Xiwu Zhang

Fatty liver disease (FLD) is the most prevalent chronic liver disease worldwide, and its prevalence continues to rise steadily each year. FLD is not only a major predisposing factor for liver fibrosis, cirrhosis, and hepatocellular carcinoma, but is also closely associated with various extrahepatic diseases such as cardiovascular disease and chronic kidney disease, imposing a heavy burden on global healthcare systems. Currently, treatment options for FLD are limited. In contrast, traditional Chinese medicine (TCM) has a long history in treating FLD and has shown certain efficacy. However, most TCM compounds face limitations, including poor water solubility, low in vivo bioavailability, and insufficient liver-targeting ability, which hinder their effective accumulation at hepatic lesion sites. This article reviews the TCM monomer compounds used in the treatment of FLD, as well as the characteristics and recent advances in passive liver-targeting drug delivery systems, active liver-targeting systems, and smart drug-targeting systems. It also elucidates the challenges and development prospects of liver-targeting strategies in TCM therapeutic applications, aiming to promote the clinical translation and application of novel liver-targeted delivery drugs derived from TCM for the treatment of FLD.

With the increasing global burden of cancer, traditional chemotherapy is limited by issues such as high toxicity and poor targeting, making the development of new therapeutic strategies an urgent priority. As natural bioactive macromolecules, herbal polysaccharides have become a hotspot in antitumor research due to their multi‑target effects, low toxicity, and excellent biocompatibility. The present review summarizes recent advances in the mechanisms of plant polysaccharides in antitumor activity and their applications in drug delivery systems. It highlights their synergistic antitumor effects through multiple pathways, including regulation of the immune microenvironment, induction of programmed cell death, modulation of the microbiota‑immune axis, and inhibition of angiogenesis and metastasis. These compounds significantly enhance the efficacy of chemotherapy and immunotherapy while reversing drug resistance. Novel formulations such as polysaccharide‑based nano‑delivery systems, selenium‑modified complexes and gel platforms have further improved drug targeting, stability, and immunomodulatory efficacy, providing a solid theoretical foundation and innovative directions for integrated traditional Chinese and Western medicine in cancer treatment.

Pruritus is a multifaceted and complicated symptom with an increasing global incidence as a result of increased environmental stressors and aging populations, making it a notable public health concern. Although research has investigated the multifaceted pathophysiological causes of pruritus, the entire range of pathophysiological processes is currently unknown. Furthermore, contemporary Western medicines continue to have drawbacks, including low efficacy and marked side effects. Traditional Chinese medicine (TCM), on the other hand, exhibits notable therapeutic potential in the treatment of pruritus due to its systemic regulatory benefits via multicomponent, multitarget and multichannel processes. The present review outlines the current understanding of the pathogenesis of pruritus and summarizes contemporary therapeutic approaches established in TCM, with a focus on summarizing the pharmacological effects and mechanisms of active constituents found in single‑agent treatment herbal remedies and compound formulations. The aim of the present review is to provide a theoretical foundation and strategic advice for the development and clinical translation of novel TCM medications with extensive regulatory functions.

Immune checkpoint inhibitors (ICIs) represent a class of novel anticancer agents that enhance T cell-mediated recognition and elimination of tumor cells by inhibiting immune checkpoints such as CTLA-4 and PD-1/PD-L1. These therapeutics are widely employed in the treatment of various malignancies, including melanoma and non-small cell lung cancer, and have markedly improved clinical outcomes. However, ICIs are associated with immune-related adverse events (irAEs). Among these, cardiovascular toxicities, though relatively uncommon (occurring in approximately 3.1% of patients receiving monotherapy and 5.8% on combination therapy), are linked with the highest mortality rates. Cardiovascular toxicities associated with ICIs mainly encompass myocarditis (incidence: 1%–2%; mortality: 39.7%–66.0%), pericarditis (case fatality rate: ~13%), and accelerated atherosclerosis. Risk profiles differ across ICI agents; CTLA-4 inhibitors, for example, demonstrate more pronounced and dose-dependent cardiotoxicity, and combination therapies are associated with higher risks compared to monotherapy. The pathogenic mechanisms are attributed to loss of immune tolerance, which involves excessive activation of T cells, triggering autoimmune responses; cross-reactive T cells targeting shared cardiac antigens; and cytokine release storms that promote systemic inflammation. Although advances have been made in the diagnosis and management of cardiovascular toxicities associated with ICIs, several challenges persist. These include an incomplete understanding of the underlying mechanisms and a lack of reliable predictive biomarkers. Research should prioritize elucidating the pathogenic pathways, refining combination therapy regimens, identifying novel therapeutic targets, and developing artificial intelligence (AI)-based predictive models. Such efforts are crucial in mitigating toxicity, enhancing patients’ quality of life, and improving long-term outcomes.

Hepatocellular carcinoma (HCC) is a leading cause of cancer‑related morbidity and mortality worldwide. HCC pathogenesis is predominantly associated with chronic liver disease, driven by a vicious cycle of persistent hepatic injury, chronic inflammation and aberrant hepatocyte regeneration. Within this complex pathological landscape, remodeling of the tumor immune microenvironment (TIME), metabolic dysregulation and gut‑liver axis imbalance collectively contribute to HCC initiation and progression. Given the limited efficacy of conventional therapeutic modalities against such multifaceted pathologies, there is an urgent need to explore novel strategies that are safe, effective and capable of multi‑target regulation. Natural polysaccharides, a class of bioactive macromolecules, have emerged as promising candidates for prevention and treatment. Polysaccharides not only directly suppress malignant phenotypes in HCC cells by modulating cell cycle progression, inducing apoptosis, and inhibiting invasion and metastasis, but also exert potent immunomodulatory effects. Specifically, they activate key immune effectors, including cytotoxic T lymphocytes, dendritic cells, natural killer cells and tumor‑associated macrophages, thereby reversing immunosuppression and reshaping the TIME. Furthermore, polysaccharides can modulate the gut microbiota and its metabolites, enrich beneficial bacterial taxa, and reinforce intestinal barrier integrity. These actions subsequently influence intrahepatic immune responses and inflammatory status, achieving systemic intervention via the ‘gut‑liver‑immune’ axis. The present review provides a systematic overview of the multifaceted mechanisms by which polysaccharides combat HCC, including direct antitumor effects, modulation of the TIME and regulation of the gut microbiota. By synthesizing current evidence, the present review aims to offer critical perspectives to advance the mechanistic understanding and facilitate the clinical translation of polysaccharides for HCC treatment.

Heart failure (HF), as the terminal stage of cardiovascular diseases, involves complex pathophysiological mechanisms that extend beyond the heart itself and involve the interactive regulation of multiple organ systems. The gut-heart axis theory reveals that the gut microbiota, functioning as a micro-organ, plays a core role in the development and progression of HF through bidirectional regulatory mechanisms. HF-induced hemodynamic disturbances reshape the gut microenvironment, leading to the collapse of intestinal physical and immune barrier functions. In this altered microenvironment, dysregulated gut bacteria release excessive pro-inflammatory metabolites while reducing protective signaling molecules, thereby activating inflammatory pathways including Toll-Like Receptor 4/Nuclear Factor-κB and NOD-like receptor protein 3 inflammasomes. Traditional Chinese medicine (TCM) is the most import integrative medicine to treat HF, and the combination of TCM and western medicine have reached certain progress. This article aims to describe the pathological feedback mechanism between HF and gut microbiota, as long as summary how TCM and western medicine treat HF through regulate gut-heart axis. In specific, modern medicine optimizes hemodynamics to improve the macroscopic microenvironment, thereby establishing a foundation for gut microbiota remodeling. TCM exerts holistic regulatory advantages through multiple components and targets, inhibiting the production of gut-derived inflammatory factors at their source by reshaping the oxygen gradient, providing prebiotic substrates, and repairing intestinal barrier integrity. These could provide a theoretical basis and research reference for precision-oriented HF prevention and management from the perspective of intestinal microecology.

Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders; current therapies can neither cure AD nor prevent its progression. The pathological hallmark of AD is the excessive deposition of abnormal proteins in the brain, primarily including β-amyloid (Aβ) and phosphorylated Tau proteins. The ubiquitin-proteasome system (UPS), a central intracellular protein degradation mechanism that removes misfolded proteins and maintains cellular homeostasis by inhibiting aberrant protein aggregation, plays an important role in the regulation of various physiological functions, as well as in the development of disease. Any abnormality in this process leads to protein misfolding and aggregation, and the accumulation and aggregation of ubiquitinated proteins is a common feature of many neurodegenerative diseases, including AD. A growing number of studies have confirmed the significance of UPS in the AD process, which may act in conjunction with other mechanisms leading to the development of AD, and may even be the direct cause of AD. UPS offers a whole new possibility for the development of drugs for AD prevention and treatment, as well as new strategies and approaches for the treatment of neurodegenerative diseases. Therefore, this review is based on UPS, describes the possible mechanisms of action of UPS in AD, and summarizes the preclinical studies of modulating UPS for the treatment of AD.

Diabetic foot ulcers (DFUs) represent devastating complications associated with high risks of amputation and mortality. The complex pathophysiology of the wound microenvironment and systemic involvement render conventional therapies costly and limited in effectiveness. Consequently, there is an urgent demand for the development of effective and comprehensive therapeutic and management strategies. Herbal medicines and their formulations can transform DFU management from passive debridement to active regeneration through multi-target synergy and holistic intervention, offering low-cost and safe alternatives. Integrating herbal active components with polymeric materials enables the development of novel delivery systems and tissue-engineered scaffolds. This interdisciplinary approach is emerging as a promising therapeutic strategy in regenerative medicine and dermal engineering. This paper compares cellular healing mechanisms in DFUs and normal wounds, elucidates the mechanisms of action of herbal medicines and their formulations in treating DFUs, and synthesizes the applications of novel delivery systems for herbal active components in DFU therapy.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death worldwide. Although low-density lipoprotein cholesterol (LDL-C) levels are well controlled by current therapies, the residual risk of ASCVD remains, and adverse cardiovascular events remain a major clinical problem worldwide. Therefore, it is necessary to identify the sources of remaining risks and formulate targeted strategies to solve these problems. In recent years, the role of gut microbiota has been rediscovered, including trimethylamine N-oxides (TMAO), secondary bile acids, lipopolysaccharides (LPS), and short chain fatty acids (SCFAs), which have been found to play a key role in the pathogenesis of ASCVD. New lipid-lowering therapeutic targets are currently under development, such as triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and lipoprotein(a). Other studies of novel therapeutic agents that target inflammatory pathways, the immune system, etc., are also seeking to address the residual risks associated with ASCVD. The purpose of this review is to evaluate residual risk factors and novel therapeutic strategies for ASCVD, with a focus on the most recent therapeutic advancements, mechanisms, and clinical treatments.

Cardiovascular diseases (CVDs) pose a serious threat to human health and represent one of the leading causes of death worldwide. Cellular autophagy, an essential intracellular self-degradation and homeostasis maintenance mechanism, plays a pivotal role in the pathogenesis of cardiovascular diseases. Traditional Chinese Medicine (TCM), with its unique theoretical framework and therapeutic principles, has demonstrated remarkable efficacy in CVDs management, garnering increasing scientific attention. In recent years, growing research attention has focused on TCM's autophagy regulation for CVDs treatment. However, most studies remain limited to cellular and animal models, with insufficient clinical data and unclear specific metabolic pathways and targets. Therefore, it is imperative to (1) investigate autophagy mechanisms in depth (2), explore methods for autophagy balance, and (3) clarify drug interactions to establish a foundation for clinical applications. This article comprehensively summarizes relevant research findings, provides an in-depth discussion of TCM's mechanisms in autophagy regulation for CVDs treatment, reviews current research status, and outlines future development trends, aiming to offer valuable theoretical foundations and therapeutic strategies for clinical CVDs management.