Evaluation indices of the temperature difference of subgrade and the optimization of mitigation measures in cold regions.

With the construction and operation of railways in cold regions, the asymmetric deformation of subgrades due to the difference in the transverse ground temperature has become a prominent issue. A comprehensive evaluation of the transverse ground temperature difference and investigation of the corresponding mitigation measures should be conducted to avoid or minimize the damage resulting from this difference, thereby improving subgrade stability and reducing deformation. In this study, the time history variations in the homogeneity and symmetry indices of the ground temperature at typical instances that reflect the spatial and temporal changes in the temperature difference of the subgrade were proposed as evaluation indices. The feasibility of these evaluation indices was verified through numerical models with different types of anti-frost berms. Subsequently, the numerical models were used to analyze the ground temperature evaluation indices of a subgrade with expanded polystyrene (EPS) insulation board and polyurethane (PU) insulation board at different locations. Additionally, the performances of each mitigation measure in eliminating or reducing the ground temperature difference were assessed and compared. The results show that all the mitigation measures could improve the homogeneity and symmetry of the ground temperature distribution. The maximum mitigation rates for the homogeneity and symmetry are 97.87% and 45.90%, respectively. This study provides a comprehensive evaluation method for the temperature difference of subgrades constructed in cold regions and a theoretical reference for the selection of anti-frost measures in the design, operation, and maintenance of subgrades in cold regions.

Study on the potential mechanism of the active components in YiYiFuZi powder in homotherapy for hetropathy of coronary heart disease and rheumatoid arthritis.

In recent years, the incidence of coronary heart disease and rheumatoid arthritis has been increasing, which has become a common public health problem worldwide. YiYiFuZi (YYFZ ) powder is a classical traditional Chinese prescription, which is commonly used to treat metabolic diseases such as rheumatoid arthritis, with an ideal curative effect, but the therapeutic mechanism is still unclear. In this study, from the perspective of clinical metabolomics, combined with network pharmacology, we sought the comorbidity mechanism and key targets of coronary heart disease and rheumatoid arthritis and the mechanism by which YYFZ powder exerts therapeutic effects, combined with molecular docking and atomic force microscopy to determine the effective components, and found that the higenamine and steroid components in YYFZ powder can bind acid sphingomyelinase enzymes to affect the sphingolipid pathway to produce therapeutic effects, which can bind to sugars existing as a glycoside.

Study on endocrine disruption effect of paclobutrazol and uniconazole on the thyroid of male and female rats based on lipidomics.

The present study investigated the effects of paclobutrazol and uniconazole on thyroid endocrine system in rats. Lipidomic analysis was performed to obtain the biomarkers of thyroid endocrine disruption induced by paclobutrazol and uniconazole. Network pharmacology was further used to discover potential targets of biomarkers related to drugs and diseases. After paclobutrazol and uniconazole administration, seven and four common biomarkers related to thyroid endocrine disruption for female and male rats were obtained, respectively. Paclobutrazol and uniconazole significantly increased the biomarker levels of PG (12:0/15:0), PS (14:0/16:0), PA (20:1/15:0) and PG (13:0/17:0) in both sexes of rats. Exposure to paclobutrazol additionally caused a significant decrease of PG (22:6/20:2), PE (24:1/18:1) and PE (24:0/18:0) in female rats, while an increase in male rats. Changes of the common biomarkers for paclobutrazol and uniconazole revealed similar endocrine disruption effect, which was higher in the females. Network pharmacology and KEGG pathway analysis indicated that the thyroid endocrine disrupting effects of paclobutrazol and uniconazole may be related to V-akt murine thymoma viral oncogene homolog (Akts), mitogen-activated protein kinase (MAPKs), epidermal growth factor receptor (EGFR), Insulin-like growth factor (IGF-1), IGF-IR and V-Raf murine sarcoma viral oncogene homolog B1 (BRAF). The results demonstrated that paclobutrazol and uniconazole could cause thyroid endocrine disorders in male and female rats, which were sex-specific, thus highlighting the importance of safe and effective application of these plant growth regulators.

Early Warning of Ischemic Stroke Based on Atherosclerosis Index Combined With Serum Markers.

CONTEXT: Ischemic stroke (IS) is a serious public health problem worldwide, threatening human life and health. Atherosclerosis is the cause of stroke. At present, there are few selective indexes that can be used to evaluate atherosclerosis in the clinic; providers rely mainly on the atherosclerotic index (AI). Disturbance of lipid metabolism is considered to be a key event leading to IS. OBJECTIVE: The purpose of this study was to discover potential biomarkers in the serum of atherosclerosis-induced IS, combined with the AI to provide early warning for the diagnosis of IS. METHODS: In this study, we used nontargeted metabolomics based on ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) to measure the changes in serum metabolites in a group of patients with IS. To verify the reproducibility of candidate biomarkers in the population, we expanded the sample size. RESULTS: Five metabolites were identified, including sphingomyelin (18:0/14:0), 1-Methylpyrrolinium, PC (18:0/18:0), LysoPC (18:0/0:0), and PC (18: 2/18:2). The combination of these 5 metabolic markers has good diagnostic and predictive ability, and the change level of these metabolites is significantly related to IS. Our results also indicate that changes in glycerophospholipid metabolism may indicate an early risk of IS development. CONCLUSION: These findings may contribute to the development of new diagnostic methods of potential biomarkers in serum combined with the AI, thereby providing early warning for the diagnosis of atherosclerosis-induced IS, and may provide a new insights for pathogenesis in IS.

Integrated Bifunctional Electrodes Based on Amorphous Co-Ni-S Nanoflake Arrays with Atomic Dispersity of Active Sites for Overall Water Splitting.

Fabrication of amorphous electrocatalysts without noble metals for cost-effective full water splitting is highly desired but remains a substantial challenge. In the present work, we report a facile strategy for exploring integrated bifunctional electrocatalysts based on amorphous cobalt/nickel sulfide nanoflake arrays self-supported on carbon cloth, by tailoring competitive coordination of metal ions between glucose and 2-aminoterephthalic acid. Ultrahigh dispersion of binary metal active sites with balanced atomic distribution enables the optimization of catalytic properties for both the oxygen evolution reaction (OER) and the hydrogen evolution reaction (HER) in an alkaline solution. The obtained catalyst exhibits remarkably enhanced OER and HER activities as compared with its oxide counterpart and analogues with different Co/Ni ratios. It requires overpotentials of 296 and 192 mV to deliver a current density of 10 mA cm-2 for the OER and HER, respectively; it retains 96.6 and 96.9% activity after 32 h of OER and 36 h of HER tests at 10 mA cm-2, respectively. As directly used an anode and a cathode in an alkaline electrolyzer, a low cell voltage of 1.60 V could endow a water splitting current of 10 mA cm-2, outperforming the benchmark RuO2 and Pt/C-based electrolyzer at 1.72 V@10 mA cm-2. The current synthetic strategy may provide more opportunities for the design and direct synthesis of amorphous catalysts for overall water splitting and beyond.

Application of lipidomics strategy to explore aging-related biomarkers and potential anti-aging mechanisms of ginseng.

Aging often leads to an increase risk of age-related diseases, and the development of anti-aging drugs have become the trend and focus of the current scientific research. In this experiment, serum samples from healthy people of different ages were analyzed based on clinical lipidomics, and a total of 10 potential biomarkers in middle-aged and youth group, 20 biomarkers in the youth and the elderly group were obtained. Furthermore, dhSph and dhCer involved above may affect the aging process through sphingolipid metabolic pathway. As the first and rate-limiting step of catalyzing de novo sphingolipid pathway, SPT may play a key role in human anti-aging, which is revealed by lipidomics liposome tracer analysis. The potential active components in ginseng on SPT was further verified by molecular docking virtual screening and atomic force microscope. Four ingredients of ginseng may reduce the levels of metabolites dhSph and dhCer by inhibiting the activity of SPT, and play an anti-aging effect by affecting the sphingolipid metabolism pathway.A clinical trials registration number: ChiCTR1900026836.

Determination of Alkaloids and Flavonoids in Sophora flavescens by UHPLC-Q-TOF/MS.

This study is based on UHPLC-Q-TOF/MS and fragment ions to achieve classification and identification of alkaloids and flavonoids in Sophora flavescens. By reviewing the available and relevant literature, the mass fragmentation rules of alkaloids and flavonoids were summarized. 0.1% formic acid water (A) and acetonitrile (B) were used as mobile phases. 37 chemical constituents were identified, including 13 alkaloids and 24 flavonoids. This research method offers a complete strategy based on the fragmentation information of characteristic fragment ions and neutral loss obtained by MS/MS to characterize the chemical composition of Sophora flavescens.

Imperatae rhizoma-Hedyotis diffusa Willd. herbal pair alleviates nephrotic syndrome by integrating anti-inflammatory and hypolipidaemic effects.

BACKGROUND: Nephrotic syndrome (NS) is a common nephropathy with a complex and diverse aetiology. Both Imperatae rhizoma and Hedyotis diffusa Willd. are herbs that are widely used as medicine and functional food. In traditional Chinese medicine theory, they are used as an herbal pair (HP) to treat inflammation-related diseases in the clinic, especially disorders of the kidney. PURPOSE: This study aimed to investigate the anti-inflammatory and hypolipidaemic effects of HP in an NS rat model and provide scientific data for its clinical application. METHODS: An NS model was established by two-dose injection of Sprague-Dawley rats with adriamycin. Seven groups, including the sham, model, HP treatment (0.25, 0.5 and 1.0 g/kg/d), prednisone (positive control, 5 mg/kg/d), and atorvastatin (positive control, 4 mg/kg/d) groups, were tested. The biochemical indexes of renal function and inflammatory cytokines were determined by ELISA kits and/or qPCR assays, and the crucial protein involved in the signalling pathway were subsequently tested by qPCR and/or Western blotting. Based on specific compounds identified by LC-Q-TOF-MS, network pharmacological study was carried out. RESULTS: The levels of BUN, Scr, Upro, UA, Alb, TC, TG, and LDL-C were significantly elevated in model rats. HP treatment for four weeks improved the renal function and the dyslipidaemia by decreasing the levels of all parameters, except BUN and Scr. HP treatment (0.5 and 1.0 g/kg/d) upregulated the expression of PPARγ, CYP7b1, and LDLR in the liver, while it down-regulated PCSK9, showing a regulatory effect on lipid metabolism disorder. The levels of TNF-α and IL-1ß in the plasma and the mRNA expression of TNF-α, IL-1ß, MCP-1, and TGF-ß1 in the kidney were decreased in HP groups, revealing its anti-inflammatory effect in NS rats. The HP exerted an alleviation effect on the inflammatory response through the NF-κB pathway by inhibiting the mRNA and protein expression of p50 and p65. There were 34 compounds identified or tentatively characterized in HP. In the network pharmacological study, PPARG(PPARγ), PCSK9, RELA(p65), and NF-κB1(p50) were the top 20 targets for HP, supporting the animal experimental results. CONCLUSION: HP exhibited protective effects on NS rats. These effects might be closely related to the inhibition of NF-κB and PCSK9-LDLR and activation of the PPARγ-CYP7B1 signalling pathways.

Cleavage rules of mass spectrometry fragments and rapid identification of chemical components of Radix Paeoniae Alba using UHPLC-Q-TOF-MS.

INTRODUCTION: Radix Paeoniae Alba (RPA) presents several pharmacological effects, including analgesia, liver protection, and toxicity reduction. RPA consists mostly of monoterpenes and their glycosides, tannins, flavonoids, and organic acids, with monoterpenes being the main active pharmaceutical ingredients. OBJECTIVE: To establish an effective method for rapid classification and identification of the main monoterpenes, flavonoids, and organic acids in RPA. METHODS: We used ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) and data post-processing technology to rapidly classify and identify the monoterpenoids, flavonoids, and organic acids in RPA. We also summarised the diagnostic product ions and neutral losses of monoterpenoids, flavonoids, and organic acids in RPA reported in the literature. RESULTS: We identified 24 components, namely 18 monoterpenoids, one flavonoid, and five organic acids. CONCLUSION: In this study, we analysed the chemically active pharmaceutical ingredients and assessed the quality of RPA. In addition, we demonstrated that UHPLC-Q-TOF-MS can be used to qualitatively classify and identify the variety of chemical components of traditional Chinese medicines (TCMs) to a certain extent. Moreover, we confirmed that mass spectrometry can be used to identify the components of TCMs.

ASBT(SLC10A2): A promising target for treatment of diseases and drug discovery.

Bile acids has gradually become a new focus in various diseases, and ASBT as a transporter responsible for the reabsorption of ileal bile acids, is a key hinge associated to the bile acids-cholesterol balance and bile acids of enterohepatic circulation. The cumulative studies have also shown that ASBT is a promising target for treatment of liver, gallbladder, intestinal and metabolic diseases. This article briefly reviewed the process of bile acids enterohepatic circulation, as well as the regulations of ASBT expression, covering transcription factors, nuclear receptors and gut microbiota. In addition, the relationship between ASBT and various diseases were discussed in this paper. According to the structural classification of ASBT inhibitors, the research status of ASBT inhibitors and potential ASBT inhibitors of traditional Chinese medicine (such resveratrol, jatrorrhizine in Coptis chinensis) were summarized. This review provides a basis for the development of ASBT inhibitors and the treatment strategy of related diseases.

Changes of Transporters and Drug-metabolizing Enzymes in Nephrotic Syndrome.

BACKGROUND: Drug-metabolizing enzymes and transporters play key roles in drug disposition and drug interactions. The alterations of their expression will influence drug pharmacokinetics and pharmacodynamics. However, the changes in the expression of enzymes and transporters in the disease state are still unclear. OBJECTIVE: Our study was to investigate the changes in the expression of main enzymes and drug transporters distributed in Adriamycin nephropathy rat liver, kidney, and intestine. METHODS: An intravenous injection with a single dose of Adriamycin (6mg/kg) was made to establish Adriamycin nephropathy (AN) model and normal groups were injected with normal saline. Serum was collected for lipid metabolism, renal, and hepatic function measurement. The real-time PCR and western blot were applied to determine the mRNA and protein expression of drug enzymes and transporters. RESULTS: In the kidney, a greater expression of Mdr1, Mrp2, Mrp4 Oat2 and Oct2 mRNA was found in AN rats as compared with control rats. In the liver, the expression of Bcrp mRNA was more doubled or tripled than control groups and downregulation of Mdr1, Mrp2, Mrp4 and Bsep gene expression was found in AN rats. Besides, we observed a downward trend of Cyp1a2, Cyp3a4 and Cyp2c9 mRNA levels in AN groups. In the duodenum, the expression of Mdr1 and Mrp3 mRNA level was decreased, while Bcrp and Mrp2 mRNA were increased. CONCLUSION: The changes in drug-metabolizing enzymes and transporters expression in AN rats were clarified, which may be beneficial for understanding the altered pharmacokinetics and pharmacodynamics of clinical drugs and reduce unexpected clinical findings for nephropathy patients.

Preparation, Microstructure, Mechanical Properties and Biocompatibility of Ta-Coated 3Y-TZP Ceramic Deposited by a Plasma Surface Alloying Technique.

A Ta coating has been successfully fabricated on the surface of zirconia polycrystals ceramic (3 mol% yttria, 3Y-TZP) by a plasma surface alloying technique. The X-ray diffraction (XRD) and scanning electron microscopy (SEM) results showed that a α-Ta coating with a continuous and compact surface morphology which consisted of a deposited layer with a thickness of 390 nm and a diffusion layer with a thickness of 200 nm covered the 3Y-TZP. Due to the effect of inhabitation the t→m transformation by the deposited Ta coating, the biaxial flexural strength caused by the phase transformation during hydrothermal aging is reduced e.g. p < 0.05 after 20 h and/or 100 h. In addition, the Ta coating shows non-cytotoxicity and improved proliferation ability of osteoblasts.

Establishing a rapid classification and identification method for the major triterpenoids of Alisma orientale.

INTRODUCTION: Alismatis Rhizoma (AR) has been widely used to treat various diseases. Its complex chemical composition has caused certain difficulties in the analysis of this traditional Chinese medicine. Therefore, it is necessary to establish a method for the rapid classification and identification of the chemical constituents of AR. OBJECTIVE: This article describes a method for the rapid classification and identification of major triterpenoids in AR. METHODOLOGY: The samples were analysed by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The assay was performed on a Waters ACQUITY UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 µm) with 0.1% formic acid in water (A), and acetonitrile (B) as mobile phase by gradient elution at a flow rate of 0.3 mL/min. In the positive ion mode, the fragment information was obtained and compared with the characteristic fragments and neutral losses described in the literature. Then, the rapid classification and identification of the chemical components from AR were achieved. RESULTS: Finally, 25 triterpene compounds of AR were identified. CONCLUSIONS: The method established in this study achieved the rapid classification and identification of chemical components in AR, which promotes the development of research methods to study the constituents of traditional Chinese medicine.

Systematic Investigation of the Effects of Long-Term Administration of a High-Fat Diet on Drug Transporters in the Mouse Liver, Kidney and Intestine.

BACKGROUND: Long-term intake of a high-fat diet is a crucial factor contributing to obesity, which has become a global public health problem. Progressive obesity subsequently leads to hepatic injury, renal damage and intestinal atrophy. Transporters expressed in the liver, kidney and intestine play important roles in the deposition of nutrients and drugs, but researchers have not clearly determined whether/how the expression of transporters changes after long-term administration of a High-Fat Diet (HFD). This study aims to explore the effects of the long-term administration of a HFD on the expression of drug transporters in the liver, kidney and intestine in mice and to provide useful information for medical applications in the clinic. METHODS: Male C57BL/6J mice were fed either a basal diet or HFD for 24 weeks, and oral glucose tolerance tests were performed after 3, 11 and 23 weeks. Serum was obtained to measure lipid metabolism, inflammatory mediators, renal function and hepatic function. Adipose tissues, kidney, pancreas and liver were collected for hematoxylin and eosin (H&E) staining after 4, 12 and 24 weeks. The mRNA and proteins expression of drug transporters in the liver, kidney and intestine were detected using real-time PCR and western blot, respectively. RESULTS: Compared with the control group, long-term HFD administration significantly increased the adipose index. The serum lipid levels, including Total Cholesterol (TC), Triglyceride (TG), and Low-Density Lipoprotein Cholesterol (LDL-C), as well as the levels of the inflammatory cytokines Interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) were significantly elevated in HFD-induced obese mice. H&E staining revealed pathological changes in the adipose cells, liver, kidney and pancreas from the obese group following the long-term administration of the HFD. The liver of the obese group presented increased mRNA expression of the efflux transporter Mrp2 and uptake transporter Oat2 at 24 weeks. The relative expression of Oat2 increased 4.08-fold and the protein expression of Oat2 was upregulated at 24 weeks in HFD-fed mice, while the mRNA expression of the uptake transporters Oct1, Oatp1b2 and Oatp1a4 decreased by 79%, 61% and 19%, respectively. The protein expression of Oct1 was significantly downregulated in obese mice at 12 weeks. The mRNA expression of the efflux transporter Mdr1a was significantly reduced in HFD-fed mice compared with the control group at 24 weeks. Western blot showed that the trend of protein level of Mdr1 was consistent with the mRNA expression. In the kidney, the level of the Oct2 mRNA increased 1.92- and 2.46-fold at 4 and 12 weeks in HFD-fed mice, respectively. The expression of the Oat1 and Oat3 mRNAs was markedly downregulated in the kidneys of mice with HFD-induced obesity at 4 weeks. The decrease of 72% and 21% in Mdr1a mRNA expression was observed in the obese model at 4 weeks and 12 weeks, respectively. Western blot showed that the protein levels of Mdr1 and Oat1 were consistent with the mRNA expression. The qPCR experiments showed a 2.87-fold increase in Bcrp mRNA expression at 24 weeks, and the expression of the Pept1 mRNA increased 2.84-fold in intestines of obese mice subjected to long-term administration of the HFD compared with control mice at 12 weeks. Western blot showed that the trend of protein levels of Mdr1 and Mrp2 were consistent with the mRNA expression. CONCLUSION: The expression of uptake and efflux transporters mRNAs and protein levels were altered in obese mice compared with control mice, providing scientific evidence for future medical applications in the clinic.

Comparison of Chemical Compositions, Antioxidant, and Anti-Photoaging Activities of Paeonia suffruticosa Flowers at Different Flowering Stages.

Paeonia suffruticosa is an ornamental, edible, and medicinal plant. The ethanolic extracts of P. suffruticosa bud and flower were examined for their antioxidant, anti-photoaging, and phytochemical properties prior to chemometric analysis. The results showed that the bud ethanolic extract (BEE) and the flower (the early flowering stage) ethanolic extract (FEE) had better antioxidant activities, and significantly increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and reduced the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the skin tissues. In total, 68 compounds, including 20 flavonoids, 15 phenolic derivatives, 12 terpenoids, 9 fatty acids, and 12 others were identified or tentatively identified by ultra-fast liquid chromatography quadrupole time-of-flight mass spectrometry (UFLC-Q-TOF-MS). Gallic acid, 1,2,3,4,6-O-pentagalloyl glucose, paeoniflorin, and oxypaeoniflorin were predominant compounds in the extracts. Taken together, P. suffruticosa flowers are a candidate for functional material in food and health related industries, and their optimal time to harvest is before the early flowering stage.

Codonopsis tangshen Oliv. Amelioration Effect on Diabetic Kidney Disease Rats Induced by High Fat Diet Feeding Combined with Streptozotocin.

Diabetic kidney disease (DKD) is the most serious microvascular complication during the development of diabetes with the characterizations of glomerular basement membrane thickening, mesangial expansion, and glomerular sclerosis, eventually leading to end-stage renal disease. This study aimed to investigate the melioration effect of Codonopisis tangshen Oliv. (COD) on the DKD model, which was established by unilateral nephrectomy (UN)-high fat diet feeding (HFD) combined with streptozotocin (STZ). After the DKD rats were oral treated with COD at a dose of 2.7 mg/kg for 4 consecutive weeks, the blood glucose, lipid metabolism, renal function, inflammatory mediators, and fibrosis-associated proteins were examined. In vivo, the COD administration obviously relieved the weight loss, water intake, and blood glucose; decreased the total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels; and improved the renal function by reducing the expression of serum creatinine, uric acid, and urinary protein compared with the model group. The levels of pro-inflammatory cytokines of tumor necrosis factor-α, interleukin-1ß, and IL-6 were significantly inhibited by COD. Meanwhile, the deposition of collagen fiber was markedly increased, and the protein and mRNA expressions of transforming growth factor-ß1 and α-smooth muscle actin were markedly elevated in DKD rats, but they were decreased to some extent after the COD treatment. In conclusion, COD exhibited a protective effect on the UN-HFD feeding combined with STZ-induced DKD model by improving the blood glucose and lipid metabolism, relieving the inflammatory response, and mitigating the renal fibrosis, which provided scientific evidence for its applications in clinic.

Asperuloside and Asperulosidic Acid Exert an Anti-Inflammatory Effect via Suppression of the NF-κB and MAPK Signaling Pathways in LPS-Induced RAW 264.7 Macrophages.

Hedyotis diffusa is a folk herb that is used for treating inflammation-related diseases in Asia. Previous studies have found that iridoids in H. diffusa play an important role in its anti-inflammatory activity. This study aimed to investigate the anti-inflammatory effect and potential mechanism of five iridoids (asperuloside (ASP), asperulosidic acid (ASPA), desacetyl asperulosidic acid (DAA), scandoside methyl ester (SME), and E-6-O-p-coumaroyl scandoside methyl ester (CSME)) that are presented in H. diffusa using lipopolysaccharide (LPS)-induced RAW 264.7 cells. ASP and ASPA significantly decreased the production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in parallel with the inhibition of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, and IL-6 mRNA expression in LPS-induced RAW 264.7 cells. ASP treatment suppressed the phosphorylation of the inhibitors of nuclear factor-kappaB alpha (IκB-α), p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK). The inhibitory effect of ASPA was similar to that of ASP, except for p38 phosphorylation. In summary, the anti-inflammatory effects of ASP and ASPA are related to the inhibition of inflammatory cytokines and mediators via suppression of the NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways, which provides scientific evidence for the potential application of H. diffusa.

Scandoside Exerts Anti-Inflammatory Effect Via Suppressing NF-κB and MAPK Signaling Pathways in LPS-Induced RAW 264.7 Macrophages.

The iridoids of Hedyotis diffusa Willd play an important role in the anti-inflammatory process, but the specific iridoid with anti-inflammatory effect and its mechanism has not be thoroughly studied. An iridoid compound named scandoside (SCA) was isolated from H. diffusa and its anti-inflammatory effect was investigated in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Its anti-inflammatory mechanism was confirmed by in intro experiments and molecular docking analyses. As results, SCA significantly decreased the productions of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and inhibited the levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α and IL-6 messenger RNA (mRNA) expression in LPS-induced RAW 264.7 macrophages. SCA treatment suppressed the phosphorylation of inhibitor of nuclear transcription factor kappa-B alpaha (IκB-α), p38, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). The docking data suggested that SCA had great binding abilities to COX-2, iNOS and IκB. Taken together, the results indicated that the anti-inflammatory effect of SCA is due to inhibition of pro-inflammatory cytokines and mediators via suppressing the nuclear transcription factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, which provided useful information for its application and development.

Forsythiae Fructus: A Review on its Phytochemistry, Quality Control, Pharmacology and Pharmacokinetics.

Forsythiae Fructus, as a traditional Chinese medicine, has been widely used both as a single herb and in compound prescriptions in Asia, mainly due to its heat-clearing and detoxifying effects. Modern pharmacology has proved Forsythiae Fructus possesses various therapeutic effects, both in vitro and in vivo, such as anti-inflammatory, antibacterial and antiviral activities. Up to now, three hundred and twenty-one compounds have been identified and sensitive analytical methods have been established for its quality control. Recently, the pharmacokinetics of Forsythiae Fructus and its bioactive compounds have been reported, providing valuable information for its clinical application. Therefore, this systematic review focused on the newest scientific reports on Forsythiae Fructus and extensively summarizes its phytochemistry, pharmacology, pharmacokinetics and standardization procedures, especially the difference between the two applied types-unripe Forsythiae Fructus and ripe Forsythiae Fructus-in the hope of providing a helpful reference and guide for its clinical applications and further studies.