Xuelin Zhou

The protective effects of compatibility of Aconiti Lateralis Radix Praeparata and Zingiberis Rhizoma on rats with heart failure by enhancing mitochondrial biogenesis via Sirt1/PGC-1α pathway

Aconiti Lateralis Radix Praeparata (Fuzi in Chinese) in combination with Zingiberis Rhizoma (Ganjiang in Chinese) is commonly applied for the treatment of heart failure for thousands of years in China. However, its therapeutic mechanism is still poorly defined. This study aimed to investigate whether the compatibility of Fuzi and Ganjiang can protect rats with acute heart failure by enhancing mitochondrial biogenesis via Sirt1/PGC-1α signaling pathway. Hemodynamic parameters, including heart rate and left ventricular maximal rate of pressure rise and decline, were recorded in rats with acute heart failure induced by Propafenone hydrochloride. The serum levels of cardiac enzymes, including creatine kinase, lactate dehydrogenase, brain natriuretic peptide and cardiac troponin T, were also determined. The gene and protein levels of Sirtuin 1 (Sirt1), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and their downstream transcription factors were measured as well. The results indicated that Fuzi-Ganjiang herbal couple provided more significant benefits by restoring the left ventricular function and cardiac enzyme activities in comparison with their single use. Moreover, this herbal couple possessed a significant cardio-protection by increasing both gene and protein levels of Sirt1 and PGC-1α. In conclusion, the compatibility of Fuzi and Ganjiang had better therapeutic effect than their single use against failing heart, and the underlying mechanisms were partially through increasing mitochondrial biogenesis via Sirt1/PGC-1α pathway.

Fuzheng Huayu capsule as an adjuvant treatment for HBV-related cirrhosis: A systematic review and meta-analysis

Fuzheng Huayu (FZHY) capsule, a formulated traditional Chinese medicine product with 6 Chinese herbs, is widely used for HBV‐related cirrhosis as an adjuvant treatment. However, the efficacy of FZHY capsule for HBV‐induced cirrhosis did not be comprehensively proved by systematic analysis. Our current analysis was aimed to assess the efficacy and safety of FZHY capsule by an evidence‐based method. Databases, including China National Knowledge Infrastructure, Wangfang, VIP medicine information system, Pubmed, Embase, and Cochrane Library, were searched, and the randomized controlled trials of FZHY capsule were used for the treatment of HBV‐associated liver cirrhosis. Meta‐analysis was performed by Review Manager 5.3. The efficacy rate, alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), albumin (ALB), Procollagen III protein (PIIIP), hyaluronic acid (HA), laminin (LN), Collagen C Type IV (IV‐C), Child‐Pugh score, portal vein diameter, spleen thickness, HBeAg negative conversion rate, and HBV‐DNA negative conversion rate were systematically assessed. The Cochrane Risk of Bias tool was used to evaluate the methodological quality of eligible studies. Nineteen studies with 1,769 patients were included in the meta‐analysis. Compared to conventional treatment, FZHY capsule was effective by increasing the efficacy. FZHY capsule was more efficient in improving ALT, AST, TBIL, PIIIP, HA, LN, IV‐C, Child‐Pugh grading score, portal vein diameter, spleen thickness, and HBV‐DNA negative conversion rate with no serious adverse reactions. Nevertheless, a variety of well‐designed randomized controlled trials are needed to confirm these findings since small samples were applied in the previous studies.

Synergistic effects of Ginseng C. A. Mey and Astragalus membranaceus (Fisch.) Bunge on activating mice splenic lymphocytes detected by microcalorimetry and the underlying mechanisms predicted by in silico network analysis

The aim of the current study was to investigate the combination effect of Ginseng C. A. Mey (ginseng) and Astragalus membranaceus (Fisch.) Bunge (astragalus) which are commonly used for strengthening immune system. In this study, the effects of ginseng, astragalus and their combination on activating mice splenic lymphocytes were studied by microcalorimetry in vitro. The parameters of Pmax, Q and Tmax of heat-production curve in spleen lymphocytes were recorded and analyzed, as well as their association with drug concentration. Through the combination index analysis, it was found that ginseng and astragalus could induce the heat generation of splenic lymphocytes. Network analysis was used to investigate the mechanisms, which showed that their combination may cause immune activation in the body through several signaling pathways such as T cell receptor signaling pathway and PI3xa0K-Akt signaling pathway.

Paeoniflorin ameliorates cholestasis via regulating hepatic transporters and suppressing inflammation in ANIT-fed rats

Paeoniflorin has shown the obvious effect on cholestasis according to our previous research. However, its mechanism has not been absolutely explored yet. This study aims at evaluating the potential effect of paeoniflorin on alpha-naphthylisothiocyanate (ANIT) -induced cholestasis by inhibiting nuclear factor kappa-B (NF-κB) and simultaneously regulating hepatocyte transporters. Cholestasis was induced by administration of ANIT. The effect of paeoniflorin on serum indices such as total bilirubin (TBIL), direct bilirubin (DBIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyltranspeptidase (γ-GT), total bile acid (TBA) and histopathology of liver were determined. Liver protein levels of NF-κB, interleukin 1β (IL-1β) and the hepatocyte transporters such as Na+/taurocholate cotransporting polypeptide (NTCP), bile salt export pump (BSEP), multidrug resistance-associated protein 2 (MRP2) and cholesterol 7α-hydroxylase (Cyp7a1) were investigated by western blotting. The results demonstrated that paeoniflorin could decrease serum ALT, AST, ALP, γ-GT, TBIL, DBIL and TBA in ANIT-treated rats. Histological examination revealed that rats treated with paeoniflorin represented fewer neutrophils infiltration, edema and necrosis in liver tissue compared with ANIT rats. Moreover, paeoniflorin significantly reduced the over expressions of NF-κB and IL-1β induced by ANIT in liver tissue. In addition, the relative protein expressions of NTCP, BSEP, MRP2 but not Cyp7a1 were also restored by paeoniflorin. The potential mechanism of paeoniflorin in alleviating ANIT-induced cholestasis seems to be related to reduce the over expressions of NF-κB and hepatocyte transporters such as NTCP, BSEP as well as MRP2.

Antimicrobial Effects of Chemical Compounds Isolated from Traditional Chinese Herbal Medicine (TCHM) against Drug-resistant Bacteria: A Review Paper

Infectious diseases caused by pathogenic bacteria seriously threaten human lives. Although antibiotic therapy is effective in the treatment of bacterial infections, the overuse of antibiotics has led to an increased risk of antibiotic resistance, putting forward urgent requirements for novel antibacterial drugs. Traditional Chinese herbal medicine (TCHM) and its constituents are considered to be potential sources of new antimicrobial agents. Currently, a series of chemical compounds purified from TCHM have been reported to fight against infections by drug-resistant bacteria. In this review, we summarized the recent findings on TCHM-derived compounds treating drug-resistant bacterial infections. Further studies are still needed for the discovery of potential antibacterial components from TCHM.

Hepatoprotective Effect of San-Cao Granule on Con A-Induced Liver Injury in Mice and Mechanisms of Action Exploration

Objective: San-Cao granule (SCG), a traditional Chinese herb formula, has been used for treating autoimmune hepatitis (AIH) in our clinics for a long time. However, its active ingredients and mechanisms of action were still unknown due to its complicated chemical compositions. In the present study, the pharmacological study of SCG on acute liver injury induced by Concanavalin A (Con A) was performed to provide a scientific evidence for SCG against liver injury. Methods: In order to screen active components and predicate mechanisms of action, an “ingredients-target-disease” interaction network was constructed by network pharmacology. Then, the pharmacological study was performed to evaluate the therapeutic effect and the underlying mechanisms of SCG on Con A-induced liver injury in mice. Results: This research demonstrated the pharmacological effect of SCG on Con A-induced liver injury, which was through improving the liver function, relieving the pathological changes of liver tissue, decreasing the level of pro-inflammatory cytokines, and thus balancing the pro- and anti-inflammatory cytokines. And the anti-inflammatory of SCG may advantage over the ursodeoxycholic acid (UDCA). Network pharmacology analysis revealed that the pharmacological effect of SCG might be related to its active ingredients of taraxanthin, dihydrotanshinone I, isotanshinone I, γ-sitosterol, 3β-acetyl-20,25-epoxydammarane-24α, and δ-7-stigmastenol. The hepatoprotective effect of SCG was reflected by suppressing Con A-induced apoptosis which was mediated by TRAIL and FASL. Conclusion: The combination of network pharmacology and experimental data has revealed the anti-apoptotic effect of SCG against Con A-induced liver injury.

The Modulatory Properties of Li-Ru-Kang Treatment on Hyperplasia of Mammary Glands Using an Integrated Approach

Background: Li-Ru-Kang (LRK) has been used in the treatment of hyperplasia of mammary glands (HMG) for several decades and can effectively improve clinical symptoms. This study aims to investigate the mechanism by which LRK intervenes in HMG based on an integrated approach that combines metabolomics and network pharmacology analyses. Methods: The effects of LRK on HMG induced by estrogen-progesterone in rats were evaluated by analyzing the morphological and pathological characteristics of breast tissues. Moreover, UPLC-QTOF/MS was performed to explore specific metabolites potentially affecting the pathological process of HMG and the effects of LRK. Pathway analysis was conducted with a combination of metabolomics and network pharmacology analyses to illustrate the pathways and network of LRK-treated HMG. Results: Li-Ru-Kang significantly improved the morphological and pathological characteristics of breast tissues. Metabolomics analyses showed that the therapeutic effect of LRK was mainly associated with the regulation of 10 metabolites, including prostaglandin E2, phosphatidylcholine, leukotriene B4, and phosphatidylserine. Pathway analysis indicated that the metabolites were related to arachidonic acid metabolism, glycerophospholipid metabolism and linoleic acid metabolism. Moreover, principal component analysis showed that the metabolites in the model group were clearly classified, whereas the metabolites in the LRK group were between those in the normal and model groups but closer to those in the normal group. This finding indicated that these metabolites may be responsible for the effects of LRK. The therapeutic effect of LRK on HMG was possibly related to the regulation of 10 specific metabolites. In addition, we further verified the expression of protein kinase C alpha (PKCα), a key target predicted by network pharmacology analysis, and showed that LRK could significantly improve the expression of PKCα. Conclusion: Our study successfully explained the modulatory properties of LRK treatment on HMG using metabolomics and network pharmacology analyses. This systematic method can provide methodological support for further understanding the complex mechanism underlying HMG and possible traditional Chinese medicine (TCM) active ingredients for the treatment of HMG.

Clinical Efficacy and Safety of Xinmailong Injection for the Treatment of Chronic Heart Failure: A Meta-Analysis

Background: Chronic heart failure (CHF) is one of the most stubborn cardiovascular disease. Xinmailong (XML), a bioactive fraction extracted from Periplaneta americana L., has been commonly used for CHF treatment in China. However, there is few comprehensive evaluation for the clinical efficacy and safety of XML for CHF. Objectives: We aimed to evaluate the beneficial and adverse effects of Xinmailong Injection (XMLI) on CHF treatment with the use of meta-analysis. Methods: In accordance with the Cochrane Handbook and transparent reporting of systematic reviews and meta-analysis protocol (CRD42018087091), seven English and Chinese electronic databases, including PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Wanfang database, VIP medicine information system and China Biomedical Literature Database (CBM), were searched to retrieve potential randomized controlled trials (RCTs) before November 2017. The eligible trials were evaluated for methodological quality. The main outcome measures were analyzed with RevMan 5.3 software. Results: 26 RCTs involving 3447 participants were subjected to meta-analysis. The total effective rate was improved by XMLI plus conventional therapy (OR 3.10, 95% CI 2.47–3.90, P < 0.00001). When compared to the conventional treatment alone, the combination of XMLI and conventional treatment increased left ventricular ejection fraction (LVEF, MD 4.93, 95% CI 3.96–5.89, P < 0.00001) and 6-min walking distance (6-MWD, MD 46.76, 95% CI 32.51 to 61.01, P < 0.00001), and decreased left ventricular end-diastolic diameter (LVEDD, MD −4.73, 95% CI−5.64 to−3.83, P < 0.00001), serum brain natriuretic peptide (BNP, MD −149.59, 95% CI −211.31 to −87.88, P < 0.00001) and N-terminal pro-brain natriuretic peptide (NT-proBNP, MD −322.35, 95% CI −517.87 to −126.83, P = 0.001). However, the frequency and severity of adverse effects was similar between these two different medications. Poor methodological quality and the limitations also existed in this study. Conclusions: The combinational use of XMLI on conventional treatment may exert better therapeutic effects on improving cardiac function in CHF patients, indicating that XMLI was suggested to be considered during the conventional treatment of CHF. High-quality and large scale RCTs are still required to confirm the impacts of XMLI.

Therapeutic Effects of a Traditional Chinese Medicine Formula Plus Tamoxifen vs. Tamoxifen for the Treatment of Mammary Gland Hyperplasia: A Meta-Analysis of Randomized Trials

As a common disorder that accounts for over 70% of all breast disease cases, mammary gland hyperplasia (MGH) causes a severe problem for the quality of patients life, and confers an increased risk of breast carcinoma. However, the etiology and pathogenesis of MGH remain unclear, and the safety and efficacy of current western drug therapy for MGH still need to be improved. Therefore, a meta-analysis was conducted by our team to determine whether a TCM formula named Ru-Pi-Xiao in combination with tamoxifen or Ru-Pi-Xiao treated alone can show more prominent therapeutic effects against MGH with fewer adverse reactions than that of tamoxifen. Studies published before June 2017 were searched based on standardized searching rules in several mainstream medical databases. A total of 27 articles with 4,368 patients were enrolled in this meta-analysis. The results showed that the combination of Ru-Pi-Xiao and tamoxifen could exhibit better therapeutic effects against MGH than that of tamoxifen (OR: 3.79; 95% CI: 3.09–4.65; P < 0.00001) with a lower incidence of adverse reactions (OR: 0.35; 95% CI: 0.28–0.43; P < 0.00001). The results also suggested that this combination could improve the level of progesterone (MD: 2.22; 95% CI: 1.72–2.71; P < 0.00001) and decrease the size of breast lump (MD: −0.67; 95% CI: −0.86 to −0.49; P < 0.00001) to a greater extent, which might provide a possible explanation for the pharmacodynamic mechanism of Ru-Pi-Xiao plus tamoxifen. In conclusion, Ru-Pi-Xiao and related preparations could be recommended as auxiliary therapy combined tamoxifen for the treatment of MGH.

Inhibition activity of a traditional Chinese herbal formula Huang-Lian-Jie-Du-Tang and its major components found in its plasma profile on neuraminidase-1

Huang-Lian-Jie-Du-Tang (HLJDT), a traditional formula with four TCM herbs, has been used for hundred years for different diseases. The current study aimed to assess the inhibitory activity of HLJDT against H1N1 neuraminidase (NA-1), and identify potent NA-1 inhibitors from its plasma profile. The in vitro NA-1 study has shown that the water extract of HLJDT potently inhibited NA-1 (IC50u2009=u2009112.6u2009μg/ml; Kiu2009=u200955.6u2009μg/ml) in a competitive mode. The IC50 values of the water extracts of its four herbs were as follows: Coptidis Rhizoma, 96.1u2009μg/ml; Phellodendri Chinensis Cortex, 108.6u2009μg/ml; Scutellariae Radix, 303.5u2009μg/ml; Gardeniae Fructus, 285.0u2009μg/ml. Thirteen compounds found in the plasma profile of HLJDT were also identified as potent NA-1 inhibitors, which included jatrorrhizine, palmatine, epiberberine, geniposide, oroxylin A, berberine, coptisine, baicalein, wogonoside, phellodendrine, wogonin, oroxylin A-7-O-glucuronide and baicalin (sorted in ascending order by their IC50 values). Their inhibitory activities were consistent with molecular docking analysis when considering crystallographic water molecules in the ligand-binding pocket of NA-1. Our current findings suggested that HLJDT can be used as a complementary medicine for H1N1 infection and its potent active compounds can be developed as NA-1 inhibitors.