Rubus Occidentalis and its bioactive compounds against cancer: From molecular mechanisms to translational advances.

BACKGROUND: Cancer ranks as the second leading cause of death globally, imposing a significant public health burden. The rise in cancer resistance to current therapeutic agents underscores the potential role of phytotherapy. Black raspberry (BRB, Rubus Occidentalis) is a fruit rich in anthocyanins, ellagic acid, and ellagitannins. Accumulating evidence suggests that BRB exhibits promising anticancer effects, positioning it as a viable candidate for phytotherapy. PURPOSE: This article aims to review the existing research on BRB regarding its role in cancer prevention and treatment. It further analyzes the effective components of BRB, their metabolic pathways, and the potential mechanisms underlying the fruit's anticancer effects. METHODS: Ovid MEDLINE, EMBASE, Web of Science, and CENTRAL were searched through the terms of Black Raspberry, Raspberry, and Rubus Occidentali up to January 2023. Two reviewers performed the study selection by screening the title and abstract. Full texts of potentially eligible studies were retrieved to access the details. RESULTS: Out of the 767 articles assessed, 73 papers met the inclusion criteria. Among them, 63 papers investigated the anticancer mechanisms, while 10 conducted clinical trials focusing on cancer treatment or prevention. BRB was found to influence multiple cancer hallmarks by targeting various pathways. Decomposition of free radicals and regulation of estrogen metabolism, BRB can reduce DNA damage caused by reactive oxygen species. BRB can also enhance the function of nucleotide excision repair to repair DNA lesions. Through regulation of epigenetics, BRB can enhance the expression of tumor suppressor genes, inducing cell cycle arrest, and promoting apoptosis and pyroptosis. BRB can reduce the energy and nutrients supply to the cancer nest by inhibiting glycolysis and reducing angiogenesis. The immune and inflammatory microenvironment surrounding cancer cells can also be ameliorated by BRB, inhibiting cancer initiation and progression. However, the limited bioavailability of BRB diminishes its anticancer efficacy. Notably, topical applications of BRB, such as gels and suppositories, have demonstrated significant clinical benefits. CONCLUSION: BRB inhibits cancer initiation, progression, and metastasis through diverse anticancer mechanisms while exhibiting minimal side effects. Given its potential, BRB emerges as a promising phototherapeutic agent for cancer treatment.

Curcumin and analogues in mitigating liver injury and disease consequences: From molecular mechanisms to clinical perspectives.

BACKGROUND: Liver injury is a prevalent global health concern, impacting a substantial number of individuals and leading to elevated mortality rates and socioeconomic burdens. Traditional primary treatment options encounter resource constraints and high costs, prompting exploration of alternative adjunct therapies, such as phytotherapy. Curcumin demonstrates significant therapeutic potential across various medical conditions, particularly emerging as a promising candidate for liver injury treatment. PURPOSE: This study aims to provide current evidence maps of curcumin and its analogs in the context of liver injury, covering aspects of biosafety, toxicology, and clinical trials. Importantly, it seeks to summarize the intricate mechanisms modulated by curcumin. METHODS: We conducted a comprehensive search of MEDLINE, Web of Science, and Embase up to July 2023. Titles and abstracts were reviewed to identify studies that met our eligibility criteria. The screening process involved three authors independently assessing the potential of curcumin mitigating liver injury and its disease consequences by reviewing titles, abstracts, and full texts. RESULTS: Curcumin and its analogs have demonstrated low toxicity in vitro and in vivo. However, the limited bioavailability has hindered their advanced use in liver injury. This limitation can potentially be addressed by nano-curcumin and emerging drug delivery systems. Curcumin plays a role in alleviating liver injury by modulating the antioxidant system, as well as cellular and molecular pathways. The specific mechanisms involve multiple pathways, such as NF-κB, p38/MAPK, and JAK2/STAT3, and the pro-apoptosis Bcl-2/Bax/caspase-3 axis in damaged cells. Additionally, curcumin targets nutritional metabolism, regulating the substance in liver cells and tissues. The microenvironment associated with liver injury, like extracellular matrix and immune cells and factors, is also regulated by curcumin. Initial evaluation of curcumin and its analogs through 12 clinical trials demonstrates their potential application in liver injury. CONCLUSION: Curcumin emerges as a promising phytomedicine for liver injury owing to its effectiveness in hepatoprotection and low toxicity profile. Nevertheless, in-depth investigations are warranted to unravel the complex mechanisms through which curcumin influences liver tissues and overall physiological milieu. Moreover, extensive clinical trials are essential to determine optimal curcumin dosage forms, maximizing its benefits and achieving favorable clinical outcomes.

Curcumin and analogues against head and neck cancer: From drug delivery to molecular mechanisms.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is one of the most life-threatening diseases which also causes economic burden worldwide. To overcome the limitations of traditional therapies, investigation into alternative adjuvant treatments is crucial. PURPOSE: Curcumin, a turmeric-derived compound, demonstrates significant therapeutic potential in diverse diseases, including cancer. Furthermore, research focuses on curcumin analogues and novel drug delivery systems, offering approaches for improved efficacy. This review aims to provide a comprehensive overview of curcumin's current findings, emphasizing its mechanisms of anti-HNSCC effects and potential for clinical application. METHOD: An electronic search of Web of Science, MEDLINE, and Embase was conducted to identify literature about the application of curcumin or analogues in HNSCC. Titles and abstracts were screened to identify potentially eligible studies. Full-text articles will be obtained and independently evaluated by two authors to make the decision of inclusion in the review. RESULTS: Curcumin's clinical application is hindered by poor bioavailability, prompting the exploration of methods to enhance it, such as curcumin analogues and novel drug delivery systems. Curcumin could exhibit anti-cancer effects by targeting cancer cells and modulating the tumor microenvironment in HNSCC. Mechanisms of action include cell cycle arrest, apoptosis promotion, reactive oxygen species induction, endoplasmic reticulum stress, inhibition of epithelial-mesenchymal transition, attenuation of extracellular matrix degradation, and modulation of tumor metabolism in HNSCC cells. Curcumin also targets various components of the tumor microenvironment, including cancer-associated fibroblasts, innate and adaptive immunity, and lymphovascular niches. Furthermore, curcumin enhances the anti-cancer effects of other drugs as adjunctive therapy. Two clinical trials report its potential clinical applications in treating HNSCC. CONCLUSION: Curcumin has demonstrated therapeutic potential in HNSCC through in vitro and in vivo studies. Its effectiveness is attributed to its ability to modulate cancer cells and interact with the intricate tumor microenvironment. The development of curcumin analogues and novel drug delivery systems has shown promise in improving its bioavailability, thereby expanding its clinical applications. Further research and exploration in this area hold great potential for harnessing the full therapeutic benefits of curcumin in HNSCC treatment.

Depression Exacerbates Dextran Sulfate Sodium-Induced Colitis via IRF5-Mediated Macrophage Polarization.

BACKGROUND AND AIMS: Patients with inflammatory bowel disease (IBD) and concurrent depression are predisposed to severer disease activity and a worse prognosis. Macrophage polarization toward the M1 phenotype may contribute to the exacerbation of IBD with comorbid depression. Moreover, interferon regulatory factor 5 (IRF5) is involved in the pathogenesis of IBD. The aim of this study was to explore the role of IRF5 in macrophage polarization in the impact of depression upon colitis. METHODS: Depressive-like behavior was induced by repeated forced swim stress. Colon length, disease activity index (DAI), colon morphology, histology, ultrastructure of epithelial barrier, lamina propria macrophage polarization, and expression of IRF5 were compared between DSS colitis rats with and without depressive-like behavior. IRF5 shRNA was constructed to affect the rat peritoneal macrophages polarization in vitro. After IRF5 shRNA lentivirus was introduced into colon by enema, the colitis severity, lamina propria macrophage polarization, and TNF-α, IL-1ß, and IL-10 of colon tissues were measured. RESULTS: The study found severer colonic inflammation in depressed versus non-depressed DSS-colitis rats. Depressed DSS-colitis rats exhibited smaller subepithelial macrophages size and reduced intracellular granule diversity compared with nondepressed DSS-colitis rats. Increased polarization toward the M1 phenotype, elevated expression of IRF5, and co-expression of IRF5 with CD86 were found in depressed versus nondepressed DSS-colitis rats. Lentivirus-mediated shRNA interference with IRF5 expression switched rat peritoneal macrophage polarization from the M1 to the M2 phenotype, downregulated TNF-α, IL-1ß expression to a greater extent in depressed versus nondepressed colitis rats. CONCLUSIONS: IRF5-mediated macrophage polarization may likely underlie the deterioration of DSS-induced colitis caused by depression.

Potentials of nanotechnology in treatment of methicillin-resistant Staphylococcus aureus.

Abuse of antibiotics has led to the emergence of drug-resistant pathogens. Methicillin-resistant Staphylococcus aureus (MRSA) was reported just two years after the clinical use of methicillin, which can cause severe infections with high morbidity and mortality in both community and hospital. The treatment of MRSA infection is greatly challenging since it has developed the resistance to almost all types of antibiotics. As such, it is of great significance and importance to develop novel therapeutic approaches. The fast development of nanotechnology provides a promising solution to this dilemma. Functional nanomaterials and nanoparticles can act either as drug carriers or as antibacterial agents for antibacterial therapy. Herein, we aim to provide a comprehensive understanding of the drug resistance mechanisms of MRSA and discuss the potential applications of some functionalized nanomaterials in anti-MRSA therapy. Also, the concerns and possible solutions for the nanomaterials-based anti-MRSA therapy are discussed.