Chinese Journal of Integrative Medicine最新文献

Objective: To assess the efficacy and safety profile of Aurantii Fructus Immaturus flavonoid (AFIF) tablets in the treatment of patients with functional dyspepsia (FD).

Methods: In this phase III, randomized, controlled clinical trial, participants diagnosed with FD from 7 medical centers across China were assigned by stratified block randomization to either AFIF treatment group (3 AFIF tablets, 0.29 g per tablet) or placebo group on the same schedule in a 3:1 ratio. The primary endpoint was the complete disappearance of 4 core FD symptoms, including postprandial fullness, early satiety, upper abdominal pain, and upper abdominal burning, following a 4-week treatment regimen (3 times daily). Secondary endpoints included the individual symptom disappearance rates and gastric emptying function after 4 weeks, as well as the disappearance rates for all 4 individual symptoms of FD at 4 weeks after treatment. Subgroup analyses included 3 clinical symptoms and 4 Chinese medicine patterns. Safety assessments included monitoring treatment-emergent adverse events (AEs), serious adverse events (SAEs), intervention-related AEs, and any AEs leading to discontinuation.

Results: Of the enrolled patients, 299 in the AFIF group and 99 in the control group were induded in the full analysis set (FAS) and safety set (SS). After 4 weeks of treatment, the complete disappearance of all 4 core FD symptoms was achieved in 31.44% (94 cases) of patients in the AFIF group compared to 6.06% (6 cases) in the placebo group (P<0.01). At 4 weeks after end of treatment, the rates of symptom disappearance were 23.43% (67 cases) in the AFIF group and 2.22% (2 cases) in the placebo group (P<0.01). Individual symptom disappearance rates were significantly higher in the AFIF group at both week 4 and 4 weeks after treatment (all P<0.01). Additionally, the patients in the AFIF group exhibited a significantly greater improvement in gastric emptying at 2 h post-meal [66.55% (50.03, 84.55)] compared to the placebo group [51.10% (44.75, 68.93), P=0.027]. At weeks 4 and 4 weeks after treatment, in the FAS, the disappearance rates of all 4 core FD symptoms remained higher in the AFIF group compared to the placebo group (all P<0.05). The per protocol set results similarly aligned with those observed in the FAS. Intervention-related AEs were reported in 6.02% (18 cases) of the AFIF group and 8.08% (8 cases) in the placebo group, with no SAEs recorded in either group. The patients in the AFIF group showed significantly higher complete symptom resolution rates of all 4 core FD symptoms at 4 weeks and 4 weeks after treatment across most subgroups, compared to the placebo group (all P<0.05). All AEs related to AFIF Tablets were mild.

Conclusion: AFIF tablets demonstrated robust efficacy in alleviating the symptoms of FD, with a favorable safety profile. (Registration No. CTR20132482).

Objective: To explore the therapeutic efficacy of Hypericum japonicum (HJ) and its active compounds in mitigating hepatic fibrosis by elucidating their anti-inflammatory and anti-apoptotic effects.

Methods: Twenty-four mice were randomly divided into 4 groups: control group, model group, HJ-1 mg/g group, and HJ-2 mg/g group. A hepatic fibrosis model was established via carbon tetrachloride (CCl₄) injection at a dose of 5 µL/g of body weight, twice weekly for 6 weeks. Subsequently, mice were gavaged with 1 mg/g or 2 mg/g HJ aqueous solution to assess its effects on liver pathological injury, liver function markers, and fibrosis markers in model mice. Integrated analyses employing network pharmacology, molecular docking, and eukaryotic transcriptomics were conducted to identify interactions between key HJ active constituents (e.g., mairin, beta-sitosterol, quercetin, kaempferol) and core targets [e.g., B-cell lymphoma-2 (Bcl-2), tumor protein p53 (TP53), tumor necrosis factor-alpha (TNF-α)], along with associated signaling pathways. Additionally, in vitro experiments were used to validate the effect of HJ active constituents on the viability of CCl₄-injured HepG2 cells, expression of inflammatory cytokines, and apoptotic pathways. The study further utilized 16S rRNA amplicon sequencing to explore the modulatory effects of HJ on gut microbiota structure and function.

Results: In vivo experiments demonstrated that HJ intervention significantly ameliorated liver pathological damage, reduced liver function markers, and downregulated α -smooth muscle actin expression in mice (P<0.01). Network pharmacology and molecular docking revealed significant binding affinity between key HJ active constituents and core targets (e.g., Bcl-2, TP53, TNF-α). Eukaryotic transcriptomic analysis further identified core differentially expressed genes modulated by HJ, which were implicated in inflammatory response regulation and extracellular matrix receptor interaction pathways. Although HJ intervention did not significantly alter gut microbiota richness, it modulated metabolic and immune functions closely associated with hepatic fibrosis. In vitro, HJ active constituents significantly increased the viability of CCl₄-injured HepG2 cells, downregulated TNF-α and interleukin-6 mRNA expression, and suppressed the mitochondrial apoptotic pathway via Bcl-2 regulation (P<0.01). Among the compounds, mairin demonstrated the most potent effect in reducing aspartate aminotransferase and hydroxyproline levels, while mairin and beta-sitosterol exerted anti-fibrotic effects by suppressing TNF-α and decreasing glutathione, respectively.

Conclusions: HJ and its active ingredients elucidate the anti-inflammatory and anti-apoptotic effects in hepatic fibrosis. Further they emerge as promising candidates for targeted therapy against hepatic fibrosis.

Objective: To evaluate the clinical efficacy and safety of Xueshuantong Injection (Lyophilized) (XST) in reducing residual inflammatory risk (RIR) in patients with unstable angina (UA).

Methods: This was a randomized, double-blind, parallel-controlled multicenter trial. Patients with UA were recruited from Xiyuan Hospital and Guang'anmen Hospital of the China Academy of Chinese Medical Sciences between January 2024 and March 2025. Eligible participants were randomly assigned to the treatment group (XST 500 mg, 30 cases) or the control group (XST 25 mg, 30 cases) in a 1:1 ratio. Both groups received intravenous XST for 10 consecutive days along with standard medical therapy. The primary outcome was change in C-reactive protein (CRP) level from baseline to post-treatment. Secondary outcomes included changes in interleukin-6 (IL-6), matrix metalloproteinase-9 (MMP-9), high-mobility group box 1 (HMGB1), vascular endothelial growth factor (VEGF), and von Willebrand factor (vWF), as well as the Canadian Cardiovascular Society (CCS) classification, and Chinese Medicine (CM) syndrome scores. Safety was evaluated by monitoring adverse event (AE) and performing laboratory tests of liver and kidney function before and after treatment.

Results: A total of 59 patients completed the trial (30 in the treatment group and 29 in the control group). After treatment, the treatment group showed significantly greater reductions in CRP levels compared to the control group (P<0.01). In addition, the treatment group exhibited significantly improved IL-6, MMP-9, and HMGB1 levels, as well as CM symptom scores and CCS classification compared to the control group (all P<0.05). No serious adverse events were reported. Compared with the control group, the treatment group receiving XST showed greater improvements in RIR and clinical symptoms in UA patients with good safety and tolerability.

Conclusion: XST shows potential to reduce RIR in patients with UA and may inform anti-inflammatory management. (Registration No. ITMCTR2025000552).

Objective: To investigate cerebral vasorelaxation of total flavonoids of Chuzhou chrysanthemum (TFCC) in rats and its mechanism.

Methods: Cerebral basilar arteries (CBA) of rats were isolated, and the vasodilation induced by TFCC (10-2,560 mg/L) following pretension with 100 nmol/L U₄₆₆₁₉ or 30 mmol/L KCl were measured using a pressure myograph system. Addition of H₂S synthase cystathionine-γ-lyase (CSE) inhibitor dl-propargylglycine (PPG, 100 µ mol/L), a large-conductance Ca²⁺-activated potassium (BK_Ca) channel blocker iberiotoxin (IBTX,100 nmol/L) and L-type Ca²⁺ channel blocker nifedipine (100 nmol/L) were added to determine the effect of pretreatment with the inhibitors on TFCC-induced vasorelaxation. KCl (30 mmol/L) was used as a contractile agent, TFCC (3.3-270 mg/L)-induced relaxation was detected by measuring the length of the long axis of rat cerebral vascular smooth muscle cells (VSMCs). Determination of the effect of pretreatment of VSMCs by IBTX or nifedipine on TFCC-induced cellular relaxation, and intracellular free Ca²⁺ concentration ([Ca²⁺]_i) was detected by fluorescent method. Endothelial cells (ECs) were co-cultured with VSMCs to observe the effect of endogenous H₂S on TFCC-induced relaxation in VSMCs.

Results: TFCC caused a concentration-dependent vasorelaxation in the rat CBA precontracted with KCl or U₄₆₆₁₉ (P<0.01). Endothelial removal markedly attenuated this vasodilation, but the remaining vasorelaxation was still significant (P<0.01). The TFCC-induced cerebral vasorelaxation was remarkably inhibited by PPG, IBTX and nifedipine (P<0.01). TFCC caused a significant relaxation of rat CBA VSMCs (P<0.01). Co-culture with wild-type cerebral ECs but not with cystathionine-γ-lyase- or 3-mercaptosulfotransferase-knockout ECs markedly enhanced TFCC-induced relaxation of VSMCs (P<0.05) and increased H₂S content (P<0.01). TFCC decreased the [Ca²⁺]_i in VSMCs (P<0.01), which was attenuated by PPG and IBTX.

Conclusions: TFCC dilated rat CBA in both endothelium-dependent and -independent manner. Its endothelium-dependent dilation was probably involved in the blockade of L-type Ca²⁺ channels caused by endothelial H₂S activating BK_Ca channels in VSMCs; its endothelium-independent relaxation was primarily from the direct blockade of the L-type Ca²⁺ channels in VSMCs.

Objective: To explore the potential of honeysuckle-derived exosome-like nanovesicles (HELNVs) for preventing cisplatin-induced acute kidney injury (AKI).

Methods: The renoprotective efficacy of HELNVs against cisplatin-induced AKI was assessed in human kidney cell-2 (HK-2) cells exposed to 100 μmol/L cisplatin for 24 h, followed by HELNVs (50-200 μg/mL) for another 24 h; the optimal therapeutic concentration was determined as 100 μg/mL. At this concentration, oxygen species (ROS) levels were measured by flow cytometry. Male C57BL/6 mice received a single intraperitoneal injection of cisplatin (30 mg/kg) to establish an AKI model and were then computer-randomized into 3 groups (n=6 per group): control group, daily intraperitoneal administration of normal saline (0.9% NaCl); the cisplatin-injured group, same NaCl regimen; the HELNVs treatment group, daily intraperitoneal administration of HELNVs (30 mg/kg) for 5 consecutive days, with euthanasia on day 6. Renal accumulation of HELNVs was tracked by small-animal multispectral imaging (peak uptake at 8-10 h). Functional assessment included serum creatinine and blood urea nitrogen (BUN) quantified with an automated biochemical analyzer. Molecular analyses included enzyme-linked immunosorbent assay (ELISA) quantification of interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor-α (TNF-α).

Results: HELNVs significantly reduced ROS, inflammatory responses, and apoptosis in cisplatin-treated HK-2 cells (P<0.01). In cisplatin-induced AKI mice, HELNVs were efficiently absorbed by kidney cells, effectively prevented oxidative damage and mitochondrial dysfunction (P<0.01). Following treatment with 30 mg/kg HELNVs, serum creatinine and BUN levels were markedly reduced (P<0.01). ELISA results showed decreased levels of IL-1β, IL-6, and TNF-α, along with up-regulated IL-10 (P<0.01).

Conclusion: HELNVs may serve as a promising therapeutic approach for ameliorating cisplatin-induced AKI, offering a potential novel treatment option for managing this condition in clinical settings.

Objective: To evaluate the therapeutic effects of Kuanxiong Aerosol (KXA) on ischemic stroke with reperfusion and elucidate the underlying pharmacological mechanisms.

Methods: In vivo pharmacological effects on ischemic stroke with reperfusion was evaluated using the transient middle cerebral artery occlusion (t-MCAO) mice model. To evaluate short-term outcome, 30 mice were randomly divided into vehicle group (n=15) and KXA group (n=15). Mice in KXA and vehicle groups received 69 mg KXA and vehicle for 1 day, respectively. To evaluate long-term outcome, 35 mice were randomly divided into sham group (n=5), vehicle group (n=15), and KXA group (n=15). Mice in KXA and vehicle groups received 69 mg KXA and vehicle for 7 days, respectively. Pathological changes in the brain were observed by 2,3,5-triphenyltetrazolium chloride or Nissl stainings, and behavioral assessments, including the Modified Neurologic Severity Score, Bederson score, rotarod test, and adhesive removal test were conducted. The penetration ability of KXA and KX (KXA without propellants) through the blood-brain barrier was assessed both in vitro using a transwell model and in vivo. Furthermore, in vitro effects of KX (5, 10, and 20 µL/L) on oxygen and glucose deprivation/re-oxygenation (OGD/R)-induced injury, transient receptor potential vanilloid type 1 (TRPV1) modulation, calcium influx, and mitochondrial function were explored through Western blot, CCK-8 assay, JC-1 staining, calcium imaging, adenosine triphosphate (ATP) and antioxidant measurements.

Results: In in vivo experiments, KXA reduced brain infarct volume and neuron loss in t-MCAO mice. Behavioral assessments showed marked improvement in the neurological deficit of t-MCAO mice with KXA treatment (P<0.05 or P<0.01). Additionally, in vitro findings indicated that KX ameliorated OGD/R-induced injury through TRPV1 channel modulation. KX increased cell viability in OGD/R-treated SH-SY5Y cells and prevented OGD/R-induced calcium overload by downregulating TRPV1 expression and constraining calcium influx through TRPV1 (P<0.05 or P<0.01). Furthermore, KXA maintained the membrane potential and function of mitochondria in OGD/R-treated SH-SY5Y cells.

Conclusions: KXA could attenuate ischemic stroke injury through TRPV1 channel modulation, indicating its potential as a promising therapeutic option for stroke in clinical practice.

Objective: To elucidate the therapeutic effect and mechanism of Compound Danshen Dripping Pill (CDDP) on cardiotoxicity caused by doxorubicin (DOX) and trastuzumab (TRZ) METHODS: Eighteen Sprague-Dawley (SD) rats were randomly divided into the normal group (normal saline), the model group (DOX/TRZ), and CDDP administration group (DOX/TRZ+CDDP), by a random number table, with 6 rats in each group. Rats' were administered either DOX or saline via tail vein injection 6 times over an 11-day period. One week later, they received either TRZ or saline via intraperitoneal injection 6 times over another 11-day period. All rats received CDDP or saline via oral gavage continuously for 36 days. Then, echocardiography was performed on the rats, and biochemical parameters of blood and heart samples were determined. Rats' feces were taken for intestinal flora testing and plasma metabolites were analyzed using untargeted metabolomics.

Results: Echocardiographic assessment in rats demonstrated that DOX/TRZ induced cardiac dysfunction, whereas CDDP significantly ameliorated this impairment (P<0.05 or P<0.01). Furthermore, results revealed that DOX/TRZ elevated cardiac injury indicators (left ventricular ejection fraction, fractional shortening, cardiac troponin I, creatine kinase, creatine kinase-MB), while CDDP treatment significantly reduced these levels (P<0.05 or P<0.01). Plasma metabolite analysis revealed enrichment in tryptophan metabolism, tricarboxylic acid cycle, and phenylalanine metabolism. Intestinal microbiota analysis showed increased richness and altered abundance of certain bacteria (Clostridia_UCG-014 and Lactobacillus) with CDDP treatment.

Conclusions: CDDP can prevent and protect against DOX/TRZ-induced cardiac injury. It influences tryptophan metabolism by modulating Clostridia_UCG-014 abundance, inhibits indole-3-carboxylic acid levels, increases kynurenine levels, thereby exerting anti-cardiotoxic effects.