Baohuoside I suppresses the NLRP3 inflammasome activation via targeting GPER to fight against Parkinson's disease.

BACKGROUND: Accumulating evidence indicates the crucial role of microglia-mediated inflammation and the NLR family pyrin domain containing 3 (NLRP3) inflammasome-mediated pyroptosis in the pathogenesis of Parkinson's disease (PD). Baohuoside I, a natural flavonoid extracted from Herba Epimedii, has been shown to possess anti-inflammatory effects, but its potential neuroprotective effects and mechanism against PD have not been documented. STUDY DESIGN AND METHODS: The anti-inflammatory effects of Baohuoside I were evaluated by LPS-induced BV2 cells or primary microglia isolated from wide type or G protein-coupled estrogen receptor (GPER) gene knockout mice. The underlying mechanism related to GPER-mediated NLRP3 inflammasome inhibition was further explored using LPS-induced GPER+/+ or GPER-/- mouse models of PD. The neuroprotective effects of Baohuoside I were detected through western blot analysis, real-time PCR, molecular docking, mouse behavioral tests, immunofluorescence, and immunohistochemistry. RESULTS: Baohuoside I significantly alleviated LPS-induced neuroinflammation by inhibiting the activation of NF-κB signal and the increase of pyroptosis levels as evidenced by the downregulated expression of pyroptosis-related proteins (NLRP3, ASC, pro-Caspase-1, IL-1ß) in microglia cells. Intragastric administration of Baohuoside I protected against LPS-induced motor dysfunction and loss of dopaminergic neurons, reduced pro-inflammatory cytokines expressions, and inhibited microglial (Iba-1) and astrocyte (GFAP) activation in the nigrostriatal pathway in LPS-induced mouse model of PD. Pretreatment with GPER antagonist G15 in microglia cells or GPER gene deletion in mice significantly blocked the inhibitory effects of Baohuoside I on LPS-induced neuroinflammation and activation of the NLRP3/ASC/Caspase-1 pathway. Molecular docking further indicated that Baohuoside I might bind to GPER directly with a binding energy of -10.4 kcal/mol. CONCLUSION: Baohuoside I provides neuroprotective effects against PD by inhibiting the activation of the NF-κB signal and NLRP3/ASC/Caspase-1 pathway. The molecular target for its anti-inflammatory effects is proved to be GPER in the PD mouse model. Baohuoside I may be a valuable anti-neuroinflammatory agent and a drug with well-defined target for the treatment of PD.

Mechanism of ShuiJingDan in Treating Acute Gouty Arthritis Flares Based on Network Pharmacology and Molecular Docking.

Purpose: This study examined the underlying mechanisms of SJD's anti-inflammatory and analgesic effects on acute GA flares. Methods: This study used pharmacology network and molecular docking methods. The active ingredients of ShuiJingDan (SJD) were obtained from the Traditional Chinese Medicine Systems Pharmacology Analysis Platform (TCMSP), and the relevant targets of GA were obtained from the Online Mendelian Inheritance in Man (OMIM) database and Therapeutic Target Database (TTD). The core drug group-target-disease Venn diagram was formed by crossing the active ingredients of SJD and the relevant targets. Gene Ontology (GO) analysis was conducted for functional annotation, DAVID was used for Kyoto Encyclopedia of Genes, and Genomes pathway enrichment analysis, and R was used to find the core targets. The accuracy of SJD network pharmacology analysis in GA treatment was verified by molecular docking simulations. Finally, a rat GA model was used to further verify the anti-inflammatory mechanism of SJD in the treatment of GA. Results: SJD mainly acted on target genes including IL1B, PTGS2, CXCL8, EGF, and JUN, as well as signal pathways including NF-κB, Toll-like receptor (TLR), IL-17, and MAPK. The rat experiments showed that SJD could significantly relieve ankle swelling, reduce the local skin temperature, and increased the paw withdrawal threshold. SJD could also reduce synovial inflammation, reduced the concentrations of interleukin-1ß (IL-1ß), IL-8, and COX-2 in the synovial fluid, and suppressed the expression of IL1B, CXCL8, and PTGS2 mRNA in the synovial tissue. Conclusion: SJD has a good anti-inflammatory effect to treat GA attacks, by acting on target genes such as IL-1ß, PTGS2, and CXCL8.

Phenolipid JE improves metabolic profile and inhibits gluconeogenesis via modulating AKT-mediated insulin signaling in STZ-induced diabetic mice.

Phenolipids are characteristic phytochemicals of Syzygium genus. However, the antidiabetic potential and underlying molecular mechanism of these components are not fully elucidated. Herein, we studied the anti-diabetic effects of jambone E (JE), a phenolipid from S. cumini, with in vitro and in vivo models. Data from current study showed that JE enhanced glucose consumption and uptake, promoted glycogen synthesis, and suppressed gluconeogenesis in insulin resistant (IR)-HepG2 cells and primary mouse hepatocytes. JE also attenuated streptozotocin-induced hyperglycemia and hyperlipidemia in type 1 diabetic (T1D) mice. Eleven metabolites (e.g. trimethylamine n-oxide, 4-pyridoxic acid, phosphatidylinositol 39:4, phenaceturic acid, and hippuric acid) were identified as potential serum biomarkers for JE's antidiabetic effects by an untargeted metabolomics approach. The further molecular mechanistic study revealed that JE up-regulated phosphorylation levels of protein kinase B (AKT), glycogen synthase kinase 3 beta, and forkhead box O1 (FoxO1), promoted nuclear exclusion of FoxO1 whilst decreased gene expression levels of peroxisome proliferator-activated receptor gamma coactivator-1 alpha, phosphoenolpyruvate carboxykinase and glucose 6-phosphatase in IR-HepG2 cells and T1D mice. Our data suggested that JE might be a potent activator for AKT-mediated insulin signaling pathway, which was confirmed by the usage of AKT inhibitor and AKT-target siRNA interference, as well as the cellular thermal shift assay. Findings from the current study shed light on the anti-diabetic effects of phenolipids in the Syzygium species, which supports the use of medicinal plants in the Syzygium genus for potential pharmaceutical applications.

Salvianolic Acid B Reduces the Inflammation of Fat Grafts by Inhibiting the NF-Kb Signalling Pathway in Macrophages.

BACKGROUND: Autologous fat grafting is a common method for soft tissue defect repair. However, the high absorption rate of transplanted fat is currently a bottleneck in the process. Excessive inflammation is one of the main reasons for poor fat transplantation. Salvianolic acid B (Sal-B) is a herbal medicine that shows promise for improving the effectiveness of fat transplantation. OBJECTIVE: The aim of this study was to improve fat graft survival by injecting Sal-B into fat grafts locally. METHODS: In vivo, 0.2 mL of Coleman fat was transplanted into nude mice along with Sal-B. The grafts were evaluated by histologic analysis at 2, 4, and 12 weeks posttransplantation and by microcomputed tomography at 4 weeks posttransplantation. In vitro ribonucleic acid sequencing, cell proliferation assays, anti-inflammatory activity assays, molecular docking studies, and kinase activity assays were performed in RAW264.7 cells to detect the potential mechanism. RESULTS: Sal-B significantly improved fat graft survival and attenuated adipose tissue fibrosis and inflammation. Sal-B also inhibited the polarization of M1 macrophages in fat grafts. In vitro, Sal-B inhibited the proliferation and activation of inflammatory pathways in RAW264.7 cells. In addition, Sal-B had an inhibitory effect on NF-κB (nuclear factor κ light polypeptide gene enhancer in B cells) signaling. This bioactivity of Sal-B may result from its selective binding to the kinase domain of the inhibitor of NF-κB kinase subunit ß. CONCLUSIONS: Sal-B could serve as a promising agent for improving the effect of fat transplantation by inhibiting the polarization of M1 macrophages through NF-κB signaling.

The Anti-inflammatory Effects of Isoflavonoids from Radix Astragali in Hepatoprotective Potential against LPS/D-gal-induced Acute Liver Injury.

Radix Astragali (RA) is an important Traditional Chinese Medicine widely used in the treatment of various diseases, such as pneumonia, atherosclerosis, diabetes, kidney and liver fibrosis. The role of isoflavonoids from RA in the treatment of liver injury remains unclear. The study aimed to explore hepatoprotective and anti-inflammatory effects of isoflavonoids from Astragalus mongholicus. Network pharmacological analysis showed that RA had a multi-target regulating effect on alleviating liver injury and inhibiting inflammation through its active ingredients, among which isoflavones were closely related to its key molecular targets. The anti-inflammatory and liver protection effects of isoflavonoids of RA were investigated using lipopolysaccharide (LPS)-induced RAW 264.7 cells in vitro and LPS/D-galactosamine (D-gal)-induced acute liver injury mice in vivo. The experimental results showed that methylnissolin (ML) and methylnissolin-3-O-ß-D-glucoside (MLG) presented more notable anti-inflammatory effects. Both of them suppressed the release of pro-inflammatory cytokines, such as iNOS, COX-2, IL-1ß, IL-6, and TNF-α in LPS-stimulated RAW 264.7 cells. In vivo investigation demonstrated that ML markedly meliorated liver injury in LPS/D-gal-induced mice. Western blot results revealed that ML and MLG down-regulated the expression of proinflammatory cytokines via NF-κB signaling pathway. The isoflavonoids, methylnissolin (ML), and methylnissolin-3-O-ß-D-glucoside (MLG), play a vital role in the hepatoprotective and anti-inflammatory effects of RA.

Predicting potential global distribution and risk regions for potato cyst nematodes (Globodera rostochiensis and Globodera pallida).

Potato cyst nematodes (PCNs), golden (yellow) cyst nematode (Globodera rostochiensis, gPCN) and pale (white) cyst nematode (G. pallida, pPCN), are important invasive pests in many countries and regions where they can cause significant yield and economic loss for agriculture. Prediction and identification of habitats suitable for PCNs are critical for developing biosecurity strategies, both pre and post border, to maximise the potential for early elimination should an incursion occur. To date, the potential global distribution of PCNs has not been thoroughly studied. Therefore, this study conducted a species distribution model to illustrate the potential global distribution of PCNs and risk regions. In this study, the Maximum Entropy Model (Maxent) associated with the Geographic Information System (GIS) was employed to reveal the potential distribution of the gPCN and pPCN. In addition to bioclimate, soil quality was also included in the model. The global cultivated lands, whether the susceptible hosts were present or not, were used to assess the maximum potential risk regions. The limitation factors for PCNs distribution were also assessed. Results showed that 66% of the global land surface was suitable for gPCN or pPCN or both, and both species can colonise more than 75% of the global cultivated lands. The coldest quarter's mean temperature and precipitation were critical limitations in unsuitable regions. In summary, the global risk maps of PCNs contribute valuable additional information that complements previous national/regional distribution predictions. The results of this distribution research will contribute practical support for decision-makers and practitioners to implement biosecurity strategies from a global perspective, that incorporate prevention or promptly enforce control practices to limit the damage caused by future incursions.

Discovery, preparation and characterization of lipid-lowering alkylphenol derivatives from Syzygium jambos fruit.

The chemical characteristics and hypolipidemic effects of alkylphenols in the fruit of Syzygium jambos were investigated in this study. Three cardanols (1-3; 1 as a new compound) and three alkylresorcinols (4-6) were isolated and identified from S. jambos fruit. Cardanols 1 and 2 (10-40 µM) suppressed lipids accumulation and reduced triglyceride content in oleic acid-overloaded HepG2 cells via the activation of AMPK/PPARα signaling pathways. Furthermore, the biological distribution of cardanols after an oral intake in mice was investigated. Compound 2 was detected in mice plasma, feces, and adipose tissues after a single oral intake (80 mg/kg body weight). In addition, an alkylphenols-enriched S. jambos fruit extract containing two bioactive compounds (95.9 and 198.6 µg/mg of compounds 1 and 2, respectively) was prepared. Findings from the current study highlight the potential usage of cardanols as well as S. jambos fruit for the management of dyslipidemia.

Solid-state multinuclear magnetic resonance and X-ray crystallographic investigation of the phosphorus...iodine halogen bond in a bis(dicyclohexylphenylphosphine)(1,6-diiodoperfluorohexane) cocrystal.

Halogen bonding to phosphorus atoms remains uncommon, with relatively few examples reported in the literature. Here, the preparation and investigation of the cocrystal bis(dicyclohexylphenylphosphine)(1,6-diiodoperfluorohexane) by X-ray crystallography and solid-state multinuclear magnetic resonance spectroscopy is described. The crystal structure features two crystallographically unique C-I...P halogen bonds [dI...P = 3.090 (5) Å, 3.264 (5) Å] and crystallographic disorder of one of the 1,6-diiodoperfluorohexane molecules. The first of these is the shortest and most linear I...P halogen bond reported to date. 13C, 19F, and 31P magic angle spinning solid-state NMR spectra are reported. A 31P chemical shift change of -7.0 p.p.m. in the cocrystal relative to pure dicyclohexylphenylphosphine, consistent with halogen bond formation, is noted. This work establishes iodoperfluoroalkanes as viable halogen bond donors when paired with phosphorus acceptors, and also shows that dicyclohexylphenylphosphine can act as a practical halogen bond acceptor.

Flowerlike Ni-NiO composite as magnetic solid-phase extraction sorbent for analysis of carbendazim and thiabendazole in edible vegetable oils by liquid chromatography-mass spectrometry.

A rapid, selective, and sensitive method was developed for the detection of carbendazim and thiabendazole in edible vegetable oil. Two benzimidazole analytes were pre-concentrated by magnetic solid phase extraction (MSPE) using flowerlike Ni-NiO composite as sorbents and followed by LC-MS/MS analysis. The flowerlike Ni-NiO composite sorbent displayed a high affinity towards benzimidazole analytes due to the reversible coordination interaction between the Ni(Ⅱ) ion and the electron-donating imidazole group. In comparison to the previous methods, this procedure is less time-consuming and simpler during sample preparation. The parameters affecting the extraction efficiency were optimized in detail. The method was validated according to SANTE/12682/2019. The limits of detection were in the range of 0.001-0.003 mg•kg-1. The recoveries ranged from 89.3% to 110.7% with inter-day and inter-day precision less than 10.9%. The results indicate that flowerlike Ni-NiO composite might be a promising alternative for MSPE of benzimidazole compounds in foods.

Curcumin Conjugated Gold Nanoclusters as Perspective Therapeutics for Diabetic Cardiomyopathy.

Accumulation of lipids in the myocardium contributes to the development of cardiac dysfunctions and various chronic diseases, such as diabetic cardiomyopathy (DCM). Curcumin (Cur) can relieve lipid accumulation problems, but its efficiency is limited by poor water solubility and biocompatibility. Herein, gold nanoclusters (AuNCs) were used to improve the efficiency of Cur, and the conjugates Curcumin-AuNCs (AuCur) were developed. In the treatment of high-fat-induced myocardial cell damage, we found that AuCur could effectively reduce intracellular lipid accumulation, the increase of reactive oxygen species (ROS), the increase of mitochondrial division, and the increase of apoptosis compared with Cur. AuCur decreased the expression of the peroxisome proliferator-activated receptors-α subtype (PPARα), and the therapeutic effect of AuCur was canceled when the expression of PPARα was enhanced. For the above reasons, AuCur treated the toxic effect of high lipid on cardiomyocytes by regulating PPARα, providing a new idea and method for the treatment of DCM.

Medium & long-chain acylcarnitine's relation to lipid metabolism as potential predictors for diabetic cardiomyopathy: a metabolomic study.

BACKGROUND: Acylcarnitine is an intermediate product of fatty acid oxidation. It is reported to be closely associated with the occurrence of diabetic cardiomyopathy (DCM). However, the mechanism of acylcarnitine affecting myocardial disorders is yet to be explored. This current research explores the different chain lengths of acylcarnitines as biomarkers for the early diagnosis of DCM and the mechanism of acylcarnitines for the development of DCM in-vitro. METHODS: In a retrospective non-interventional study, 50 simple type 2 diabetes mellitus patients and 50 DCM patients were recruited. Plasma samples from both groups were analyzed by high throughput metabolomics and cluster heat map using mass spectrometry. Principal component analysis was used to compare the changes occurring in the studied 25 acylcarnitines. Multivariable binary logistic regression was used to analyze the odds ratio of each group for factors and the 95% confidence interval in DCM. Myristoylcarnitine (C14) exogenous intervention was given to H9c2 cells to verify the expression of lipid metabolism-related protein, inflammation-related protein expression, apoptosis-related protein expression, and cardiomyocyte hypertrophy and fibrosis-related protein expression. RESULTS: Factor 1 (C14, lauroylcarnitine, tetradecanoyldiacylcarnitine, 3-hydroxyl-tetradecanoylcarnitine, arachidic carnitine, octadecanoylcarnitine, 3-hydroxypalmitoleylcarnitine) and factor 4 (octanoylcarnitine, hexanoylcarnitine, decanoylcarnitine) were positively correlated with the risk of DCM. Exogenous C14 supplementation to cardiomyocytes led to increased lipid deposition in cardiomyocytes along with the obstacles in adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathways and affecting fatty acid oxidation. This further caused myocardial lipotoxicity, ultimately leading to cardiomyocyte hypertrophy, fibrotic remodeling, and increased apoptosis. However, this effect was mitigated by the AMPK agonist acadesine. CONCLUSIONS: The increased plasma levels in medium and long-chain acylcarnitine extracted from factors 1 and 4 are closely related to the risk of DCM, indicating that these factors can be an important tool for DCM risk assessment. C14 supplementation associated lipid accumulation by inhibiting the AMPK/ACC/CPT1 signaling pathway, aggravated myocardial lipotoxicity, increased apoptosis apart from cardiomyocyte hypertrophy and fibrosis were alleviated by the acadesine.

Timing and efficacy of transjugular intrahepatic portosystemic shunt in patients with pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome.

There is no specific treatment for pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome (PA-HSOS). It is not clear when transjugular intrahepatic portosystemic shunt (TIPS) should be implemented in PA-HSOS patients. This study aimed to evaluate the timing of TIPS using total bilirubin (TBIL) as a measure, and to investigate efficacy of TIPS. We retrospectively analyzed the medical records of 10 PA-HSOS patients, among whom 4 patients had received TIPS (TIPS group), and the remaining patients were assigned to the internal medicine group. In the TIPS group, the TBIL level before TIPS was 84.4 ± 45.2 µmol/L (> 3 mg/dL), and TBIL levels were increased to different degrees after TIPS. With the extension of time, serum TBIL levels gradually decreased, and no liver failure occurred. With regards to the short-term outcomes, 3 patients recovered, 1 developed chronic illness and 0 died in the TIPS group. Moreover, 0 patients recovered, 5 developed chronic illness and 1 died in the internal medicine group. The rank sum test of group design revealed significant differences in clinical outcomes (P = 0.02). It was suggested that when the internal medicine effect of PA-HSOS patients is poor, TIPS should be considered, which is no trestricted to the limit of 3 mg/dL TBIL. It was also found TIPS effectively promote the recovery of liver function and reduce the occurrence of chronicity.

Clinical Observation on the Nursing Effect of Mindfulness-Based Stress Reduction Combined with Solution-Focused Brief Therapy in Uremic Peritoneal Dialysis Patients and Influence on Nutritional Status.

OBJECTIVE: To explore the nursing effect of mindfulness-based stress reduction (MBSR) combined with solution-focused brief therapy (SFBT) in uremic peritoneal dialysis (PD) patients and its influence on nutritional status. METHODS: A prospective study was conducted on 108 uremia patients undergoing PD who were admitted to the First People's Hospital of Wenling from March 2018 to December 2020. In accordance with the wishes of the patients, according to random number method, the patients were divided into control group (n = 54) and experimental group (n = 54). Patients in the control group were given routine care. Patients in the experimental group were given MBSR combined with SFBT. The clinical data, biochemical indicators, complication, compliance, nutritional status, and quality of life of the two groups were compared. RESULTS: After intervention, the serum hemoglobin, serum albumin levels, and urea clearance index of the experimental group were higher than those of the control group (P < 0.05). Compared with the control group, the experimental group had a lower incidence of complications (P < 0.05). After intervention, the compliance score of the experimental group was higher than that of the control group (P < 0.05). After intervention, the malnutrition inflammation score of the experimental group was lower than that of the control group (P < 0.05). After intervention, the Kidney Disease and Quality of Life-36 scores of the experimental group were higher than those of the control group (P < 0.05). CONCLUSION: MBSR combined with SFBT has a good nursing effect in uremia patients undergoing PD and can increase the patient's treatment compliance, improve the quality of life, and improve the nutritional status.

Role of TLR4/MyD88 Signaling Pathway in the Occurrence and Development of Uremia-Induced Myocardial Hypertrophy and Possible Mechanism.

The morbidity and mortality of cardiovascular disease (CVD) are relatively high. Studies have shown that most patients with chronic kidney disease (CKD) die from cardiovascular complications. Clinically, the pathophysiological state in which heart disease and kidney disease are causal and influence each other is called cardiorenal syndrome (CRS). Myocardial hypertrophy is the key stage of the heart structure changing from reversible to irreversible. It is an important pathophysiological basis for heart failure. Therefore, this study intends to start with the end-stage uremic phase of CKD to construct an animal model of uremia in rats to study the relationship between uremia, TLR4/MyD88 signaling pathway, and myocardial hypertrophy. The results showed that the uremic rats showed slow weight gain and were thinner. At 12 weeks (w), the serum creatinine and urea nitrogen of the uremic rats increased, and the global hypertrophy index increased. Detecting the expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor (MyD88) in blood samples of rats, we found that the expression of TLR4 and MyD88 increased at 12 w in the uremia group; pathological observation showed that at 4 weeks of uremia model rats, renal tissue compensatory hypertrophy, renal fibrous membrane proliferation, renal parenchyma atrophy, a large number of fibrous proliferation and inflammatory cell infiltration in the interstitium, and protein casts in the renal tubules were observed. Myocardial cells were obviously hypertrophy and disordered. At 12 w, renal tubules were obviously expanded, the epithelium was flat, the brush border disappeared, and the interstitial fibrous connective tissue of the myocardial tissue was proliferated. The detection of TLR4 and MyD88 in kidney tissue and myocardial tissue revealed that the positive expression of TLR4 and MyD88 gradually increased over time. Therefore, the final result of the study is that uremia can gradually lead to myocardial hypertrophy and TLR4 and MyD88 are highly expressed in serum, kidney, and myocardial tissues of uremic rats, suggesting that TLR4 and MyD88 may be related to the degree of uremic disease and the myocardium caused by it. Hypertrophy is related.

Chemical Characterization and Hepatoprotective Effects of a Standardized Triterpenoid-Enriched Guava Leaf Extract.

Nutraceutical/pharmaceutical agents capable of maintaining redox and inflammation homeostasis are considered as candidates for the prevention and/or treatment of liver diseases. Psidium guajava (commonly known as guava) leaf is a commercially available functional food that has been reported to possess hepatoprotective property. However, the hepatoprotective constituents in guava leaf are not known. In the current study, a standardized triterpenoid-enriched extract of guava leaves (TGL) was developed. A new ursolic acid derivative, namely 2α,3ß,6ß,23,30-pentahydroxyurs-11,13(18)-dien-28,20ß-olide (1), and 23 known triterpenoids were isolated and identified from TGL. The hepatoprotective effects of TGL were evaluated through a model using acetaminophen (APAP)-exposed C57BL/6 male mice. Pretreatment of TGL (75 and 150 mg/kg) restored the mice hepatic architecture, improved the serum ALT and AST levels, and reduced the hepatic ROS and MDA contents. Further molecular mechanistic study revealed that TGL modulated Nrf2 and MAPK signaling pathways to alleviate APAP-induced oxidative and inflammatory stress in liver. In addition, the new compound 1 from TGL showed protective effects against APAP-induced cytotoxicity via activation of the Nrf2 pathway in HepG2 cells. Overall, this is the first report on the hepatoprotective effects of a standardized triterpenoid-enriched extract of guava leaves, which supports its potential nutraceutical application in liver disease management.

A Comparison of Solubility, Stability, and Bioavailability between Astilbin and Neoastilbin Isolated from Smilax glabra Rhizoma.

Astilbin and neoastilbin are two flavonoid stereoisomers. In the present study, their solubility, stability, and bioavailability were compared in a rat. The results revealed that the water solubility of astilbin and neoastilbin was 132.72 µg/mL and 217.16 µg/mL, respectively. The oil-water distribution coefficient (log P) of astilbin and neoastilbin in simulated gastric fluid (SGF) was 1.57 and 1.39, and in simulated intestinal fluid (SIF) was 1.09 and 0.98, respectively. In SIF, about 78.6% astilbin remained after 4 h of incubation at 37 °C, while this value was 88.3% for neoastilbin. Most of the degraded astilbin and neoastilbin were isomerized into their cis-trans-isomer, namely neoisoastilbin and isoastilbin, respectively, and the decomposed parts were rare. For bioavailability comparison in a rat, an HPLC method for trace amounts of astilbin and neoastilbin determination in plasma was developed, and the pretreatment of plasma was optimized. A pharmacokinetic study showed that the absolute bioavailability of astilbin and neoastilbin in a rat showed no significant difference with values of 0.30% and 0.28%, respectively.

Case of professor Xu ZOU's acupuncture technique for "benefiting kidney and strengthening anti-pathogenic qi" in promoting the absorption of COVID-19.

A case of the absorption of corona virus disease 2019 (COVID-19) promoted by professor Xu ZOU's acupuncture technique for "benefiting kidney and strengthening anti-pathogenic qi" is introduced. A female patient suffered from COVID-19, 64 years old, had been treated with acupuncture and Chinese herb granules for 10 days on the base of the oral administration of moxifloxacin. In the re-examination, the chest CT image indicated that the absorption of COVID-19 was obvious as compared with before, the nucleic acid test of novel corona virus was negative and the patient narrated no obvious discomfort. Acupuncture therapy plays its active adjuvant effect in the whole process of the treatment of COVID-19.

The active fraction of Garcinia yunnanensis suppresses the progression of colorectal carcinoma by interfering with tumorassociated macrophage-associated M2 macrophage polarization in vivo and in vitro.

Colorectal cancer (CRC) is the third most common solid tumor worldwide and has shown resistance to several immunotherapies, particularly immune checkpoint blockade therapy, which is effective in many other types of cancer. Our previous studies indicated that the active fraction of Garcinia yunnanensis (YTE-17), had potent anticancer activities by regulating multiple signaling pathways. However, knowledge regarding the mechanism and effect of YTE-17 in the prevention of CRC is limited. This study tested the effects of YTE-17 on colon cancer development in vivo by using two murine models: the carcigenic azoxymethane/dextran sulfate sodium (AOM/DSS)-induced CRC model and a genetically induced model using ApcMin/+ mice. Here, the tumor load, tumor number, histology, and even some oncogenes were used to evaluate the effect of YTE-17. The intragastric administration of YTE-17 for 12 weeks significantly decreased CRC incidence, tumor number and size, immunity, and some tumor-associated macrophage (TAM) markers, including CD206, Arg-1, IL-10, and TGF-ß. Importantly, the macrophages depletion by clodronate (CEL) also played a role in reducing the tumor burden and inhibiting tumor development, which were not affected by YTE-17 in the ApcMin/+ mice. Moreover, the YTE-17 treatment attenuated CRC cell growth in a co-culture system in the presence of macrophages. Consistently, YTE-17 effectively reduced the tumor burden and macrophage infiltration and enhanced immunity in the AOM/DSS and ApcMin/+ colon tumor models. Altogether, we demonstrate that macrophages in the microenvironment may contribute to the development and progression of CRC cells and propose YTE-17 as a new potential drug option for the treatment of CRC.

Effects of Chaga Medicinal Mushroom Inonotus obliquus (Agaricomycetes) Extracts on NOS-cGMP-PDE5 Pathway in Rat Penile Smooth Muscle Cells.

Some medicinal mushrooms have effects on sexual dysfunctions. Nitric oxide synthase (NOS)-cyclic gua-nosine monophosphate (cGMP)-phosphodiesterase 5 enzyme (PDE5) pathway is one of the pathophysiological basis of erectile dysfunction (ED). The normal erectile function involves the synthesis of nitric oxide (NO), and the subsequent accumulation of cGMP, whereas cGMP degradation is specifically controlled by PDE5, which promotes corporal smooth muscle cell (SMC) tone and terminates erection. The antioxidant activities of Inonotus obliquus (chaga) water extracts (IO1) and water extraction and alcohol precipitation extracts (IO2) were compared using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assay and oxygen radical absorbance capacity (ORAC) method. Three subtypes of NOS (nNOS, iNOS, and eNOS) and PDE5 protein expressions were tested by Western blotting, and cGMP was determined by ELISA on a rat corporal primary SMC. The results revealed that IO2, which had a significantly higher polysaccharide content than IO1, showed a significantly higher ORAC value and a significantly lower half inhibitory concentration for DPPH scavenging activity than IO1. We observed that both IO1 and IO2 increased the expression of eNOS and iNOS significantly compared with the control. Furthermore, when compared with the control, IO1 increased PDE5 expression significantly, while IO2 showed no effect. The different impacts on PDE5 might be the reason that IO2, not IO1, showed significant inducible effect on cGMP compared with the control. This is to our knowledge, the first study exploring the effect of I. obliquus on NOS-cGMP-PDE5 pathway on SMC. The results provide a possible selection of I. obliquus for the treatment of ED.

Metabolism, Excretion, and Tissue Distribution of Astilbin-Zein Nanoparticles in Rats.

The excretion, tissue distribution, and metabolic profile of astilbin in rat were studied by HPLC and UPLC-QTOF-MS. Astilbin underwent isomerization in the small intestine, and its four isomers were found in feces. Besides, taxifolin, the aglycone of astilbin, and its further metabolites by gut microbes through hydrogenation, dehydration, and ring-fission were found. The total feces excretion of astilbin was about 14.4% of administration. The forming of zein-caseinate nanoparticles can significantly delay and reduce the feces excretion of astilbin. Astilbin and its isomers were absorbed in their intact form. The main metabolites found in plasma and tissues were the methylated products. Astilbin was rapidly distributed in various tissues including brain and maintained relatively high concentration in heart. Compared with other tissues, significantly higher concentration and longer duration of astilbin were found in the gastrointestinal tract. Astilbin and its isomers were excreted in their intact and methylated form in urine.