Bright Luminescence of Free Radical TEMPO Enabled by Electrochemiluminescence Technique.

Radicals can feature theoretically 100% light utilization owing to their nonelectron spin-forbidden transition and represent the most advanced luminescent materials at present. 2,2,6,6-Tetramethyl-1-piperidinyloxy (TEMPO) acts as a typically stable radical with very broad applications. However, their luminescent properties have not been discovered to date. In the present work, we observed the bright electrochemiluminescence (ECL) emission of TEMPO with a higher efficiency (72.3%) via the electrochemistry and coreactant strategies for the first time. Moreover, the radical-based ECL achieved high detection toward boron acid with a lower limit of detection (LOD) of 1.9 nM. This study offers a new approach to generate emissions for some unconventional luminophores and makes a major breakthrough in the field of new luminescent materials as well.

Resistant Dextrin Protects Rats Against Streptozotocin Induced Gestational Diabetes Mellitus via Alteration of TLR4/MyD88/NF-κB Signaling Pathway.

Objective: Gestational diabetes mellitus (GDM) is a metabolic disorder that occurs in 3-5% of pregnancies. The inflammatory response is essential to the development of GDM. Resistant dextrin is a natural fiber and exhibits an antidiabetic effect against diabetes. We investigate resistant dextrin's preventive role and underlying mechanism against STZ-induced GDM. Material and method: Female Wistar rats were utilized, and GDM was induced in pregnant rats using STZ. The levels of glycated hemoglobin (HbA1c), resistin, serum-c-peptide, free fatty acid, antioxidant, hepatic glycogen, lipid, inflammatory cytokines, apoptosis, and inflammatory parameters were estimated. mRNA expression of Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), nuclear factor kappa B (NF-κB) and NOD-like receptor protein 3 (NLRP3) was estimated. We also estimated the histopathology of pancreatic and liver tissue. Result: Body weight, plasma insulin, fetal body weight, and blood glucose levels were all considerably (P < .001) improved by resistant dextrin, while placental weight and blood sugar levels were also decreased. Resistant dextrin significantly (P < .001) suppressed the levels of HbA1c, resistin, serum-c-peptide, and hepatic glycogen and improved the free fatty acid (FFA) level. Resistant dextrin significantly (P < .001) altered the level of adiponectin, leptin, intercellular Adhesion Molecule 1 (ICAM-1), and visfatin; antioxidant parameters such as malonaldehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), glutathione S-transferase GST, inflammatory cytokines like tumor necrosis factor- α (TNF-α), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-2 (IL-2), interferon- γ (INF-γ), interleukin-10 (IL-10); apoptosis parameters include Bcl-2, caspase-3, and Bax, respectively. Resistant dextrin significantly (P < .001) suppressed the mRNA expression of NF-κB, MyD88, NLRP3, and TLR4. Resistant dextrin altered the histopathological changes in the pancreas and hepatic tissue. Discussion and Conclusion: In short, resistant dextrin demonstrated a protective effect against STZ-induced GDM by modulating the TLR4/MyD88/NF-κB signaling pathway.

The pharmacological mechanism of Abelmoschus manihot in the treatment of chronic kidney disease.

Abelmoschus manihot (A.manihot) is a herbaceous flowering medicinal plant and flavonoids are its main pharmacological active ingredients. A.manihot is listed in the 2020 edition of the Chinese Pharmacopoeia for the treatment of chronic kidney disease (CKD). A.manihot significantly reduces proteinuria in CKD, and the effectiveness and safety of A.manihot in the treatment including primary glomerulonephropathy and diabetic kidney disease (DKD) have been proved by several randomized controlled trials (RCT). Emerging pharmacological studies have explored the potential active small molecules and the underlying mechanisms in A.manihot. The active constituents of A.manihot are mainly seven flavonoids, including hibifolin, hyperoside, isoquercetin, rutin, quercetin, myricetin, and quercetin-3-O-robinobioside. The mechanisms of action mainly include alleviating renal fibrosis, reducing the inflammatory response and decreasing the apoptosis of podocytes. In this review, we summarize the updated information of active components and molecular mechanisms of A.manihot on chronic kidney disease.

Investigating the Mechanism of Action of Schisandra chinensis Combined with Coenzyme Q10 in the Treatment of Heart Failure Based on PI3K-AKT Pathway.

Purpose: To study the active components, drug targets and mechanism of Schisandra chinensis (S.chinensis) combined with coenzyme Q10 (CQ10) in the treatment of heart failure (HF). Methods: Network pharmacology combined with the gene expression omnibus chip method to analyze the main pathways by which S.chinensis combined with CQ10 functioned to treat heart failure. Subsequently, the biological activities of the major pathway key proteins and their corresponding compounds were verified by molecular docking techniques. Finally, the molecular mechanism of S. chinensis combined with CQ10 for the treatment of heart failure was verified using a rat heart failure model induced by isoproterenol hydrochloride and using hematoxylin-eosin staining, TUNEL, immunohistochemistry and Western blot. Results: Network pharmacology combined with experimental validation suggests that the mechanism of action of S.chinensis combined with CQ10 in the treatment of heart failure may involve CQ10, Citral, Schisandrone, Schisanhenol B, Gomisin O, Schisandrin C and other components, which may synergistically inhibit the PI3K-AKT signaling pathway and affect the expression of AKT1, PIK3CG and other targets on this pathway. In addition, S. chinensis combined with CQ10 could effectively improve the cardiac coefficients of rats with heart failure, reduce the area of myocardial fibrosis and lowered the serum levels of IL-1ß and TNF-α in heart failure rats, as well as reduced cardiac myocyte apoptosis, increased Bcl-2 expression and decreased p-PI3K/PI3K, p-AKT/AKT, P65 and Bax expression in cardiac tissue. Comparison of the results showed that the combination of S.chinensis and CQ10 was more effective compared with CQ10 alone, ie, the ability of S.chinensis combined with CQ10 in improving cardiac function, inhibiting cardiomyocyte apoptosis and reducing inflammatory response lies in the synergistic effect of PI3K/AKT signaling pathway. Conclusion: The therapeutic effect of S.chinensis combined with CQ10 on heart failure, which may occur through the inhibition of PI3K/AKT signaling pathway.

Potent antiviral activity of Agrimonia pilosa, Galla rhois, and their components against SARS-CoV-2.

Agrimonia pilosa (AP), Galla rhois (RG), and their mixture (APRG64) strongly inhibited SARS-CoV-2 by interfering with multiple steps of the viral life cycle including viral entry and replication. Furthermore, among 12 components identified in APRG64, three displayed strong antiviral activity, ursolic acid (1), quercetin (7), and 1,2,3,4,6-penta-O-galloyl-ß-d-glucose (12). Molecular docking analysis showed these components to bind potently to the spike receptor-binding-domain (RBD) of the SARS-CoV-2 and its variant B.1.1.7. Taken together, these findings indicate APRG64 as a potent drug candidate to treat SARS-CoV-2 and its variants.

Effectiveness and safety of Chinese herbal medicines for hepatitis B virus-related acute-on-chronic liver failure: study protocol for a multicenter randomized controlled trial.

OBJECTIVE: To conduct a multicenter randomized controlled trial of the efficacy of standardized Chinese herbal medicines (CHMs) against acute- on-chronic liver failure (ACLF) and provide reproducible and high-level evidence for clinical practice. METHODS: This is a prospective, multicenter, centrally randomized controlled trial. Patients diagnosed with hepatitis B virus-related ACLF (n = 510) will be allocated to the standard medical therapy or CHM group at a 1∶1 ratio. Two CHMs will be used on the basis of the traditional Chinese medicine syndrome: Liangxue Jiedu granules for excess syndromes and Yiqi Jiedu granules for deficiency syndromes. The primary outcome is transplant-free survival at week 12. The secondary outcomes are (a) transplant-free survival at week 24, (b) liver function as assessed using the model for end-stage liver disease score at week 12, (c) liver function as assessed using the Child-Pugh score at week 12, and (d) the incidence of complications at week 12. DISCUSSION: The effectiveness and safety of CHM formulations will be assessed following treatment for ACLF.

Anti-viral activity of compounds from Agrimonia pilosa and Galla rhois extract mixture.

Hepatitis C virus (HCV) infection is a significant health problem, with a worldwide prevalence of about 170 million. Recently, the development of direct acting antiviral (DAA) as a therapeutic agent for HCV has been rapidly increasing. However, DAA has a side effect and is costly. Therefore, it is still necessary to develop a therapeutic agent to treat HCV infection using products. Agrimonia pilosa (AP) and Galla rhois (RG) are traditional medicines and are known to display therapeutic activity on various diseases. Notably, they have been reported to have an anti-viral effect on HBV and influenza virus infections. It is expected that anti-viral activity will increase when two extracts are mixed. To investigate their anti-viral activity, the expression level of HCV Core 1b and NS5A was measured. Remarkably, AP, RG, and their mixed compound (APRG64) strongly inhibited the expression of viral proteins, which led us to identify their metabolites. A total of 14 metabolites were identified using liquid chromatography mass spectrometry (LC-MS). These metabolites were evaluated for their anti-HCV activity to identify active ingredients. In conclusion, our results unveiled that anti-HCV activity of Agrimonia pilosa and Galla rhois extract mixture could lead to the development of a novel therapy for HCV infection.

Clinical characteristics of 96 patients with drug-induced acute liver failure: a comparison between Traditional Chinese and Western Medicine.

OBJECTIVE: To compare the causes, clinical symptoms, laboratory test results, and prognosis in patients with acute liver failure (ALF) induced by traditional Chinese medicines (TCM) and by Western Medicines (WM). METHODS: The medical histories of patients who were diagnosed with drug-induced ALF (DALF) (n = 96) after hospitalization in the 302 Military Hospital between January 2010 and December 2015 were retrospectively examined. RESULTS: Fifty-eight of the 96 DALF patients (60.4%) had a hepatocellular pattern of DALF, 16 patients (16.7%) had a cholestatic pattern, and 22 patients (22.9%) had a mixed pattern. DALF resolved in 24 patients (25.0%). Twenty-five patients (26.0%) developed chronic liver injury, 43 patients (44.8%) died, and 4 patients (4.2%) underwent liver transplantation. There were 42 ALF patients (43.8%) who received WM, and 32 ALF patients (33.3%) who received TCM. TCM-induced ALF patients had a higher average age [42.4 ± 18.4) vs (33.5 ± 17.9) years, P = 0.04] and higher creatinine and urine nitrogen levels [(155.2 ± 108.8) vs (97.5 ± 130.4) mmol/L, P = 0.047; (9.1 ± 7.7) vs (4.3 ± 5.0) mmol/L, P = 0.002, respectively]. Patients with TCM-induced ALF exhibited an increased risk of renal injury [odds ratio (OR), 3.75; 95% confidence interval (CI), 1.330-10.577]. The 14 patients with TCM-induced ALF who died exhibited higher creatinine levels than the 18 patients with TCM-induced ALF patients who survived [(218.7 ± 111.6) vs (105.8 ± 78.4) mmol/L, P = 0.002]. They were also more likely to exhibit ascites (85.7% vs 44.4%, P = 0.017) and hepatorenal syndrome (78.6% vs 22.2%, P = 0.002). CONCLUSION: TCM-induced ALF was more likely to be accompanied by renal injury than was WM-induced ALF, especially in TCM-induced ALF patients who died.

Rhubarb-based Chinese herbal formulae for hepatic encephalopathy: a systematic review and Meta-analysis.

OBJECTIVE: To evaluate the effectiveness and safety of rhubarb-based Chinese herbal formulae (RCHF), which are widely used to treat hepatic encephalopathy (HE) in China. METHODS: Nine online databases were searched from inception to November 22, 2016. Eligible studies were randomized controlled trials of Traditional Chinese Medicine (TCM) treatment for adult patients (≥ 18 years old) with HE. Outcomes such as mortality rate, clinical response rate, blood ammonia level, and alanine aminotransferase were evaluated between TCM group and control group. RESULTS: Thirty studies involving 2661 HE patients were analyzed. Most studies used RCHF treatment. Compared with conventional treatment as usual, lactulose, and vinegar, RCHF were associated with significant improvement in clinical response rate [risk ratio (RR) = 1.33, 95% confidence interval (CI) = 1.25, 1.43, I 2 = 0%; RR = 1.26, 95% CI = 1.14, 1.38, I 2 = 22%; and RR = 1.19, 95% CI = 1.06, 1.33, I 2 = 0%, respectively] and significant reductions in levels of blood ammonia and alanine aminotransferase. Only minor RCHF-associated adverse events, such as abdominal pain (0.3%), anal tenesmus (0.3%), and diarrhea (2.3%), were reported, and there were no significant differences in these events between the treatment group and the three types of control group. CONCLUSION: The findings suggest that RCHF may be an alternative treatment option for HE patients. More rigorous multicenter studies with larger samples and longer observational periods are needed to confirm these findings.

[Clinical analysis of two diagnosis methods for herb-induced liver injury].

To compare the consistency and difference of herb-induced liver injury between two methods in guidelines for clinical diagnosis and treatment of liver injury related to Chinese herbal medicine in China (2016) and guidelines for the diagnosis and treatment of drug-induced liver injury in China(2015). This retrospective analysis included 390 patients with herb-induced liver injury who had a history of suspicious Chinese herbal medicines or patent medicines; the patients with integrative Chinese and western medicines were excluded from this study. The results indicated that there were 14(4%) extremely probable patients (>8 points), 185(47%) highly probable patients (6-8 points) and 191(49%) probable patients(3-5 points) in 390 cases with guidelines for diagnosis and treatment of drug-induced liver injury of China (2015). While when guidelines for clinical diagnosis and treatment of liver injury related to Chinese herbal medicine in China (2016) was used for 390 patients, the results indicated that there were 5 (1%) cases with proven diagnosis, 163(42%) cases with clinical diagnosis, and 222(57%) cases with suspected diagnosis. Statistics showed that two methods had a consistency of 43% and difference of 14%. The research results showed that Guidelines for clinical diagnosis and treatment of liver injury related to Chinese herbal medicine in China(2016) was more suitable for the diagnosis of herb-induced liver injury. Due to the limitations of retrospective case study, further more prospective studies would be needed.

Sensitive determination of kaempferol using carbon dots as a fluorescence probe.

In this study, a new sensitive and convenient method for the determination of kaempferol (Kae) based on the fluorescence quenching of fluorescent carbon dots (C-dots) was developed. The C-dots were prepared by simply mixing acetic acid, water and diphosphorus pentoxide. This green synthesis approach proceeds rapidly and gives large quantities of C-dots. The fluorescence of the C-dots decreased obviously with the increase of Kae concentration. The effect of other interfering substances on the fluorescence intensity of C-dots showed low interference. Under the optimum conditions, a linear correlation was established between fluorescence intensity ratio Fo/F and the concentration of Kae in the range of 3.5-49 µM with a detection limit (S/N=3) of 38.4 nM. The proposed method has been successfully applied to determination of Kae in xindakang tablets and human serum samples with recovery in the range of 94.6-109.0%. The C-dots could be a promising fluorescence probe for the detection of Kae owing to its low-cost production, easy operation, low cytotoxicity, and excellent biocompatibility.

Causes, Features, and Outcomes of Drug-Induced Liver Injury in 69 Children from China.

BACKGROUND/AIMS: Drug-induced liver injury (DILI) is a frequent cause of pediatric liver disease; however, the data on DILI are remarkably limited. METHODS: All 69 children hospitalized with DILI between January 2009 and December 2011 were retrospectively studied. RESULTS: A total of 37.7% of the children had medical histories of respiratory infection. The clinical injury patterns were as follows hepatocellular 89.9%, cholestatic 2.9%, and mixed 7.2%. Liver biopsies from 55 children most frequently demonstrated chronic (47.3%) and acute (27.3%) hepatitis. Hypersensitivity features, namely, fever (31.9%), rash (21.7%), and eosinophilia (1.4%), were found. Twenty-four children (34.8%) developed chronic DILI. Antibiotics (26.1%) were the most common Western medicines (WMs) causing DILI, and the major implicated herbs were Ephedra sinica and Polygonum multiflorum. Compared with WM, the children whose injuries were caused by Chinese herbal medicine (CHM) showed a higher level of total bilirubin (1.4 mg/dL vs. 16.6 mg/dL, p=0.004) and a longer prothrombin time (11.8 seconds vs. 17.3 seconds, p=0.012), but they exhibited less chronic DILI (2/15 vs. 18/39, p=0.031). CONCLUSIONS: Most cases of DILI in children are caused by antibiotics or CHM used to treat respiratory infection and present with hepatocellular injury. Compared with WM, CHM is more likely to cause severe liver injury, but liver injury caused by CHM is curable.

[Clinical Analysis of Drug-induced Liver Injury Caused by Polygonum multiflorum and its Preparations].

OBJECTIVE: To analyze hepatotoxicity of Polygonum multiflorum and clinical character- istics of drug-induced liver injury (DILI) caused by Polygonum multiflorum and its preparations. METHODS: A retrospective study was performed in 158 patients treated at 302 Military Hospital between January 2009 and January 2014. All of them had used Polygonum multiflorum and its preparations before the onset of DILI, and their clinical characteristics and prognoses were analyzed. RESULTS: Of the 158 DILI patients who used Polygonum multiflorum or its preparations, 92 (58.2%) combined with Western medicine or Chinese herbal preparations without Polygonum multiflorum; 66 patients (41.8%) used Polygonum mult florum and its preparations alone. In 66 DILI patients induced by Polygonum multiflorum or its preparations alone, 51 cases (77.3%) were induced by Polygonum multiflorum compounds and 22.7% by single Po- lygonum multiflorum; 4 cases (6.1%) were caused by crude Polygonum multiflorum and 62 (93.9%) by processed Polygonum multiflorum and its preparations. Clinical injury patterns were hepatocellular 92.4% (61 cases), cholestatic 1.5% (1 case), and mixed 6.1% (4 cases). Pathological examination was per- formed by liver biopsy in 32 cases (48.15%), manifested as hepatocellular degeneration and necrosis, fibroplasia, Kupffer cells with pigment granule, and a large number of eosinophil infiltration, were ob- served. Four patients were developed into liver failure, 4 into cirrhosis, and 1 died. CONCLUSION: Polygo- num multiflorum and its preparations could induce DILI, but clinical diagnosis of Polygonum multiflorum induced hepatotoxicity should be cautious.

Combining Oxymatrine or Matrine with Lamivudine Increased Its Antireplication Effect against the Hepatitis B Virus In Vitro.

Some recent clinical reports have shown that the combination of oxymatrine, a phyto-derived drug, with lamivudine (3TC) could improve its curative effect against hepatitis B virus (HBV) infection. However, the experimental data in support of this combination strategy are lacking. In this study, we investigated the anti-HBV activity of the combination of 3TC and either oxymatrine or matrine on HepG2 2.2.15 in vitro. The activities of the combination and the solo compound, each in different concentrations, were compared on the 3rd, 6th, and 9th experimental days. The cytotoxicity results showed that the nontoxic concentrations of both oxymatrine and matrine to HepG2 2.2.15 cells were 800 µg/mL. We found that the single use of oxymatrine below 100 µg/ml, matrine below 200 µg/ml, and 3TC below 30 µg/ml showed weak inhibitory effects on the secretion of hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and HBV-DNA in culture media; the combination of 3TC (30 µg/ml) with oxymatrine (100 µg/ml) or matrine (100 µg/ml) showed significant inhibitory effects that were higher than or equivalent to the single use of 3TC at 100 µg/ml. The results provide a new impetus to develop novel, multicomponent anti-HBV drugs through the combination of natural products with nucleoside analogs to enhance their activity.

[GC-MS analysis on the chemical constituents of essential oil from bark of Horsfieldia hainanensis].

OBJECTIVE: To analyze the constituents of the essential oil from the bark of Horsfieldia hainanensis. METHODS: The volatile oil was obtained by steam distillation. The chemical constituents were separated and identified by gas chromatography-mass spectrometry (GC-MS). The relative contents were determined by area normalization. RESULTS: The extraction rate of the bark of Horsfieldia hainanensis was 0.14%. 32 compounds were separated and identified, which accounted for 98.62% of the essential oil. The main chemical components of the essential oil were Copaene (25.55%), Naphthalene, 1,2,3,5,6,8a-hexahydro-4,7-dimethyl-1-(1-methylethyl)-(11.14%), Hexanedioic acid, bis(2-ethylhexyl) ester (8.09%) , 9-Octadecenoic acid (7.04%), etc. CONCLUSION: It has provided scientific foundation for exploitation and utilization of Horsfieldia hainanensis.