Objective To investigate the antifibrotic effect of combined treatment with sodium arsenite (SA, biotransformation product of arsenic trioxide) and N-acetylcysteine (NAC) on pulmonary fibrosis. Methods L929 fibroblasts were treated with SA or NAC for 24 h before measuring cell viability. The combination drug ratio was determined by examining the effects of different ratios of SA and NAC on viability of L929 cells, and the cell migration ability was detected using scratch assay and Transwell assay. Immunofluorescence assay was used to detect the effects of combined administration of SA and NAC on the expressions of α-smooth muscle actin (α-SMA), collagen type I α1 (COL1A1), and reactive oxygen species (ROS) level in transforming growth factor-β1 (TGF-β1)-induced L929 cells. A mouse model of idiopathic pulmonary fibrosis was established induced by bleomycin, after intervention with SA or NAC for 28 d, the survival and body weight changes of mice were observed. Hematoxylin-eosin (HE) and Masson staining were used to observe pathological changes in lung tissue. The total protein content, TGF-β1 level in bronchoalveolar lavage fluid (BALF), and hydroxyproline (Hyp) level in lung tissue were detected. Immunofluorescence assay was used to detect the expressions of α-SMA, COL1A1, CD86 and CD206 in lung tissue. Results The synergistic effect of SA and NAC combination therapy was related to their ratio. When SA∶NAC = 2∶1, the combination could significantly inhibit viability and migration of L929 cells (P < 0.001), and was superior to the monotherapy group (P < 0.01, 0.001). The combined administration of SA and NAC (2∶1) significantly down-regulated the expressions of α-SMA and COL1A1 in L929 cells induced by TGF-β1 (P < 0.001), and reduced ROS level (P < 0.01). The in vivo experimental results showed that compared with model group, the combined administration of SA and NAC (2∶1) could prolong the survival cycle of mice, increase body weight, reduce lung tissue damage and collagen deposition, decrease the total protein content, TGF-β1 level in BALF and Hyp level in liver tissue (P < 0.01, 0.001), reduce the expression of α-SMA and COL1A1 in lung tissue (P < 0.001), inhibit M2 polarization of lung tissue macrophages (P < 0.001), and had no significant toxic effects on major organs. Conclusion The combination of SA and NAC has a synergistic anti-pulmonary fibrosis effect, providing experimental evidence for the treatment of idiopathic pulmonary fibrosis with arsenic agents combined with thiol donors.

Objective To investigate the mechanism by which Huangqi (Astragali Radix)-Danshen (Salviae Miltiorrhizae Radix et Rhizoma) herb pair (HQ-DS) in treating hepatic fibrosis (HF) via regulating the endogenous retroviruses (ERVs)/retinoic acid-inducible gene I-like receptors (RLRs)/type I interferon (IFN-I) signaling pathway. Methods The components of HQ-DS extract and drug-containing serum were analyzed and identified using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). A total of 48 male C57BL/6J mice were randomly divided into control group, model group, HQ-DS low-, medium-, high-dose (4.55, 9.10, 18.20 g/kg) groups and silymarin (100 mg/kg) group, with eight mice in each group. A mouse model of HF was established using carbon tetrachloride (CCl₄), and after drug intervention, liver function related indicators in serum were detected. The pathological changes of liver tissue through hematoxylin eosin (HE) staining, Masson and Sirius red staining were observed. Flow cytometry was used to detect macrophage infiltration in liver tissue. Western blotting was used to detect the expressions of fibrosis related proteins in liver tissue. High-throughput transcriptome sequencing was used to analyze changes in gene transcription levels in liver tissue. The expressions of factors related to the ERVs/RLRs/IFN-I signaling pathway in liver tissue were detected using qRT-PCR, Western blotting and ELISA. A HF model was established in Mavs^-/- mice and intervened with HQ-DS to verify the mechanism of HQ-DS’s anti-HF effect. In vitro experiments were conducted using CCK-8 assay to evaluate the effect of HQ-DS on the activity of iBMDM cells stimulated by lipopolysaccharides (LPS) and nigericin. Immunofluorescence detection of dsRNA expression was performed, qRT-PCR and Western blotting were used to further verify the inhibitory effect of HQ-DS on the activation of ERVs. Results Compared with control group, the body weight of mice in model group was increased slowly, with vacuolar degeneration and inflammatory cell infiltration in liver tissue, liver function related indicators in serum were significantly increased (P < 0.001), and the expressions of factors related to the ERVs/RLRs/IFN-I signaling pathway in liver tissue were significantly increased (P < 0.001). Compared with model group, HQ-DS and silymarin intervention significantly improved the slow growth of body weight in mice (P < 0.01, 0.001), significantly reduced the degree of vacuolar degeneration and inflammatory infiltration in liver tissue, significantly reduced liver function related indicators in serum (P < 0.01, 0.001), effectively alleviated the process of HF, and significantly reduced the expressions of factors related to the ERVs/RLRs/IFN-I signaling pathway in liver tissue (P < 0.05, 0.01, 0.001). Subsequent verification of the underlying mechanisms revealed that in Mavs^-/- mice, the elevation of pro-inflammatory factors induced by CCl₄ was markedly suppressed (P < 0.001), the mRNA expression levels of factors associated with the ERVs/RLRs/IFN-I signaling pathway were significantly downregulated (P < 0.001). However, following the administration of HQ-DS, there was no significant change in the mRNA expression levels of inflammatory factors and factors related to the ERVs/RLRs/IFN-I pathway. In cell experiments, compared with model group, HQ-DS significantly increased iBMDM cell viability (P < 0.001), reduced dsRNA accumulation, and downregulated the expressions of core genes in ERVs and IFN-I pathways (P < 0.05, 0.01, 0.001), while inhibited the expressions of key proteins [phosphorylated TANK binding kinase 1 (p-TBK1), phosphorylated interferon regulatory factor 3 (p-IRF3)] in RLRs pathway (P < 0.05, 0.01, 0.001). Conclusion HQ-DS alleviates inflammatory injury and ameliorates the progression of HF in mice by inhibiting ERVs/RLRs/IFN-I signaling pathway.

Objective To explore the protective effect of herb pair Kuxingren (Armeniacae Semen Amarum)-Kushen (Sophorae Flavescentis Radix) on bleomycin-induced idiopathic pulmonary fibrosis (IPF) in rats and investigate its mechanism. Methods SD rats were randomly divided into control group, model group, pirfenidone (200 mg/kg) group, Armeniacae Semen Amarum-Sophorae Flavescentis Radix low-, medium-and high-dose (1, 2, 4 g/kg) groups. The IPF rat model was established by one-time tracheal instillation of bleomycin sulfate (5 mg/kg). After drug intervention, the pathological changes in lung tissue were observed using hematoxylin-eosin (HE) and Masson staining. ELISA was used to detect the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6 and hydroxyproline (Hyp) in serum and bronchoalveolar lavage fluid. TUNEL staining was used to detect cell apoptosis in lung tissue. The expressions of α-smooth muscle actin (α-SMA), collagen type I (collagen-I) and fibronectin-1 (FN-1) in lung tissue were detected by immunofluorescence. Western blotting was used to detect the expressions of p-p38, phosphorylated extracellular signal regulated kinase (p-ERK), phosphorylated c-Jun N-terminal kinase (p-JNK), B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in lung tissue. Transforming growth factor-β1 (TGF-β1) was used to induce human lung fibroblasts (MRC-5) in vitro model. After intervention with Armeniacae Semen Amarum-Sophorae Flavescentis Radix containing serum, cell proliferation activity was detected using CCK-8 method. TUNEL staining was used to detect cell apoptosis. The expressions of α-SMA, collagen-I and FN-1 were detected by immunofluorescence. Western blotting was used to detect the expressions of p-RAF, phosphorylated mitogen activated protein kinase (p-MEK), p-ERK, Cyclin D1, proliferating cell nuclear antigen (PCNA), Bax and Bcl-2 proteins. Results In the in vivo experiment, compared with control group, the body weight of rats in model group was decreased (P < 0.01), the dry wet mass ratio and lung index of lung tissue were increased (P < 0.01), the lung tissue showed significant inflammatory infiltration, thickening and edema of alveolar space, and the cell apoptosis rate of lung tissue was decreased (P < 0.01), the levels of inflammatory factors in serum and bronchoalveolar lavage fluid were increased (P < 0.01), the protein expressions of α-SMA, collagen-I, FN-1, p-p38, p-ERK, p-JNK and Bcl-2 in lung tissue were significantly up-regulated (P < 0.01), while the protein expression of Bax was significantly down-regulated (P < 0.01). Compared with model group, the body weight of rats in each treatment group were increased (P < 0.01), the dry wet mass ratio and lung index of lung tissue were decreased (P < 0.01), the pathological changes of lung tissue were significantly improved, the cell apoptosis rate of lung tissue was increased (P < 0.01), the levels of inflammatory factors in serum and bronchoalveolar lavage fluid were decreased (P < 0.05, 0.01), the expressions of α-SMA, collagen-I, FN-1, p-p38, p-ERK, p-JNK and Bcl-2 proteins in lung tissue were significantly down-regulated (P < 0.01), and the expression of Bax protein was significantly up-regulated (P < 0.01). In the in vitro experiments, compared with control group, cell proliferation activity in model group was increased (P < 0.01), cell apoptosis rate was decreased (P < 0.01), α-SMA, collagen-Ⅰ, FN-1, p-RAF, p-MEK, p-ERK, Cyclin D1, PCNA, Bcl-2 protein expressions were increased (P < 0.01), and Bax protein expression was decreased (P < 0.01). Compared with model group, Armeniacae Semen Amarum-Sophorae Flavescentis Radix containing serum and RAF inhibitor GW5074 intervention resulted in a decrease in cell proliferation activity (P < 0.05, 0.01), an increase in cell apoptosis rate (P < 0.01), a decrease in the expressions of α-SMA, collagen-I, FN-1, p-RAF, p-MEK, p-ERK, Cyclin D1, PCNA, Bcl-2 proteins (P < 0.05, 0.01), and an increase in Bax protein expression (P < 0.05, 0.01). Conclusion Armeniacae Semen Amarum-Sophorae Flavescentis Radix exerts an anti-IPF effect by regulating RAF/MEK/ERK signaling pathway, inhibiting inflammatory response, suppressing cell proliferation and promoting cell apoptosis.

Objective To explore the effect and mechanism of Yanggan Ruanjian Wan (养肝软坚丸, YGRJW) in prevention and treatment of hepatic fibrosis (HF) based on in vivo and in vivo experiments and transcriptome sequencing technology. Methods LX-2 cell activation model was induced by transforming growth factor-β1 (TGF-β1), CCK-8 method, cell scratch assay, qRT-PCR and Western blotting were used to detect the effects of YGRJW-medicated serum on cell viability, proliferation, expressions of inflammatory cytokines [interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α)] and fibrosis markers [α-smooth muscle actin (α-SMA), collagen type I alpha 1 chain (COL1A1), collagen type III alpha 1 chain (COL3A1)]. Transcriptome sequencing was employed to identify differentially expressed genes and key pathways in activated LX-2 cells treated with YGRJW-containing serum, followed by validation through qRT-PCR and immunofluorescence experiments. A HF model was induced in mice via intraperitoneal injection of a 10% carbon tetrachloride (CCl₄)-containing corn oil solution. After drug intervention, the therapeutic effects of YGRJW on HF mice were comprehensively evaluated by measuring body weight, organ indices, liver and kidney function, pathological changes in liver tissue, expressions of inflammatory factors and fibrosis markers in liver tissue, as well as levels of inflammatory factors and four liver fibrosis indicators in serum, while also verifying the effect of YGRJW on potential pharmacodynamic targets and key pathway indicators. Results In vitro experiments demonstrated that 10% YGRJW-containing serum significantly inhibited LX-2 cell activation after 24 h (P < 0.01) and downregulated mRNA expression levels of inflammatory factors and fibrosis markers (P < 0.05, 0.01, 0.001), with superior inhibitory effects compared to 10% silybinin-containing serum. Transcriptomic analysis and validation results showed that YGRJW may exert anti-HF effects through the colony stimulating factor 3 receptor (CSF3R)/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway. Compared with model group, YGRJW drug containing serum intervention could significantly downregulate the mRNA and protein expressions of CSF3R, JAK2 and STAT3 (P < 0.05, 0.01). The in vivo experimental results showed that YGRJW could significantly improve the slow growth of body weight in HF mice (P < 0.05), reduce liver index, spleen index, liver and kidney function indicators (P < 0.05, 0.01, 0.001), alleviate liver tissue inflammation infiltration and collagen deposition, reduce the mRNA expression levels of TGF-β, TNF-α, IL-6, α-SMA, COL1A1, COL3A1 and tissue inhibitor of metalloproteinases-1 (TIMP-1) in liver tissue (P < 0.05, 0.01, 0.001), increase the mRNA expression level of fibroblast growth factor 7 (FGF7) (P < 0.05, 0.01), and reduce levels of inflammatory factors and four indicators of liver fibrosis in serum (P < 0.05, 0.01, 0.001), and downregulated mRNA and protein expressions of CSF3R, JAK2, STAT3 in liver tissue (P < 0.05, 0.01). Conclusion YGRJW exerts anti-HF effects by regulating CSF3R/JAK2/STAT3 signaling pathway, to inhibit hepatic stellate cell (HSC) activation and reducing extracellular matrix (ECM) deposition.

Objective To evaluate the causal associations of gut microbiota, immune cells and serum metabolites with idiopathic pulmonary fibrosis (IPF) based on the multi-omics Mendelian randomization (MR) framework, screen core causal genes, and predict intervening traditional Chinese medicine (TCM) and compounds, so as to provide genetic evidence for the early diagnosis and TCM intervention of IPF. Methods Genetic instrumental variables (IVs) of gut microbiota, serum metabolites and immune cells were extracted, and their causal associations with IPF were analyzed by two-sample MR. Adjacent genes of IVs were annotated to obtain the "microbiota-immunity-metabolism" causal gene set. Integrated with IPF transcriptome data, candidate causal genes were screened by differentially expressed genes (DEGs) analysis and weighted gene co-expression network analysis (WGCNA). Diagnostic models were constructed by machine learning to screen core genes. Immune cell infiltration and single-cell RNA sequencing profiles were analyzed. Potential intervening TCM and compounds were predicted via Comparative Toxicogenomics Database (CTD) and Integrated Traditional Chinese Medicine Database (ITCM), followed by molecular docking verification. Results Two-sample MR identified 2 gut microbiota taxa (Lactobacillaceae as protective factor, Proteobacteria as risk factor), 19 immune cell phenotypes (nine protective, ten risk) and 26 serum metabolites (12 protective, 14 risk) that were significantly causally associated with IPF (P < 0.05). A total of 21 candidate causal genes were obtained by integrated analysis, and 5 core genes were screened by machine learning: adaptor protein complex 5 subunit mu 1 (AP5M1), SRY-box transcription factor 11 (SOX11), zinc finger and MIZ-type containing 2 (ZMIZ2), fragile histidine triad (FHIT) and cyclin dependent kinase 6 (CDK6), all with potential diagnostic value. Immune infiltration showed increased activated mast cells and monocytes, and decreased M0/M2 macrophages and activated natural killer cells in IPF tissues. Single-cell analysis revealed the highest enrichment of FHIT in multiple cell types. A total of 150 kinds of potential intervention Chinese medicine were screened. The high frequency Chinese medicine included Sangbaipi (Mori Cortex), Yuejihua (Rosae Chinensis Flos), Yanhusuo (Corydalis Rhizoma), etc. The active ingredients included kaempferol, naringenin, wogonin, sanguinarine, etc. Molecular docking confirmed that the core compound could stably bind to the target. Conclusions This study reveals the causal associations of gut microbiota, immune cells and serum metabolites with IPF, and identifies AP5M1, SOX11, ZMIZ2, FHIT and CDK6 as potential candidate diagnostic biomarkers for IPF. It also predicts the potential intervention value of active compounds such as kaempferol, naringenin and palmatine, as well as TCM including Morus alba and Rosa chinensis, providing genetic evidence and theoretical support for the diagnosis and treatment of IPF.

Objective To investigate the chemical constituents from the whole plant of Physalis angulata and their anti-inflammatory activities. Methods Various chromatographic techniques were employed for the isolation and purification of compounds, and their structures were elucidated by spectroscopic methods including NMR, MS, and UV. The cytotoxicity against mouse macrophage RAW264.7 cells was evaluated using the SRB assay, while the in vitro anti-inflammatory activity was determined via the Griess assay. Results Five compounds were isolated from the methanol extract of the whole plant of P. angulata and identified as 6- 5β,6β:14α,17:14β,26-triepoxy-13α,15β-dihydroxy-1-keto-11,15-cyclo-13,14-secoergostan-2-en-18,26-olide (1), physalin B (2), physalin F (3), physalin XI (4), and aspergillus triazolate A (5). Compounds 2—5 exhibited inhibitory effects on NO production in RAW264.7 cells, with IC₅₀ values ranging from (1.97 ± 0.12) to (6.73 ± 0.71) μmol/L. Conclusion Compound 1 is a new compound, named 5,6-epoxyphysalin IX. Compounds 4 and 5 showed significant anti-inflammatory activities.

Objective Novel Diels-Alder-type adducts from the stems and branches of Morus nigra were investigated, and their peroxisome proliferator-activated receptor gamma (PPARγ) binding activity was preliminarily evaluated. Methods Systematic isolation and purification were carried out by multiple chromatographic methods including silica gel, AB-8 macroporous resin, polyamide, Sephadex LH-20 gel and ODS reversed-phase column chromatography. Structures of the isolated compounds were identified by modern spectroscopic techniques including high-resolution electrospray ionization mass spectrometry（HR-ESI-MS）and nuclear magnetic resonance spectroscopy (¹H-NMR, ¹³C-NMR). The in vitro activities of some compounds were evaluated by PPARγ ligand-binding assay. Results Six Diels-Alder adducts were isolated from the ethanol extract of M. nigra twigs and identified as (5aR,10aR,14S)-2-((1S,2R,3S)-2-(2,4-dihydroxybenzoyl)-2',4'-dihydroxy-5-methyl-1,2,3,6-tetrahydro-[1,1'-biphenyl]-3-yl)-1,3,8, 14-tetrahydroxy-13,13- dimethyl-11H-10a,5a-(epoxypropano)benzofuro[3,2-b]chromen-11-one (1), sanggenon O (2), sanggenon C (3), mulberrofuran F (4), cathayanin B (5), and mulberrofuran G (6). Compound 1 exhibited weak PPARγ ligand-binding activity at 10 μmol/L. Compound 3 exhibited moderate ligand-binding activity toward PPARγ at 10 μmol/L, which was obviously weaker than that of its biosynthetic precursor sanggenol F (SGF). Conclusion Compound 1 is a new compound, named nigragenon Q, it is formed by an intermolecular [4+2] cycloaddition between a sanggenone-type dihydroflavone and a chalcone. Oxidation of the C-2 isoprenyl side chain enables its connection to C-3 via an oxygen bridge, furnishing a six-membered ring and constructing a unique [4,4,3] bridged ring system. Compound 3 exhibited moderate PPARγ ligand-binding activity.

Objective The in vitro co-incubation method was employed to investigate the metabolic transformation regularity of Semen Cuscutae-Fructus Lycii (SC-FL) mediated by gut microbiota in premature ovarian insufficiency (POI) rats. Methods SC-FL and its thirteen monomer components were co-incubated with gut microbial communities from POI rats in vitro, followed by UPLC-Q-TOF-MS for qualitative analysis. Results A total of 85 compounds were characterized from the SC-FL co-incubated samples, including 61 prototypical components (e.g., rutin), 13 metabolites (e.g., methyl hyperoside), and 11 kinds of components that exist in the prototype at the same time and can be metabolized by other components, (e.g., isorhamnetin). Hyperoside was characterized by five metabolites, rutin by seven, quercitrin by six, astragalin by seven, isoquercitrin by five, quercetin by seven, isorhamnetin by four, kaempferol by five, apigenin by four, chlorogenic acid by nine, ferulic acid by three, scopoline by four, and scopoletin lactone by three. Conclusion The metabolic transformation reactions mediated by the intestinal microbiota in POI rats mainly include Phase I metabolic reactions such as hydrolysis, reduction-hydrogenation, and hydroxylation reactions, and Phase II metabolic reactions such as methylation reactions. Reverse traceability analysis of the metabolic conditions of each component revealed that isorhamnetin, quercetin, kaempferol and apigenin were mutually metabolically transformed in the intestinal flora of POI rats These findings provide important evidence for elucidating the pharmacodynamic material basis and mechanisms of SC-FL in POI, and lay a foundation for subsequent research on optimizing SC-FL efficacy through gut microbiota modulation.

Objective On the basis of the requirements of ancient prescriptions, combined with modern technical means, the ancient decoction and modern decoction methods of Gualou (Trichosanthis Fructus) were compared. Methods Trichosanthis Fructus was soaked in rice wine (ancient method) and purified water (modern method) for 30 min, then decocted for 180 min. Samples were analyzed by UHPLC-Q-Exactive Orbitrap MS on a Hypersil GOLD aQ column (100 mm × 2.1 mm, 1.9 μm), with 0.1% formic acid acetonitrile–0.1% formic acid water as mobile phase by gradient elution (0.3 mL/min, 35 °C, 1 μL). ESI data were acquired in positive and negative modes (m/z 100—1 500). Data were processed using Thermo Scientific Xcalibur. Chemical constituents in different Trichosanthis Fructus decoctions were identified and analyzed based on MS data, reference standards, literature, and fragmentation patterns. Results Compared with the conventional modern decoction method, the ancient decoction method of Trichosanthis Fructus yielded more compound types. A total of 44 compounds were identified in ancient decoction samples versus 39 in modern decoction samples. The contents of major components such as arginine, lysine, guanine, adenine,and hypoxanthine were significantly higher in the ancinet decoction than in the modern decoction. Histidine, citrulline, 5-hydroxymethylfurfural, medicarpin, vanillic acid, chrysoeriol, diosmetin, kaempferide, and paeonol were identified exclusively in the ancient decoction samples of Trichosanthis Fructus. Conclusion This study confirmed that the ancient decoction method can more effectively extract or transform the chemical components in Trichosanthis Fructus, which may be the material basis for its unique clinical efficacy. It is worthy of attention and further research in clinical application.

Objective To clarify whether the combined use of sodium dodecyl sulfate (SDS) and hydroxypropyl methylcellulose (HPMC) can improve the dissolution behavior of baicalin-imperatorin co-amorphous system (Bai-Imp-CAS), and explore the mechanism of combination benefit. Methods A series of Bai-Imp CAS with different ratios of SDS and HPMC were prepared by the spray-drying method. Powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) were adopted to characterize the solid-state properties of samples. Dispersion performance was evaluated by determining caking rate and dispersion time, and wettability was analyzed via contact angle and surface free energy measurements. The optimal ratio of SDS to HPMC was determined based on dispersion performance. According to the requirements of the 2025 Edition of Chinese Pharmacopoeia, the in vitro dissolution of the optimal SDS/HPMC (2∶1)-CAS was investigated and compared with those of SDS-CAS and HPMC-CAS. UV-visible spectrophotometry was used to detect the nucleation time and crystal growth rate of the two drugs. Results All spray-dried products were identified as co-amorphous systems. The caking rate of SDS/HPMC (2∶1)-CAS was (15.30 ± 1.55)%, which was significantly lower than that of single excipient groups. There was no significant difference in dispersion time between SDS/HPMC (2∶1)-CAS and SDS-CAS. The water contact angle of SDS/HPMC (2∶1)-CAS was 24.23°, with a surface free energy of 57.54 mJ/m², indicating favorable wettability. The in vitro dissolution results showed that the area under curve (AUC) values of baicalin and imperatorin in SDS/HPMC (2∶1)-CAS were (38 661.00 ± 375.32) and (4 565.00 ± 434.65) μg·h/mL, respectively, both significantly higher than those of SDS-CAS and HPMC-CAS. The early dissolution profile of SDS/HPMC (2∶1)-CAS was similar to that of SDS-CAS, while its dissolution decline rate in the middle and late stages was consistent with HPMC-CAS. Crystallization kinetics demonstrated that HPMC alone or combined with SDS could inhibit the nucleation of the two drugs and the crystal growth of baicalin, but exert no obvious effect on the crystal growth of imperatorin. SDS had no significant influence on the nucleation and crystal growth of both drugs. Conclusion SDS/HPMC (2∶1)-CAS shows the best dispersibility, and SDS and HPMC can jointly boost the dissolution of both drugs. The mechanism works by sequentially complementing each other's functions to improve the dissolution of Bai-Imp-CAS: SDS mainly drives fast initial dispersion and prevents aggregation, while also indirectly inhibiting crystallization by lowering local supersaturation; HPMC directly inhibits crystal growth during the mid to late stages of dissolution. Together, they create a combined “indirect and direct” effect on crystal inhibition, helping to maintain a supersaturated state. This strategy offers a fresh approach for designing co-amorphous systems for poorly soluble drug combinations, and it can reduce the amount of SDS needed, giving a “less is more” advantage for clinical translation.