Chinese Journal of Integrative Medicine最新文献

Objective: To evaluate the clinical effect and safety of Xinfuli Granules (, XFLG) in improving patients with heart failure (HF) of qi deficiency and blood stasis syndrome.

Methods: In this singlecenter randomized controlled trial, HF patients were randomized (1:1) to either the XFLG group (178 cases) or the control group (178 cases). Patients in the control group received standard HF therapy. In addition, patients in the XFLG group were administered XFLG (10 g, 3 times daily) for 12 weeks. The primary outcomes observed were the composite of all-cause mortality and HF-related hospitalization; and secondary outcomes included changes in left ventricular ejection fraction (LVEF), N-terminal pro-brain natriuretic peptide (NT-pro BNP), New York Heart Association (NYHA) functional class, Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, Chinese medicine (CM) syndrome score, Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7) scores.

Results: After 12 weeks, the XFLG group demonstrated a significantly lower incidence of the primary endpoint compared to the control group (hazard ratio, 0.566; 95% confidence interval: 0.325-0.988; P<0.05). Besides, the XFLG group showed greater improvements in LVEF and NT-pro BNP reduction (P<0.05 or P<0.01). Compared with the control group, the total effective rate of NYHA functional class and CM syndrome was significantly higher; the MLHFQ, PHQ-9, and GAD-7 scores were significantly lower in the XFLG group (P<0.05 or P<0.01).

Conclusions: XFLG combined with standard HF therapy significantly reduced the risk of all-cause mortality and HF-related hospitalization composite events, improved cardiac function, and quality of life, alleviated depressive and anxiety states in HF patients, with a favorable safety profile. These results support XFLG as a promising adjunctive treatment for HF with qi deficiency and blood stasis. (Registration No. ChiCTR2100049197).

Objective: To investigate the potential anti-liver fibrosis (LF) effects of Dendrobium officinale polysaccharides (DOPs) and to further explore the involvement of the antioxidant and anti-inflammatory mechanisms of the transforming growth factor-beta 1 (TGF-β1) and Wnt signaling pathways.

Methods: Seventy male Sprague-Dawley rats were assigned to 5 groups in a randomized block design: control, model, colchicine (COL, 0.1 mg/kg), low-dose DOP (LDD, 0.05 g/kg), and high-dose DOP (HDD, 0.1 g/kg) groups (n=14 per group). LF rat model was induced via subcutaneous injection of carbon tetrachloride (CCl₄). Serum markers of oxidative stress, liver function, and LF were monitored. Pathological examination of liver tissue was performed using hematoxylin and eosin (HE) and Masson's trichrome staining, followed by staging evaluation using the meta-analysis of histological data in viral hepatitis scoring system. Quantitative analysis of the core components of extracellular matrix (ECM) and the regulatory factors [e.g., tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix metalloproteinase-1 (MMP-1)], TGF-β1, and Wnt/β-catenin signaling pathway were performed using real-time quantitative polymerase chain reaction and Western blot, respectively. In addition, the therapeutic effect of DOPs on LF was further evaluated using acoustic radiation force pulses (AFRI) and contrast-enhanced ultrasound (CEUS).

Results: Compared with the model group, HDD dramatically improved liver appearance and index, and alleviated extensive hepatocyte degeneration, interstitial fibrous proliferation, and pseudolobuli formation (P<0.01). Moreover, HDD downregulated mRNA and protein levels of α-smooth muscle actin, type I collagen, and type III collagen in the liver tissue of rats, while maintaining the MMP-1/TIMP-1 ratio by upregulating MMP-1 and downregulating TIMP-1 (P<0.05 or P<0.01). The ARFI and CEUS examination results also confirmed that HDD had significant anti-LF effects. HDD inhibited activation of the TGF-β and Wnt/β-catenin signaling pathways by reducing mRNA and protein levels of TGF-β1, Wnt-1 and β-catenin, while increasing the expression of dickkopf-1 (P<0.05 or P<0.01).

Conclusions: DOPs achieved an anti-LF effect by inhibiting TGF-β1 and Wnt/β-catenin signaling. ARFI and CEUS can be used to evaluate the liver stiffness, microcirculation disorders, and drug efficacy in LF and cirrhosis.

Objective: To investigate the anti-colorectal cancer (CRC) activity and its potential molecular mechanism of euscaphic acid (EA), a triterpene component from Rosa roxburghii Tratt (RRT), in vitro and in vivo.

Methods: EA in RRT was isolated and analyzed for pharmacophore-based virtual screening, and enrichment analysis was performed. HCT116 and CT26 cells were used for in vitro experiments. Meanwhile, we constructed a CT26 syngeneic tumor BALB/c mice model and performed in vivo experiments. Finally, the mitochondrial apoptosis and reactive oxygen species (ROS)/mitogen-activated protein kinase (MAPK) signaling pathway-related proteins were detected by Western blot.

Results: EA could inhibit the viability of HCT116 and CT26 cell lines, suppress the biological behaviors including proliferation, migration, and invasion, and induce apoptosis in vitro (P<0.05 or P<0.01). Meanwhile, in vivo experiments showed that EA significantly inhibited the growth of CRC graft tumors (P<0.05 or P<0.01). EA could decrease mitochondrial membrane potential and increase caspase-3/9 activities (P<0.05 or P<0.01). Furthermore, EA promoted the cellular ROS accumulation accompanied by activation of the MAPK signaling pathway, and interestingly, the phosphorylation level of extracellular regulated protein kinases (ERK) was higher (P<0.05 or P<0.01). In addition, the above process could be reversed by the free radical scavenger N-acetylcysteine (P<0.05 or P<0.01).

Conclusions: EA could inhibit the growth of CRC cell lines both in vitro and in vivo, and activate the mitochondrial pathway through the ROS/MAPK signaling pathway to induce apoptosis in CRC cell lines. This supports the antitumor potential of triterpene acids from RRT.

Objective: To explore the effects of acupuncture in comparison with sham acupuncture on cognitive functions in patients with relapsing-remitting multiple sclerosis (RRMS).

Methods: In this randomized controlled trial, 31 RRMS patients in the acupuncture group were treated with traditional Chinese acupuncture based on the treatment principle of calming the mind, reinforcing qi and blood, and 31 patients in the control group were treated with sham acupuncture (shallow needling at non-acupuncture points) twice a week for 12 weeks. The primary outcome was the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) score, which was evaluated by a psychologist at baseline and after 12 weeks of treatment. The secondary outcomes were the Symptom Checklist 90-Revised (SCL-90-R), Pittsburgh Sleep Quality Index (PSQI), and Fatigue Severity Scale (FSS) scores. The participants were provided with contact information from the researchers with constant access to report any adverse symptoms.

Results: In total, 62 participants were enrolled and allocated to the acupuncture group (31 cases) or control group (31 cases). After 12 weeks of acupuncture treatment, BICAMS including Symbol Digit Modalities Test (SDMT), California Verbal Learning Test-2 (CVLT-2) and delayed CVLT-2 scores were significantly improved in comparison with the control group (P<0.01). However, the changes in the Brief Visuospatial Memory Test-Revised (BVMT-R) and delayed BVMT-R scores related to visual/spatial memory did not differ significantly between the two groups (both P>0.05). The FSS, PSQI, and SCL-90-R scores were significantly reduced after 12-week treatment in the acupuncture group compared to the control group (P<0.05 or P<0.01). No life-threatening adverse events occurred throughout the study.

Conclusions: Twelve weeks of acupuncture treatment was effective in improving immediate and short-term auditory/verbal memory, attention and processing speed; reducing fatigue and decreasing sleep latency and the use of sleeping medications; alleviating depression, somatization, obsessive-compulsive and paranoid disorders in patients with RRMS. (Iranian Registry of Clinical Trials, No. IRCT20220101053582N1).

Objective: To explore the potential apoptotic mechanisms of 3 Morchella extracts (Morchella conica, Morchella esculenta and Morchella delicosa) on breast and colon cancer cell lines using apoptotic biomarkers.

Methods: Human breast cell line (MCF-7) and colon cancer cell line (SW-480) were treated with methanol and ethanol extracts of 3 Morchella species with concentration ranging from 0.0625 to 2 mg/mL. After that their effects on gene expression of apoptosis related markers (pro-apoptotic markers including Bax, caspase-3, caspase-7, and caspase-9, and the antiapoptotic marker including Bcl-2) were determined using reverse transcription polymerase chain reaction.

Results: All Morchella extracts reduced breast and colon cancer cells proliferation at half inhibitory concentration (IC₅₀) of 0.02 ±0.01 to 0.68 ±0.30 mg/mL. As expected, all Morchella extracts significantly increased gene expressions of Bax, caspase-3, caspase-7, and caspase-9 and downregulated the gene expression of Bcl-2 in MCF-7 and SW-480 cell lines (P<0.05).

Conclusions: Morchella extracts demonstrated significant anti-proliferative activity against breast and colon cancer cell lines via an apoptosis induction mechanism. Anticancer activity of Morchella extracts and activation of apoptosis in breast and colon cancer cells suggest that it may be used to develop chemotherapeutic agents against cancer in future.

Objectives: To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis.

Methods: Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats.

Results: Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05).

Conclusion: The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.

Objective: To explore the mechanism of colon dialysis with Yishen Decoction (YS) in improving the autophagy disorder of intestinal epithelial cells in chronic renal failure (CRF) in vivo and in vitro.

Methods: Thirty male SD rats were randomly divided into normal, CRF, and colonic dialysis with YS groups by a random number table method (n=10). The CRF model was established by orally gavage of adenine 200 mg/(kg•d) for 4 weeks. CRF rats in the YS group were treated with colonic dialysis using YS 20 g/(kg•d) for 14 consecutive days. The serum creatinine (SCr) and urea nitrogen (BUN) levels were detected by enzyme-linked immunosorbent assay. Pathological changes of kidney and colon tissues were observed by hematoxylin and eosin staining. Autophagosome changes in colonic epithelial cells was observed with electron microscopy. In vitro experiments, human colon cancer epithelial cells (T84) were cultured and divided into normal, urea model (74U), YS colon dialysis, autophagy activator rapamycin (Ra), autophagy inhibitor 3-methyladenine (3-MA), and SIRT1 activator resveratrol (Re) groups. RT-PCR and Western blot were used to detect the mRNA and protein expressions of zonula occludens-1 (ZO-1), Claudin-1, silent information regulator sirtuin 1 (SIRT1), LC3, and Beclin-1 both in vitro and in vivo.

Results: Colonic dialysis with YS decreased SCr and BUN levels in CRF rats (P<0.05), and alleviated the pathological changes of renal and colon tissues. Expressions of SIRT1, ZO-1, Claudin-1, Beclin-1, and LC3II/I were increased in the YS group compared with the CRF group in vivo (P<0.05). In in vitro study, compared with normal group, the expressions of SIRT1, ZO-1, and Claudin-1 were decreased, and expressions of Beclin-1, and LC3II/I were increased in the 74U group (P<0.05). Compared with the 74U group, expressions of SIRT1, ZO-1, and Claudin-1 were increased, whereas Beclin-1, and LC3II/I were decreased in the YS group (P<0.05). The treatment of 3-MA and rapamycin regulated autophagy and the expression of SIRT1. SIRT1 activator intervention up-regulated autophagy as well as the expressions of ZO-1 and Claudin-1 compared with the 74U group (P<0.05).

Conclusion: Colonic dialysis with YS could improve autophagy disorder and repair CRF intestinal mucosal barrier injury by regulating SIRT1 expression in intestinal epithelial cells.