Publications by authors named "Jinao Duan"

123 Publications

Pulmonary Edema in COVID-19 Patients: Mechanisms and Treatment Potential.

Front Pharmacol 2021 7;12:664349. Epub 2021 Jun 7.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.

COVID-19 mortality is primarily driven by abnormal alveolar fluid metabolism of the lung, leading to fluid accumulation in the alveolar airspace. This condition is generally referred to as pulmonary edema and is a direct consequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. There are multiple potential mechanisms leading to pulmonary edema in severe Coronavirus Disease (COVID-19) patients and understanding of those mechanisms may enable proper management of this condition. Here, we provide a perspective on abnormal lung humoral metabolism of pulmonary edema in COVID-19 patients, review the mechanisms by which pulmonary edema may be induced in COVID-19 patients, and propose putative drug targets that may be of use in treating COVID-19. Among the currently pursued therapeutic strategies against COVID-19, little attention has been paid to abnormal lung humoral metabolism. Perplexingly, successful balance of lung humoral metabolism may lead to the reduction of the number of COVID-19 death limiting the possibility of healthcare services with insufficient capacity to provide ventilator-assisted respiration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2021.664349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215379PMC
June 2021

Ultrafiltration strategy combined with nanoLC-MS/MS based proteomics for monitoring potential residual proteins in TCMIs.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 Jul 30;1178:122818. Epub 2021 May 30.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address:

Traditional Chinese medicine injections (TCMIs) containing complex constituents frequently cause unpredictable adverse reactions. The residual heterologous proteins in TCMIs may be one kind of the sensitized constituents. However, few methods were developed to identify and monitor the residual proteins of TCMIs in industry. Here, we described a method combining the advantages of ultrafiltration and mass spectrometry-based proteomics for monitoring the potential residual proteins in Re Du Ning injection (RDNI) intermediates and preparations. We identified and quantified both de novo peptides and the proteins matched against databases of three raw plants by using PEAKS software. Interesting, we found there was a significant decrease of peptides and proteins in No. 3-5 of RDNI intermediates and some even disappeared. Besides, we found this method could greatly reduce the interference of contaminants in proteomics experiments. The rapid and accurate method proposed in this paper could be used for monitoring potential residual proteins in TCMIs to guarantee their quality and safety.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jchromb.2021.122818DOI Listing
July 2021

Anti-inflammatory and analgesic actions of bufotenine through inhibiting lipid metabolism pathway.

Biomed Pharmacother 2021 Aug 28;140:111749. Epub 2021 May 28.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, College of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210023, China.

Inflammation is a primary defense and immune response. However, under pathological conditions, the inflammation processes always become uncontrolled and lead to chronic diseases. Bufotenine, as a natural component from toad venom, showed great potential for development as a novel anti-inflammation and analgesia agent. This study aimed to investigate the therapeutic effects of bufotenine against inflammation and pain on animal models with a focus on lipid metabolism. In pharmacological studies, bufotenine significantly inhibited the swelling rates on formalin-induced paw edema model, and increased paw withdrawal mechanical thresholds (PWMTs) in von Frey test and thermal pain thresholds (TPTs) in hot-plate test. High-sensitivity lipidomics analysis revealed the effects might be related to the down-regulation of inflammatory mediators from cyclooxygenase (COX), lipoxygenase (LOX), cytochrome P450 (CYP450), linoleic acid (LA), docosahexaenoic acid (DHA) and other pathways. The activities might result from the binding of bufotenine and its receptors, including sigma-1 receptor and 5-Hydroxytryptamine receptor 3A, thus regulating lipid metabolism pathway. The research provided a systemic evidence for the actions and mechanism of bufotenine. It suggested that the natural compound might be a potential candidate for reducing inflammatory pain disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopha.2021.111749DOI Listing
August 2021

Rapid screening of lipase inhibitors in licorice extract by using porcine pancreatic lipase immobilized on FeO magnetic nanoparticles.

Food Funct 2021 Jun;12(12):5650-5657

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources and Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China. and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, PR China.

Chalcones, a class of natural lipase inhibitors, have received substantial attention from researchers in recent years. Although many kinds of chalcones are typically distributed in G. inflata, there is little literature about the anti-lipase activity of G. inflata extracts (GIEs). In the present study, a ligand fishing strategy for fast screening of lipase inhibitors from GIEs was thus proposed. Porcine pancreatic lipase (PPL) was firstly immobilized on carboxyl modified Fe3O4 magnetic nanoparticles (MNPs) to obtain PPL functionalized MNPs ([email protected]), and then the [email protected] were incubated with a bioactive fraction to fish out the ligands. Eight ligands were obtained and identified as one flavone together with seven chalcones. Licochalcone A, licochalcone D and licochalcone E inhibited pancreatic lipase (PL) with IC50 of 4.9, 3.2 and 5.8 μM, respectively. Meanwhile, investigation of the structure-activity relationship also revealed that isopentenyl and hydroxyl substituents at ring A were essential for the noncovalent inhibitory potency of the chalcones.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0fo03352aDOI Listing
June 2021

Bruceine A induces cell growth inhibition and apoptosis through PFKFB4/GSK3β signaling in pancreatic cancer.

Pharmacol Res 2021 Jul 14;169:105658. Epub 2021 May 14.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address:

Pancreatic cancer is one of the most aggressive cancers with a poor prognosis and 5-year low survival rate. In the present study, we report that bruceine A, a quassinoid found in Brucea javanica (L.) Merr. has a strong antitumor activity against human pancreatic cancer cells both in vitro and in vivo. Human proteome microarray reveals that 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4) is the candidate target of bruceine A and both fluorescence measurement and microscale thermophoresis suggest bruceine A binds to PFKFB4. Bruceine A suppresses glycolysis by inhibiting PFKFB4, leading to cell cycle arrest and apoptosis in MIA PaCa-2 cells. Furthermore, glycogen synthase kinase-3 β (GSK3β) is identified as a downstream target of PFKFB4 and an PFKFB4-interacting protein. Moreover, bruceine A induces cell growth inhibition and apoptosis through GSK3β, which is dysregulated in pancreatic cancer and closely related to the prognosis. In all, these findings suggest that bruceine A inhibits human pancreatic cancer cell growth via PFKFB4/GSK3β-mediated glycolysis, and it may serve as a potent agent for curing human pancreatic cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phrs.2021.105658DOI Listing
July 2021

Immobilized lipase catalytic synthesis of phenolamides and their potential against α-glucosidase.

J Biotechnol 2021 Jun 18;334:51-57. Epub 2021 Apr 18.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources and Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, PR China; Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, PR China. Electronic address:

Although coumaroyltyramine (CT) derivatives are one kind of phenolamides with remarkable biological activities, the low content in plants would inhibit their potential use in food and pharmaceutical industries. Therefore, it is necessary to screen an efficient method to produce CT derivatives. A green and efficient method by using lipase as catalyst to synthesize a series of CT derivatives, was thus proposed. To obtain optimum reaction conditions, the effects of various parameters on conversion rate were firstly evaluated. An in vitro α-glucosidase inhibitory assay of synthesized compounds was then carried out, and the structure-activity relationship of these compounds was conducted. Under the optimum conditions (MTBE, Nu/S: 2/1, E/S: 20/1, 50 °C and 24 h), the conversion rates of synthesized compounds were above 65 %. The bioassay results indicated that N-trans-caffeoyltyramine and N-trans-feruloyltyramine had potent activities against α-glucosidase with IC of 30.08 μM and 31.94 μM, respectively. The structure-activity relationship results showed that the presence of -OH or -OCH group at C-3 position could boost the activities of CT derivatives. Meanwhile, the presence of -OH group at C-4 position and double bound on caffeoyl moiety as well as the presence of -OH group at C-4' position was essential for the activities of CT derivatives.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbiotec.2021.04.002DOI Listing
June 2021

Crosstalk between gut microbiota and intestinal mucosal immunity in the development of ulcerative colitis.

Infect Immun 2021 Feb 1. Epub 2021 Feb 1.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210023, PR China

Ulcerative colitis (UC), a nonspecific inflammatory disease, is characterized by inflammation and mucosal damage in the colon, and its prevalence in the worldwide is increasing. Nevertheless, the exact pathogenesis of UC is still unclear. Accumulating data have suggested that its pathogenesis is multifactorial, involving genetic predisposition, environmental factors, microbial dysbiosis and dysregulated immune responses. Generally, UC is aroused by inappropriate immune activation based on the interaction of host and intestinal microbiota. The relationship between microbiota and host immune system in the pathogenesis of UC is complicated. However, increasing evidence indicates that the shift of microbiota composition can substantially influence intestinal immunity. In this review, we primarily focus on the delicate balance between microbiota and gut mucosal immunity during UC progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/IAI.00014-21DOI Listing
February 2021

A Powerful HPLC-ELSD Method for Simultaneous Determination of Fecal Bile Acids in T2DM Rats Interfered by Sanhuang Xiexin Tang.

J Chromatogr Sci 2021 Feb 2. Epub 2021 Feb 2.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, PR China.

Bile acids (BAs) as important endogenous ligands can activate farnesoid X receptor (FXR) and G-protein-coupled bile acid receptor 1 (GPBAR1, also known as TGR5) signaling to regulate glycolipid metabolism. In this study, a simple, reliable and sensitive analysis method for simultaneous determination of four BAs from rat feces based on high-performance liquid chromatography with evaporative light scattering detector (HPLC-ELSD) was developed. Chromatographic analysis was performed with the mobile phases of acetonitrile and 0.2% formic acid. All the standard curves exhibited good linearity (R2 ≥ 0.99). The relative standard deviations of precision, stability and repeatability varied from 1.27 to 3.96%, 2.20 to 3.89% and 3.00 to 4.31%, respectively. The validated method was successfully applied to investigate the variation of four BAs in feces from T2DM rats after oral administration of Sanhuang Xiexin Tang (SXT). Data showed that SXT could remarkably increase the contents of conjunct BAs and decrease the contents of free BAs, which might contribute to ameliorate the symptoms of T2DM rats.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/chromsci/bmaa144DOI Listing
February 2021

Rapid qualitative identification and quantitative analysis of Flos Mume based on Fourier transform near infrared spectroscopy.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Mar 15;249:119344. Epub 2020 Dec 15.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China. Electronic address:

Flos Mume, an ancient Chinese plant, is widely used for food and medicine. There are numerous varieties of Flos Mume, whose main active components are chlorogenic acid, hyperoside and isoquercitrin. Currently, Flos Mume varieties are mainly distinguished by physical appearance and they have not been scientifically indexed for identification. Fourier transform near infrared spectroscopy (FT-NIR) is a technique that when combined with chemometrics, determines internal components of samples and classifies them. Here, to distinguish between different Flos Mume varieties, we used a qualitative identification model based on FT-NIR. Various model parameters indicated its stability and high predictive performance. We developed a rapid, non-destructive method of simultaneously analyzing 8 components but found that only neochlorogenic acid, chlorogenic acid, rutin, hyperoside, and isoquercitrin have application value. Other components were excluded due to low concentration and poor prediction. Chemometric analysis found that chlorogenic acid become an ingredient which is quite different in the different categories. The content of chlorogenic acid were the highest among these components. Different varieties of Flos Mume were distinguished based on chlorogenic acid content, indicating that chlorogenic acid has potential to become a key indicator for application in quality evaluation. The established FT-NIR model for chlorogenic acid detection had excellent predictive capacity. FT-NIR was the first time applied to Flos Mume and our findings offer theoretical reference for the rapid identification and quantitative analysis of Flos Mume based on FT-NIR. Flos Mume could be evaluated for quality quickly and easily by means of FT-NIR spectroscopy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.saa.2020.119344DOI Listing
March 2021

Evaluation of analgesic and anti-inflammatory actions of indolealkylamines from toad venom in mice using lipidomics and molecular docking.

J Ethnopharmacol 2021 Apr 13;269:113677. Epub 2020 Dec 13.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, And Jiangsu Key Laboratory for High Technology Research of TCM Formulae, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China. Electronic address:

Ethnopharmacological Relevance: Toad venom is one of widely used traditional Chinese medicines due to its analgesic and anti-inflammatory activities. However, hydrophilic alkaloids from toad venom, which may have certain pharmacological activities, have not been systematic studied.

Aim Of The Study: The aim of the study was to identify the indolealkylamines (IAAs) from toad venom and investigate the analgesic and anti-inflammatory actions.

Materials And Methods: The alkaloids were extracted and identified by high-resolution mass spectrometry. The analgesic abilities were determined using hot-plate test, formalin test and von Frey test. High-sensitivity lipidomics was used to investigate the regulatory function of IAAs on inflammatory eicosanoids. Besides, network pharmacology and molecular docking were used to demonstrate the candidate targets of IAAs.

Results: 22 constituents have been characterized by high performance liquid chromatography (HPLC)-Triple TOF 5600, including six specific IAAs (serotonin, N-methyl serotonin, bufotenine, bufotenidine, bufothionine and dehydrobufotenine). Pharmacological studies showed that the IAAs from toad venom exerted significant analgesic activities at doses of 5, 15 and 45 mg/kg in vivo. Moreover, lipids analysis revealed IAAs might down-regulate inflammatory mediators from COX, LOX, DHA and LA pathways in formalin models, thus showing anti-inflammatory effect. The potent pharmacological function might because of the binding of IAAs and protein targets, such as sigma-1 receptor.

Conclusion: The studies provided a systemic evidence for the analgesic and anti-inflammatory activities of IAAs from toad venom. It suggested that IAAs might be a potential candidate to reduce inflammatory pain disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2020.113677DOI Listing
April 2021

Characteristic and Mechanism of Drug-Herb Interaction Between Acetylsalicylic Acid and Danhong Injection Mediated by Organic Anion Transporters.

Front Pharmacol 2020 2;11:577012. Epub 2020 Oct 2.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China.

The mixture of and (Danhong injection, DHI) is widely prescribed in China for the treatment of cardiovascular and cerebrovascular diseases. In most cases, DHI is used in combination with acetylsalicylic acid (aspirin, ASA). However, the interaction between DHI and ASA remains largely undefined. The purpose of this study is to explore the interaction profile and mechanism between DHI and ASA. The frequency of drug combination of DHI and ASA was analyzed based on 5,183 clinical cases. The interaction characteristics were evaluated by analyzing the pharmacokinetics and disposition profile of salicylic acid (SA, the primary metabolite of ASA) in rats. The interaction mechanisms were explored through evaluating the hydrolysis of ASA regulated by ASA esterase, the tubular secretion of SA mediated by influx and efflux transporters, and the tubular reabsorption of SA regulated by urinary acidity-alkalinity. The inhibitory potential of DHI on organic anion transporters (OATs) was further verified in aristolochic acid I (AAI) induced nephropathy. Clinical cases analysis showed that DHI and ASA were used in combination with high frequency of 70.73%. In drug combination of DHI and ASA, the maximum plasma concentration of SA was significantly increased by 1.37 times, while the renal excretion of SA was significantly decreased by 32.54%. The mechanism study showed that DHI significantly inhibited the transport function, gene transcription and protein expression of OATs. In OATs mediated AAI nephropathy, DHI significantly reduced the renal accumulation of AAI by 55.27%, and alleviated renal damage such as glomerulus swelling, tubular blockage and lymphocyte filtration. In drug combination of DHI and ASA, DHI increased the plasma concentration of SA not through enhancing the hydrolysis of ASA, and the tubular reabsorption of SA was not significantly affected. Inhibition of tubular secretion of SA mediated by OATs might be the reason that contributes to the decrease of SA renal excretion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2020.577012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7562828PMC
October 2020

Targeting the gut microbial metabolic pathway with small molecules decreases uremic toxin production.

Gut Microbes 2020 11;12(1):1-19

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine , Nanjing, China.

Uremic toxins are a class of toxins that accumulate in patients with chronic kidney disease (CKD). Indoxyl sulfate (IS), a typical uremic toxin, is not efficiently removed by hemodialysis. Modulation of IS production in the gut microbiota may be a promising strategy for decreasing IS concentration, thus, delaying CKD progression. In the present study, we identified isoquercitrin (ISO) as a natural product that can perturb microbiota-mediated indole production without directly inhibiting the growth of microbes or the indole-synthesizing enzyme TnaA. ISO inhibits the establishment of H proton potential by regulating the gut bacteria electron transport chain, thereby inhibiting the transport of tryptophan and further reducing indole biosynthesis. This non-microbiocidal mechanism may enable ISO to be used as a therapeutic tool, specifically against pathologies triggered by the accumulation of the microbial-produced toxin IS, as in CKD. Herein, we have shown that it is possible to inhibit gut microbial indole production using natural components. Therefore, targeting the uremic toxin metabolic pathway in gut bacteria may be a promising strategy to control host uremic toxin production.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/19490976.2020.1823800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577114PMC
November 2020

Lizhong decoction ameliorates ulcerative colitis in mice via modulating gut microbiota and its metabolites.

Appl Microbiol Biotechnol 2020 Jul 17;104(13):5999-6012. Epub 2020 May 17.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, People's Republic of China.

Ulcerative colitis (UC), a kind of inflammatory bowel disease, is generally characterized by chronic, persistent, relapsing, and nonspecific ulceration of the bowel, which is widespread in the world. Although the pathogenesis of UC is multifactorial, growing evidence has demonstrated that gut microbiota and its metabolites are closely related to the development of UC. Lizhong decoction (LZD), a well-known classical Chinese herbal prescription, has been used to clinically treat UC for long time, but its mechanism is not clear. In this study, 16S rRNA gene sequencing combining with untargeted metabolomics profiling was used to investigate how LZD worked. Results indicated that LZD could shape the gut microbiota structure and modify metabolic profiles. The abundance of opportunistic pathogens such as Clostridium sensu stricto 1, Enterobacter, and Escherichia-Shigella correlated with intestinal inflammation markedly decreased, while the levels of beneficial bacteria including Blautia, Muribaculaceae_norank, Prevotellaceae UCG-001, and Ruminiclostridium 9 elevated in various degrees. Additionally, fecal metabolite profiles reflecting microbial activities showed that adenosine, lysoPC(18:0), glycocholic acid, and deoxycholic acid notably decreased, while cholic acid, α-linolenic acid, stearidonic acid, and L-tryptophan significantly increased after LZD treatment. Hence, based on the systematic analysis of 16S rRNA gene sequencing and metabolomics of gut flora, the results provided a novel insight that microbiota and its metabolites might be potential targets for revealing the mechanism of LZD on amelioration of UC.Key Points • The potential mechanism of LZD on the amelioration of UC was firstly investigated.• LZD could significantly shape the structure of gut microbiota.• LZD could notably modulate the fecal metabolic profiling of UC mice. Graphical abstract.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00253-020-10665-1DOI Listing
July 2020

Comparative Analysis of the Chemical Consistency Between the Traditional and Mixed Decoction of Maimendong Decoction by Ultra-Performance Liquid Chromatography Coupled to Quadrupole with Time-of-Flight Mass Spectrometry (UPLC-QTOF-MS)-Based Chemical Profiling Approach.

J Chromatogr Sci 2020 Jun;58(6):549-561

Jiangsu Key Laboratory for High Technology Research of Traditional Chinese Medicine Formulae Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China.

Take Maimendong Decoction (MMDD), one of the Chinese classic herbal formulas, as an object to evaluate the chemical consistency between traditional decoction and mixed decoction. The ultra-performance liquid chromatography coupled to quadrupole with time-of-flight mass spectrometry-based chemical profiling approach has been utilized. A total of 48 major peaks are detected from these two decoctions under the present chromatographic and mass spectrometry conditions. The results of negative ion mode show nine significant inconsistencies. Liquiritin, ginsenoside Ro and ginsenoside Rg5/Rk1 are detected with higher intensity in traditional preparation sample than the mixed decoction, while licoisoflavone A is higher in mixed decoction samples than the traditional one. The mechanisms involved in the chemical changes were assumed to be anti-inflammation, anti-oxidative stress and so on, suggesting these two different preparation approaches of MMDD may lead to a possibility of discrepant clinical outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/chromsci/bmz104DOI Listing
June 2020

Frankincense and myrrh and their bioactive compounds ameliorate the multiple myeloma through regulation of metabolome profiling and JAK/STAT signaling pathway based on U266 cells.

BMC Complement Med Ther 2020 Mar 23;20(1):96. Epub 2020 Mar 23.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.

Background: Frankincense and myrrh are used as traditional anti-inflammatory and analgesic medicines in China. It has been reported that frankincense and myrrh have significant anti-tumor activities. The present study was designed to investigate the inhibitory efficacy of frankincense ethanol extracts (RXC), myrrh ethanol extracts (MYC), frankincense -myrrh ethanol extracts (YDC), frankincense -myrrh water extracts (YDS) and their main compounds on U266 human multiple myeloma cell line.

Methods: The inhibition effects of cell proliferation was evaluated by MTT assays. Cell culture supernatant was collected for estimation of cytokines. Western blot analysis was designed to investigate the regulatory of JAK/STAT signal pathway. In addition, cell metabolomics based on the ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) had been established to investigate the holistic efficacy of frankincense and myrrh on U266 cells. Acquired data were processed by partial least-squares discriminant analysis (PLS-DA) and orthogonal projection to latent structures squares-discriminant analysis (OPLS-DA) to identify potential biomarkers.

Results: RXC, MYC significantly inhibited the proliferation of U266 cells at dose of 25-400 μg/mL, YDC and YDS at the dose of 12.5-400 μg/mL. 3-O-acetyl-α-boswellic acid, 3-acetyl-11 keto-boswellic acid and 11-keto-boswellic acid had the most significant anti- multiple myeloma activities in the 10 compounds investigated, therefore these 3 compounds were selected as representatives for Elisa assay and western blotting experiments. All the extracts and active compounds ameliorated the secretion of cytokines and down-regulated the expression of JAK/STAT signaling pathway-related proteins. Comparing RXC, MYC, YDC and YDS-treated U266 cells with vehicle control (DMSO), 13, 8, 7, 7 distinct metabolites and 2, 2, 3, 0 metabolic target pathways involved in amino acid metabolism, lipid metabolism, vitamin metabolism, arachidonic acid were identified, respectively.

Conclusions: Taken together our results suggest that the frankincense and myrrh and their bioactive compounds inhibit proliferation of U266 multiple myeloma cells by regulating JAK/STAT signaling pathway and cellular metabolic profile.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12906-020-2874-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7092432PMC
March 2020

A review of Behcet's disease from the perspectives of both Western and Chinese medicine.

J Tradit Chin Med 2019 02;39(1):139-152

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.

Behcet's disease is a condition with a complicated and unclear etiology that comprises multi-systemic, chronic, inflammatory vasculitis. Behcet's disease can affect every tissue and organ in the body, and is characterized by recurrent oral and genital ulcers, ocular inflammation, skin lesions, and other manifestations. The incidence of Behcet's disease has a distinct regional specificity, and is most prevalent along the Silk Road, a route that stretched between the Mediterranean, Middle East and Far East. This article reviews the recent literature to evaluate the prevalence, clinical manifestations, pathogenesis and mechanism, and current treatments of Behcet's disease. Furthermore, the etiology of Behcet's disease will be evaluated from the aspect of Traditional Chinese Medicine (TCM) syndrome differentiation. As Behcet's disease is complex and intractable, its treatment warrants further research. Traditionally, Behcet's disease is treated with Western Medicine (WM) via medications that act locally and systemically; this WM treatment protocol usually has a good effect, but relapse can occur after reducing the dosage. Thus, it may be ideal to treat Behcet's disease via a combination of WM and TCM. Recent studies have indicated that such a combination of Chinese and Western treatments has a better effect than either treatment alone. The aim of the present review is to describe the clinical features of Behcet's disease, and to outline its possible pathogenesis in terms of both TCM and WM. Based on these findings, the present review proposes a Behcet's disease treatment protocol composed of a combination of Chinese and WM that can effectively improve the occurrence of relapse caused by the reduction of the dosage of Western medication.
View Article and Find Full Text PDF

Download full-text PDF

Source
February 2019

Author Correction: Transcriptome and digital gene expression analysis unravels the novel mechanism of early flowering in Angelica sinensis.

Sci Rep 2020 Jan 31;10(1):1888. Epub 2020 Jan 31.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-58024-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994468PMC
January 2020

The effect of deoxyschizandrin on chronic unpredictable mild stress-induced depression.

Biotechnol Appl Biochem 2021 Feb 7;68(1):52-59. Epub 2020 Feb 7.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, China.

The purpose of the present study was to evaluate the antidepressant effect of deoxyschizandrin (DEO) in chronic unpredictable mild stress (CUMS)-induced mice. The mice were subjected to CUMS paradigm for 8 weeks. From the sixth week, the mice were intragastrically treated with DEO once daily for continuous 3 weeks. The behavior tests including sucrose preference test (SPT), forced swimming test (FST), tail suspension test (TST), and open field test were conducted. Additionally, the expressions of TLR4, MyD88, TRAF6, p-NF-κBp65, NLRP3, cleaved caspase-1, cleaved IL-1β, GluR, and PSD95 in hippocampus were detected by western blot. The concentrations of IL-6 and TNF-α in hippocampus were determined by enzyme linked immune sorbent assay (ELISA). The dendritic spine density was observed by Golgi-Cox staining. As a result, the treatment with DEO relieved anhedonia in SPT, and reduced immobile duration in FST and TST. DEO treatment effectively attenuated the CUMS-caused alterations of TLR4, MyD88, TRAF6, p-NF-κBp65, NLRP3, cleaved caspase-1, cleaved IL-1β, GluR, and PSD95. Furthermore, DEO could reduce the hippocampal inflammatory cytokine content and increase the density of dendritic spine. In conclusion, the present work indicated that DEO exhibited antidepressant effect on CUMS-induced depressive mice, which was possible due to the TLR4/NF-κB/NLRP3 pathway and the amelioration of dendritic spine density through GluR/PSD95 cascade.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/bab.1893DOI Listing
February 2021

Modulation of microbially derived short-chain fatty acids on intestinal homeostasis, metabolism, and neuropsychiatric disorder.

Appl Microbiol Biotechnol 2020 Jan 21;104(2):589-601. Epub 2019 Dec 21.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, People's Republic of China.

A diverse range of symbiotic gut bacteria codevelops with the host and is considered a metabolic "organ" that not only facilitates harvesting of nutrients from the dietary components but also produces a class of metabolites. Many metabolites of gut microbes have an important impact on host health. For example, an inventory of metabolic intermediates derived from bacterial protein fermentation may affect host physiology and pathophysiology. Additionally, gut microbiota can convert cholesterol to bile acids and further into secondary bile acids which can conversely modulate microbial community. Moreover, new research identifies that microbes synthesize vitamins for us in the colon. Here, we will review data implicating a major class of bacterial metabolites through breaking down dietary fiber we cannot process, short-chain fatty acids (SCFAs), as crucial executors of alteration of immune mechanisms, regulation of metabolic homeostasis, and neuroprotective effects to combat disease and improve health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00253-019-10312-4DOI Listing
January 2020

Scutellariae radix and coptidis rhizoma ameliorate glycolipid metabolism of type 2 diabetic rats by modulating gut microbiota and its metabolites.

Appl Microbiol Biotechnol 2020 Jan 22;104(1):303-317. Epub 2019 Nov 22.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, People's Republic of China.

Scutellariae radix (Scutellaria baicalensis Georgi, SR) and coptidis rhizoma (Coptis chinensis Franch, CR) are both widely used traditional Chinese medicines and have been used together to treat T2DM with synergistic effects in the clinical practices for thousands of years, but their combination mechanism is not clear. Accumulating evidences have implicated gut microbiota as important targets for the therapy of T2DM. Thus, this study aimed to unravel the cooperation mechanism of SR and CR on the amelioration of T2DM based on the systematic analysis of metagenome and metabolome of gut microbiota. Bacterial communities were analyzed based on high-throughput 16S rRNA gene sequencing. Furthermore, ultra high-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS) was used to analyze variations of microbial metabolites in feces and the contents of short chain fatty acids (SCFAs) in the cecum were determined by a gaschromatography-flame ionization detector (GC-FID). 16S rRNA gene sequencing results revealed that T2DM rats treated with SR, CR, and the combination of SR and CR (SC) exhibited changes in the composition of the gut microbiota. The SCFAs-producing bacteria such as Bacteroidales S24-7 group_norank, [Eubacterium] nodatum group, Parasutterella, Prevotellaceae UCG-001, Ruminiclostridium, and Ruminiclostridium 9 in T2DM rats were notably enriched after treatment with SR, CR, and their combination. In contrast, secondary bile acid-producing bacteria such as Escherichia-Shigella strongly decreased in numbers. The perturbance of metabolic profiling in T2DM rats was obviously improved after treatment, exhibiting a lower level of secondary bile acids and a numerical increase of microbially derived SCFAs. Moreover, the correlation analysis illustrated a close relationship among gut microbiota, its metabolites, and T2DM-related indexes. The findings indicated that the crosstalk between microbiota-derived metabolites and the host played an important role in the progress of T2DM and might provide a novel insight regarding gut microbiota and its metabolites as potential new targets of traditional Chinese medicines. Furthermore, this work also suggested that the integration of various omics methods and bioinformatics made a useful template for drug mechanism research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00253-019-10174-wDOI Listing
January 2020

Target lipidomics approach to reveal the resolution of inflammation induced by Chinese medicine combination in Liu-Shen-Wan against realgar overexposure to rats.

J Ethnopharmacol 2020 Mar 20;249:112171. Epub 2019 Aug 20.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Jiangsu Key Laboratory of Efficacy and Safety Evaluation of TCM, Nanjing University of Chinese Medicine, Nanjing, China.

Ethnopharmacological Relevance: Liu-Shen-Wan (LSW) is one of the popular over-the-counter drugs in Asia, which contains realgar (AsS), used for the treatment of upper respiratory tract inflammation and skin infections. However, the safety and potential risk of this arsenic remain unknown.

Aim Of The Study: The aim of this study was to determine total arsenic in tissue and investigate effects of regular dose and overdose LSW exposure on rat liver.

Materials And Methods: We used a target lipidomics approach to quantify inflammatory eicosanoids and employed ICP-MS to determine total arsenic in tissue.

Results: The results showed that oral administration of 8 and 40 mg/kg LSW (1 and 5 fold human-equivalent dose) induced light changes of liver lipidomic profile in rats, which was associated with anti-inflammatory function of LSW. In our recent report, we observed that 41 and 134 mg/kg realgar (40 and 132 fold human-equivalent dose) stimulated rat liver inflammation through up-regulation of pro-inflammatory LOX-derived, CYP-derived HETEs and COX-derived PGs. However, we found that LSW in the form of drug combination, containing 41 and 134 mg/kg realger, could not stimulate these similar inflammatory responses in rats, although the liver total arsenic levels of the realger and LSW groups were same.

Conclusion: The downregulation of pro-inflammatory response showed that the LSW containing realger is safer than realger alone administrated to rats. These results suggested that Chinese medicines combination could reduce realgar-derived arsenic toxicity in rats.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2019.112171DOI Listing
March 2020

Discovery and Rational Design of a Novel Bowman-Birk Related Protease Inhibitor.

Biomolecules 2019 07 14;9(7). Epub 2019 Jul 14.

Natural Drug Discovery Group, School of Pharmacy, Queen's University Belfast, Belfast, Northern Ireland BT7 1NN, UK.

Anuran amphibian skin secretions are a rich source of peptides, many of which represent novel protease inhibitors and can potentially act as a source for protease inhibitor drug discovery. In this study, a novel bioactive Bowman-Birk type inhibitory hexadecapeptide of the Ranacyclin family from the defensive skin secretion of the Fukien gold-striped pond frog, , was successfully isolated and identified, named PPF-BBI. The primary structure of the biosynthetic precursor was deduced from a cDNA sequence cloned from a skin-derived cDNA library, which contains a consensus motif representative of the Bowman-Birk type inhibitor. The peptide was chemically synthesized and displayed a potent inhibitory activity against trypsin (Ki of 0.17 µM), as well as an inhibitory activity against tryptase (Ki of 30.73 µM). A number of analogues of this peptide were produced by rational design. An analogue, which substituted the lysine (K) at the predicted P position with phenylalanine (F), exhibited a potent chymotrypsin inhibitory activity (Ki of 0.851 µM). Alternatively, a more potent protease inhibitory activity, as well as antimicrobial activity, was observed when P was replaced by lysine, forming K-PPF-BBI. The addition of the cell-penetrating peptide Tat with a trypsin inhibitory loop resulted in a peptide with a selective inhibitory activity toward trypsin, as well as a strong antifungal activity. This peptide also inhibited the growth of two lung cancer cells, H460 and H157, demonstrating that the targeted modifications of this peptide could effectively and efficiently alter its bioactivity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/biom9070280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6681222PMC
July 2019

Transcriptome and digital gene expression analysis unravels the novel mechanism of early flowering in Angelica sinensis.

Sci Rep 2019 07 11;9(1):10035. Epub 2019 Jul 11.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China.

Angelica sinensis (Oliv.) Diels is a widely used medicinal plant mainly originated in Gansu, China. Angelica sinensis is greatly demanded in the clinical practice of Chinese medicine due to its broad pharmacological activities of hematopoietic and anti-inflammatory properties. But, the percentage of early flowering in Angelica sinensis arrives to 20%~30%, which severely affects its quality and quantity. Here, transcriptome profiling and digital gene expression analysis were applied to study the mechanism of early flowering in Angelica sinensis. A total of 49,183,534 clean reads were obtained and assembled into 68,262 unigenes, and 49,477 unigenes (72.5%) could be annotated to a minimum of one database in the Nr, Nt, Swiss-Pro, GO, COG and KEGG. Taking the above transcriptome data as a reference, digital gene expression result showed that 5,094 genes expression level were significant changed during early flowering. These annotated genes offered much information promoting that the biosynthesis of secondary metabolites pathway, the hormone signal transduction pathway, and the transcription regulation system may be closely related to the early flowering phenomenon of Angelica sinensis. Further expression patterns of key genes contribute to early flowering were analyzed using quantitative real-time PCR. The transcriptome result offered important gene expression information about early flowering in Angelica sinensis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-46414-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6624268PMC
July 2019

Xiexin Tang ameliorates dyslipidemia in high-fat diet-induced obese rats via elevating gut microbiota-derived short chain fatty acids production and adjusting energy metabolism.

J Ethnopharmacol 2019 Sep 18;241:112032. Epub 2019 Jun 18.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, PR China. Electronic address:

Ethnopharmacological Relevance: Traditional herbal medicine has been taken as a new and effective approach to treat many chronic diseases. Xiexin Tang (XXT), a compound recipe composed of Dahuang (Rheum palmatum L.), Huangqin (Scutellaria baicalensis Georgi) and Huanglian (Coptis chinensis Franch.), has been reported to have hypoglycemic and hypolipidemic effects, but its mechanism remains unclear. Our previous study found that Xiexin Tang markedly ameliorated the composition of the gut microbiota, especially for some short chain fatty acids (SCFAs) producing bacteria, and then notably increased SCFAs production. However, the mechanism of XXT on the fermentation of gut bacteria and further improvement of obesity is not yet clear.

Aim Of The Study: This study aimed to unravel the molecular mechanism of XXT on the amelioration of obesity.

Materials And Methods: Here, high-fat diet-induced obese rat model was established to investigate the intervention efficacy following oral administration of XXT. Additionally, the expressions of key enzymes of gut microbe-derived SCFAs biosynthesis and key targets in the signaling pathway of energy metabolism were investigated by ELISA and qPCR analysis.

Results: Results showed that XXT could notably correct lipid metabolism disorders, alleviate systematic inflammation, improve insulin sensitivity and reduce fat accumulation. Additionally, XXT could increase gut microbiota-derived SCFAs-producing capacity by enhancing mRNA levels and activities of SCFA-synthetic key enzymes such as acetate kinase (ACK), methylmalonyl-CoA decarboxylase (MMD), butyryl-CoA: acetate CoA transferase (BUT) and butyrate kinase (BUK), which markedly decreased the adenosine triphosphate (ATP) contents, elevated adenosine diphosphate (ADP) and adenosine monophosphate (AMP) levels and further lowered the energy charge (EC) in obese rats via activating peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)/uncoupling protein-2 (UCP-2) signaling pathway. What's more, XXT could notably ameliorate dyslipidemia via increasing the gene expression of 5'-AMP-activated protein kinase (AMPK) and blocking mammalian target of rapamycin (mTOR) signaling pathway.

Conclusions: Taken together, our data provided a novel insight into the role of XXT in losing weight from energy metabolism regulation, which unraveled the molecular mechanism of XXT on the alleviation of dyslipidemia and fat heterotopic accumulation. The study provided useful information for XXT in clinical application to treat obesity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2019.112032DOI Listing
September 2019

High Resolution Mass Profile of Bufadienolides and Peptides Combing with Anti-Tumor Cell Screening and Multivariate Analysis for the Quality Evaluation of Bufonis Venenum.

Molecules 2019 May 20;24(10). Epub 2019 May 20.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.

In order to evaluate the quality of Bufonis Venenum commercial herbs, a three-step qualitative and quantitative research study was performed. Firstly, we tried to identify small molecules and peptides in Bufonis Venenum using pre-fractionation chromatography and high-resolution mass spectrometry. The database search of the small molecules and peptides of Bufonis Venenum revealed that the dried venom consisted of free/conjugated-type bufadienolides and peptides with a mass range of 0.4-2 kDa. Secondly, we used partial least squares (PLS) multivariate statistical analysis to screen bufadienolides markers (VIP > 1.5) responsible for the anti-tumor cell activity of Bufonis Venenum, including 21 identified bufadienolides and 7 unknown compounds. It is noticeable that these bufadienolide markers could not be recognized by traditional HPLC-UV based spectrum-effect relationship analysis (correlation coefficient ranging from -0.24 to 0.40). Finally, we proposed a weight coefficient-based corrected total contents of 9 bufadienolides as a quality evaluation indicator, which had good correlation with inhibitory effects on tumor cells of commercial Bufonis Venenum. The correlation coefficient increased from 0.4 to 0.6. Thus, our pre-fractionation chromatography and mass spectrometry strategy had significant advancement over the traditional spectrum-effect relationship method for chemical marker identification. These results could be crucial and helpful in the development of a quality evaluation method that could reflect the pharmacological activity of Bufonis Venenum.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules24101943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572007PMC
May 2019

Enzymatic in situ saccharification of herbal extraction residue by a medicinal herbal-tolerant cellulase.

Bioresour Technol 2019 Sep 4;287:121417. Epub 2019 May 4.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources and Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China. Electronic address:

Herbel-tolerant strains exhibit considerable environmental and commercial values not only due to their harmless treatment of herbal-extraction residues (HERs) but also because of their use in preparing high-quality cellulase cocktails. In this study, three typical HERs were evaluated for enzymatic in situ saccharification performance. A HERs-tolerance fungus, identified as Penicillium oxalicum G2, can grow in 1.5% (w/v) Radix isatidis residues (RIR), thereby exhibiting the highest FPase (2.2 U/mL), carboxymethyl cellulase (13.3 U/mL), and β-glucosidase (4.6 U/mL) activities. The most effective production of cellulase cocktail was achieved via orthogonal experiment in a system with pH 6.0, 30 °C, and 96 h. Cellulase cocktail from P. oxalicum G2 can directly saccharify the extraction RIR, thereby achieving a maximum reducing sugar yield of 7.2 mg/mL, which is 1.7-fold higher than those of commercial cellulases. Results illustrate the potential of P. oxalicum G2 for enzymatic in situ saccharification.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biortech.2019.121417DOI Listing
September 2019

A novel, highly-water-soluble apigenin derivative provides neuroprotection following ischemia in male rats by regulating the ERK/Nrf2/HO-1 pathway.

Eur J Pharmacol 2019 Jul 14;855:208-215. Epub 2019 Mar 14.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources and Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China; Jiangsu Key Laboratory for High Technology Research of TCM Formulae, State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China. Electronic address:

6"-O-succinylapigenin [apigenin-7-O-(6'-O-succinyl)-glucoside], a novel compound, is identified in chamomile. Although it is highly produced by Bacillus amyloliquefaciens FJ18, its bioactivity remains unknown. The neuroprotective effects and antioxidative mechanism of 6''-O-succcinylapigenin in the middle cerebral artery occlusion model in male rats was investigated in this study. The structure of this compound was determined by spectroscopic data analysis. After 2 h of occlusion and 24 h of reperfusion, magnetic resonance imaging and assessed neurological scores following middle cerebral artery occlusion (MCAO) in male rats to determine the infarction size and neurological deficits, respectively. In addition, we tested protein levels of the nuclear factor E2-related factor 2 (Nrf2), Kelch-like ECH-associated protein1 (Keap1), heme oxygenase-1 (HO-1), and extracellular-signal-regulated kinase (ERK), to investigate the mechanism of antioxidative action of 6''-O-succcinylapigenin. Finally, we employed immunofluorescence to determine the location of Nrf2 and Keap1 in HT22 cells cultured in vitro. Our results revealed that administration of 6''-O-succcinylapigenin induced a decrease in both infarct volume and neurological scores following MCAO, and significantly increased the activity of HO-1 and nuclear Nrf2 in vivo. Similarly, immunofluorescence assays indicated that Nrf2 is highly expressed in the nucleus following treatment with 6''-O-succcinylapigenin in vitro. Our study suggests that 6''-O-succcinylapigenin exerts an anti-ischemic effect by activating the ERK/Nrf2/HO-1 pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejphar.2019.03.024DOI Listing
July 2019

Improved dialysis removal of protein-bound uremic toxins by salvianolic acids.

Phytomedicine 2019 Apr 16;57:166-173. Epub 2018 Dec 16.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address:

Background: Indoxyl sulfate (IS) and p-cresyl sulfate (pCS) are two key protein-bound uremic toxins that accumulate in patients with end-stage renal disease. IS and pCS cannot be efficiently removed by conventional hemodialysis because they are highly bound to proteins. One promising means to optimize the removal of protein-bound uremic toxins involves using binding competitors to liberate uremic toxins from protein-binding partners.

Purpose: In this study, we try to identify potential binding competitors that can enhance the dialysis removal of IS and pCS in natural compounds of phytomedicine.

Methods: We employed microdialysis to evaluate whether Danhong injection (DHI) and its salvianolic acids can increase the free fractions of IS and pCS and thus improve their dialysis efficiency in vitro. Furthermore, we confirmed the positive effects of DHI and salvianolic acids in vivo on chronic kidney disease model rats in which IS and pCS had heavily accumulated.

Results: DHI significantly increased the dialysis efficiency of IS and pCS by 99.13% and 142.00% in vitro (10-fold dilution), respectively, and by 135.61% and 272.13% in vivo (4.16 ml/kg). Salvianolic acids including lithospermic acid (LA), salvianolic acid A (SaA), tanshinol (DSS), caffeic acid (CA), salvianolic acid B (SaB), protocatechuic aldehyde (PA) and rosmarinic acid (RA) significantly enhanced the dialysis removal of IS and pCS in a concentration-dependent manner. LA, the best competitor of the tested salvianolic acids, increased dialysis efficiency levels of IS and pCS by 197.23% and 198.31% in vitro (400 μM), respectively, and by 119.55% and 127.56% in vivo (24.69 mg/kg).

Conclusion: The removal of protein-bound uremic toxins IS and pCS using DHI or salvianolic acids as protein-bound competitors is superior to previously reported strategies and drugs and may contribute to clinical hemodialysis therapeutic practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phymed.2018.12.018DOI Listing
April 2019

Exploratory Cortex Metabolic Profiling Revealed the Sedative Effect of Amber in Pentylenetetrazole-Induced Epilepsy-Like Mice.

Molecules 2019 Jan 28;24(3). Epub 2019 Jan 28.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization/State Key Laboratory Cultivation Base for Traditional Chinese Medicine Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.

Epilepsy is a common clinical syndrome characterized by sudden and recurrent attacks and temporary central nervous system dysfunction caused by excessive discharge of neurons in the brain. Amber, a fossilized organic substance formed by the resins of conifers and leguminous plants, was prescribed to tranquilize the mind in China. In this paper, the antiepileptic effect of amber was evaluated by a pentylenetetrazole (PTZ)-induced epileptic model. An untargeted metabolomics approach was applied to investigate metabolic changes in the epileptic model, which was based on HILIC-UHPLC-MS/MS multivariate statistical analysis and metabolism network analysis. The outcome of this study suggested that 35 endogenous metabolites showed marked perturbations. Moreover, four metabolism pathways were mainly involved in epilepsy. After treatment by amber, the endogenous metabolites had a marked tendency to revert back to the situation of the control group which was consistent with phenobarbital. This study characterized the pentylenetetrazole-induced epileptic model and provided new evidence for the sedative effect of amber.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules24030460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6384605PMC
January 2019

Lipidomic profiling of subchronic AsS exposure identifies inflammatory mediators as sensitive biomarkers in rats.

Metallomics 2019 03;11(3):576-585

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.

Arsenic sulfide compounds provide nearly all of the world's supply of arsenic. However, the risk of arsenic trisulfide exposure is still not fully investigated. Here, we systemically assessed the toxicology of As4S4 in rats by combining arsenic metabolite detection, routine testing and lipidomic profiling. It was revealed that the oral administration of As4S4 for two months increased the total arsenic content in the liver reaching a saturation level. Further analysis by anion exchange chromatography coupled with inductively coupled plasma mass spectrometry (ICP-MS) technology showed no trace of inorganic arsenic, but there was significant presence of dimethylarsinic acid (DMA), in the livers of rats. This arsenic metabolite was less toxic to rats and did not induce overt liver pathology and functional injury. In contrast, lipidomic profiling provided a comprehensive map of lipids and uncovered a more complex inflammatory response, exhibiting more sensitive change to arsenic exposure. We observed that metabolites of cyclooxygenase, including PGF2α, dhk PGF2α, 15k PGF2α, 8-iso-PGF2a, PGE2, dhk PGE2, PGD2, 15d-PGD2, and PGJ2, were significantly elevated. But mediators from lipoxygenase, cytochrome P450, docosahexaenoic acid, and eicosapentaenoic acid pathways were not markedly affected. In summary, we identified DMA as the predominant arsenic species in the livers of rats, and found cyclooxygenase-derived lipids as the inflammatory mediators before the development of overt liver injury for subchronic As4S4 exposure. These mediators could translate into potential metabolic biomarkers in early arsenic risk assessment and as targets for therapeutic intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c8mt00181bDOI Listing
March 2019
-->