The increasing emergence and dissemination of multidrug-resistant (MDR) bacterial pathogens have intensified the need for new antibiotics and alternative therapeutic strategies. Flavonoids, a diverse group of bioactive natural compounds found in plants, have shown significant promise as antibacterial agents. Flavonoids inhibit bacterial growth through various mechanisms, including disruption of cell wall synthesis, prevention of biofilm formation, disruption of cell membrane integrity, and inhibition of bacterial efflux pumps. These actions not only reduce bacterial viability but also enhance the efficacy of conventional antibiotics, offering a potential solution to antibiotic resistance. However, challenges such as poor bioavailability limit their clinical application. Recent advances in nanotechnology-based drug delivery systems, chemical modifications, and formulation techniques have shown promise in improving flavonoid bioavailability and therapeutic efficacy. This review evaluates the antibacterial mechanisms of flavonoids, explores their potential synergistic effects with antibiotics, and highlights strategies to overcome bioavailability issues. Our findings underscore the importance of continued research on flavonoids as promising candidates for innovative antibacterial therapies aimed at combating MDR bacterial infections.

In 2022, human breast cancer (HBC) and canine mammary tumors (CMTs) remained the most prevalent malignant tumors worldwide, with high recurrence and lethality rates, posing a significant threat to human and dog health. The development of breast cancer involves multiple signaling pathways, highlighting the need for effective inhibitory drugs that target key proteins in these pathways. This article reviews the dysregulation of the EGFR, PI3K/AKT/mTOR, Hippo, pyroptosis, and PD-1/PD-L1 signaling pathways in HBC and CMT, as well as the corresponding drugs used to inhibit tumor growth, with the aim of providing theoretical support for the development of more efficient drugs.

Crocin, a carotenoid component of Crocus sativus L. belonging to the Iridaceae family, has demonstrated cardioprotective effects. To investigate the cellular mechanisms of these cardioprotective effects, here we studied the influence of crocin on L-type Ca²⁺current (I_Ca-L), intracellular Ca²⁺ ([Ca²⁺]_i), and contraction of isolated rat cardiomyocytes by using the whole-cell patch-clamp technique and video-based edge detection and dual excitation fluorescence photomultiplier systems. Crocin inhibited I_Ca-L in a concentration-dependent manner with the half-maximal inhibitory concentration (IC₅₀) of 45 μmol/L and the maximal inhibitory effect of 72.195% ± 1.54%. Neither current–voltage relationship of I_Ca-L, reversal potential of I_Ca-L, nor the activation/inactivation of I_Ca-L was significantly changed. Crocin at 1 μmol/L reduced cell shortening by 44.64% ± 2.12% and the peak value of the Ca²⁺ transient by 23.66% ± 4.52%. Crocin significantly reduced amplitudes of myocyte shortening and [Ca²⁺]_i with an increase in the time to reach 10% of the peak (Tp) and a decrease in the time to 10% of the baseline (Tr). Thus, the cardioprotective effects of crocin may be attributed to the attenuation of [Ca²⁺]_i through the inhibition of I_Ca-L in rat cardiomyocytes and negative inotropic effects on myocardial contractility.

Isorhamnetin (ISO) is a natural flavonoid compound that has become a main research topic in recent years due to its multitargeted antitumor properties. In this paper, we systematically review the molecular basis of the inhibition of malignant tumors by ISO, including through the regulation of the cell cycle, PI3K/AKT/mTOR pathway, MAPK pathway, apoptosis/autophagy-related pathways, and the tumor microenvironment. We also explore its synergistic effects with chemotherapy/targeted therapies and its potential for clinical translation. Experimental studies have shown that ISO can not only directly inhibit tumor proliferation by inducing tumor cell cycle arrest, mitochondria-dependent apoptosis, and endoplasmic reticulum stress, but also enhance antitumor immune responses by regulating the immune microenvironment. Pharmacokinetic studies have shown that novel delivery systems, such as nano-formulations, significantly enhance the bioavailability of ISO. Notably, ISO has demonstrated unique advantages in attenuating the nephrotoxicity of chemotherapeutic agents, protecting normal cells, and reversing tumor resistance. However, the optimal dosing regimen, dose–effect relationship, and cross-species applicability need to be further validated by large-scale preclinical animal experiments and clinical trials. This paper provides a theoretical basis for the development and application of ISO for the treatment of malignant tumors and highlights its potential value in animal models.

Programmed death ligand-1 (PD-L1) is highly expressed in a variety of cancer cells and suggests a poorer prognosis for patients. The natural compound isorhamnetin (ISO) shows promise in treating cancers and causing damage to canine mammary tumor (CMT) cells. We investigated the mechanism of ISO in reducing PD-L1 expression in CMT cells. Clustered, regularly interspaced short palindromic repeat-associated protein 9 (CRISPR/Cas9) was used to mediate CD274 knockout in U27 cells. Then, monoclonal cells were screened and cultured. Nucleotide sequencing and expression of PD-L1 were detected. Additionally, we examined cell migration, invasion, and damage. Immunofluorescent staining of PD-L1 was examined in U27 cells. The signaling pathways were measured by Western blotting. Murine xenotransplantation models and murine immunocompetent allograft mammary tumor models were established to evaluate the effect of ISO therapy. Expression of Ki-67, caspase3, and PD-L1 were analyzed by immunohistochemistry. A pull-down assay was used to explore which proteins could bind to ISO. Canine EGFR protein was purified and used to detect whether it directly binds to ISO using a surface plasmon resonance assay. ISO inhibited the EGFR-STAT3-PD-L1 signaling pathway and blocked cancer growth, significantly increasing the survival rate of healthy cells. The cell membrane receptor EGFR was identified as a direct target of ISO. ISO could be exploited as an antineoplastic treatment of CMT by targeting EGFR to suppress PD-L1 expression.

In our research, we explored a natural substance called Oxymatrine, found in a traditional Chinese medicinal plant, to fight against a common bird flu virus known as H9N2. This virus not only affects birds but can also pose a threat to human health. We focused on how this natural compound can help in stopping the virus from spreading in cells that line the lungs of birds and potentially humans. Our findings show that Oxymatrine can both directly block the virus and boost the body’s immune response against it. This dual-action mechanism is particularly interesting because it indicates that Oxymatrine might be a useful tool in developing new ways to prevent and treat this type of bird flu. Understanding how Oxymatrine works against the H9N2 virus could lead to safer and more natural ways to combat viral infections in animals and humans, contributing to the health and well-being of society. The H9N2 Avian Influenza Virus (AIV) is a persistent health threat because of its rapid mutation rate and the limited efficacy of vaccines, underscoring the urgent need for innovative therapies. This study investigated the H9N2 AIV antiviral properties of Oxymatrine (OMT), a compound derived from traditional Chinese medicine, particularly focusing on its interaction with pulmonary microvascular endothelial cells (PMVECs). Employing an array of in vitro assays, including 50% tissue culture infectious dose, Cell Counting Kit-8, reverse transcription-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blot, we systematically elucidated the multifaceted effects of OMT. OMT dose-dependently inhibited critical antiviral proteins (PKR and Mx1) and modulated the expression of type I interferons and key cytokines (IFN-α, IFN-β, IL-6, and TNF-α), thereby affecting TLR3 signaling and its downstream elements (NF-κB and IRF-3). OMT’s antiviral efficacy extended beyond TLR3-mediated responses, suggesting its potential as a versatile antiviral agent. This study not only contributes to the growing body of research on the use of natural compounds as antiviral agents but also underscores the importance of further investigating the broader application of OMT for combating viral infections.