Biological activity of usnic acid and its derivatives: Part 2. effects on higher organisms. Molecular and physicochemical aspects

Usnic acid (UA) is a commercially available lichen metabolite. Its biological activity is diverse, and it is of interest for pharmacopoeia. The second part of the review is dedicated to the biological action of UA and its derivatives on higher organisms. Effects exhibited by UA at the cellular level and the molecular and physicochemical aspects of its biological activity are considered. Special attention is placed on the possibility of modifying the biological activity of UA by change of its bioavailability or modification of its molecular structure.     

Advances in production and structural derivatization of the promising molecule ursolic acid

Ursolic acid (UA) is a ursane-type pentacyclic triterpenoid compound, naturally produced in plants via specialized metabolism and exhibits vast range of remarkable physiological activities and pharmacological manifestations. Owing to significant safety and efficacy in different medical conditions, UA may serve as a backbone to produce its derivatives with novel therapeutic functions. This review aims to provide ideas for exploring more diverse structures to improve UA pharmacological activity and increasing its biological yield to meet the industrial requirements by systematically reviewing the current research progress of UA. We first provides an overview of the pharmacological activities, acquisition methods and structural modifications of UA. Among them, we focused on the synthetic modifications of UA to yield valuable derivatives with enhanced therapeutic potential. Furthermore, harnessing the essential advances for green synthesis of UA and its derivatives by advent of metabolic engineering and synthetic biology are of great concern. In this regard, all pivotal advances for enhancing the production of UA have been discussed. In combination with the advantages of UA biosynthesis and transformation strategy, large-scale microbial production of UA is a promising platform for further exploration.     

Lichens: a promising source of antibiotic and anticancer drugs

Lichens are symbiotic associations between fungi and a photosynthetic alga and/or cyanobacteria. Lichenized fungi have been found to produce a wide array of secondary metabolites, most of which are unique to the lichenized condition. These secondary metabolites have shown an impressive range of biological activities including antibiotics, antifungal, anti-HIV, anticancer, anti-protozoan, etc. This review focuses primarily on the antibiotic and anticancer properties of lichen secondary chemicals. We have reviewed various publications related to antibiotic and anticancer drug therapies emphasizing results about specific lichens and/or lichen compounds, which microbes or cancer cells were involved and the main findings of each study. We found that crude lichen extracts and various isolated lichen compounds often demonstrate significant inhibitory activity against various pathogenic bacteria and cancer cell lines at very low concentrations. There were no studies examining the specific mechanism of action against pathogenic bacteria; however, we did find a limited number of studies where the mechanism of action against cancer cell lines had been explored. The molecular mechanism of cell death by lichen compounds includes cell cycle arrest, apoptosis, necrosis, and inhibition of angiogenesis. Although lichens are a reservoir for various biologically active compounds, only a limited number have been tested for their biological significance. There is clearly an urgent need for expanding research in this area of study, including in depth studies of those compounds which have shown promising results as well as a strong focus on identifying specific mechanisms of action and extensive clinical trials using the most promising lichen based drug therapies followed by large scale production of the best of those compounds.     

Antibacterial activity of oleanolic and ursolic acids and their derivatives

Bacterial resistance to antibiotics is increasing at an alarming rate and many commonly used antibiotics are no longer effective. Thus, there is considerable interest in investigating novel antibacterial compounds, such as the plant-derived pentacyclic triterpenoids, including oleanolic acid (OA), ursolic acid (UA) and their derivatives. These compounds can be isolated from many medicinal and crop plants and their antibacterial, antiviral, antiulcer and anti-inflammatory effects are well documented. OA and UA are active against many bacterial species, particularly Gram-positive species, including mycobacteria. They inhibit bacterial growth and survival, and the spectrum of minimal inhibitory concentration (MIC) values is very broad. In addition, OA, UA and their derivatives display potent antimutagenic activity. Studies to identify the cellular targets and molecular mechanisms of OA and UA action were initiated a few years ago and it has already been demonstrated that both acids influence bacterial gene expression, the formation and maintenance of biofilms, cell autolysis and peptidoglycan turnover. Before these compounds can be used clinically as antimicrobial agents, further extensive studies are required to determine their cytotoxicity and the optimum mode of their application.     

Molecular and cellular bases of iron metabolism in humans

Iron is a microelement with the most completely studied biological functions. Its wide dissemination in nature and involvement in key metabolic pathways determine the great importance of this metal for uniand multicellular organisms. The biological role of iron is characterized by its indispensability in cell respiration and various biochemical processes providing normal functioning of cells and organs of the human body. Iron also plays an important role in the generation of free radicals, which under different conditions can be useful or damaging to biomolecules and cells. In the literature, there are many reviews devoted to iron metabolism and its regulation in proand eukaryotes. Significant progress has been achieved recently in understanding molecular bases of iron metabolism. The purpose of this review is to systematize available data on mechanisms of iron assimilation, distribution, and elimination from the human body, as well as on its biological importance and on the major iron-containing proteins. The review summarizes recent ideas about iron metabolism. Special attention is paid to mechanisms of iron absorption in the small intestine and to interrelationships of cellular and extracellular pools of this metal in the human body.     

The increasing role of phosphatidylethanolamine as a lipid receptor in the action of host defence peptides

Host defence peptides (HDPs) are antimicrobial agents produced by organisms across the prokaryotic and eukaryotic kingdoms. Many prokaryotes produce HDPs, which utilise lipid and protein receptors in the membranes of bacterial competitors to facilitate their antibacterial action and thereby survive in their niche environment. As a major example, it is well established that cinnamycin and duramycins from Streptomyces have a high affinity for phosphatidylethanolamine (PE) and exhibit activity against other Gram-positive organisms, such as Bacillus. In contrast, although eukaryotic HDPs utilise membrane interactive mechanisms to facilitate their antimicrobial activity, the prevailing view has long been that these mechanisms do not involve membrane receptors. However, this view has been recently challenged by reports that a number of eukaryotic HDPs such as plant cyclotides also use PE as a receptor to promote their antimicrobial activities. Here, we review current understanding of the mechanisms that underpin the use of PE as a receptor in the antimicrobial and other biological actions of HDPs and describe medical and biotechnical uses of these peptides, which range from tumour imaging and detection to inclusion in topical microbicidal gels to prevent the sexual transmission of HIV.     

太赫兹辐射及其生物效应研究进展

随着太赫兹源和探测技术的不断进步，太赫兹技术迅速发展并在众多领域有着广泛的应用前景. 特别是在生物医学领域，太赫兹技术有望成为一种新型治疗手段. 本文首先介绍了太赫兹的电磁波特点及3种太赫兹波产生方式. 其次介绍了太赫兹辐射在生物上的两大效应：热效应和非热效应. 最后从细胞和生物体两大层面上，详细介绍了太赫兹辐射对不同细胞的生物效应和一些相关分子通路改变，以及太赫兹辐射在不同生物体上的作用效果，为太赫兹生物相关研究人员提供参考.     

Inhibitory effect of ursolic acid derivatives on hydrogen peroxide- and glutathione-mediated degradation of hemin: A possible additional mechanism of action for antimalarial activity

Compounds obtained by the condensation of ursolic acid (UA) with 1,4-bis(3-aminopropyl)piperazines have previously been shown as cytocidal to Plasmodium falciparum strains. Preliminary results indicated that the inhibition of β-hematin formation (one of the possible mechanisms of action of antimalarial drugs) was achieved by a few of these molecules with varying efficiencies. To gain further insight in the antimalarial action of UA derivatives, we report here the results of additional pathways that may explain their in vitro cytocidal activity such as inhibition of hemin degradation by H₂O₂ or glutathione (GSH). H₂O₂-mediated hemin degradation was drastically reduced by hydroxybenzyl-substituted UA derivatives while UA and intermediate compounds displayed weaker inhibitory actions. The results of GSH-mediated hemin degradation inhibition did not parallel those of H₂O₂ degradation as hydroxybenzyl-substituted UA only proved to be a weak inhibitor. As H₂O₂ interaction with the iron moiety of hemin is the first step towards its degradation, we assume that the interaction of our products with the ferric ion in the hemin structure is of upmost importance in inhibiting its peroxidative degradation. A two-step mechanism of action implying (1) stacking of the acetylursolic acid structure to hemin and (2) additive protection of hemin ferric iron from H₂O₂ by hydroxyphenyl groups through steric hindrance and/or trapping of oxygen reactive species in the direct neighborhood of ferric iron can be put forward. For GSH degradation pathway, grafting of UA structure with a piperazine structure gave the best inhibition, pleading for the implication of this latter moiety in the inhibitory process.     

Biological functions and the practical use of chitin

The review is dedicated to chitin--a wide-spread in nature polyaminosaccharide. Its main physico-chemical properties and biological role in the cell are analyzed. The review centres round the practical use of chitin and its derivatives. Natural resources, modern modes for production and application of chitin and its derivatives in industry, medicine, biotechnology and agriculture are discussed.     

Relationships between structure and mutagenic activity of environmental chemicals

This review analyzes relationships between chemical structure and biological activity for several series of compounds. Its focus is on mutagenicity and carcinogenicity and the predictability of these properties on the basis of the chemical structure. Examples are selected from monocyclic aromatic amines, benzidine derivatives, aminoazobenzene derivatives, nitrofurans, aflatoxins, and sterigmatocystins. Results from mutagenicity tests in Salmonella typhimurium are summarized, and their correlation with carciogenicity is discussed. The review is concluded with generalizations on the usefulness of studies on relationships between chemical structure and mutagenic activity.     

Chitosan as antimicrobial agent: applications and mode of action

Chitosan, a hydrophilic biopolymer industrially obtained by N-deacetylation of chitin, can be applied as an antimicrobial agent. The current review of 129 references describes the biological activity of several chitosan derivatives and the modes of action that have been postulated in the literature. It highlights the applications of chitosan as an antimicrobial agent against fungi, bacteria, and viruses and as an elicitor of plant defense mechanisms.     

Lichens as a potential natural source of bioactive compounds: a review

Biological activity of material whether known in folk medicine or observed in planned screening program has been the starting point in the drug research. The general pattern is the isolation of active principles, elucidation their structures, followed by attempts for modulation of its activity potential by chemical modification. Lichens are valuable plant resources and are used as medicine, food, fodder, perfume, spice, dyes and for miscellaneous purposes throughout the world. Lichens are well known for the diversity of secondary metabolites that they produce. Compounds isolated from various lichen species have been reported to display diverse biological activities. Here we review the medicinal efficacy of lichen substances, which intends to explore the pharmaceutical potential of lichen substances.     

Biologically active secondary metabolites from myxobacteria

New chemical structures with proven biological activity still are badly needed for a host of applications and are intensively screened for. Suitable compounds may be used as such, or in the form of their derivatives or, equally important, may serve as lead compounds for designing synthetic analogs. One way to new compounds is the exploitation of new producer organisms. During the past 15 years the myxobacteria have been shown in our laboratories to be a rich source of novel secondary metabolites, many of the compounds showing interesting and sometimes unique mechanisms of action. About 50 basic structures and nearly 300 structural variants have been elucidated, and almost all of them turned out to be new compounds. Several myxobacterial substances may have a good chance of an application.     

Mechanism of action of an old antibiotic revisited: Role of calcium ions in protonophoric activity of usnic acid

Usnic acid (UA), an old antibiotic and one of the first described mitochondrial uncouplers, has demonstrated many beneficial activities, such as antimicrobial, antiviral, antitumour and anti-inflammatory properties. Here, we performed a thorough investigation of effects of usnic acid and its analogues on artificial planar bilayer lipid membrane (BLM), rat liver mitochondria and bacteria. Surprisingly enough, all of the three hydroxyl groups of UA appeared to be involved in its proton-shuttling activity on BLM. We ascribed this fact to an ability of UA to form complexes with calcium ions, aiding it in cycling protons across the membrane. Actually, the addition of calcium ions markedly stimulated the UA-induced electrical current across BLM. By using the calcium ionophore A23187, we proved the involvement of calcium ions in the UA uncoupling action on isolated rat liver mitochondria. The calcium-chelating property of UA was demonstrated here by the method of extracting metal ions into a hydrophobic phase. Modification of any of the hydroxyl groups in UA dramatically reduced not only the UA-induced current across BLM and the UA-mediated calcium extraction, but also the uncoupling activity of UA in mitochondria and the inhibiting effect of UA on the growth of Bacillus subtilis. The ability of UA to cause dissipation of membrane potential in isolated liver mitochondria and bacterial cells was shown here for the first time. In view of the data obtained, the protonophoric activity of UA is considered to make a significant contribution to its antibacterial action.     

The presence and activity of progesterone in the plant kingdom

Steroids are present in living organisms as one of the most essential groups of compounds. Continuous research has led to new discoveries and the revision of existing information concerning the occurrence and the role of steroids, both in animals and plants. This article will focus on reviewing the literature studying progesterone in the plant kingdom, including its discovery, its occurrence in different plant species as well as its biological activity and molecular basis of action. This review will present and discuss the current data in addition to introducing potential directions for further research on the subject of progesterone in plants.     

Corosolic acid and its structural analogs: A systematic review of their biological activities and underlying mechanism of action

BackgroundThe corosolic acid (CA), also known as plant insulin, is a pentacyclic triterpenoid extracted from plants such as Lagerstroemia speciosa. It has been shown to have anti-diabetic, anti-inflammatory and anti-tumor effects. Its structural analogs ursolic acid (UA), oleanolic acid (OA), maslinic acid (MA), asiatic acid (AA) and betulinic acid (BA) display similar individual pharmacological activities to those of CA. However, there is no systematic review documenting pharmacological activities of CA and its structural analogues. This study aims to fill this gap in literature.PurposeThis systematic review aims to summarize the medical applications of CA and its analogues.MethodsA systematic review summarizes and compares the extraction techniques, pharmacokinetic parameters, and pharmacological effects of CA and its structural analogs. Hypoglycemic effect is one of the key inclusion criteria for searching Web of Science, PubMed, Embase and Cochrane databases up to October 2020 without language restrictions. ‘corosolic acid’, ‘ursolic acid’, ‘oleanolic acid’, ‘maslinic acid’, ‘asiatic acid’, ‘betulinic acid’, ‘extraction’, ‘pharmacokinetic’, ‘pharmacological’ were used to extract relevant literature. The PRISMA guidelines were followed.ResultsAt the end of the searching process, 140 articles were selected for the systematic review. Information of CA and five of its structural analogs including UA, OA, MA, AA and BA were included in this review. CA and its structural analogs are pentacyclic triterpenes extracted from plants and they have low solubilities in water due to their rigid scaffold and hydrophobic properties. The introduction of water-soluble groups such as sugar or amino groups could increase the solubility of CA and its structural analogs. Their biological activities and underlying mechanism of action are reviewed and compared.ConclusionCA and its structural analogs UA, OA, MA, AA and BA are demonstrated to show activities in lowering blood sugar, anti-inflammation and anti-tumor. Their oral absorption and bioavailability can be improved through structural modification and formulation design. CA and its structural analogs are promising natural product-based lead compounds for further development and mechanistic studies.     

Genetic effects of acridine compounds.

Acridines and a very large number of acridine derivatives are used in enormous quantities both in medicine and industry. The mutagenic action of these compounds has been demonstrated in a wide variety of organisms and is known to occur both in the dark as well as in the presence of light (photodynamic action). At the molecular level, acridines have been shown to cause frameshift mutations of both the addition and deletion types, a characteristic which has been of tremendous help in elucidating the nature of the genetic code. These and various other biological effects of acridines, such as inhibition of DNA repair, curing of plasmids and cell-growth inhibition, are examined in this review.     

昆虫群落中天敌间的致死干扰竞争作用

致死干扰竞争作用(lethal interference competition)是近些年来才被人们认识到的更为复杂的种间竞争关系, 是昆虫天敌间竞争的一种极端形式, 广泛存在于寄生性天敌昆虫之间。本文从其定义、 作用机制、 方式及其与害虫生物防治的相互关系几个方面介绍了天敌群落中的这一典型的种间相互关系。根据作用机制的不同, 可将致死干扰竞争作用分为外竞争和内竞争; 其通常的作用方式包括多寄生(超寄生)、 复寄生、 杀卵作用、 寄主取食、 物理攻击和生理抑制等。深入全面地研究这一种间关系对于有效生防作用物的筛选和引入, 以及整个生防系统群落的稳定性具有重要意义。     

Characteristics of lichen lectins and their role in symbiosis

Lectins are proteins or glycoproteins of non-immune origin which bind reversibly to carbohydrates that are exposed on cellular surfaces and mediate cellular recognition processes in a variety of biological interactions. Though initially discovered in plants, lectins from various sources including lichens, have been extensively studied by researchers all over the world. The symbiotic interaction between a fungus (mycobiont) and its photosynthetic partner (photobiont), usually an alga, constitutes a lichen. Some lichen lectins displays activity to human or animal erythrocytes. Although only a few lichen lectins have been examined to date, their characteristics suggest that they play an important role in the symbiotic interactions of this association. Lectin binding and the related enzymatic activity with respect to algal cell recognition illustrates a finely tuned mechanistic system which involved in the lichen symbiosis. This review provides an overview of the characteristics of lichen lectins and an insight into lectin-mediated symbiotic interactions and the galectin encoding genes. Future prospects for lichen lectin research in different areas are also highlighted.