically important enzymes in common diseases. A mechanistic overview was investigated to explain the mechanism of these food bases enzyme inhibitors. The enzyme inhibition potential of medicinal food plants and their isolated substances was searched in Ovid, PubMed, Science Direct, Scopus, and Google Scholar. Cholinesterase, amylase, glucosidase, xanthine oxidase, tyrosinase, urease, lipoxygenase, and others were inhibited by crude extracts, solvent fractions, or isolated pure chemicals from medicinal food plants. Several natural compounds have shown tyrosinase inhibition potential, including quercetin, glabridin, phloretin-4-O-β-D-glucopyranoside, lupinalbin, and others. Some of these compounds' inhibitory kinetics and molecular mechanisms are also discussed. Phenolics and flavonoids inhibit enzyme activity best among the secondary metabolites investigated. Several studies showed flavonoids' significant antioxidant and anti-inflammatory activities, highlighting their medicinal potential. Overall, many medicinal food plants, their crude extracts/fractions, and isolated compounds have been studied, and some promising compounds depending on the enzyme have been found. Still, more studies are recommended to derive potential pharmacologically active functional foods.

In this context, phytochemicals were extracted from Ranunculus constantinopolitanus using ethyl acetate (EA), ethanol, ethanol/water (70%), and water solvent. The analysis encompassed quantification of total phenolic and flavonoid content using spectrophotometric assays, chemical profiling via high performance liquid chromatography-mass spectrometry/mass spectrometry (HPLC-MS/MS) for the extracts, and assessment of antioxidant activity via 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), Cupric reducing antioxidant capacity (CUPRAC), ferric reducing antioxidant power (FRAP), metal chelating (MCA), and phosphomolybdenum (PBD) assays. Moreover, antimicrobial activity was assessed against four different bacterial strains, as well as various yeasts. Enzyme inhibitory activities were evaluated against five types of enzymes. Additionally, the extracts were examined for their anticancer and protective effects on several cancer cell lines and the human normal cell line. All of the extracts exhibited significant levels of ferulic acid, kaempferol, and caffeic acid. All tested extracts demonstrated antimicrobial activity, with Escherichia coli and Pseudomonas aeruginosa being most sensitive to EA and ethanol extracts. Molecular docking studies revealed that kaempferol-3-O-glucoside strong interactions with AChE, BChE and tyrosinase. In addition, network pharmacology showed an association between gastric cancer and kaempferol-3-O-glucoside. Based on the results, R. constantinopolitanus can be a potential reservoir of bioactive compounds for future bioproduct innovation and pharmaceutical industries., 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 Ltd. All rights reserved.)

Background: Methods like the bio-synthesis of silver nanoparticles (Ag NPs) using plant extracts have become promising due to their eco-friendly approach. The study aimed to examine the utilization of Garcinia gummi-gutta fruit phytochemicals as agents in the biosynthesis of Ag NPs, evaluation of the antimicrobial, antioxidant, and anti-cancerous properties, as well as the photocatalytic ability of bio-synthesized Ag NPs against Crystal Violet (CV), a triphenylmethane dye., Methods: The characterization of the physical properties of the Ag NPs synthesized via the green route was done using UV-Vis spectrophotometry (UV-Vis), X-ray Diffraction (XRD), Fourier Transform Infrared Spectrophotometry (FTIR), Scanning Electron Microscopy (SEM), Zeta potential analysis, and Transmission Electron Microscopy (TEM). The dye degradation efficiency of CV was determined using synthesized Ag NPs under UV light by analyzing the absorption maximum at 579 nm. The antimicrobial efficacy of Ag NPs against E. coli, S. aureus, Candida tropicalis, and Candida albicans was examined using the broth dilution method. The antioxidant and anti-cancer properties of the synthesized Ag NPs were assessed using the DPPH and MTT assays., Results: The UV analysis revealed that the peak of synthesized Ag NPs was 442 nm. Data from FTIR, XRD, Zeta potential, SEM, and TEM analysis confirmed the formation of nanoparticles. The SEM and TEM analysis identified the presence of spherical nanoparticles with an average size of 29.12 nm and 24.18 nm, respectively. Maximum dye degradation efficiency of CV was observed at 90.08% after 320 min without any silver leaching, confirming the photocatalytic activity of Ag NPs. The bio-efficiency of the treatment was assessed using the Allium cepa root growth inhibition test, toxicity analysis on Vigna radiata, and Brine shrimp lethality assay., Conclusions: The findings revealed the environmentally friendly nature of green Ag NPs over physical/chemically synthesized Ag NPs. The synthesized Ag NPs can effectively be used in biomedical and photocatalytic applications., Competing Interests: Given the role as Guest Editor and Editorial Member, Jen-Tsung Chen had no involvement in the peer-review of this article and has no access to information regarding its peer-review. Full responsibility for the editorial process for this article was delegated to Graham Pawelec. The authors declare no conflict of interest., (© 2023 The Author(s). Published by IMR Press.)

The sea is a vast ecosystem that has remained primarily unexploited and untapped, resulting in numerous organisms. Consequently, marine organisms have piqued the interest of scientists as an abundant source of natural resources with unique structural features and fascinating biological activities. Marine macrolide is a top-class natural product with a heavily oxygenated polyene backbone containing macrocyclic lactone. In the last few decades, significant efforts have been made to isolate and characterize macrolides' chemical and biological properties. Numerous macrolides are extracted from different marine organisms such as marine microorganisms, sponges, zooplankton, molluscs, cnidarians, red algae, tunicates, and bryozoans. Notably, the prominent macrolide sources are fungi, dinoflagellates, and sponges. Marine macrolides have several bioactive characteristics such as antimicrobial (antibacterial, antifungal, antimalarial, antiviral), anti-inflammatory, antidiabetic, cytotoxic, and neuroprotective activities. In brief, marine organisms are plentiful in naturally occurring macrolides, which can become the source of efficient and effective therapeutics for many diseases. This current review summarizes these exciting and promising novel marine macrolides in biological activities and possible therapeutic applications., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

This study aimed to investigate the anti-neuropathic pain activity and its underlying molecular mechanism of Ajugarin-I (Aju-I) in a rat model of diabetic neuropathic pain. The rats were given a single injection of 60 mg/kg of streptozotocin (STZ) intraperitoneally (i.p.) to induce diabetic neuropathic pain. After two weeks, rats were given Aju-I (1 and 5 mg/kg/day) i.p. for four consecutive weeks. The results demonstrated that in diabetic rats, treatment with Aju-I decreased STZ-induced hyperglycemia. It reduced the pain hypersensitivity (mechanical, thermal, and cold nociception) caused by STZ. It effectively restored STZ-associated pathological changes in the pancreas. In the sciatic nerve and spinal cord, it attenuated STZ-associated histopathological alterations and DNA damage. It suppressed oxidative stress by increasing the expression of nuclear factor-erythroid factor 2-related factor 2 (Nrf2), thioredoxin (Trx), and heme oxygenase (HO-1), but decreasing the immunoreactivity of Kelch-like ECH-associated protein 1 (Keap1). Additionally, TRPV1 (transient receptor potential vanilloid 1) and TRPM8 (transient receptor potential melastatin 8) expression levels were considerably reduced by Aju-I treatment. It enhanced antioxidant levels and suppressed inflammatory cytokines production. Taken together, this research suggests that Aju-I treatment reduces pain behaviors in the STZ model of diabetic neuropathy via modulating Nrf2/Keap-1/HO-1 signaling and TRPV1/TRPM8 nociceptors., 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.)

Plants are an important source of drug development and numerous plant derived molecules have been used in clinical practice for the ailment of various diseases. The Toll-like receptor-4 (TLR-4) signaling pathway plays a crucial role in inflammation including rheumatoid arthritis. The TLR-4 binds with pro-inflammatory ligands such as lipopolysaccharide (LPS) to induce the downstream signaling mechanism such as nuclear factor κappa B (NF-κB) and mitogen activated protein kinases (MAPKs). This signaling activation leads to the onset of various diseases including inflammation. In the present study, 22 natural compounds were studied against TLR-4/AP-1 signaling, which is implicated in the inflammatory process using a computational approach. These compounds belong to various classes such as methylxanthine, sesquiterpene lactone, alkaloid, flavone glycosides, lignan, phenolic acid, etc. The compounds exhibited different binding affinities with the TLR-4, JNK, NF-κB, and AP-1 protein due to the formation of multiple hydrophilic and hydrophobic interactions. With TLR-4, rutin had the highest binding energy (-10.4 kcal/mol), poncirin had the highest binding energy (-9.4 kcal/mol) with NF-κB and JNK (-9.5 kcal/mol), respectively, and icariin had the highest binding affinity (-9.1 kcal/mol) with the AP-1 protein. The root means square deviation (RMSD), root mean square fraction (RMSF), and radius of gyration (RoG) for 150 ns were calculated using molecular dynamic simulation (MD simulation) based on rutin's greatest binding energy with TLR-4. The RMSD, RMSF, and RoG were all within acceptable limits in the MD simulation, and the complex remained stable for 150 ns. Furthermore, these compounds were assessed for the potential toxic effect on various organs such as the liver, heart, genotoxicity, and oral maximum toxic dose. Moreover, the blood-brain barrier permeability and intestinal absorption were also predicted using SwissADME software (Lausanne, Switzerland). These compounds exhibited promising physico-chemical as well as drug-likeness properties. Consequently, these selected compounds portray promising anti-inflammatory and drug-likeness properties.

COVID-19 (SARS-CoV-2) is a viral disease that causes acute respiratory syndrome, which has increased the morbidity and mortality rate throughout the world. World Health Organization has declared this COVID-19 outbreak as pandemic and classified health emergency throughout the world. In the recent past, outbreaks of SARS and MERS have shown the interspecies transmission potential of coronaviruses and limitations of already prescribed drugs to overcome this global public health issue. Therefore, there is a dire need to identify a new regimen of targeted drugs from natural compounds having anti-COVID19 potential. This study aimed at screening 1018 brown algal natural compounds (many of them previously reported to have immunomodulatory effects) having probable anti-COVID19 potentials. The source compounds were extracted from MarinLit, a database dedicated to marine natural products and screened against COVID-19 main protease. The top seven compounds were further analysed, and their interactions with the active site were visualized. This study will further warrant screening the potent compounds against the virus in-vitro conditions., Competing Interests: None., (© 2021 SAAB. Published by Elsevier B.V. All rights reserved.)

Carotenoids in food substances are believed to have health benefits by lowering the risk of diseases. Lutein, a carotenoid compound, is one of the essential nutrients available in green leafy vegetables (kale, broccoli, spinach, lettuce, and peas), along with other foods, such as eggs. As nutrition plays a pivotal role in maintaining human health, lutein, as a nutritional substance, confers promising benefits against numerous health issues, including neurological disorders, eye diseases, skin irritation, etc. This review describes the in-depth health beneficial effects of lutein. As yet, a minimal amount of literature has been undertaken to consider all its promising bioactivities. The step-by-step biosynthesis of lutein has also been taken into account in this review. Besides, this review demonstrates the drug interactions of lutein with β-carotene, as well as safety concerns and dosage. The potential benefits of lutein have been assessed against neurological disorders, eye diseases, cardiac complications, microbial infections, skin irritation, bone decay, etc. Additionally, recent studies ascertained the significance of lutein nanoformulations in the amelioration of eye disorders, which are also considered in this review. Moreover, a possible approach for the use of lutein in bioactive functional foods will be discussed., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Electrons exchange amongst the chemical species in an organism is a pivotal concomitant activity carried out by individual cells for basic cellular processes and continuously contribute towards the maintenance of bioenergetic networks plus physiological attributes like cell growth, phenotypic differences and nutritional adaptations. Humans exchange matter and energy via complex connections of metabolic pathways (redox reactions) amongst cells being a thermodynamically open system. Usually, these reactions are the real lifeline and driving forces of health and disease in the living entity. Many shreds of evidence support the secondary role of reactive species in the cellular process of control apoptosis and proliferation. Disrupted redox mechanisms are seen in malaises, like degenerative and metabolic disorders, cancerous cells. This review targets the importance of redox reactions in the body's normal functioning and the effects of its alterations in cells to obtain a better understanding. Understanding the redox dynamics in a pathological state can provide an opportunity for cure or diagnosis at the earlier stage and serve as an essential biomarker to predict in advance to give personalized therapy. Understanding redox metabolism can also highlight the use of naturally available antioxidant in the form of diet., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Camel Urine (CU) is composed of components that have antitumor properties and other therapeutic benefits. Regardless of short-term preliminary CU genotoxicity is reported, comprehensive genotoxic studies are limited. In this study, sensitive in vitro and in vivo genotoxic bioassays such as mitotic index (MI), chromosomal aberrations (CA), micronucleated polychromatic erythrocytes (MPE), and analysis of primary spermatocytes were employed. The adventitious roots of Allium cepa L. and mice (Mus musculus), as an experimental mammalian system, were employed to assess the MI and CA of CU induced by sodium nitrate and cyclophosphamide respectively. In contrast, other clastogenic assays were studied in mice (Mus musculus). Twenty-eight days of four repeated doses (2.5, 5, 25, and 50 mL/kg BW) of CU were tested and compared with three doses (10, 25, and 50 mg/kg BW) cyclophosphamide as a positive control and deionized water as the negative control. The results proved that cytological examination of CU was cytotoxic since a decrease in mitotic activity (16.8-1.1) was observed, since the significant reduction in cell proliferation in A. cepa L. and also in mice bone marrow cells. On the other hand, CU did not induce a clastogenic effect since no significant stickiness, fragment, multinucleoli were observed compared to the control group. Additionally, the data showed that CU decreased the CA when mice had received cyclophosphamide (25 mg BW) followed by CU doses. CU was found to be cytotoxic but no clastogenic effect. Furthermore, it possesses anticlastogenic properties. The observed results suggest that CU in whole or the metabolites present in CU could be a potent drug target. Further research is warranted to study the complete metabolites profiling and to study the molecular mechanisms., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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.

Marine habitats are well-known for their diverse life forms that are potential sources of novel bioactive compounds. Evidence from existing studies suggests that these compounds contribute significantly to the field of pharmaceuticals, nutraceuticals, and cosmeceuticals. The isolation of natural compounds from a marine environment with protease inhibitory activity has gained importance due to drug discovery potential. Despite the increasing research endeavours focusing on protease inhibitors' design and characterization, many of these compounds have failed to reach final phases of clinical trials. As a result, the search for new sources for the development of protease inhibitors remains pertinent. This review focuses on the diverse marine protease inhibitors and their structure-activity relationships. Furthermore, the potential of marine protease inhibitors in drug discovery and molecular mechanism inhibitor binding are critically discussed., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Mertensia maritima (L.) Gray is threatened with extinction owing to climate change, poor seed germination, and ocean warming. In vitro explant-culture is used for ex situ preservation and plantlet massive production. In vitro cell and organ cultures serve as an alternative plant material source to investigate the biological activities and phytochemical profiles of rare plants. We aimed to develop an efficient callus and shoot production protocol and investigate bioactive metabolites, antioxidants, and enzyme inhibitory potential of M. maritima calli, shoots, and in vivo seedlings. The effects of combinations of different plant growth regulators, 6-BA (N 6 -benzyladenine), 6-KN (Kinetin), TDZ (Thidiazuron), and NAA (1-Naphthylacetic acid), in MS (Murashige and Skoog) nutrient medium were studied. The highest callus proliferation was obtained after 5-week cultivation over a 16-h photoperiod on growth medium MS enriched with 4 µM each of 6-BA and NAA. The medium with 2 µM 6-BA and 4 µM 6-KN had the best shoot induction rate (91.1%) with a mean of 13.4 shoots. The combination of two cytokinins (6-BA and 6-KN) was found to be effective in M. maritima shoot regeneration. The rooting frequency was 100% in ½ MS with Indole-3-butyric acid (IBA 2 µM). The number of detected compounds and chemical composition in the M. maritima shoots and seedlings extracts were similar. The total amount of phenolics in the shoots was 216.4% and 369.5% higher than in seedlings and calli, respectively. The total amount of flavonoids in the shoots was 241.1% and 429.3% higher than in seedlings and calli, respectively. The best antioxidant activity was obtained in the shoots, followed by seedlings and calli. However, the order was seedlings > calli > shoots regarding metal chelating ability. The strongest acetylcholinesterase inhibition properties were obtained in the calli, followed by seedlings and shoots. However, the tested samples can be ranked as seedlings > shoots > calli in butylcholinestrase inhibition assay. This study is the first report on the enzyme inhibitory effects of M. maritima extracts, providing valuable contributions to the scientific community.

Neurological sicknesses are serious, multifactorial, debilitating disorders that may cause neurodegeneration. Neuroprotection is the protection of the structure and capacity of neurons from affronts emerging from cell injuries instigated by an assortment of specialists or neurodegenerative diseases. Various neurodegenerative diseases, including Alzheimer's, Parkinson's, and epilepsy, afflict many people worldwide, with increasing age representing the leading risk factor. Crocin is a natural carotenoid compound which was found to have therapeutic potentials in the management of the neurological disease. In this review, we focused on the restorative capabilities of Crocin as a neuroprotective agent. The general neuroprotective impact and the various conceivable basic components identified with Crocin have been examined. In light of the substantial proof indicating the neuro-pharmacological viability of Crocin to different exploratory standards, it is concluded that Crocin exerts direct antioxidant, antiapoptotic and anti-inflammatory activities by multiple signaling pathways. Besides, Crocin was found to elevate dopamine level in the brain during the experimental model of Parkinson's disease. Thus, this compound has been demonstrated to be a promising option for the treatment of neurodegenerative diseases, with few adverse effects. It ought to be further considered as a potential contender for neuro-therapeutics, concentrating on the mechanistic and clinical evidence for its effects., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Schistosomiasis, a parasitic disease caused by trematodes of the genus Schistosoma , is the second most prevalent parasitic disease in the world. It affects around 200 million people. Clinical treatment, prophylaxis, and prevention are performed in countries susceptible to schistosomiasis. In the pharmacological treatment for an acute form of schistosomiasis, the use of antiparasitics, mainly praziquantel, is more common. As an alternative way, prevention methods such as reducing the population of intermediate hosts (mollusks) with molluscicides are important in the control of this disease by interrupting the biological cycle of this etiological parasite. Despite the importance of pharmacological agents and molluscicides, they have side effects and environmental toxicity. In addition, they can lead to the development of resistance enhancing of parasites, and lead to the search for new and effective drugs, including resources of vegetal origin, which in turn, are abundant in the affected countries. Thus, the purpose of this review is to summarize recent studies on botanical products with potential for the control of schistosomiasis, including anti-Schistosoma and molluscicide activities. In addition, species and plant derivatives according to their origin or geographical importance indicating a possible utility of local resources for countries most affected by the disease are presented.

In recent years, natural products have reemerged as biotherapeutic options, with several dietary carotenoids, viz. astaxanthin, fucoxanthin, siphonaxanthin, β-cryptoxanthin, α-carotene, β-carotene, and lycopene, developing as potential candidates for chemoprevention and chemotherapeutics of breast, colorectal, lung, and prostate cancers. The potent cytotoxic and antiproliferative effects of carotenoids against various cancer cells are mediated by a wide range of molecular mechanisms modulating oxidative stress and redox balance, mitogen-activated protein kinases (MAPK) and other cellular signaling proteins, transcription factors, caspase cascade pathways of apoptosis, cell cycle progression and proliferation, angiogenesis, metastasis, gap junction intercellular communication (GJIC), and multidrug resistance (MDR). This review discusses recent evidence demonstrating the crucial roles of carotenoids in these cellular and molecular events of cancer cell cytotoxicity. In addition, recent case-control and cohort studies are discussed to support the potential role of carotenoids in cancer prevention and therapy., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Seaweeds have been exploited as both food products and therapeutics to manage human ailments for centuries. This study investigated the metabolite profile of five seaweeds ( Halimeda spp., Spyridia hypnoides (Bory de Saint-Vincent) Papenfuss, Valoniopsis pachynema (G. Martens) Børgesen, Gracilaria fergusonii J. Agardh and Amphiroa anceps (Lamarck) Decaisne using ultra-high-performance liquid chromatography coupled with electrospray ionization mass spectrometry (UHPLC-ESI-MS/MS). Furthermore, these seaweeds were assessed for antioxidant and inhibitory effects against α-amylase, α-glucosidase, acetyl-cholinesterase (AChE), butyryl-cholinesterase (BChE) and tyrosinase. Valoniopsis pachynema and A. anceps yielded the highest flavonoid (4.30 ± 0.29 mg RE/g) and phenolic content (7.83 ± 0.08 mg RE/g), respectively. Additionally, A. anceps exhibited significant antioxidant properties with all assays and significantly depressed BChE (IC 50 = 6.68 ± 0.83 mg/mL) and α-amylase activities (IC 50 = 5.34 ± 0.14 mg/mL). Interestingly, the five seaweeds revealed potent inhibitory effects against tyrosinase activity. In conclusion, A. anceps might be considered as a key source of phytoantioxidants and a potential candidate to develop nutritional supplements. Besides, the five tested seaweeds warrant further study and may be exploited as promising natural sources for managing hyperpigmentation., Competing Interests: Funding: This research received no external funding.

Seaweeds are among the significant currently exploited marine plant resources which are gaining full applications in culinary, cosmetic, pharmaceutical, and biotechnological processes. Much attention has been devoted to seaweeds based on their proven health benefits and is considered as a rich source of structurally different bioactive metabolites for the discovery of novel functional food-based pharmacophores/drugs. Nonetheless, there is still a dearth of updated compilation and analysis of the in-depth pharmacological activities of these compounds. This review, therefore, aims to provide a piece of up-to-date detailed information on the major compounds isolated from various seaweed species together with their in-vitro and in-vivo biological properties. These compounds were found to possess broad pharmacological properties and inhibitory enzyme activities against critical enzymes involved in the aetiology of noncommunicable diseases. However, their toxicity, clinical efficacy, mechanisms of action, and interaction with conventional foods, are still less explored and require more attention in future studies., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Ethnobotanical evidences report the use of Rhododendron luteum Sweet (Ericaceae) in traditional medicinal systems. However, R. luteum has been associated to the occurrence of 'mad honey' poisoning. In the present study, the ethyl acetate, methanol, and water extracts of R. luteum were investigated for their in vitro antioxidant, enzyme inhibition, and cytotoxic properties. The cytotoxicity of R. luteum extracts on A549 lung cancer cell line was evaluated using MTT cell viability assay. Besides, HPLC-ESI-MS n approach was employed to elucidate the secondary metabolite profiles of R. luteum in order to establish any structure-activity relationship. Methanol and water extracts of R. luteum possessed highest radical scavenging and reducing properties while the ethyl acetate extract showed highest metal chelating properties. In terms of enzyme inhibition, the methanol and ethyl acetate extracts of R. luteum, possessing epigallocatechin, were active inhibitors of cholinesterase enzymes, α-glucosidase, and tyrosinase. Water extract caused growth inhibition of A549 cells with 207.2 μg/ml IC 50 value. Though R. luteum has received little scientific attention due to the occurrence of grayanotoxins in the plant, however, data presented in this work shows promising biological activity of R. luteum and highlighted its role as a potential source of antioxidant and key enzyme inhibitors., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

A growing number of evidences from clinical and preclinical studies have shown that dysregulation of microRNA (miRNA) function contributes to the progression of cancer and thus miRNA can be an effective target in therapy. Dietary phytochemicals, such as quercetin, are natural products that have potential anti-cancer properties due to their proven antioxidant, anti-inflammatory, and anti-proliferative effects. Available experimental studies indicate that quercetin could modulate multiple cancer-relevant miRNAs including let-7, miR-21, miR-146a and miR-155, thereby inhibiting cancer initiation and development. This paper reviews the data supporting the use of quercetin for miRNA-mediated chemopreventive and therapeutic strategies in various cancers, with the aim to comprehensively understand its health-promoting benefits and pharmacological potential. Integration of technology platforms for miRNAs biomarker and drug discovery is also presented., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Lung cancer is the most common cancer-related death worldwide. Natural compounds have shown high biological and pharmaceutical relevance as anticancer agents. Retinoids are natural derivatives of vitamin A having many regulatory functions in the human body, including vision, cellular proliferation and differentiation, and activation of tumour suppressor genes. Retinoic acid (RA) is a highly active retinoid isoform with promising anti-lung cancer activity. The abnormal expression of retinoid receptors is associated with loss of anticancer activities and acquired resistance to RA in lung cancer. The preclinical promise has not translated to the general clinical utility of retinoids for lung cancer patients, especially those with a history of smoking. Newer retinoid nano-formulations and the combinatorial use of retinoids has been associated with lower toxicity and more favorably efficacy in both the preclinical and clinical settings. Here, we highlight epidemiological and clinical therapeutic studies involving retinoids and lung cancer. We also discuss the biological actions of retinoids in lung cancer, which include effects on cancer stem cell differentiation, angiogenesis, metastasis, and proliferative. We suggest that the use of retinoids in combination with conventional and targeted anticancer agents will broaden the utility of these potent anticancer compounds in the lung cancer clinic., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

In the present study, the biological properties, including, the enzyme inhibitory and antioxidant activities, as well as, the phytochemical profile of the ethyl acetate, methanol, and water extracts of Rubus sanctus Schreb. and Rubus ibericus Juz. leaves were determined using in vitro bioassays. Wide range of phytochemicals, including, hydroxybenzoic acids, hydroxycinnamic acids, acylquinic acids, ellagitannins, flavonoids, and triterpenoid saponins were determined using UHPLC-ESI/HRMS technique. The ethyl acetate and methanol extracts of the studied Rubus species effectively inhibited acetyl and butyryl cholinesterase. On the other hand, R. sanctus water extract showed low inhibition against α-amylase and prominent inhibitory action against α-glucosidase. Data collected from this study reported the radical scavenging and reducing potential of the studied Rubus species. Investigation of the protective effects of the different extracts of R. sanctus and R. ibericus in experimental model of ulcerative colitis was performed. The extracts were also tested on spontaneous migration of human colon cancer cells (HCT116) in wound healing experimental paradigm. Only R. sanctus methanol extract inhibited spontaneous HCT116 migration in the wound healing test. Our results suggested that R. sanctus and R. ibericus may be potential candidates as sources of biologically-active compounds for the development of nutraceuticals, pharmaceuticals, and/or cosmetics., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

This study attempts to compare the pharmaceutical potential (antioxidant and key enzyme inhibition of clinical relevance) of organic and aqueous extracts of Parentucellia latifolia (L.) Caruel subsp. latifolia (L.) Caruel as well as phytochemical composition. The phytochemical compounds were evaluated by spectrophotometric methods (for total amounts) and HPLC-ESI-DAD-MS n (for individual compounds). The extracts were screened for antioxidant abilities by in vitro assays. Inhibition effects were also investigated against a set of enzymes linked to major health problems. Generally, the methanol (MeOH) and aqueous extracts displayed higher scavenging abilities on radicals and reductive effects when compared with the ethyl acetate (EtOAc) extract. On the other hand, the EtOAc extract was the most active inhibitor on cholinesterases (1.81-1.88 mg GALAE/g), amylase (0.70 mmol ACAE/g), glucosidase (2.85 mmol ACAE/g) and lipase (33.24 mg OE/g). The highest TPC was observed in the aqueous extract (25.07 mg GAE/g) while MeOH extract possessed the highest level of TFC (44.15 mg RE/g) and TPAC (3.46 mg CE/g). LC-MS n metabolite profiling indicated that loganin and its isomers, rutin, and luteolin-O-hexoside were the most abundant compounds. Our results suggest that P. latifolia may be valuable source of phyto-agents for the management of noncommunicable diseases., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Onion, ( Allium cepa L.), is one of the most consumed and grown vegetable crops in the world. Onion bulb, with its characteristic flavor, is the third most essential horticultural spice with a substantial commercial value. Apart from its culinary virtues, A. cepa is also used traditionally for its medicinal virtues in a plethora of indigenous cultures. Several publications have been produced in an endeavor to validate such traditional claims. Nonetheless, there is still a dearth of up-to-date, detailed compilation, and critical analysis of the traditional and ethnopharmacological propensities of A. cepa . The present review, therefore, aims to systematically review published literature on the traditional uses, pharmacological properties, and phytochemical composition of A. cepa. A. cepa was found to possess a panoply of bioactive compounds and numerous pharmacological properties, including antimicrobial, antioxidant, analgesic, anti-inflammatory, anti-diabetic, hypolipidemic, anti-hypertensive, and immunoprotective effects. Although a large number of in vitro and in vivo studies have been conducted, several limitations and research gaps have been identified which need to be addressed in future studies.

Although foliar application of seaweed extracts on plant growth and development has and is extensively studied, reliable knowledge and understanding of the mode of action of particular compound(s) responsible for enhancing plant growth is lacking. A brown seaweed Ecklonia maxima is widely used commercially as a biostimulant to improve plant growth and crop protection. Eckol, a phenolic compound isolated from E. maxima has recently shown stimulatory effects in maize, indicating its potential use as a plant biostimulant. Cabbage is a widely cultivated vegetable crop throughout the world, which requires high input of fertilizers and is susceptible to several aphid borne diseases. This study was conducted to evaluate the effect of foliar application of eckol on the growth, phytochemical constituents and myrosinase activity (aphid resistance capacity) of commercially cultivated cabbage. Foliar application of eckol (10(-6) M) significantly enhanced shoot and root length, shoot and root fresh and dry weight, leaf area and leaf number. This treatment also showed a significant increase in photosynthetic pigments (chlorophyll 'a', chlorophyll 'b', total chlorophyll and carotenoid) compared to the untreated plants. The levels of protein, proline and iridoid glycosides were significantly higher in cabbage leaves with eckol treatment. All the control plants were severely infested with cabbage aphid (Brevicoryne brassicae) but no infestation was observed on the eckol-sprayed plants, which can be attributed to an increase in myrosinase activity. This study reveals dual effects (plant growth promoting and insect repelling) of eckol on cabbage plants that need further investigations both under field conditions and in other brassicaceous species., (Copyright © 2015 Elsevier B.V. All rights reserved.)

In our continuing search for biologically active natural product(s) of plant origin, Buddleja saligna, a South African medicinal plant, was screened in line with its traditional use for antidiabetic (yeast alpha glucosidase inhibitory) and antiplasmodial (against a chloroquine sensitive strain of Plasmodium falciparum (NF54)) activities. The hexane fraction showed the most promising activity with regards to its antidiabetic (IC(50) = 260 ± 0.112 µg/ml) and antiplasmodial (IC(50) = 8.5 ± 1.6 µg/ml) activities. Using activity guided fractionation three known terpenoids (betulonic acid, betulone and spinasterol) were isolated from this species for the first time. The compounds displayed varying levels of biological activities (antidiabetic: 27.31 µg/ml ≥ IC(50) ≥ 5.6 µg/ml; antiplasmodial: 14 µg/ml ≥ IC(50) ≥ 2 µg/ml) with very minimal toxicity.

Main Conclusion: Eckol, a major phenolic compound isolated from brown seaweed significantly enhanced the bulb size and bioactive compounds in greenhouse-grown Eucomis autumnalis. We investigated the effect of eckol and phloroglucinol (PG) (phenolic compounds) isolated from the brown seaweed, Ecklonia maxima (Osbeck) Papenfuss on the growth, phytochemical and auxin content in Eucomis autumnalis (Mill.) Chitt. The model plant is a popular medicinal species with increasing conservation concern. Eckol and PG were tested at 10(-5), 10(-6) and 10(-7) M using soil drench applications. After 4 months, growth parameters, phytochemical and auxin content were recorded. When compared to the control, eckol (10(-6) M) significantly improved bulb size, fresh weight and root production while the application of PG (10(-6) M) significantly increased the bulb numbers. However, both compounds had no significant stimulatory effect on aerial organs. Bioactive phytochemicals such as p-hydroxybenzoic and ferulic acids were significantly increased in eckol (10(-5) M) and PG (10(-6) M) treatments, compared to the control. Aerial (1,357 pmol/g DW) and underground (1,474 pmol/g DW) parts of eckol-treated (10(-5) M) plants yielded the highest concentration of indole-3-acetic acid. Overall, eckol and PG elicited a significant influence on the growth and physiological response in E. autumnalis. Considering the medicinal importance of E. autumnalis and the increasing strains on its wild populations, these compounds are potential tools to enhance their cultivation and growth.

Enzyme inhibitors are now included in all kinds of drugs essential to treat most of the human diseases including communicable, metabolic, cardiovascular, neurological diseases and cancer. Numerous marine algae have been reported to be a potential source of novel enzyme inhibitors with various pharmaceutical values. Thus, the purpose of this review is to brief the enzyme inhibitors from marine algae of therapeutic potential to treat common diseases. As per our knowledge this is the first review for the potential enzyme inhibitors from marine origin. This review contains 86 algal enzyme inhibitors reported during 1989-2013 and commercial enzyme inhibitors available in the market. Compounds in the review are grouped according to the disease conditions in which they are involved; diabetes, obesity, dementia, inflammation, melanogenesis, AIDS, hypertension and other viral diseases. The structure-activity relationship of most of the compounds are also discussed. In addition, the drug likeness properties of algal inhibitors were evaluated using Lipinski's 'Rule of Five'., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Alpha-glucosidase inhibitors play a potential role in the treatment of type 2 diabetes by delaying glucose absorption in the small intestine. Ecklonia maxima, a brown alga which grows abundantly on the west coast of South Africa, is used to produce alginate, animal feed, nutritional supplements and fertilizer. The crude aqueous methanol extract, four solvent fractions and three phlorotannins: 1,3,5-trihydroxybenezene (phloroglucinol) (1), dibenzo [1,4] dioxine-2,4,7,9-tetraol (2) and hexahydroxyphenoxydibenzo [1,4] dioxine (eckol) (3) isolated from E. maxima were evaluated for antiradical and alpha-glucosidase inhibitory activities. All the phlorotannins tested had strong antioxidant activities on DPPH free radicals with EC50 values ranging from 0.008 to 0.128μM. Compounds 2 and 3 demonstrated stronger antioxidant activity and an alpha-glucosidase inhibitory property than positive controls. These results suggest that E. maxima could be a natural source of potent antioxidants and alpha-glucosidase inhibitors. This study could facilitate effective utilization of E. maxima as an oral antidiabetic drug or functional food ingredient with a promising role in the formulation of medicines and nutrition supplements., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Croton species are used in folk medicine in the management of infections, inflammation and oxidative stress-related diseases. In order to isolate, characterize and evaluate the bioactive constituents of Croton menyharthii Pax leaf extracts, repeated column fractionation of the ethyl acetate fraction from a 20% aqueous methanol crude extract afforded three flavonols identified by NMR (1D and 2D) spectroscopic methods as myricetrin-3-O-rhamnoside (myricetrin, 1), quercetin-3-O-rhamnoside (2) and quercetin (3) along with an indole alkaloid, (E)-N-(4-hydroxycinnamoyl)-5-hydroxytryptamine, [trans-N-(p-coumaroyl) serotonin, 4]. All the compounds are reported from the leaf extract of this plant for the first time. The crude extracts, four solvent fractions (hexane, DCM, ethyl acetate and butanol) and isolated compounds obtained from the leaves were evaluated for their inhibitory effects on selected bacteria, a fungus (Candida albicans), cyclooxygenase (COX-2), α-glucosidase and acetylcholinesterase (AChE). Amongst the compounds, quercetin (3) was the most active against Bacillus subtilis and Candida albicans while myricetrin-3-O-rhamnoside (1) and trans-N-(p-coumaroyl) serotonin (4) were the most active compounds against Escherichia coli, Klebsiella pneumonia and Staphylococcus aureus. The inhibitory activity of myricetrin-3-O-rhamnoside (1) against COX-2 was insignificant while that of the other three compounds 2-4 was low. The AChE inhibitory activity of the alkaloid, trans-N-(p-coumaroyl) serotonin was high, with a percentage inhibitory activity of 72.6% and an IC50 value of 15.0 µg/mL. The rest of the compounds only had moderate activity. Croton menyharthii leaf extracts and isolated compounds inhibit α-glucosidase at very low IC50 values compared to the synthetic drug acarbose. Structure activity relationship of the isolated flavonols 1-3 is briefly outlined. Compounds 1-4 and the leaf extracts exhibited a broad spectrum of activities. This validates the ethnomedicinal use of the plant in folk medicine.