The effect of respiratory muscle training on children and adolescents with cystic fibrosis: a systematic review and meta-analysis.

BACKGROUND: Cystic fibrosis is a chronic genetic disease that can affect the function of the respiratory system. Previous reviews of the effects of respiratory muscle training in people with cystic fibrosis are uncertain and do not consider the effect of age on disease progression. This systematic review aims to determine the effectiveness of respiratory muscle training in the clinical outcomes of children and adolescents with cystic fibrosis. METHODS: Up to July 2023, electronic databases and clinical trial registries were searched. Controlled clinical trials comparing respiratory muscle training with sham intervention or no intervention in children and adolescents with cystic fibrosis. The primary outcomes were respiratory muscle strength, respiratory muscle endurance, lung function, and cough. Secondary outcomes included exercise capacity, quality of life and adverse events. Two review authors independently extracted data and assessed study quality using the Cochrane Risk of Bias Tool 2. The certainty of the evidence was assessed according to the GRADE approach. Meta-analyses where possible; otherwise, take a qualitative approach. RESULTS: Six studies with a total of 151 participants met the inclusion criteria for this review. Two of the six included studies were published in abstract form only, limiting the available information. Four studies were parallel studies and two were cross-over designs. There were significant differences in the methods and quality of the methodology included in the studies. The pooled data showed no difference in respiratory muscle strength, lung function, and exercise capacity between the treatment and control groups. However, subgroup analyses suggest that inspiratory muscle training is beneficial in increasing maximal inspiratory pressure, and qualitative analyses suggest that respiratory muscle training may benefit respiratory muscle endurance without any adverse effects. CONCLUSIONS: This systematic review and meta-analysis indicate that although the level of evidence indicating the benefits of respiratory muscle training is low, its clinical significance suggests that we further study the methodological quality to determine the effectiveness of training. TRIAL REGISTRATION: The protocol for this review was recorded in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42023441829.

Composition analysis of Compound Shenhua Tablet, a seven-herb Chinese medicine for IgA nephropathy: evaluation of analyte-capacity of the assays.

Compound Shenhua Tablet, a medicine comprising seven herbs, is employed in treating IgA nephropathy. This study aimed to meticulously analyze its chemical composition. Based on a list of candidate compounds, identified through extensive literature review pertinent to the tablet's herbal components, the composition analysis entailed the systematic identification, characterization, and quantification of the constituents. The analyte-capacity of LC/ESI-MS-based and GC/EI-MS-based assays was evaluated. The identified and characterized constituents were quantified to determine their content levels and were ranked based on the constituents' daily doses. A total of 283 constituents, classified into 12 distinct categories, were identified and characterized in the Compound Shenhua Tablet. These constituents exhibited content levels of 1-10 982 µg·g-1, with daily doses of 0.01-395 µmol·d-1. The predominant constituents, with daily doses of ≥ 10 µmol·d-1, include nine organic acids (citric acid, quinic acid, chlorogenic acid, cryptochlorogenic acid, gallic acid, neochlorogenic acid, isochlorogenic acid C, isochlorogenic acid B, and linoleic acid), five iridoids (specnuezhenide, nuezhenoside G13, nuezhenidic acid, secoxyloganin, and secologanoside), two monoterpene glycosides (paeoniflorin and albiflorin), a sesquiterpenoid (curzerenone), a triterpenoid (oleanolic acid), and a phenylethanoid (salidroside). Additionally, there were 83, 126, and 55 constituents detected in the medicine with daily doses of 1-10, 0.1-1, and 0.01-0.1 µmol·d-1, respectively. The combination of the LC/ESI-MS-based and GC/EI-MS-based assays demonstrated a complementary relationship in their analyte-capacity for detecting the constituents present in the medicine. This comprehensive composition analysis establishes a solid foundation for further pharmacological research on Compound Shenhua Tablet and facilitates the quality evaluation of this complex herbal medicine.

Si-Ni-San Reduces Hepatic Lipid Deposition in Rats with Metabolic Associated Fatty Liver Disease by AMPK/SIRT1 Pathway.

Background: Metabolic associated fatty liver disease (MAFLD) is a chronic disease characterized by excessive lipid deposition in the liver without alcohol or other clear liver-damaging factors. AMP-activated protein kinase (AMPK)/silencing information regulator (SIRT)1 signaling pathway plays an important role in MAFLD development. Si-Ni-San (SNS), a traditional Chinese medicine, has shown reducing hepatic lipid deposition in MAFLD rats, however, the underlying mechanisms of SNS are barely understood. Purpose: The aim of this research was to investigate the mechanisms of SNS in reducing hepatic lipid deposition in MAFLD rats by regulating AMPK/SIRT1 signaling pathways. Methods: The components of SNS were determined by high performance liquid chromatography with mass spectrometry (HPLC-MS) analysis. MAFLD rats were induced by high-fat and high-cholesterol diet (HFHCD), and treated by SNS. SNS-containing serum and Compound C (AMPK inhibitor) were used to treat palmitic acid (PA)-induced HepG2 cells. To elucidate the potential mechanism, lipid synthesis-related proteins (SREBP-1c and FAS), fatty acid oxidation (PPARα and CPT-1), and AMPK/SIRT1 signaling pathway (p-AMPK and SIRT1) were assessed by Western blot. Results: SNS improved serum lipid levels, liver function and reduced hepatic lipid deposition in MAFLD rats. SNS-containing serum reduced lipid deposition in PA-induced HepG2 cells. SNS could up-regulate protein expressions of PPARα, CPT-1, p-AMPK and SIRT1, and down-regulate protein expressions of SREBP-1c and FAS. Similar effects of SNS-containing serum were observed in PA-induced HepG2 cells. Meanwhile, Compound C weakened the therapeutic effects of SNS-containing serum on lipid deposition. Conclusion: SNS could reduce hepatic lipid deposition by inhibiting lipid synthesis and promoting fatty acid oxidation, which might be related with activating the AMPK/SIRT1 signaling pathway. This study could provide a theoretical basis for the clinical use of SNS to treat MAFLD.

Novel assays for quality evaluation of XueBiJing: Quality variability of a Chinese herbal injection for sepsis management.

XueBiJing is an intravenous five-herb injection used to treat sepsis in China. The study aimed to develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS)- or liquid chromatography-ultraviolet (LC-UV)-based assay for quality evaluation of XueBiJing. Assay development involved identifying marker constituents to make the assay therapeutically relevant and building a reliable one-point calibrator for monitoring the various analytes in parallel. Nine marker constituents from the five herbs were selected based on XueBiJing's chemical composition, pharmacokinetics, and pharmacodynamics. A selectivity test (for "similarity of response") was developed to identify and minimize interference by non-target constituents. Then, an intercept test was developed to fulfill "linearity through zero" for each analyte (absolute ratio of intercept to C response, <2%). Using the newly developed assays, we analyzed samples from 33 batches of XueBiJing, manufactured over three years, and found small batch-to-batch variability in contents of the marker constituents (4.1%-14.8%), except for senkyunolide I (26.5%).

Substrates, Plants, and Their Combinations for Water Purification of Urban Household Aquaponics Systems.

To make full use of urban household balcony space, an urban aquaponics system for balconies was constructed to investigate the purification effects of four different substrates (volcanic stone, ceramic pellets, ceramic rings, and nanorods) and six plants (mung bean sprouts, hollow cabbage, water celery, lettuce, leek, and water chestnut) on fish culture wastewater. Through the determination of contaminants such as nitrogen and phosphorus and through the use of 16SrDNA sequencing technology, the substrate material and plant combinations with the best purification effects were screened. The results show that volcanic stone and nanorods have strong purification capacities. Compared to the other substrate types, there were more unique bacterial species on the surface of volcanic stone, among which amoeba species were the most dominant (92.42%). Among the six tested plant species, mung bean sprouts had the highest contribution to nitrogen uptake (94.96%), and water chestnut had the highest contribution to phosphorus uptake at 12.07%. Finally, the combination of nanorods and water celery was the best at purifying the wastewater. This study provides a theoretical basis and new ideas for the construction of urban aquaponics systems on balconies, which will help to achieve green farming and the efficient utilization of water resources.

Novel assays for quality evaluation of XueBiJing:Quality variability of a Chinese herbal injection for sepsis management / 药物分析学报

XueBiJing is an intravenous five-herb injection used to treat sepsis in China.The study aimed to develop a liquid chromatography-tandem mass spectrometry(LC-MS/MS)-or liquid chromatography-ultraviolet(LC-UV)-based assay for quality evaluation of XueBiJing.Assay development involved identifying marker constituents to make the assay therapeutically relevant and building a reliable one-point cali-brator for monitoring the various analytes in parallel.Nine marker constituents from the five herbs were selected based on XueBiJing's chemical composition,pharmacokinetics,and pharmacodynamics.A selectivity test(for"similarity of response")was developed to identify and minimize interference by non-target constituents.Then,an intercept test was developed to fulfill"linearity through zero"for each analyte(absolute ratio of intercept to C response,＜2％).Using the newly developed assays,we analyzed samples from 33 batches of XueBiJing,manufactured over three years,and found small batch-to-batch variability in contents of the marker constituents(4.1％-14.8％),except for senkyunolide I(26.5％).

Smad3-Targeted Therapy Protects against Cisplatin-Induced AKI by Attenuating Programmed Cell Death and Inflammation via a NOX4-Dependent Mechanism.

BACKGROUND: Transforming growth factor-ß (TGF-ß)/Smad signaling is the central mediator in renal fibrosis, yet its functional role in acute kidney injury (AKI) is not fully understood. Recent evidence showed that TGF-ß/Smad3 may be involved in the pathogenesis of AKI, but its functional role and mechanism of action in cisplatin-induced AKI are unclear. OBJECTIVES: Demonstrating that Smad3 may play certain roles in cisplatin nephropathy due to its potential effect on programmed cell death and inflammation. METHODS: Here, we established a cisplatin-induced AKI mouse model with Smad3 knockout mice and created stable in vitro models with Smad3 knockdown tubular epithelial cells. In addition, we tested the potential of Smad3-targeted therapy using 2 in vivo protocols - lentivirus-mediated Smad3 silencing in vivo and use of naringenin, a monomer used in traditional Chinese medicine and a natural inhibitor of Smad3. RESULTS: Disruption of Smad3 attenuated cisplatin-induced kidney injury, inflammation, and NADPH oxidase 4-dependent oxidative stress. We found that Smad3-targeted therapy protected against loss of renal function and alleviated apoptosis, RIPK-mediated necroptosis, renal inflammation, and oxidative stress in cisplatin nephropathy. CONCLUSIONS: These findings show that Smad3 promotes cisplatin-induced AKI and Smad3-targeted therapy protects against this pathological process. These findings have substantial clinical relevance, as they suggest a therapeutic target for AKI.

Malayoside, a cardenolide glycoside extracted from Antiaris toxicaria Lesch, induces apoptosis in human non-small lung cancer cells via MAPK-Nur77 signaling pathway.

Lung cancer is the leading cause of cancer deaths in the world. Non-small cell lung cancer (NSCLC), with poor prognosis and resistance to chemoradiotherapy, is the most common histological type of lung cancer. Therefore, it is necessary to develop new and more effective treatment strategy for NSCLC. Nur77, an orphan member of the nuclear receptor superfamily, induces apoptosis in cancer cells including NSCLC cells, by high expression and translocation to mitochondria. Small molecules trigger expression and mitochondrial localization of Nur77 may be an ideal anti-cancer drug candidate. Here, we report malayoside, a cardiac glycoside in the extract of Antiaris toxicaria Lesch., had different sensitivities to NSCLC cells. Malayoside induced apoptosis in NCI-H460 cells. Meanwhile, malayoside induced Nur77 expression and mitochondrial localization, and its induction of apoptosis was Nur77-dependent. To investigate the molecular mechanism of malayoside inducing Nur77 and apoptosis, we found that malayoside activated MAPK signaling pathway, including both ERK and p38 phosphorylation. The suppression of MAPK signaling activation inhibited the expression of Nur77 and apoptosis induced by malayoside. Our studies in nude mice showed that malayside potently inhibited the growth of tumor cells in vivo. Furthermore, the anti-cancer effect of malayosidwas in vivo was also related to the elevated expression of Nur77, p-ERK, and p-p38 proteins. Our results suggest that malayoside possesses an anti-NSCLC activity in vitro and in vivo mainly via activation of MAPK-Nur77 signaling pathway, indicating that malayoside is a promising chemotherapeutic candidate for NSCLC.

Deciphering the Formulation Secret Underlying Chinese Huo-Clearing Herbal Drink.

Herbal teas or herbal drinks are traditional beverages that are prevalent in many cultures around the world. In Traditional Chinese Medicine, an herbal drink infused with different types of medicinal plants is believed to reduce the 'Shang Huo', or excessive body heat, a status of sub-optimal health. Although it is widely accepted and has a very large market, the underlying science for herbal drinks remains elusive. By studying a group of herbs for drinks, including 'Gan' (Glycyrrhiza uralensis Fisch. Ex DC.), 'Ju' (Dendranthema morifolium (Ramat.) Tzvelev), 'Bu' (Microcos paniculata L.), 'Jin' (Lonicera japonica Thunb.), 'Xia' (Prunella vulgaris L.), and 'Ji' (Plumeria rubra L.), the long-term jargon is connected with the inflammation of modern immunology through a few pro-inflammatory markers. In vitro studies have indicated that cellular inflammation is lowered by Ju and Jin either individually or synergistically with Gan. Among all herbs, only Gan detoxicated cellular toxicity of Bu in a dose dependent manner. The synergistic formulation of Ju and Gan, or Jin and Gan, in a reduction of Shang Huo, was tested in vivo. Both combinations exhibited a lower percentage of neutrophils, monocytes, and CD4+/CD8+ ratio in the blood, as well as inflammatory cytokines. Furthermore, body weight in the combinatory groups was more stable than treatments using single herbs. The combination of old traditional oriental methods with Western science logistics, has resulted in the formulation of different herbs into one concoction for the use of detoxification and synergism.

Traditional Chinese medicine injection for promoting blood circulation and removing blood stasis in treating angina pectoris of coronary heart disease: A protocol for systematic review and network meta-analysis.

BACKGROUND: As a common cardiovascular disease, the morbidity and mortality of coronary heart disease (CHD) are increasing year by year. In recent years, many RCTs have proved that compared with conventional therapy, the combination of TCMIs for promoting blood circulation and removing blood stasis can improve clinical efficacy. However, there is still a lack of direct comparative study between different kinds of TCMIs. Therefore, based on the NMA, this study compares the curative effects of various TCMIs for promoting blood circulation and removing blood stasis in treating CHD to provide a reference for clinical medication. METHODS: We will search PubMed, Web of Science, Embase, The Cochrane Library, China National Knowledge Infrastructure, The Chongqing VIP Chinese Science and Technology Periodic Database, Wanfang Database, and China Biomedical Literature Database for the randomized controlled trials of Danhong injection, Xuesaitong injection, Dengzhanxixin injection, and Salvianolate injection in the treatment of CHD, and we will also manually retrieve from the following databases: Chinese Clinical Trial Register, conference papers, and unpublished studies or references. According to the pre-established inclusion and exclusion criteria, 2 researchers independently screened the literature, extracted the data, and evaluated the RCTs' quality. The primary outcome indicators are the total effective rate of improving angina pectoris symptoms and electrocardiogram improvement. Secondary indicators were angina pectoris attack frequency, angina pectoris attack time, hemorheology, and inflammatory factor level. And use Stata 16.0 software for mesh meta-analysis. Evidence will be checked using the classification of recommendation, evaluation, development, and evaluation. RESULTS: In this study, from the perspective of different kinds of TCMIs for promoting blood circulation and removing blood stasis, we will compare the curative effects of varying treatment measures and rank the curative effects. CONCLUSION: This study will evaluate the efficacy of different kinds of TCMIs for promoting blood circulation and removing blood stasis in the treatment of CHD and help clinicians improve their clinical effectiveness. UNIQUE INPLASY NUMBER: INPLASY202130103.

Regulatory effect of traditional Chinese medicine on gut microbiota in patients with atherosclerosis: A protocol for systematic review and meta-analysis.

BACKGROUND: Atherosclerosis is the pathological basis of many cardiovascular and cerebrovascular diseases, and its pathogenesis is complex. Recent studies revealed a significant role of gut microbiota in the onset and development of atherosclerosis. Traditional Chinese medicine has rich clinical experience and unique advantages in the treatment of atherosclerosis. A large number of studies have proved that traditional Chinese medicine has the functions of reducing blood lipid, regulating gut microbiota, and resisting inflammation. The aim of this systematic review is to observe the randomized controlled trial of traditional Chinese medicine in treating gut microbiota, so as to evaluate the effectiveness and safety of traditional Chinese medicine in treating atherosclerosis patients. METHODS: The English database (PubMed, Web of Science, Embase, the Cochrane Library) and Chinese database (China National Knowledge Infrastructure, the Chongqing VIP Chinese Science, and Technology Periodic Database, Wanfang Database, and China Biomedical Literature Database) will be searched up to October 2020. We will also manually search the Chinese clinical trial register, conference papers, and unpublished studies or references. Randomized control trials of traditional Chinese medicine treatment of atherosclerosis were collected comprehensively, and 2 researchers will independently screen literature, data extraction, and evaluation the quality of literature methodology. The primary outcomes are lipid metabolism and gut microbiota and their metabolites. The secondary outcomes are the change of inflammatory markers. Meta-analysis was performed by RevMan 5.3.5 software. The Grades of Recommendation, Assessment, Development, and Evaluation will be used to evaluate the outcome quality of evidence. RESULTS: This study will comprehensively review the existing evidence of traditional Chinese medicine in treating atherosclerosis from the perspective of gut microbiota. CONCLUSION: This study will provide information on the effectiveness and safety of traditional Chinese medicine in treating atherosclerosis from the perspective of gut microbiota. UNIQUE INPLASY NUMBER: INPLASY2020110056.

Polysaccharides of Scrophularia ningpoensis Hemsl.: Extraction, Antioxidant, and Anti-Inflammatory Evaluation.

The roots of Scrophularia ningpoensis Hemsl. are a famous traditional Chinese medicinal herb and are also used as health food. However, information about polysaccharides from S. ningpoensis (SNPS) is very limited. We applied the ultrasonic-assisted extraction (UAE) process to extract SNPS. The UAE conditions were optimized using single-factor experiments and response surface analysis. Under the optimized conditions of ultrasonic power of 550 W, extraction time of 26 min, and extraction temperature at 50°C, the highest yield of 13.47% ± 1.63% was obtained, which was in accordance with the predicted value of 13.71%. In comparison with traditional hot water extraction, the optimized UAE method significantly increased the extraction yield with lower extraction temperature and shorter extraction time. Furthermore, the in vitro antioxidant evaluation showed that EC50 values of SNPS were 2.43 ± 0.21, 4.40 ± 0.35, and 0.56 ± 0.062 mg/mL for 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) radical, hydroxyl free radical, and 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assay, respectively. The anti-inflammatory potential of SNPS was detected in lipopolysaccharide (LPS) induced ICR mice. Real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay showed that SNPS significantly improved LPS-stimulated inflammatory response by decreasing mRNA and protein expression of interleukin (IL)-6 and tumour necrosis factor (TNF)-α in a dose-dependent manner. In conclusion, the extraction process of SNPS established in this study is reliable, and SNPS possesses potential antioxidant and anti-inflammatory activities, which will provide a theoretical basis for guiding the clinical application of S. ningpoensis.

Four new steroids from the leaves and twigs of Dysoxylum pallens and their cytotoxic activities.

Four previously undescribed steroids, identified as (3S,7S,8S,9S,10R,13S,14S,16S,17R,20S)-7α-methoxy-ergosta-5,24(28)-dien-3ß,16ß,20-triol (1), ergosta-5,24(28)-dien-3ß,7α,16ß-triol (2), ergosta-5,25-dien-3ß,7α,16ß,20-tetrol (3) and 7α,16ß,24α-trihydroxy-varninasterol (4), as well as five known analogues (5-9), were isolated from the leaves and twigs of Dysoxylum pallens Hiern (Meliaceae). Their structures were elucidated based on extensive spectroscopic analysis such as HR-ESI-MS, 1D and 2D NMR, UV, and IR. The absolute configuration of compound 1 was determined by X-ray diffraction analysis. Selected compounds were evaluated for their cytotoxic activities. Compounds 1, 2, and 8 exhibited moderate cytotoxic activity against HL-60, Hela, and HepG2 tumor cell lines with IC50 ranged from 11.09 to 17.51 µM.

Immunomodulatory and Antioxidant Activities of a Polysaccharide from Ligustrum vicaryi L. Fruit.

Ligustrum vicaryi L. is a hybrid of Ligustrum ovalifolium Hassk. var. aureo-marginatum and Ligustrum vulgale L., belonging to the Oleaceae family. It is often used as an ornamental shrub due to its golden leaves. However, its medical value is yet to be discovered. Recently, plant polysaccharides have attracted comprehensive attention owing to their biological properties, including immunomodulatory and antioxidant activities. This study aimed to extract, purify, and characterize the polysaccharide from the Ligustrum vicaryi L. fruit and investigate its immunomodulatory and antioxidant activities. The Ligustrum vicaryi L. fruit polysaccharide (LVFP) was obtained by ultrasonic extraction, ethanol precipitation, macroporous resin separation, and dialysis bag purification. The physicochemical properties of the LVFP were elucidated using Fourier-transform infrared spectrometry, high-performance ion chromatography, and high-performance gel filtration chromatography. The results indicated that the LVFP consisted of rhamnose, arabinose, galactose, and glucose in a ratio of 1.79 : 7.55 : 4.58 : 1.54, and its molecular weight was 88,949 Da. The immunomodulatory and antioxidant activities of the LVFP were investigated using a cyclophosphamide- (Cy-) induced immunosuppressed mouse model. The results demonstrated that the LVFP significantly increased spleen and thymus indexes, enhanced the phagocytic function of neutrophils, activated B and T lymphocytes, and upregulated serum levels of IL-10 and TNF-α. Moreover, we observed that the LVFP relieved Cy-induced liver damage by increasing superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) levels. These results suggested that the LVFP has the immunomodulatory and antioxidant activities, therefore laying a foundation for the application of the LVFP in the pharmaceutical and functional food industries.

7-Hydroxycoumarin protects against cisplatin-induced acute kidney injury by inhibiting necroptosis and promoting Sox9-mediated tubular epithelial cell proliferation.

BACKGROUND: 7-Hydroxycoumarin (7-HC), also known as umbelliferon, is commonly found in Chinese herbs (e.g. Eucommiae Cortex, Prunellae Spica, Radix Angelicae Biseratae). Previous laboratory studies have indicated that 7-HC has anti-inflammatory, anti-oxidative, and anti-tumor effects. Cisplatin is a widely used chemotherapeutic agent for cancer. Nephrotoxicity is one of the limiting side effects of cisplatin use. PURPOSE: This study aimed to evaluate the renoprotective effect of 7-HC in a cisplatin-induced acute kidney injury (AKI) mouse model. METHODS: AKI was induced in male C57BL/6 mice (aged 6-8 weeks) by a single intraperitoneal injection of cisplatin at 20 mg/kg. The mice received 7-HC at 30, 60, and 90 mg/kg intraperitoneally before or after cisplatin administration. Renal function, necroptosis, and cell proliferation were measured. Mechanisms underlying the reno-protective effect of 7-HC were explored in renal tubular epithelial cells treated with or without cisplatin. RESULTS: In-vivo experiments showed that 7-HC significantly improved the loss in kidney function induced by cisplatin, as indicated by lower levels of serum creatinine and blood urea nitrogen, in AKI mice. Consistent herewith, cisplatin-induced tubular damage was alleviated by 7-HC as shown by morphological (periodic acid-Schiff staining) and kidney injury marker (KIM-1) analyses. We found that 7-HC suppressed renal necroptosis via the RIPK1/RIPK3/MLKL pathway and accelerated renal repair as evidenced by the upregulation of cyclin D1 in cisplatin-induced nephropathy. In-vitro experiments showed that knockdown of Sox9 attenuated the suppressive effect of 7-HC on KIM-1 and reversed the stimulatory effect of 7-HC on cyclin D1 expression in cisplatin-treated HK-2 cells, indicating that 7-HC may protect against AKI via a Sox9-dependent mechanism. CONCLUSION: 7-HC inhibits cisplatin-induced AKI by suppressing RIPK1/RIPK3/MLKL-mediated necroptosis and promoting Sox9-mediated tubular epithelial cell proliferation. 7-HC may serve as a preventive and therapeutic agent for AKI.

Aspidoptoids A-D: Four New Diterpenoids from Aspidopterys obcordata Vine.

Four new diterpenoids, named aspidoptoids A-D (1-4), together with two known analogues (5-6) were isolated from Aspidopterys obcordata vine. Aspidoptoids A-B (1-2) are the first examples of phenylethylene-bearing 20-nor-diterpenoids of which aspidoptoid B (2) possesses a rare 3,10-oxybridge. Their structures and absolute configuration were determined by extensive spectroscopic analyses (IR, HRESIMS, 1D and 2D NMR) and electronic circular dichroism (ECD) calculation. In addition, all the isolates were evaluated for their cytotoxic activities and inhibitory effects on the nitric oxide (NO) production.

Pharmacological Network Reveals the Active Mechanism of Qi-Replenishing, Spleen-Strengthening, Phlegm-Dispelling, and Blood-Nourishing Fufang on Coronary Heart Disease.

This study aimed to investigate the potential targets and pathways of qi-replenishing, spleen-strengthening, phlegm-dispelling, and blood-nourishing Fufang in the treatment of coronary heart disease (CHD). The composition of Fufang was identified, followed by screening of the active components using ADME. The targets of active components were predicted and screened based on the TCMSP and BATMAN databases and were cross-validated using the CTD database and DisGeNET. A functional enrichment analysis was performed using the ClueGO + CluePedia plugins and clusterProfiler in the R package. The protein-protein interaction (PPI) network was constructed using the STRING database and Cytoscape. Finally, a pharmacological network was constructed. A total of 27 overlapping targets were obtained after cross-validation. ALB, IL-6, and TNF were the hub genes in the PPI network. The pharmacological network included 59 nodes and 189 relation pairs. Among the 59 nodes, there were 2 herbal medicine nodes (Salvia miltiorrhiza and Astragalus mongholicus), 8 chemical component nodes (magnesium lithospermate B, neocryptotanshinone II, heteratisine, daphneolone, tanshinone IIA, tanshinone IIB, soyasapogenol B, and astragaloside II), 27 target protein nodes (such as ALB, TNF, IL-6, NFKB1, APOA1, APOA2, CYP1A1, and CYP1A2), and 22 pathway nodes (such as the toll-like receptor signaling pathway, IL-17 signaling pathway, and TNF signaling pathway). Therefore, we found that the genes TNF, IL-6, NFKB1, ALB, CYP1A1, CYP1A2, APOA1, and APOA2 might be important targets of the key active compounds neocryptotanshinone II and astragaloside II. These genes targeted by the key active compounds might regulate inflammation-related pathways and the level of albumin and cholesterol in CHD.

[Evaluation of key production processes of Chan Taoren formula granules based on characteristic chromatogram and D-amygdalin transfer rate].

This study aimed to establish characteristic chromatogram and content determination method for Chan Taoren formula granules,evaluate the production processes of Chan Taoren formula granules based on the correlation of characteristic chromatogram and the transfer rate of D-amygdalin,and clarify the key control points. The optimized analytical method was carried out on a Waters CORTECS C18 column(4. 6 mm×150 mm,2. 7 µm) with acetonitrile-0. 1% phosphoric acid aqueous solution as the mobile phase at a flow rate of 0. 6 m L·min-1. The detection wavelength was 207 nm,and the column temperature was 20 ℃ ． As compared with the standard decoction of Chan Taoren,there were five characteristic peaks in the decoction pieces,extracts,concentrates,spray-dried powders and formula granules,basically consistent in relative retention time and peak pattern; in addition,the transfer rate of D-amygdalin from Chan Taoren pieces to the formula granules was within the transfer rate range of standard decoction. The average transfer rate of D-amygdalin was 56.65%,72.85%,94.58% and 99.29% respectively in the extraction,concentration,spray drying and granulation processes. Therefore,the factors affecting D-amygdalin in the extraction process were further studied. The results showed that D-amygdalin was easily converted to L-amygdalin in the water extraction process,leading to a low transfer rate of D-amygdalin in this process.D-amygdalin was unstable under alkaline conditions and prone to isomerization. Both liquid to solid ratio and extraction time had significant effects on the extraction rate of D-amygdalin. In this study,the key links in the production process of Chan Taoren formula granules was clarified based on the characteristic chromatogram and the quantity transmission of D-amygdalin,which provided a theoretical basis for production and quality control.

Hesperetin derivative attenuates CCl4-induced hepatic fibrosis and inflammation by Gli-1-dependent mechanisms.

Hepatic fibrosis, a common pathological feature and leading cause of various chronic liver diseases, still lacks effective therapy. Hesperetin derivative (HD) is a derivative of Traditional Chinese Medicine monomer isolated from the fruit peel of Citrusaurantium L. (Rutaceae). In the present study, we revealed the anti-fibrotic effects of HD in CCl4-induced mouse hepatic fibrosis model and in TGF-ß1-activated LX-2 cells, in vivo and in vitro. Results showed that HD prevented CCl4-induced liver injury and histological damage. Consistently, HD inhibited the up-regulation of liver fibrogenesis markers α-SMA, Col1α1, Col3α1 and TIMP-1 in primary hepatic stellate cells (HSCs) and suppressed inflammatory responses in primary liver macrophages from hepatic fibrosis mice. Furthermore, HD promoted the apoptosis of activated HSCs, a key step in the onset of fibrosis regression. Mechanistically, the Hedgehog pathway was involved in HD-treated hepatic fibrosis, and HD specifically contributed to attenuate the aberrant expression of Glioma associated oncogene-1 (Gli-1). Interestingly, blockade of Gli-1 removed the inhibitory effect of HD on activated HSCs, indicating that Gli-1 may play a pivotal role in mediating the anti-fibrotic effect of HD in hepatic fibrosis. Collectively, our results suggest that HD may be a potential anti-fibrotic Traditional Chinese Medicine monomer for the treatment of hepatic fibrosis.