Siweixizangmaoru Decoction Alleviates Rheumatoid Arthritis by Enhancing Pol β-Mediated Attenuation of DNA Damage and Suppression of cGAS/STING/NF-κB/NLRP3-Associated Pyroptosis
Aug 2026· Pharmaceuticals· Vol 19, pp. 1302· 0 citations· 48 references
Medicine
TL;DR
Results showed that SXD attenuated RA progression and reduced inflammatory cytokine levels in rat serum and cell culture supernatants, and support the partial involvement of Pol β-associated processes in the anti-arthritic effects of SXD.
Abstract
Objective: Siweixizangmaoru decoction (SXD), a classical Tibetan prescription documented in the medical text Four Medical Tantras, has shown therapeutic activity in experimental rheumatoid arthritis (RA). However, its candidate active constituents and underlying mechanisms remain unclear. Methods: In this study, serum-absorbed constituents following SXD administration were profiled using ultra-high-performance liquid chromatography coupled with quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS), and network pharmacology was employed to identify core targets and candidate active constituents of SXD against RA. Candidate active constituents were further screened using cell-based assays, and the selected constituents were quantified using HPLC fingerprint analysis. Both in vivo (CIA rat model) and in vitro (RAW264.7 pyroptosis model) systems were used to investigate the pharmacological effects and mechanisms of SXD. Results: A total of 11 absorbed constituents were identified in the serum of SXD-treated rats, and four preliminary candidate active constituents, including chebulagic acid, kaempferol, gentiopicroside, and berberine, were screened. The combined in vivo and in vitro results showed that SXD attenuated RA progression and reduced inflammatory cytokine levels in rat serum and cell culture supernatants. At the molecular level, SXD increased Pol β expression and reduced DNA damage markers, cytosolic dsDNA accumulation, and cGAS/STING-, NF-κB-, and NLRP3-associated signaling. Pol β knockdown partially reduced the effects of SXD. Conclusions: These findings support the partial involvement of Pol β-associated processes in the anti-arthritic effects of SXD.
BXGG partially reversed CTX-associated reductions in body weight, thymus and spleen indices and partially restored serum interleukin-2, interleukin-4 (IL-4), and interferon-gamma (IFN-γ) levels, and white blood cell, lymphocyte, platelet, and reticulocyte counts.
Introduction: Ai Da Lotion is widely used for eczema in the clinic; however, its active ingredients and molecular mechanism remain unclear.
Objective: We set out to define the molecular basis for how Ai Da Lotion—a compound traditional Chinese medicine preparation—acts to treat eczema, with the goal of generating sound scientific support for its clinical use and modern translational development.
Methods: In this study, we combined ultra high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry profiling with network pharmacology and molecular docking to identify the formula’s bioactive constituents and key targets, then validated these findings in keratinocyte-based models of eczema.
Results: Chemical profiling identified 889 constituents, and physicochemical screening narrowed these to 42 candidate active compounds. Target network analysis uncovered 37 core nodes, with Janus kinase 1 (JAK1) and signal transducer and activator of transcription 3 (STAT3) emerging as the dominant regulatory pair. Two lead compounds—8-deoxylactucin and 6β-hydroxymethandrostenolone—bound JAK1 and STAT3 with high affinity (binding energy <−7.6 kcal/mol). Functionally, Ai Da Lotion promoted keratinocyte migration, attenuated oxidative stress, stabilized mitochondrial membrane potential, and suppressed Caspase-3–mediated apoptosis. These protective effects were recapitulated upon JAK1/STAT3 overexpression and blocked by selective pathway inhibition, indicating that the formula works primarily through JAK1/STAT3 modulation.
Conclusion: Our results provide a mechanistic basis for Ai Da Lotion and illustrate a practical strategy for dissecting the pharmacology of complex herbal dermatological preparations.
Yuan Li, Yangyang Liu, Zixiao Jiang et al.· Eurasian Journal of Medicine...· 0 citations
BACKGROUND
Atherosclerosis (AS) is a common chronic disease and the primary pathological basis for myocardial infarction, stroke, and other disabling conditions. Danggui Buxue Decoction (DBD) is a classic formula in Traditional Chinese Medicine (TCM) normally used for deficiency patterns. However, whether DBD can alleviate atherosclerosis, which bioactive constituents are responsible, and which molecular mechanisms are involved remain to be further investigated.
PURPOSE
This study aims to characterize the absorbed bioactive components of DBD and decipher the multi-target mechanisms by which it counteracts atherosclerosis, providing a scientific rationale for its clinical application.
METHODS
This study employs an integrated approach combining network pharmacology, WGCNA, and machine learning screening strategies, supported by experimental validation, to systematically elucidate the active pharmaceutical ingredients and molecular mechanisms of anti-AS effects of serum-absorbed constituents of DBD after oral administration.
RESULTS
Network pharmacology and machine learning analyses predicted CD36, TRPM2, and TNF-α as three core targets for DBD intervention in AS. CETSA and BLI experiments further confirmed stable binding of Ligustilide and Tectoridin in DBD to these targets. In vivo and in vitro experiments demonstrated that the combined treatment of Ligustilide and Tectoridin effectively inhibit macrophage foaming, mitigate oxidative damage, and downregulate inflammatory cytokine release.
CONCLUSION
This study successfully identified Ligustilide and Tectoridin as the primary bioactive constituents of DBD against atherosclerosis. By modulating CD36, TRPM2, and TNF-α, these compounds synergistically inhibit foam cell formation and inflammation, offering a novel pharmacological perspective on the anti-AS efficacy of DBD.
Xin Li, Shui-Hong Zheng, Yu-Qiong Song et al.· Phytomedicine· 0 citations
BACKGROUND
Zaoshi Huatan Xiefei Formula (ZHXF) is a Chinese medicine prescription used in the treatment of severe pneumonia (SP). Although clinical studies have confirmed its efficacy in improving pneumonia, the specific bioactive components and their intricate regulatory pathwaysremain incompletely understood.
PURPOSE
This research aims to identify the active components of ZHXF, along with its potential targets and molecular mechanisms for treating SP.
METHODS
The main active ingredients of ZHXF and its blood chemical components were determined by UPLC-Q-Exactive Orbitrap MS. The core targets and biological immune regulatory mechanisms through which ZHXF improves SP were predicted using an integrated approach of network pharmacology, molecular docking, MD simulation, SPR, and proteomics. The protective effect of ZHXF on SP, along with its potential targets and mechanisms, was validated through experiments.
RESULTS
130 ingredients of ZHXF were identified by UPLC-Q-Exactive Orbitrap MS, five were confirmed as its primary bioactive ingredients in the blood. Network pharmacology analysis showed that modulating the MAPK and NF-κB pathways is a key mechanism through which ZHXF improves SP. Molecular docking, MD simulations, and SPR indicated that the key components of ZHXF bind effectively to ERK1/2, JNK, and P38, thereby suppressing MAPK/NF-κB pathway expression. Proteomic analysis further revealed VCAM1 as the core target of ZHXF, indicating that ZHXF alleviates the impact of lung inflammation by regulating leukocyte transendothelial migration. In vitro study have confirmed the ZHXF inhibitory effect on leukocyte transendothelial migration. In vivo experiments have shown that ZHXF can significantly alleviate pulmonary inflammation symptoms in SP mice, and this protective effect on lung tissue was achieved through the inhibition of leukocyte transendothelial migration.
CONCLUSION
This study confirms that ZHXF improves lung inflammation by suppressing the activation of the MAPK/NF-κB pathway and regulating VCAM1 mediated leukocyte transendothelial migration. This study provides a novel perspective for the treatment of SP with ZHXF.
In vitro, LJFE dose-dependently activated the Keap1/Nrf2/HO-1 signalling axis and suppressed excessive NO release in LPS-challenged macrophages, and support the potential of LJFE for further development as an immune-enhancing functional food ingredient.
Mei Peng, Xiong Pan, Guanping Yao et al.· Frontiers in Pharmacology· 0 citations
OBJECTIVE
To investigate the therapeutic effects of Yibi Decoction (YBD) in rheumatoid arthritis (RA) and to elucidate the underlying mechanisms, with a particular focus on the JAK/STAT signaling pathway.
METHODS
Network pharmacology analysis was employed to predict the bioactive compounds and potential therapeutic targets of Yibi Decoction. A collagen-induced arthritis (CIA) rat model was established to validate the predicted effects in vivo. Western blotting, enzyme-linked immunosorbent assay (ELISA), and histopathological analyses were conducted to evaluate alterations in joint tissues and serum inflammatory biomarkers.
RESULTS
Network pharmacology analysis identified 128 bioactive components in YBD, among which quercetin and luteolin were predicted to be key active compounds. In CIA rats, YBD treatment significantly downregulated the expression of IL-6, IL-17, IL-23, JAK2, and STAT3 in ankle joint tissues (P < 0.05), and markedly reduced serum levels of anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor (P < 0.05). In parallel, the arthritis index was significantly decreased, and histopathological examination revealed substantial attenuation of synovial hyperplasia and cartilage destruction.
DISCUSSION
These findings suggest that YBD exerts anti-rheumatoid arthritis effects through a multi-component, multi-target regulatory mechanism involving inhibition of the JAK/STAT signaling pathway. Quercetin and luteolin may contribute to these effects by suppressing pro-inflammatory cytokine production and ameliorating joint pathological changes.
CONCLUSION
YBD ameliorates rheumatoid arthritis by suppressing the JAK/STAT signaling pathway and associated inflammatory responses, thereby providing a mechanistic basis for its potential therapeutic application in rheumatoid arthritis.