Nano-and microcarriers as drug delivery systems for usnic acid: Review of literature

Usnic acid is one of the most investigated lichen secondary metabolites, with several proven biological properties with potential medical relevance. However, its unfavorable physico-chemical properties, as well as observed hepatotoxicity, have discouraged wide-range utilization of usnic acid as a promising therapeutic agent. In accordance with the growing research interest in the development of nanotechnology, especially in the arena of preparations based on natural sources of medicinal compounds, usnic acid incorporated into nano-and microsized colloidal carriers has been a subject of a large number of publications. Therefore, this review discusses the overall results of the studies dealing with usnic acid encapsulated into lipid-based, polymeric and nonorganic micro-and/or nanocarriers, as potential drug delivery systems for this natural compound, in an attempt to introduce its usage as a potential antitumor, antimicrobial, wound-healing, antioxidative and anti-inflammatory drug

Extract of the talus of Usnea barbata (L.) Weber ex F. H. Wigg., Parmeliaceae in the emulsion vehicles stabilized with biodegradable emulsifiers: preformulation and formulation investigations

Uvod Lokalna terapija antibiotskim preparatima predstavlja pogodan način prevencije i/ili lečenja određenih infekcija kože, ali ima i niz ograničenja koja su vezana kako za lekovite supstance sa antimikrobnim delovanjem, tako i za podloge koje se koriste kao njihovi nosači. Pored porasta rezistencije bakterija, nedostatak dermalne primene antibiotika je i njihova slaba penetracija u kožu, ali i toksičnost nekih od njih prema humanim ćelijama. Usled toga, nameće se potreba za pronalaženjem novih supstanci sa antimikrobnom aktivnošću širokog spektra dejstva i poboljšanom dermalnom raspoloživošću/bezbednosnim profilom. Kao potencijalni izvori ovakvih supstanci sve više se istražuju lišajevi, među kojima se naročito istakla Usnea barbata (L.) Weber ex F.H. Wigg., Parmeliaceae (jevrejska ili lišaj brada). Iako se brojna biološka svojstva lišaj brade pripisuju usninskoj kiselini, novija istraživanja ukazala su na neke prednosti upotrebe njenog ekstrakta dobijenog primenom natkritičnog ugljen-dioksida (CO2) u odnosu na ovu supstancu per se. Sa druge strane, poznato je da su emulzioni sistemi (naročito kremovi), kao najpopularniji nosači lekovitih supstanci u dermatološkim preparatima, često stabilizovani tradicionalnim anjonskim/nejonskim mešanim emulgatorima, koji mogu izazvati neželjene reakcije, posebno na oboleloj koži. Pored toga, značajan uticaj kozmetičke industrije na dermofarmaciju je, uz porast zabrinutosti za zaštitu životne sredine, stavio u fokus istraživanja savremenih emulgatora povoljnijeg ekološkog i dermatološkog profila, koji istovremeno mogu da obezbede poboljšane senzorne osobine kremova za primenu na koži. Cilj istraživanja Cilj istraživanja ove doktorske disertacije bio je razvoj emulzionog sistema tipa hidrofilnog krema sa biorazgradivim alkil poligukozidnim (APG) emulgatorima prirodnog porekla, kao nosača za ekstrakt talusa U. barbata sa kvantifikovanom usninskom kiselinom, kroz procenu koloidne strukture, fizičke stabilnosti i biofarmaceutskih karakteristika, te ispitivanja efikasnosti i bezbednosti prototip formulacije gotovog proizvoda, koji bi našao potencijalnu primenu kao alternativa antibiotskim preparatima u lokalnoj terapiji infekcija kože...Introduction Local therapy with antibiotic preparations represents the preferable way of prevention and/or treatment of some skin infections but also has a number of limitations connected to antimicrobial agents on one the hand and vehicles used as their carriers, on the other. Aside from bacterial resistance growth, a major problem regarding dermal application of antibiotics is their poor penetration into the skin, and also toxicity to human cells, documented for some of them. Therefore, there is a growing interest in the research concerning new substances with broad-spectrum antimicrobial activity and improved dermal availability/safety profile. Lately, various lichens are being intensively investigated as potential sources of such substances, among which Usnea barbata (L.) Weber ex F. H. Wigg., Parmeliaceae (old man’s beard) has been singled out, as one of the most frequently investigated. Although various biological properties of old man’s beard have been attributed to usnic acid, recent research suggested certain benefits of usage of its extract obtained using supercritical carbon dioxide (CO2), compared to this compound per se. On the other hand, it is well established that the emulsion systems (particularly creams), as the most popular carriers in dermatological preparations, are often stabilized using conventional anionic/non-ionic emulsifiers, known to cause adverse effects, especially in the diseased skin. Besides that, a major impact of the cosmetic industry on dermopharmacy, alongside with the growing environmental concerns, has put in the focus research of contemporary emulsifiers with favorable dermatological and ecological profile, which are also able to provide enhanced sensory properties of creams for skin application. Aim The aim of this doctoral dissertation was the development of an emulsion system of hydrophilic cream type based on biodegradable alkyl polyglucoside (APG) emulsifiers, as a potential carrier for the extract of the talus of U. barbata with quantified usnic acid, throughout the assessment of colloidal structure, physical stability and biopharmaceutical characteristics and also evaluation of efficacy and safety of the prototype formulation of the final product, which could potentially serve as an alternative to the antibiotic preparations in the local treatment of skin infections..

Chemical composition and biological activities of the extracts and secondary metabolites of lichens belonging to the genus Usnea, Parmeliaceae

Lichens represent a promising source of antimicrobial, cytotoxic and antioxidant agents. Their great pharmacological potential lies in the fact that they represent specific symbiotic organisms and thus possess natural roles allowing them to be highly adaptable to different environmental conditions. On the other hand, stated biological activities of lichens with prospective medicinal significance may be connected to their long-term use in traditional treatment of various ailments. Genus Usnea from the Parmeliaceae family is certainly one of the best studied in terms of chemical composition and biological properties of its extracts and/or isolated compounds. In the first part of the study, a detailed review of literature has been performed yielding a detailed report on the investigations of biological activities of the lichens belonging to this genus. In the second part of the study, chemical composition of the lichens from the genus was described and, additionally, a survey of the biological properties of the most representative secondary metabolites in these lichens has been reported. It could be concluded that the extracts and/or isolated compounds from the lichens belonging to the genus Usnea may be considered a valuable source of prospective drug candidates with potential clinical relevance

Cytotoxic activity of supercritical CO2 extract of old man's beard in L929 fibrosarcoma cell line

Old man’s beard (Usnea barbata) is one of the most investigated lichens which biological properties (such as antimicrobial, anti-inflammatory and cytotoxic activities) have been proven in several scien- tific studies. Stated properties of old man’s beard have been attributed mainly to its major secondary metabolite - a dibenzofuran derivative, usnic acid. The aim of the current study was to examine cyto- toxic activity of the quantified supercritical CO2 extract and pure usnic acid in parallel against L929 fibrosarcoma cells. Our results indicated the tested extract to be more toxic towards the investigated cell line compared to usnic acid per se, despite the high amount of this compound (81.41% (w/w)) revealed in the extract using HPLC. Such result may be connected to the unidentified compounds present in the supercritical CO2 extract that could be responsible for apoptosis and oxidative stress in the exerted cytotoxicity of the investigated extract, but not usnic acid. Our study supports further in- vestigations of supercritical CO2 extract of U. barbata as a prospective therapeutic agent with potential relevance in the treatment of sarcoma

Chemical analysis and antimicrobial activity of essential oils from wild laurel of National park Skadar lake, Montenegro

Laurus nobilis L., Lauraceae, u narodu poznat kao lovor, je cvetni, zimzeleni žbun koji samoniklo raste u većem delu Crne Gore, a često se uzgaja i koristi kao aromatična, začinska i lekovita biljka. Cilj ovog istraživanja je bio da se analizira hemijski sastav etarskog ulja (EU) ploda i lista, a zatim testira antibakterijska i antifungalna aktivnost EU na sledećim sojevima: Staphylococcus aureus ATCC25923, Enterococcus faecalis ATCC29212, Bacillus subtilis ATCC6633 Escherichia coli ATCC25922, Klebsiella pneumoniae ATCC13083, Salmonella Abony NCTC6017, Pseudomonas aeruginosa ATCC27853 i Candida albicans ATCC10231. Ispitivanje kvalitativnog i kvantitativnog sastava etarskih ulja lista i plodova lovora izvršeno je gasnohromatografskom tehnikom spregnutom sa masenom spektrometrijom (GC-MS). Utvrđeno je da je etarsko ulje ploda bogato 1,8-cineolom (33,3%), α-terpenil acetatom (7,0%), α-pinenom (5,8%), β-elemenom (5,7%), sabinenom (5,3%), β- pinenom (4,0%), borneolom (2,1%) i terpinen-4-olom (2,1%). Najvažnije komponente identi�ikovane u EU listova su 1,8-cineol (35,1%), α-terpinil acetat (10,4%) i linalol (7,6%), između ostalih, a u skladu su sa prethodno dobijenim literaturnim podacima (1). Dodatno, ispitivana su antibakterijska i antifungalna svojstva EU lista i ploda lovora bujon mikrodilucionom metodom. EU ploda je pokazao antibakterijsko i antifungalno svojstvo protiv skoro svih testiranih sojeva mikroorganizama, dok je EU lista inhibiralo sledeće sojeve: Staphylococcus aureus ATCC25923, Enterococcus faecalis ATCC29212, Bacillus subtilis ATCC6633 i Candida albicans ATCC10231. Escherichia coli ATCC25922 je bakterijski soj koji je pokazao najveću otpornost na etarska ulja lovora, kako ploda, tako i lista. Dobijeni rezultati za etarska ulja lovora i 1,8 -cineol, koji je njihov glavni sastojak, su u skladu sa prethodnim studijama (2).Laurus nobilis L., Lauraceae, popularly known as laurel, is a flowering, evergreen bush which grows wildly in most parts of Montenegro, and is often cultivated and used as an aromatic, flavoring spice and medicinal plant. The aim of this research was to analyze the chemical composition of the essential oil (EO) of fruit and leaf, and afterwards antibacterial and antifungal activity of EOs on the following strains: Staphylococcus aureus ATCC25923, Enterococcus faecalis ATCC29212, Bacillus subtilis ATCC6633 Escherichia coli ATCC25922, Klebsiella pneumoniae ATCC13083, Salmonella Abony NCTC6017, Pseudomonas aeruginosa ATCC27853 i Candida albicans ATCC10231. The qualitative and quantitative composition of the EOs of fruit and leaves was carried out by using a gas chromatographic analysis coupled with mass spectrometry (GC-MS). The EO of fruit was found to be rich 1,8-cineole (33.3%), α-terpinyl acetate (7.0%), α-pinene (5.8%), β-elemene (5.7%), sabinene (5.3%), β-pinene (4.0%), borneol (2.1%) and terpinene-4-ol (2.1%). The most important components identified in the leaves EO were 1,8-cineol (35.1%), α-terpinyl acetate (10.4%) and linalool (7.6%), among others, are in line with previous literature reports (1). In addition, the antibacterial and antifungal properties of leaf and fruit laurel EOs were examined according to the broth microdilution method. The fruit EO showed antibacterial and antifungal activities against almost all strains of the microorganisms tested, whereas the leaf EO was able to inhibit: Staphylococcus aureus ATCC25923, Enterococcus faecalis ATCC29212, Bacillus subtilis ATCC6633 and Candida albicans ATCC10231. Escherichia coli ATCC25922 was bacterial strain that showed the highest resistance to both tested laurel EOs. The results obtained herein for laurel EO and 1,8-cineole as its main constituent are in accordance with previous studies (2).Treći naučni simpozijum Saveza farmaceutskih udruženja Srbije sa međunarodnim učešćem „Lekovi za specifične populacije pacijenata: inovacijama ka unapređenju zdravstvenih ishoda“, Niš, Srbija, 26. oktobar 2023

Antimikrobna aktivnost izolata korena omana

Elecampane (Inula helenium L., Asteraceae), a well-known traditional medicinal herb, and its root (Inulae radix) have been used as antiseptics, expectorants, diuretics and bactericidal agents. The aim of this study was to investigate the antimicrobial activity of different Inulae radix isolates against microorganisms that commonly cause skin infections. The essential oil obtained by hydrodistillation (IH-HD) and Sohxlet extracts, ether (IH-SOX-E) and ethanol (IH-SOX-Et) fractions were investigate The isolates were dissolved in DMSO at the concentration of 2560 to 0.625 μg/mL. The antimicrobial activity was tested by using the microdilution method against reference bacterial strains and clinical isolates from skin swabs. IH-SOX-E exhibited a strong antimicrobial activity against all tested strains, IH-HD as well, with the exception of S. aureus, ATCC 25923 (moderate activity), while IH-SOX-Et showed a strong activity only against clinical isolate of C. albicans. The results of our study indicate that elecampane root isolates may be used for incorporation into phytopreparations for topical application in treating skin infections, especially those caused by C. Albicans the most possible sites for interactions with other compounds.Oman (Inula helenium L., Asteraceae) je cenjena lekovita biljka, čiji je koren poznat po antiseptičnom ekspektorantnom, diuretičnom i baktericidnom delovanju. Cilj rada bio je ispitivanje antimikrobne aktivnosti različitih izolata korena omana, Inulae radix protiv mikroorganizama koje uobičajeno izazivaju infekcije kože. Ispitivani su etarsko ulje dobijeno hidrodestilacijom (IH-HD) i Sohxlet ekstrakti i to etarska (IH-SOX-E) i etanolna (IH-SOX-Et) frakcija. Izolati su rastvoreni u DMSO u koncentraciji od 2560 do 0,625 μg/mL. Antimikrobna aktivnost ispitivana je mikrodilucionom metodom u bujonu na referentnim bakterijskim sojevima i kliničkim izolatima iz briseva kože. IH-SOX-E ispoljila je jaku antimikrobnu aktivnost prema svim testiranim mikroorganizmima, IH-HD takođe, osim prema Streptococcus aureus ATCC 25923 (umerena aktivnost), a IH-SOX-Et jaku aktivnost pokazala je jedino prema kliničkom izolatu Candida albicans. Rezultati naših ispitivanja pokazuju da se izolati korena omana mogu koristiti za inkorporiranje u fitopreparate namenjene za spoljašnju primenu kod kožnih infekcija, naročito gljivičnih infekcija izazvanih C. albicans

Evaluation of Anticancer and Antioxidant Activity of a Commercially Available CO2 Supercritical Extract of Old Man's Beard (Usnea barbata)

There is a worldwide ongoing investigation for novel natural constituents with cytotoxic and antioxidant properties. The aim of this study was to investigate chemical profile and stated biological activities of the supercritical CO2 extract (SCE) of old man's beard compared to the extracts obtained using the conventional techniques (Soxhlet extracts and macerate). The most abundant compound identified was usnic acid, which content was inversely proportional to the polarity of the solvent used and was the highest in the SCE, which was the sample revealing the highest cytotoxic activity in tested tumor cell lines (B16 mouse melanoma and C6 rat glioma), with lower IC50 values compared to pure usnic acid. Further investigations suggested both SCE and usnic acid to induce apoptosis and/ or autophagy in B16 and C6, indicating higher cytotoxicity of SCE to be related to the higher degree of ROS production. A good correlation of usnic acid content in the extracts and their antioxidant capacity was established, extricating SCE as the most active one. Presented results support further investigations of SCE of old man's beard as a prospective therapeutic agent with potential relevance in the treatment of cancer and/ or in oxidative stress-mediated conditions

Derivatives of L-Ascorbic Acid in Emulgel: Development and Comprehensive Evaluation of the Topical Delivery System

The dual controlled release of emulgels makes them efficient drug delivery systems of increasing interest. The framework of this study was to incorporate selected L-ascorbic acid derivatives into emulgels. From the formulated emulgels, the release profiles of actives were evaluated considering their different polarities and concentrations, and consequently their effectiveness on the skin via a long-term in vivo study that lasted for 30 days was determined. Skin effects were assessed by measuring the electrical capacitance of the stratum corneum (EC), trans-epidermal water loss (TEWL), melanin index (MI) and skin pH. In addition, the sensory and textural properties of emulgel formulations were compared with each other. The changes in the rate of the release of the L-ascorbic acid derivatives were monitored using the Franz diffusion cells. The obtained data were statistically significant, and indicated an increase in the degree of hydration of the skin and skin whitening potential, while no significant changes in TEWL and pH values were detected. The consistency, firmness and stickiness of the emulgels were estimated by volunteers applying the established sensory evaluation protocol. In addition, it was revealed that the difference in hydrophilic/lipophilic properties of L-ascorbic acid derivatives influenced their release profiles without changing their textural characteristics. Therefore, this study highlighted emulgels as L-ascorbic acid suitable carrier systems and one of the promising candidates as novel drug delivery systems

Lady’s mantle (Alchemilla vulgaris L., Rosaceae): A review of traditional uses, phytochemical profile, and biological properties

Lady’s mantle (Alchemilla vulgaris L. syn. Alchemilla xanthochlora Rothm., Rosaceae) has been commonly used in folk medicine to heal inflammations in the mouth, bleeding of the nose, furuncules, gynaecological (menorrhagia and dysmenorrhoea), and gastrointestinal disorders. Although therapeutic indications for Lady’s mantle are non-specific diarrhoea and gastrointestinal complaints, it has been reported to exert, as well, a variety of biological activities, including wound healing, antimicrobial, neuroprotective, gastroprotective, cytotoxic, and antioxidant. Lady’s mantle presents a valuable source of natural bioactive compounds, mostly phenolic compounds – a large amount of tannins, phenolcarboxylic acids, and flavonoids, being responsible for the abovementioned effects. In this work, a literature review of biological properties, investigated in in vitro and in vivo experiments in regard to the determined chemical profile is presented. In addition, the data reported are discussed, and the directions for further investigations are proposed