[Research progress on active ingredients of Coicis Semen].

As a common medicinal and edible resource in China, Coicis Semen has a long history of cultivation and medicinal use. Traditional Chinese medicine(TCM) clinically believes that Coicis Semen has the effect of strengthening the spleen and tonifying the lungs, clearing heat and dampness, removing pus and paralysis, and stopping diarrhea. Therefore, it is used to treat edema, foot odor, spleen deficiency, diarrhea, and other symptoms. The above effects are closely related to the active ingredients of Coicis Semen, such as esters, fatty acids, polysaccharides, proteins, as well as phenolic acids, sterols, flavonoids, lactams, triterpenes, alkaloids, and adenosine. Modern research has found that Coicis Semen also has anti-cancer, anti-inflammatory, antioxidant, hypoglycemic, and hypotensive effects and other pharmacological activities, and it can improve immunity and regulate lipid metabolism. Coicis Semen is widely distributed in China, mainly produced in Guizhou, Yunnan, Fujian, Sichuan, and other places, and the quality of Coicis Semen from different origins varies. From ancient times to the present, Coicis Semen processing methods have experienced the process from simple to complex, and the types of auxiliary materials are more extensive, such as soil, bran, and river sand. These processing methods have been inherited from generation to generation. Nowadays, the commonly used methods are bran-fried, stir-fried, sand-fried, etc. In this paper, by reviewing the relevant literature in China and abroad in recent years, the main active ingredients and related pharmacological effects of Coicis Semen are sorted out, and the effects of different origins and processing methods on the chemical composition of Coicis Semen are summarized, with a view to providing references for the comprehensive development and utilization of Coicis Semen and the further study of its mechanism of action.

Vasoprotective Effects of Hyperoside against Cerebral Ischemia/Reperfusion Injury in Rats: Activation of Large-Conductance Ca2+-Activated K+ Channels.

Hyperoside (Hyp), a kind of Chinese herbal medicine, exerts multiple therapeutic effects on many diseases. However, the role and mechanisms of Hyp in vascular pathophysiology in ischemic stroke need to be further established. The study aimed to investigate the role of (large-conductance Ca2+-activated K+) BK channels on the vasoprotection of Hyp against cerebral ischemia and reperfusion (I/R) injury in rats. The concentration gradient of Hyp was pretreated in both the middle cerebral artery occlusion and reperfusion model and oxygen-glucose deprivation/reoxygenation (OGD/R) model of primary vascular smooth muscle cells (VSMCs) in rats. A series of indicators were detected, including neurological deficit score, infarct volume, malondialdehyde (MDA), superoxide dismutase (SOD), cerebral blood flow (CBF), cell viability, membrane potential, and BK channels α- and ß1-subunits expression. The results showed that Hyp significantly reduced infarct volume and ameliorated neurological dysfunction in I/R-injured rats. Besides, the effects of I/R-induced reduction of BK channels α- and ß1-subunits expression were significantly reversed by Hyp in endothelial-denudated cerebral basilar arteries. Furthermore, the protective effect against I/R-induced increases of MDA and reduction of SOD as well as CBF induced by Hyp was significantly reversed by iberiotoxin (IbTX). In OGD/R-injured VSMCs, downregulated cellular viability and BK channels ß1-subunits expression were remarkably reversed by Hyp. However, neither OGD/R nor Hyp affected BK channels α-subunits expression, and Hyp failed to induced hyperpolarization of VSMCs. Moreover, the protective effect against OGD/R-induced reduction of cell viability and SOD level and increases of MDA production induced by Hyp was significantly reversed by IbTX in VSMCs. The study indicates that Hyp has the therapeutic potential to improve vascular outcomes, and the mechanism is associated with suppressing oxidative stress and improving CBF through upregulating BK channels.

Effects of a Macroporous Resin Extract of Dendrobium officinale Leaves in Rats with Hyperuricemia Induced by Anthropomorphic Unhealthy Lifestyle.

Aim: Hyperuricemia (HUA) has received increased attention in the last few decades due to its global prevalence. Our previous study found that administration of a macroporous resin extract of Dendrobium officinale leaves (DoMRE) to rats with HUA that was induced by exposure to potassium oxazine combined with fructose and a high-purine diet led to a significant reduction in serum uric acid (SUA) levels. The aim of this study was to explore the effects of DoMRE on hyperuricemia induced by anthropomorphic unhealthy lifestyle and to elucidate its possible mechanisms of action. Methods: Dosages (5.0 and 10.0 g/kg/day) of DoMRE were administered to rats daily after induction of HUA by anthropomorphic unhealthy lifestyle for 12 weeks. The levels of UA in the serum, urine, and feces; the levels of creatinine (Cr) in the serum and urine; and the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum were all measured using an automatic biochemical analyzer. The activities of xanthine oxidase (XOD) and adenosine deaminase (ADA) in the serum, liver, and intestine tissue supernatant were measured using appropriate kits for each biological target. The expressions levels of UA transporters (ABCG2 and GLUT9), tight junction (TJ) proteins (ZO-1 and occludin), and inflammatory factors (IL-6, IL-8, and TNF-α) in the intestine were assayed by immunohistochemical (IHC) staining. Hematoxylin and eosin (H&E) staining was used to assess histological changes in the renal and intestinal tissues. Results: DoMRE treatment significantly reduced SUA levels and concomitantly increased fecal UA (FUA) levels and the fractional excretion of UA (FEUA) in HUA rats. Furthermore, DoMRE significantly reduced both the XOD activity in the serum, liver, and intestine and the ADA activity in the liver and intestine. DoMRE also effectively regulated the expression of GLUT9 and ABCG2 in the intestine, and it significantly upregulated the expression of the intestinal TJ proteins ZO-1 and occludin. Therefore, DoMRE reduced the damage to the intestinal barrier function caused by the increased production of inflammatory factors due to HUA to ensure normal intestinal UA excretion. Conclusion: DoMRE demonstrated anti-HUA effects in the HUA rat model induced by an anthropomorphic unhealthy lifestyle, and the molecular mechanism appeared to involve the regulation of urate transport-related transporters (ABCG2 and GLUT9) in the intestine, protection of the intestinal barrier function to promote UA excretion, and inhibition of XOD and ADA activity in the liver and intestine to inhibit UA production in the HUA-induced rats.

Chemical and metabolic profiling of Codonopsis Radix extract with an integrated strategy using ultra-high-performance liquid chromatography coupled with mass spectrometry.

Codonopsis radix was commonly used as food materials or herbal medicines in many countries. However, the comprehensive analysis of chemical constituents, and in vivo xenobiotics of Codonopsis radix remain unclear. In the present study, an integrated strategy with feature-based molecular networking using ultra-high-performance liquid chromatography coupled with mass spectrometry was established to systematically screen the chemical constituents and the in vivo xenobiotics of Codonopsis radix. A step-by-step manner based on a composition database, visual structure classification, discriminant ions, and metabolite software prediction was proposed to overcome the complexities due to the similar structure of chemical constituents and metabolites of Codonopsis radix. As a result, 103 compounds were tentatively characterized, 20 of which were identified by reference standards. Besides, a total of 50 xenobiotics were detected in vivo, including 26 prototypes and 24 metabolites, while the metabolic features of the pyrrolidine alkaloids were elucidated for the first time. The metabolism reactions of pyrrolidine alkaloids and sesquiterpene lactones included oxidation, methylation, hydration, hydrogenation, demethylation, glucuronidation, and sulfation. This study provided a generally applicable approach to the comprehensive investigation of the chemical and metabolic profile of traditional Chinese medicine and offered reasonable guidelines for further screening of quality control indicators and pharmacodynamics mechanism of Codonopsis radix.

Simultaneous determination of multiple constituents of Qi-Lin pill by UPLC-MS/MS: Applications to pharmacokinetics and testicular tissue distribution in rats.

Qi-Lin pill (QLP) is an effective traditional Chinese medicine prescription (TCMP) that has been used for the treatment of the oligoasthenozoospermia in China. Recently, some articles described the pharmacological effects of QLP and multiple ingredients in QLP contribute to its effects. However, the pharmacokinetic and target tissue distribution data of QLP are still unknown. In the present study, according to the Bioanalytical Method Validation Guidance of FDA, a sensitive and selective UPLC-MS/MS method was developed and validated for simultaneous determination of multiple constituents in rat plasma and testicular tissue, including morusimic acid A, codonopyrridium B, magnoflorine, emodin, 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside (THSG), ecliptasaponin A, paeoniflorin, albiflorin, gallic acid, danshensu, salvianolic acid A, catechin, isosinensetin, nobiletin, formononetin, calycosin, icariside II, icariin and epimedin C. For 19 analytes, the LLOQs reached 0.01-4 ng/mL. And all calibration curves showed favorable linearity (r ≥ 0.9903) in linear ranges. The intra-day and inter-day precision (relative standard deviation) for all analytes was less than 14.92 %, and the accuracies (as relative error) were in the range of - 6.44 % to 6.22 %. Extraction recoveries and matrix effects of analytes and IS were acceptable. All analytes were stable during the assay and storage in plasma samples. The method was successfully applied for the pharmacokinetics and testis distribution of multiple chemical constituents in QLP after a single oral dose. As a result, high exposure of danshensu, gallic acid, paeoniflorin and albiflorin were observed in rat plasma and testicular tissue. Among the flavonoids, isosinensetin and nobiletin had high exposure in testicular tissue. Moreover, alleviation of progesterone reduction was evaluated in H2O2-induced R2C leydig cells, and danshensu, gallic acid, paeoniflorin, albiflorin and nobiletin showed potent activity. Therefore, these five components were considered to be the effective components of QLP due to their relatively high exposure in vivo and biological activity. This finding also provided relevant information on action mechanism of QLP in the treatment of oligoasthenozoospermia.

Nitidine chloride induces cardiac hypertrophy in mice by targeting autophagy-related 4B cysteine peptidase.

Nitidine chloride (NC) is a standard active component from the traditional Chinese medicine Zanthoxylum nitidum (Roxb.) DC. (ZN). NC has shown a variety of pharmacological activities including anti-tumor activity. As a number of anti-tumor drugs cause cardiotoxicity, herein we investigated whether NC exerted a cardiotoxic effect and the underlying mechanism. Aqueous extract of ZN (ZNE) was intraperitoneally injected into rats, while NC was injected into beagles and mice once daily for 4 weeks. Cardiac function was assessed using echocardiography. We showed that both ZNE administered in rats and NC administered in mice induced dose-dependent cardiac hypertrophy and dysfunction, whereas administration of NC at the middle and high dose caused death in Beagles. Consistently, we observed a reduction of cardiac autophagy levels in NC-treated mice and neonatal mouse cardiomyocytes. Furthermore, we demonstrated that autophagy-related 4B cysteine peptidase (ATG4B) may be a potential target of NC, since overexpression of ATG4B reversed the cardiac hypertrophy and reduced autophagy levels observed in NC-treated mice. We conclude that NC induces cardiac hypertrophy via ATG4B-mediated downregulation of autophagy in mice. Thus, this study provides guidance for the safe clinical application of ZN and the use of NC as an anti-tumor drug.

Untargeted metabolomics analysis of serum and follicular fluid samples from women with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder with well-established metabolic abnormalities. In the present study, untargeted metabolomics technology was applied to analyze the serum and follicular fluid samples from women with polycystic ovary syndrome and healthy controls using 1H nuclear magnetic resonance (NMR). METHODS: Seventy samples for PCOS analysis were collected in hospital of Shandong University of Traditional Chinese Medicine (Jinan, China), NMR was used as analytical technology and multivariate analysis was applied to analyze metabolomics difference in PCOS and healthy controls. RESULTS: Significant metabolic differences were found in both serum and follicular fluid samples with orthogonal partial least-squares discriminant analysis (OPLS-DA). Three discriminated metabolites (1-Methylhistidine, threonine and Citrate) in both serum and follicular fluid were altered in PCOS patients. Abnormal energy metabolism, lipid metabolism and amino acid metabolism were detected in PCOS patients. Furthermore, more significantly changed amino acids were discovered in follicular fluid samples. CONCLUSIONS: Our findings would provide a resource for further investigations on metabolic disturbance in PCOS patients.

Nitrative inactivation of thioredoxin-1 loses its protective effect in bleomycin-induced pulmonary fibrosis.

Pulmonary fibrosis is common in the development of inflammatory lung diseases with no effective clinical drug treatment currently. As an essential redox enzyme, thioredoxin (Trx) has been reported to be involved in pulmonary fibrosis, but the mechanism is to be revealed. Therefore, in bleomycin-indued pulmonary fibrosis model in C57 mice, Trx activity and nitrated Trx were examined.,p38-MAPK apoptosis pathway was determined in lung tissues. Additionally, before BLM administration, C57/BL6 mice were treated with aminoguanidine (AG, a peroxynitrite scavenger), recombinant human Trx-1 (rhTrx-1), or SIN-1 (a peroxynitrite donor) nitrated Trx-1 (N-Trx-1). In bleomycin (BLM)-induced pulmonary fibrosis model in C57/BL6 mice, we observed that nitrated Trx increased, while its activity decreased, with the increase of alveolar epithelial cells (AECs)apoptosis by p38-MAPK pathway. We demonstrated that AG or rhTrx-1, but not N-Trx-1 significantly reduced pulmonary fibrosis. Taken together, the results above revealed that blockade of Trx-1 nitration, or supplementation of exogenous rhTrx-1, might represent novel therapies to attenuate pulmonary fibrosis in idiopathic pulmonary fibrosis patients.

[Medication law and mechanism of traditional Chinese medicine in prevention and treatment of epidemic diseases: based on traditional Chinese medicine theory of cold pestilence].

Epidemic diseases have caused huge harm to the society. Traditional Chinese medicine(TCM) has made great contributions to the prevention and treatment of them. It is of great reference value for fighting diseases and developing drugs to explore the medication law and mechanism of TCM under TCM theory. In this study, the relationship between the TCM theory of cold pestilence and modern epidemic diseases was investigated. Particularly, the the relationship of coronavirus disease 2019(COVID-19), severe acute respiratory syndrome(SARS), and influenza A(H1 N1) with the cold pestilence was identified and analyzed. The roles of TCM theory of cold pestilence in preventing and treating modern epidemic diseases were discussed. Then, through data mining and textual research, prescriptions for the treatment of cold pestilence were collected from major databases and relevant ancient books, and their medication laws were examined through analysis of high-frequency medicinals and medicinal pairs, association rules analysis, and cluster analysis. For example, the prescriptions with high confidence levels were identified: "Glycyrrhizae Radix et Rhizoma-Bupleuri Radix-Paeoniae Radix Alba" "Glycyrrhizae Radix et Rhizoma-Pinelliae Rhizoma-Bupleuri Radix", and TCM treatment methods with them were analyzed by clustering analysis to yield the medicinal combinations: "Zingiberis Rhizoma-Aconiti Lateralis Radix Praeparata-Ginseng Radix et Rhizoma" "Poria-Atractylodis Macrocephalae Rhizoma" "Cinnamomi Ramulus-Asari Radix et Rhizoma" "Citri Reticulatae Pericarpium-Perillae Folium" "Pinelliae Rhizoma-Magnoliae Officinalis Cortex-Atractylodis Rhizoma" "Paeoniae Radix Alba-Angelicae Sinensis Radix-Glycyrrhizae Radix et Rhizoma-Bupleuri Radix-Scutellariae Radix-Rhizoma Zingiberis Recens" "Ephedrae Herba-Armeniacae Semen Amarum-Gypsum Fibrosum" "Chuanxiong Rhizoma-Notopterygii Rhizoma et Radix-Angelicae Dahuricae Radix-Platycodonis Radix-Saposhnikoviae Radix". Then, according to the medication law for cold pestilence, the antiviral active components of medium-frequency and high-frequency medicinals were retrieved. It was found that these components exerted the antiviral effect by inhibiting virus replication, regulating virus proteins and antiviral signals, and suppressing protease activity. Based on network pharmacology, the mechanisms of the medicinals against severe acute respiratory syndrome coronavirus(SARS-CoV), 2019 novel coronavirus(2019-nCoV), and H1 N1 virus were explored. It was determined that the key targets were tumor necrosis factor(TNF), endothelial growth factor A(VEGFA), serum creatinine(SRC), epidermal growth factor receptor(EGFR), matrix metalloproteinase 9(MMP9), mitogen-activated protein kinase 14(MAPK14), and prostaglandin-endoperoxide synthase 2(PTGS2), which were involved the mitogen-activated protein kinase(MAPK) pathway, advanced glycation end-products(AGE)-receptor for AGE(RAGE) pathway, COVID-19 pathway, and mTOR pathway. This paper elucidated the medication law and mechanism of TCM for the prevention and treatment of epidemic diseases under the guidance of TCM theory of cold pestilence, in order to build a bridge between the theory and modern epidemic diseases and provide reference TCM methods for the prevention and treatment of modern epidemic diseases and ideas for the application of data mining to TCM treatment of modern diseases.

Natural Herbal Medicine as a Treatment Strategy for Myocardial Infarction through the Regulation of Angiogenesis.

Methods: We conducted a literature search on the bioactive components of medicinal plants and their effects on angiogenesis after MI. We searched for articles in Web of Science, MEDLINE, PubMed, Scopus, Google Scholar, and China National Knowledge Infrastructure databases before April 2021. Results: In this article, we summarized the mechanisms by which copper ions, microRNA, Akt1, inflammation, oxidative stress, mitochondria, and pericytes are involved in angiogenesis after myocardial infarction. In addition, we reviewed the angiogenic effects of natural herbal medicines such as Salvia miltiorrhiza Bunge Bunge, Carthamus tinctorius L., Pueraria lobata, Astragalus, Panax ginseng C.A. Mey., Panax notoginseng (Burkill) F.H. Chen, Cinnamomum cassia (L.) J. Presl, Rehmannia glutinosa (Gaertn.) DC., Leonurus japonicus Houtt, Scutellaria baicalensis Georgi., and Geum macrophyllum Willd. Conclusions: Some herbs have the effect of promoting angiogenesis. In the future, natural proangiogenic drugs may become candidates for the treatment of cardiovascular diseases.

Clinical practice guideline for transurethral plasmakinetic resection of prostate for benign prostatic hyperplasia (2021 Edition).

Benign prostatic hyperplasia (BPH) is highly prevalent among older men, impacting on their quality of life, sexual function, and genitourinary health, and has become an important global burden of disease. Transurethral plasmakinetic resection of prostate (TUPKP) is one of the foremost surgical procedures for the treatment of BPH. It has become well established in clinical practice with good efficacy and safety. In 2018, we issued the guideline "2018 Standard Edition". However much new direct evidence has now emerged and this may change some of previous recommendations. The time is ripe to develop new evidence-based guidelines, so we formed a working group of clinical experts and methodologists. The steering group members posed 31 questions relevant to the management of TUPKP for BPH covering the following areas: questions relevant to the perioperative period (preoperative, intraoperative, and postoperative) of TUPKP in the treatment of BPH, postoperative complications and the level of surgeons' surgical skill. We searched the literature for direct evidence on the management of TUPKP for BPH, and assessed its certainty generated recommendations using the grade criteria by the European Association of Urology. Recommendations were either strong or weak, or in the form of an ungraded consensus-based statement. Finally, we issued 36 statements. Among them, 23 carried strong recommendations, and 13 carried weak recommendations for the stated procedure. They covered questions relevant to the aforementioned three areas. The preoperative period for TUPKP in the treatment of BPH included indications and contraindications for TUPKP, precautions for preoperative preparation in patients with renal impairment and urinary tract infection due to urinary retention, and preoperative prophylactic use of antibiotics. Questions relevant to the intraoperative period incorporated surgical operation techniques and prevention and management of bladder explosion. The application to different populations incorporating the efficacy and safety of TUPKP in the treatment of normal volume (< 80 ml) and large-volume (≥ 80 ml) BPH compared with transurethral urethral resection prostate, transurethral plasmakinetic enucleation of prostate and open prostatectomy; the efficacy and safety of TUPKP in high-risk populations and among people taking anticoagulant (antithrombotic) drugs. Questions relevant to the postoperative period incorporated the time and speed of flushing, the time indwelling catheters are needed, principles of postoperative therapeutic use of antibiotics, follow-up time and follow-up content. Questions related to complications incorporated types of complications and their incidence, postoperative leukocyturia, the treatment measures for the perforation and extravasation of the capsule, transurethral resection syndrome, postoperative bleeding, urinary catheter blockage, bladder spasm, overactive bladder, urinary incontinence, urethral stricture, rectal injury during surgery, postoperative erectile dysfunction and retrograde ejaculation. Final questions were related to surgeons' skills when performing TUPKP for the treatment of BPH. We hope these recommendations can help support healthcare workers caring for patients having TUPKP for the treatment of BPH.

Octreotide-based therapies effectively protect mice from acute and chronic gastritis.

Gastritis is a common inflammation of stomach with multiple pathogenesis. This study was designed to investigate the protective effects of oral octreotide (OCT) against ethanol-induced acute gastric injury and H. pylori-induced chronic gastritis via promoting gastric mucosa restoration, reducing gastric acid secretion and inflammation. Male C57BL/6J mice were randomly divided and treated with three doses of OCT (0.5, 2.5, 10 mg/kg) alone or combined respectively with 10 mg/kg omeprazole (OME), 0.2 g/L metronidazole (MTZ)/0.1 g/L clarithromycin (CLR) in drinking water. Oxidative stress analysis, bacterial load analysis, qPCR, gastric histopathology examinations were performed in our study. Ethanol-induced acute gastric ulcer was restored by OCT alone at doses of 2.5 mg/kg, or combined with OME as indicated by markedly reducing Gastrin, Il-6 and Il1b expression through induction of Muc5ac and Occludin, significantly improving hyperacidity and gastric bleeding. As well, OCT combined with MTZ/CLR restored the integrity of gastric mucosa damaged by H. pylori via elevating the expression of Muc5ac and somatostatin receptor 2, decreasing inflammation and increasing the number of chorionic or glands. Besides, OCT is more suitable for long-term medication in the treatment of chronic gastritis than OME. In conclusion, our results proved that the newly developed oral OCT-based therapies were more effective to reverse gastric mucosa damage and inflammation in ethanol and H. pylori infection-induced gastric injury, it is of great significance for supplementing new clinical regimens for the treatment of acute and chronic gastritis.

The spleen-strengthening and liver-draining herbal formula treatment of non-alcoholic fatty liver disease by regulation of intestinal flora in clinical trial.

Objective: As a metabolic disease, one important feature of non-alcoholic fatty liver disease (NAFLD) is the disturbance of the intestinal flora. Spleen-strengthening and liver-draining formula (SLF) is a formula formed according to the theory of "One Qi Circulation" (Qing Dynasty, 1749) of Traditional Chinese Medicine (TCM), which has shown significant therapeutic effect in patients with NAFLD in a preliminary clinical observation. In this study, we aim to explore the mechanism of SLF against NAFLD, especially its effect on glucolipid metabolism, from the perspective of intestinal flora. Methods: A prospective, randomized, controlled clinical study was designed to observe the efficacy and safety of SLF in the treatment of NAFLD. The study participants were randomly and evenly divided into control group and treatment group (SLF group). The control group made lifestyle adjustments, while the SLF group was treated with SLF on top of the control group. Both groups were participated in the study for 12 consecutive weeks. Furthermore, the feces of the two groups were collected before and after treatment. The intestinal flora of each group and healthy control (HC) were detected utilizing 16S rRNA gene sequencing. Results: Compared with the control group, the SLF group showed significant improvements in liver function, controlled attenuation parameter (CAP), and liver stiffness measurement (LSM), meanwhile, patients had significantly lower lipid and homeostasis model assessment of insulin resistance (HOMA-IR) with better security. Intestinal flora 16S rRNA gene sequencing results indicated reduced flora diversity and altered species abundance in patients with NAFLD. At the phylum level, Desulfobacterota levels were reduced. Although Firmicutes and Bacteroidetes did not differ significantly between HC and NAFLD, when grouped by alanine transaminase (ALT) and aspartate transaminase (AST) levels in NAFLD, Firmicutes levels were significantly higher in patients with ALT or AST abnormalities, while Bacteroidetes was significantly lower. Clinical correlation analysis showed that Firmicutes positively correlated with gender, age, ALT, AST, LSM, and Fibroscan-AST (FAST) score, while the opposite was true for Bacteroidetes. At the genus level, the levels of Alistipes, Bilophila, Butyricimonas, Coprococcus, Lachnospiraceae_NK4A136 group Phascolarctobacterium, Ruminococcus, UCG-002, and UCG-003 were reduced, whereas abundance of Tyzzerella increased. There was no statistically significant difference in Firmicutes and Bacteroidota levels in the SLF group before and after treatment, but both bacteria tended to retrace. At the genus level, Coprococcus (Lachnospiraceae family), Lachnospiraceae_NK4A136 group (Lachnospiraceae family), and Ruminococcus (Ruminococcaceae family) were significantly higher in the SLF group after treatment, and there was also a tendency for Bilophila (Desulfovibrionaceae family) to be back-regulated toward HC. Conclusions: SLF can improve liver function and glucolipid metabolism in patients with NAFLD and lower down liver fat content to some extent. SLF could be carried out by regulating the disturbance of intestinal flora, especially Coprococcus, Lachnospiraceae_NK4A136 group, and Ruminococcus genus.

Effects of Macroporous Resin Extract of Dendrobium officinale Leaves in Rats with Hyperuricemia Induced by Fructose and Potassium Oxonate.

AIMS AND OBJECTIVES: Fructose, as a ubiquitous monosaccharide, can promote ATP consumption and elevate circulating Uric Acid (UA) levels. Our previous studies have confirmed that the macroporous resin extract of Dendrobium officinale leaves (DoMRE) could reduce the UA level of rats with hyperuricemia induced by a high-purine diet. This study aimed to investigate whether DoMRE had a UA-lowering effect on rats with hyperuricemia caused by fructose combined with potassium oxonate, so as to further clarify the UA-lowering effect of DoMRE, and to explore the UAlowering effect of DoMRE on both UA production and excretion. MATERIALS AND METHODS: Rats with hyperuricemia induced by fructose and potassium oxonate were administered with DoMRE and vehicle control, respectively, to compare the effects of the drugs. At the end of the experiment, the Serum Uric Acid (SUA) and Creatinine (Cr) levels were measured using an automatic biochemical analyzer, the activities of xanthine oxidase (XOD) were measured using an assay kit, and the protein expressions of Urate Transporter 1 (URAT1), glucose transporter 9 (GLUT9), and ATP-Binding Cassette Superfamily G member 2 (ABCG2) were assessed using immune-histochemical and western blot analyses. Hematoxylin and eosin staining was used to assess the histological changes in the kidney, liver, and intestine. RESULTS: Fructose and potassium induced hyperuricemia in rats. Meanwhile, the activities of XOD were markedly augmented, the expression of URAT1 and GLUT9 was promoted, and the expression of ABCG2 was reduced, which were conducive to the elevation of UA. However, exposure to DoMRE reversed these fructose- and potassium oxonate-induced negative alternations in rats. The activities of XOD were recovered to the normal level, reducing UA formation; the expressions of URAT1, ABCG2, and GLUT9 returned to the normal level, resulting in an increase in renal urate excretion. CONCLUSION: DoMRE reduces UA levels in rats with hyperuricemia induced by fructose combined with potassium oxonate by inhibiting XOD activity and regulating the expression of ABCG2, URAT1, and GLUT9. DoMRE is a potential therapeutic agent for treating hyperuricemia through inhibiting UA formation and promoting UA excretion.

Pingchuan formula improves allergic asthma in mice through inhibiting nuclear factor-kappa B / mitogen-activated protein kinase signaling pathway.

OBJECTIVE: To examine the role and decipher the mechanism of Pingchuan formula (PCF) in treating allergic asthma. METHODS: The mice were treated with saline, dexamethasone (DXM) and PCF for 1 week after the asthma model was established and their respiratory function including respiratory resistance (RI), pulmonary dynamic compliance (Cdyn) and maximum voluntary ventilation (MVV) were measured. In addition, cellular changes in bronchoalveolar lavage fluid (BALF) and pathological changes in lung biopsy as well as the expression level of -smooth muscle actin (α-SMA), transforming growth factor-beta1 (TGF-α1) in BALF and interleukin-5 (IL-5), interleukin-13 (IL-13), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), nuclear factor-kappa B-p65 (NF-κBp65), inhibitor-α of nuclear transcription factor κB (IκBα), p38 mitogen-activated protein kinase (p38MAPK), c-jun n-terminal kinase (JNK) and its phosphorylated proteins in lung tissue were also examined and compared among different groups. RESULTS: Our data suggested that the respiratory functions were significantly improved and the pathological changes ameliorated in the DXM group and the PCF group compared to the model group. Both DXM and PCF effectively decreased the number of eosinophils, lymphocytes, and neutrophils in BAL as well as the secretion of α-SMA and TGF-α1, IL-5, IL-13, while increased the expression of TNF-α and IFN-γ. Furthermore, our study indicated that the NF-κBp65, IκBα, p38MAPK and JNK pathways were inhibited under the treatment of PCF. CONCLUSION: Our data indicated that PCF can attenuate the inflammatory response in asthma through inhibiting the NF-κB/MAPK signaling pathway. This study not only supported the use of PCF in allergic asthma in clinic but also shed light upon afurther understanding of thediseasepathogenesis.

Highly Efficient Far-Red/NIR-Absorbing Neutral Ir(III) Complex Micelles for Potent Photodynamic/Photothermal Therapy.

A critical issue in photodynamic therapy (PDT) is inadequate reactive oxygen species (ROS) generation in tumors, causing inevitable survival of tumor cells that usually results in tumor recurrence and metastasis. Existing photosensitizers frequently suffer from relatively low light-to-ROS conversion efficiency with far-red/near-infrared (NIR) light excitation due to low-lying excited states that lead to rapid non-radiative decays. Here, a neutral Ir(III) complex bearing distyryl boron dipyrromethene (BODIPY-Ir) is reported to efficiently produce both ROS and hyperthermia upon far-red light activation for potentiating in vivo tumor suppression through micellization of BODIPY-Ir to form "Micelle-Ir". BODIPY-Ir absorbs strongly at 550-750 nm with a band maximum at 685 nm, and possesses a long-lived triplet excited state with sufficient non-radiative decays. Upon micellization, BODIPY-Ir forms J-type aggregates within Micelle-Ir, which boosts both singlet oxygen generation and the photothermal effect through the high molar extinction coefficient and amplification of light-to-ROS/heat conversion, causing severe cell apoptosis. Bifunctional Micelle-Ir that accumulates in tumors completely destroys orthotopic 4T1 breast tumors via synergistic PDT/photothermal therapy (PTT) damage under light irradiation, and enables remarkable suppression of metastatic nodules in the lungs, together without significant dark cytotoxicity. The present study offers an emerging approach to develop far-red/NIR photosensitizers toward potent cancer therapy.

Pingchuan formula attenuates airway mucus hypersecretion via regulation of the PNEC-GABA-IL13-Muc5ac axis in asthmatic mice.

BACKGROUND/AIMS: Asthma is a common chronic respiratory disease. It has been reported that Pingchuan formula (PCF) can control asthma attacks by reducing airway inflammation, muscle spasm and mucus secretion. However, PCF's mechanism for reducing airway mucus hypersecretion remains unclear. This study aimed to investigate the effect of PCF on airway mucus secretion in asthmatic mice and to explore changes in the PNEC-GABA-IL13-Muc5ac axis. METHODS: Male Babl/c mice were used to establish the asthma model via sensitisation with OVA. Mice were randomly divided into Normal, OVA, DEX, and PCF groups. After treatment, lung histopathology was observed with H&E and PAS staining. BALF levels of IL-5 and IL-13 were detected using ELISA. The levels of mRNA and protein expression for GAD1, GABAARß1, GABAARα1 and Muc5ac in the lung tissue were measured by RT-PCR and Western blot assays. PNECs were observed with AgNOR staining. RESULTS: PCF treatment effectively reduced goblet cell (P < 0.01) and PNEC (P < 0.05) proliferation, lung tissue inflammation and airway mucus hypersecretion. In addition, PCF also markedly downregulated mRNA and protein expression of GAD1, GABAARß1, GABAARα1 and Muc5ac (P < 0.05, compared with OVA), thus inhibiting the GABA-IL-13 pathway in the lung tissue of asthmatic mice. CONCLUSION: These findings suggest that PCF controls asthma attacks by reducing airway inflammation and mucus hypersecretion via the PNEC-GABA-IL13-Muc5ac axis.

[Effect of Tiaoshen Jianpi acupuncture therapy on gut microbiota and fecal short-chain fatty acids in patients with diarrhea type irritable bowel syndrome].

OBJECTIVE: To observe the clinical therapeutic effect of Tiaoshen Jianpi acupuncture therapy (acupuncture for regulating the mind and strengthening the spleen) on the gut microbiota and the content of fecal short-chain fatty acids (SCFAs) in patients with diarrhea type irritable bowel syndrome (IBS-D). METHODS: A total of 20 patients with IBS-D and 20 healthy subjects were included. The patients with IBS-D were treated with Tiaoshen Jianpi acupuncture therapy at Baihui (GV 20), Yintang (GV 29), Tianshu (ST 25), Shangjuxu (ST 37), Zusanli (ST 36), Sanyinjiao (SP 6) and Taichong (LR 3). The treatment was given once every two days, 3 times weekly, consecutively for 6 weeks. No intervention was provided for the healthy subjects. Before and after treatment, the IBS symptom severity score (IBS-SSS) was observed in the patients. The fecal samples were collected before and after treatment separately in the patients and in the healthy subjects. Using 16S rRNA sequencing technique, the structure and diversity of gut microbiota were analyzed. Using high-performance liquid chromatography, the content of SCFAs was detected. RESULTS: After treatment, the abdominal pain severity score, the abdominal pain days score, the satisfaction in bowel movement score, the life interference score and the total IBS-SSS score were all lower than those before treatment in the patients with IBS-D (P<0.05). Compared with the healthy subjects, Firmicutes was increased (P<0.05), Bacteroidetes and Proteobacteria were decreased (P<0.05), and Shannon index was reduced (P<0.05) and Simpson index was increased in patients with IBS-D before treatment (P<0.05). Compared before treatment, Firmicutes was decreased (P<0.05), Bacteroidetes and Proteobacteria were increased (P<0.05), and Shannon index was increased (P<0.05) and Simpson index was reduced in the patients with IBS-D after treatment (P<0.05). Besides, the content of SCFAs was reduced after treatment (P<0.05). CONCLUSION: Tiaoshen Jianpi acupuncture therapy relieves abdominal pain and diarrhea, which may be related to regulating the structure and diversity of gut microbiota and reducing the content of fecal SCFAs in the patients with IBS-D.

Babao Dan improves neurocognitive function by inhibiting inflammation in clinical minimal hepatic encephalopathy.

BACKGROUND AND PURPOSE: Inflammation has been considered a precipitating event that contributes to neurocognitive dysfunction in minimal hepatic encephalopathy (MHE). Inhibition TLR-4 related inflammation can effectively improve neurocognitive dysfunction of MHE. Our previous study showed that Babao Dan (BBD) effectively inhibited inflammation and ameliorated neurocognitive function in rats with acute hepatic encephalopathy (HE) and chronic HE. The mechanism may lie in the regulation of TLR4 signaling pathway. Therefore, this study aimed to evaluate the role of BBD in the treatment of MHE patients with cirrhosis and to elucidate the underlying mechanism by which BBD regulated TLR4 pathway to alleviate inflammation. METHODS: A randomized controlled trial (n = 62) was conducted to evaluate the clinical efficacy between BBD plus lactulose (n = 31) and lactulose alone (n = 31) in MHE patients by testing neurocognitive function (NCT-A and DST), blood ammonia, liver function (ALT, AST and TBIL) and blood inflammation (IL-1ß, IL-6 and TNF-α). Afterward, we detected NO, inflammatory cytokines (IL-1ß, IL-6 and TNF-α) and the phosphorylation of P65, JNK, ERK as well as P38 in LPS-activated rat primary bone marrow-derived macrophages (BMDMs), peritoneal macrophages (PMs), and mouse primary BMDMs/PMs/microglia/astrocytes, to investigate the underlying mechanism of BBD inhibiting inflammation through TLR4 pathway. Also, the survival rate of mice, liver function (ALT, AST), blood inflammation (IL-1ß, IL-6 and TNF-α), inflammatory cytokines (IL-1ß, IL-6 and TNF-α) and histopathological changes in the liver, brain and lung were measured to assess the anti-inflammatory effect of BBD on neurocognitive function in endotoxin shock/endotoxemia mice. RESULTS: BBD combined with lactulose significantly ameliorated neurocognitive function by decreasing NCT-A (p＜0.001) and increasing DST (p＜0.001); inhibited systemic inflammation by decreasing IL-1ß (p＜0.001), IL-6(p＜0.001) and TNF-α (p＜0.001); reduced ammonia level (p = 0.005), and improved liver function by decreasing ALT(p = 0.043), AST(p = 0.003) and TBIL (p = 0.026) in MHE patients. Furthermore, BBD inhibited gene and protein expression of IL-1ß, IL-6 and TNF-α as well as NO in rat primary BMDMs/PMs, and mouse primary BMDMs/PMs/microglia/astrocytes in a dose-dependent manner. BBD inhibited the activation of mouse primary BMDMs/PMs/microglia/astrocytes by regulating TLR4 pathway involving the phosphorylation of P65, JNK, ERK and P38. Also, BBD reduced the mortality of mice with endotoxin shock/endotoxemia; serum levels of ALT, AST, IL-1ß, IL-6 and TNF-α; gene expression of IL-1ß, IL-6 and TNF-α in the liver, brain and lung, and tissue damage in the liver and lung. CONCLUSION: Our study provided for the first time clinical and experimental evidence supporting the use of BBD in MHE, and revealed that BBD could play a crucial role in targeting and regulating TLR4 inflammatory pathway to improve neurocognitive function in MHE patients.