Review: Usnic acid-induced hepatotoxicity and cell death

Kwong, Sukfan P.; Wang, Changhong

doi:10.1016/j.etap.2020.103493

Cited by 24 publications

(8 citation statements)

References 76 publications

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“…Usnic acid is the main secondary metabolite responsible for its pharmacological potential [ 23 ]. The pharmaceutical applications of UA as an antibacterial agent are limited by its poor water solubility [ 24 ] and significant hepatotoxicity [ 25 ]. Therefore, the nanosystems with usnic acid must be able to increase its bio-disponibility, tolerance, and antibacterial effects [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

Phenolic Secondary Metabolites and Antiradical and Antibacterial Activities of Different Extracts of Usnea barbata (L.) Weber ex F.H.Wigg from Călimani Mountains, Romania

et al. 2022

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Phenolic compounds represent an essential bioactive metabolites group with numerous pharmaceutical applications. Our study aims to identify and quantify phenolic constituents of various liquid and dry extracts of Usnea barbata (L.) Weber ex F.H. Wigg (U. barbata) from Calimani Mountains, Romania, and investigate their bioactivities. The extracts in acetone, 96% ethanol, and water with the same dried lichen/solvent ratio (w/v) were obtained through two conventional techniques: maceration (mUBA, mUBE, and mUBW) and Soxhlet extraction (dUBA, dUBE, and dUBW). High-performance liquid chromatography with diode-array detection (HPLC-DAD) was performed for usnic acid (UA) and different polyphenols quantification. Then, the total phenolic content (TPC) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical scavenging activity (AA) were determined through spectrophotometric methods. Using the disc diffusion method (DDM), the antibacterial activity was evaluated against Gram-positive and Gram-negative bacteria known for their pathogenicity: Staphylococcus aureus (ATCC 25923), Streptococcus pneumoniae (ATCC 49619), Pseudomonas aeruginosa (ATCC 27853), and Klebsiella pneumoniae (ATCC 13883). All extracts contain phenolic compounds expressed as TPC values. Five lichen extracts display various UA contents; this significant metabolite was not detected in dUBW. Six polyphenols from the standards mixture were quantified only in ethanol and water extracts; mUBE has all individual polyphenols, while dUBE shows only two. Three polyphenols were detected in mUBW, but none was found in dUBW. All U. barbata extracts had antiradical activity; however, only ethanol and acetone extracts proved inhibitory activity against P. aeruginosa, S. pneumoniae, and S. aureus. In contrast, K. pneumoniae was strongly resistant (IZD = 0). Data analysis evidenced a high positive correlation between the phenolic constituents and bioactivities of each U. barbata extract. Associating these extracts’ properties with both conventional techniques used for their preparation revealed the extraction conditions’ significant influence on lichen extracts metabolites profiling, with a powerful impact on their pharmacological potential.

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Section: Introductionmentioning

confidence: 99%

Phenolic Secondary Metabolites and Antiradical and Antibacterial Activities of Different Extracts of Usnea barbata (L.) Weber ex F.H.Wigg from Călimani Mountains, Romania

et al. 2022

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“…It was used to induce human weight loss [ 29 ], although unwanted hepatotoxic effects were also triggered [ 30 ]. In addition, UA highlights antimicrobial [ 31 ], insecticidal [ 32 ], anticholinergic [ 33 ], antioxidant [ 34 ], pro-oxidant [ 35 ], antigenotoxic [ 36 ], genotoxic [ 37 ], teratogenic [ 38 ], anti-inflammatory [ 39 ], analgesic and antipyretic [ 40 ], mutagenic and carcinogenic [ 41 ], anticancer [ 42 ], and cytotoxic [ 43 ] activities. Numerous researchers have shown the pharmacological actions of usnic acid and Usnea sp.…”

Section: Introductionmentioning

confidence: 99%

Usnic Acid and Usnea barbata (L.) F.H. Wigg. Dry Extracts Promote Apoptosis and DNA Damage in Human Blood Cells through Enhancing ROS Levels

et al. 2021

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Nowadays, numerous biomedical studies performed on natural compounds and plant extracts aim to obtain highly selective pharmacological activities without unwanted toxic effects. In the big world of medicinal plants, Usnea barbata (L) F.H. Wigg (U. barbata) and usnic acid (UA) are well-known for their therapeutical properties. One of the most studied properties is their cytotoxicity on various tumor cells. This work aims to evaluate their cytotoxic potential on normal blood cells. Three dry U. barbata extracts in various solvents: ethyl acetate (UBEA), acetone (UBA), and ethanol (UBE) were prepared. From UBEA we isolated usnic acid with high purity by semipreparative chromatography. Then, UA, UBA, and UBE dissolved in 1% dimethyl sulfoxide (DMSO) and diluted in four concentrations were tested for their toxicity on human blood cells. The blood samples were collected from a healthy non-smoker donor; the obtained blood cell cultures were treated with the tested samples. After 24 h, the cytotoxic effect was analyzed through the mechanisms that can cause cell death: early and late apoptosis, caspase 3/7 activity, nuclear apoptosis, autophagy, reactive oxygen species (ROS) level and DNA damage. Generally, the cytotoxic effect was directly proportional to the increase of concentrations, usnic acid inducing the most significant response. At high concentrations, usnic acid and U. barbata extracts induced apoptosis and DNA damage in human blood cells, increasing ROS levels. Our study reveals the importance of prior natural products toxicity evaluation on normal cells to anticipate their limits and benefits as potential anticancer drugs.

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“…Natural product UA has been reported with the capacity to stimulate the ATF3 expression, which would target the subcellular mitochondria and produce significant ROS to initiate oxidative stresses. , However, the solubility and bioavailability of UA were extremely low, restricting its biological applications . On the other hand, mitochondria-targeting complex Ir-NH 2 reported by our group has indicated the antiproliferation capacity to NSCLC A549 cells via the mitophagy blockage with p62 accumulation (Scheme a), while the upregulation of the PD-L1 level was not significant.…”

Section: Results and Discussionmentioning

confidence: 92%

Iridium(III)-Based PD-L1 Agonist Regulates p62 and ATF3 for Enhanced Cancer Immunotherapy

Deng,

Wang,

et al. 2024

J. Med. Chem.

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Anti-PD-L1 immunotherapy, a new lung cancer treatment, is limited to a few patients due to low PD-L1 expression and tumor immunosuppression. To address these challenges, the upregulation of PD-L1 has the potential to elevate the response rate and efficiency of anti-PD-L1 and alleviate the immunosuppression of the tumor microenvironment. Herein, we developed a novel usnic acid-derived Iridium(III) complex, Ir-UA, that boosts PD-L1 expression and converts “cold tumors” to “hot”. Subsequently, we administered Ir-UA combined with anti-PD-L1 in mice, which effectively inhibited tumor growth and promoted CD4+ and CD8+ T cell infiltration. To our knowledge, Ir-UA is the first iridium-based complex to stimulate the expression of PD-L1 by explicitly regulating its transcription factors, which not only provides a promising platform for immune checkpoint blockade but, more importantly, provides an effective treatment strategy for patients with low PD-L1 expression.

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Review: Usnic acid-induced hepatotoxicity and cell death

Cited by 24 publications

References 76 publications

Phenolic Secondary Metabolites and Antiradical and Antibacterial Activities of Different Extracts of Usnea barbata (L.) Weber ex F.H.Wigg from Călimani Mountains, Romania

Phenolic Secondary Metabolites and Antiradical and Antibacterial Activities of Different Extracts of Usnea barbata (L.) Weber ex F.H.Wigg from Călimani Mountains, Romania

Usnic Acid and Usnea barbata (L.) F.H. Wigg. Dry Extracts Promote Apoptosis and DNA Damage in Human Blood Cells through Enhancing ROS Levels

Iridium(III)-Based PD-L1 Agonist Regulates p62 and ATF3 for Enhanced Cancer Immunotherapy

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