The inhibitory effects of flavonoids on monoamine oxidases (MAOs) have attracted great interest since alterations in monoaminergic transmission are reported to be related to neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases and psychiatric disorders such as depression and anxiety, thus MAOs may be considered as targets for the treatment of these multi-factorial diseases. In the present study, four Sideritis flavonoids, xanthomicrol (1), isoscutellarein 7-O-[6'''-O-acetyl-β-D-allopyranosyl-(1→2)]-β-D-glucopyranoside (2), isoscutellarein 7-O-[6'''-O-acetyl-β-D-allopyranosyl-(1→2)]-6''-O-acetyl-β-D-glucopyranoside (3) and salvigenin (4) were docked computationally into the active site of the human monoamine oxidase isoforms (hMAO-A and hMAO-B) and were also investigated for their hMAO inhibitory potencies using recombinant hMAO isoenzymes. The flavonoids inhibited hMAO-A selectively and reversibly in a competitive mode. Salvigenin (4) was found to be the most potent hMAO-A inhibitor, while xanthomicrol (1) appeared as the most selective hMAO-A inhibitor. The computationally obtained results were in good agreement with the corresponding experimental values. In addition, the x-ray structure of xanthomicrol (1) has been shown. The current work warrants further preclinical studies to assess the potential of xanthomicrol (1) and salvigenin (4) as new selective and reversible hMAO-A inhibitors for the treatment of depression and anxiety.

This work aimed to evaluate the phenolic content and in vitro antioxidant, antimicrobial and enzyme inhibitory activities of the methanol extracts and their fractions of two edible halophytic Limonium species, L. effusum (LE) and L. sinuatum (LS). The total phenolic content resulted about two-fold higher in the ethyl acetate fraction of LE (522.82 ± 5.67 mg GAE/g extract) than in that of LS (274.87 ± 1.87 mg GAE/g extract). LC-MS/MS analysis indicated that tannic acid was the most abundant phenolic acid in both species (71,439.56 ± 3643.3 µg/g extract in LE and 105,453.5 ± 5328.1 µg/g extract in LS), whereas hyperoside was the most abundant flavonoid (14,006.90 ± 686.1 µg/g extract in LE and 1708.51 ± 83.6 µg/g extract in LS). The antioxidant capacity was evaluated by DPPH and TAC assays, and the stronger antioxidant activity in ethyl acetate fractions was highlighted. Both species were more active against Gram-positive bacteria than Gram negatives and showed considerable growth inhibitions against tested fungi. Interestingly, selective acetylcholinesterase (AChE) activity was observed with LE and LS. Particularly, the water fraction of LS strongly inhibited AChE (IC₅₀ = 0.199 ± 0.009 µg/mL). The ethyl acetate fractions of LE and LS, as well as the n-hexane fraction of LE, exhibited significant antityrosinase activity (IC₅₀ = 245.56 ± 3.6, 295.18 ± 10.57 and 148.27 ± 3.33 µg/mL, respectively). The ethyl acetate fraction and methanol extract of LS also significantly inhibited pancreatic lipase (IC₅₀ = 83.76 ± 4.19 and 162.2 ± 7.29 µg/mL, respectively). Taken together, these findings warrant further investigations to assess the potential of LE and LS as a bioactive source that can be exploited in pharmaceutical, cosmetics and food industries.

Background: Achilles tendon (AT) midsubstance injuries may heal suboptimally, especially in athletes. Transforming growth factor–beta 3 (TGF-β3) shows promise because of its recently discovered tendinogenic effects. Using poly(lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA-b-PEG) nanoparticles (NPs) may enhance the results by a sustained-release effect. Hypothesis: The application of TGF-β3 will enhance AT midsubstance healing, and the NP form will achieve better outcomes. Study Design: Controlled laboratory study. Methods: A total of 80 rats underwent unilateral AT transection and were divided into 4 groups: (1) control (C); (2) empty chitosan film (Ch); (3) chitosan film containing free TGF-β3 (ChT); and (4) chitosan film containing TGF-β3–loaded NPs (ChN). The animals were sacrificed at 3 and 6 weeks. Tendons were evaluated for morphology (length and cross-sectional area [CSA]), biomechanics (maximum load, stress, stiffness, and elastic modulus), histology, immunohistochemical quantification (types I and III collagen [COL1 and COL3]), and gene expression (COL1A1, COL3A1, scleraxis, and tenomodulin). Results: Morphologically, at 3 weeks, ChT (15 ± 2.7 mm) and ChN (15.6 ± 1.6 mm) were shorter than C (17.6 ± 1.8 mm) ( P = .019 and = .004, respectively). At 6 weeks, the mean CSA of ChN (10.4 ± 1.9 mm ² ) was similar to that of intact tendons (6.4 ± 1.1 mm ² ) ( P = .230), while the other groups were larger. Biomechanically, at 3 weeks, ChT (42.8 ± 4.9 N) had a higher maximum load than C (27 ± 9.1 N; P = .004) and Ch (29.2 ± 5.7 N; P = .005). At 6 weeks, ChN (26.9 ± 3.9 MPa) had similar maximum stress when compared with intact tendons (34.1 ± 7.8 MPa) ( P = .121); the other groups were significantly lower. Histologically, at 6 weeks, the mean Movin score of ChN (4.5 ± 1.5) was lower than that of ChT (6.3 ± 1.8). Immunohistochemically, ChN had higher COL3 (1.469 ± 0.514) at 3 weeks and lower COL1 (1.129 ± 0.368) at 6 weeks. COL1A1 gene expression was higher in ChT and ChN at 3 weeks, but COL3A1 gene expression was higher in ChN. Conclusion: The application of TGF-β3 had a positive effect on AT midsubstance healing, and the sustained-release NP form improved the outcomes, more specifically accelerating the remodeling process. Clinical Relevance: This study demonstrated the effectiveness of TGF-β3 on tendon healing on a rat model, which is an important step toward clinical use. The novel method of using PLGA-b-PEG NPs as a drug-delivery system with sustained-release properties had promising results.

In various renal injuries, tissue damage occurs and platelet activation is observed. Recent studies suggest that some factors, such as serotonin, are released into microenvironment upon platelet activation following renal injury. In the present study, we aimed to investigate whether platelets and platelet-released serotonin are involved in the functional regulation of renal proximal tubular epithelial cells (PTECs). PTECs were obtained by primary cell culture and treated with platelet lysate (PL) (2 × 10⁶/mL, 4 × 10⁶/mL, 8 × 10⁶/mL) or serotonin (1 μM or 5 μM) for 12 or 24 h. Phenotypic transdifferentiation of epithelial cells into myofibroblasts were demonstrated under light microscope and confirmed by the determination of α-smooth muscle actin gene expression. Serotonin and PL were shown to induce epithelial–mesenchymal transdifferentiation of PTECs. After stimulation of PTECs with serotonin or PL, matrix metalloproteinase-2, tissue inhibitor of metalloproteinase-1, and collagen-α1 gene expressions, which were reported to be elevated in renal injury, were determined by real-time PCR and found to be upregulated. Expressions of some inflammatory cytokines such as tumor necrosis factor-α, interleukin-6, and transforming growth factor-β1 were found to be increased in both protein and gene levels. Recently there is no published report on the effect of serotonin on renal PTECs. Results obtained in this study have lightened the role of serotonin and platelet-mediated effects of serotonin on fibrotic and inflammatory processes in PTECs.