1. Structurally diverse biflavonoids from Dysosma versipellis and their bioactivity
Yan-Jun Sun, Rui-Jie Han, Hong-Yun Bai, Hao-Jie Wang, Meng Li, Ying-Ying Si, Jun-Min Wang, Jian-Hong Gong, Hui Chen, Wei-Sheng Feng RSC Adv. 2022 Dec 7;12(54):34962-34970. doi: 10.1039/d2ra06961j. eCollection 2022 Dec 6.
Five pairs of new biflavonoid enantiomers, (±)-dysosmabiflavonoids A-E (1-5), two new biflavonoids, dysosmabiflavonoids F-G (6-7), and four biosynthetically related precursors (8-11) were isolated from the roots and rhizomes of Dysosma versipellis. Their structures were elucidated by extensive spectroscopic analysis, including HR-ESI-MS and 2D NMR. Their absolute configurations were determined by comparison of the calculated and experimental ECD spectra. All isolated compounds were evaluated for AChE inhibitory activity. Compounds 6 and 7 exhibited more potent inhibitory activities with IC50 values of 1.42 and 0.73 µM, respectively, than their biosynthetically related precursors kaempferol (8, 17.90 µM) and quercetin (9, 3.96 µM). The preliminary structure-activity relationship study indicated that the connection mode of biflavonoid subunits, oxidation degree of the C ring, and 3,4-dihydroxy group of the B ring were important structural factors for AChE inhibitory activity. Racemates 1-5 and their corresponding levorotatory and dextrorotatory enantiomers were tested for their potential to impede the generation of NO in lipopolysaccharide-stimulated RAW264.7 cells, and their mushroom tyrosinase inhibitory effect. Racemate 1 displayed more potent mushroom tyrosinase inhibitory activity (IC50, 28.27 µM) than the positive control kojic acid (IC50, 32.59 µM). D. versipellis may have therapeutic potential for melanogenesis disorders and neurodegenerative diseases.
2. Chemical Composition, Antioxidant, Anti-Tyrosinase, Anti-Cholinesterase and Cytotoxic Activities of Essential Oils of Six Algerian Plants
Kadour Cheraif, Boulanouar Bakchiche, Abdelaziz Gherib, Sanaa K Bardaweel, Melek Çol Ayvaz, Guido Flamini, Roberta Ascrizzi, Mosad A Ghareeb Molecules. 2020 Apr 8;25(7):1710. doi: 10.3390/molecules25071710.
In this study, the essential oils (EOs) of six Algerian plants (Artemisia campestris L., Artemisia herba-alba Asso, Juniperus phoenicea L., Juniperus oxycedrus L., Mentha pulegium L. and Lavandula officinalis Chaix) were obtained by hydrodistillation, and their compositions determined by GC-MS and GC-FID. The antioxidant activity of the EOS was evaluated via 2,2'-diphenyl-1-picrylhydrazyl (DPPH), ferric-reducing/antioxidant power (FRAP) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) assays. Moreover, their cytotoxic effect was evaluated-as well as their tyrosinase, acetyl- and butyryl-cholinesterase (AChE and BuChE) inhibitory activities. The chemical analyses detected 44, 45, 51, 53, 26 and 40 compounds in EOs of A. campestris, A. herba-alba, J. phoenicea, J. oxycedrus, M. pulegium and L. officinalis, respectively. A. campestris EO was mainly composed of β-pinene (20.7%), while A. herba-alba EO contained davanone D (49.5%) as the main component. α-Pinene (41.8%) was detected as the major constituent in both J. phoenicea (41.8%) and J. oxycedrus (37.8%) EOs. M. pulegium EO was characterized by pulegone as the most abundant (76.9%) compound, while linalool (35.8%) was detected as a major constituent in L. officinalis EO. The antioxidant power evaluation revealed IC50 values ranging from 2.61 to 91.25 mg/mL for DPPH scavenging activity, while the FRAP values ranged from 0.97-8.17 µmol Trolox equivalents (TX)/g sample. In the ABTS assay, the values ranged from 7.01 to 2.40 µmol TX/g sample. In the presence of 1 mg/mL of the samples, tyrosinase inhibition rates ranged from 11.35% to 39.65%, AChE inhibition rates ranged from 40.57% to 73.60% and BuChE inhibition rates ranged from 6.47% to 72.03%. A significant cytotoxic effect was found for A. herba-alba EO. The obtained results support some of the traditional uses of these species in food preservation and for protection against several diseases.
3. Identification of a new shared HLA-A2.1 restricted epitope from the melanoma antigen tyrosinase
J P Riley, S A Rosenberg, M R Parkhurst J Immunother. 2001 May-Jun;24(3):212-20.
Tyrosinase has many advantages as a target antigen for the immunotherapy of patients with melanoma because it is expressed in nearly all melanoma specimens with a high degree of cellular homogeneity, and its distribution in normal tissues is limited to melanocytes. To broaden our ability to direct cellular immune responses against this protein, we pursued an investigation to identify new shared human leukocyte antigen (HLA)-A2.1 restricted epitopes from tyrosinase. Peptides were synthesized that fit a permissive HLA-A2.1 binding motif and did not span common sites of polymorphism. The binding affinity of each peptide to HLA-A2.1 relative to a standard peptide with intermediate binding affinity was evaluated in a competitive inhibition assay. Twelve peptides were selected that had binding affinities within 80% of that of the standard peptide, and these were used to stimulate peripheral blood mononuclear cells (PBMC) in vitro from three HLA-A2.1+ patients with metastatic melanoma. Cytotoxic T lymphocytes that specifically recognized peptide-pulsed target cells as well as HLA-A2.1+ tyrosinase+ melanoma cells were raised from one patient with tyrosinase:8-17 (CLLWSFQTSA). To evaluate further the immunogenicity of this peptide, PBMC from 23 HLA-A2.1+ patients were stimulated in vitro with tyrosinase:8-17. Eleven bulk T-cell cultures demonstrated specific peptide recognition, and six of these also recognized HLA-A2.1+ tyrosinase+ melanoma cells. These data suggest that tyrosinase:8-17 may be clinically useful for the treatment of patients with melanoma.
