Stroke is the second leading cause of disability and mortality worldwide, imposing a substantial socioeconomic burden on individuals and healthcare systems. Annually, approximately 14 million people experience stroke, with ischemic stroke comprising nearly 85% of cases, of which 10% to 20% involve large vessel occlusions. Currently, recombinant tissue plasminogen activator (tPA) remains the only approved pharmacological intervention. However, its utility is limited due to a narrow therapeutic window and low recanalization rates, making it applicable to only a minority of patients. Therefore, there is an urgent need for novel therapeutic strategies, including pharmacological advancements and combinatory treatments. Small-molecule natural medicines, particularly those derived from traditional Chinese herbs, have demonstrated significant therapeutic potential in ischemic stroke management. These compounds exert multiple neuroprotective effects, such as antioxidation, anti-inflammatory action, and inhibition of apoptosis, all of which are critical in mitigating stroke-induced cerebral damage. This review comprehensively examines the pathophysiology of acute ischemic stroke (AIS) and highlights the recent progress in the development of small-molecule natural medicines as promising therapeutic agents for cerebral ischemic stroke.
Humans ; Ischemic Stroke/physiopathology* ; Animals ; Neuroprotective Agents/therapeutic use* ; Drugs, Chinese Herbal/chemistry* ; Biological Products/therapeutic use* ; Stroke/drug therapy*

Arthritis, encompassing osteoarthritis (OA), rheumatoid arthritis (RA), and gouty arthritis (GA), is a prevalent inflammatory disease that significantly impacts quality of life. Natural products (NPs), derived from animals, plants, marine organisms, and microorganisms, have demonstrated beneficial effects in arthritis treatment both domestically and internationally. These natural compounds offer advantages in drug discovery due to their skeletal diversity, structural complexity, and multi-effect, multi-target, and low-toxicity properties compared to conventional small-molecule medicines. However, unclear mechanisms have hindered the development and clinical application of NPs. This review summarizes recent experimental studies from the past decade on natural medicine for arthritis treatment, emphasizing key NPs with therapeutic effects on OA, RA, and GA. It examines the effects and molecular mechanisms of NPs acting on different cells to treat arthritis. Furthermore, this review provides insights into the future prospects of NP research in this field, which is crucial for advancing NP-based arthritis treatments.
Humans ; Biological Products/therapeutic use* ; Animals ; Arthritis, Rheumatoid/drug therapy* ; Arthritis, Gouty/drug therapy* ; Arthritis/drug therapy* ; Osteoarthritis/drug therapy*

Glioma, the most prevalent primary tumor of the central nervous system (CNS), is also the most lethal primary malignant tumor. Currently, there are limited chemotherapeutics available for glioma treatment, necessitating further research to identify and develop new chemotherapeutic agents. A significant approach to discovering anti-glioma drugs involves isolating antitumor active ingredients from natural products (NPs) and optimizing their structures. Additionally, targeted drug delivery systems (TDDSs) are employed to enhance drug solubility and stability and overcome the blood-brain barrier (BBB). TDDSs can penetrate deep into the brain, increase drug concentration and retention time in the CNS, and improve the targeting efficiency of NPs, thereby reducing adverse effects and enhancing anti-glioma efficacy. This paper reviews the research progress of anti-glioma activities of NPs, including alkaloids, polyphenols, flavonoids, terpenoids, saponins, quinones, and their synthetic derivatives over the past decade. The review also summarizes anti-glioma mechanisms, such as suppression of related protein expression, regulation of reactive oxygen species (ROS) levels, control of apoptosis signaling pathways, reduction of matrix metalloproteinases (MMPs) expression, blocking of vascular endothelial growth factor (VEGF), and reversal of immunosuppression. Furthermore, the functions and advantages of NP-based TDDSs in anti-glioma therapy are examined. The key information presented in this review will be valuable for the research and development of NP-based anti-glioma drugs and related TDDSs.
Humans ; Glioma/metabolism* ; Biological Products/therapeutic use* ; Animals ; Brain Neoplasms/genetics* ; Drug Delivery Systems ; Antineoplastic Agents/therapeutic use* ; Blood-Brain Barrier/metabolism* ; Apoptosis/drug effects*

Myocardial infarction is a cardiovascular disease (CVD) with high morbidity and mortality, which can trigger a cascade of cardiac pathophysiological changes, including fibrosis, inflammation, ischemia-reperfusion injury (IRI), and ventricular remodeling, ultimately leading to heart failure (HF). While conventional pharmacological treatments and clinical reperfusion therapy may enhance short-term prognoses and emergency survival rates, both approaches have limitations and adverse effects. Natural products (NPs) are extensively utilized as therapeutics globally, with some demonstrating potentially favorable therapeutic effects in preclinical and clinical pharmacological studies, positioning them as potential alternatives to modern drugs. This review comprehensively elucidates the pathophysiological mechanisms during myocardial infarction and summarizes the mechanisms by which NPs exert cardiac beneficial effects. These include classical mechanisms such as inhibition of inflammation and oxidative stress, alleviation of cardiomyocyte death, attenuation of cardiac fibrosis, improvement of angiogenesis, and emerging mechanisms such as cardiac metabolic regulation and histone modification. Furthermore, the review emphasizes the modulation by NPs of novel targets or signaling pathways in classical mechanisms, including other forms of regulated cell death (RCD), endothelial-mesenchymal transition, non-coding ribonucleic acids (ncRNAs) cascade, and endothelial progenitor cell (EPC) function. Additionally, NPs influencing a particular mechanism are categorized based on their chemical structure, and their relevance is discussed. Finally, the current limitations and prospects of NPs therapy are considered, highlighting their potential for use in myocardial infarction management and identifying issues that require urgent attention.
Humans ; Myocardial Infarction/genetics* ; Biological Products/therapeutic use* ; Animals ; Oxidative Stress/drug effects* ; Signal Transduction/drug effects*

The host-microbe co-metabolism system, generating diverse exogenous and endogenous bioactive molecules that influence the host's immune and metabolic functions, plays a crucial role in the pathogenesis of atherosclerosis. Recent studies have elucidated the interaction between natural medicines and this co-metabolism system. Upon oral administration, natural medicine ingredients can undergo transformation by gut microbiota, potentially enhancing their bioavailability or anti-atherogenic efficacy. Furthermore, natural medicines can exert anti-atherogenic effects via modulation of endogenous host-microbe co-metabolism. This review presents an updated understanding of the dual association between natural medicines and host-microbe co-metabolites. It explores the critical function of microbial exogenous metabolites derived from natural medicines and uncovers the mechanisms underlying natural medicines' intervention on key nodes of endogenous host-microbe co-metabolism. These insights may offer new perspectives for cardiovascular disease (CVD) treatment and guide future drug discovery efforts.
Humans ; Atherosclerosis/metabolism* ; Gastrointestinal Microbiome/drug effects* ; Biological Products/therapeutic use* ; Animals ; Host Microbial Interactions/drug effects*

Metabolic dysfunction-associated fatty liver disease (MAFLD), characterized by fatty acid overload, secondary chronic inflammation, and fibrosis, has become the most prevalent chronic liver disease globally. While no effective pharmacotherapy exists for MAFLD, mitigating inflammatory responses represents a promising approach to preventing the progression from steatosis to severe steatohepatitis. The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, which detects endogenous danger and stress signals, has emerged as a significant target for inflammatory disease treatment, as transcriptional inactivation of its components demonstrates the therapeutic potential for MAFLD. Natural products targeting NLRP3 inflammasome activation have shown promising efficacy in MAFLD therapy. This review synthesizes the current understanding of NLRP3 inflammasome activation and therapeutic targets for NLRP3 homeostasis. Additionally, natural products reported to inhibit NLRP3 inflammasome for MAFLD improvement are categorized according to their mechanisms of action. The review also addresses limitations and future directions regarding natural products targeting NLRP3 inflammasome in MAFLD treatment. Enhanced understanding of NLRP3 inflammasome activation mechanisms in MAFLD and the identification of novel natural products supported by mechanistic research will significantly advance MAFLD treatment.
Humans ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology* ; Inflammasomes/metabolism* ; Biological Products/therapeutic use* ; Animals ; Fatty Liver/immunology*

Accurate prediction of drug-target interactions (DTIs) plays a pivotal role in drug discovery, facilitating optimization of lead compounds, drug repurposing and elucidation of drug side effects. However, traditional DTI prediction methods are often limited by incomplete biological data and insufficient representation of protein features. In this study, we proposed KG-CNNDTI, a novel knowledge graph-enhanced framework for DTI prediction, which integrates heterogeneous biological information to improve model generalizability and predictive performance. The proposed model utilized protein embeddings derived from a biomedical knowledge graph via the Node2Vec algorithm, which were further enriched with contextualized sequence representations obtained from ProteinBERT. For compound representation, multiple molecular fingerprint schemes alongside the Uni-Mol pre-trained model were evaluated. The fused representations served as inputs to both classical machine learning models and a convolutional neural network-based predictor. Experimental evaluations across benchmark datasets demonstrated that KG-CNNDTI achieved superior performance compared to state-of-the-art methods, particularly in terms of Precision, Recall, F1-Score and area under the precision-recall curve (AUPR). Ablation analysis highlighted the substantial contribution of knowledge graph-derived features. Moreover, KG-CNNDTI was employed for virtual screening of natural products against Alzheimer's disease, resulting in 40 candidate compounds. 5 were supported by literature evidence, among which 3 were further validated in vitro assays.
Alzheimer Disease/drug therapy* ; Biological Products/therapeutic use* ; Humans ; Neural Networks, Computer ; Machine Learning ; Drug Discovery/methods* ; Algorithms ; Drug Evaluation, Preclinical/methods*

Humans ; Drug Monitoring/methods* ; Child ; Inflammatory Bowel Diseases/drug therapy* ; Immunosuppressive Agents/therapeutic use* ; China ; Biological Products/therapeutic use*

In recent years, there has been a growing interest in the research on NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome inhibitors in the treatment of inflammatory diseases. The NLRP3 inflammasome is integral to the innate immune response, and its abnormal activation can lead to the release of pro-inflammatory cytokine, consequently facilitating the progression of various pathological conditions. Therefore, investigating the pharmacological inhibition pathway of the NLRP3 inflammasome represents a promising strategy for the treatment of inflammation-related diseases. Currently, the Food and Drug Administration(FDA) has not approved drugs targeting the NLRP3 inflammasome for clinical use due to concerns regarding liver toxicity and gastrointestinal side effects associated with chemical small molecule inhibitors in clinical trials. Natural small molecule compounds such as polyphenols, flavonoids, and alkaloids are ubiquitously found in animals, plants, and other natural substances exhibiting pharmacological activities. Their abundant sources, intricate and diverse structures, high biocompatibility, minimal adverse reactions, and superior biochemical potency in comparison to synthetic compounds have attracted the attention of extensive scholars. Currently, certain natural small molecule compounds have been demonstrated to impede the activation of the NLRP3 inflammasome via various action mechanisms, so they are viewed as the innovative, feasible, and minimally toxic therapeutic agents for inhibiting NLRP3 inflammasome activation in the treatment of both acute and chronic inflammatory diseases. Hence, this study systematically examined the effects and potential mechanisms of natural small molecule compounds derived from traditional Chinese medicine on the activation of NLRP3 inflammasomes at their initiation, assembly, and activation stages. The objection is to furnish theoretical support and practical guidance for the effective clinical application of these natural small molecule inhibitors.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Inflammasomes/metabolism* ; Inflammation/drug therapy* ; Anti-Inflammatory Agents/therapeutic use* ; Humans ; Animals ; Disease Models, Animal ; Biological Products/therapeutic use* ; Drug Discovery ; Medicine, Chinese Traditional/methods*

OBJECTIVE: To assess the impact of long-term biologic therapy on metabolic biochemical parameters in moderate to severe plaque psoriasis patients. METHODS: The study included patients over 18 years old who had been treated by biological agents for at least 24 weeks for moderate to severe plaque psoriasis from Novermber 2015 to January 2024. According to the biological agents the patients used, they were divided into three groups: interleukin-17 (IL-17) inhibitor group, IL-23 and IL-12/23 inhibitor group and tumor necrosis factor-α (TNF-α) inhibitor group. The metabolic biochemical parameters of each group were evaluated and compared before and after the administration of the biologic therapies. RESULTS: A total of 174 patients with moderate to severe plaque psoriasis were included in the long-term treatment with biologics, including 127 males (73.00%), 47 females (27.00%), with a median age of 38.00 (31.50, 49.00) years and a median duration of psoriasis of 12.00 (10.00, 20.00) years. The median duration of biologic treatment was 61.00 (49.00, 96.25) weeks, ranging from 26 to 301 weeks. There were 101 patients in the IL-17 inhibitor group, 38 patients in the IL-23 and IL-12/23 inhibitor group, and 35 patients in the TNF-α inhibitor group. After long-term treatment with IL-17 inhibitors, no statistically significant changes were observed in body weight, body mass index (BMI), alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting glucose (GLU), total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) compared with baseline measurements (P>0.05). However, low-density lipoprotein cholesterol (LDL-C) levels were significantly reduced [(2.90±0.75) mmol/L vs. (3.05±0.79) mmol/L, t=－2.100, P=0.038], while uric acid (UA) levels showed a significant increase [(401.13±99.13) μmol/L vs. (364.94±91.11) μmol/L, t=5.215, P < 0.001]. The group with normal UA levels before treatment showed a significant increase after long-term application of biological agents compared with before treatment [(370.69± 89.59) μmol/L vs. (324.66±64.50) μmol/L, t=5.856, P < 0.001]. Following long-term application of IL-23 and IL-12/23 inhibitors, no statistically significant differences were observed in body weight, BMI, ALT, AST, GLU, TC, TG, HDL-C and UA levels when compared with baseline measurements (P> 0.05). However, LDL-C levels exhibited a significant reduction from baseline [(2.85±0.74) mmol/L vs. (3.12±0.68) mmol/L, t=－2.082, P=0.045]. After long-term treatment with TNF-α inhibitor, there were no significant differences in body weight, BMI, ALT, AST, GLU, TC, TG, HDL-C, LDL-C and UA compared with baseline measurements (P>0.05). CONCLUSION Long-term application of IL-17 inhibitors in moderate to severe plaque psoriasis patients may result in elevated uric acid levels, particularly in patients with normal uric acid levels before treatment. The long-term use of IL-17 inhibitors, IL-23 inhibitors or IL-12/23 inhibitors might reduce LDL-C levels.
Humans ; Psoriasis/blood* ; Male ; Female ; Adult ; Middle Aged ; Interleukin-17/antagonists & inhibitors* ; Interleukin-23/antagonists & inhibitors* ; Tumor Necrosis Factor-alpha/antagonists & inhibitors* ; Interleukin-12/antagonists & inhibitors* ; Biological Therapy ; Biological Products/therapeutic use* ; Triglycerides/blood* ; Cholesterol, LDL/blood* ; Cholesterol, HDL/blood*