Arctium lappa (Burdock): Insights from ethnopharmacology potential, chemical constituents, clinical studies, pharmacological utility and nanomedicine.

Arctium lappa L. is a medicinal edible homologous plant, commonly known as burdock or bardana, which belongs to the Asteraceae family. It is widely distributed throughout Northern Asia, Europe, and North America and has been utilized for hundreds of years. The roots, fruits, seeds, and leaves of A. lappa have been extensively used in traditional Chinese Medicine (TCM). A. lappa has attracted a great deal of attention due to its possession of highly recognized bioactive metabolites with significant therapeutic potential. Numerous pharmacological effects have been demonstrated in vitro and in vivo by A. lappa and its bioactive metabolites, including antimicrobial, anti-obesity, antioxidant, anticancer, anti-inflammatory, anti-diabetic, anti-allergic, antiviral, gastroprotective, hepatoprotective, and neuroprotective activities. Additionally, A. lappa has demonstrated considerable clinical efficacies and valuable applications in nanomedicine. Collectively, this review covers the properties of A. lappa and its bioactive metabolites, ethnopharmacology aspects, pharmacological effects, clinical trials, and applications in the field of nanomedicine. Hence, a significant attention should be paid to clinical trials and industrial applications of this plant with particular emphasis, on drug discovery and nanotechnology.

Saudi Arabian Plants: A Powerful Weapon against a Plethora of Diseases.

The kingdom of Saudi Arabia (SA) ranks fifth in Asia in terms of area. It features broad biodiversity, including interesting flora, and was the historical origin of Islam. It is endowed with a large variety of plants, including many herbs, shrubs, and trees. Many of these plants have a long history of use in traditional medicine. The aim of this review is to evaluate the present knowledge on the plants growing in SA regarding their pharmacological and biological activities and the identification of their bioactive compounds to determine which plants could be of interest for further studies. A systematic summary of the plants' history, distribution, various pharmacological activities, bioactive compounds, and clinical trials are presented in this paper to facilitate future exploration of their therapeutic potential. The literature was obtained from several scientific search engines, including Sci-Finder, PubMed, Web of Science, Google Scholar, Scopus, MDPI, Wiley publications, and Springer Link. Plant names and their synonyms were validated by 'The Plant List' on 1 October 2021. SA is home to approximately 2247 plant species, including native and introduced plants that belong to 142 families and 837 genera. It shares the flora of three continents, with many unique features due to its extreme climate and geographical and geological conditions. As plants remain the leading supplier of new therapeutic agents to treat various ailments, Saudi Arabian plants may play a significant role in the fight against cancer, inflammation, and antibiotic-resistant bacteria. To date, 102 active compounds have been identified in plants from different sites in SA. Plants from the western and southwestern regions have been evaluated for various biological activities, including antioxidant, anti-cancer, antimicrobial, antimalarial, anti-inflammatory, anti-glycation, and cytotoxic activities. The aerial parts of the plants, especially the leaves, have yielded most of the bioactive compounds. Most bioactivity tests involve in vitro assessments for the inhibition of the growth of tumour cell lines, and several compounds with in vitro antitumour activity have been reported. More in-depth studies to evaluate the mode of action of the compounds are necessary to pave the way for clinical trials. Ecological and taxonomical studies are needed to evaluate the flora of SA, and a plan for the conservation of wild plants should be implemented, including the management of the protection of endemic plants.

Insights into the Role of Natural Products in the Control of the Honey Bee Gut Parasite (Nosema spp.).

The honey bee is an important economic insect due to its role in pollinating many agricultural plants. Unfortunately, bees are susceptible to many pathogens, including pests, parasites, bacteria, and viruses, most of which exert a destructive impact on thousands of colonies. The occurrence of resistance to the therapeutic substances used against these organisms is rising, and the residue from these chemicals may accumulate in honey bee products, subsequently affecting the human health. There is current advice to avoid the use of antibiotics, antifungals, antivirals, and other drugs in bees, and therefore, it is necessary to develop alternative strategies for the treatment of bee diseases. In this context, the impact of nosema diseases (nosemosis) on bee health and the negative insults of existing drugs are discussed. Moreover, attempts to combat nosema through the use of alternative compounds, including essential oils, plant extracts, and microbes in vitro and in vivo, are documented.

In Vitro Induction of Apoptosis in Isolated Acute Myeloid Leukemia Cells: The Role of Anastatica hierochuntica Methanolic Extract.

Anastatica hierochuntica L. (Cruciferae) has been known in Egyptian folk medicine as a remedy for gastrointestinal disorders, diabetes and heart diseases. Despite the wide usage, A. hierochuntica research provides insufficient data to support its traditional practice. The cytotoxicity of A. hierochuntica methanolic extract was investigated on acute myeloid leukemia blasts (AML) and normal human peripheral leucocytes (NHPL). The phytochemical identification of bioactive compounds using 1H-NMR and LC-ESI-MS was also performed. A. hierochuntica extract caused non-significant cytotoxicity on NHPL, while the cytotoxicity on AML was significant (IC50: 0.38 ± 0.02 µg/mL). The negative expression of p53, upregulation of Caspase-3 and increase in the BAX/BCL-2 ratio were reported at the protein and mRNA levels. The results suggest that A. hierochuntica extract induced AML cell death via the p53-independent mitochondrial intrinsic pathway and further attention should be paid to this plant as a promising natural anticancer agent.

Screening for natural and derived bio-active compounds in preclinical and clinical studies: One of the frontlines of fighting the coronaviruses pandemic.

BACKGROUND: Starting December 2019, mankind faced an unprecedented enemy, the COVID-19 virus. The world convened in international efforts, experiences and technologies in order to fight the emerging pandemic. Isolation, hygiene measure, diagnosis, and treatment are the most efficient ways of prevention and intervention nowadays. The health organizations and global care systems screened the available resources and offered recommendations of approved and proposed medications. However, the search for a specific selective therapy or vaccine against COVID-19 remains a challenge. METHODS: A literature search was performed for the screening of natural and derived bio-active compounds which showed potent antiviral activity against coronaviruses using published articles, patents, clinical trials website (https://clinicaltrials.gov/) and web databases (PubMed, SCI Finder, Science Direct, and Google Scholar). RESULTS: Through the screening for natural products with antiviral activities against different types of the human coronavirus, extracts of Lycoris radiata (L'Hér.), Gentiana scabra Bunge, Dioscorea batatas Decne., Cassia tora L., Taxillus chinensis (DC.), Cibotium barometz L. and Echinacea purpurea L. showed a promising effect against SARS-CoV. Out of the listed compound Lycorine, emetine dihydrochloride hydrate, pristimerin, harmine, conessine, berbamine, 4`-hydroxychalcone, papaverine, mycophenolic acid, mycophenolate mofetil, monensin sodium, cycloheximide, oligomycin and valinomycin show potent activity against human coronaviruses. Additionally, it is worth noting that some compounds have already moved into clinical trials for their activity against COVID-19 including fingolimod, methylprednisolone, chloroquine, tetrandrine and tocilizumab. CONCLUSION: Natural compounds and their derivatives could be used for developing potent therapeutics with significant activity against SARS-COV-2, providing a promising frontline in the fighting against COVID-19.

Exploring natural products-based cancer therapeutics derived from egyptian flora.

ETHNOPHARMACOLOGICAL RELEVANCE: Egyptian plants are a rich source of natural molecules, representing considerable biodiversity due to climate variations between the Northern, Southern, Eastern and Western regions of the country. Sinai is considered a precious nature reserves preserving flora, fauna, marine organisms, and historical habitats with ancient origins. Here, traditional medicinal approaches have been used for hundreds of years. Healthy lifestyles, low levels of stress and microbial infections, and a dependence on flora and herbal medicine might in combination explain why the burden of cancer is lower in some regions than in others. AIM OF THE STUDY: The primary aim of this review is to document the plants and natural products that are used as foods and medicines in Egypt, in general, and in Sinai, in particular, with a focus on those with demonstrated anticancer activities. The documented traditional uses of these plants are described, together with their chemical and pharmacological activities and the reported outcomes of clinical trials against cancer. MATERIALS AND METHODS: A literature search was performed to identify texts describing the medicinal plants that are cultivated and grown in Egypt, including information found in textbooks, published articles, the plant list website (http://www.theplantlist.org/), the medicinal plant names services website (http://mpns.kew.org/mpns-portal/), and web databases (PubMed, Science Direct, and Google Scholar). RESULTS AND DISCUSSION: We collected data for most of the plants cultivated or grown in Egypt that have been previously investigated for anticancer effects and reported their identified bioactive elements. Several plant species, belonging to different families and associated with 67 bioactive compounds, were investigated as potential anticancer agents (in vitro studies). The most potent cytotoxic activities were identified for the families Asteraceae, Lamiaceae, Chenopodiaceae, Apocynaceae, Asclepiadaceae, Euphorbiaceae, Gramineae, and Liliaceae. The anticancer activities of some species, such as Punica granatum L., Nerium oleander L., Olea europea L., Matricaria chamomilla L., Cassia acutifolia L., Nigella sativa L., Capsicum frutescens L., Withania somnifera L., and Zingiber officinale Roscoe, have been examined in clinical trials. Among the various Egyptian plant habitats, we found that most of these plants are grown in the North Sinai, New-Delta, and Giza Governorates. CONCLUSION: In this review, we highlight the role played by Egyptian flora in current medicinal therapies and the possibility that these plants may be examined in further studies for the development of anticancer drugs. These bioactive plant extracts form the basis for the isolation of phytochemicals with demonstrated anticancer activities. Some active components derived from these plants have been applied to preclinical and clinical settings, including resveratrol, quercetin, isoquercetin, and rutin.

Hydroxyl substituted benzoic acid/cinnamic acid derivatives: Tyrosinase inhibitory kinetics, anti-melanogenic activity and molecular docking studies.

The inhibition of tyrosinase is an established strategy for treating hyperpigmentation. Our previous findings demonstrated that cinnamic acid and benzoic acid scaffolds can be effective tyrosinase inhibitors with low toxicity. The hydroxyl substituted benzoic and cinnamic acid moieties of these precursors were incorporated into new chemotypes that displayed in vitro inhibitory effect against mushroom tyrosinase. The most active compound, (2-(3-methoxyphenoxy)-2-oxoethyl (E)-3-(4-hydroxyphenyl) acrylate) 6c, inhibited tyrosinase with an IC50 of 5.7 µM, while (2-(3-methoxyphenoxy)-2-oxoethyl 2, 4-dihydroxybenzoate) 4d had an IC50 of 23.8 µM. In comparison, the positive control, kojic acid showed tyrosinase inhibition with an IC50 = 16.7 µM. Analysis of enzyme kinetics revealed that 6c and 4d displayed noncompetitive reversible inhibition of the second tyrosinase enzymatic reaction with Ki values of 11 µM and 130 µM respectively. In silico docking studies with mushroom tyrosinase (PDB ID 2Y9X) predicted possible binding modes in the catalytic site for these active compounds. The phenolic para-hydroxy group of the most active compound 6c is predicted to interact with the catalytic site Cu++ ion. The methoxy part of this compound is predicted to form a hydrogen bond with Arg 268. Compound 6c had no observable toxic effects on cell morphology or cell viability at the highest tested concentration of 91.4 µM. When dosed at 91.4 µM onto B16F10 melanoma cells in vitro6c showed anti-melanogenic effects equivalent to kojic acid at 880 µM. 6c displayed no PAINS (pan-assay interference compounds) alerts. Our results show that compound 6c is a more potent tyrosinase inhibitor than kojic acid and is a candidate for further development. Our exposition of the details of the interactions between 6c and the catalytic pocket of tyrosinase provides a basis for rational design of additional potent inhibitors of tyrosinase, built on the cinnamic acid scaffold.

Alpinia zerumbet (Pers.): Food and Medicinal Plant with Potential In Vitro and In Vivo Anti-Cancer Activities.

BACKGROUND/AIM: Plants play an important role in anti-cancer drug discovery, therefore, the current study aimed to evaluate the biological activity of Alpinia zerumbet (A. zerumbet) flowers. METHODS: The phytochemical and biological criteria of A. zerumbet were in vitro investigated as well as in mouse xenograft model. RESULTS: A. zerumbet extracts, specially CH2Cl2 and MeOH extracts, exhibited the highest potent anti-tumor activity against Ehrlich ascites carcinoma (EAC) cells. The most active CH2Cl2 extract was subjected to bioassay-guided fractionation leading to isolatation of the naturally occurring 5,6-dehydrokawain (DK) which was characterized by IR, MS, 1H-NMR and 13C-NMR. A. zerumbet extracts, specially MeOH and CH2Cl2 extracts, exhibited significant inhibitory activity towards tumor volume (TV). Furthermore, A. zerumbet extracts declined the high level of malonaldehyde (MDA) as well as elevated the levels of superoxide dismutase (SOD) and catalase (CAT) in liver tissue homogenate. Moreover, DK showed anti-proliferative action on different human cancer cell lines. The recorded IC50 values against breast carcinoma (MCF-7), liver carcinoma (Hep-G2) and larynx carcinoma cells (HEP-2) were 3.08, 6.8, and 8.7 µg/mL, respectively. CONCLUSION: Taken together, these findings open the door for further investigations in order to explore the potential medicinal properties of A. zerumbet.

Plants mentioned in the Islamic Scriptures (Holy Qur'ân and Ahadith): Traditional uses and medicinal importance in contemporary times.

ETHNOPHARMACOLOGICAL RELEVANCE: Over the past thousand years, Islamic physicians have collected cultural, philosophical, sociological and historical backgrounds for understanding diseases and medications. The Prophet Mohammed (Peace Be Upon Him (PBUH) said: "There is no disease that Allah has created, except that Allah also has created its cure." Therefore, Islamic scholars are encouraged to explore and use both traditional and modern forms of medicine. AIM OF THE STUDY: (1) To identify some of the medicinal plants mentioned in the Holy Qur'ân and Ahadith textbooks of the period 700-1500 AD; (2) to compare them with presently used traditional medicines; (3) to evaluate their value based on modern research; and (4) to investigate the contributions of Islamic scholars to the development of the scientific branches, particularly medicine. MATERIALS AND METHODS: A literature search was performed relating to 12 medicinal plants mentioned in the Holy Qur'ân and Ahadith using textbooks, Al-Azhar scholars, published articles, the plant list website (http://www.theplantlist.org/), the medicinal plant names services website (http://mpns.kew.org/mpns-portal/) and web databases (PubMed, Science Direct, and Google Scholar). RESULTS AND DISCUSSION: The Islamic Golden Age was a step towards modern medicine, with unique insights and multi-disciplinary aspects. Traditional Islamic Medicine has had a significant impact on the development of various medical, scientific and educational activities. Innumerable Muslim and non-Muslim physicians have built on the strong foundation of Traditional Islamic Medicine by translating the described natural remedies and effects. The influences of different ancient cultures on the traditional uses of natural products were also documented in Islamic Scriptures in the last part of the second millennium. The divine teachings of Islam combine natural and practical healing and incorporate inherited science and technology. CONCLUSION: In this review, we discuss Traditional Islamic Medicine with reference to both medical recommendations mentioned in the Holy Qur'ân and Prophetic Traditional Medicine (al-Tibb al-Nabawi). Although the molecular mechanisms and functions of some of the listed medicinal plants and their derivatives have been intensively studied, some traditional remedies have yet to be translated into clinical applications.

Metal nanoparticles fabricated by green chemistry using natural extracts: biosynthesis, mechanisms, and applications.

Nanoparticles (NPs) are new inspiring clinical targets that have emerged from persistent efforts with unique properties and diverse applications. However, the main methods currently utilized in their production are not environmentally friendly. With the aim of promoting a green approach for the synthesis of NPs, this review describes eco-friendly methods for the preparation of biogenic NPs and the known mechanisms for their biosynthesis. Natural plant extracts contain many different secondary metabolites and biomolecules, including flavonoids, alkaloids, terpenoids, phenolic compounds and enzymes. Secondary metabolites can enable the reduction of metal ions to NPs in eco-friendly one-step synthetic processes. Moreover, the green synthesis of NPs using plant extracts often obviates the need for stabilizing and capping agents and yields biologically active shape- and size-dependent products. Herein, we review the formation of metallic NPs induced by natural extracts and list the plant extracts used in the synthesis of NPs. In addition, the use of bacterial and fungal extracts in the synthesis of NPs is highlighted, and the parameters that influence the rate of particle production, size, and morphology are discussed. Finally, the importance and uniqueness of NP-based products are illustrated, and their commercial applications in various fields are briefly featured.

Cardenolides: Insights from chemical structure and pharmacological utility.

Cardiac glycosides (CGs) are a class of naturally occurring steroid-like compounds, and members of this class have been in clinical use for more than 1500 years. They have been used in folk medicine as arrow poisons, abortifacients, heart tonics, emetics, and diuretics as well as in other applications. The major use of CGs today is based on their ability to inhibit the membrane-bound Na+/K+-ATPase enzyme, and they are regarded as an effective treatment for congestive heart failure (CHF), cardiac arrhythmia and atrial fibrillation. Furthermore, increasing evidence has indicated the potential cytotoxic effects of CGs against various types of cancer. In this review, we highlight some of the structural features of this class of natural products that are crucial for their efficacy, some methods of isolating these compounds from natural resources, and the structural elucidation tools that have been used. We also describe their physicochemical properties and several modern biotechnological approaches for preparing CGs that do not require plant sources.

Essential oils of aromatic Egyptian plants repel nymphs of the tick Ixodes ricinus (Acari: Ixodidae).

Due to the role of Ixodes ricinus (L.) (Acari: Ixodidae) in the transmission of many serious pathogens, personal protection against bites of this tick is essential. In the present study the essential oils from 11 aromatic Egyptian plants were isolated and their repellent activity against I. ricinus nymphs was evaluated Three oils (i.e. Conyza dioscoridis L., Artemisia herba-alba Asso and Calendula officinalis L.) elicited high repellent activity in vitro of 94, 84.2 and 82%, respectively. The most active essential oil (C. dioscoridis) was applied in the field at a concentration of 6.5 µg/cm2 and elicited a significant repellent activity against I. ricinus nymphs by 61.1%. The most repellent plants C. dioscoridis, C. officinalis and A. herba-alba yielded essential oils by 0.17, 0.11 and 0.14%, respectively. These oils were further investigated using gas chromatography-mass spectrometry analysis. α-Cadinol (10.7%) and hexadecanoic acid (10.5%) were the major components of C. dioscoridis whereas in C. officinalis, α-cadinol (21.2%) and carvone (18.2%) were major components. Artemisia herba-alba contained piperitone (26.5%), ethyl cinnamate (9.5%), camphor (7.7%) and hexadecanoic acid (6.9%). Essential oils of these three plants have a potential to be used for personal protection against tick bites.

Isonicotinohydrazones as inhibitors of alkaline phosphatase and ecto-5'-nucleotidase.

A series of isonicotinohydrazide derivatives was synthesized and tested against recombinant human and rat ecto-5'-nucleotidases (h-e5'NT and r-e5'NT) and alkaline phosphatase isozymes including both bovine tissue-non-specific alkaline phosphatase (b-TNAP) and tissue-specific calf intestinal alkaline phosphatase (c-IAP). These enzymes are implicated in vascular calcifications, hypophosphatasia, solid tumors, and cancers, such as colon, lung, breast, pancreas, and ovary. All tested compounds were active against both enzymes. The most potent inhibitor of h-e5'NT was derivative (E)-N'-(1-(3-(4-fluorophenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl)ethylidene)isonicotinohydrazide (3j), whereas derivative (E)-N'-(4-hydroxy-3-methoxybenzylidene)isonicotinohydrazide (3g) exhibited significant inhibitory activity against r-e5'NT. In addition, the derivative (E)-N'-(4'-chlorobenzylidene)isonicotinohydrazide (3a) was most potent inhibitor against calf intestinal alkaline phosphatase and the derivative (E)-N'-(4-hydroxy-3-methoxybenzylidene)isonicotinohydrazide (3g) was found to be most potent inhibitor of bovine tissue-non-specific alkaline phosphatase. Furthermore, putative binding modes of potent compounds against e5'NT (human and rat e5'NT) and AP (including b-TNAP and c-IAP) were determined computationally.

Design, synthesis, molecular docking studies and in vitro screening of ethyl 4-(3-benzoylthioureido) benzoates as urease inhibitors.

Thioureas are exceptionally versatile building blocks towards the synthesis of wide variety of heterocyclic systems, which also possess extensive range of pharmacological activities. The substituted benzoic acids were converted into corresponding acid chlorides, these acid chlorides were then treated with potassium thiocyanate in acetone and then the reaction mixture was refluxed for 1-2h afford ethyl 4-(3-benzoylthioureido)benzoates thioureas in good yields. All the newly synthesized compounds were evaluated for their urease inhibitory activities and were found to be potent inhibitors of urease enzyme. Compounds 1f and 1g were identified as the most potent urease inhibitors (IC50 0.21 and 0.13 µM, respectively), and was 100-fold more potent than the standard inhibitors. Further molecular docking studies were carried out using the crystal structure of urease to find out the binding mode of the inhibitors with the enzyme.

Synthesis of (+/-)-6-O-methyl and 7-demethylannulatomarin.

Synthesis of 6-O-methyl and 7-demethyl derivatives of annulatomarin (1) (6,8-dihydroxy-7-methoxy-3-phenyl-3,4-dihydroisocoumarin) isolated from the aerial parts of Hypericum annulatum is described. The key step involves an efficient, microwave-accelerated solvent and catalyst-free condensation of methyl benzoate with 3,4,5-trimethoxyhomophthalic acid (2) to afford 6,7,8-trimethoxy-3-phenylisocoumarin (3). Saponification of the latter to keto acid (4) followed reduction to furnish 6,7,8-trimethoxy-3-phenyl-3,4-dihydroisocoumarin (5), which was either regioselectively demethylated to ( +/- )-6-O-methylannulatomarin (6) or completely demethylated to ( +/- )-7-demethylannulatomarin (7).

Synthesis of 6,8-dihydroxy-3-(2'-acetyl-3',5'-dihydroxyphenyl)methylisocoumarin related to feralolide.

Base-catalyzed self-condensation of 3,5-dimethoxyhomophthalic acid (2) directly furnished the 6,8-dimethoxy-3-(2'-carboxy-3',5'-dimethoxyphenyl)methylisocoumarin (3) which on successive treatment with oxalyl chloride, diazomethane and hydrolysis afforded the corresponding 2'-acetylisocoumarin (5). Complete demethylation of the latter yielded the 6,8-dihydroxy-3-(2'-acetyl-3',5'-dihydroxyphenyl)methylisocoumarin (6) related to the natural product feralolide (1a).