Salidroside alleviates simulated microgravity-induced bone loss by activating the Nrf2/HO-1 pathway.

BACKGROUND: Bone loss caused by microgravity exposure presents a serious threat to the health of astronauts, but existing treatment strategies have specific restrictions. This research aimed to investigate whether salidroside (SAL) can mitigate microgravity-induced bone loss and its underlying mechanism. METHODS: In this research, we used hindlimb unloading (HLU) and the Rotary Cell Culture System (RCCS) to imitate microgravity in vivo and in vitro. RESULTS: The results showed that salidroside primarily enhances bone density, microstructure, and biomechanical properties by stimulating bone formation and suppressing bone resorption, thereby preserving bone mass in HLU rats. In MC3T3-E1 cells cultured under simulated microgravity in rotary wall vessel bioreactors, the expression of osteogenic genes significantly increased after salidroside administration, indicating that salidroside can promote osteoblast differentiation under microgravity conditions. Furthermore, the Nrf2 inhibitor ML385 diminished the therapeutic impact of salidroside on microgravity-induced bone loss. Overall, this research provides the first evidence that salidroside can mitigate bone loss induced by microgravity exposure through stimulating the Nrf2/HO-1 pathway. CONCLUSION: These findings indicate that salidroside has great potential for treating space-related bone loss in astronauts and suggest that Nrf2/HO-1 is a viable target for counteracting microgravity-induced bone damage.

Salidroside enhances NO bioavailability and modulates arginine metabolism to alleviate pulmonary arterial hypertension.

BACKGROUND: Salidroside (SAL), derived from Rhodiola, shows protective effects in pulmonary arterial hypertension (PAH) models, but its mechanisms are not fully elucidated. OBJECTIVES: Investigate the therapeutic effects and the mechanism of SAL on PAH. METHODS: Monocrotaline was used to establish a PAH rat model. SAL's impact on oxidative stress and inflammatory responses in lung tissues was analyzed using immunohistochemistry, ELISA, and Western blot. Untargeted metabolomics explored SAL's metabolic regulatory mechanisms. RESULTS: SAL significantly reduced mean pulmonary artery pressure, right ventricular hypertrophy, collagen deposition, and fibrosis in the PAH rats. It enhanced antioxidant enzyme levels, reduced inflammatory cytokines, and improved NO bioavailability by upregulating endothelial nitric oxide synthase (eNOS), soluble guanylate cyclase (sGC), cyclic guanosine monophosphate (cGMP), and protein kinase G (PKG) and decreases the expression of endothelin-1 (ET-1). Metabolomics indicated SAL restored metabolic balance in PAH rats, particularly in arginine metabolism. CONCLUSIONS: SAL alleviates PAH by modulating arginine metabolism, enhancing NO synthesis, and improving pulmonary vascular remodeling.

Moscatilin, a potential therapeutic agent for cancer treatment: insights into molecular mechanisms and clinical prospects.

Moscatilin, a bibenzyl derivative from the Dendrobium genus, has been traditionally used in Chinese medicine. Recent studies suggest its potential as a powerful anticancer agent due to its diverse pharmacological properties.This review aims to consolidate current research on moscatilin's anticancer mechanisms, structure-activity relationships, and therapeutic potential to assess its viability for clinical use. A literature search was performed in PubMed/MedLine, Scopus, and Web of Science.The search focused on "cancer," "moscatilin," "anticancer," "bioactivity," "dendrobium," and "pharmacological properties." Relevant studies on molecular mechanisms, preclinical and clinical efficacy, and bioavailability were reviewed. Moscatilin exhibits significant anticancer effects in lung, breast, colorectal, and pancreatic cancers. It induces apoptosis via the JNK/SAPK pathway, inhibits cell proliferation, and suppresses metastasis. Structure-activity relationship studies reveal that phenolic groups and a two-carbon bridge are crucial for its efficacy. Additionally, moscatilin shows good bioavailability and a favorable safety profile, with low toxicity to healthy cells. Moscatilin demonstrates considerable potential as an anticancer agent, targeting multiple cancer progression pathways. Further clinical trials are essential to confirm its therapeutic efficacy and safety in humans.

Combinatorial therapy with sub-effective Ro25-6981 and ZL006 ameliorates depressive-like behavior in single or combined stressed male mice.

Major depression is a severe neuropsychiatric disorder that poses a significant challenge to health. However, development of an effective therapy for the disease has long been difficult. Here, we investigate the efficacy of a novel combinatorial treatment employing sub-effective doses of Ro25-6981, an antagonist targeting GluN2B-containing NMDA receptors, in conjunction with ZL006, an inhibitor of the PSD95/nNOS, on mouse models of depression. We employed social isolation, chronic restraint stress, or a combination of both to establish a depressed mouse model. Treatment with the drug combination reduced depressive-like behaviors without affecting locomotor activity in mice subjected to social isolation or chronic restraint stress. Furthermore, the combination therapy ameliorated depressive-like behaviors induced by combined stress of chronic restraint followed by social isolation. Mechanistic studies revealed that the combined treatment downregulated the hippocampal nitric oxide level. However, the therapeutic benefits of this combination were negated by the activation of NMDA receptors with a low dose of NMDA or by increasing nitric oxide levels with l-arginine. Moreover, the combinatorial treatment had negligible effects on object memory and contextual fear memory. Our data establish a combined therapy paradigm, providing a potential strategy targeting major depression.

Therapeutic potential of salidroside in type I diabetic erectile dysfunction: Attenuation of oxidative stress and apoptosis via the Nrf2/HO-1 pathway.

The primary objective of this work was to delve into the potential therapeutic advantages and dissect the molecular mechanisms of salidroside in enhancing erectile function in rats afflicted with diabetic microvascular erectile dysfunction (DMED), addressing both the whole-animal and cellular dimensions.We established a DMED model in Sprague‒Dawley (SD) rats and conducted in vivo experiments. The DMED rats were administered varying doses of salidroside, the effects of which on DMED were compared. Erectile function was evaluated by applying electrical stimulation to the cavernous nerves and measuring intracavernous pressure in real time. The penile tissue underwent histological examination and Western blotting. Hydrogen peroxide (H2O2) was employed in the in vitro trial to induce an oxidative stress for the purpose of identifying alterations in cell viability. The CCK-8 assay was used to measure the viability of corpus cavernous smooth muscle cells (CCSMCs) treated with vs. without salidroside. Flow cytometry was utilized to detect alterations in intracellular reactive oxygen species (ROS). Apoptosis was assessed through Western blotting and TdT-mediated dUTP nick-end labelling (TUNEL). Animal and cellular experiments indicate that the Nrf2/HO-1 signalling pathway may be upregulated by salidroside, leading to the improvement of erectile function in diabetic male rats by alleviating oxidative stress and reducing apoptosis in corpus cavernosum tissue.

Efficacy of GluN2B-Containing NMDA receptor antagonist for antitumor and antidepressant therapy in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the predominant subtype of lung cancer. Evidence suggests that the ionotropic glutamate receptor N-methyl-D-aspartate (NMDA) receptor, a critical molecule in the central nervous system, is expressed in NSCLC. However, the specific expression patterns, subcellular localization, functional modulation, and pathological implications of NMDA receptor subtypes in NSCLC have not been fully elucidated. In this study, we employed a multi-disciplinary approach, combining biochemical and molecular biology with electrophysiological recordings and behavioral assays, to investigate these aspects. We reveal the expression of GluN2B-containing NMDA receptors in A549 and H460 NSCLC cell lines and the induction of NMDA receptor-mediated currents by glutamate in A549 cells. Furthermore, the GluN2B-specific inhibitors ifenprodil and Ro 25-6981 significantly reduced cell viability and migration, while promoting apoptosis. Importantly, intraperitoneal administration of ifenprodil in nude mice inhibited the growth of subcutaneous tumors derived from A549 and H460 cells and ameliorated depression-like behaviors. These findings underscore the potential antiproliferative effects of ifenprodil and Ro 25-6981 and suggest that GluN2B-containing NMDA receptors may represent novel therapeutic targets for NSCLC, with the added benefit of potential antidepressant action.

Evaluating the Impact of Oleocanthal and Oleacein on Skin Aging: Results of a Randomized Clinical Study.

The prevalence of skin aging and the request for effective treatments have driven dermatological research towards natural solutions. This study investigates the anti-aging efficacy of two bioactive natural polyphenols, Oleocanthal and Oleacein, in a skincare formulation. A single-blind, randomized clinical trial involved 70 participants, using a comprehensive exclusion criterion to ensure participant safety and study integrity. Participants applied the Oleocanthal and Oleacein 1% serum formulation twice daily for 30 days. The efficacy was objectively assessed using the VISIA® Skin Analysis System at baseline, after 15 days, and after 30 days. Results indicated significant wrinkle reduction in most groups. For women aged 45-79 years, the mean change was -33.91% (95% CI: -46.75% to -21.07%). For men aged 20-44 years, it was -51.93% (95% CI: -76.54% to -27.33%), and for men aged 45-79 years, it was -46.56% (95% CI: -58.32% to -34.81%). For women aged 20-44 years, the change was -25.68% (95% CI: -63.91% to 12.54%), not statistically significant. These findings highlight the potential of EVOO-derived polyphenols in anti-aging skincare, particularly for older adults. This research paves the way for further exploration into natural compounds in dermatology, particularly for aging skin management.

Exploring the Role of Phenolic Compounds in Chronic Kidney Disease: A Systematic Review.

Chronic kidney disease (CKD) presents a formidable global health concern, affecting one in six adults over 25. This review explores the potential of phenolic compounds in managing CKD and its complications. By examining the existing research, we highlight their diverse biological activities and potential to combat CKD-related issues. We analyze the nutritional benefits, bioavailability, and safety profile of these compounds. While the clinical evidence is promising, preclinical studies offer valuable insights into underlying mechanisms, optimal dosages, and potential side effects. Further research is crucial to validate the therapeutic efficacy of phenolic compounds for CKD. We advocate for continued exploration of their innovative applications in food, pharmaceuticals, and nutraceuticals. This review aims to catalyze the scientific community's efforts to leverage phenolic compounds against CKD-related challenges.

Acteoside delays the fibrosis process of diabetic nephropathy by anti-oxidation and regulating the autophagy-lysosome pathway.

Renal fibrosis is the final pathological change of kidney disease, it has also been recognized to be critical for the final progression of diabetic nephropathy (DN) to kidney failure. Acteoside (ACT) is a phenylethanoid glycoside widely distributed in dicotyledonous plants. It has many pharmacological activities, such as anti-oxidation, anti-inflammation, anti-cancer, neuroprotection, cardiovascular protection, anti-diabetes, bone and cartilage protection, liver and kidney protection, and antibacterial activity. This study aims to investigate the protective effects of ACT on renal interstitial fibrosis in rats with DN induced by intraperitoneal injection of streptozocin (STZ) combined with unilateral nephrectomy and its mechanism. In vivo and in vitro, the effects of ACT on reactive oxygen species (ROS) level, oxidative tubular injury, as well as damage of autophagic flux and lysosome in the DN model were detected. Results indicate that administration of ACT delayed the progression of renal interstitial fibrosis in DN by anti-oxidation and regulating the autophagy-lysosome pathway, which may potentially be attributed to the regulatory influence of ACT on transcription factor EB (TFEB).

Salidroside inhibits the ferroptosis to alleviate lung ischemia reperfusion injury via the JAK2/STAT3 signalling pathway.

OBJECTIVE: The present study aims to investigate the protective potential of salidroside in both lung ischemia/reperfusion injury (LIRI) mice model and cell hypoxia/reoxygenation (H/R)model and the involvement of ferroptosis and JAK2/STAT3 pathway. MATERIALS AND METHODS: After we established the IR-induced lung injury model in mice, we administered salidroside and the ferroptosis inhibitor, ferrostatin-1, then assessed the lung tissue injury, ferroptosis (levels of reactive oxygen species level, malondialdehyde and glutathione), and inflammation in lung tissues. The levels of ferroptosis-related proteins (glutathione peroxidase 4, fibroblast-specific protein 1, solute carrier family 1 member 5 and glutaminase 2) in the lung tissue were measured with Western blotting. Next, BEAS-2B cells were used to establish an H/R cell model and treated with salidroside or ferrostatin-1 before the cell viability and the levels of lactate dehydrogenase (LDH), inflammatory factor, ferroptosis-related proteins were measured. The activation of the JAK2/STAT3 signaling pathway was measured with Western blotting, then its role was confirmed with STAT3 knockdown. RESULTS: Remarkably, salidroside was found to alleviate ferroptosis, inflammation, and lung injury in LIRI mice and the cell injury in H/R cell model. Severe ferroptosis were observed in LIRI mice models and H/R-induced BEAS-2B cells, which was alleviated by salidroside. Furthermore, salidroside could inhibit JAK2/STAT3 activation induced by LIRI. STAT3 knockdown could enhance the effect of salidroside treatment on H/R-induced cell damage and ferroptosis in vitro. CONCLUSIONS: Salidroside inhibits ferroptosis to alleviate lung ischemia reperfusion injury via the JAK2/STAT3 signaling pathway.

Natural products for the treatment of age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is a chronic retinal disease that significantly influences the vision of the elderly. PURPOSE: There is no effective treatment and prevention method. The pathogenic process behind AMD is complex, including oxidative stress, inflammation, and neovascularization. It has been demonstrated that several natural products can be used to manage AMD, but systematic summaries are lacking. STUDY DESIGN AND METHODS: PubMed, Web of Science, and ClinicalTrials.gov were searched using the keywords "Biological Products" AND "Macular Degeneration" for studies published within the last decade until May 2023 to summarize the latest findings on the prevention and treatment of age-related macular degeneration through the herbal medicines and functional foods. RESULTS: The eligible studies were screened, and the relevant information about the therapeutic action and mechanism of natural products used to treat AMD was extracted. Our findings demonstrate that natural substances, including retinol, phenols, and other natural products, prevent the development of new blood vessels and protect the retina from oxidative stress in cells and animal models. However, they have barely been examined in clinical studies. CONCLUSION: Natural products could be highly prospective candidate drugs used to treat AMD, and further preclinical and clinical research is required to validate it to control the disease.

The effects of Anchusa azurea methanolic extract on burn wound healing: Histological, antioxidant, and anti-inflammatory evaluation.

Anchusa azurea one of the medicinal plants that has been traditionally used for treat burn wounds. However, the traditional claim that A.azurea can hasten burn wound healing has not been supported by scientific studies. This experiment used a male Wistar rats model to investigate the activity of A. azurea aerial parts methanolic extract in burn wound healing. To determine their ability to help in healing burn wounds in rat models, the active components of the aerial parts of A. azurea were extracted with 80% methanol, then, 1% and 10% ointments were prepared from the extract, and applied topically. The LCMS chromatography of A. azurea plant extract showed different active ingredients, including phenolic compounds, flavonoids, fatty acids, and others. The plant extract's investigated as anti-inflammatory, antioxidant, and histological effects on the burn wound healing process. The results showed a significant (p-value < 0.025) rate of burn wound healing with 78.6% and 84.8% contraction, respectively using 1% and 10% (w/w) extract ointments after 12 days. These results were corroborated by histological observations such as collagen deposition, re-epithelialization, and repair of the remaining skin tissues without any sign of cutaneous toxicity. The plant extract showed significant (p-value < 0.025) antioxidant effect at the highest tested dose of 500 µg/mL, scavenging 89.78% of the DPPH with an IC50 of 213.6 µg/mL. These results confirmed by histological changes observations of collagen deposition, re-epithelialization, and reformation of remaining skin tissues without any signs of dermal toxicity. The plant extract exhibited significant (p-value < 0.025) level of antioxidant agents, by scavenging 89.78% of the DPPH at 500 µg/mL with IC50 of 213.6 µg/mL. Additionally, all pro-inflammatory cytokines examined, including IL-6 and IL-10, the results exhibited reduction in IL-6 level and increase IL-10 level. The aerial extract of the A. azurea plant revealed a wealth of several significant active ingredients, including phenolic compounds, flavonoids, fatty acids, and others, suggesting the potential for anti-inflammatory, burn wound-healing, and antioxidant medications. These findings can open an avenue to find new therapeutics for burn wounds healing, anti-inflammatory and antioxidant properties.

The Glabridin from Huangqin Decoction Prevents the Development of Ulcerative Colitis into Colitis-Associated Colorectal Cancer by Modulating MMP1/MMP3 Activity.

BACKGROUND AND AIM: Huangqin decoction (HQD) is a Chinese medicine used to treat colitis and colorectal cancer (CRC). However, the specific compounds and mechanisms of HQD remain unclear despite its good curative clinical results. Through bioinformatics, network pharmacology, and experiments, this study aims to explore the progressive mechanisms of colitis-associated colorectal cancer (CAC) from ulcerative colitis (UC) while examining the protective effects of HQD and its compounds against this. METHODS: Bioinformatics was utilized to identify the hub genes between UC and CRC, and their clinical predictive significance, function, and expression were validated. Employing network pharmacology in combination with hub genes, key targets of HQD for preventing the development of UC into CAC were identified. Molecular docking and molecular dynamics (MD) were utilized to procure compounds that effectively bind to these targets and their transcription factors (TFs). Finally, the expression and mechanism of key targets were demonstrated in mice with UC or CAC. RESULTS: (1) Joint analysis of UC and CRC gene sets resulted in 14 hub genes, mainly related to extracellular matrix receptor binding, biological processes in the extracellular matrix, focal adhesion and neutrophil migration; (2) Network pharmacology results show HQD has 133 core targets for treating UC and CRC, acting on extracellular matrix, inflammatory bowel disease, chemical carcinogen receptor activation and other pathways; (3) The intersection of hub genes and core targets yielded two key targets, MMP1 and MMP3; (4) STAT3 is a shared TF of MMP1 and MMP3. (5) Molecular docking and MD verified that the dockings between Glabridin and STAT3/MMP1/MMP3 are stable and reliable; (6) In murine vivo experiments verified that Glabridin reduces inflammation, extracellular matrix degradation, and the occurrence of epithelial-mesenchymal transition to prevent UC transforming into CAC by inhibiting the phosphorylation of STAT3 and regulating the activity of MMP1/3.

The role of Cistanches Herba and its ingredients in improving reproductive outcomes: A comprehensive review.

BACKGROUND: Infertility patients account for an astonishing proportion of individuals worldwide. Due to its complex etiology and challenging treatment, infertility has imposed significant psychological and economic burdens on many patients. C. Herba (Cistanche tubulosa (Schenk) Wight and Cistanche deserticola Ma), renowned as one of the most prominent Chinese herbal medicines (CHMs), is abundant in diverse bioactive compounds that exhibit therapeutic effects on many diseases related to oxidative stress (OS) and disorders of sex hormone levels. OBJECTIVE: Due to the limited drugs currently used in clinical practice to improve reproductive outcomes and their inevitable side effects, developing safe and effective new medications for infertility is of significance. This article comprehensively reviewed the phytochemicals of C. Herba, focusing on their efficacy and mechanisms on infertility and their safety for the first time, aiming to offer valuable insights for the development and application of C. Herba, and for developing novel strategies for treating infertility. METHODS: We used "Cistanche" and its known bioactive components in combination with "sperm", "testicles", "epididymis", "ovaries", "uterus", and "infertility" as keywords to search in PubMed, Web of Science, Scopus and CNKI up to November 2023. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guideline was followed. RESULTS: The therapeutic effects of C. Herba on infertility are mainly attributed to echinacoside (ECH), verbascoside (VB), salidroside (SAL), polysaccharides, and betaine. They can effectively improve spermatogenic dysfunction, gonadal dysfunction and erectile dysfunction (ED) by exerting anti-oxidation, sex hormones regulation and anti-hypoxia. Moreover, they can also improve premature ovarian failure (POF), ovarian and uterine cancer, oocyte maturation by exerting anti-oxidation, anti-apoptosis, and anti-cancer. C. Herba and its active ingredients also exhibit pleasing safety. CONCLUSION: C. Herba is a promising source of natural medicine for infertility. Additionally, compared to current therapeutic drugs, its favorable safety also supports its development as a nutritional supplement. However, high-quality clinical studies are required to validate its effectiveness for the development of novel therapeutic strategies.

Identification of an inhibitory pocket in falcilysin provides a new avenue for malaria drug development.

Identification of new druggable protein targets remains the key challenge in the current antimalarial development efforts. Here we used mass-spectrometry-based cellular thermal shift assay (MS-CETSA) to identify potential targets of several antimalarials and drug candidates. We found that falcilysin (FLN) is a common binding partner for several drug candidates such as MK-4815, MMV000848, and MMV665806 but also interacts with quinoline drugs such as chloroquine and mefloquine. Enzymatic assays showed that these compounds can inhibit FLN proteolytic activity. Their interaction with FLN was explored systematically by isothermal titration calorimetry and X-ray crystallography, revealing a shared hydrophobic pocket in the catalytic chamber of the enzyme. Characterization of transgenic cell lines with lowered FLN expression demonstrated statistically significant increases in susceptibility toward MK-4815, MMV000848, and several quinolines. Importantly, the hydrophobic pocket of FLN appears amenable to inhibition and the structures reported here can guide the development of novel drugs against malaria.

Inhalation of 2, 4-di-tert-butylphenol-Loaded micelles suppresses respiratory syncytial virus infection in mice.

Human respiratory syncytial virus (RSV) is a common cause of respiratory infections in infants, young children, and elderly people. However, there are no effective treatments or vaccines available in most countries. In this study, we explored the anti-RSV potential of 2, 4-Di-tert-butylphenol (2, 4-DTBP), a compound derived from Houttuynia cordata Thunb. To overcome the poor solubility of 2, 4-DTBP, we encapsulated it in polymeric micelles and delivered it by inhalation. We found that 2, 4-DTBP-loaded micelles inhibited RSV infection in vitro and improved survival, lung pathology, and viral clearance in RSV-infected mice. Our results suggested that 2, 4-DTBP-loaded micelle is a promising novel therapeutic agent for RSV infection.

Evaluation of the protective and therapeutic effects of extra virgin olive oil rich in phenol in experimental model of neonatal necrotizing enterocolitis by clinical disease score, inflammation, apoptosis, and oxidative stress markers.

BACKGROUND AND AIM: Necrotizing Enterocolitis (NEC) is an inflammation-associated ischemic necrosis of the intestine. To investigate the effects of extra virgin olive oil (EVOO) on inflammation, oxidative stress, apoptosis, and histological changes in NEC-induced newborn rats. MATERIALS AND METHODS: 24 rats were randomly divided into three groups: control, NEC and NEC + EVOO. NEC induction was performed using hypoxia-hyperoxia, formula feeding, and cold stress. The NEC + EVOO group received 2 ml/kg EVOO with high phenolic content by gavage twice a day for 3 days. 3 cm of bowel including terminal ileum, cecum, and proximal colon was excised. RESULTS: Weight gain and clinical disease scores were significantly higher in the NEC + EVOO group than in the NEC group (p < 0.001). EVOO treatment caused significant decreases in IL1ß, IL6 levels (p = 0.016, p = 0.029 respectively) and EGF, MDA levels (p = 0.032, p = 0.013 respectively) compared to NEC group. Significant decreases were observed in IL6 gene expression in the NEC + EVOO group compared to the NEC group (p = 0.002). In the group NEC + EVOO, the number of Caspase-3 positive cells was found to be significantly reduced (p < 0.001) and histopathological examination revealed minimal changes and significantly lower histopathological scores (p < 0.001). CONCLUSION: Phenol-rich EVOO prevents intestinal damage caused by NEC by inhibiting inflammation, oxidative stress, apoptosis.

The Promising Role of Polyphenols in Skin Disorders.

The biochemical characteristics of polyphenols contribute to their numerous advantageous impacts on human health. The existing research suggests that plant phenolics, whether consumed orally or applied directly to the skin, can be beneficial in alleviating symptoms and avoiding the development of many skin disorders. Phenolic compounds, which are both harmless and naturally present, exhibit significant potential in terms of counteracting the effects of skin damage, aging, diseases, wounds, and burns. Moreover, polyphenols play a preventive role and possess the ability to delay the progression of several skin disorders, ranging from small and discomforting to severe and potentially life-threatening ones. This article provides a concise overview of recent research on the potential therapeutic application of polyphenols for skin conditions. It specifically highlights studies that have investigated clinical trials and the use of polyphenol-based nanoformulations for the treatment of different skin ailments.

Extra-Virgin Olive Oil in Alzheimer's Disease: A Comprehensive Review of Cellular, Animal, and Clinical Studies.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is characterized by several pathological hallmarks, including the deposition of amyloid-ß (Aß) plaques, neurofibrillary tangles, blood-brain barrier (BBB) dysfunction, increased oxidative stress, and neuroinflammation. Current treatment options include monoclonal antibody drugs, acetylcholinesterase, and n-methyl-d-aspartate (NMDA) antagonists. Although those treatments provide some improvements in patients' quality of life, they fail to prevent or cure AD. Current research aims to identify novel targets and tools for AD prevention and modification. In this context, several studies showed the beneficial effect of the Mediterranean diet in the prevention and treatment of AD. One integral component of the Mediterranean diet is olive oil and extra-virgin olive oil (EVOO), which is high in phenolic compounds. EVOO and other olive-related phenolic compounds have been shown to reduce the risk of developing mild cognitive impairment (MCI) and AD. In this review, we discuss the mechanisms by which EVOO and phenolic compounds exert neuroprotective effects, including modulation of AD pathologies and promotion of cognitive health. Findings indicate that EVOO and its phenolic constituents influence key pathological processes of AD, such as Aß aggregation, tau phosphorylation, and neuroinflammation, while also enhancing BBB integrity and reducing oxidative stress. The human studies cited reveal a consistent trend where the consumption of olive oil is associated with cognitive benefits and a decreased risk of AD and related dementias. In conclusion, EVOO and its phenolic compounds hold promising potential for the prevention and treatment of AD, representing a significant shift towards more effective strategies against this complex neurodegenerative disorder.

Induction of ferroptosis by natural phenols: A promising strategy for cancer therapy.

In recent years, heightened interest surrounds the exploration of natural phenols as potential agents for cancer therapy, specifically by inducing ferroptosis, a unique form of regulated cell death characterized by iron-dependent lipid peroxidation. This review delves into the roles of key natural phenols, flavonoids, phenolic acids, curcumin, and stilbenes, in modulating ferroptosis and their underlying mechanisms. Emphasizing the significance of amino acid, lipid, and iron metabolism, the study elucidates the diverse pathways through which these phenols regulate ferroptosis. Notably, curcumin, a well-known polyphenol, exhibits multifaceted interactions with cellular components involved in ferroptosis regulation, providing a distinctive therapeutic avenue. Stilbenes, another phenolic class, demonstrate promising potential in influencing lipid metabolism and iron-dependent processes, contributing to ferroptotic cell death. Understanding the intricate interplay between these natural phenols and ferroptosis not only illuminates complex cellular regulatory networks but also unveils potential avenues for novel cancer therapies. Exploring these compounds as inducers of ferroptosis presents a promising strategy for targeted cancer treatment, capitalizing on the delicate balance between cellular metabolism and regulated cell death mechanisms. This article synthesizes current knowledge, aiming to stimulate further research into the therapeutic potential of natural phenols in the context of ferroptosis-mediated cancer therapy.