Curcuma is a traditional Chinese medicine that has been utilized for centuries in the treatment of various diseases. Terpenoids, particularly monoterpenes and sesquiterpenes, constitute the primary bioactive components of the essential oil derived from Curcuma species. Among these, curdione—one of the key active constituents—has been identified in 25 Curcuma species, with the highest concentration reported in the rhizome essential oil of Curcuma trichosantha Gagnep. Curdione can also be synthesized through chemical methods, and its regio- and stereo-selectivity can be further optimized via chemo-bio transformations. This compound demonstrates significant therapeutic potential, including anticancer, anti-thrombotic, anti-inflammatory, anti-viral, anti-fungal, anti-diabetic, and multi-organ protective properties. Despite these promising biological activities, its clinical application is hindered by poor water solubility and potential toxicity. This review summarizes current knowledge on the natural sources, chemical synthesis, chemo-bio transformations, metabolism, pharmacokinetics, pharmacological effects, potential toxicities, and molecular mechanisms of curdione. Furthermore, perspectives on future drug development are discussed with the aim of promoting the clinical translation of this promising natural compound.

Mesenchymal stem cells (MSCs) are widely utilized in disease treatment and regenerative medicine due to their potent immunomodulatory properties and capacity for tissue repair. However, limitations—including insufficient migratory capacity, suboptimal survival, proliferation, differentiation potential, and variable immunomodulatory responses—significantly hinder their clinical translation and therapeutic impact. Natural products have been shown to enhance MSC homing, stress resilience, immune regulation, and lineage-specific differentiation through multi-target mechanisms, thereby emerging as promising, safe, and practical strategies to improve the in vivo performance of MSC-based therapies. This review examines the key translational challenges associated with MSCs, elucidates the mechanistic basis by which natural products regulate the in vivo fate of MSCs, and explores the potential of integrating natural product adjuvants with MSC therapy for enhanced clinical outcomes.

Taohong Siwu Decoction (THSWD), a traditional Chinese medicinal formulation, has been demonstrated to significantly modulate key signaling pathways implicated in atherosclerosis (AS). This review examines the complex mechanisms through which THSWD influences critical pathways, including nuclear factor kappa-B (NF-κB), phosphatidylinositol 3-kinase (PI3K)/serine-threonine kinase (AKT), Toll-like receptor 4 (TLR4), mitogen-activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR), that play pivotal roles in AS pathogenesis. By synthesizing experimental evidence and existing literature, the review summarizes how THSWD and its bioactive constituents regulate these signaling cascades to ameliorate AS. Furthermore, it highlights the distinctive therapeutic advantages of traditional Chinese medicine (TCM) compounds in managing chronic diseases driven by multi-target and multifactorial mechanisms. Analyzing disease targets from the perspective of signaling pathways enhances the scientific validation of clinical efficacy for such formulations, thereby offering novel insights for future research.

Chronic heart failure (CHF) remains a global health challenge with limited therapeutic options. Mitochondrial dysfunction is a key pathological feature, and traditional Chinese medicine (TCM) shows unique potential in targeting this mechanism. Evidence from human and animal models of heart failure indicates that TCM can restore mitochondrial function by regulating mitochondrial Ca²⁺ homeostasis, oxidative stress, energy metabolism, mitochondrial dynamics, and mitophagy. TCM-based treatment of CHF offers notable clinical advantages, including improved therapeutic efficacy, enhanced cardiac function, and reduced incidence of major cardiovascular events. Experimental studies demonstrate that TCM decoctions and monomers modulate signaling pathways such as PPAR-RXRα, NF-κB, and PI3K/AKT to alleviate oxidative stress. TCM also increases AMPK activity via phosphorylation of PGC-1α, indirectly promoting mitochondrial biogenesis; attenuates calcium influx and enhances Ca²⁺ reuptake, thereby ameliorating myocardial mitochondrial dysfunction in CHF; and improves CHF by rebalancing mitochondrial dynamics and autophagy.

Epigallocatechin-3-gallate (EGCG), a major polyphenolic compound in green tea, exhibits anti-viral activity against multiple viruses, including hepatitis B virus (HBV). However, its role in HBV replication and the underlying mechanisms remain incompletely understood. In this study, we investigated the effects of EGCG on HBV replication and its modulation of autophagy using two established HBV cell models. Our results show that EGCG significantly reduces secreted levels of hepatitis B surface antigen (HBsAg) and HBV deoxyribonucleic acid (DNA), as well as intracellular HBV DNA replicative intermediates, encapsidated pregenomic ribonucleic acid (pgRNA), and core protein (HBc), without affecting total HBV messenger RNAs (mRNAs) or pgRNA levels. EGCG enhances autophagic flux, evidenced by increased autophagosome formation and accelerated turnover of the selective autophagy receptor p62 and LC3-Ⅱ. This enhanced autophagy promotes HBc degradation. Pharmacological inhibition of autophagy with 3-methyladenine (3-MA), chloroquine (CQ), or bafilomycin A1 (BafA1) abolished the suppressive effect of EGCG on HBV. Notably, treatment with CQ or BafA1 together with EGCG markedly increased HBV production by blocking autophagic degradation and inducing accumulation of autophagosomes—effects similar to those induced by the autophagy activator rapamycin, which facilitates HBV replication. Mechanistically, EGCG activates the adenosine 5'-monophosphate-activated protein kinase (AMPK)/transcription factor EB (TFEB) signaling axis, leading to enhanced lysosomal biogenesis and ATP production, thereby promoting autophagic clearance. Pharmacological or genetic inhibition of AMPK attenuated TFEB transcriptional activity, suppressed lysosomal biogenesis and ATP generation, impaired autophagic degradation, increased HBc levels, and ultimately enhanced HBV replication. Conversely, pharmacological activation of AMPK produced opposing effects. These findings reveal a novel mechanism by which EGCG inhibits HBV: EGCG promotes autophagic degradation of the viral core protein via activation of the AMPK/TFEB signaling pathway.

Ulcerative colitis (UC) is a persistent, diffuse intestinal inflammation and ranks among the most challenging chronic diseases worldwide. Atractylodes lancea (Thunb.) DC. and Atractylodis macrocephala Koidz. are traditional Chinese medicines (TCMs) with a long history of clinical application, particularly for gastrointestinal disorders. Both Atractylodis Rhizoma (AR) and Atractylodis Macrocephala Rhizoma (AM) have shown significant efficacy in managing UC; however, the underlying mechanism by which the AR-AM herbal pair promotes intestinal mucosal healing remains poorly understood. The therapeutic effects of the ethanolic extract of AR-AM (EEAR-AM) were evaluated in a murine UC model induced by dextran sodium sulfate (DSS). A network pharmacology approach was employed to explore the anti-UC properties of EEAR-AM, including identification of active compounds, prediction of potential targets, and construction of a protein-protein interaction (PPI) network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were subsequently performed to preliminarily elucidate the mechanisms of EEAR-AM in UC treatment. Finally, the proposed molecular mechanisms were validated in both DSS-induced UC mice and Caco-2 cells. In vivo results demonstrated that EEAR-AM significantly attenuated DSS-induced weight loss, reduced colon shortening, lowered the disease activity index (DAI) score, and modulated the spleen coefficient. Moreover, EEAR-AM improved colonic tissue architecture, reduced inflammatory infiltration, restored goblet cell density, enhanced mucin MUC2 expression, and elevated levels of tight junction (TJ) proteins. Additionally, EEAR-AM suppressed the expression of matrix metalloproteinase 2 (MMP-2) and MMP-9. Network pharmacology analyses indicated that EEAR-AM may ameliorate intestinal mucosal dysfunction through modulation of the exchange protein directly activated by cAMP 1 (Epac1)/Ras-associated protein 1 (Rap1) pathway and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathways. These actions potentially enhance cellular barrier integrity and reduce the release of inflammatory mediators. Western blotting results confirmed that EEAR-AM activated the Epac1/Rap1 pathway while downregulating the PI3K/AKT pathway in both DSS-induced UC mice and Caco-2 cells, consistent with predictions from network pharmacology. This study represents the first evidence that the EEAR-AM herbal pair improves intestinal mucosal barrier function in UC, with therapeutic effects likely mediated by activation of the Epac1/Rap1 pathway and inhibition of the PI3K/AKT pathway.

Oxaliplatin (OXA) is a widely used chemotherapeutic agent whose clinical utility is limited by OXA-induced peripheral neuropathy (OIPN). Sarco/endoplasmic reticulum Ca²⁺-ATPase (SERCA) transports Ca²⁺ from the cytoplasm into the endoplasmic reticulum (ER), thereby maintaining intracellular Ca²⁺ homeostasis. Schefflera kwangsiensis Merr. ex H.L. Li (SKM) is traditionally used to treat neuropathic pain conditions such as trigeminal neuralgia and sciatica, and its active component Schekwanglupaside C has been identified as a potent SERCA activator. In this study, an OIPN mouse model was established by intraperitoneal administration of OXA (4 mg·kg⁻¹) on days 1, 2, 8, 9, 15, and 16. SERCA2b mRNA and protein expression in dorsal root ganglia (DRG) were evaluated by quantitative polymerase chain reaction (qPCR) and immunofluorescence. Mechanical allodynia was assessed using the Von Frey test. DRG neuronal excitability was examined by whole-cell current-clamp recordings, whereas oxidative stress and neuronal apoptosis/necrosis were assessed using the reactive oxygen species (ROS)-sensitive probe 2',7'-dichlorofluorescin diacetate (H₂DCFDA) and fluorescein isothiocyanate (FITC)/propidium iodide (PI) dual staining. This study identifies SERCA2b as a novel therapeutic target for OIPN. We observed that SERCA2b mRNA and protein levels were significantly downregulated during OIPN progression. Treatment with the SERCA agonist CDN1163 (CDN), the ethyl acetate extract of SKM (SKM.Ext), or duloxetine (DLX) attenuated neuronal pathology, restored DRG neuron soma diameter, and reduced the expression of pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α). Pre-incubation of DRG neurons with CDN1163 or SKM.Ext for 1 h significantly attenuated OXA-induced hyperexcitability and reduced the abnormal increase in voltage-gated sodium channel (VGSC) current density. Inhibition of oxidative stress with N-acetyl-L-cysteine (NAC) significantly restored SERCA expression in OIPN, indicating that oxidative stress downregulates SERCA2b in DRG. Collectively, these findings demonstrate that activation of SERCA2b by CDN1163 or Schefflera kwangsiensis extract enhances SERCA2b expression, reduces DRG neuronal sensitization, and alleviates OIPN. This work supports SERCA2b as a novel therapeutic target for OXA-induced neuropathy and expands the potential clinical analgesic indications of Schefflera kwangsiensis.

Colorectal cancer (CRC), one of the leading causes of cancer-related mortality globally, urgently requires complementary and alternative therapies. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a promising anti-cancer strategy. Dendrobium officinale (D. officinale), a renowned traditional Chinese medicinal herb, is widely used in several Asian countries for its nutritional and therapeutic benefits. Although D. officinale has demonstrated anti-tumor effects, the molecular mechanisms underlying its action against CRC remain incompletely characterized. This study aimed to elucidate the role of D. officinale in suppressing CRC through the induction of ferroptosis and its regulatory effects on glutathione peroxidase 4 (GPX4), a key suppressor of ferroptosis. In vitro assays were conducted using HCT116 and SW480 CRC cell lines, and in vivo efficacy was evaluated in BALB/c nude mice bearing CRC xenografts. D. officinale significantly reduced CRC cell viability and proliferation in vitro and suppressed tumor growth in vivo. Induction of ferroptosis was evidenced by elevated levels of Fe²⁺, malondialdehyde (MDA), and lipid peroxidation, along with a depleted glutathione/oxidized glutathione disulfide (GSH/GSSG) ratio. Notably, these effects were reversed by ferroptosis inhibitors, including ferrostatin-1 (Fer-1) and deferoxamine. Consistently, D. officinale markedly downregulated GPX4 expression. Overexpression of GPX4 rescued D. officinale-induced ferroptosis, whereas GPX4 silencing exacerbated this effect. D. officinale suppresses CRC by triggering GPX4-dependent ferroptosis, providing a novel, naturally derived therapeutic approach. These findings bridge traditional medicine and modern oncology, establishing a foundation for developing targeted CRC treatments.

Huperzine A (HupA) is a highly selective, reversible acetylcholinesterase (AChE) inhibitor that exhibits neuroprotective effects and is clinically used to manage benign memory decline. However, the specific relationship between the pharmacokinetic (PK) profile of HupA and cerebral acetylcholine (ACh) dynamics remains poorly characterized. Here, we characterize the PK-pharmacodynamic (PD) properties of HupA in rats under both physiological and pathological conditions. Following a single intramuscular injection, HupA exhibits a short half-life but rapid brain penetration, while multiple dosing significantly enhances its brain exposure. In a middle cerebral artery occlusion (MCAO) rat model, HupA demonstrates increased brain distribution. Furthermore, HupA elevates ACh concentrations across multiple brain regions, concurrently modulating several monoamine neurotransmitters. Using a minimal physiologically based pharmacokinetic-pharmacodynamic (mPBPK-PD) modeling approach, cerebral ACh dynamics were accurately predicted based on the pharmacokinetics of HupA in systemic circulation. The developed mPBPK-PD model exhibits robust predictive performance and holds potential for guiding the optimization of clinical dosing regimens and improving the therapeutic efficacy of HupA.

Five novel sulfur-containing benzyl metabolites, designated as gastrabenzylsulfoxides A and B (1 and 2), gastrabenzylsulfinate A (3) and gastrabenzylsulfides A and B (4 and 5), along with four known compounds (6−9), were isolated from the aqueous extracts of Gastrodia elata. Compounds 1 and 4 are 4-hydroxy-3-(4′-hydroxybenzyl)benzyl-substituted sulfoxide and sulfide, respectively, which are unprecedented in natural products. Compound 3 represents a rare sulfinate. Several isolates and their sulfone and disulfide analogs (10−13) were synthesized to evaluate their anti-inflammatory activity. Notably, the synthesized sulfone 10 demonstrated significant alleviation of symptoms in multiple in vivo inflammatory models.

Four new sesquiterpenoids (1−4), including the first reported instance of a novel 2,3-seco oplopane carbon skeleton (1), together with 19 known analogues, were isolated from the flower buds of Tussilago farfara (coltsfoot). The challenging determination of relative and absolute configurations—particularly in flexible side chains and substituents—was achieved for the first time through an integrated approach combining spectroscopic analyses, chemical derivatization, chiral gas chromatography (GC), and quantum chemical calculations. All compounds were evaluated for anti-diabetic activity using an insulin-stimulated glucose uptake model in C2C12 myotubes and for anti-inflammatory activity via a lipopolysaccharide (LPS)-induced nitric oxide (NO) inhibition assay in RAW264.7 macrophages. Six compounds significantly enhanced glucose uptake, and mechanistic investigation of compound 3 revealed activation of the insulin receptor substrate 1 (IRS-1)/protein kinase B (Akt)/glycogen synthase kinase 3β (GSK-3β) signaling pathway. Twenty-one compounds exhibited marked inhibition of NO production; among them, compounds 2 and 6 dose-dependently suppressed inducible nitric oxide synthase (iNOS) expression and nuclear factor κB (NF-κB) phosphorylation.