Decoction regulating phytochemicals' micromorphology changes and anti-inflammation activity enhancements originated from herb medicine supermolecules.

BACKGROUND: Mahuang Fuzi decoction (MGF) is composed of three herb medicines that has been clinically used to treat inflammatory diseases for a long history. At present, more and more active phytochemicals' aggregations have been found during the thermodynamic process of herb medicine decoction, and revealing the clinical efficacy of herb medicine through supramolecular strategies is the focus of current research. However, it is not clear whether decoction induced supermolecules' morphological changes to modify activity. METHODS: Dynamic light scattering (DLS) and field emission scanning electron microscopy (FESEM) were used to analyze the micromorphology of MGF, MGF SA (MGF supermolecules), and MIX (physical mixture of MGF single decoction). The interaction and thermodynamic parameters of single herbs in a decoction were investigated by Isothermal titration calorimetry (ITC). The phytochemicals were systematically analyzed by ultra high performance liquid chromatography-Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry (UHPLC-Q-Orbitrap HRMS). Under the safe dose on RAW264.7 cells, NO, IL-6 and TNF-α were determined by Enzyme-Linked ImmunoSorbent Assay (ELISA) method. NF-κB p65 translocation from the cytoplasm into the nucleus was examined using the immunofluorescence assay and the western blot, respectively. Furthermore, Metabolomics was used to discover potential biomarkers and the associated metabolic pathways of MGF SA treatment. RESULTS: There were nanoscale aggregations in MGF, and the micromorphology of the extracted MGF SA consisted of uniform particles; while the MIX micromorphology had no uniformity. ITC showed that the interaction MH-GC and FZ-GC were a spontaneous exothermic reaction, indicating that their phytochemicals had the property of self-assembly. Though the micromorphology between MGF, MGF SA, and MIX was obviously different, UHPLC-Q-Orbitrap HRMS results displayed that the main phytochemicals of MGF and MIX had nearly the same components. Interestingly, MGF and MGF SA could significantly inhibit the production of NO, and had better inhibition effect on the expression of nuclear protein NF-κB p65 than MIX, among which MGF SA had the best effect. Further investigation indicated that the perturbance of metabolic profiling in RAW264.7 inflammatory cells was obviously reversed by MGF SA. CONCLUSIONS: The decoction enriched the key active phytochemicals and regulated the formation of homogeneous nanoparticles in MGF SA. The supermolecules in MGF SA significantly enhanced its anti-inflammatory activity, primarily affecting the NF-κB signaling pathway and the biosynthesis and metabolism of arginine in RAW264.7 inflammatory cells. Current study displayed that co-decocting herbal medicine were beneficial to the treatment of diseases than the mixture of the single herbs' extraction.

Possible Involvement of Perineuronal Nets in Anti-Depressant Effects of Electroacupuncture in Chronic-Stress-Induced Depression in Rats.

Acupuncture can alleviate depression-like behaviors. However, the neural mechanisms behind the anti-depressive effect remain unknown. Perineuronal net (PNN) abnormalities have been reported in multiple psychiatric disorders. This study investigated the modulation and neural mechanism of PNNs in the anti-depressant process of electroacupuncture (EA) at Baihui (GV20) and Yintang (GV29) points. A rat depression model was induced by chronic unpredicted mild stress (CUMS). The results revealed that CUMS, applied for four weeks, specifically reduces PNNs around parvalbumin (PV). In addition, EA and fluoxetine treatments reverse the decrease in PNNs+ cell density and the ratio of PV and PNN double-positive cells to PV+ neurons in the medial prefrontal cortex (mPFC) after CUMS. Furthermore, EA treatment can reverse the decrease in the protein expression of PNN components (aggrecan and brevican) in the mPFC caused by stress. After EA treatment, the decreased expression of GAD67, GLuA1, and PSD95 in the mPFC induced by CUMS for four weeks was also reversed. PNN degradation in mPFC brain areas potentially interferes with the anti-depressant benefits of EA in rats with depression induced by CUMS. EA treatment did not increase PNNs+ cell density and the ratio of PV and PNN double-positive cells to PV+ neurons after PNNs degradation in the mPFC brain region of rats. This finding indicated that the mechanism of acupuncture's anti-depressant effect may be based on reversing the CUMS-induced decline in PNN expression, the functional impairment of γ-aminobutyric acid (GABA) neurons, and the regulation of excitatory synaptic proteins expression.

Comparative efficacy of glucagon-like peptide 1 (GLP-1) receptor agonists, pioglitazone and vitamin E for liver histology among patients with nonalcoholic fatty liver disease: systematic review and pilot network meta-analysis of randomized controlled trials.

INTRODUCTION: There is no conclusive evidence comparing the efficacy of glucagon-like peptide 1 (GLP-1) receptor agonists to the other guidelines recommended pharmacotherapy for nonalcoholic fatty liver disease (NAFLD). Therefore, we aim to compare the effects of GLP-1 receptor agonists, pioglitazone and vitamin E in patients with NAFLD. METHODS: We searched PubMed, Embase, Web of Science and Cochrane Library up to 11 April 2022. Randomized clinical trials (RCTs) comparing GLP-1 receptor agonists, pioglitazone and vitamin E against placebo or other active controls in patients with NAFLD were included. RESULTS: Nine RCTs including 1482 patients proved eligible. GLP-1 receptor agonists ranked first in steatosis, ballooning necrosis, γ-glutamyl transferase, body weight, body mass index, and triglycerides. Administration of GLP-1 receptor agonists, as compared with placebo, was associated with improvement in liver histology [steatosis (OR = 4.11, 95% CI: 2.83, 5.96), ballooning necrosis (OR = 3.07, 95% CI: 2.14, 4.41), lobular inflammation (OR = 1.86, 95% CI: 1.29, 2.68), fibrosis (OR = 1.52, 95% CI: 1.06, 2.20)]. CONCLUSIONS: GLP-1 receptor agonists were as effective as pioglitazone and vitamin E for liver histology among patients with NAFLD. GLP-1 receptor agonists might be considered as an alternative or complementary treatment in the future clinical practice. [Figure: see text].

[Contamination level and population exposure assessment of chloropropanol esters in edible vegetable oil in Shandong Province from 2016 to 2020].

OBJECTIVE: To investigate the contamination of 2-chloropropanol esters and 3-chloropropanol esters in commercial edible vegetable oils in Shandong Province, and to assess the dietary 3-chloropropanol esters exposure and the health risk of intaking 3-chloropropanol esters. METHODS: From 2016 to 2020, 406 individually packaged edible vegetable oils were collected from stores and farmers' markets in 16 prefecture-level cities in Shandong Province. According to the 2016 National Food Contamination and Harmful Factors Risk Monitoring Manual, using gas chromatography-triple quadrupole tandem mass spectrometry detection, isotope internal standard method for quantification, laboratory determination of 2-chloropropanol ester and 3-chloropropanol in vegetable oil ester content. Combined with population weight, oil consumption and monitoring data, the point assessment method was used to evaluate the exposure of residents in Shandong Province to 3-chloropropanol esters. RESULTS: The detection rate of 3-chloropropanol ester was 92.4%(375/406), the concentration range was<limit of detection(LOD)-18.4 mg/kg, the median was 0.470 mg/kg, the average was 0.833 mg/kg, and the maximum value was 18.4 mg/kg in rice oil; the detection rate of 2-chloropropanol ester was 88.7%(360/406), the concentration range was <LOD-8.46 mg/kg, the median value was 0.204 mg/kg, the average value was 0.432 mg/kg, and the maximum value was 8.46 mg/kg in rice oil. The average exposure of each age group was less than the tolerable daily intake, and the high-end exposure of the children(2-6 years old) and adolescents(7-10 years old) group was greater than the tolerable daily intake. CONCLUSION: The contamination of chloropropanol esters of edible vegetable oil in Shandong Province from 2016 to 2020 is widespread, and the highest detection value appears in rice oil. Children(2-6 years old) and adolescents(7-10 years old) in high-risk situations ingest 3-chloropropanol esters present health risks.

Studies on the mechanism of energy metabolism via AMPK/PGC-1α signaling pathway induced by compatibility of Ligusticum chuanxiong Hort and Gastrodia.

AMP-activated protein kinase (AMPK) regulates overall energy consumption and energy intake through cytokines. Ligusticum striatum DC (CX) combined with Gastrodia elata Blume (TM) has been used for migraine treatment for millennia. When used alone in clinical practice, CX causes symptoms of thirst, irritability, and yellow urine and has influenced the levels of cytokines such as AMP that activate the AMPK pathway of energy metabolism. However, relationships between this compatibility prescription, integral biological energy metabolism, and the AMPK pathway remain unclear. Studies were performed by treating normal rats with physiological saline, CX extract, CX coupled TM extract, and TM extracts separately for 4 weeks. Food intake, water intake, urine output, stool output, and body weight were monitored once a week by the metabolic cage method. Values of FBG, BUN, TP, TC and TG in blood samples were detected approaching the whole blood automatic detector from 1 to 4 weeks. Na+ -K+ -ATPase, Ca2+ -Mg2+ -ATPase, cAMP, and cGMP activity were determined by the enzyme-linked immunosorbent assay (ELISA); the biological samples that were obtained at 1, 2, 3, and 4 weeks after drug administration were tested by GC-TOF-MS. Then real-time PCR and Western Blot were applied to detect changes in expression of some substances involved in energy metabolism. The results demonstrated that administering CX alone increased energy input, mobility, and respiratory exchange ratio, accelerated energy consumption, and caused inflammatory infiltration in the liver. CX coupled with TM led to lower energy metabolism and liver damage in comparison with CX used alone. Moreover, CX-treated rats harbored higher levels of differential metabolites (including pyrophosphate, oxaloacetic acid, and galactinol). Glycerophospholipid metabolism and the citrate cycle are closely related to the differential metabolites above. In addition, CX-induced unbalanced energy metabolism depends on cAMP activation mediated by the AMPK/PGC-1α pathway in rats. Our findings suggest that CX-induced energy metabolism imbalance was corrected after coupling with TM by mediating the AMPK/PGC-1α pathway.

Electroacupuncture Attenuated Phenotype Transformation of Vascular Smooth Muscle Cells via PI3K/Akt and MAPK Signaling Pathways in Spontaneous Hypertensive Rats.

OBJECTIVE: To investigate whether the antihypertensive mechanism of electroacupuncture (EA) is associated with attenuating phenotype transformation of vascular smooth muscle cells (VSMCs) via phosphoinositide3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) signaling pathways. METHODS: Eight Wistar-ktoyo (WKY) rats were set as normal blood pressure group (normal group). A total of 32 spontaneous hypertensive rats (SHRs) were randomly divided into 4 groups using random number tables: a model group, an EA group, an EA+PI3K antagonist group (EA+P group), and an EA+p38 MAPK agonist+extracellular signal-regulated kinase (ERK) agonist group (EA+M group) (n=8/group). SHRs in EA group, EA+P group and EA+M group received EA treatment 5 sessions per week for continuous 4 weeks, while rats in the normal and model groups were bundled in same condition. The systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) of each rat was measured at 0 week and the 4th week. After 4-week intervention, thoracic aorta was collected for hematoxylin-eosin (HE) staining, immunohistochemistry [the contractile markers α-smooth muscle actin (α-SMA) and calponin and the synthetic marker osteopontin (OPN)] and Western blot [α-SMA, calponin, OPN, PI3K, phosphorylated-Akt (p-Akt), Akt, p-p42/44 ERK, total p42/44 ERK, p-p38 MAPK and total p38 MAPK]. RESULTS: EA significantly reduced SBP, DBP and MAP (P<0.01). HE staining showed that the wall thickness of thoracic aorta in EA group was significantly decreased (P<0.01). From results of immunohistochemistry and Western blot, EA increased the expression of α-SMA and calponin, and decreased the expression of OPN (P<0.01). In addition, the expression of PI3K and p-Akt increased (P<0.01), while the expression of p-p42/44 ERK and p-p38 MAPK decreased in EA group (P<0.01). However, these effects were reversed by PI3K antagonist, p38 MAPK agonist and ERK agonist. CONCLUSIONS: EA was an effective treatment for BP management. The antihypertensive effect of EA may be related with inhibition of phenotypic transformation of VSMCs, in which the activation of PI3K/Akt and the repression of MAPK pathway were involved.

A novel hydrogel based on Bletilla striata polysaccharide for rapid hemostasis: Synthesis, characterization and evaluation.

The purpose of this study is to develop a new polysaccharide-based hydrogel. The Box-Behnken design was used to optimize the optimal synthesis conditions of the hydrogel, with the swelling parameters as indicators. The findings of rheologic tests confirm that free radical polymerization and the introduction of linear polymers improved the mechanical strength of the hydrogel. Combined with the characterization results, the gel mechanism of BSP-g-PAA/PVA DN hydrogel was proposed. The intermolecular association and entanglement increase, which effectively dissipates energy, thereby enhancing the mechanical properties of the hydrogel. In vitro blood compatibility experiments show that DN hydrogel has a low hemolysis rate and a good coagulation effect. The material is non-cytotoxic to L929 cells. The hepatic haemorrhage and mouse-tail amputation models of rats and mice were used to further evaluate the in vivo wound sealing and hemostatic properties of the hydrogel. The blood loss and hemostatic time were significantly lower than those of the control group, indicating that the hydrogel has excellent hemostatic effects. Therefore, the obtained BSP-g-PAA/PVA DN network hydrogel has good comprehensive properties and is expected to be used as a hemostatic material or a precursor of a drug carrier and a tissue engineering scaffold.

Tai Chi for Chronic Obstructive Pulmonary Disease (COPD): An Overview of Systematic Reviews.

OBJECTIVE: Since current systematic reviews (SRs) show that results of effectiveness on Tai Chi for chronic obstructive pulmonary disease (COPD) are inconsistent, the purpose of this study is to find the reasons of the disparity by comprehensively appraising the related SRs. METHODS: Six databases were systematically searched from the inception date to April 17, 2021. The methodological quality, the risk of bias, the reporting quality, and the quality of evidence were independently assessed by two reviewers with the AMSTAR 2, ROBIS, PRISMA, and GRADE. RESULTS: A total of 12 studies met the inclusion criteria: 10 SRs were rated critically low quality and two SRs were low quality by AMSTAR 2. By the ROBIS, four out of 12 SRs were rated as "low risk". According to PRISMA, nine out of 12 SRs were adequately reported over 80%. With the GRADE tool, three out of 12 SRs rated the FEV1 as "Moderate", one out of 12 SRs (1/12, 9%) rated the FEV1/FVC (%) as "Moderate", three out of 12 SRs assessed the 6MWD as "Moderate", three out of 12 SRs evaluated the SGRQ as "Moderate", and the remaining evidence was fully rated as "Low" or "Very Low". CONCLUSION: We found that the methodological quality, risk of bias, reporting quality, and quality of evidence of the included SRs on Tai Chi for COPD were suboptimal. These limitations may have a negative impact on SRs, consequently leading to inconsistent results. Further well-conducted SRs with less risk of bias, more rigorous methodology, normative reporting and high-quality of evidence are needed to provide robust evidence on Tai Chi for COPD. REGISTRATION NUMBER: This study has been registered in the PROSPERO International Prospective Register of Systematic Reviews (registration number: CRD42019126600).

[Progress in pathophysiology and integrated traditional Chinese and Western medicine of post-intensive care syndrome].

With the continuous improvement of treatment ability in intensive care unit (ICU), many critically ill and complex patients have survived due to the development of technology. However, most of them suffer from the psychological and physiological problems of post-intensive care syndrome (PICS). Therefore, the early identification and prevention of PICS is particularly critical. We should understand the pathophysiological mechanism of PICS, strictly implement ABCDEFG bundle management measures [including airway management (A), breath (B), reasonable analgesia and sedation treatment (C), prevention of delirium (D), early rehabilitation (E), family engagement (F), good communication (G)] during ICU hospitalization, and pay attention to reasonable nutritional support, optimizing blood glucose management, providing positive psychological intervention and support to patients through family members' encouragement and accompanying, ICU diary and other forms, following up the health status of patients transferred out/discharged from ICU, providing multi-disciplinary and professional continuing medical services, finding the entry point and timing of traditional Chinese medicine intervention, and giving full play to the advantages of integrated traditional Chinese and Western medicine treatment, which can improve the quality of life of patients. This article reviews the pathophysiological mechanism, risk factors, prevention and management measures, traditional Chinese medicine syndrome differentiation and treatment of PICS, in order to improve the early identification, diagnosis and treatment of critical patients with PICS, and improve the prognosis of patients.

Comparison of trace element concentrations in freshwater fish and marine fish consumed in Shandong Province, China, and their potential risks to human health.

This study provides the primary data of ten trace element concentrations from four highly consumed cultured freshwater fish species in comparison to six marine fish collected from markets of the Shandong province, China, and evaluates the potential human health risks from consuming these fish. A significant difference in five metal concentrations (Cr, As, Se, Cd, Pb) was found between freshwater and marine fish. With the exception of chromium, the other four element contents in marine fish were higher than those in freshwater fish. According to estimated daily intake (EDI), target hazard quotient (THQ), total target hazard quotient (TTHQ), and the permissible safety limits prescribed by various agencies, consumption of the examined fish species is safe for human health. However, chromium in freshwater fish and arsenic in marine fish should still be a cause for concern in terms of human health, especially for fisher folk communities and populations that frequently consume fish.

Catecholic alkaloid sulfonates and aromatic nitro compounds from Portulaca oleracea and screening of their anti-inflammatory and anti-microbial activities.

Acidic compounds were enriched from a water decoction of Portulaca oleracea using 717 anion exchange resin column chromatography. A total of 22 compounds including 9 catecholamine derivatives, of which six were rare sulfonic acid derivatives, and 9 nitro derivatives, were further isolated through various column chromatographic methods, and their structures were elucidated by interpreting their spectroscopic data and ECD calculations. Among them, 16 compounds were isolated from P. oleracea for the first time, 8 of which were undescribed compounds and four compounds were natural products. Pharmacological screening indicated that cis-3-(3-nitro-4-hydroxyphenyl)-methyl acrylate exhibited anti-inflammatory activity, measured as inhibition of nitric oxide production in LPS-stimulated RAW264.7 macrophage cells, with an EC50 value of 18.0 µM, The compounds showed only weak anti-microbial activity with (2R)-(+)-2-chloro-3-(3-nitro-4-hydroxyphenyl)-propionic acid methyl ester inhibiting Candida albicans with a MIC of 256 µg/mL, and 3-methoxy-4,5-dinitrophenol inhibiting Shigella sonnei with a MIC of 512 µg/mL.

Fluoride in tea from Shandong Province, China and exposure assessment.

In this study fluoride in 170 tea samples from Shandong province (China) was determined using a selective ion electrode. The fluoride concentrations ranged from 31.2 to 338 mg/kg with an average of 119 mg/kg. The mean fluoride concentrations were 164, 121, 98.7 and 96.8 mg/kg, which corresponded to Pu'erh tea, green tea, oolong tea and black tea, respectively. Moreover, 4.7% of the analysed samples exceed the legal limit of 200 mg/kg recommended by China. The estimated daily intake of fluoride via drinking tea for an adult was between 0.655 and 1.07 mg/person/day, which were lower than the provisional maximum tolerable daily intake value of 3.5 mg/person/day set by the National Health and Family Planning Commission of the People's Republic of China. In future, maintaining a surveillance programme to monitor the trend of fluoride in tea is necessary for food safety and human health.

Bu-Yin-Qian-Zheng Formula Ameliorates MPP+-Induced Mitochondrial Dysfunction in Parkinson's Disease via Parkin.

As a typical traditional Chinese medicine, Bu-Yin-Qian-Zheng Formula (BYQZF) has been shown to have neuroprotective effects in patients with Parkinson's disease (PD), particularly by ameliorating mitochondrial dysfunction and regulating expression of the parkin protein. However, the underlying mechanisms by which BYQZF affects mitochondrial function through parkin are unclear. Accordingly, in this study, we evaluated the mechanisms by which BYQZF ameliorates mitochondrial dysfunction through parkin in PD. We constructed a parkin-knockdown cell model and performed fluorescence microscopy to observe transfected SH-SY5Y cells. Quantitative real-time reverse transcription polymerase chain reaction and western blotting were conducted to detect the mRNA and protein expression levels of parkin. Additionally, we evaluated the cell survival rates, ATP levels, mitochondrial membrane potential (ΔΨm), mitochondrial morphology, parkin protein expression, PINK1 protein expression, and mitochondrial fusion and fission protein expression after treatment with MPP+ and BYQZF. Our results showed that cell survival rates, ATP levels, ΔΨm, mitochondrial morphology, parkin protein levels, PINK1 protein levels, and mitochondrial fusion protein levels were reduced after MPP+ treatment. In contrast, mitochondrial fission protein levels were increased after MPP+ treatment. Moreover, after transient transfection with a negative control plasmid, the above indices were significantly increased by BYQZF. However, there were no obvious differences in these indices after transient transfection with a parkin-knockdown plasmid. Our findings suggest that BYQZF has protective effects on mitochondrial function in MPP+-induced SH-SY5Y cells via parkin-dependent regulation of mitochondrial dynamics.