Molecular mechanism of modified Huanglian Wendan decoction in the treatment of polycystic ovary syndrome.

To investigate the mechanism of modified Huanglian Wendan decoction in the intervention of polycystic ovary syndrome (PCOS) by network pharmacology and molecular docking. The ingredients and targets of modified Huanglian Wendan decoction were retrieved from the traditional Chinese medicine Systems Pharmacology database. Related targets of PCOS were screened by Comparative Toxicogenomics Database database. Cytoscape 3.7.2 (https://cytoscape.org/) was used to draw the target network diagram of "traditional Chinese medicine - ingredient - PCOS," STRING database was used to construct the target protein interaction network. NCA tool of Cystoscape 3.7.2 was used to carried out topology analysis on PPI network, core components and key targets were obtained. Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis were carried out for the intersection targets by David database. AutoDockTools 1.5.6 software (https://autodock.scripps.edu/) was used to conduct molecular docking verification of key components and key targets. Ninety-one ingredients of the modified Huanglian Wendan decoction and 23,075 diseases targets were obtained, 155 Intersection targets of the drug and disease were obtained by R language, Veen plot was drawn. Gene ontology enrichment analysis obtained 432 biological processes, 67 cell components, 106 molecular functions. Fifty-four Kyoto encyclopedia of genes and genomes enrichment pathways (P < .05) including tumor necrosis factor, hypoxia-induced factors-1, calcium, and drug metabolism-cytochrome P450 signaling pathway. Molecular docking showed quercetin, luteolin, kaempferol, and baicalein were stable in docking with core targets. Network pharmacology and molecular docking were used to preliminarily study the mechanism of action of modified Huanglian Wendan decoction in the treatment of PCOS, which laid foundation for future experimental research and clinical application.

A network pharmacology study of mechanism and efficacy of Jiawei Huanglian-Wendan decoction in polycystic ovary syndrome with insulin resistance.

Polycystic ovary syndrome (PCOS) is a common reproductive metabolic disorder, normally accompanied by insulin resistance (IR). The specific pathogenesis of this disease remains unclear. To identify the underlying pathogenesis of PCOS with IR and explore the potential efficacy and mechanism of Jiawei Huanglian-Wendan decoction (JHWD) by a network pharmacology approach. The effective components and the potential drug and disease-related targets are retrieved. Drug-disease overlapped targets are being obtained by Venny analysis. The construction of protein-protein interaction network relied on Search Tool for the Retrieval of Interacting Genes/Proteins database (STRING), after uploading drug-disease overlapped targets. The drug-component-target-disease interaction network map was displayed , after importing their data into Cytoscape 3.7.2 software. Bioinformatics analyses are being performed by Metascape and Kyoto Encyclopedia of Genes and Genomes databases, respectively. Further, molecular docking analysis was carried out using AutoDock software. Finally, the influence of JHWD is verified by means of traditional Chinese medicine syndrome score, the rate of resumption of normal menstrual cycles and regular ovulation, the blood lipid levels, the blood glucose and insulin levels, and the inflammatory cytokines in PCOS with IR patients. Four primary interaction networks of JHWD are constructed. The enrichment analysis of PCOS-IR-related targets demonstrated that the top enriched pathways in the development of PCOS with IR are pathways in cancer, metabolic, phosphoinositide-3-kinase-protein kinase B signaling, lipid and atherosclerosis, and mitogen-activated protein kinase signaling pathways. Molecular docking analysis revealed strong binding interactions of the key targets with the active components. Further confirmations showed that the active components of JHWD exhibited significant clinical efficacy in improving the clinical syndromes, menstrual cyclicity and ovulatory function, and significantly reducing the blood lipid levels, blood glucose and insulin levels, and inflammatory cytokines in PCOS with IR patients. The combination of the network pharmacological analysis and clinical validation stated that the active compounds in JHWD could regulate glycolipid metabolism, reduce IR, and exert anti-inflammatory effects in the treatment of PCOS with IR, promoting Chinese classical formulations.

Study the Mechanism of Gualou Niubang Decoction in Treating Plasma Cell Mastitis Based on Network Pharmacology and Molecular Docking.

Objective: Explore the potential molecular mechanisms behind the therapeutic functions of Gualou Niubang decoction (GLNBD) in the treatment of plasma cell mastitis (PCM) by network pharmacology and molecular docking. Methods: GLNBD is a formula of Chinese traditional medicine consisting of 12 herbs. The potential active ingredients of GLNBD and their target genes were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database, and PCM-related target genes were obtained from GeneCards, OMIM, and NCBI databases, using R language to obtain intersection targets; then, the STRING database and Cytoscape software were used to establish protein-protein interaction networks and herb ingredient target networks. DAVID was used to perform GO and KEGG pathway enrichment analyses on the intersection target. PyMoL-2.5.0 and AutoDock Tools-1.5.6 were used to verify the molecular docking. Results: 164 ingredients and 58 intersection targets were obtained in the treatment of PCM by GLNBD. Four key active compounds and four key proteins were identified. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that biological functions of potential target genes were associated with negative regulation of the apoptotic process, response to hypoxia, positive regulation of transcription, and DNA-templated, with related pathways involving the pathway in cancer, phosphatidylinositol 3-kinase (PI3K) Akt signaling pathway, and AGE-RAGE signaling pathway in diabetic complications. Moreover, the binding activities of key target genes and essential active compounds of Chinese herbal medicines in GLNBD were further validated by molecular docking. The results showed that the docking results were stable and had good binding ability. Conclusion: This study suggested that four potential key active components, including quercetin, luteolin, fisetin, and kaempferol, were identified in GLNBD, which could interact with ALB, EGFR, IL-6, and VEGFA modulating the activation of the pathway in cancer, PI3K-Akt pathway, and AGE-RAGE signaling pathway in diabetic complications.

Successful conservative treatment of placenta accreta with traditional Chinese medicine: A case report.

RATIONALE: Currently, placenta accreta treatment mainly includes nonconservative surgical and conservative treatments such as Traditional Chinese medicine (TCM). This report describes the case of a 37-year-old woman who suffered incomplete placenta accreta after vaginal delivery and was cured by TCM. TCM treatment of placenta accreta has its own unique advantages, including low toxicity and few side effects, unaffected breastfeeding, and retention of the uterus, which can ensure the expulsion of residual placenta and be beneficial to patients' physical and mental health. PATIENT CONCERNS: Symptoms included a small amount of vaginal bleeding and occasional lesser abdominal pain. The patient showed lesser abdominal tenderness, a red tongue moss with petechial hemorrhage, and a hesitant pulse. The reproductive history was G3P2L2A1. In addition, the patient was afraid of having her uterus removed due to incomplete placental separation. DIAGNOSES: The case was diagnosed as placental accreta. Ultrasound is the preferred method of diagnosis, and biomarkers, such as beta hCG, assist in screening for placental accreta. Doppler ultrasonography showed that in the bottom of the right uterine cavity, there was an uneven echo group of 7.6 × 4.6 cm, which was not clearly demarcated from the posterior wall; the muscle layer became thinner, with a thinnest part of 0.19 cm, and abundant blood flow signals were observed (Fig. 1JOURNAL/medi/04.03/00005792-202102190-00086/figure1/v/2021-02-16T234818Z/r/image-tiff). The beta hCG was 580.92 mIu/ml. INTERVENTIONS: The patient initially underwent curettage therapy 9 days after delivery, but it failed due to excessive intraoperative bleeding. The patient then turned to TCM treatment. The doctor prescribed a multi-herbal formula. OUTCOMES: After 4 months, the residual placenta was expelled, and the patient's symptoms disappeared completely. No adverse and unexpected events occurred during treatment. During 3 months of follow-up, the patient had no abdominal pain, abnormal vaginal bleeding, or other complications. LESSONS: This study shows that TCM is safe and effective for treating placenta accreta, and it is worth recommending TCM as a conservative treatment along with other treatments. In practice, however, we find that the earlier TCM treatment is applied, the better the effect; therefore, early intervention with TCM is particularly important.

Effects of Yixintai Pills on Myocardial Cell Apoptosis in Rats With Adriamycin-Induced Heart Failure.

OBJECTIVE: To study the effects of Yixintai pills on myocardial cell apoptosis in rats with adriamycin (ADR)-induced heart failure (HF) and the mechanism of action. METHODS: Sixty healthy male Wistar rats randomly were divided into Control, Model, Captopril, and Yixintai pill groups. A rat model of ADR-induced HF was constructed by intraperitoneal injection of ADR (2.5 mg/kg). The control group was given an equal volume of normal saline; the Yixintai pill and Captopril groups were given corresponding mediations (5 mg/kg) by lavage. After 4 weeks of treatment, fasting blood was collected to detect the contents of plasma rennin activity (PRA), angiotensin II (AngII), and aldosterone (ALD). B ultrasound was used to detect the heart structure, and the heart weight/body weight (HW/BW) ratio was calculated. The pathology of myocardial tissues was observed by HE staining. The apoptosis of myocardial cells was detected by TUNEL assay. The expression levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in serum were analyzed by ELISA, and the protein expression levels of protein kinase B (Akt), phosphorylated (p)-Akt, glycogen synthase kinase-3ß (GSK-3ß) and p-GSK-3ß in myocardial tissues were measured by Western blotting. RESULTS: Compared with the Control group, the PRA, AngII, ALD, left ventricular posterior wall thickness at end-systole (LVPWs), left ventricular posterior wall thickness at end-diastole (LVPWd), interventricular septal thickness at end-systole (IVSs), interventricular septal thickness at end-diastole (IVSd), HW/BW, TNF-α and IL-6 of model group increased significantly (P < .05). PRA, AngII, ALD, LVPWs, LVPWd, IVSs, IVSd, HW/BW, TNF-α and IL-6 of the Yixintai pill and Captopril groups were significantly lower than those of the Model group (P < .05). There were no significant differences in the indices between the Yixintai pill and Captopril groups (P > .05). In the Model group, lamellar necrosis, vacuolar degeneration, increased myocardial fibers and lamellar dissolution of myocardial cells were found in myocardial tissues. However, the myocardial cells of the Control group were neatly arranged and clearly structured, and only a few ones underwent fibrosis. There were mild myocardial fibrosis and vacuolar degeneration in the Yixintai pill and Captopril groups, and the degeneration and hyperplasia of myocardial fibers were obviously relieved. Compared with the Control group, the apoptosis index (AI) of the Model group increased significantly (P < .05). The AI values of the Yixintai pill and Captopril groups were significantly lower than those of the Model group (P < .05). Compared with the Control group, the expression levels of p-Akt and p-GSK-3ß in the Model group decreased significantly (P < .05). The expression levels of p-Akt and p-GSK-3ß in the Yixintai pill and Captopril groups were significantly higher than those of the Model group (P < .05), whereas the former 2 groups had similar results (P > 0.05). CONCLUSION: Yixintai pills may inhibit myocardial cell apoptosis and ventricular remodeling in rats by up-regulating PI3K/Akt/GSK-3ß signal, thus protecting the heart function.

[A literature review on Chinese medicine syndrome and syndrome elements of chronic fatigue syndrome].

OBJECTIVE: To research the distribution characteristics of Chinese medicine (CM) syndrome and syndrome elements of chronic fatigue syndrome (CFS) by analyzing literature in recent 20 years. METHODS: Relevant literature on treating CFS by syndrome differentiation of CM at home were retrieved by computer and manual ways. Database were established by using EpiData 3.1 to conduct frequency analysis of syndrome and syndrome elements. RESULTS: The most common clinical syndromes were Xin-Pi deficiency syndrome, Gan stagnation Pi deficiency syndrome, Gan-Shen yin deficiency syndrome, Gan qi stagnation syndrome, and Pi-Wei qi deficiency syndrome. Disease locations were sequenced as Pi, Gan, Shen, and Xin. The clinical pathogenesis of CFS was characterized by deficiency of vital energy, complicated with intermingled excess and deficiency. Asthenia of healthy energy was mainly manifested as qi deficiency, blood deficiency, and yin deficiency, while excess of sthenia was mainly manifested as qi stagnation, phlegm dampness, and static blood. CONCLUSIONS: Research of CM syndrome starting from syndrome elements can better unify and standardize clinical syndrome differentiation. Results of literature analysis can provide reference for further studies.

Preparation of a novel rape pollen shell microencapsulation and its use for protein adsorption and pH-controlled release.

This study aims to synthesize hollow microspheres (HMS) from rape pollen via H3PO4 hydrothermal carbonization. The rape pollen hollow shell was used as the carrier and bovine serum albumin as a model protein. The properties of HMS were characterized by scanning electron microscope (SEM), solid-state nuclear magnetic resonance and elemental analysis. The SEM images clearly showed that the HMS had perfect spherical morphology and porous hollow surface. In the separated filtrate, a large number of sucroses were detected by high-performance liquid chromatography, suggesting that the hydrolysis of starch molecules occurred during the hydrothermal process. The formation of HMS was that the rape pollen inclusion was removed from rape pollen shell to preserve integral HMS by H3PO4 hydrothermal. The HMS possessed amphiphilic surfaces, which was suitable for protein adsorpion and pH-controlled release application.

Chinese herbal medicine Shenqi Detoxification Granule inhibits fibrosis in adenine induced chronic renal failure rats.

BACKGROUND: Progressive fibrosis accompanies all chronic renal disease, connective tissue growth factor (CTGF,) and platelet-derived growth factor-B, (PDGF-B,) play important roles in extra-cellular matrix abnormal accumulation, while endothelin-1 (ET-1) nitric oxide (NO,) are related to endothelial dysfunction, which mediates the progression of renal fibrosis. Shenqi Detoxification Granule (SDG), a traditional Chinese herbal formula, has been used for treatment of chronic renal failure in clinic for many years. MATERIALS AND METHODS: In order to evaluate the efficacy, and explore the mechanism of SDG to inhibit the progression of renal fibrosis, study was carried out using the adenine-induced Wister rats as the CRF model, and losartan as postive control drug. Levels of serum creatinine [Scr], and blood urea nitrogen (BUN), albumin (ALB), 24hrs, urine protein (24hUP), triacylglycerol (TG), and cholesterol (CHO), together with ET-1, and NO were detected. Pathological changes of renal tissues were observed by HE, staining. In addition, CTGF and PDGF-B expression were analyzed by immuno-histo-chemistry. RESULTS: The results indicated that SDG can effectively reduce Scr, BUN, 24hUP, TG, and CHO levels, increase ALB levels, inhibit renal tissue damage in CRF rats, and the mechanism maybe reduce PDGF-B, CTGF expression and ET-1/NO. CONCLUSION: Shenqi Detoxification Granule is a beneficial treatment for chronic renal failure.

Characterization of genes expressed in response to cadmium exposure in the earthworm Eisenia fetida using DDRT-PCR.

The transition metal cadmium is a pervasive and persistent environmental contaminant that is both a human toxicant and a carcinogen. To inhibit cadmium-induced damage, cells increase the expression of genes encoding stress-response proteins. The transcription of many stress-responsive genes, including those that encode metallothioneins, glutathione-S-transferases (GSTs) and heat shock proteins have been reported. The aim of this work was to investigate in Eisenia fetida the genes whose expressions are regulated following exposure to cadmium. mRNA differential display reverse transcription-polymerase chain reaction was used to analyze gene expression in E. fetida exposed to 50mg/l cadmium solution. Among the derived cDNA clones sequenced, we found 15 genes up-regulated and 12 down-regulated in response to cadmium exposure. The translated amino acid sequences of eight clones were similar to the Lumbricus terrestris hemoglobin dodecamer, Tribolium castaneum membrane protein, Escherichia coli UMN026 DNA-binding transcriptional activator, Brugia malayi immunoglobulin, Homo sapiens cell growth-inhibiting protein, Apis mellifera poly U binding factor, Escherichia fergusonii copper transporter, and the mRNA that encodes E. coli K-12 cytoplasmic insertase into membrane protein. Five cDNA fragments presented no homology with known gene sequences, suggesting that these sequences may either encode proteins not yet identified or correspond to untranslated regions of mRNA molecules. In-depth functional analyses of these genes are needed to reveal their exact roles.

Effects of Ningdong granule on the dopamine system of Tourette's syndrome rat models.

ETHNOPHARMACOLOGICAL RELEVANCE: Ningdong granula (NDG) is a traditional Chinese medicine (TCM) preparation for the treatment of Tourette's syndrome (TS). AIM OF THE STUDY: To explore the effects of NDG on stereotyped behavior, homovanillic acid (HVA) in sera, dopamine (DA) and dopamine D2 receptor (DRD2) in striatum in TS rats. MATERIALS AND METHODS: Sixty-four rats were randomly divided into control group and three experimental groups. TS rat models were induced by intraperitoneal injection (i.p.) of Apomorphine (Apo, 2 mg/kg) in the experimental groups. After Apo i.p., rats were intragastrically injected (i.g.) with NDG at 370 mg/kg (NDG+Apo group), haloperidol (Hal) at 1.0 mg/kg (Hal+Apo group), and normal saline (0.9%) at 10 ml/kg (control group and Apo group), respectively, once a day for 12 weeks. The behaviors of the rats were observed and recorded each day. After 12 weeks, all rats were sacrificed and sera and striatum were collected. The levels of HVA in sera, DA in striatum were examined by ELISA, and the expression of DRD2 mRNA in striatum was measured by RT-PCR. RESULTS: NDG could increase the HVA content in sera (P<0.05), meanwhile downregulate the expression of DRD2 mRNA in striatum (P<0.05), and inhibit the stereotyped behaviors induced by Apo (P<0.01) in TS rats, the same effects with Hal. NDG could also reduce the DA content in striatum (P<0.01), while Hal could not. CONCLUSIONS: NDG could effectively inhibit the stereotyped behaviors in TS rats, and the mechanisms may be related to the suppression of DA system by increasing the content of HVA in sera, decrease the content of DA and repressing the expression of DRD2 mRNA in striatum.

Effects of gastrodin on the dopamine system of Tourette's syndrome rat models.

Gastrodin is used in traditional Chinese medicine to treat Tourette's syndrome (TS). This study evaluated the effects of gastrodin on the dopamine system. TS rat models were established by intraperitoneal injection of apomorphine. After intervention by gastrodin, stereotyped behaviors of TS rats were significantly inhibited and levels of homovanillic acid (HVA) were significantly increased. We conclude that gastrodin effectively inhibited stereotyped behaviors and controlled TS symptoms by promoting dopamine metabolism, thereby increasing levels of HVA in sera.

Neuroprotective effects of chlorogenic acid against apoptosis of PC12 cells induced by methylmercury.

Chlorogenic acid (CGA) widely exists in edible and medicinal plants. We aimed to evaluate the effect of CGA on the protection from apoptosis by methylmercury (MeHg) in PC12 cells. Cell viability was evaluated by MTT assay. Apoptosis was assayed by flow cytometry detection. Caspase-3 activity was measured by confocal microscopy. Intracellular GSH levels were determined by bicinchoninic acid protein assay. Intracellular reactive oxygen species (ROS) was assessed by means of chloromethyl-dihydrodichlorofluorescein diacetate. Glutathione peroxidase (GPx) activity was determined by UV. In order to elucidate the action of CGA, the protective effects of CGA were compared to Vit.E. CGA was effective at protecting PC12 cells against MeHg-induced damage in dose-dependent manner. CGA not only suppressed the generation of ROS, the decrease of activity in GPx and the decrease of GSH, but also attenuated caspase-3 activation in PC12 cells by MeHg. CGA eventually protected PC12 cells against MeHg-induced apoptosis. The results highlighted that CGA may exert neuroprotective effects through its antioxidant actions.

Combined human growth hormone and lactulose for prevention and treatment of multiple organ dysfunction in patients with severe chronic hepatitis B.

AIM: To evaluate the efficiency and safety of combined recombinant human growth hormone (rhGH) and lactulose for treatment and/or prevention of multiple organ dysfunction in patients with chronic severe hepatitis B. METHODS: Forty-eight inpatients with chronic severe hepatitis B were randomly divided into rhGH group (n=28) and control group (n=20). In rhGH group, 4-4.5 IU of rhGH was injected intramuscularly once daily for 2-4 wk, and 100 mL of enema containing 30 mL of lactulose, 2 g of metronidazole and 0.9% saline was administered every 2 d for 2-4 wk. Their symptoms and complications were noted. Liver and kidney functions were analyzed by an Olympus analyzer. Serum GH, IGF-1, IGFBP1 and IGFBP3 were measured by ELISA. RESULTS: Clinical symptoms of 90% of these patients in rhGH group were obviously improved. The total effectiveness in rhGH group was better than that in control group (75% vs 40%, P<0.05). After 2- and 4-wk treatment of rhGH respectively, serum albumin (26.1+/-4.1 vs 30.2+/-5.3, 31.9+/-5.1 g/L), prealbumin (79.6+/-28.0 vs 106.6+/-54.4, 108.4+/-55.0 g/L), cholesterol (76.3+/-16.7 vs 85.6+/-32.3, 96.1+/-38.7 mg/dL), and IGFBP1 (56.8+/-47.2 vs 89.7+/-50.3 ng/mL after 2 wk) were significantly increased compared to control group (P<0.05). However, serum GH was decreased. The increase of serum IGF1 and IGFBP3 after rhGH treatment was also observed. CONCLUSION: rhGH in combination with lactulose may be beneficial to the prevention and treatment of multiple organ dysfunction in patients with chronic severe hepatitis.