Sakuranetin and its therapeutic potentials - a comprehensive review.

Sakuranetin (SKN), a naturally derived 7-O-methylated flavonoid, was first identified in the bark of the cherry tree (Prunus spp.) as an aglycone of sakuranin and then purified from the bark of Prunus puddum. It was later reported in many other plants including Artemisia campestris, Boesenbergia pandurata, Baccharis spp., Betula spp., Juglans spp., and Rhus spp. In plants, it functions as a phytoalexin synthesized from its precursor naringenin and is the only known phenolic phytoalexin in rice, which is released in response to different abiotic and biotic stresses such as UV-irradiation, jasmonic acid, cupric chloride, L-methionine, and the phytotoxin coronatine. Till date, SKN has been widely reported for its diverse pharmacological benefits including antioxidant, anti-inflammatory, antimycobacterial, antiviral, antifungal, antileishmanial, antitrypanosomal, glucose uptake stimulation, neuroprotective, antimelanogenic, and antitumor properties. Its pharmacokinetics and toxicological properties have been poorly understood, thus warranting further evaluation together with exploring other pharmacological properties such as antidiabetic, neuroprotective, and antinociceptive effects. Besides, in vivo studies or clinical investigations can be done for proving its effects as antioxidant and anti-inflammatory, antimelanogenic, and antitumor agent. This review summarizes all the reported investigations with SKN for its health-beneficial roles and can be used as a guideline for future studies.

Ziziphus oenoplia Mill.: A Systematic Review on Ethnopharmacology, Phytochemistry and Pharmacology of an Important Traditional Medicinal Plant.

BACKGROUND: Ziziphus oenoplia Mill. (Family- Rhamnaceae) an important shrub, often found throughout the hot regions of tropical Asia and northern Australia, is commonly well known as Jackal jujube in English. It is a folk herbal medicine used as an abdominal pain killer and antidiarrhoeal agent. OBJECTIVE: The review aims to provide up-to-date information on the vernacular information, botanical characterization, distribution, ethnopharmacological uses, pharmacological activities, and chemical constituents of Z. oenoplia for possible exploitation of treatment for various diseases and to suggest future investigations. METHODS: This review was performed by studying online resources relating to Z. oenoplia and diverse resources, including scientific journals, books, and worldwide accepted databases from which information was assembled to accumulate significant information and relevant data in one place. RESULTS: Investigations on Z. oenoplia have been focused on its pharmacological activities, including its antimicrobial, antidiabetic, antihepatotoxic, antiulcer, antiplasmodial, anticancer, wound healing, anthelmintic, antioxidant, analgesic and antinociceptive, hypolipidemic activity, anti-inflammatory, immunomodulatory and antidiarrheal activities. Phytochemical studies resulted in the isolation of fatty acids, flavonoids, phenols, pentacyclic triterpenes, hydroxycarboxylic acids, aliphatic hydroxy ether, and cyclopeptide alkaloids. CONCLUSION: Most of the ethnopharmacological relevance of Z. oenoplia is justified, but more studies are needed. Further investigations are necessary to fully understand the mode of action of the active constituents and to exploit its preventive and therapeutic potentials.

GreenMolBD: Nature Derived Bioactive Molecules' Database.

BACKGROUND: One of the essential resources for developing new drugs are naturally derived biologically active lead compounds. Biomedical researchers and pharmaceutical companies are highly interested in these plant-derived molecules to develop the new drug. In this process, collective information of the plants and their phytoconstituents with different properties and descriptors would greatly benefit the researchers to identify the hit, lead or drug-like compound. AIM AND OBJECTIVE: Therefore, the work intended to develop a unique and dynamic database Green- MolBD to provide collective information regarding medicinal plants, such as their profile, chemical constituents, and pharmacological evidence. We also aimed to present information of phytoconstituents, such as in silico description, quantum, drugability and biological target information. METHODS: For data mining, we covered all accessible literature and books, and for in silico analysis, we employed a variety of well-known software and servers. The database is integrated by MySQL, HTML, PHP and JavaScript. RESULTS: GreenMolBD is a freely accessible database and searchable by keywords, plant name, synonym, common name, family name, family synonym, compound name, IUPAC name, InChI Key, target name, and disease name. We have provided a complete profile of individual plants and each compound's physical, quantum, drug likeliness, and toxicity properties (48 type's descriptor) using in silico tools. A total of 1846 associated targets related to 6,864 compounds already explored in different studies are also incorporated and synchronized. CONCLUSION: This is the first evidence-based database of bioactive molecules from medicinal plants specially grown in Bangladesh, which may help explore and foster nature-inspired rational drug discovery.

A Comprehensive Review on Linum usitatissimum Medicinal Plant: Its Phytochemistry, Pharmacology, and Ethnomedicinal Uses.

BACKGROUND: Linum usitatissimum or flax has been broadly utilized in numerous milieus worldwide as a primeval medicinal plant because of its health benefits in diverse types of diseases. OBJECTIVE: The objective of this review is to assemble the latest information on the botanical description, distribution, conventional uses, and biochemical constituents, along with the pharmacological activities and toxicity of flax. METHODS: For this purpose, data on Linum was accumulated from scientific journals, books, and worldwide acknowledged scientific databases via a library and electronic search. RESULTS: Phytochemical analysis showed that the major chemical constituents of L. usitatissimum are ω-3 fatty acid, phytoestrogenic-lignans (secoisolariciresinol diglucoside-SDG), phenols, flavonoids, sterols, proteins, antioxidants as well as various soluble and insoluble fibres. Among them, secoisolariciresinol diglucosides (SDG) are the major bioactive compounds of L. usitatissimum with prospective pharmacological accomplishments. Pure compounds and crude extracts isolated from L. usitatissimum exhibited significant anti-cancer, antioxidant, anti-microbial, anti-inflammatory, anti-obesity, antidiabetic, anti-diarrheal, anti-malarial, hepato-protective, reno-protective, immunosuppressive, antiarrhythmic, and cognitive effects. Studies indicated that the toxicological effect from the consumption of flaxseed is because of its cyanogenic glycosides, linatine, and cadmium, but the level does not seem to be adequately concentrated to contribute to any physiological impact. CONCLUSIONS: Further studies are expected to comprehend the detailed mode of action of its dynamic constituents as potent therapeutics and to completely reveal its preventive and healing potentials.

Adhatoda vasica (Nees.): A Review on its Botany, Traditional uses, Phytochemistry, Pharmacological Activities and Toxicity.

BACKGROUND: Adhatoda vasica (Nees.) of the family Acanthaceae has been used in the Southeast tropical zone as it is efficacious against headache, colds, cough, whooping cough, fever, asthma, dyspnea, phthisis, jaundice, chronic bronchitis, and diarrhea. It exhibits commendable pharmacological activities. OBJECTIVE: The aim of the review is to provide a systematic overview of pharmacological activities with toxicity and clinical assessment, phytochemistry of A. vasica along with its characterization, geographical observation, phenology, traditional uses, as well as an organized representation of the findings. METHOD: The overall information of A. vasica was collected from various resources, including books, review papers, research papers, and reports which were obtained from an online search of globallyaccepted scientific databases. ChemDraw software was used to draw the compound's structure. RESULTS: Phytochemical review on A. vasica has led to the collection of 233 compounds of different types such as alkaloids, flavonoids, essential oils, terpenoids, fatty acids, phenols, etc. It is a promising source of potential phytopharmaceutical agent that exhibits diverse pharmacological activities, including antibacterial, antifungal, hepatoprotective, anti-ulcer, abortifacient, antiviral, antiinflammatory, thrombolytic, hypoglycemic, anti-tubercular, antioxidant, and antitussive activities. CONCLUSIONS: Sufficient number of studies on ethnopharmacology, traditional uses, and pharmacological activities of A. vasica are conducted. Furthermore, it is necessary to study the activity of chemical constituents for new drug design and discovery from natural products.

Brassica oleracea var. capitata f. alba: A Review on its Botany, Traditional uses, Phytochemistry and Pharmacological Activities.

BACKGROUND: Brassica oleracea var. capitata f. alba (white cabbage) is a cruciferous vegetable used as a vegetable and traditional medicine all over the world. Different preparation from several parts of the plant- roots, shoots, leaves, and the whole plant are used to treat a wide range of diseases, including diabetes, cancer, gastric, inflammation, hypertension, hypercholesterolemia, bacterial, oxidation, and obesity. OBJECTIVE: The aim of the current review is to evaluate the botany, distribution, traditional uses, phytochemistry, and pharmacological activities of B. oleracea var. capitata. Moreover, this review will guide to fill the existing gaps in information and highlight additional research prospects in the field of phytochemistry and pharmacology. METHOD: Various resources, including research papers, review papers, books, and reports, were collected to obtain overall information on Brassica oleracea var. capitata, which were obtained by an online search of worldwide-accepted scientific databases. Phytochemical constituents' structures were drawn by ChemDraw software. RESULTS: About 72 isolated phytochemical compounds of B. oleracea var. capitata have been collected from different articles, which included different types of compounds such as alkaloids, flavonoids, organic acids, glucosinolates, steroids, hydrocarbons, etc. Crude extracts and phytoconstituents of B. oleracea var. capitata have various pharmacological effects, including antidiabetic, anticancer, antihypertensive, anticholesterolemic, antioxidant, anti-inflammatory, antibacterial, anti-obesity, anticoagulant, and hepatoprotective. We have enlisted all these pharmacological data along with all the phytochemical constituents of Brassica oleracea var. capitata. CONCLUSION: The study was focused on the traditional uses, pharmacological activities, and phytochemistry of Brassica oleracea var. capitata, and the findings indicated that B. oleracea var. capitata is an important medicinal plant that shows several pharmacological effects. We hope our review of this plant will provide more basic and useful information and fill some research gaps for further investigation and drug design. Although we found some important traditional uses and pharmacological activities of Brassica oleracea var. capitata, there is insufficient work in the field of phytochemical activities.

Biological Role of AKT and Regulation of AKT Signaling Pathway by Thymoquinone: Perspectives in Cancer Therapeutics.

BACKGROUND: AKT/PKB is an important enzyme with numerous biological functions, and its overexpression is related to carcinogenesis. AKT stimulates different signaling pathways that are downstream of activated tyrosine kinases and phosphatidylinositol 3-kinase, hence functions as an important target for anti-cancer drugs. OBJECTIVE: In this review article, we have interpreted the role of AKT signaling pathway in cancer and the natural inhibitory effect of Thymoquinone (TQ) in AKT and its possible mechanisms. METHOD: We have collected the updated information and data on AKT, its role in cancer and the inhibitory effect of TQ in AKT signaling pathway from Google Scholar, PubMed, Web of Science, Elsevier, Scopus, and many more. RESULTS: Many drugs are already developed, which can target AKT, but very few among them have passed clinical trials. TQ is a natural compound, mainly found in black cumin, which has been found to have potential anti-cancer activities. TQ targets numerous signaling pathways, including AKT, in different cancers. In fact, many studies revealed that AKT is one of the major targets of TQ. The preclinical success of TQ suggests its clinical studies on cancer. CONCLUSION: This review article summarizes the role of AKT in carcinogenesis, its potent inhibitors in clinical trials, and how TQ acts as an inhibitor of AKT and TQ's future as a cancer therapeutic drug.

Phytochemistry, Traditional Uses and Pharmacological Properties of Enhydra fluctuans Lour: a Comprehensive Review.

BACKGROUND: Enhydra fluctuans Lour, a tropical herb, commonly known as helencha or harkuch, belongs to the family Asteraceae. It is an edible semi-aquatic herbaceous vegetable plant with serrate leaves and grows commonly in different parts of the world. Enhydra fluctuans possesses potential pharmacological role against inflammation, cancer, diarrhea, microbial infection, diabetes, etc. Aim: This review aims to provide the most current information on the botanical characterization, distribution, traditional uses, chemical constituents, as well as the pharmacological activities of Enhydra fluctuans Lour. MATERIALS AND METHODS: The recently updated information on Enhydra fluctuans was gathered from scientific journals, books, and worldwide accepted scientific databases via a library and electronic search PubMed, Elsevier, Google Scholar, Springer, Scopus, Web of Science, Wiley online library. All of the full-text articles and abstracts related to Enhydra were screened. The most important and relevant articles were carefully chosen for study in this review. RESULTS: Crude extracts and isolated compounds of Enhydra fluctuans Lour have been reported to be pharmacologically active against cytoprotective, analgesic and anti-inflammatory, antimicrobial, anticancer, antidiarrheal, antihelmintic, CNS depressant, hepatoprotective, thrombolytic, antidiabetic, antioxidant, phagocytic and cytotoxic, and neuroprotective potential activities. DISCUSSION: Phytochemical analysis from different studies has reported Germacranolide, Sesquiterpene lactone, Flavonoid, Essential oil, Steroid, Diterpenoid, Melampolide, Sesquiterpene lactone, and Isoflavone glycoside as major compounds of Enhydra fluctuans Lour. CONCLUSION: However, more research is needed to explore the mode of action of bioactive components of the plant and its therapeutic capabilities.

Design of novel viral attachment inhibitors of the spike glycoprotein (S) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) through virtual screening and dynamics.

To date, the global COVID-19 pandemic has been associated with 11.8 million cases and over 545481 deaths. In this study, we have employed virtual screening approaches and selected 415 lead-like compounds from 103 million chemical substances, based on the existing drugs, from PubChem databases as potential candidates for the S protein-mediated viral attachment inhibition. Thereafter, based on drug-likeness and Lipinski's rules, 44 lead-like compounds were docked within the active side pocket of the viral-host attachment site of the S protein. Corresponding ligand properties and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profile were measured. Furthermore, four novel inhibitors were designed and assessed computationally for efficacy. Comparative analysis showed the screened compounds in this study maintain better results than the proposed mother compounds, VE607 and SSAA09E2. The four designed novel lead compounds possessed more fascinating output without deviating from any of Lipinski's rules. They also showed higher bioavailability and the drug-likeness score was 0.56 and 1.81 compared with VE607 and SSAA09E2, respectively. All the screened compounds and novel compounds showed promising ADMET properties. Among them, the compound AMTM-02 was the best candidate, with a docking score of -7.5 kcal/mol. Furthermore, the binding study was verified by molecular dynamics simulation over 100 ns by assessing the stability of the complex. The proposed screened compounds and the novel compounds may give some breakthroughs for the development of a therapeutic drug to treat SARS-CoV-2 proficiently in vitro and in vivo.

A Review of Saurauia roxburghii Wall. (Actinidiacaea) as a Traditional Medicinal Plant, Its Phytochemical Study and Therapeutic Potential.

Saurauia roxburghii Wall. is an interesting plant, found growing chiefly along the eastern and south-eastern countries of Asia. The various ethnic groups of these regions use the plant as a medication for relieving a wide spectrum of diseases and conditions, including indigestion, boils, fever, gout, piles, eczema, asthma, ulcers, bronchitis, epilepsy, and hepatitis B. This review aims to appraise the vernacular information, botanical characterization, geographical distribution, traditional uses, phytochemistry, and pharmacological activities of S. roxburghii as well as to conduct a critical analysis on the findings. To understand the therapeutic potential and provide an overall idea about the ethnomedicinal practices, phytochemistry, and pharmacological activities of S. roxburghii, relevant information was collected via a library and electronic search of online journals, books, and reputed databases. Phytochemical examination revealed the presence of alkaloids, glycosides, O-glycosides, flavonoids, carbohydrates, saponins, steroids, reducing sugars, tannins, phlobatannins, and triterpenoids. The sterols were identified as Stigmasterol and beta-Sitosterol. The triterpenes were found to be Ursolic acid, Corosolic acid, Maslinic acid, 24-Hydroxy corosolic acid, 3b,7b,24-trihydroxy-urs-12-en-28-oic acid, Oleanolic acid, beta-Amyrin, cis-3-O-p-Hydroxycinnamoyl ursolic acid, trans-3-O-p- Hydroxycinnamoyl ursolic acid, and 7,24-dihydroxyursolic acid. Several in-vivo and in-vitro tests revealed anti-bacterial, anti-cancer, anti-diabetic, anti-oxidant, and anti-viral activities of the plant leaves. Detailed analysis of the information collected on S. roxburghii suggested some promising leads for future drug development. However, many scientific gaps were found in the study of this and further extensive investigation is needed to fully understand the mechanism of action of the active constituents and exploit its therapeutic promises.

Structure-based identification of potent VEGFR-2 inhibitors from in vivo metabolites of a herbal ingredient.

Vascular endothelial growth factor receptor-2 (VEGFR-2) is one of the regulatory elements of angiogenesis that is expressed highly in various diseases and is also essential for solid tumor growth. The present study was aimed at identifying potent inhibitors of VEGFR-2 by considering herbal secondary metabolites; as natural molecules are less toxic than synthetic derivatives. A structure-based virtual screening protocol consisting of molecular docking, MM-GBSA and ADME/T analysis was initially used to screen a library of in vivo metabolites of the herbal ingredient. Using a fixed cutoff value, four potent virtual hits were identified from molecular docking, ADME/T and binding affinity calculations, which were considered further for molecular dynamics (MD) simulation to broadly describe the binding mechanisms to VEGFR-2. The results suggested that these molecules have high affinity for the catalytic region of VEGFR-2, and form strong hydrophobic and polar interactions with the amino acids involved in the binding site of ATP and linker regions of the catalytic site. Subsequently, the stability of the docked complexes and binding mechanisms were evaluated by MD simulations, and the energy of binding was calculated through MM-PBSA analysis. The results uncovered two virtual hits, designated ZINC14762520 and ZINC36470466, as VEGFR-2 inhibitors, and suggested that they bind to kinase domain in an ATP-competitive manner. These virtual hits will offer a suitable starting point for the further design of their various analogs, allowing a rational search for more effective inhibitors in the future. Graphical abstract.

Prospecting and Structural Insight into the Binding of Novel Plant-Derived Molecules of Leea indica as Inhibitors of BACE1.

BACKGROUND: Alzheimer disease (AD) can be considered as the most common age related neurodegenerative disorder and also an important cause of death in elderly patients. A number of studies showed the correlation of this disease pathology with BACE1 inhibitor and it is also evident that BACE1 inhibitor can function as a very potent strategy in treating AD. METHODS: In this present study, we aimed to prospect for novel plant-derived BACE1 inhibitors from Leea indica and to realise structural basis of their interactions and mechanisms using combined molecular docking and molecular dynamics based approaches. An extensive library of Leea indica plant derived molecule was compiled and computationally screened for inhibitory action against BACE1 by using virtual screening approaches. Furthermore, induced fit docking and classical molecular dynamics along with steered molecular dynamics simulations were employed to get insight of the binding mechanisms. RESULTS: Two triterpenoids, ursolic acid and lupeol were identified through virtual screening; wherein, lupeol showed better binding free energy in MM/GBSA, MM/PBSA and MM/GBVI approaches. Furthermore classical and steered dynamics revealed the favourable hydrophobic interactions between the lupeol and the residues of flap or catalytic dyadof BACE1; however, ursolic acid showed disfavorable interactions with the BACE1. CONCLUSION: This study therefore unveiled the potent BACE1 inhibitor from a manually curated dataset of Leea indica molecules, which may provide a novel dimension of designing novel BACE1 inhibitors for AD therapy.