Phytomedicine最新文献

Background: Primary dysmenorrhea is associated with aberrant uterine contractility, inflammatory activation, and oxidative stress, resulting in nociceptive hypersensitivity and impaired quality of life. Lycopodium serratum Thunb. var. longipetiolatum Spring. (LS), a fern endemic to Taiwan, has been traditionally used to alleviate menstrual disorders; however, its mechanistic basis remains undefined.

Purpose: This study aimed to investigate the chemical constituents, uterine relaxant, and antinociceptive effects of LS extracts, and to elucidate their molecular mechanisms in dysmenorrhea.

Methods: Ethanolic extracts of LS and their solvent-partitioned fractions, ethyl acetate (LSE-EA), n-butanol (LSE-BuOH), and aqueous (LSE-H₂O) were characterized by LC-MS/MS for phenolic constituents. The relaxant and antinociceptive effects were assessed in ex vivo uterine contraction assays induced by prostaglandin F₂α (PGF₂α), oxytocin, acetylcholine, and carbachol, and in acetic acid- and oxytocin-induced pain models in ICR mice. Western blot, biochemical, and histopathological analyses were performed to delineate molecular and oxidative pathways.

Results: LSE-EA exhibited the strongest inhibition of uterine contraction and pain responses. LC-MS/MS identified ferulic acid, caffeic acid, and chlorogenic acid as major metabolites. Mechanistically, LSE-EA downregulated oxytocin receptor (OTR) and myosin light chain kinase (MLCK), suppressed TLR-4/NF-κB/COX-2 and ERK activation, reduced uterine IL-6 expression, and attenuated oxidative stress, as evidenced by decreased malondialdehyde levels and restoration of redox balance.

Conclusion: Lycopodium serratum extract confers protection against dysmenorrhea through concurrent suppression of Ca²⁺-dependent uterine contraction, inflammatory signaling, and oxidative stress. These findings identify LSE-EA as a novel bioactive fraction with therapeutic potential in redox-mediated uterine dysfunction.

Background: Traditional Chinese medicine (TCM) compatibility (TCMC) is an important form of clinical application of TCM, and proper compatibility are key to ensuring the safe use of TCM. However, reports of liver injury associated with the combination of Epimedii Folium (EF) and Psoraleae Fructus (PF), a commonly used pair of TCM in clinical, have gradually increased in recent years. The mechanism underlying this phenomenon remains unclear, which significantly hinders the development of risk prevention and control strategies for the EF and PF combination.

Methods: Bone marrow-derived macrophages (BMDMs) were employed to establish an in vitro inflammasome activation model for screening susceptibility factors of idiosyncratic liver injury exacerbated by the combination of EF and PF. Subsequently, a classical idiosyncratic liver injury evaluation model was utilized to objectively assess the susceptibility of the combined treatment in aggravating liver injury. Finally, mechanisms underlying the combined use of EF and PF in exacerbating idiosyncratic liver injury were systematically evaluated through RNA-seq, flow cytometry, immunofluorescence, and immunohistochemistry.

Results: The combined use of EF and PF significantly enhanced the activation of the inflammasome. Specifically, Icariside I, a main compound of EF, synergistically promoted the activation of the NLRP3 inflammasome induced by bavachinin, a main compound of PF, while bavachinin directly activated inflammasome components such as NLRP3, NLRC4, and AIM2, leading to enhanced inflammasome activation, increased inflammation, increased apoptosis, and exacerbated oxidative stress, ultimately exacerbating liver injury. In addition, RNA-seq and GSEA analyses further confirm the association between the exacerbation of liver injury and abnormal activation of inflammasomes. Therefore, inflammasome-promoting TCM, such as EF, and inflammasome-activating TCM, such as PF, should be avoided in combination with immune-activated populations, and co-administration with drugs that downregulate inflammasome activation can reduce toxicity.

Conclusion: In summary, this study proposes a precision toxicity control strategy represented by exacerbate idiosyncratic liver injury caused by the combination of EF and PF, offering new insights to ensure its clinical safety and thereby reduce the occurrence of TCM-related liver injury events.

Background: Isodeoxyelephantopin (IDET) is a sesquiterpene lactone isolated from traditional herb Elephantopus scaber, which is known for its anti-inflammatory activities. While our previous study demonstrated that IDET inhibits NLRP3 expression in an acute peritonitis model, its therapeutic potential in chronic inflammatory diseases such as ulcerative colitis (UC), as well as the underlying mechanisms involving inflammasome signaling, have not yet been fully elucidated.

Purpose: This research was designed to explain the protective capacity of IDET in UC and to clarify how IDET modulates IL-1β-mediated inflammatory responses through the TXNIP/NLRP3 signaling pathway, by integrating in vitro and in vivo experimental systems.

Results: IDET significantly reduced dextran sulfate sodium (DSS)-induced colitis in mice, improving disease scores, reducing inflammation, and preserving colon histology. Mechanistically, IDET exerted a multi-tiered suppression of the inflammasome pathway, which suppresses IL-1β-driven inflammation. Firstly, it disrupted the upstream priming signal by downregulating NLRP3 expression through NF-κB signaling pathway. Secondly, it inhibited inflammasome assembly, as evidenced by reduced ASC oligomerization and NLRP3-ASC interaction. Consequently, IDET reduced the cleavage of pro-caspase-1 and pro-IL-1β, resulting in an approximately 4-fold reduction in mature IL-1β secretion. A key finding was that IDET interfered with the activation signal by attenuating the TXNIP-NLRP3 interaction, according to immunoprecipitation and molecular docking results.

Conclusions: Extending our previous findings on its anti-acute inflammatory activity, this study demonstrates that IDET alleviates experimental ulcerative colitis by targeting multiple stages of NLRP3 inflammasome activation. The results highlight the translational potential of IDET, a natural compound, for treating chronic intestinal inflammation.

Background: Diabetic retinopathy (DR) pathogenesis is driven by the dysregulation of an interconnected network of regulated cell death (RCD) modalities, including apoptosis, autophagy-dependent cell death, pyroptosis, and ferroptosis. Current therapies often fail to address this upstream cellular damage. Natural products (NPs), with their inherent polypharmacology, offer a promising strategy to modulate this complex network.

Purpose: This review advances a framework conceptualizing DR as the collapse of a dynamic RCD network and positions NPs as "RCD network modulators". We delineate how these agents can restore homeostasis and overcome the limitations of existing mono-target therapies.

Methods: A systematic literature search was conducted using Web of Science and PubMed, integrating keywords related to "natural products", "diabetic retinopathy", and specific "regulated cell death" modalities. All animal experiments adhered to ethical guidelines and complied with both international and institutional ethical standards.

Results: NPs simultaneously engage the master regulatory nodes-mitochondrial dysfunction, hyperactivation of the inflammasome, and oxidative stress. By modulating the Bcl-2 rheostat, normalizing autophagic flux, suppressing NLRP3 assembly, and activating Nrf2/SIRT1 pathways, NPs orchestrate a "network rewiring" to halt DR progression. However, clinical translation is significantly constrained by pharmacokinetic challenges, including low oral bioavailability and poor ocular penetration.

Conclusion: DR pathology emerges from network-level RCD dysregulation. NPs, which function as modulators of the RCD network, represent a compelling therapeutic shift toward addressing the root drivers of retinal degeneration.

Background: Anemoside B4 (AB4), a pentacyclic triterpenoid saponin, exhibits potent anti-inflammatory and antioxidant activities; however, it has poor oral bioavailability. Hypobaric hypoxia (HH) can induce high-altitude acute lung injury (ALI) through inflammatory response and oxidative stress pathways, highlighting the need for effective targeted therapies.

Purpose: This study aimed to develop an AB4 dry powder inhaler (DPI) for improving lung deposition and bioavailability, and to evaluate its prophylactic efficacy against high-altitude ALI.

Methods: AB4 inhalable microparticles were prepared by antisolvent precipitation and developed into a DPI formulation. Aerodynamic properties were characterized by mass median aerodynamic diameter (D₅₀) and fine particle fraction (FPF). Anti-inflammatory activity was assessed in vitro using an LPS-stimulated alveolar macrophage model. An in vivo HH/LPS co-induced rat model of high-altitude ALI was established to investigate pharmacodynamic effects and bioavailability.

Results: AB4 DPI exhibited excellent aerodynamics (D₅₀: 1.92 μm; FPF: 62.86 ± 10.51%). It inhibited LPS-induced release of TNF-α, IL-6, and IL-1β. Inhalation of AB4 DPI attenuated pulmonary inflammation in vivo and restored oxidative balance by reducing malondialdehyde (MDA) and myeloperoxidase (MPO) levels while increasing superoxide dismutase (SOD) activity. The absolute bioavailability reached 18.61 ± 5.81%, representing a 74.44-fold increase compared to oral administration (0.25 ± 0.19%).

Conclusion: This study successfully combined a traditional Chinese medicine component with advanced particle engineering technology to develop an efficient non-invasive pulmonary drug delivery system. AB4 DPI retained bioactivity while markedly addressing the pharmacokinetic limitations of oral administration, offering a clinically promising prophylactic strategy against high-altitude ALI.