Ischemic stroke (IS) is a common neurological disorder associated with high disability rates and mortality rates. At present, recombinant tissue plasminogen activator (r-tPA) is the only US(FDA)-approved drug for IS. However, due to the narrow therapeutic window and risk of intracerebral hemorrhage, r-tPA is currently used in less than 5% of stroke patients. Natural compounds have been widely used in the treatment of IS in China and have a wide range of therapeutic effects on IS by regulating multiple targets and signaling pathways. The keywords “ischemia stroke, traditional Chinese Medicine, Chinese herbal medicine, natural compounds” were used to search the relevant literature in PubMed and other databases over the past five years. The results showed that JAK/STAT, NF-κB, MAPK, Notch, Nrf2, and PI3K/Akt are the key pathways, and SIRT1, MMP9, TLR4, HIF-α are the key targets for the natural compounds from traditional Chinese medicine in treating IS. This study aims to update and summarize the signaling pathways and targets of natural compounds in the treatment of IS, and provide a base of information for the future development of effective treatments for IS.

Diabetic retinopathy (DR) is a universal microvascular complication of diabetes mellitus (DM), which is the main reason for global sight damage/loss in middle-aged and/or older people. Current clinical analyses, like hemoglobin A1c, possess some importance as prognostic indicators for DR severity, but no effective circulating biomarkers are used for DR in the clinic currently, and studies on the latent pathophysiology remain lacking. Recent developments in omics, especially metabolomics, continue to disclose novel potential biomarkers in several fields, including but not limited to DR. Therefore, based on the overview of metabolomics, we reviewed progress in analytical technology of metabolomics, the prominent roles and the current status of biomarkers in DR, and the update of potential biomarkers in various DR-related samples via metabolomics, including tear as well as vitreous humor, aqueous humor, retina, plasma, serum, cerebrospinal fluid, urine, and feces. In this review, we underscored the in-depth analysis and elucidation of the common biomarkers in different biological samples based on integrated results, namely, alanine, lactate, and glutamine. Alanine may participate in and regulate glucose metabolism through stimulating N-methyl-D-aspartate receptors and subsequently suppressing insulin secretion, which is the potential pathogenesis of DR. Abnormal lactate could cause extensive oxidative stress and neuroinflammation, eventually leading to retinal hypoxia and metabolic dysfunction; on the other hand, high-level lactate may damage the structure and function of the retinal endothelial cell barrier via the G protein-coupled receptor 81. Abnormal glutamine indicates a disturbance of glutamate recycling, which may affect the activation of Müller cells and proliferation via the PPP1CA–YAP–GS–Gln–mTORC1 pathway.

Although cancer chemopreventive agents have been confirmed to effectively protect high-risk populations from cancer invasion or recurrence, only over ten drugs have been approved by the U.S. Food and Drug Administration. Therefore, screening potent cancer chemopreventive agents is crucial to reduce the constantly increasing incidence and mortality rate of cancer. Considering the lengthy prevention process, an ideal chemopreventive agent should be nontoxic, inexpensive, and oral. Natural compounds have become a natural treasure reservoir for cancer chemoprevention because of their superior ease of availability, cost-effectiveness, and safety. The benefits of natural compounds as chemopreventive agents in cancer prevention have been confirmed in various studies. In light of this, the present review is intended to fully delineate the entire scope of cancer chemoprevention, and primarily focuses on various aspects of cancer chemoprevention based on natural compounds, specifically focusing on the mechanism of action of natural compounds in cancer prevention, and discussing in detail how they exert cancer prevention effects by affecting classical signaling pathways, immune checkpoints, and gut microbiome. We also introduce novel cancer chemoprevention strategies and summarize the role of natural compounds in improving chemotherapy regimens. Furthermore, we describe strategies for discovering anticancer compounds with low abundance and high activity, revealing the broad prospects of natural compounds in drug discovery for cancer chemoprevention. Moreover, we associate cancer chemoprevention with precision medicine, and discuss the challenges encountered in cancer chemoprevention. Finally, we emphasize the transformative potential of natural compounds in advancing the field of cancer chemoprevention and their ability to introduce more effective and less toxic preventive options for oncology.

Ferulic acid (FA), a hydroxycinnamic acid derivative, is a key bioactive component in traditional medicinal plants including Angelica sinensis and Asafoetida. Accumulating evidence supports its therapeutic efficacy in inflammatory disorders, such as rheumatoid arthritis (RA) and ulcerative colitis (UC). FA exerts anti-inflammatory effects through (1) the regulation of inflammatory cytokine levels; (2) modulation of signaling pathways such as nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and janus kinase/signal transducer and activator of transcription (JAK/STAT); (3) amelioration of oxidative stress; and (4) regulation of immune cell homeostasis. At the pharmacokinetic level, studies show that FA is rapidly absorbed but exhibits low bioavailability, mainly due to the influence of metabolic pathways and food matrix characteristics. This review systematically summarizes the literature on the anti-inflammatory effects of FA, covering molecular mechanisms, pharmacokinetic characteristics, and application scenarios. Preclinical studies show that FA has low toxicity and good safety, demonstrating potential for development as a novel anti-inflammatory drug. However, its clinical translation is hindered by bottlenecks such as low bioavailability and insufficient human clinical data. Future research should prioritize developing novel drug delivery systems and conducting large-scale clinical trials to facilitate its clinical translation.

The discovery of effective constituents of traditional Chinese medicine (TCM) is an important approach in new drug development. Several well-known drugs, such as artemisinin, berberine, and ephedrine have been developed using this approach. However, the efficacy and safety of TCM, two key issues for drug development based on TCM clinical experience, remain unclear worldwide. The discovery strategy of relevant constituents is the most important step for determining efficacy and safety, which still a key scientific problem that restricts the development of new drugs. Furthermore, TCM formulas used as clinical drugs address a specific TCM syndrome (Zheng), and the complexity of the formula and vagueness of the syndrome make the identification of the effective constituents related to clinical effectiveness challenging. Over decades, researchers have developed transdisciplinary technologies and research methodologies to identify effective constituents in vivo. In this paper, the history of strategy development for identifying the effective constituents related to the clinical efficacy of TCM is reviewed and summarized. The main approaches include the phytochemical method, which involves the classical systematic separation and screening (extraction, separation, purification, structure identification, and activity test); bioactivity-guided separation; serum pharmacochemistry of TCM in vivo; and Chinmedomics, which connects in vivo constituents with the biomarkers of the relevant TCM syndrome. Chinmedomics is a promising strategy that conforms to the theory and characteristics of TCM. By clarifying the effective constituents, targets and pathways of medicines, it can promote the discovery of lead compounds and the research of innovative drugs, and continuously promote the modernization of TCM. Graphical http://links.lww.com/AHM/A64.