Colon adenocarcinoma (COAD) is characterized by the metabolic reprogramming, such as the Warburg effect, which drives tumor progression and immunosuppression. Hypoxia-inducible factor 1[Formula: see text] (HIF-1[Formula: see text] and lactate dehydrogenase A (LDHA) are critical regulators of this metabolic shift, but existing therapies are insufficiently specific to it. This study investigates the antitumor mechanisms of cannabidiol, a non-psychoactive phytocannabinoid, by using integrative multi-omics and functional validation. Single-cell transcriptomics revealed that cannabidiol reduced tumor cell proportions and suppressed glycolytic activity in COAD. Network pharmacology identified PTGS2 as a central target, with proteomic data confirming its overexpression in COAD tissues and association with poor prognosis. , cannabidiol inhibited COAD cell proliferation, migration, and colony formation while downregulating HIF-1[Formula: see text], LDHA, and GLUT1 expression. Metabolic assays demonstrated associated dose-dependent reductions in ATP production, glucose uptake, and lactate levels. Rescue experiments using the HIF-1[Formula: see text] agonist DMOG partially reversed cannabidiol's antiglycolytic and antitumor effects, and thus confirmed pathway dependency. Synergy with the glycolysis inhibitor 2-DG enhanced therapeutic efficacy, which highlighted cannabidiol's potential to overcome metabolic resistance. These findings establish cannabidiol as a novel inhibitor of HIF-1[Formula: see text]/LDHA-driven glycolysis, and thus provide a translational strategy for metabolic vulnerability in COAD.

Many herbal and traditional medicines show promise in the treatment of diverse diseases, but their molecular mechanisms in different dynamic pathological contexts remain poorly understood. Several herbally-derived agents have entered pharmaceutical development, and there are ongoing efforts to define the pharmacotherapeutic effects of natural ingredients. Gambogic acid (GA), a caged xanthone from the dry resin of the widely used traditional Chinese medicinal herb Hook.f., has demonstrated therapeutic potential against chronic inflammation, cancer, cardiovascular disorders, and other conditions. However, its mechanisms of action, pharmacokinetics, and toxicological profile remain unclear. Furthermore, no comprehensive review exists on nanotechnology-based delivery strategies for this compound. In this review, we summarize current knowledge of the molecular targets and signaling pathways of GA, systematically assess the available pharmacokinetic data, safety considerations, and nanoplatform delivery systems, and highlight promising directions for future applications. Despite substantial preclinical evidence, the clinical translation of GA is hindered by poor drug availability. This review provides a critical synthesis of existing evidence and outlines strategies to advance the therapeutic development of this traditional medicine-derived compound.

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.

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" () 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.

Fructus Ligustri Lucidi (FLL), the fruit of , is used in traditional Chinese medicine to treat aging-related symptoms. This study aimed to explore the regulatory effects of the -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 -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 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 -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.

Ischemic stroke seriously endangers both the health and quality of life of patients. The gut microbiota, which plays a crucial role in modulating communication between the gut and the nervous system, has emerged as a promising target for therapeutic interventions in stroke. Electroacupuncture (EA), which is associated with intestinal immunity, has been proven to exert significant beneficial effects in ischemic stroke, but its exact mechanism remains unclear. In this study, we investigated the regulatory mechanism of EA on the microbiome-gut-brain axis following ischemic stroke. In rat models of ischemic stroke, EA treatment significantly reduced cerebral infarct volume and neuronal damage following cerebral ischemia-reperfusion injury, and also modulated the composition, diversity, and taxonomic distribution of the gut microbiota. Fecal microbiota transplantation from EA-treated donors significantly reduced cerebral infarct volume and neuronal damage in the ischemic hemisphere of recipient mice, and likewise upregulated Treg cell expression to suppress immune-inflammatory responses in the brain. These results indicate that, through modulation of the gut microbiota, which in turn regulates Treg-mediated immune-inflammatory responses, EA ameliorates cerebral ischemic injury to thereby improve the prognosis of ischemic stroke patients. This study provides new perspectives on the efficacy of EA in the treatment of ischemic stroke.

L., an ancient medicinal tree with origins tracing back over 280 million years, holds a unique place in both traditional and modern therapeutic systems. Widely used in East Asian ethnomedicine, and increasingly validated by pharmacological research, it serves as a rich source of bioactive compounds like terpene trilactones (ginkgolides, bilobalide), flavonoids (quercetin, kaempferol), alkaloids, proanthocyanidins, alkyl phenols, and organic/phenolic acids. This review provides a critical synthesis of traditional uses, phytochemical constituents, and pharmacological activities, and highlights its anti-oxidant, anti-inflammatory, anticancer, neuroprotective, and vasoprotective properties. In addition, recent advances in the structural transformation and semi-synthetic modification of ginkgolides are presented to offer insights into their structure-activity relationships. Beyond therapeutic roles, exhibits notable potential in non-pharmaceutical domains, which include its use as a natural colorant and photoprotective agent in cosmetics, and as a bio-based material in textile dyeing. Through a systematic examination of peer-reviewed literature, this review underscores multifaceted value as a promising botanical resource for both medicinal and industrial innovation.

The growing global burden of metabolic syndrome (MetS), a key driver of multiple chronic diseases, highlights the limited treatment options for its multifactorial pathophysiology. Tanshi-Tiaoti Decoction (TTD), a Chinese herbal formula comprised of (Tangerine peel), (Raw coix seed/Job's tears), (Radish seed), (Lotus leaf), (Kelp), and (Raw hawthorn fruit), demonstrates efficacy in the clinical management of MetS. However, its underlying molecular mechanisms remain incompletely elucidated. This study indicates that TTD restored gut microbiota homeostasis and bile acid (BA) profiles in high-fat diet (HFD)-induced MetS mice. TTD significantly attenuated body weight gain, fasting glucose levels, serum triglycerides, and hepatic steatosis. TTD corrected gut microbiota dysbiosis, most notably by reducing the Firmicutes/Bacteroidetes ratio. Fecal microbiota transplantation (FMT) validated the fact that the gut microbiome mediates TTD's therapeutic effects. TTD regulated BA biosynthesis through this microbial modulation, and thus specifically increased hyodeoxycholic acid (HDCA). HDCA, which has been identified as the signature BA during TTD treatment, phenocopied TTD's therapeutic effects against MetS by both activating the BA receptor TGR5 and subsequently promoting beige adipocyte browning. Collectively, TTD ameliorates MetS by reshaping microbial-mediated BA pools, and in particular elevates HDCA levels to thereby activate TGR5 and induce beige adipocyte browning. These findings support TTD as a promising herbal-based therapeutic strategy for the treatment of MetS.

Cancer remains a major global health challenge, which drives the ongoing search for effective and less toxic treatment options. Due to its demonstrated anticancer properties, Artesunate (ART), a well-established antimalarial agent, has gained increasing attention as a promising candidate for oncological applications. This systematic review provides a comprehensive evaluation of ART's therapeutic potential by examining its anticancer efficacy, underlying molecular mechanisms, synergistic capacity, and pharmacological toxicity. An extensive search of the PubMed and Web of Science databases identified relevant peer-reviewed experimental and clinical studies that investigated ART's anticancer activity. The data were systematically extracted with an emphasis on research methodologies, treatment regimens, and mechanistic pathways. Evidence from and studies confirms ART's broad efficacy against a range of malignancies, including hematological cancers such as lymphoma, acute myeloid leukemia, and multiple myeloma, and various solid tumors such as lung, pancreatic, colorectal, hepatocellular, breast, ovarian, bladder, gastric, cervical, glioblastoma, melanoma, retinoblastoma, and esophageal cancers. ART exerts its anticancer effects through multiple pathways, including ROS-mediated programmed cell death, ferroptosis induction, mitochondrial dysfunction, the inhibition of proliferation, and the disruption of key signaling networks such as NF-κB, STAT3, and Wnt/β-catenin cascades. Additionally, ART has been shown to enhance the efficacy of conventional chemotherapeutic agents like cisplatin and gemcitabine while also reducing associated toxicities and overcoming drug resistance. These attributes highlight ART's considerable potential as a versatile anticancer agent that exhibits multiple - mechanisms of action and favorable compatibility with existing therapies. However, further rigorous clinical studies are essential to fully establish its therapeutic utility and facilitate its integration into modern oncology practice.

Alzheimer's disease (AD) currently lacks effective therapeutics, but blood-brain-barrier-penetrating flavonoids show promising therapeutic potential. To address this critical need, we employed a novel network medicine framework to systematically identify flavonoid compounds for AD therapy by quantifying their network proximity to AD targets. Our systematic screening identified 48 potential anti-AD flavonoids, of which luteolin, quercetin, apigenin (API), and baicalein demonstrated significant neuroprotective effects in A[Formula: see text]25-35-induced rat pheochromocytoma (PC12) cell models. Of these, API emerged as the most promising candidate. A network pharmacological analysis revealed that API likely exerts its anti-AD effects through modulating apoptosis and inflammatory response, and AKT1 and NFKBIA were identified as key therapeutic targets. Experimental validation demonstrated that API treatment impeded the HO-induced decline in the mitochondrial membrane potential of PC12 cells, suppressed apoptosis, and mitigated neuronal damage. Furthermore, API downregulated the AKT/NF-[Formula: see text]B signal pathway, promoted microglial M2 polarization, and attenuated LPS-induced neuroinflammation in BV2 cells. API also alleviated the toxic effects of M1 microglia on neurons. This network-based screening strategy provides an innovative approach for developing new AD therapeutics.

As cancer continues to pose a significant threat to human health, the search for effective therapeutic agents has become a critical focus in medical research. Cordyceps is a fungus used in traditional Chinese medicine (TCM) valued for its potential health benefits, which include boosting energy, supporting the immune system, and acting as an anti-oxidant. Cordycepin, also known as 3[Formula: see text]-deoxyadenosine, is a bioactive nucleoside derived from Cordyceps. This compound recently has garnered widespread attention for its potential anticancer properties. Through systematic integration of our prior experimental evidence with literature retrieval from PubMed, we confirmed its efficacy in inducing apoptosis, suppressing proliferation, and blocking metastasis across a broad range of cancer types. These effects are primarily attributed to its modulation of key signaling pathways, such as MAPK, AMPK, mTOR, and Wnt/[Formula: see text]-catenin, all of which play crucial roles in various malignant conditions. In addition, cordycepin's ability to modulate immune responses through the regulation of adenosine receptor (AR), and in particular the A3 adenosine receptor (A3AR), has gained attention as an innovative strategy for enhancing the effectiveness of immunotherapy. Recent advancements in improving cordycepin's biostability, bioavailability, and transport efficiency within the body system have further supported the clinical application of this compound in medical oncology. This review highlights key research findings and explores promising future directions with the aim of contributing to ongoing studies in cancer management.

Inflammation is a pathological process implicated in a wide range of diseases, and is orchestrated by complex regulatory networks at both transcriptional and post-transcriptional levels. A growing body of evidence supports the understanding that numerous natural compounds exhibit robust anti-inflammatory activity, structural diversity, low toxicity, and minimal side effects. These qualities make them promising leads for therapeutic development. Within the framework of Traditional Chinese Medicine (TCM), which has been extensively applied in the management of chronic conditions, specific herbal remedies, such as for rheumatoid arthritis, and and for cardiovascular regulation, have clinically relevant efficacy. In recent years, bioactive peptides (BAPs) derived from Chinese medicinal herbs, including peptides from and , have drawn considerable international attention for their anti-inflammatory potential. This review delineates the principal methodologies for the extraction, isolation, and purification of anti-inflammatory peptides derived from medicinal herbs, highlights recent advances in their therapeutic application for inflammatory disorders, critically assesses existing barriers to clinical translation, and outlines future research priorities.

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) and a 5 mg/kg/d subcutaneous injection of Isoproterenol (ISO) was used to induce myocardial fibrosis in mice . 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.

Notoginsenoside R1 (NGR1), a natural triterpenoid saponin, is extracted from , and has cardiovascular and cerebrovascular protective effects due to anti-inflammatory, anti-oxidant, and anti-apoptotic properties. Previous research has suggested a protective role for NGR1 in myocardial ischemia/reperfusion (MI/R) injury. However, the potential mechanisms involved have not been fully elucidated. Thus, the objective of our study was to validate the protective role of NGR1 in MI/R injury and to investigate its underlying mechanisms. Results showed that, in mice, NGR1 substantially improved heart function, reduced infarct area, and inhibited cardiomyocyte apoptosis. Mechanistically, network pharmacological predictions suggested that NGR1 could inhibit apoptosis by activating the Wnt signaling pathway. Experimentally, the protective effects of NGR1 in inhibiting cardiomyocyte apoptosis, improving cardiac function, and reducing infarct size were significantly attenuated with the use of the Wnt signaling inhibitor XAV-939. Collectively, our investigation demonstrated that NGR1 improves myocardial injury triggered by ischemia/reperfusion (I/R) by enhancing Wnt/[Formula: see text]-catenin pathway activity, which in turn suppresses apoptosis.

The incidence of non-alcoholic fatty liver disease (NAFLD) has increased and become a serious global public health problem in recent years. The currently generally used clinical treatments have disadvantages such as side effects, limitations, and poor patient compliance. Traditional Chinese medicine (TCM) has a pharmacological effect with multiple components, multiple targets, and multiple pathways, emphasizing a "holistic concept" and "differential diagnosis and treatment," which is compatible with the complex pathogenesis of GM and NAFLD. Previous studies have demonstrated a close relationship between the gut microbiome (GM) and the occurrence and progression of NAFLD. However, the mechanisms between GM and NAFLD are complex. This paper not only analyzes the relationship between the GM and the pathogenesis of NAFLD but also discusses in detail how various TCM active metabolites and Chinese herbal formulas could exert a therapeutic effect on NAFLD by regulating the GM and its metabolites. Furthermore, this paper innovatively explores how TCM regulates the abundance of five major bacterial phyla, and their representative genera, to improve the pathogenesis of NAFLD. In summary, this review article proposes innovative ideas and options for the prevention and treatment of NAFLD with focus on GM regulation, and provides a theoretical basis for the development of new drugs from traditional Chinese medicine.

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.

Formononetin exhibits potent anti-oxidative and anti-inflammatory properties, but its precise therapeutic targets and mechanisms in diabetic kidney disease (DKD) remain insufficiently defined. This study evaluated the nephroprotective potential of formononetin using both (HK-2 cells) and (db/db mice) DKD models. By integrating network pharmacology and RNA sequencing, the antifibrotic actions of formononetin were further elucidated. Mechanistic investigations revealed that the compound reduced renal fibrosis by suppressing TGF-[Formula: see text]1, FN, and [Formula: see text]-SMA expression, and also alleviated renal dysfunction markers, including UACR, Scr, BUN, 24hUTP, KIM-1, and NGAL. These effects were mediated through the modulation of two key pathways such that the inhibition of the PI3K/AKT/mTOR cascade reduced inflammatory and fibrotic signaling, while the activation of the p38/MAPK axis enhanced autophagic flux, and thus promoted tubular epithelial cell homeostasis. Collectively, these findings support formononetin as a promising candidate for DKD therapy due to its combined anti-inflammatory and pro-autophagic mechanisms.