Exploring the Anti-Pulmonary Fibrosis Mechanism of Jingyin Granule by Network Pharmacology Strategy.

Pulmonary fibrosis (PF) is a clinically common disease caused by many factors, which will lead to lung function decline and even respiratory failure. Jingyin granule has been confirmed to have anti-inflammatory and antiviral effects by former studies, and has been recommended for combating H1N1 influenza A virus (H1N1) infection and Coronavirus disease 2019 (COVID-19) in China. At present, studies have shown that patients with severe COVID-19 infection developed lung fibrotic lesions. Although Jingyin granule can improve symptoms in COVID-19 patients, no study has yet reported whether it can attenuate the process of PF. Here, we explored the underlying mechanism of Jingyin granule against PF by network pharmacology combined with in vitro experimental validation. In the present study, the active ingredients as well as the corresponding action targets of Jingyin granule were firstly collected by TCMSP and literature data, and the disease target genes of PF were retrieved by disease database. Then, the common targets were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and then a PPI network and an ingredient-target network were constructed. Next, UPLC-MS was used to isolate and identify selected representative components in Jingyin granule. Finally, LPS was used to induce the A549 cell fibrosis model to verify the anti-PF effect of Jingyin granule in vitro. Our results indicated that STAT3, JUN, RELA, MAPK3, TNF, MAPK1, IL-6, and AKT1 were core targets of action and bound with good affinity to selected components, and Jingyin granule may alleviate PF progression by Janus kinase 2/signal transducers and activators of transcription (JAK2/STAT3), the mammalian nuclear factor-κB (NF-κB), the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), tumor necrosis factor (TNF), and the extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling pathways. Overall, these results provide future therapeutic strategies into the mechanism study of Jingyin granule on PF.

Evaluating the Therapeutic Mechanisms of Selected Active Compounds in Houttuynia cordata Thunb. in Pulmonary Fibrosis via Network Pharmacology Analysis.

Pulmonary fibrosis, a common outcome of pulmonary interstitial disease of various different etiologies, is one of the most important causes of respiratory failure. Houttuynia cordata Thunb. (family: Saururaceae) (H. cordata), as has been reported, is a Chinese herbal medicine commonly used to treat upper respiratory tract infection and bronchitis. Our previous study has proven that sodium houttuyfonate (an additional compound from sodium bisulfite and houttuynin) had beneficial effects in the prevention of pulmonary fibrosis (PF) induced by bleomycin (BLM) in mice. In the present study, network pharmacology was used to investigate the efficiency and potential mechanisms of H. cordata in PF treatment. Upon manual collection from the literature and databases such as TCMSP and TCM-ID, 10 known representative ingredients of H. cordata species were screened. Then, the prediction of the potential active ingredients, action targets, and signaling pathways were conducted through the Gene Ontology (GO), protein-protein interaction (PPI),and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The results of network pharmacology prediction suggested that H. cordata may act through multiple signaling pathways to alleviate PF, including the phosphatidylinositol 3-kinase-protein kinase B (PI3K/AKT) pathways, mitogen-activated protein kinase (MAPK) pathways, the tumor necrosis factor (TNF) pathways, and interleukin-17 (IL-17) signaling pathways. Molecular docking experiments showed that the chemical constituents of H. cordata had good affinity with TNF, MAPK1, and AKT1, and using lipopolysaccharide (LPS)-induced A549 cells, a model was established to verify the anti-pulmonary fibrosis effects and related mechanisms of H. cordata-relevant constituents. Finally, these evidences collectively suggest H. cordata may alleviate PF progression via PI3K/Akt, MAPK, and TNF signaling pathways and provide novel insights to verify the mechanism of H. cordata in the treatment of PF.

Sodium Houttuyfonate Inhibits Bleomycin Induced Pulmonary Fibrosis in Mice.

Pulmonary fibrosis (PF) could severely disrupt the normal lung architecture and function with fatal consequences. Currently, there is no effective treatment for PF or idiopathic pulmonary fibrosis (IPF). The aim of this study was to investigate the effects of Sodium Houttuyfonate (SH) on bleomycin (BLM) induced PF mice model. Our results indicated that SH could attenuate BLM induced lung injury by reducing the inflammation, fibrogenesis and lung/body weight ratio. The proposed mechanisms for the protective effects of SH include: 1) improvement of pulmonary function in BLM mice, for instance, it can elevate the vital capacity (VC), increase the forced expiratory flow at 50% of forced vital capacity (FEF50) and improve other pulmonary function indices; 2) inhibition of collagen formation in BLM mice; 3) attenuation of the elevation of inflammatory cytokines, such as interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α), which are triggered by BLM administration; 4) reduction of the mRNA level and protein production of transforming growth factor-ß1 (TGF-ß1) in BLM mice. Furthermore, it was found that the protective effects of SH against BLM induced PF in mice was comparable to that of prednisone acetate (PA) tablets, a widely used drug for immunological diseases. Although Houttuynia Cordata Thunb has been widely used in China for lung infection and inflammation, the mechanism has not yet been fully elucidated. Our study provides the evidence that SH is an effective compound against pulmonary injury, irritation and fibrogenesis.

Relationships between pharmacokinetics and efficacy of Xie-xin decoction in rats with experimental ulcerative colitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Xie-xin decoction (XXD) has been used as a classic formula in China for the treatment of gastrointestinal dysfunction such as ulcerative colitis (UC). However, no potential action mechanisms and active compounds had been systematically investigated. AIM OF THE STUDY: To explore the effectiveness and the material basis of XXD in trinitrobenzene sulfonic acid (TNBS)-induced UC rats. MATERIALS AND METHODS: XXD was administered orally for 8 days at a dosage of 2 or 4g/kg/day. Plasma pharmacokinetic properties and colon tissue concentrations of multiple compounds from XXD were detected. Tissue damage scores, production of interleukin (IL)-10 and myeloperoxidase (MPO), expression of tumor necrosis factor-alpha (TNF-α) and nuclear factor-kappa Bp65 (NF-κBp65) in colon tissues were examined. Canonical correlation analysis was performed to evaluate the relationships between pharmacokinetics and efficacy to elucidate significantly active compounds of XXD. RESULTS: XXD promoted the recovery of colitis and inhibited the colonic inflammation damage in UC rats by reducing the level of MPO and the expression of TNF-α and NF-κBp65, and increasing the production of IL-10 in colon tissues. Efficacy of XXD was positively related with AUC of five plasma compounds (baicalin, berberine, wogonoside, wogonin, and rhein) and concentrations of six colon tissue compounds (coptisine, jatrorrhizine, palmatine, berberine, baicalein and emodin), respectively. CONCLUSIONS: The multiple compounds in plasma and colon tissues from XXD might be the main material basis for therapeutic potentials in UC rats.

Effects of total glucosides from paeony (Paeonia lactiflora Pall) roots on experimental atherosclerosis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Total glucosides of paeony (TGP), compounds extracted from the roots of Paeonia lactiflora Pall, have been used as an anti-inflammatory drug for the treatment of rheumatoid arthritis (RA) in China. Inflammation plays a critical role in the development of atherosclerotic vascular disease. Risk of cardiovascular diseases is significantly higher in patients with RA than in normal population. It has a great significance to study the effects of TGP on atherosclerosis. AIM OF THE STUDY: To investigate the effects of TGP on atherosclerosis induced by excessive administration of vitamin D and cholesterol in rats and study the mechanisms involved. MATERIALS AND METHODS: Atherosclerosis was induced by excessive administration of vitamin D and cholesterol in rats. TGP was intragastrically administered for 15 weeks. The serum concentrations of total cholesterol (TC), triglyceride (TG), low density lipoprotein-cholesterol (LDL-C) and high density lipoprotein-cholesterol (HDL-C) were measured by automatic biochemistry analyzer. Apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB) were determined by immunoturbidimetry method, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and C-reactive protein (CRP) were measured by enzyme-linked immunosorbent assay (ELISA) method. The morphological changes of aorta were observed with optical microscopy. RESULTS: Compared to controls, TGP significantly lowered the serum level of TC, TG, LDL-C, ApoB, TNF-alpha, IL-6 and CRP, increased the ratios of HDL-C/LDL-C and ApoA1/ApoB, decreased the intima-media thickness (IMT) of abdominal aortal wall and improved the morphological change of the aorta. CONCLUSIONS: TGP may attenuate the development of atherosclerotic disease. The beneficial effects are associated with its lowering blood lipids and inhibiting the expression of inflammatory cytokines.

[Influence of Tinglizi on collagen volume fraction and perivascular collagen area in left ventricle tissue of cardiac hypertrophy induced by abdominal aortic banding in rats].

OBJECTIVE: To evaluate the influence of Tinglizi on collagen volume fraction (CVF) and perivascular collagen volume area (PVCA ) in left ventricle tissue of cardiac hypertrophy induced by abdominal aortic banding in rats. METHOD: Ventricular remodeling was induced by abdominal aortic banding (AAB) in rats. After 30 day treatment, the systolic blood pressure (SBP), diastolic blood pressure (DBP); heart rate (HR) were measured. The histological assay consisted of the HE stain for determining the myo-cardium cell cross section and collagen stain (Van Gieson' method) for determining collagen content, including collagen volume fracton (CVF) and perivascular collagen volume area (PVCA). RESULT: The experimental data demonstrated that Tinglizi decreased SBP, DBP, HR and could significantly reduce the total collagen content (CVF, PVCA) and lessen the myocardium cell cross section (P < 0.05). CONCLUSION: Tinglizi may decrease the total collagen content of ventricle and attenuate the ventricular remodeling induced by abdominal aortic banding.

[Semen descurainiae inhibits CYP11B1, CYP11B2 and TGF-beta1 mRNA expression in left ventricular].

OBJECTIVE: To investigate the effects of Semen descurainiae and Captopril on CYP11B1, CYP11B2 and TGF-beta1 mRNA expression of heart tissue in rats treated with Abdominal Aortic Banding. METHODS: Ventricular remodeling was induced by abdominal aortic banding (AAB) in rats. After 30 days' treatment, the ratios of LVW/BW (left ventricle weight/body weight), HW/BW (heart weight/body weight) were calculated; Then the CYP11B, CYP11B2 and TGF-beta1 mRNA expression of left ventricle were detected by Real-time PCR, respectively. RESULTS: The experimental data demonstrated that Semen descurainiae decreased the indexes of LVW/BW and HW/BW, down-regulated CYP11B, CYP11B2 and TGF-beta1 mRNA expression in left ventricle (P<0.05). CONCLUSION: Semen desceurainiae can significantly inhibit the experimental ventricular remodeling; the mechanism is related to its ability to attenuate the mRNA expression of CYP11B1, CYP11B2 and TGF-beta1 in left ventricle. The inhibition of aldosterone key gene expression by Semen descurainiae may contribute to its effect on restraint cardiac remodeling.

[Experimental research of Shuanghuang Shengbai granule on hematopoietic cells of leucopenia model mice].

OBJECTIVE: To investigate the leukogenic function of Shuanghuang Shengbai (SHSB) granule and the related mechanisms. METHOD: Mouse leukopenic models were induced by radiation. Mice were divided into normal control group, model control group, positive control group-Li kejun tablet group and three different dose (high, middle, low-dose) groups of SHSB granule. The peripheral hemogram, thymus index (TI), spleen index (SI), bone marrow nucleated cell (BMNC) and colony forming unit-spleen (CFU-S) were evaluated. The proliferation of bone marrow cells was determined. The in vitro cultured colony forming unit granulocyte macrophage (CFU-GM) was estimated. The index of CD34+ cell in BMNC were determined by flow cytometry. The ultra-micro structure of bone marrow were observed by electromicroscope. RESULT: (1)SHSB rranule could increase the WBC of model mice; (2)SHSB granule could increase BMNC and promote the proliferation of bone marrow cell; (3)SHSB granule could increase CFU-S, CFU-GM and CD34+ cell index in BMNC of model mice significantly; (4)SHSB Granule could also protect the bone marrow hemotopoietic microenvironment from the harm of radiation; (5)SHSB granule could increase the SI of model mice, indicating the enhancement of immunological function. CONCLUSION: SHSB granule has apparent leukogenic function. The mechanism may be related to enhancing the proliferation of hematopoietic cells and protecting the bone marrow hemotopoietic microenvironment.

[Effect of Shuanghuang Shengbai granule on radiotherapy or chemotherapy induced leukopenia in mice].

OBJECTIVE: To observe the effect of Shuanghuang Shengbai granule on mice leukopenia induced by ip cyclophosphamide (CTX) or radiation. METHOD: Mice leukopenia models were induced by ip CTX or radiation, and then treated with Shuanghuang Shengbai granule per oral. The peripheral hemogram, thymus index, spleen index, bone marrow nucleated cell (BMNC) and colony forming unit-spleen (CFU-S) were detected. The bone marrow cell differentiation was examined. The pathological slices of bone marrow were observed. RESULT: Shuanghuang Shengbai granule could increase the WBC, BMNC, CFU-S of model mice significantly; Shuanghuang Shengbai granule could make the granulocyte and erythrocyte index recovered to normal level and it could also protect the bone marrow hemotopoietic microenvironment from the harm of radiation. CONCLUSION: Shuanghuang Shengbai granule has apparent leukogenic function.

[The bioactivity of angiotensin II and the effects of related Chinese Herbs].

OBJECTIVE: To review the bioactivity of angiotensin II and the effects of Chinese herbs on it. METHOD: The correlative documents published in recent years were summarized. RESULT: Angiotensin II plays an important role in the development of many diseases, such as hypertension, arteriosclerosis, myocardial lesion due to ischemia and reperfusion, cardiac hypertrophy and fibrosis, dysfunction of fibrinolytic system, thrombosis, renal failure etc. Some Chinese herbs inhibit the actions of angiotensin II. CONCLUSION: Further researches must be done to investigate the bioactivity of angiotensin II and the effects of Chinese herbs on preventing the body tissue from being impaired by it.