Qiliqiangxin capsule alleviates cardiac hypertrophy and cardiac dysfunction by regulating miR-382-5p/ATF3 axis.

Qiliqiangxin Capsule (QL) was investigated for its possible role in cardiac hypertrophy in this study. QL (0.5 mg/mL) was pre-treated in Neonatal Mouse Ventricular Cardiomyocytes (NMVCs) before induction of cardiomyocyte hypertrophy by Angiotensin II (Ang-II). Immunofluorescence staining for α-actinin was conducted to determine cell surface area. Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP) of hypertrophy markers were examined. Ang-II infusion was given to stimulate cardiac hypertrophy in mice. The cardiac function of mice was detected by echocardiography, and the pathological status of myocardial tissue was observed. The surface of cardiomyocytes was enlarged by Ang-II, and ANP and BNP levels were increased. QL processing could save these changes. miR-382-5p was upregulated in Ang-II-treated NMVCs, and reducing miR-382-5p could further enhance the therapeutic effect of QL while elevating miR-382-5p weakened the protective effect of QL. QL could inhibit miR-382-5p expression to negatively regulate Activated Transcription Factor 3 (ATF3) expression. Enhancing ATF3 expression rescued miR-382-5p upregulation-mediated role in NMVCs. In addition, QL alleviated Ang-II-stimulated cardiac hypertrophy and cardiac dysfunction in mice. QL may alleviate cardiac hypertrophy and cardiac dysfunction via the miR-382-5p/ATF3 axis.

Yin B ，Jiang X ，Chang X ，Song C ... -  《-》

Matairesinol blunts adverse cardiac remodeling and heart failure induced by pressure overload by regulating Prdx1 and PI3K/AKT/FOXO1 signaling.

Zhang T ，Li L ，Mo X ，Xie S ，Liu S ，Zhao N ，Zhang H ，Chen S ，Zeng X ，Wang S ，Deng W ，Tang Q ... -  《-》

[Mechanism of Tongfu Lifei decoction inhibiting the programmed death-1/programmed death-ligand 1 signaling pathway in THP-1 cells by regulating microRNA-146a].

Lyu B ，Li L ，Huang R ，Zhou X ，Han L ... -  《-》

Sishen pills inhibit inflammatory dendritic cell differentiation via miR-505-3p mediated E-cadherin downregulation in ulcerative colitis.

Ulcerative colitis (UC) is an autoimmune disease that is highly susceptible to recurrence, which is still a lack of effective drugs with minor side effects in clinic. Intervention of inflammatory differentiation of dendritic cells (DCs) might be an effective strategy to treat UC. Sishen Pills (SSP) is a classic Chinese herbal formula which has been demonstrated the protective effect of UC, but the mechanism remains unclear. To elucidate the protective effects of SSP against UC in mice and reveal its regulatory mechanism of DCs and the key active ingredients for the UC treatment based on transcriptomics, network pharmacology and experiments validation in vivo and vitro. The key active ingredients of SSP were detected and screened integrating LC-MS/MS and network pharmacology. A mouse UC model was induced with 3% sodium dextran sulfate and treated with SSP for 14 days to evaluate the efficacy. ELISA was used to detect the levels of IL-6, IL-1β and TNF-α in the colon; flow cytometry was used to detect the expression levels of DCs and their subpopulations; whole transcriptomic sequencing of differential RNAs in the colon and RT-PCR to detect key miRNAs to verify the sequencing results. Mouse bone marrow-derived dendritic cells (BMDCs) were isolated, an inflammatory model was constructed using 100 ng/ml LPS, and the effects of SSP on DC proliferation and apoptosis and their surface co-stimulatory molecule expression were examined; IL-6, IL-1β, TNF-α levels were measured by ELISA; RT-PCR and WB were performed to detect miR-505-3p, CDH1, E-cadherin expression. BMDCs with low expression of miR-505-3p were constructed by lentiviral transfection for further validation. The potential key ingredient was re-validated in vivo and vitro experiment. Animal experiments showed that SSP alleviated DSS-induced UC symptoms and colonic pathological injury in mice, and inhibited IL-6, IL-1β, TNF-α secretion and inflammatory DC proliferation and activation maturation. Network pharmacology predicted that evodiamine, isobavachalcone, curcumin, and engenol may play a key role in SSP. RNA sequencing revealed that miR-505-3p, as the differential miRNA, shared a large number of transcription factors with E-cadherin, and was involved in inflammatory differentiation regulation. In vivo experiments confirmed that SSP accelerated apoptosis, slowed down proliferation, inhibited inflammatory differentiation and IL-6, IL-1β, and TNF-α secretion in BMDCs, and decreased miR-505-3p, CDH1, and E-cadherin levels. After knocking down miR-505-3p, SSP could not regulate the inflammatory differentiation and IL-6, IL-1β, TNF-α level in BMDCs. Additionally, evodiamine was found and verified to be the key active ingredient of SSP in preventing the inflammatory differatiation of DCs. SSP prevented the inflammatory differentiation of DCs by downregulating the expression of miR-505-3p, in which Evodiamine may played a key role.

Huang J ，Zhong Y ，Cheng N ，Zhang Z ，Huang L ，Song L ，Cheng S ，Zhao H ，Liu D ... -  《-》

Xuebijing improves inflammation and pyroptosis of acute lung injury by up-regulating miR-181d-5p-mediated SPP1 inactivation.

Xuebijing (XBJ) is widely applied in the treatment of Acute Lung Injury (ALI). This study focused on the potential mechanism of XBJ in Lipopolysaccharide (LPS)-induced ALI. The rat ALI model was established by injection of LPS (10 mg/kg) and pretreated with XBJ (4 mL/kg) three days before LPS injection. BEAS-2B cell line was stimulated with LPS (1 μg/mL) and ATP (5 mM) to induce pyroptosis, and XBJ (2 g/L) was pretreated 24h before induction. The improvement effects of XBJ on pulmonary edema, morphological changes, and apoptosis in ALI lung tissue were evaluated by lung wet/dry weight ratio, HE-staining, and TUNEL staining. Inflammatory cytokines in lung tissue and cell supernatant were determined by ELISA. pyroptosis was detected by flow cytometry. Meanwhile, the expressions of miR-181d-5p, SPP1, p-p65, NLRP3, ASC, caspase-1, p20, and GSDMD-N in tissues and cells were assessed by RT-qPCR and immunoblotting. The relationship between miR-181d-5p and SPP1 in experimental inflammation was reported by dual luciferase assay. XBJ could improve inflammation and pyroptosis of ALI by inhibiting contents of inflammatory cytokines, and levels of inflammation- and pyroptosis-related proteins. Mechanistically, XBJ could up-regulate miR-181d-5p and inhibit SPP1 in ALI. miR-181d-5p can target the regulation of SPP1. Depressing miR-181d-5p compensated for the ameliorative effect of XBJ on ALI, and overexpressing SPP1 suppressed the attenuating effect of XBJ on LPS-induced inflammation and pyroptosis. XBJ can regulate the miR-181d-5p/SPP1 axis to improve inflammatory response and pyroptosis in ALI.

Wu X ，Xin R ，Zhang Y ，Yang C ，Sun F ，Wang Y ，Zheng F ... -  《-》