Chrysophanol is a unique anthraquinone having broad-spectrum therapeutic potential along with ecological importance. It is the first polyketide that has been reported to be biosynthesized in an organism-specific manner. The traditional Chinese and Korean medicinal systems provide evidence of the beneficial effects of chrysophanol on human health. The global distribution of chrysophanol encountered in two domains of life (bacteria and eukaryota) has motivated researchers to critically evaluate the properties of this compound. A plethora of literature is available on the pharmacological properties of chrysophanol, which include anticancer, hepatoprotective, neuroprotective, anti-inflammatory, antiulcer, and antimicrobial activities. However, the pharmacokinetics and toxicity studies on chrysophanol demand further investigations for it to be used as a drug. This is the first comprehensive review on the natural sources, biosynthetic pathways, and pharmacology of chrysophanol. Here we reviewed recent advancements made on the pharmacokinetics of the chrysophanol. Additionally, we have highlighted the knowledge gaps of its mechanism of action against diseases and toxicity aspects.

Honey is an excellent source of polyphenolic compounds that are effective in attenuating quorum sensing (QS), a chemical process of cell-to-cell communication system used by the opportunistic pathogen Pseudomonas aeruginosa to regulate virulence and biofilm formation. However lower water solubility and inadequate bioavailability remains major concerns of these therapeutic polyphenols. Its therapeutic index can be improved by using nano-carrier systems to target QS signaling potently. In the present study, we fabricated a unique drug delivery system comprising selenium nanoparticles (SeNPs; non-viral vectors) and polyphenols of honey (HP) for enhancement of anti-QS activity of HP against P. aeruginosa PAO1. The developed selenium nano-scaffold showed superior anti-QS activity, anti-biofilm efficacy, and anti-virulence potential in both in-vitro and in-vivo over its individual components, SeNPs and HP. LasR is inhibited by selenium nano-scaffold in-vitro. Using computational molecular docking studies, we have also demonstrated that the anti-virulence activity of selenium nano-scaffold is reliant on molecular binding that occurs between HP and the QS receptor LasR through hydrogen bonding and hydrophobic interactions. Our preliminary investigations with selenium-based nano-carriers hold significant promise to improve anti-virulence effectiveness of phytochemicals by enhancing effective intracellular delivery.

Quorum sensing (QS) regulates group behaviors of Candida albicans such as biofilm, hyphal growth, and virulence factors. The sesquiterpene alcohol farnesol, a QS molecule produced by C. albicans , is known to regulate the expression of virulence weapons of this fungus. Fluconazole (FCZ) is a broad-spectrum antifungal drug that is used for the treatment of C. albicans infections. While FCZ can be cytotoxic at high concentrations, our results show that at much lower concentrations, quercetin (QC), a dietary flavonoid isolated from an edible lichen ( Usnea longissima ), can be implemented as a sensitizing agent for FCZ-resistant C. albicans NBC099, enhancing the efficacy of FCZ. QC enhanced FCZ-mediated cell killing of NBC099 and also induced cell death. These experiments indicated that the combined application of both drugs was FCZ dose dependent rather than QC dose dependent. In addition, we found that QC strongly suppressed the production of virulence weapons—biofilm formation, hyphal development, phospholipase, proteinase, esterase, and hemolytic activity. Treatment with QC also increased FCZ-mediated cell death in NBC099 biofilms. Interestingly, we also found that QC enhances the anticandidal activity of FCZ by inducing apoptotic cell death. We have also established that this sensitization is reliant on the farnesol response generated by QC. Molecular docking studies also support this conclusion and suggest that QC can form hydrogen bonds with Gln969, Thr1105, Ser1108, Arg1109, Asn1110, and Gly1061 in the ATP binding pocket of adenylate cyclase. Thus, this QS-mediated combined sensitizer (QC)-anticandidal agent (FCZ) strategy may be a novel way to enhance the efficacy of FCZ-based therapy of C. albicans infections.

The genus Usnea Adans. (Parmeliaceae; lichenized Ascomycetes) is a typical group of mostly pale grayish-green fruticoselichens that grow as leafless mini-shrubs. More than 360 species of Usnea are known in the world. Usnea has long been thought to have treat various illnesses in addition to its historical use as dyes, cosmetics, preservatives, and deodorants, particularly in eastern countries such as China, Japan, Taiwan, India and Europe. The current review focuses on the traditional uses and phytochemistry aspects of different Usnea species, and discusses the pharmacological findings and toxicology of their extracts and isolated compounds. The available compilation of data will provide a new base for future perspectives and highlight the need for further studies of this potent herbal source to harvest more beneficial therapeutic drugs. Nineteen species of the genus Usnea are found to be important folk medicines all over the world. It is evident from the comparative analysis of the searched literature that the genus Usnea has been used for various purposes for centuries and its long and traditional medicinal history was well documented in the past. As per ancient records and recent scientific literature, the species of genus Usnea have been used as promising traditional medicines, exerting an array of therapeutic properties to relieve sore throats, bronchitis, cold, flu, infection, and indigestion. Phytochemical analysis confirms the general presence of a wide range of metabolites, polysaccharides, fatty acids, phenolic acids, flavonoids, terpenes, sterols, depsides, depsidones, and benzofurans. As specific constituents, usnic acid, polyphenols, and depsides have been considered as main efficacy component for antibacterial and antifungal activities. In addition, pharmacological analysis also revealed that other pure compounds and crude extracts of Usnea species prove to be significant anti-cancer, anti-proliferative, anti-oxidant, anti-viral, anti-inflammatory, anti-ulcer, hepatoprotective, and anti-genotoxic agents. However, there is a need for more precise investigations to examine the clinical value of both isolated pure compounds and crude extracts and to elucidate their mechanisms of action. Apart from clinical validation and elucidation of their mechanism of action, biosafety studies of the compounds are also important to legitimately use the potential bioactive compounds for the further development of future lead drugs.