Traditional Chinese Drug Research Articles

Multifunctional Porous Nanohybrid Based on Graphene-Like Tungsten Disulfide on Poly(3,4-ethoxylenedioxythiophene) for Supercapacitor and Electrochemical Nanosensing of Quercetin

A multifunctional porous nanohybrid was designed for supercapacitor and nanosensor for voltammetric detection of Chinese traditional herbal drug quercetin (Qu) extracted from lotus leaves using graphene-like tungsten disulfide (WS2) nanosheet onto a porous and conductive poly(3,4-ethoxylenedioxythiophene) (PEDOT). Conducting PEDOT with a rough, porous, irregular surface was synthesized by one-step electropolymerization of commercially available monomer in acetonitrile solution, then WS2/PEDOT was facilely obtained by drop-coating WS2 nanosheet dispersion onto the synthesized PEDOT. WS2/PEDOT porous nanohybrid displayed a high capacitance characteristic with specific capacitance of 70.64 F·g−1 at a current density of 0.2 A·g−1, good cycling stability with capacitance retention of 90.74% after 5000 cycles and excellent voltammetric responses for Qu in linear ranges from 1.5 × 10−7 to 1 × 10−4 mol l−1 with a limit of detection (LOD) of 50 nM and sensitivity of 1.76 μA μm−1 cm−2 under the optimum operation conditions. The developed nanohybrid sensor was employed for the electrochemical detection of Qu in real sample with acceptable recoveries in comparison with high-performance liquid chromatography. This work will provide an experimental basis for nanosensing platform integrated with supercapacitor as self-powered electrochemical energy storage system in the near future.

Icariin controlled release on a silk fibroin/mesoporous bioactive glass nanoparticles scaffold for promoting stem cell osteogenic differentiation.

The treatment of bone defects caused by various reasons is still a major problem in orthopedic clinical work. Many studies on osteogenic implant materials have used various biologically active factors such as osteogenic inducers, but these biologically active factors have various side effects. Therefore, in this study, silk fibroin (SF) was used as a scaffold material, mesoporous bioactive glass nanoparticles (MBGNs) as a sustained release carrier, and the traditional Chinese drug icariin (ICA) was loaded to promote bone formation. The experiments in this study have proven that SF/MBGNs-ICA scaffolds can successfully load and release ICA for a long time, and the sustained-release ICA can promote the proliferation and differentiation of BMSCs for a long time. This controlled-release ICA organic/inorganic two-component scaffold material is expected to become a new bone grafting solution.

Natural Product Luteolin Rescues THAP-Induced Pancreatic β-Cell Dysfunction through HNF4α Pathway.

Endoplasmic reticulum stress (ER stress) plays a main role in pancreatic [Formula: see text]-cell dysfunction and death because of intracellular Ca[Formula: see text] turbulence and inflammation activation. Although several drugs are targeting pancreatic [Formula: see text]-cell to improve [Formula: see text]-cell function, there still lacks agents to alleviate [Formula: see text]-cell ER stress conditions. Therefore we used thapsigargin (THAP) or high glucose (HG) to induce ER stress in [Formula: see text]-cell and aimed to screen natural molecules against ER stress-induced [Formula: see text]-cell dysfunction. Through screening the Traditional Chinese drug library ([Formula: see text] molecules), luteolin was finally discovered to improve [Formula: see text]-cell function. Cellular viability results indicated luteolin reduced the THAP or HG-induced [Formula: see text]-cell death and apoptosis through MTT and flow cytometry assay. Moreover, luteolin improved [Formula: see text]-cell insulin secretion ability under ER stress conditions. Also ER stress-induced intracellular Ca[Formula: see text] turbulence and inflammation activation were inhibited by luteolin treatment. Mechanically, luteolin inhibited HNF4[Formula: see text] signaling, which was induced by ER stress. Moreover, luteolin reduced the transcriptional level of HNF4[Formula: see text] downstream gene, such as Asnk4b and HNF1[Formula: see text]. Conversely HNF4[Formula: see text] knockdown abolished the effect of luteolin on [Formula: see text]-cell using siRNA. These results suggested the protective effect of luteolin on [Formula: see text]-cell was through HNF4[Formula: see text]/Asnk4b pathway. In conclusion, our study discovered that luteolin improved [Formula: see text]-cell function and disclosed the underlying mechanism of luteolin on [Formula: see text]-cell, suggesting luteolin is a promising agent against pancreatic dysfunction.

Chinese herbal medicine resources: Where we stand

In recent years, the development of Chinese herbal medicine (CHM) has been challenged by shortages of CHM resources and drug safety concerns related to end products. There have been significant efforts by Chinese scholars to tackle these challenges, which are revealed by analyzing the research trend of CHM resources via surveying Chinese Traditional and Herbal Drugs (Zhong Cao Yao), a representative journal in CHM. Our study focused on 781 articles in CHM resources from 2013 to 2018 and included four subject areas: germplasm resources, quality analysis and evaluation, cultivation, and bioengineering of CHM. Discussion and prospective for future investigations were also presented, including: construct the core germplasm of medicinal plants and expand germplasms; combine molecular research with field experiments and promote the deeper study of cultivation of CHM plants; improve the quality evaluation method of CHM and strengthen the identification of Chinese patented medicines; promote the sustainable development of CHM resources by utilizing bioengineering and synthetic biology. This study helps international scholars understand the status quo of CHM research and provides theoretical support for the healthy, modern, and international development of CHM, and it will facilitate the sustainable development of the traditional Chinese medicine industry.

Synthesis and Biological Evaluation of the Matrine Derivatives as a Novel Family of Potential Anticancer Agents.

FufangKushen injection' was a Chinese Traditional anticancer drug, which has been widely used to treat cancer in combination with other anticancer drugs. Our goal is to synthesize a series of novel 13-dithiocarbamates matrine derivatives using matrine (1) as the lead compound, and evaluate the biological activities of the obtained compounds. The in vitro cytotoxicity of the target compounds against three human cancer cell lines (Hep3B, LM3 and BeL-7404) was evaluated. To investigate the mechanism of biological activity, cell cycle analysis was performed. The results revealed that compounds 6o and 6v displayed the most significant anticancer activity against three cancer cell lines with IC50 values in the range of 3.42-8.05 μM, which showed better activity than the parent compound (Matrine). SAR analysis indicated that the introduction of a substituted amino dithiocarbamate might significantly enhance the antiproliferative activity. During the newly synthesized compounds, matrine analog 6v exhibited a potent effect against three human tumor cell lines. The mode of action of 6v was to inhibit the G0/G1 phase arrest. Therefore, compound 6v has been selected as a novel-scaffold lead to further structural optimizations or as a chemical probe for exploring anticancer pathways of this kind of compounds.

Chondroprotective and antiarthritic effects of Daphnetin used in vitro and in vivo osteoarthritis models

AimsDaphnetin (DAP) is a traditional Chinese drug usually used to treat cardiovascular diseases. Studies have confirmed the anti-inflammatory, antioxidant, anti-bacterial and insecticidal, anti-tumor and neuro-protective effects of DAP. However, its anti-arthritic potential remains unexplored. The aim of this study is to investigate the in vitro and in vivo chondroprotective effects of DAP. Main methodsThe effect of DAP on primary rabbit chondrocytes was examined using recombinant human IL-1β for 24 h. For the in vivo studies, rabbits were randomly divided into groups: a normal control group and osteoarthritis (OA) groups. The OA groups received three different doses of DAP for 4 or 8 weeks. The anti-arthritic effect of DAP was assessed using histopathological examinations, qRT-PCR, western blotting and immunohistochemical analysis. Key findingsBoth in vitro and in vivo results indicate that DAP exerts a protective effect against IL-1β in chondrocytes. In vitro, DAP inhibits the expression of IL-6, IL-12, MMP-3, MMP-9 and MMP-13, induced by IL-1β in rabbit chondrocytes, and stimulates the production of IL-10. The inhibitory effect of DAP on the MMPs is partially regulated by the inhibition of the PI3K/AKT, MAPK and NF-κB signaling pathways. The effect of DAP on OA may be attributed to the suppression of inflammatory factor secretion, chondrocyte apoptosis observed by the decrease in pro-apoptotic Caspase-3 and BAX, and the activation of anti-apoptotic BCL-2. SignificanceDAP has a broad range of prospects in the treatment of OA, which provides a novel therapeutic strategy for OA.

Dual-responsive (pH/temperature) Pluronic F-127 hydrogel drug delivery system for textile-based transdermal therapy

A dual-responsive hydrogel (pH/temperature) was developed from a thermos-responsive polymer, pluronic F-127 (PF127), and pH-responsive polymers, N,N,N-trimethyl chitosan (TMC) and polyethylene glycolated hyaluronic acid (PEG-HA). Gallic acid, the principal component of the traditional Chinese drug Cortex Moutan was loaded into the hydrogel (PF127/TMC/PEG-HA) for possible application in textile-based transdermal therapy as Cortex Moutan has been proven to be an effective drug for the treatment of atopic dermatitis (AD). TMC and PEG-HA were synthesized, characterized (1H-NMR and FTIR), and added to the formulations to enhance drug release from the hydrogels, and increase the drug targeting of the carriers. The thermo-responsive properties of the hydrogel were assessed by dynamic viscosity analysis and the tube inversion method, and the pH-responsiveness of the formulation was determined by changing the pH of the external media. Rheology study of the hydrogels showed that complex viscosity and storage/loss moduli for PF127/TMC/PEG-HA hydrogel formulation are higher than PF127 hydrogel. The microstructure analysis by reflection SAXS indicated similar type of frozen inhomogeneity of hydrogel formulations. Various characterizations such as FTIR, SEM, TEM, zeta potential, and degradation of the hydrogel formulation indicated that the PF127/TMC/PEG-HA hydrogel showed better physico-chemical properties and morphology than did the PF127 hydrogel, and drug release was also higher for the PF127/TMC/PEG-HA hydrogel than for PF127. The drug release from hydrogels followed more closely first-order rate model than other rate models.

Rapid identification of ginseng medicinal materials by differential scanning calorimetry

Objective To explore a quick and simple method to identify ginseng medicinal materials. Methods Twenty types of ginseng medicinal materials were collected. The effects of two important factors: temperature and heating rate on differential scanning calorimetry (DSC) were investigated. The DSC features were used to quickly identify Radix et Rhizoma Notoginseng, Radix et Rhizoma Ginseng, Radix Panacis Quinquefolii and Panna ginseng C.A.Mey. Results The optimal experimental conditions for rapid identification of Radix et Rhizoma Notoginseng, Radix et Rhizoma Ginseng, Radix Panacis Quinquefolii and Panna ginseng C.A.Mey by DSC were determined: temperature range 30-400 ℃, heating rate 30 ℃/min. Under these conditions, the characteristic peak temperature and thermal enthalpy value can be used to distinguish four kinds of ginseng. Conclusions The experiment shows that the DSC method has the advantages of simple operation, rapid measurement, good reproducibility, easy analysis of the spectrum and less sample consumption. It is a new method for quickly identifying Chinese medicinal materials of ginseng genus. Key words: Panax; Calorimetry, differential scanning; Traditional Chinese drug identification

Traditional Uses, Bioactive Constituents, Biological Functions, and Safety Properties of Oviductus ranae as Functional Foods in China.

Oviductus ranae is an animal-based traditional Chinese material widely used as tonics in China for hundreds of years. Various bioactive components are present in OR including proteins, amino acids, steroids, fatty acids, phospholipids, nucleosides, vitamins, hydantoins, and mineral elements. These constituents exert a myriad of biological functions such as immunomodulatory, antioxidant, antifatigue, antiaging, estrogen-like, hepatoprotective, hypolipidemic, antiosteoporotic, antidepressant, antitumor, antitussive, expectorant, anti-inflammatory, and antiasthmatic activities. Unlike other traditional Chinese crude drugs recorded in Chinese Pharmacopoeia, OR is seldom prescribed as medicine but often consumed as nutraceuticals to optimize health. In this review, the traditional uses, bioactive constituents, biological functions, and safety properties of OR as functional foods in China were summarized and discussed. It is expected that this review will provide useful information for anyone who is interested in OR.

A comparison of the efficacy of Chinese herbal medicines in the treatment of primary dysmenorrhea: A network meta-analysis protocol.

Introduction:Chinese herbal medicines (CHM) have been commonly used in the treatment of primary dysmenorrhea in East Asia. Several systematic reviews have been conducted to assess the clinical efficacy of CHM in the treatment of primary dysmenorrhea. However, their comparative efficacy is still unclear. Therefore, the purpose of this study is to conduct a network meta-analysis (NMA) to systematically compare the advantages of different CHM in the treatment of primary dysmenorrhea.Methods and analysis:The following electronic databases will be searched in this study: Web of Science, PubMed, Cochrane Library, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, Chinese Scientific Journal Database, and Wan-fang Database. Search terms include (Chinese herbal medicine or Chinese patent medicine or medicinal plants or phytotherapy or traditional medicine or Chinese herbal drugs or plant extracts or herbal medicine or herbal extract or herb or traditional Chinese medicine) and (primary dysmenorrhea or dysmenorrhea or painful menstruation) and (randomized controlled trial). The language will be limited to Chinese and English, and the search date will be up to May 2019. The included studies must be randomized controlled trials (RCTs) with patients diagnosed with primary dysmenorrhea. CHM must be used as interventions in the experimental group. While in the control group, studies that used a different herbal medicine, nonsteroidal anti-inflammatory drugs (NSAIDs), or placebo will be included. The primary outcomes include clinical efficacy and visual analog scale (VAS), and the secondary outcomes include adverse events and quality of life. Four reviewers will independently extract the data and assess the qualities of the studies. Statistical analysis will be conducted with R package for each outcome.Ethics and dissemination:Ethical approval is not required as this NMA is based on published studies. The completed NMA will be published in a peer-reviewed scientific journal.Trial registration number:PROSPERO CRD42018095254.

Excavating precursors from the traditional Chinese herb Polygala tenuifolia and Gastrodia elata: Synthesis, anticonvulsant activity evaluation of 3,4,5-trimethoxycinnamic acid (TMCA) ester derivatives

Epilepsy is a group of neurological disorders characterized by recurrent seizures that disturbs about 60 million people worldwide. In this article, a novel series of 3,4,5-trimethoxycinnamic acid (TMCA) ester derivatives 1–35 were designed inspired from the traditional Chinese herb pair drugs Polygala tenuifolia and Gastrodia elata and synthesized followed by in vivo and in silico evaluation of their anticonvulsant potential. All the synthesized derivatives were biologically evaluated for their anticonvulsant potential using two acute model of seizures induced in mice, the maximal electroshock (MES) and sc-pentylenetetrazole (PTZ) models. Simultaneously, the motor impairment as a surrogate of acute neurotoxicity and in vitro screening of cytotoxicity against HepG-2 cells line were assessed through the rotarod performance test and CCK-8 assay, respectively. In addition, the physicochemical and pharmacokinetic parameters of the active compounds were determined. Our results showed that compounds 5, 7, 8, 13, 20, 25, 28, 30 and 32 exhibited preferable anticonvulsant activity in primary evaluation, with compounds 28 and 32 being the most promising anticonvulsant agents in according to results of subsequent pharmacology and toxicity evaluation. Additionally, the molecular modeling experiments predicted good binding interactions of part of the obtained active molecules with the gamma-aminobutyric acid (GABA) transferas. Therefore, it could be concluded that the synthesized derivatives 28 and 32 would represent useful lead compounds for further investigation in the development of anticonvulsant agents.

Role of 2-Dimensional Autocorrelation Descriptors in Predicting Antimalarial Activity of Artemisinin and its Aanalogues: A QSAR Study.

Malaria, one of the World's biggest billers' is on the schedule for biomedical research and public health policies. The introduction of the artemisinin, a Chinese traditional drug from Artemisia annua is a revolution in the treatment of malaria. Artemisinin-based combination treatment (ACT) is considered to be the best strategy for uncomplicated Falciparum malaria. The presence of 1,2,4-trioxane system in artemisinin is responsible for its antimalarial activity. In this study, twenty-nine analogues of artemisinin were taken into account for QSAR studies along with artemisinin. The most active analogue of artemisinin 21 was energy minimized. All the structures were prepared from the active conformer 21 and energy was minimized to the stable state using MMFF94 force field using ChemBioDraw-12. Genetic Algorithm is used to decide the descriptors best required for the model generation. The test set and training set division were done by using hierarchal clustering module available with NCSS statistical software. The antimalarial activity of the artemisinin and its substituted analogues has been analyzed through the multiple linear regression (MLR) using various physiochemical and structural descriptors obtained from PADEL software. The models were prepared using the Sigma Plot version 11. The calculated 2D autocorrelation descriptors and the MLR model suggest that artemisinin and its analogues hold the scope in the optimization of antimalarial activity.

An integrated serum and urinary metabonomic research of Rhizoma Curcumae-Rhizoma Sparganii drug pair in hysteromyoma rats based on UPLC-Q-TOF-MS analysis

Ethnopharmacological relevanceRhizoma Curcumae and Rhizoma Sparganii (RCRS), a celebrated traditional Chinese medicine drug pair, has been used to treat hysteromyoma (HY). Aim of the studyWe aimed to identify the endogenous biomarkers of RCRS against HY. Materials and methodsHY rat model was established by injecting intramuscularly estradiol benzoate and progesterone injection from inner thigh in sequence. Body weight, uterus morphological indexes, immunohistochemistry (IHC) and hematoxylin and eosin (HE) staining experiments were used to evaluate the efficacy of RCRS (The rats were treated with RCRS extract, which was made by soxhlet reflux method. The rats were administrated intragastrically with 2 mL of RCRS extract). UPLC-Q-TOF-MS based metabonomics was adopted to analyze the serum and urine biomarkers from HY rats before and after RCRS treatment. Principle component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were utilized to identify differences of metabolic profiles in rats among the four groups. Results16 potential biomarkers from serum and 18 potential biomarkers from urine in both positive and negative mass spectrometry detection modes were identified, primarily related to Linoleic acid metabolism and Glyoxylate and dicarboxylate metabolism. RCRS drug pair has therapeutic effects on rats with HY via the regulation of multiple metabolic pathways. ConclusionsThis study provides a useful method to get insight into the integrated metabonomic mechanism of RCRS drug pair on HY rats.

Analysis of adverse drug reactions induced by compound Kushen injection in Qingdao central hospital

Objective The adverse drug reaction (ADR) reports of compound Kushen injection in Qingdao Central Hospital were analyzed to improve the level of safe and rational use of drugs. Methods We investigated 35 cases of severe ADR reports induced by compound Kushen injection in Qingdao Central Hospital from 2016.09 to 2018.03 retrospectively. Then the type of report, relevance evaluation and prognosis, ADR occurrence and recovered time, involved system/organs and main clinical manifestations were analyzed. Results The new moderate and new severe ADR incident were 51.4% of 35 ADR reports. Twenty-nine cases of the ADR were occurred 30 minutes after injection. Twenty-three cases of ADR clinical symptoms can be recovered after 30 minutes. The main ADR was the digestive system reaction, followed by the neural system, respiratory system and cardiovascular system. Conclusions It is important to pay attention to the occurrence of compound Kushen injection ADR and strengthen its monitoring. Key words: Traditional Chinese drug adverse reaction; Compound Kushen injection; Adverse drug reaction reporting systems; Drug monitoring; Rational use of drugs

Endothelium corneum gigeriae galli extract inhibits calcium oxalate formation and exerts anti-urolithic effects

Ethnopharmacological relevanceTraditional Chinese Medicine is preferred because of its safety and minimal/reduced side effects. Endothelium Corneum Gigeriae Galli (ECGG) extract, a traditional Chinese drug consisting of the dried gizzard membrane of Gallus gallus domesticus Brisson, was assessed for its effects and mechanism on urolithiasis. Aims of studyTo evaluate the effects of ECGG extract on calcium oxalate (CaOx) crystal formation in vitro, and assess the anti-urolithic effects of ECGG extract in vivo and explore the underlying mechanism. Materials and methodsIn vitro, CaOx crystals were treated with ECGG extract (0.05, 0.2, and 0.8 g/mL), and assessed by scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray powder diffraction and electrical conductivity. Then, a rat model of renal calculi was established by ethylene glycol and ammonium chloride treatment, and ECGG extract (5.0, 10.0 and 20.0 g/kg) was administered orally. After treatment, urine, serum and kidney bioindicators were analyzed, as well as kidney's pathological features. ResultsIn the presence of ECGG extract, calcium oxalate dihydrate (COD) crystals with typical tetragonal bipyramidal morphology were obtained; meanwhile, the formation of calcium oxalate monohydrate (COM), a major urinary stone component, was inhibited; in addition, the equilibration time of the chemical reaction of Ca2+ and C2O42− ions was delayed in a concentration dependent manner. ECGG extract actually showed anti-urolithic effects; the incidence rates of crystal formation in the kidney in the model, low, middle and high dose groups were 100%, 90%, 70% and 60%, respectively, with a dose-dependent alleviation of kidney stone amounts and kidney damage. Treatment with middle and high ECGG extract doses significantly decreased urine uric acid and oxalic acid amounts, serum creatinine, urea nitrogen and uric acid contents, and kidney tissue oxalic acid and calcium levels, while increasing kidney and urinary magnesium and superoxide dismutase levels (P < 0.05). ConclusionECGG extract has outstanding anti-urolithic effects, potentially with included bioorganic molecules inducing COD crystal nucleation and growth. Therefore, ECGG extract is a promising drug for preventing and treating urolithiasis.

Discussion on application of principal component analysis in analysis of traditional Chinese medicines and natural drugs

Principal component analysis is a widely used chemometric method. In this paper, the development history of principal component analysis was summarized, and then its basic principle was elaborated. Afterwards, its applications in the analysis of traditional Chinese medicines and natural drugs were classified and discussed with some representative examples. Finally, the prospect of its application was outlooked at the end of this paper.

The intervention effect of zuogui pill on chronic kidney disease-mineral and bone disorder regulatory factor

Chronic kidney disease-mineral and bone disorder (CKD-MBD) play a critical role in the pathogenesis of cardiovascular complications in patients with chronic kidney disease (CKD). Zuogui pill as a traditional Chinese herbal drug has been used for nourish kidney essence improve bone malnutrition of renal bone disease by regulating the metabolism of calcium and phosphorus and participating in osteoblast metabolism. In the present study, 5/6 nephrectomy rat model was used to reveal the mechanism of zuogui pill in treatment of CKD-MBD. Compared with sham rats, the levels of serum phosphorus, PTH, iPTH and creatinine were significantly decreased, while the serum calcium level was significantly increased, and the Cbfa1 protein level was significantly decreased and FGF23 protein level was significantly increased by Zuogui pill treatment. Compared with model rats, the BMD of rat was significantly increased by Zuogui pill treatment. Histological analysis revealed that the kidney injury of rats with CKD was significantly reduced by zuogui pill treatment. Compared with model rats, the CYP27B1 mRNA level was significantly increased, and the PTH mRNA level and NaPiIIa protein level were significantly decreased in the kidney by zuogui pill treatment. We inferred that zuogui pill exhibited potential therapeutic effects on CKD-MBD in the rats by regulating bone metabolism and nourish kidney.

An Integrated Strategy to Qualitatively Differentiate Components of Raw and Processed Viticis Fructus Based on NIR, HPLC and UPLC-MS Analysis.

Viticis Fructus is a traditional Chinese herbal drug processed by various methods to achieve different clinical purposes. Thermal treatment potentially alters chemical composition, which may impact on effectiveness and toxicity. In order to interpret the constituent discrepancies of raw versus processed (stir-fried) Viticis Fructus, a multivariate detection method (NIR, HPLC, and UPLC-MS) based on metabonomics and chemometrics was developed. Firstly, synergy interval partial least squares and partial least squares-discriminant analysis were employed to screen the distinctive wavebands (4319 - 5459 cm-1) based on preprocessed near-infrared spectra. Then, HPLC with principal component analysis was performed to characterize the distinction. Subsequently, a total of 49compounds were identified by UPLC-MS, among which 42compounds were eventually characterized as having a significant change during processing via the semiquantitative volcano plot analysis. Moreover, based on the partial least squares-discriminant analysis, 16 compounds were chosen as characteristic markers that could be in close correlation with the discriminatory near-infrared wavebands. Together, all of these characterization techniques effectively discriminated raw and processed products of Viticis Fructus. In general, our work provides an integrated way of classifying Viticis Fructus, and a strategy to explore discriminatory chemical markers for other traditional Chinese herbs, thus ensuring safety and efficacy for consumers.

Ginsenoside Rg1 and Acori Graminei Rhizoma Attenuates Neuron Cell Apoptosis by Promoting the Expression of miR-873-5p in Alzheimer's Disease.

Alzheimer's disease (AD) severely threatens human health in their old age, however the potential etiology underlying it is still unclear. Both Ginsenoside Rg1 (GRg1) and Acori graminei Rhizoma (AGR) are the traditional Chinese herbal drug, while their potential role in AD remains need further identification. Both SAMP1 and SAMP8 mice were employed as the control and AD mice. Morris water maze method was used to detect the cognitive function of the mice, TUNEL assay was performed to determine cell apoptosis. Real-time PCR and western blot were carried out to measure gene expression. The relationship between miR-873-5p and HMOX1 was determined using luciferase reporter assay. Comparing with SAMP1, the cognitive function was impaired and cell apoptosis was increased in SAMP8 mice. GRg1 + AGR treatment significantly attenuated the symptom of AD. The expression of miR-873-5p was decreased, while HMOX1 was increased in SAMP8 mice. GRg1 + AGR treatment significantly promoted the expression of miR-873-5p, but decreased HMOX1. MiR-873-5p targets HMOX1 to regulate its expression. Aβ1-42 stimulation decreased the expression of miR-873-5p, but increased HMOX1 in PC12 cells. GRg1 + AGR treatment reversed the effect of Aβ1-42, while miR-873-5p inhibitor abolished the effect of GRg1 + AGR. In vivo experiments confirmed the protect role of GRg1 + AGR in AD. GRg1 + AGR suppressed neuron cell apoptosis by regulating the expression of miR-873-5p in AD.

A Crude 1-DNJ Extract from Home Made Bombyx Batryticatus Inhibits Diabetic Cardiomyopathy-Associated Fibrosis in db/db Mice and Reduces Protein N-Glycosylation Levels.

The traditional Chinese drug Bombyx Batryticatus (BB), which is also named the white stiff silkworm, has been widely used in Chinese clinics for thousands of years. It is famous for its antispasmodic and blood circulation-promoting effects. Cardiomyocyte hypertrophy, interstitial cell hyperplasia, and myocardial fibrosis are closely related to the N-glycosylation of key proteins. To examine the alterations of N-glycosylation that occur in diabetic myocardium during the early stage of the disease, and to clarify the therapeutic effect of 1-Deoxynojirimycin (1-DNJ) extracted from BB, we used the db/db (diabetic) mouse model and an approach based on hydrophilic chromatography solid-phase extraction integrated with an liquid Chromatograph Mass Spectrometer (LC-MS) identification strategy to perform a site-specific N-glycosylation analysis of left ventricular cardiomyocyte proteins. Advanced glycation end products (AGEs), hydroxyproline, connective tissue growth factor (CTGF), and other serum biochemical indicators were measured with enzyme-linked immunosorbent assays (ELISA). In addition, the α-1,6-fucosylation of N-glycans was profiled with lens culinaris agglutinin (LCA) lectin blots and fluorescein isothiocyanate (FITC)-labelled lectin affinity histochemistry. The results indicated that 1-DNJ administration obviously downregulated myocardium protein N-glycosylation in db/db mice. The expression levels of serum indicators and fibrosis-related cytokines were reduced significantly by 1-DNJ in a dose-dependent manner. The glycan α-1,6-fucosylation level of the db/db mouse myocardium was elevated, and the intervention effect of 1-DNJ administration on N-glycan α-1,6-fucosylation was significant. To verify this result, the well-known transforming growth factor-β (TGF-β)/Smad2/3 pathway was selected, and core α-1,6-fucosylated TGF-β receptor II (TGFR-βII) was analysed semi-quantitatively with western blotting. The result supported the conclusions obtained from LCA lectin affinity histochemistry and lectin blot analysis. The expression level of α-1,6-fucosyltransferase (FUT8) mRNA was also detected, and the results showed that 1-DNJ administration did not cause obvious inhibitory effects on FUT8 expression. Therefore, the mechanism of 1-DNJ for relieving diabetic cardiomyopathy (DCM)-associated fibrosis can be concluded as the inhibition of N-acetylglucosamine (N-GlcNAc) formation and the reduction of substrate concentration.