Cancer causes millions of deaths globally every year. At its later stages, cancers are primarily treated with systemic therapies which do not provide an effective cure; the remaining cancer cells ultimately acquire drug resistance, relapse, and metastasize. In particular, polyploid giant cancer cells (PGCCs), which arise in response to diverse cellular stressors such as therapeutic pressure, modulate the tumor microenvironment (TME) and immunity involved in cancer development. However, without the knowledge of well-established signaling cascades targeting PGCCs, the current treatment options for these cells remain limited. This review provides a summary of the latest research associated with PGCC formation and treatment outcomes in common metastatic cancers. In addition, we highlight how some traditional Chinese medicine (TCM) and their bioactive compounds may serve as prospective agents for arresting PGCCs through cell cycle regulation, cell death induction, and TME modulation. Specifically, we identify how these processes are closely associated with the initiation, self-renewal, and termination phases of the PGCC life cycle. Based on the principle in TCM of "strengthening vital qi to eliminate pathogenic factors," the most efficacious herbs for counteracting PGCCs have been identified as Coptis chinensis, Oldenlandia diffusa, Scutellaria baicalensis, Salvia miltiorrhiza, Curcuma longa, Astragali radix, and Panax ginseng. The bioactive compounds of these herbs include berberine, oleanolic acid, wogonin, tanshinone IIA, curcumin, Astragaloside IV, and ginsenoside Rh2. Given the multi-target characteristics of TCM, network pharmacology was performed to allow for an integrative approach to elucidating underlying mechanisms. In particular, TCM administration may modulate both the p53 signaling pathway and cell cycle-related proteins. This, in turn, alleviates PGCC-induced tumor recurrence and resistance. Collectively, this review emphasizes the central role of PGCCs in advanced cancer progression while strengthening the mechanistic insights of TCM in PGCC-oriented therapy.
Atherosclerosis (AS), a major cause of cardiovascular diseases, is driven by dysregulated programmed cell death (PCD) pathways. These pathways, including apoptosis, pyroptosis, ferroptosis, autophagy, and necroptosis, contribute to plaque instability. Traditional Chinese Medicine (TCM) offers a multi-targeted approach for modulating these pathways, but its molecular mechanisms in AS remain inadequately explored. This review aims to investigate the modulatory effects of TCM on PCD pathways in AS, its therapeutic potential for enhancing plaque stability, and the underlying molecular mechanisms. A narrative literature review based on relevant preclinical in vitro and in vivo studies was conducted on TCM bioactive constituents and formulas. These included studies on tonifying herbs like Radix Astragali, Radix Ginseng, and Radix Glycyrrhizae, the extracts of Radix Salviae liguliobae, and classical prescriptions such as Danshen Prescription, Huayu Qutan Recipe, Modified Taohong Siwu Decoction, Xuezhikang, Gualou Xiebai Decoction, and Mai Ji Tong Granules. The relevant data were obtained from searches of major international and Chinese biomedical databases including PubMed, Web of Science, Embase, Cochrane Library, the China Biology Medicine Database, CNKI, Wanfang, and CSTJ. The evidence indicates that these interventions modulate PCD-related pathways to thereby inhibit pathological cell death, enhance protective autophagy, and influence cellular homeostasis, inflammation, oxidative stress, lipid accumulation, and efferocytosis. TCM's multi-component nature addresses the limitations of single-target Western therapies, and thus provides a holistic strategy for AS management. However, gaps remain in the mechanistic understanding and pharmacokinetic profiles of TCM constituents that hinder clinical application. This review emphasizes TCM's potential as a complementary therapy for AS. It likewise suggests the need for further studies to identify bioactive compounds and integrate TCM with precision medicine in order to achieve better therapeutic outcomes.
Type 2 diabetes mellitus (T2DM), a globally prevalent chronic metabolic disorder, imposes a significant worldwide public health burden. As a vital "microbial organ" within the human body, the balance of the gut microbiota (GM) structure and function is crucial for maintaining host metabolic health. Short-chain fatty acids (SCFAs), the metabolic products of GM, serve as key signaling molecules that play central roles in maintaining intestinal homeostasis, regulating systemic energy metabolism, and improving insulin sensitivity. Dysregulation of the "GM-SCFA axis" has emerged as a core pathological mechanism in the onset and progression of T2DM. Traditional Chinese Medicine (TCM) possesses unique advantages in T2DM treatment through its "holistic regulation and multi-targeted intervention," which enables precise modulation of the GM-SCFA axis. This paper provides a systematic review of the pathological mechanisms by which dysregulation of the GM-SCFA axis induces T2DM, and specifically covers energy metabolism disorders, insulin resistance, intestinal barrier impairment, chronic low-grade inflammatory activation, abnormal bile acid metabolism regulation, and disrupted gut-pancreatic axis and gut-brain axis signaling. Using keywords such as TCM, GM, SCFAs, and T2DM, we conducted an extensive literature search across databases including PubMed, Google Scholar, and Web of Science for publications from the past decade. This systematic review examines the application of TCM in regulating the "GM-SCFA axis" from multiple perspectives: Chinese herbal compounds (e.g., Zuogui Jiangtang Qinggan Formula, Gegen Qinlian Decoction), Chinese patent medicines (e.g., Shouhui Tongbian Capsules, Compound Danshen Dripping Pills), single-herb Chinese medicines (e.g., Edgeworthia gardneri, Alpinia oxyphylla), single-component compounds from TCM (e.g., Cyclocarya paliurus polysaccharide, Achyranthes bidentata polysaccharide water-soluble 1), and other TCM therapies (e.g., tuina, acupuncture). This study aims to systematically explore the mechanisms by which dysregulation of the "GM-SCFA axis" induces T2DM while providing novel therapeutic strategies for T2DM prevention and treatment using TCM. It also seeks to establish scientific foundations for developing novel TCM intervention strategies targeting the "GM-SCFA axis" in T2DM management.
Fructus Ligustri Lucidi (FLL), the fruit of Ligustrum lucidum, is used in traditional Chinese medicine to treat aging-related symptoms. This study aimed to explore the regulatory effects of the n-butanol phenol glycosides-enriched fraction of FLL on muscular function and senescence-relevant biological events, such as fibrosis, senescence-associated secretory phenotypes (SASPs), activity of the renin-angiotensin system (RAS), and insulin resistance, in skeletal muscle. Naturally aging rats and D-gal-induced aging mice, both of which underwent bilateral ovariectomy, were orally administered with the n-butanol fraction of FLL for 8 weeks by intragastric gavage. Muscular functions were determined by the grip strength test and weight-loaded swimming test. The frozen sections of muscle tissue were subjected to several types of staining, and senescence-associated hallmarks, (pro)fibrotic factors, RAS components, and insulin signaling were detected in the serum and muscle by ELISA, PCR, and immunoblotting. The FLL fraction elevated muscle mass, improved muscle strength, and augmented the cross-sectional area of gastrocnemius fibers. It furthermore reversed changes in the expression of myogenic regulatory factors, inhibited the SASP and protein expression of senescent hallmarks, repressed the over-activity of muscular RAS (renin/Ang II), and reduced the fibrotic area and expression of type I and III collagens in the gastrocnemius. Moreover, abnormal alterations in protein expression (IRß/IRS-1/AKT/GSK-3ß signaling) were improved in the muscle. The in vivo study of 20-month-old ovariectomized rats confirmed the benefits of this fraction on muscle mass and myofiber area, as well as its inhibitory effects on both the accumulation of SA-ß-gal and collagen molecules and enhanced muscle myostatin levels and RAS activity. In addition, it promoted the distribution percentage of type IIb myofibers in the tibialis anterior muscle. Collectively, the n-butanol phenol glycosides-enriched fraction of FLL could be a potential source for novel and/or lead drugs for the treatment of muscle atrophy and sarcopenia in elderly women.
Breast cancer (BC) is a major cause of cancer-related mortality worldwide. While mainstream anticancer therapies have improved clinical outcomes, they are often associated with significant toxicity and drug resistance. Traditional Chinese medicine (TCM) has received increasing recognition as a valuable complementary approach in oncology. This review summarizes the current evidence supporting the integrative use of TCM in BC management. Clinical studies indicate that TCM formulations can alleviate the adverse effects induced by chemotherapy and targeted therapy to thereby enhance patients' quality of life and treatment adherence. As an adjuvant, TCM also shows the potential to improve both the efficacy of conventional treatments and survival outcomes. Preclinical investigations reveal that bioactive herbal compounds exert multi-target antitumor effects by modulating key mechanisms such as programmed cell death, proliferation, metastasis, cell-cycle progression, drug resistance, aerobic glycolysis, and antitumor immunity. Furthermore, advanced drug delivery systems are being developed to overcome the inherent limitations of herbal compounds. However, challenges which warrant further investigation, including heterogeneous study designs, the standardization of formulations, and potential herb-drug interactions, remain under-explored. Overall, TCM represents a promising complementary strategy for BC. Future efforts should prioritize well-designed clinical trials, mechanistic elucidation, and the development of integrated precision medicine models to optimize patient care.
Programmed death (PD-1) is an important immune checkpoint receptor expressed on the surface of T cells, B cells and natural killer (NK) cells. PD-L1 (B7-H1) is a critical ligand for PD-1, and is widely expressed in a variety of cancer cells, immune cells, and normal histocytes. It has been established that the PD-1/PD-L1 interaction can produce an immunosuppressive effect by suppressing T cell proliferation, cytokine secretion, and cytotoxicity. Currently, PD-1 and PD-L1 inhibitors are known to be promising anticancer agents that reverse the antitumor immune function of T cells by inhibiting the PD-1/PD-L1 axis. The monotherapy of PD-1/PD-L1 blockade, while effective in treating cancers, is limited by a low response rate, immune-related adverse events (irAEs), and drug resistance. Their combinations with surgery, chemotherapy, radiotherapy, immunotherapy, hormone therapy, and traditional Chinese medicine (TCM), due to a synergistic effect, have broadened the frontier of cancer research. Following a holistic principle, TCM serves as an adjuvant therapy with PD-1/PD-L1 blockade, and provides benefits through complicated mechanisms. We specifically focused on the profound significance of TCM's assistance of PD-1/PD-L1 blockade, and the opportunities and challenges of treating cancers with both TCM and PD-1/PD-L1 blockade.
Cancer continues to pose significant challenges to global health systems due to its substantial disease burden and complex pathogenesis, and current therapies often demonstrate unsatisfactory outcomes. The inherent problems of tumor heterogeneity and individual variability lead to diverse responses to identical interventions, and result in uncertainty in treatment outcomes. Concomitant factors such as stress, mental health and diet also collectively impact patients' overall health, and thereby affect cancer progression in turn. Therefore, the comprehensive evaluation of patients' multidimensional profiles and the implementation of personalized treatments is imperative. This integrated approach not only enhances prognostic outcomes, but also improves quality of life. As a complementary therapeutic option, Traditional Chinese Medicine (TCM) has good efficacy in symptom alleviation and quality-of-life improvement. This holistic approach emphasizes the interconnectedness of human physiological systems and their harmonious balance with the external environment. TCM interventions are tailored to individual clinical manifestations, which enables the development of personalized treatment regimens. This review elucidates the clinical applications of TCM in individualized cancer treatment, and delineates its strategic framework for oncology management. It incorporates the innovative concept of "State-target differentiation and treatment" (Bianzheng Lunzhi) proposed by academician Tong Xiaolin, which integrates macro and micro perspectives into the diagnostic and therapeutic framework. The aim of this review is to advance evidence-based TCM approaches for the treatment of malignant tumors, and provide a more scientific and systematic methodology for individualized cancer treatment in TCM.
Ulcerative colitis (UC) is a common, chronic, and nonspecific inflammatory bowel disease which significantly impair patients' quality of life, and is characterized by a prolonged disease course and frequent relapses. Due to their localized therapeutic action and low incidence of adverse effects, Chinese herbal enemas have garnered increasing attention in clinical settings. This study aims to systematically evaluate the therapeutic potential of Chinese herbal enemas in UC management. Randomized controlled trials (RCTs) evaluating Chinese herbal enemas for UC, published up to April 19, 2025, were systematically searched. A network meta-analysis was performed using Stata 17.0, and the combined effect sizes were reported as the mean difference or relative risk with corresponding 95% confidence intervals. A total of 41 RCTs involving 2883 UC patients were ultimately included, and data on the risk of bias assessment were reported. When compared with mesalazine (MES) monotherapy, combination therapies, such as MES combined with Qingbai Guanchang Ye or MES combined with Qingchi San, and monotherapies including Huangkui Lianchang Tang and Baitouweng Tang, demonstrated statistically significant improvements in clinical outcomes. Subgroup analyses were also conducted. The clinical effectiveness of these interventions was also influenced by Traditional Chinese Medicine (TCM) syndrome differentiation and disease severity, which underscores the importance of individualized, stratified treatment approaches. Our study data showed that Chinese herbal enema therapy appears to be both clinically effective and safe in the management of UC, and supported both stratified TCM therapy and the refinement of UC treatment guidelines. Future research is needed to prioritize high-quality, large-scale RCTs to validate these findings.
Malignant tumors remain a leading cause of global mortality and pose significant public health challenges. However, Traditional Chinese Medicine (TCM) and its natural products offer unique therapeutic potential in oncology which may help to address these challenges. Mitophagy, a selective form of autophagy, is a key regulator of mitochondrial quality, metabolic balance, and programmed cell death, and has dual roles in tumor initiation, progression, and therapeutic responses. The canonical PINK1/Parkin and receptor-mediated BNIP3, NIX, and FUNDC1 pathways coordinate both the removal of damaged mitochondria and adaptation to stress to thus influence tumor cell survival, proliferation, metastasis, and chemoresistance. This review systematically summarizes the mitophagy-related molecular mechanisms present in tumors, and highlights the multifaceted anticancer effects exerted by TCM via mitophagy. TCM exerts chemo-preventive effects on precancerous lesions, induces apoptosis, ferroptosis, and other forms of programmed cell death, reprograms tumor metabolism, and modulates inflammatory signaling, immune cell function, and immunogenic cell death to thereby collectively reshape the tumor immune microenvironment. Beyond its antitumor activities, TCM alleviates cancer-related fatigue through mitophagy regulation in the skeletal muscle. Moreover, combination therapies involving mitophagy modulators enhance TCM efficacy. Further studies which integrate single-cell omics, spatial metabolomics, and functional imaging are needed in order to define context-specific mitophagy regulation, optimize combination strategies, establish reliable biomarkers, and thus position TCM as a promising approach for personalized and integrative cancer therapy.
The gut microbiota serves as a crucial modulator of host immunity and plays a pivotal role in regulating airway inflammation, maintaining immune balance, and affecting the course of associated diseases through gut-lung axis interactions. Recent studies increasingly demonstrate that patients with chronic inflammatory airway diseases (CIAD) commonly exhibit gut dysbiosis. This imbalance in gut microbiota can promote pulmonary inflammation and airway remodeling by affecting the synthesis of short-chain fatty acids (SCFAs), impairing intestinal mucosal barrier integrity, and disrupting immune regulation. With increasing attention to the gut-lung axis, microbiota-targeted therapeutic strategies have attracted growing attention. Traditional Chinese medicine (TCM), characterized by its multi-component composition, multi-target approach, and holistic regulatory properties, holds unique advantages in restoring gut microbial balance for the treatment of CIAD. This paper systematically reviews the therapeutic potential of TCMs and their bioactive constituents in managing CIAD through gut microbiota modulation. By regulating gut microbial composition and stimulating the generation of SCFAs, TCMs exert anti-inflammatory, immunomodulatory, and gut barrier-protective effects. TCMs thus offer novel perspectives and promising therapeutic strategies for CIAD treatment.
Ulcerative colitis (UC) is a growing global health concern, but there remains a lack of natural food sources and multi-targeted drugs to effectively it. Codonopsis pilosula (dangshen, DS), a medicinal food used in traditional Chinese medicine, offers more comprehensive benefits than conventional drugs due to the numerous active compounds, such as lobetyolin, tangshenoside I, codonopsine, succinic acid, and raffinose, it contains. DS can be safely incorporated into diets to enhance UC treatment compliance and continuous management. This study explored the therapeutic effects and mechanisms of DS using microbial sequencing, metabolomics, and experimental validation. DS alleviated UC symptoms in mice to ultimately achieve reduced weight loss, colon shortening, disease activity, and histopathology scores. It lowered pro-inflammatory cytokine levels (IL-6, IL-1β, TNF-[Formula: see text], balanced Th17 and Treg cells, and enhanced the intestinal barrier integrity by upregulating tight junction proteins (ZO-1, occludin, E-cadherin). In addition, DS significantly reduced the abundance of pathogenic Escherichia-Shigella by modulating the composition of the intestinal flora and increasing the production of tryptophan metabolites (5-hydroxyindole-3-acetic acid (5-HIAA) and kynurenic acid (KYNA)) through probiotic bacteria, like Alistipes and Lactobacillus, which act as aromatic hydrocarbon receptor (AhR) ligands. We found that Alistipes onderdonkii cultured in vitro produced 5-HIAA, and that DS could further increase 5-HIAA levels. In addition, both 5-HIAA and DS activated AhR in turn. The diminished efficacy of DS in UC after colony clearance was accompanied by a decrease in the level of AhR, which suggests the importance of bacterial-derived metabolites as mediators of the efficacy of DS. The metabolomics results showed that DS mainly exerted its regulatory effects by modulating arachidonic acid metabolism and tryptophan metabolism. Based on our data, which elucidated the relationship between AhR and anti-inflammatory effects, we identified the AhR/NF-κBp65 signaling pathway as a potential pharmacological mechanism by which DS is associated with UC amelioration.
Ferroptosis is a novel type of cell death that depends on iron ions and lipid peroxidation. An increasing number of studies have shown that ferroptosis can inhibit the progression of digestive system tumors, enhance the sensitivity of tumor cells to drugs, and reduce drug resistance. Traditional Chinese medicine (TCM) has been widely utilized in the field of tumor treatment, and has recently achieved remarkable research results in regulating the ferroptosis of tumor cells. This review systematically expounds on the specific molecular mechanisms through which TCM regulates ferroptosis in digestive system tumors (including hepatocellular carcinoma, gastric cancer, colorectal cancer, and pancreatic cancer). It covers various intervention strategies, including TCM small molecules like terpenoids, flavonoids, phenols, saponins, and alkaloids, nanoparticles loaded with active ingredients like novel nanoparticle-encapsulated berberine and NPBer, compound formulas such as Banxia Xiexin Decoction and Compound Gegen Decoction, and external treatments such as acupuncture. Studies have indicated that TCM, through its multi-target and multi-pathway action mechanism, affects pathways such as iron metabolism, lipid metabolism, and anti-oxidant defense to thereby promote ferroptosis and consequently inhibit tumor growth and metastasis. This provides new strategies and scientific evidence for the treatment of digestive system tumors. The purpose of this paper is to provide innovative ideas and theoretical support for the further exploration of TCM in the field of tumor treatment.
The global incidence and mortality of cancer continue to increase, and various chemotherapeutic agents, while highly effective, are associated with serious side effects like immunosuppression, metabolic dysfunction, and drug resistance. As a complementary or alternative approach, traditional Chinese medicine (TCM), which is known for its multi-target mechanisms and low toxicity, has garnered increasing attention in cancer research. Magnolia officinalis (M. officinalis) is a member of the Magnoliaceae family, and dried bark from its stems, roots, and branches is its primary medicinal part. According to TCM theory, M. officinalis may resolve dampness, eliminate phlegm, promote qi circulation, and relieve stagnation, and it has been widely applied in the treatment of gastrointestinal disorders. Modern pharmacological studies have identified bioactive compounds, including lignans, volatile oils, alkaloids, and polysaccharides, in M. officinalis, but the mechanisms underlying these pharmacological effects are still unclear and their clinical applications are limited by the lack of robust clinical evidence. We conducted a systematic review of both contemporary research databases (e.g., PubMed, CNKI, ScienceDirect, and other Chinese medical databases) and classic TCM literature to compile the bioactive components of M. officinalis, their pharmacological mechanisms in oncology, and recent preclinical progress. We also discuss the prospects and challenges of developing M. officinalis as an anticancer agent to provide a theoretical basis for its future development and clinical application.
Diabetic kidney disease (DKD) is one of the most common microvascular complications associated with diabetes mellitus. However, the existing treatment approaches, aimed at delaying the onset of DKD, exhibit limited efficacy. The flavonoid nobiletin has demonstrated substantial lipid-lowering and insulin-sensitizing effects in mice exhibiting metabolic dysfunction, but the therapeutic potential and mechanism of nobiletin in the context of DKD remains to be comprehensively elucidated. In this study, the active components of polymethoxylated flavonoids (PMFs) were identified via UPLC. A DKD rat model was established through a high-fat diet and the administration of streptozotocin via intraperitoneal injection. The effect and mechanism of nobiletin on DKD was evaluated by histological, biochemical, molecular, and multi-omics analysis. We found that treatment with PMFs and nobiletin inhibited ferroptosis and EMT in high glucose and insulin-induced models, protected the glomerular filtration barrier integrity, and concurrently suppressed ROS, Fe[Formula: see text], and MDA while increasing the GSH level. Animal experiments indicated that nobiletin treatment markedly impeded the progression of DKD and alleviated both EMT and endothelial dysfunction. Moreover, nobiletin significantly preserved the integrity of the intestinal barrier and enriched the diversity of gut microbiota. In conclusion, our findings indicate that nobiletin could attenuate DKD and concomitantly limit ferroptosis and EMT, and that the gut-kidney axis played an important role in its effects.
Diabetic kidney disease (DKD) is a major microvascular complication of diabetes, and recent evidence highlights the gut-kidney axis as a critical target in its prevention and treatment. Traditional Chinese Medicine (TCM) has demonstrated its unique advantages in regulating this axis through multi-target and multi-pathway mechanisms. This review summarizes research progress on TCM interventions that modulate the inflammatory pathways of the gut-kidney axis in DKD. Literature from recent years was collected from PubMed, Web of Science, and CNKI, with a particular focus on studies investigating the roles of TCM monomers and formulas in microbiota regulation, intestinal barrier protection, and inflammatory signaling. TCM compounds such as resveratrol, astragalus polysaccharides (APS), and ginsenosides, as well as classical formulas including Yi-Shen-Hua-Shi Granule, Tangshen Formula, and Huangkui Capsule (HKC), were found to restore gut microbial balance, increase short-chain fatty acid production, and inhibit key inflammatory pathways like NF-κB, NLRP3, JAK/STAT, and TGF-β1/Smad. These effects collectively alleviate oxidative stress, suppress renal inflammation and fibrosis, and improve metabolic and immune homeostasis. The findings suggest that TCM can effectively intervene in DKD progression by targeting gut-derived inflammation and immune dysregulation, and thereby provides a theoretical and experimental basis for integrative DKD therapy centered on gut-kidney axis modulation.
Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by chronic inflammation, cartilage degradation, and disrupted cellular homeostasis. Traditional Chinese medicine (TCM) has been widely applied in OA management, and exhibits distinct therapeutic advantages due to its multi-component and multi-target pharmacological properties. This review summarizes the molecular mechanisms by which TCM exerts therapeutic effects in OA, and offers a particular focus on the modulation of key signaling pathways involved in inflammation, apoptosis, autophagy, oxidative stress, and cartilage metabolic balance. Relevant studies were retrieved from the PubMed, Web of Science, Embase, and ScienceDirect databases, from their inception up to November 2025, and systematically analyzed. Evidence from experimental studies involving representative active compounds (e.g., Icariin, Geniposide, Ginsenoside Rb1, and Bilobalide) and classical formulas (such as Duhuo Jisheng Decoction, Yougui Pills, and Osteoking) indicates that TCM alleviates inflammation by inhibiting NF-κB, MAPK, and JAK/STAT signaling; promotes autophagy and metabolic homeostasis through regulation of the PI3K/Akt and AMPK pathways; attenuates oxidative stress via activation of the Nrf2 pathway; and maintains cartilage matrix equilibrium by modulating Wnt/β-catenin, TGF-β/Smad, and Notch signaling. TCM therefore exerts disease-modifying effects in OA through coordinated regulation of multiple signaling pathways, which both highlights its ethnopharmacological value and supports the rational development of TCM-based therapeutic strategies for OA.
The global incidence and prevalence of autoimmune diseases are increasing, and there is thus a need to develop novel, effective, and affordable therapeutic agents for autoimmune diseases. Triptolide (TP), a bioactive diterpenoid epoxide isolated from Tripterygium wilfordii Hook F, exhibits potent immunosuppressive and anti-inflammatory activities, and can be a potential therapeutic for multiple autoimmune diseases. The therapeutic effects of TP can be attributed to multiple mechanisms, including the inhibition of T cell and B cell activation, the restoration of T helper 17 cell/regulatory T cell balance, the suppression of pro-inflammatory cytokines, and the modulation of critical signaling pathways like the NF-κB, JAK/STAT, and PI3K/Akt pathways. TP alleviates pathological conditions by regulating oxidative stress responses and influencing gut microbiota composition. However, the clinical application of TP is limited due to severe dose-dependent and time-dependent toxic effects on the liver, kidneys, reproductive system, and other organs. Recent studies have highlighted several strategies, such as chemical structure modification, nanocarrier-based delivery systems, engineered exosomes, and combination pharmacotherapy, to both improve therapeutic efficacy and mitigate systemic toxicity. To provide insights for its safe clinical translation, this review systematically summarizes the pharmacological mechanisms, therapeutic potential, and toxicological challenges of TP in autoimmune diseases.
Astragaloside IV (ASIV), the main active component of the traditional Chinese medicine HuangQi, exhibits ameliorating effects on myocardial fibrosis through unclear mechanisms. To investigate the effects of ASIV on Endothelial-to-mesenchymal transition (EndMT) in myocardial fibrosis, 10 ng/mL TGF-β1 was used to induce EndMT in human umbilical vein endothelial cells (HUVECs) in vitro, and a 5 mg/kg/d subcutaneous injection of Isoproterenol (ISO) was used to induce myocardial fibrosis in mice in vivo. The drug affinity-responsive target stability (DARTS) was used to identify the target proteins of ASIV in endothelial cells. The results showed that ASIV could significantly inhibit the TGF-β1-induced EndMT, which includes changes in cytoskeletal structure, the expression of EndMT markers, cell migration potency, and cell glycolysis rate. ASIV significantly ameliorated ISO-induced myocardial fibrosis in mice and inhibited EndMT in heart tissues. The Ras homolog gene family member A (RhoA) protein was found to be a possible direct binding target of ASIV in endothelial cells. The binding affinity between ASIV and RhoA was confirmed by molecular docking and the cellular thermal shift assay (CETSA). ASIV inhibited the RhoA-related pathway in the heart tissues of myocardial fibrosis mice. In addition, siRNA knockdown of RhoA expression or treatment with RhoA agonists was found to significantly affect the inhibition of EndMT by ASIV. The results suggested that ASIV could significantly inhibit the EndMT by binding with RhoA, and that the inhibition of EndMT by ASIV contributed to its amelioratory effects on myocardial fibrosis. This discovery provided a theoretical basis for the application of ASIV and HuangQi in the treatment of myocardial fibrosis.
Chronic airway diseases are a group of diseases, such as chronic obstructive pulmonary disease (COPD) and bronchial asthma (BA), characterized pathologically by chronic airway inflammation, airway chronic mucus hypersecretion, and airway remodeling. Patients usually present with chronic coughing, expectoration, and dyspnea, and recurrent exacerbation is an important causative factor of increased mortality, along with the important triggers. Currently, existing treatment options cannot meet the clinical needs of chronic airway diseases. Ginseng's great potential for treating chronic airway diseases has been confirmed by various clinical and basic studies, and traditional Chinese medicine compounds composed mainly of ginseng can both improve the symptoms of coughing and expectoration and reduce the number of acute exacerbations. Ginseng and its main biologically active ingredients exhibit the multifaceted mechanisms of effectively improving airway inflammation, mitigating airway mucus secretion, and reducing airway remodeling, which underscores their effectiveness in airway disease treatment. This study was conducted for the further elucidation and extension of the possible value of ginseng in chronic airway diseases. This review summarizes recent studies on the efficacy of ginseng in chronic airway disease treatment, discusses the pharmacological effects of ginseng and ginsenosides, and highlights their roles in the prevention and treatment of chronic airway diseases, airway diseases caused by airway inflammation and high airway mucus secretion, and airway remodeling-induced lung diseases. Finally, this study also predicted future research directions. Findings in this study may lay a robust foundation for investigating ginseng in chronic airway diseases, its underlying mechanisms, and its clinical development and practical application.
The activation of the NLRP3 inflammasome is critical to inducing microglial activation and pyroptosis following cerebral ischemia/reperfusion (I/R). Suppressing the neurotoxicity of activated microglia has become an effective approach for treating cerebral I/R injury. Rhein is an anthraquinone compound found in rheum, and possesses anti-inflammatory, antagonistic, and antifibrotic effects. This study assessed whether rhein influences NLRP3 inflammasome activation, pyroptosis, and the polarization of microglia after cerebral I/R or oxygen-glucose deprivation and reoxygenation (OGD/R). Cerebral I/R models were established in Sprague-Dawley rats via transient middle cerebral artery occlusion (tMCAO) surgery, and OGD/R models were established in BV-2 cells using a hypoxic chamber. After treatment with rhein, the infarction/edema ratio, BV-2 cell viability, expression of NLRP3 inflammasome, and levels of microglial polarization and pyroptosis were detected. Finally, NLRP3 inhibitors (MCC950) were used to assess whether rhein exerted its effects by inhibiting the activation of the NLRP3 inflammasome in regulating pyroptosis and polarization of microglia. Rhein permeated the blood-brain barrier of rats after tMCAO, protected against tMCAO-induced brain injury, and inhibited microglial NLRP3 inflammasome activation and pyroptosis after tMCAO or OGD/R. It also suppressed tMCAO- or OGD/R-induced polarization of the M1 phenotype in microglia, and skewed them toward the M2 phenotype. Moreover, co-administration of rhein and MCC950 synergistically enhanced both the inhibition of the NLRP3 inflammasome activation/pyroptosis axis and the regulation of microglial polarization after tMCAO or OGD/R. Rhein exerts neuroprotective effects by regulating microglial pyroptosis and polarization through inhibiting the activation of NLRP3 inflammasome after tMCAO or OGD/R.