Sepsis­induced cardiac dysfunction and pathogenetic mechanisms (Review).

Sepsis is a manifestation of the immune and inflammatory response to infection, which may lead to multi­organ failure. Health care advances have improved outcomes in critical illness, but it still remains the leading cause of death. Septic cardiomyopathy is heart dysfunction brought on by sepsis. Septic cardiomyopathy is a common consequence of sepsis and has a mortality rate of up to 70%. There is a lack of understanding of septic cardiomyopathy pathogenesis; knowledge of its pathogenesis and the identification of potential therapeutic targets may reduce the mortality rate of patients with sepsis and lead to clinical improvements. The present review aimed to summarize advances in the pathogenesis of cardiac dysfunction in sepsis, with a focus on mitochondrial dysfunction, metabolic changes and cell death modalities and pathways. The present review summarized diagnostic criteria and outlook for sepsis treatment, with the goal of identifying appropriate treatment methods for this disease.

Molecular Mechanism Pathways of Natural Compounds for the Treatment of Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, and its incidence continues to increase each year. Yet, there is still no definitive drug that can stop its development. This review focuses mainly on lipotoxicity, oxidative stress, inflammation, and intestinal flora dysbiosis to understand NAFLD's pathogenesis. In this review, we used NCBI's PubMed database for retrieval, integrating in vivo and in vitro experiments to reveal the therapeutic effects of natural compounds on NAFLD. We also reviewed the mechanisms by which the results of these experiments suggest that these compounds can protect the liver from damage by modulating inflammation, reducing oxidative stress, decreasing insulin resistance and lipid accumulation in the liver, and interacting with the intestinal microflora. The natural compounds discussed in these papers target a variety of pathways, such as the AMPK pathway and the TGF-ß pathway, and have significant therapeutic effects. This review aims to provide new possible therapeutic lead compounds and references for the development of novel medications and the clinical treatment of NAFLD. It offers fresh perspectives on the development of natural compounds in preventing and treating NAFLD.

HPLC Fingerprint Analysis of Rana chensinensis Eggs from Different Habitats and Their Antitussive Effect.

In this paper, a novel fingerprint method was established for the quality control of Rana chensinensis eggs (RE) by high-performance liquid chromatography (HPLC). Cluster analysis and principal component analysis were performed. Besides, the antitussive effect of RE was explored. The analysis was achieved on a Kromasil 100-5C18 (4.6 mm × 250 mm, 5 µm) column by gradient elution using methanol-0.1% phosphoric acid solution as the mobile phase. The influence of RE on cough latent periods and cough times of mice was investigated via an ammonia cough-inducing experiment. The validated HPLC method was precise, reproducible, and stable. The HPLC fingerprints of 10 batches of RE samples displayed 31 well-resolved common peaks in the chromatogram. Three of these peaks were identified and assigned to 1-methyl hydantoin, estradiol, and 4-cholestene-3-one. The similarities of 10 batches of samples were more than 0.95. RE from different origins could be classified into three groups via SPSS 23.0 software, suggesting RE samples from various provinces (Jilin, Liaoning, and Heilongjiang) can be well distinguished via the established method. High dose and middle dose of the RE group can significantly prolong the cough latent periods of mice (P < 0.05 or P < 0.01) and inhibit the cough times of mice (P < 0.01), indicating RE had a good antitussive effect. HPLC fingerprint combined with multicomponent determination can be an efficient and useful method for monitoring the quality of RE. This study also provided a more comprehensive strategy for the quality evaluation of RE.

Component-Effect Relationship between HPLC Fingerprints and Lipid-Lowering Activity of Buyang Huanwu Decoction.

Buyang Huanwu Decoction (BHD) has lipid-lowering and antioxidant effects. In this study, HPLC was used to establish the fingerprint of extracts from different polar parts of BHD. Through the L02 cell lipid deposition model induced by oleic acid, extracts from different polar parts of BHD were administered for treatment. Oil red O staining, TG detection, and MDA detection were used to determine lipid deposition and antioxidant activity. The component-effect relationship is established by using grey relational analysis and PLSR analysis. The results showed that the extracts from different polar parts of BHD could reduce the levels of TG and MDA. The grey relational analysis showed that the peaks that contributed greatly to the reduction of TG and MDA were peaks 3, 16, 14, 10, 1, 15, 2, and 11, respectively. Peaks 1, 4, 9, 10, 14, 16, and 17 could reduce TG and MDA through PLSR analysis. According to the results of grey relational analysis and PLSR analysis, peaks 1, 10, 14, and 16 may have good lipid-lowering and antioxidant effects. This study provides a certain preliminary basis for follow-up research on lipid-lowering drugs.

Molecular Mechanistic Pathways Targeted by Natural Compounds in the Prevention and Treatment of Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is one of the most common complications of diabetes, and its prevalence is still growing rapidly. However, the efficient therapies for this kidney disease are still limited. The pathogenesis of DKD involves glucotoxicity, lipotoxicity, inflammation, oxidative stress, and renal fibrosis. Glucotoxicity and lipotoxicity can cause oxidative stress, which can lead to inflammation and aggravate renal fibrosis. In this review, we have focused on in vitro and in vivo experiments to investigate the mechanistic pathways by which natural compounds exert their effects against the progression of DKD. The accumulated and collected data revealed that some natural compounds could regulate inflammation, oxidative stress, renal fibrosis, and activate autophagy, thereby protecting the kidney. The main pathways targeted by these reviewed compounds include the Nrf2 signaling pathway, NF-κB signaling pathway, TGF-ß signaling pathway, NLRP3 inflammasome, autophagy, glycolipid metabolism and ER stress. This review presented an updated overview of the potential benefits of these natural compounds for the prevention and treatment of DKD progression, aimed to provide new potential therapeutic lead compounds and references for the innovative drug development and clinical treatment of DKD.

Establishment and Development of a Quality Evaluation Method for Sangbaipi Decoction.

BACKGROUND: Sangbaipi decoction (SD), a traditional Chinese "Ancient Classical Prescription" consisting of eight medicinal materials, is usually used to treat asthma due to excess lung Qi and phlegm fire. OBJECTIVE: To establish a comprehensive quality evaluation method for SD. METHODS: HPLC fingerprint analysis, hierarchical cluster analysis (HCA), and principal component analysis (PCA) were applied for the quality control of SD prepared from different batches of medicinal materials. A total of 10 batches of SD samples were prepared and analyzed. RESULTS: A total of 24 common peaks and six active components (gardenoside, rutin, berberine, palmatine, baicalein, and wogonin) were identified in the HPLC fingerprint of SD. The ten batches of SD samples were divided into four groups via HCA and PCA. The HPLC fingerprint similarities of the 10 batch samples were 0.934 or higher. The precision, stability, repeatability, and other methodological indexes suggested that the developed method met the requirements for qualitative fingerprint research. CONCLUSION: The results indicated that HPLC fingerprints combined with PCA and multicomponent determination can be successfully applied to SD quality control. This study also provides a basis for a more comprehensive quality evaluation method for SD. HIGHLIGHTS: The fingerprint of SD, a TCM famous classical formula, was established by HPLC in this paper. Moreover, contents of six pharmacodynamic related components in SD were determined simultaneously in order to establish a comprehensive quality evaluation method of SD. This study can also provide a basis for raw material selection, quality evaluation, extraction process, preparation development and pharmacodynamic material basis research of SD.

Study on the Effect of Deep Eutectic Solvent Liquid Phase Microextraction on Quality Standard, Antitussive, and Expectorant of Sangbaipi Decoction.

The SD was extracted with a new green eutectic solvent, and the extraction method of TCM decoction was developed. In the quantitative analysis by HPLC, choline chloride phenol was selected as the eutectic solvent, THF was used as the extractant, and investigation of DES type, DES molar ratio, DES-to-THF ratio, vortex time, and material-to-liquid ratio was carried out. The experimental results showed that the optimal extraction method was as follows: the molar ratio of DES was 1 : 3, and the material-liquid ratio was 5 : 1200 (mL/µL). The volume ratio of DES to THF was 1200 : 800 (µL), the vortex time was 3 min, and the extraction was repeated two times. The eutectic solvent liquid phase microextraction method was adopted to optimize the extraction method of SD and reduce the complicated processing, long time, and low efficiency of traditional methods. At the same time, in the mouse ammonia water inducing cough and phenol red excretion and expectorant experiments, SD high- and medium-dose groups have a significant inhibitory effect on the frequency of antitussive in mice and both can increase the excretion of phenol red to varying degrees, indicating that SD has good cough-relieving and expectorant effect. The present study suggests a scientific basis and basis for the clinical research and quality standard formulation of SD.

Effective Extraction of Palmatine and Berberine from Coptis chinensis by Deep Eutectic Solvents-Based Ultrasound-Assisted Extraction.

The effective components of Coptis chinensis were extracted by ultrasound-assisted technology, and the contents of palmatine and berberine were used as indexes by using Coptis chinensis as raw material and eutectic solvent as extractant. In addition, the effects of hydrogen bond donor type, molar ratio of hydrogen bond donor to acceptor, material-liquid ratio, water content of eutectic solvent system, sonication time, power, and ultrasonic temperature on the extraction rate of palmatine and berberine were studied. The optimum extraction technology of palmatine and berberine from Coptis chinensis was determined by single-factor experiment and response surface optimization test. As a result, it showed that the eutectic solvent system was constructed with choline chloride as hydrogen bond acceptor and phenol as hydrogen bond donor, with a molar ratio of 1 : 3. In addition, water content of the eutectic solvent system was 30%, ratio of material to liquid was 30 g/mL, ultrasonic time was 30 min, ultrasonic power was 200 W, and ultrasonic temperature was 60°C. At this time, the contents of palmatine and berberine in Coptis chinensis were 16.7145 mg/g and 57.4013 mg/g, respectively, which were predicted to be the same as the value, and the extraction effect was better than that of traditional extraction solvent method.

Application of a new validated HPLC-DAD method for simultaneous determination of ten active components in Xiedu San.

In this research, a sensitive high-performance liquid chromatography-diode array detector (HPLC-DAD) method was established and validated for simultaneous detection of ten active constituents (gallic acid, catechin, berberine, palmatine, baicalin, baicalein, wogonin, rhein, emodin and chrysophanol) in Xiedu San, a traditional Chinese medicine compound preparation with effects of clearing away heat and toxic materials. The analysis was achieved on Agilent ZORBAX SB-C18 column (5µm, 250mm×4.6mm) with the temperature of 30°C. Gradient elution was applied using methanol (A)-0.1% phosphoric acid solution (B) as mobile phase at the flow rate of 1.0mL• min-1. The determination was performed at the wavelength of 225, 245, 278 and 348 nm along with the sample volume of 5µL. The tested constituents demonstrated good linear relationships within their respective determination ranges (r>0.9995). Average recoveries varied from 99.97% to 101.12% with RSDs of 0.71% to 1.92%. The contents of tested constituents ranged from 0.970 to 24.602 mg•g-1. The developed method was proved to be simple, accurate and sensitive, which can provide a quantitative analysis method for the quality evaluation and quality control of Xiedu San.

Simultaneous Determination of Eight Components in Leonuri Herba from Different Habitats by HPLC-DAD.

A HPLC-DAD method was established for the simultaneous determination of eight components in Leonuri Herba from different habitats, as well as providing methodological reference for quality control of Leonuri Herba. In this study, absolute ethanol extracts of the medicinal material were considered as the sample solutions to be analyzed. Agilent ZORBAX SB-C18 column (250 mm × 4.6 mm, 5 µm) was used for determination maintained at the temperature of 30°C. Gradient elution was performed with a mobile phase of methanol (B)-0.1% phosphoric acid solution (A) at the flow rate of 1.0 mL·min-1. The analysis was carried out at the wavelength of 225, 280 and 320 nm. The measured eight components showed good linear relationships within their own concentration range. Average recoveries ranged from 98.83 to 100.36% with RSDs of 1.14~1.97%. The proposed method was found to be simple, accurate and reproducible, which provided an effective quantitative analytical method for quality control of Leonuri Herba from different habitats.

Analysis of Antioxidant Capacity of Chromones in Saposhnikoviae Radix Obtained by Ultrasonic-Assisted Deep Eutectic Solvents Extraction.

In this paper, ultrasonic-assisted deep eutectic solvent (DES) extraction was applied to the acquisition of chromones (cimicifugin, prim-o-glucosylcimifugin, and 5-o-methylvisamminoside) from Saposhnikoviae radix (SR). The extraction effects of 11 prepared DESs were screened taking contents of chromones as indexes. Furthermore, the optimum extraction conditions were confirmed using a single-factor test and response surface optimization test. Scavenging activities of DPPH anion and ABTS cation radicals of different SR extracts (DES, methanol, and ethanol) were studied. The analysis results of best extraction conditions optimized by Design-Expert software were as follows: extraction time (40 min), extraction temperature (60°C), and the solid/liquid ratio (32 mL/g). Scavenging rates of the DES extract for DPPH anion radical and ABTS cation radical were found to be 75.31% and 65.71%, which were higher than those of methanol and ethanol extracts. In conclusion, the developed extraction method can be regarded as a safe, green, and more effective approach for the extraction of chromones in SR.

Antitussive and Anti-inflammatory Dual-active Agents Developed from Natural Product Lead Compound 1-Methylhydantoin.

Natural products play an important role in drug discovery. This work employed a natural product 1-methylhydantoin as the lead compound to develop novel dual-active drugs. 1-Methylhydantoin was isolated from Oviductus Ranae, which is a traditional Chinese medicine that has been used for tussive and inflammation treatment for a long time. An in silico study screened the more active 1-methylhydantoin derivatives. Antitussive assessment indicated that the newly synthesized agent had similar bioactivity with the natural product. An anti-inflammatory model used xylene induced ear edema model. At the same dosage (100 mg/Kg), the newly prepared agent had an inhibition rate 53.18% which was much higher than that of the lead compound (22.69%). The results might be ascribed to the cyclooxygenases-1 (COX-1) and cyclooxygenases-2 (COX-2) selectivity, and the fitness of the compound, and the binding pocket. The anti-particulate matter (PM 2.5) acute pneumonia was evaluated through an in vivo model constructed by nasal instillation with PM 2.5 suspension. The results of the above models suggested that this novel agent had remarkable antitussive, anti-inflammatory, and anti-PM 2.5 acute pneumonia activities.

Simultaneous Determination of Six Active Components in Danggui Kushen Pills via Quantitative Analysis of Multicomponents by Single Marker.

In this paper, a valid evaluation method for the quality control of Danggui Kushen pills (DKP) has been established based on quantitative analysis of multicomponents by single marker (QAMS). Gallic acid, matrine, oxymatrine, catechin, ferulic acid, and rutin were selected as the indexes for quality evaluation of DKP. The analysis was achieved on an Agilent ZORBAX SB-C18 column (250 mm × 4.6 mm, 5 µm) via gradient elution. Gallic acid was used as internal standard to determine the relative correction factors (RCF) between gallic acid and other five constituents in DKP. The contents of those components were calculated at the same time. The accuracy of QAMS method was verified by comparing the contents of six components calculated by external standard (ES) method with those of the QAMS method. It turned out that there was no significant difference between the quantitative results of QAMS method and external standard method. The proposed QAMS method was proved to be accurate and feasible according to methodological experiments, which provided an accurate, efficient, and economical approach for quality evaluation of DKP.