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.

Nature-Derived Hit, Lead, and Drug-Like Small Molecules: Current Status and Future Aspects Against Key Target Proteins of Coronaviruses.

BACKGROUND: COVID-19 pandemic, the most unprecedented event of the year 2020, has brought millions of scientists worldwide in a single platform to fight against it. Though several drugs are now in the clinical trial, few vaccines are available on the market already, but the lack of an effect of those is making the situation worse. AIM OF THE STUDY: In this review, we demonstrated comprehensive data of natural antiviral products showing activities against different proteins of Human Coronaviruses (HCoV) that are responsible for its pathogenesis. Furthermore, we categorized the compounds into the hit, lead, and drug based on the IC50/EC50 value, drug-likeness, and lead-likeness test to portray their potentiality to be a drug. We also demonstrated the present status of our screened antiviral compounds with respect to clinical trials and reported the lead compounds that can be promoted to clinical trial against COVID-19. METHODS: A systematic search strategy was employed focusing on Natural Products (NPs) with proven activity (in vitro, in vivo, or in silico) against human coronaviruses, in general, and data were gathered from databases like PubMed, Web of Science, Google Scholar, SciVerse, and Scopus. Information regarding clinical trials retrieved from the Clinical Trial Database. RESULTS: Total "245" natural compounds were identified initially from the literature study. Among them, Glycyrrhizin, Caffeic acid, Curcumin is in phase 3, and Tetrandrine, Cyclosporine, Tacrolimus, Everolimus are in phase 4 clinical trial. Except for Glycyrrhizin, all compounds showed activity against COVID-19. CONCLUSION: In summary, our demonstrated specific small molecules with lead and drug-like capabilities clarified their position in the drug discovery pipeline and proposed future research against COVID-19.

Whole proteome screening and identification of potential epitopes of SARS-CoV-2 for vaccine design-an immunoinformatic, molecular docking and molecular dynamics simulation accelerated robust strategy.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the most cryptic pandemic outbreak of the 21st century, has gripped more than 1.8 million people to death and infected almost eighty six million. As it is a new variant of SARS, there is no approved drug or vaccine available against this virus. This study aims to predict some promising cytotoxic T lymphocyte epitopes in the SARS-CoV-2 proteome utilizing immunoinformatic approaches. Firstly, we identified 21 epitopes from 7 different proteins of SARS-CoV-2 inducing immune response and checked for allergenicity and conservancy. Based on these factors, we selected the top three epitopes, namely KAYNVTQAF, ATSRTLSYY, and LTALRLCAY showing functional interactions with the maximum number of MHC alleles and no allergenicity. Secondly, the 3D model of selected epitopes and HLA-A*29:02 were built and Molecular Docking simulation was performed. Most interestingly, the best two epitopes predicted by docking are part of two different structural proteins of SARS-CoV-2, namely Membrane Glycoprotein (ATSRTLSYY) and Nucleocapsid Phosphoprotein (KAYNVTQAF), which are generally target of choice for vaccine designing. Upon Molecular Docking, interactions between selected epitopes and HLA-A*29:02 were further validated by 50 ns Molecular Dynamics (MD) simulation. Analysis of RMSD, Rg, SASA, number of hydrogen bonds, RMSF, MM-PBSA, PCA, and DCCM from MD suggested that ATSRTLSYY is the most stable and promising epitope than KAYNVTQAF epitope. Moreover, we also identified B-cell epitopes for each of the antigenic proteins of SARS CoV-2. Findings of our work will be a good resource for wet lab experiments and will lessen the timeline for vaccine construction.Communicated by Ramaswamy H. Sarma.

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.

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.