[Bupleuri Radix-Paeoniae Radix Alba medicated plasma exerts effects on HepG2 hepatoma cells by regulating miR-1297/PTEN signaling axis].

The present study aimed to investigate the effect and mechanism of Bupleuri Radix-Paeoniae Radix Alba medicated plasma on HepG2 hepatoma cells by regulating the microRNA-1297(miR-1297)/phosphatase and tensin homologue deleted on chromosome 10(PTEN) signaling axis. Real-time quantitative PCR(RT-qPCR) was carried out to determine the mRNA levels of miR-1297 and PTEN in different hepatoma cell lines. The dual luciferase reporter assay was employed to verify the targeted interaction between miR-1297 and PTEN. The cell counting kit-8(CCK-8) was used to detect cell proliferation, and the optimal concentration and intervention time of the medicated plasma were determined. The cell invasion and migration were examined by Transwell assay and wound healing assay. Cell cycle distribution was detected by PI staining, and the apoptosis of cells was detected by Annexin V-FITC/PI double staining. The mRNA levels of miR-1297, PTEN, protein kinase B(Akt), and phosphatidylinositol 3-kinase(PI3K) were determined by RT-qPCR. Western blot was employed to determine the protein levels of PTEN, Akt, p-Akt, caspase-3, caspase-9, B-cell lymphoma-2(Bcl-2), and Bcl-2-associated X protein(Bax). The results showed that HepG2 cells were the best cell line for subsequent experiments. The dual luciferase reporter assay confirmed that miR-1297 could bind to the 3'-untranslated region(3'UTR) in the mRNA of PTEN. The medicated plasma inhibited the proliferation of HepG2 cells, and the optimal intervention concentration and time were 20% and 72 h. Compared with the blank plasma, the Bupleuri Radix-Paeoniae Radix Alba medicated plasma, miR-1297 inhibitor, miR-1297 inhibitor + medicated plasma all inhibited the proliferation, invasion, and migration of HepG2 cells, increased the proportion of cells in the G_0/G_1 phase, decreased the proportion of cells in the S phase, and increased the apoptosis rate. The medicated plasma down-regulated the mRNA levels of miR-1297, PI3K, and Akt and up-regulated the mRNA level of PTEN. In addition, it up-regulated the protein levels of PTEN, Bax, caspase-3, and caspsae-9 and down-regulated the protein levels of p-Akt, p-PI3K, and Bcl-2. In conclusion, Bupleuri Radix-Paeoniae Radix Alba medicated plasma can inhibit the expression of miR-1297 in HepG2 hepatoma cells, promote the expression of PTEN, and negatively regulate PI3K/Akt signaling pathway, thereby inhibiting the proliferation and inducing the apoptosis of HepG2 cells.

Humanistic Health Management and Cancer: Associations of Psychology, Nutrition, and Exercise with Cancer Progression and Pathogenesis.

The incidence rate of cancer is increasing year by year due to the aging of the population, unhealthy living, and eating habits. At present, surgery and medication are still the main treatments for cancer, without paying attention to the impact of individual differences in health management on cancer. However, increasing evidence suggests that individual psychological status, dietary habits, and exercise frequency are closely related to the risk and prognosis of cancer. The reminder to humanity is that the medical concept of the unified treatment plan is insufficient in cancer treatment, and a personalized treatment plan may become a breakthrough point. On this basis, the concept of "Humanistic Health Management" (HHM) is proposed. This concept is a healthcare plan that focuses on self-health management, providing an accurate and comprehensive evaluation of individual lifestyle habits, psychology, and health status, and developing personalized and targeted comprehensive cancer prevention and treatment plans. This review will provide a detailed explanation of the relationship between psychological status, dietary, and exercise habits, and the regulatory mechanisms of cancer. Intended to emphasize the importance of HHM concept in cancer prevention and better prognostic efficacy, providing new ideas for the new generation of cancer treatment.

Efficacy of Hypertonic Dextrose Proliferation Therapy for the Treatment of Rotator Cuff Lesions: A Meta-Analysis.

Background: One of the most prevalent disorders of the shoulder is rotator cuff tendinosis, which is a major contributor to shoulder discomfort and shoulder joint dysfunction. Rotator cuff tendinosis occurs in 0.3% to 5.5% of people worldwide and is diagnosed in 0.5% to 7.4% of people in China annually. We performed a meta-analysis to assess whether hypertonic dextrose proliferation therapy, a form of prolotherapy, improves the well-being of patients with rotator cuff injuries. Methods: We screened the literature by searching the PubMed, Embase, Cochrane Library, and Web of Science databases for the search terms prolotherapy, hypertonic dextrose, and rotator cuff. We identified and evaluated studies that treated individuals with rotator cuff lesions with hypertonic dextrose proliferation therapy (intervention) or a placebo (control). The outcome measures for patients with rotator cuff lesions were the visual analog scale score, the shoulder pain and disability index, and other metrics. These metrics were used to evaluate the effects of hypertonic dextrose proliferation therapy on individuals with rotator cuff diseases by meta-analysis. Results: The meta-analysis used data from 6 studies. In the 6 studies, the visual analog scale scores improved in the intervention and control categories, with greater improvement for the intervention category compared with the control category (standardized mean difference [SMD], 1.10 [95% CI, 0.37-1.83]; P = .04). In the studies that measured other outcomes, greater improvement for the intervention category compared with the control category was seen for the shoulder pain and disability index score (SMD, 8.13 [95% CI, 5.34-10.91]; P < .01), flexion (SMD, 5.73 [95% CI, 0.99-10.47]; P < .01), and abduction (SMD, 6.49 [95% CI, 0.66-12.31]; P < .05). There were no statistically significant differences of internal rotation between the intervention and control categories (SMD, -1.74 [95% CI, -4.25 to 0.78]; P = .18) and external rotation (SMD, 2.78 [95% CI, -0.13 to 5.69]; P = .06). Conclusion: The findings of this study suggest that individuals with rotator cuff injuries may benefit from hypertonic dextrose proliferation therapy based on the visual analog scale score, the shoulder pain and disability index score, flexion, and abduction. These results must, nevertheless, be supported by high-caliber follow-up research.

The association of normal-range serum phosphorus with immunoglobulin A nephropathy progression: a retrospective cohort study.

PURPOSE: The relationship between serum phosphorus and immunoglobulin A (IgA) nephropathy progression remains uncertain, especially normal-range serum phosphorus. Therefore, we herein examined the relationship between the normal-range serum phosphorus and the progression of IgA nephropathy. METHODS: One hundred sixty-two patients with primary IgA nephropathy were divided into three groups according to tertiles of baseline serum phosphorus (first tertile: 0.73-1.04 mmol/L; second tertile: 1.04-1.21 mmol/L; third tertile: 1.21-1.60 mmol/L). Estimated glomerular filtration rate (eGFR) was calculated using the chronic kidney disease epidemiology collaboration. The composite outcome was defined as a decrease of at least 50% in eGFR from baseline or end-stage kidney disease (ESKD). The association of serum phosphorus with IgA nephropathy progression was estimated using Cox proportional hazards models, adjusting for potential confounders. RESULTS: During a median 16 month follow-up period, 15 patients reached a composite outcome. In the crude Cox proportional hazard model, baseline serum phosphorus as a continuous variable was associated with increased risk for adverse renal outcomes [hazard ratio (HR) = 63.510, 95% confidence interval (CI) = 3.953-1020.284, P = 0.003], and the high tertile of serum phosphorus group had an increased risk of the composite outcome by using the low tertile group as the reference (HR = 11.895, 95% CI = 1.522-92.993, P = 0.018). After adjustment for traditional risk factors, the high tertile of serum phosphorus group was significantly related to IgA nephropathy progression compared with the low tertile group (HR = 9.424, 95% CI = 1.019-87.165, P = 0.048). CONCLUSIONS: Relatively higher serum phosphorus levels within the normal range were significantly associated with the progression of IgA nephropathy.

Global Analysis of 2-Hydroxy Fatty Acids by Gas Chromatography-Tandem Mass Spectrometry Reveals Species-Specific Enrichment in Echinoderms.

Abnormal levels of 2-hydroxy fatty acids (2-OH FAs) are characterized in multiple diseases, and their quantification in foodstuffs is critical to identify the sources of supplementation for potential treatment. However, due to the structural complexity and limited available standards, the comprehensive profiling of 2-OH FAs remains an ongoing challenge. Herein, an innovative approach based on gas chromatography-tandem mass spectrometry (GC-MS/MS) was developed to determine the full profile of these FA metabolites. MS and MS/MS spectra of the trimethylsilyl (TMS) derivatives of 2-OH fatty acid methyl esters (FAMEs) were collected for peak annotation by their signature fragmentation patterns. The structures were further confirmed by validated structure-dependent retention time (RT) prediction models, taking advantage of the correlation between the RT, carbon chain length, and double bond number from commercial standards and pseudostandards identified in the whole-brain samples from mice. An in-house database containing 50 saturated and monounsaturated 2-OH FAs was established, which is expandible when additional molecular species with different chain lengths and backbone structures are identified in the future. A quantitation method was then developed by scheduled multiple reaction monitoring (MRM) and applied to investigate the profiling of 2-OH FAs in echinoderms. Our results revealed that the levels of total 2-OH FAs in sea cucumber Apostichopus japonicas (8.40 ± 0.28 mg/g dry weight) and starfish Asterias amurensis (7.51 ± 0.18 mg/g dry weight) are much higher than that in sea urchin Mesocentrotus nudus (531 ± 108 µg/g dry weight). Moreover, 2-OH C24:1 is the predominant molecular species accounting for 67.9% of the total 2-OH FA in sea cucumber, while 2-OH C16:0 is the major molecular species in starfish. In conclusion, the current innovative GC-MS approach has successfully characterized distinct molecular species of 2-OH FAs that are highly present in sea cucumbers and starfish. Thus, these findings suggest the possibility of developing future feeding strategies for preventing and treating diseases associated with 2-OH FA deficiency.

Eudesmane-type sesquiterpenoids from the aerial parts of Artemisia lavandulaefolia and their anti-pancreatic cancer activities.

Five undescribed eudesmane sesquiterpenoids, artemilavanins A-E, and one undescribed rearranged eudesmane sesquiterpenoid, artemilavanin F, were isolated from the 95% ethanol extract of the aerial parts of Artemisia lavandulaefolia DC., along with ten known compounds. The structures and configurations of undescribed compounds were mainly elucidated by spectroscopic analyses and single-crystal X-ray diffraction analysis. Among all isolated compounds, artemilavanin F exhibited inhibitory activity on PANC-1 pancreatic cancer cells with IC50 of 9.69 ± 2.39 µM. Artemilavanin F inhibited PANC-1 cell proliferation by induction of G2/M cell cycle arrest and apoptosis mediated by downregulation of cyclin-dependent kinases and accumulation of reactive oxygen species. Moreover, artemilavanin F inhibited the colony formation, cell migration and sphere formation of PANC-1 cells, indicating the suppression of stem-cell-like phenotype of PANC-1 cells. Further results confirmed that the expression of cancer stem cell markers such as Bmi1, CD44, CD133 were inhibited by artemilavanin F. Downregulation of epithelial-mesenchymal transition (EMT) markers such as N-cadherin and Oct-4 indicated the potential of artemilavanin F in prevention of metastasis.

Modulatory Effects of Co-Fermented Pu-erh Tea with Aqueous Corn Silk Extract on Gut Microbes and Fecal Metabolites in Mice Fed High-Fat Diet.

Pu-erh tea is recognized for its weight loss effects, but its potential association with gut microbiota and metabolites remains unclear. This research explored the alterations in gut flora and metabolite composition upon treatment with a co-fermented Pu-erh tea with an aqueous corn silk extract (CPC) in obese mice by employing integrated 16S ribosomal RNA gene sequencing and untargeted metabolomics processes. For 8 weeks, mice were fed control, high-fat, and high-fat diets which included a 46 mg/mL CPC extract. The CPC extract the alleviated high-fat diet (HFD), it stimulated systemic chronic inflammation, and it reduced the body weight, daily energy consumption, and adipose tissue weight of the mice. It also modified the gut microbiota composition and modulated the Lactobacillus, Bifidobacterium, Allobaculum, Turicibacter, and Rikenella genera. Fecal metabolomics analysis revealed that the CPC extract influenced the caffeine, cysteine, methionine, tryptophan, biotin metabolism pathways, primary bile acid, and steroid biosynthesis. This research revealed that the CPC extract could inhibit HFD-stimulated abnormal weight gain and adipose tissue accumulation in mice, and modulate mice gut microbiota composition and multiple metabolic pathways.

Dietary Eicosapentaenoic Acid Containing Phosphoethanolamine Plasmalogens Remodels the Lipidome of White Adipose Tissue and Suppresses High-Fat Diet Induced Obesity in Mice.

SCOPE: Dietary supplementation of docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) can alter the lipidome profiles of adipocytes, thereby counteract obesity. DHA/EPA in the form of phospholipids demonstrates higher bioavailability than triglyceride or ethyl ester (EE), but their effects on the lipidome and metabolic changes during obesity are still unknown. METHODS AND RESULTS: High-fat diet-induced obese mice are treated with different molecular forms of EPA, and EPA supplemented as phosphoethanolamine plasmalogens (PlsEtn) has a superior effect on reducing fat mass accumulation than phosphatidylcholine (PC) or EE. The lipidomics analysis indicates that EPA in form of PlsEtn but not PC or EE significantly decreases total PC and sphingomyelin content in white adipose tissue (WAT). Some specific polyunsaturated fatty acid -containing PCs and ether phospholipids are increased in EPA-PlsEtn-fed mice, which may attribute to the upregulation of unsaturated fatty acid biosynthesis and fatty acid elongation reactions in WAT. In addition, the expression of genes related to fatty acid catabolism is also promoted by EPA-PlsEtn supplementation, which may cause the decreased content of saturated and monounsaturated fatty acid-containing PCs. CONCLUSIONS: EPA-PlsEtn supplementation is demonstrated to remodel lipidome and regulate the fatty acid metabolic process in WAT, indicating it may serve as a new strategy for obesity treatment in the future.

Qualitative and quantitative determination of chemical constituents in Jinbei oral liquid, a modern Chinese medicine for coronavirus disease 2019, by ultra-performance liquid chromatography coupled with mass spectrometry.

Introduction: Traditional Chinese medicine (TCM) has the advantages of syndrome differentiation and rapid determination of etiology, and many TCM prescriptions have been applied to the clinical treatment of coronavirus disease 2019 (COVID-19). Among them, Jinbei Oral Liquid (Jb.L) has also shown an obvious curative effect in the clinic, but the related material basic research is relatively limited. Methods: Therefore, in this process, a systematic data acquisition and mining strategy was established using ultra-high- performance liquid chromatography coupled with quadruple time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Results and Discussion: With the optimized conditions, a total of 118 peaks were tentatively characterized, including 43 flavonoids, 26 phenylpropanoids, 14 glycosides, 9 phthalides, 8 alkaloids and others. To determine the content of relevant pharmacological ingredients, we firstly exploited the ultra-performance liquid chromatography method coupled with triple-quadrupole tandem mass spectrometry (UPLC-QqQ-MS/MS) method for simultaneous detection of 31 active ingredients within 17 min, and the validation of methodology showed that this method has good precision and accuracy. Moreover, analyzing the pharmacology of 31 individual of the medicinal material preliminarily confirmed the efficacy of Jb.L and laid a foundation for an in-depth study of network pharmacology.

Polydopamine-guarded metal-organic frameworks as co-delivery systems for starvation-assisted chemo-photothermal therapy.

Cutting off glucose provision by glucose oxidase (GOx) to famish tumors can be an assistance with chemotherapy to eliminate cancer cells. Co-encapsulation of GOx and chemotherapeutics (doxorubicin) within pH-sensitive metal-organic frameworks (MOFs) could disorder metabolic pathways of cancer cells and generate excessive intracellular reactive oxygen species (ROS), together. To prevent premature leach of GOx from the porous channels of MOFs, polydopamine (PDA) was deposited on the surface of MOFs, which endowed the delivery system with photothermal conversion ability. Our nanoscaled co-delivery system (denoted as DGZPNs) remains stable with low amount of drug leakage under simulated physiological conditions in vitro and internal environment, while they are triggered to release doxorubicin (DOX) and GOx in acid tumor microenvironment and at high temperature for reinforced chemotherapy. NIR laser irradiation also activates superior photothermal conversion efficiency of PDA (36.9 %) to initiate hyperthermia to ablate tumor tissue. After being phagocytized by 4 T1 cells (breast cancer cells), the DGZPNs delivery system showed a superior therapeutic efficacy with a tumor growth inhibition of 88.9 ± 6.6 % under NIR irradiation, which indicated that the starvation-assisted chemo-photothermal therapy prompts the significant advance of synergistic therapy in a parallelly controlled mode.

Modulation of the p38 MAPK Pathway by Anisomycin Promotes Ferroptosis of Hepatocellular Carcinoma through Phosphorylation of H3S10.

Hepatocellular carcinoma (HCC) is a prevalent malignant tumor worldwide. Ferroptosis is emerging as an effective target for tumor treatment as it has been shown to potentiate cell death in some malignancies. However, it remains unclear whether histone phosphorylation events, an epigenetic mechanism that regulates transcriptional expression, are involved in ferroptosis. Our study found that supplementation with anisomycin, an agonist of p38 mitogen-activated protein kinase (MAPK), induced ferroptosis in HCC cells, and the phosphorylation of histone H3 on serine 10 (p-H3S10) was participated in anisomycin-induced ferroptosis. To investigate the anticancer effects of anisomycin-activated p38 MAPK in HCC, we analyzed cell viability, colony formation, cell death, and cell migration in Hep3B and HCCLM3 cells. The results showed that anisomycin could significantly suppress HCC cell colony formation and migration and induce HCC cell death. The hallmarks of ferroptosis, such as abnormal accumulation of iron and elevated levels of lipid peroxidation and malondialdehyde, were detected to confirm the ability of anisomycin to promote ferroptosis. Furthermore, coincubation with SB203580, an inhibitor of activated p38 MAPK, partially rescued anisomycin-induced ferroptosis. And the levels of p-p38 MAPK and p-H3S10 were successively increased by anisomycin treatment. The relationship between p-H3S10 and ferroptosis was revealed by ChIP sequencing. The reverse transcription PCR and immunofluorescence results showed that NCOA4 was upregulated both in mRNA and protein levels after anisomycin treatment. And by C11-BODIPY staining, we found that anisomycin-induced lipid reactive oxygen species was reduced after NCOA4 knockdown. In conclusion, the anisomycin-activated p38 MAPK promoted ferroptosis of HCC cells through H3S10 phosphorylation.

Network pharmacology-based prediction of active compounds in the Wenyang Jiedu Huayu formula acting on acute-on-chronic liver failure with experimental support in vitro and in vivo.

Acute-on-chronic liver failure (ACLF) is characterized by undermined liver function, massive necrosis/apoptosis of hepatocytes, and hepatic inflammatory cell recruitment, leading to multiorgan failure. Traditional Chinese medicine (TCM) has been widely applied in clinical and experimental studies of ACLF. In this study, 23 compounds with 6,386 drug targets were obtained from Wenyang Jiedu Huayu (WYJDHY), and 8,096 genes were identified as ACLF disease targets, among which 3,132 were overlapping co-targets. Expression profile analysis identified 105 DEGs among the co-targets, which were associated with biological activities such as lymphocyte activation, immune response regulation, and pathways such as Th17 cell differentiation and NF-κB signaling. After PPI analysis and network construction, atractylenolide I (AT-1) has been identified as the hub active ingredient of the WYJDHY formula. LPS stimulation inhibited rat hepatocytes' BRL 3A cell viability, promoted cell apoptosis, increased the levels of ALT, AST, IL-6, and VCAM-1 within the culture medium, and activated NF-κB signaling, whereas AT-1 treatment significantly attenuated LPS-induced toxicity on BRL 3A cells. Furthermore, the NF-κB signaling inhibitor PDTC exerted effects on LPS-stimulated BRL 3A cells similar to those of AT-1, and the combination of PDTC and AT-1 further attenuated LPS-induced toxicity on BRL 3A cells. In vivo, AT-1 alone or with PDTC improved the symptoms and local inflammation in ACLF model rats. In conclusion, 23 active ingredients of six herbs in the WYJDHY formula were retrieved, and 105 co-targets were differentially expressed in ACLF. AT-1 exerts protective effects on LPS-stimulated hepatocytes and ACLF rats, possibly by inhibiting the NF-κB pathway.

A Multifunctional Photoacoustic/Fluorescence Dual-Mode-Imaging Gold-Based Theranostic Nanoformulation without External Laser Limitations.

Theranostics is a new type of biomedical technology that organically combines the diagnosis and therapy of diseases. Among molecular imaging techniques, the integration of photoacoustic (PA) and fluorescence (FL) imaging modes with high sensitivity and imaging depth provides precise diagnostic outcomes. Gold nanorods (Au NRs) are well-known contrast agents for PA imaging and photothermal therapy. However, their high toxicity, poor biocompatibility, rapid clearance, and the need for an external laser source limit their application. Therefore, modification of Au NRs with carbon-based nanomaterials (CBNs) is done to obtain a multifunctional dual-mode gold-based nanoformulation (mdGC), which preforms dual-mode imaging of PA and FL. The results show that mdGC promotes tumor cell apoptosis and exhibits good antitumor performance through the mitochondria-mediated apoptotic pathway by increasing the production of intracellular reactive oxygen species, reducing mitochondrial membrane potential, and regulating the expression of apoptosis-related genes. The targeting rate of mdGC to tumor tissue is up to 20.71 ± 1.94% ID g-1 ; the tumor growth inhibition rate is as high as 80.44% without external laser sources. In general, mdGC is a potential multifunctional diagnostic and therapy integrated nanoformulation.

Moxibustion for anorexia in COVID-19: A protocol for systematic review and meta-analysis.

BACKGROUND: As the outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread over the world, the World Health Organization has declared the outbreak of COVID-19 an international public health emergency. Besides typical respiratory symptoms and signs of COVID-19, digestive symptoms and liver injury have been frequently reported during the course of the disease. The purpose of this study was to evaluate the efficacy and safety of moxibustion in the treatment of anorexia in patients with COVID-19. METHODS: According to the retrieval strategies, randomized controlled trials on moxibustion therapies for C19-A will be obtained from the China National Knowledge Infrastructure, WanFang Data, Chinese Scientific Journals Database, PubMed, Embase, and Cochrane Library, regardless of publication date or language. Studies will be screened based on inclusion and exclusion criteria, and the Cochrane risk bias assessment tool will be used to evaluate the quality of the literature. The network meta-analysis will be performed with the Markov chain Monte Carlo method and carried out with Stata 14.2 and WinBUGS 1.4.3 software. Ultimately, the quality of the evidence obtained from the results will be evaluated. RESULTS: This study will evaluate whether moxibustion therapy can effectively treat anorexia in patients with COVID-19. CONCLUSION: This study will provide evidence for whether moxibustion therapy is beneficial to the treatment of anorexia in patients with COVID-19. TRIAL REGISTRATION NUMBER: CRD42022302499.

[Professor YANG Ji-guo's experience in treatment of functional gastrointestinal diseases with acupuncture combined with umbilicus moxibustion].

Professor YANG Ji-guo's clinical experience in treatment of functional gastrointestinal diseases was summerized. Professor YANG Ji-guo believes that this disease is caused by the deficiency of six fu organs. Dysfunction of six fu organs in descending transportation is the basic pathogenesis. The principle of acupoint selection includes benefiting gastrointestinal functions, unblocking and purging six fu, soothing liver qi and calming down the mind. In treatment, acupuncture is combined with umbilicus moxibustion. In acupuncture, the deqi promoting technique by rotating and trembling needle is adopted. Focusing on the deficiency of six fu organs, umbilicus moxibustion is adopted to benefit the spleen and stomach and harmonize the functions of six fu organs for both biao (symptoms) and ben (root cause).

seco-Prezizanne Sesquiterpenes and Prenylated C6-C3 Compounds from the Fruits of Illicium lanceolatum A. C. Smith.

Two new seco-prezizaane-type sesquiterpenes, 2ß-hydroxy-6-deoxyneoanisatin (1) and 3,4-anhydro-2-oxo-1α-hydroxy-6-deoxyneoanisatin (2), and two new prenylated C6 -C3 compounds, illilanceofunones A (3) and B (4), were obtained from the fruits of Illicium lanceolatum, along with four known prenylated C6 -C3 compounds (5-8). Their structures were proposed through HR-ESI-MS, 1 H, 13 C, and 2D NMR data interpretation. Moreover, the absolute configuration of 1 and 2 were further assigned by single-crystal X-ray diffraction analysis and electronic circular dichroism (ECD) calculations, respectively. Illihenryipyranol A (6) exhibited neuroprotective activity against MPP+ -induced PC12 cell damage in a dose-dependent manner.

Sterol sulfate alleviates atherosclerosis via mediating hepatic cholesterol metabolism in ApoE-/- mice.

Compared with terrestrial organisms, the sterols in sea cucumber exhibit a sulfate group at the C-3 position. Our previous study demonstrated that dietary sterol sulfate was superior to phytosterol in alleviating metabolic syndrome by ameliorating inflammation and mediating cholesterol metabolism in high-fat-high-fructose diet mice, which indicated its potential anti-atherosclerosis bioactivity. In the present study, administration with sea cucumber-derived sterol sulfate (SCS) significantly decreased the cholesterol level in oleic acid/palmitic acid-treated HepG2 cells, while no significant changes were observed in the triacylglycerol level. RNA-seq analysis showed that the metabolic changes were mostly attributed to the steroid biosynthesis pathway. ApoE-/- mice were used as an atherosclerosis model to further investigate the regulation of SCS on cholesterol metabolism. The results showed that SCS supplementation dramatically reduced atherosclerotic lesions by 45% and serum low-density lipoprotein cholesterol levels by 59% compared with the model group. Dietary SCS inhibited hepatic cholesterol synthesis via downregulating SREBP-2 and HMGCR. Meanwhile, SCS administration increased cholesterol uptake via enhancing the expression of Vldlr and Ldlr. Noticeably, SCS supplementation altered bile acid profiles in the liver, serum, gallbladder and feces, which might cause the activation of FXR in the liver. These findings provided new evidence about the high bioactivity of sterols with the sulfate group on atherosclerosis.

Dietary n-3 PUFA Deficiency Increases Vulnerability to Scopolamine-Induced Cognitive Impairment in Male C57BL/6 Mice.

BACKGROUND: DHA (22:6n-3), a long-chain n-3 PUFA, is essential for normal brain development and function. Our previous study demonstrated that DHA significantly improves scopolamine-induced dementia. However, there are no reports on the relation between n-3 PUFA deficiency and scopolamine-induced cognitive impairment. OBJECTIVES: The aim of this study was to evaluate whether n-3 PUFA deficiency increases vulnerability to scopolamine-induced cognitive impairment. METHODS: Male and female C57BL/6 mice were mated and fed an n-3 PUFA-adequate [containing 2.88% α-linolenic acid (ALA; 18:3n-3)] or -deficient (containing 0.09% ALA) diet for 2 consecutive generations. The corresponding second-generation male offspring were kept on the same diet as their mothers after weaning, and were randomly assigned to 2 subgroups at 7 wk of age, in which they were intraperitoneally injected with saline [fed n-3 PUFA-adequate (Con) or -deficient (Def) diet] or scopolamine [5 mg/kg body weight; fed n-3 PUFA-adequate (Sco) or -deficient (Def + Sco) diet] once per day for 7 d before killing. Behavioral performance was analyzed using the Morris Water Maze test. Fatty acid composition, protein expression, and indicators of cholinergic and oxidative stress in the brain were measured. RESULTS: The Def group showed lower brain DHA (-63.7%, P ≤ 0.01) and higher n-6 PUFA (+65.5%, P ≤ 0.05) concentrations than the Con group. The Def + Sco group and the Sco group showed poorer spatial learning and memory (escape latency on the sixth day: +60.3% and +36.8%; platform crossings: -43.9% and -28.2%, respectively) and more obvious cholinergic dysfunction (acetylcholine: -47.6% and -27.7%, respectively), oxidative stress (glutathione peroxidase: -64.2% and -32.5%, respectively), apoptosis [B-cell lymphoma 2 (BCL2)-associated X protein/BCL2: +230.8% and +153.8%; phosphorylated P38/P38: +232% and +130%, phosphorylated c-Jun N-terminal kinase (JNK)/JNK: +104.5% and +58.8%, respectively], neuroinflammation (IL-1ß: +317.6% and +95%, respectively), and neurodevelopmental delay (brain-derived neurotrophic factor: -54.4% and -7.25%, respectively) than their corresponding saline-treated controls. CONCLUSIONS: Dietary n-3 PUFA deficiency significantly decreases brain DHA concentrations and increases vulnerability to scopolamine-induced cognitive impairment in C57BL/6 male mice.

Sea cucumbers-derived sterol sulfate alleviates insulin resistance and inflammation in high-fat-high-fructose diet-induced obese mice.

Sea cucumbers are widely consumed in traditional medicine and food. Sea cucumbers-derived sulfated sterol exhibits a sulfate group at C-3 position, which is different from phytosterol with a hydroxyl group. However, the effect of sterol sulfate on metabolic syndrome remains unknown. The purpose of the present study is to investigate the alleviation of sterol sulfate on high-fat-high-fructose diet (HFFD)-induced insulin resistance and inflammation. After 2 weeks feeding with HFFD, male C57BL/6J mice were continuously fed with HFFD plus 0.4 % (w/w) sterol sulfate or phytosterol for 6 weeks. The OGTT was carried out at 7 weeks. At the end of the experimental period, the changes of glycogen, circulating glucose, insulin, pro-inflammatory cytokine and adiponectin were measured. H&E staining was used to observe the morphological changes in adipose tissue. Furthermore, the underlying molecular mechanisms were investigated. Dietary sterol sulfate was superior to phytosterol in reducing body weight gain, adipocyte hypertrophy, and levels of circulating glucose and insulin, as well as increasing the glycogen content of tissues. Furthermore, sterol sulfate ameliorated insulin resistance mainly due to the inhibition of gluconeogenesis, the promotion of glycogen synthesis and GLUT4 translocation by activating PI3K/Akt signaling pathway. Additionally, sterol sulfate effectively attenuated inflammation by increasing serum adiponectin and reducing pro-inflammatory cytokine release. Sterol sulfate exhibited a more significant effect than phytosterol in alleviating HFFD -induced insulin resistance and inflammation, which might be closely related to the sulfate group. The results might provide insights into the prevention and alleviation of metabolic syndrome.

Phytochemical identification of Lithocarpus polystachyus extracts by ultra-high-performance liquid chromatography-quadrupole time-of-flight-MS and their protein tyrosine phosphatase 1B and α-glucosidase activities.

Lithocarpus polystachyus leaves exhibit antidiabetic activity and is consumed as a herbal tea in China. In this study, phytochemical profiles of L. polystachyus leaves were identified and characterized by ultra-high-performance liquid chromatography-quadrupole time-of-flight-MS in both positive and negative ion modes. A total of 17 compounds were tentatively characterized and identified by accurate mass and characteristic fragment ions. The total phenolic contents in the leaf extracts ranged from 9.0 to 13.4 g gallic acid equivalents/100 g of dry weight (DW). In addition, the effect of these extracts on inhibiting the activities of α-glucosidase and protein tyrosine phosphatase 1B (PTP1B) were evaluated. L. polystachyus extracts demonstrated significant inhibition of α-glucosidase (more than 88.1% at a concentration of 1.25 mg/mL) and acarbose (93.6% at a concentration of 5 mg/mL) while the PTP1B inhibition rate was over 84.3%. The antioxidant capacities of the leaf extracts were determined using 2,2-diphenyl-1-picrylhydrazyl, ABTS, and ferric reducing ability of plasma methods and ranged from 50.5 to 72.5 g trolox, from 43.2 to 77.7 g trolox, and from 5.0 to 10.6 g butylated hydroxytoluene (BHT; equaling trolox or BHT per 100 g of DW), respectively. Based on these results, L. polystachyus can be considered as a functional food owing to its antidiabetic and antioxidative activities, which are attributed to its rich phenolic and dihydrochalcone contents.