Hydroxytyrosol (HT), the main phenolic compound in olives and olive products, has antioxidative, anti-inflammatory, neuroprotective, and other physiological functions. The effects of HT on depression are unclear. The aim of this study was to explore the effects of HT on chronic unpredictable mild stress (CUMS) induced depressive-like behaviors. Mice were exposed to CUMS for 9 weeks and then treated with HT beginning in the second week and continuing for 7 weeks. Behavioral, biochemical, and molecular tests were conducted at the end of the experiment. The sucrose preference was significantly decreased in the CUMS group versus the healthy control group. Also, immobility times in forced swimming and tail suspension tests were increased in CUMS-induced mice, but treatment with HT significantly reversed this change. HT ameliorated oxidative stress in CUMS-exposed mice by enhancing superoxide dismutase activity and reducing reactive oxygen species and malondialdehyde levels in the hippocampus. HT administration significantly suppressed microglia activation and inhibited the expression of tumor necrosis factor alpha and interleukin 1 beta in the hippocampus versus the untreated group. The expression level of glial fibrillary acidic protein (GFAP) and the number of GFAP-immunoreactive astrocytes in the hippocampus were significantly augmented by HT. Furthermore, HT treatment increased the expression of hippocampal brain-derived neurotrophic factor (BDNF), phosphorylated tropomyosin receptor kinase B (p-TrkB), and phosphorylated c-AMP response element binding protein (p-CREB) compared with the untreated CUMS group. Overall, HT improved CUMS-induced depressive-like behaviors in mice by alleviating oxidative stress and neuroinflammation and by enhancing the BDNF/TrkB/CREB signaling pathway.

Tilapia (Oreochromis mossambicus) skin high value-added compounds have not been fully utilized in tilapia processing. Here, the protective effects of tilapia skin peptides (TSP) on primary ovarian failure (POF) and their underlying mechanisms in mice were investigated. Cyclophosphamide (CP) was injected intraperitoneally (ip) for 14 days (10 mg kg⁻¹ d⁻¹) to establish a mouse model of POF. At the same time, the mice were given intragastrically (ig) TSP for 30 days (250 mg kg⁻¹ d⁻¹, 500 mg kg⁻¹ d⁻¹, and 1000 mg kg⁻¹ d⁻¹, respectively). The ovarian index, estrous cycle, hormone level, changes in the number of follicles at various levels, and biochemical tests were carried out at the end of the experiment. The body weight and ovarian index of mice in the POF group were markedly lower than that of the control group. Treatment with TSP reversed these changes significantly. TSP administration significantly restored the estrous cycle disorder of the mice versus that of the POF group. The level changes of progesterone (P), estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) induced by CP were significantly reversed by TSP treatment. TSP inhibited oxidative stress in CP-induced mice by enhancing the total superoxide dismutase (T-SOD) activity and reducing malondialdehyde (MDA) levels in the ovaries. TSP improved the apoptosis of ovarian granulosa cells in CP-induced mice compared with the POF group. Furthermore, TSP regulated the Bcl-2/Bax/caspase-3 apoptosis pathway and enhanced the Nrf2/HO-1 signaling pathway. In conclusion, TSP could improve CP-induced POF via alleviating ovarian oxidative stress and granulosa cell apoptosis.

KD improves depression-like behaviors induced by CUMS by reducing neuroinflammation and promoting neurogenesis.

Dry eye disease (DED) is a common chronic ophthalmic disorder, and there is no effective treatment to cure it. It is urgent to find new antidry eye compounds. Here, the effects and underlying mechanisms of tilapia skin peptides (TSP) on DED were investigated. In vitro, human corneal epithelial cells (HCECs) were cultured in a hypertonic medium containing TSP for 12h. The MTT assay, calcein-AM/PI staining, reactive oxygen (ROS) analysis, and western blot were performed at the end of the experiments. In the in vivo model of DED, mice eyes were dropped with 0.3 benzalkonium chloride (BAC) and 0.1% TSP for 14 days. Mice were treated with BAC and TSP twice daily with a 10-hour time interval between treatments. After treatment, phenolic red cotton experiment, tear ferning test, and histology assay were carried out. In vitro, TSP significantly restored the cell viability of HCECs challenged by NaCl. In vivo, tear secretion function and tear fern-like crystal levels were considerably improved in the DED group after treatment with TSP. Mechanically, TSP impend the DED development by regulating Bax/Bcl-2 signal pathway, inhibiting iNOS and COX-2 protein expression, moderating ROS/Nrf2/HO-1 axis, inhibiting cell apoptosis in the corneal regions, increasing the number of conjunctival goblet cells, and arresting corneal epithelial thinning. In conclusion, TSP ameliorated DED-like disorder in BAC-induced DED mice and cell damage in NaCl-induced HCECs. TSP improved DED by suppressing apoptosis, inflammation, and oxidative stress. Consequently, this study reveals the beneficial activity of TSP in DED.

RTEE ameliorates depressive-like behaviors in mice by alleviating hippocampal neuroinflammation and apoptosis, and rescuing neurogenesis.