Optimization of Flavonoid Extraction from Abelmoschus manihot Flowers Using Ultrasonic Techniques: Predictive Modeling through Response Surface Methodology and Deep Neural Network and Biological Activity Assessment.

Understanding the optimal extraction methods for flavonoids from Abelmoschus manihot flowers (AMF) is crucial for unlocking their potential benefits. This study aimed to optimize the efficiency of flavonoid extraction from AMF. After comparing extraction methods, the ultrasonic cell crusher demonstrated superior performance over conventional techniques. Four key factors-solid-to-liquid ratio (1:10 to 1:50 g·mL-1), ethanol concentration (55% to 95%), ultrasonic time (10 to 50 min), and ultrasonic power (5% to 25% of 900 W)-were investigated and normalized using the entropy weight method. This led to a comprehensive evaluation (CE). Optimization of extraction conditions for the ultrasonic cell crusher was achieved through response surface methodology and a deep neural network model, resulting in optimal parameters: ethanol volume fraction of 66%, solid-to-liquid ratio of 1:21 g/mL, extraction efficiency of 9%, and extraction duration of 35 min, yielding a CE value of 23.14 (RSD < 1%). Additionally, the inhibitory effects of the optimized extracts against Streptococcus mutans (S. mutans) were assessed. The results revealed that AMF extract (AMFE) exhibits inhibitory effects on S. mutans, with concomitant inhibition of sucrase and lactate dehydrogenase (LDH). The MIC of AMFE against planktonic S. mutans is 3 mg/mL, with an MBC of 6 mg/mL. Within the concentration range of 1/8 MIC to 2 MIC of AMFE, the activities of sucrase and LDH decreased by 318.934 U/mg prot and 61.844 U/mg prot, respectively. The antioxidant activity of AMFE was assessed using the potassium ferricyanide reduction and phosphomolybdenum methods. Additionally, the effect of AMFE on DPPH, ABTS, and ·OH free radical scavenging abilities was determined. The concentrations at which AMFE exhibited over 90% scavenging rate for ABTS and DPPH free radicals were found to be 0.125 mg/mL and 2 mg/mL, respectively.

Enhanced efficacy with reduced toxicity of chemotherapy drug 5-fluorouracil by synergistic treatment with Abnormal Savda Munziq from Uyghur medicine.

BACKGROUND: Abnormal Savda Munziq (ASMq) is a traditional prescription in Uyghur Medicine, and its treatment of complex diseases such as tumors and asthma has been proven to be effective in Uyghur medical clinical practice. The efficacy-enhancing and toxicity-reducing properties of ASMq were studied on mice with transplanted cervical cancer (U27) tumors, which were treated with 5-fluorouracil (5-FU) in this work. METHODS: To investigate the synergistic effect of ASMq and 5-FU on U27 cells, inhibitory effects on cell proliferation were determined through a MTT assay. 48 Kunming mice which were randomly divided in to 6 groups: control group, model group, 5-FU group, 5-FU combine with ASMq low-dose group, 5-FU combine with ASMq medium-dose group, and 5-FU combine with ASMq high- dose group, the inhibition rate of the tumor, the viscera indexes, and the content of serum tumor necrosis factor-α (TNF-α), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined. The expression levels of transforming growth factor-ß1 (TGF-ß1) and human papillomavirus type 16 E2 (HPV16 E2) protein were assessed by Western blot. Pathological changes in the liver were observed. RESULT: The inhibition rates of tumors, the 5-FU + ASMq.H group(80.64%), 5-FU + ASMq.M group (90.67%), 5-FU + ASMq.L group (72.03%) and 5-FU group (66.89%), clearly indicated that the effects of tumor inhibition. The thymus index and spleen index were increased, and the serum concentration of TNF-α increased while ALT and AST concentrations were decreased, and TNF-α protein expression were increased while TGF-ß1 and HPV16 E2 were decreased. ASMq might can improve livers central vein hyperemia and interstitial edema, and preserve the radial structure of the hepatic cords. CONCLUSIONS: The results suggested that ASMq might reduce toxicity and enhance the efficacy of the chemotherapeutic drug 5-fluorouracil in the treatment of cervical carcinoma.

Protective effects of traditional Uighur medicine-seeds of Nigella glandulifera Freyn extracts against ccl4-induced acute hepatic injury in mice.

To explore the protective effects of Traditional Uighur medicine Seeds of Nigella glandulifera Freyn (SNF) extracts against CCl4-induced acute hepatic injury in mice. Hepatic injury mice models induced by intraperitoneal injection of 0.1% CCl4 olive oil were established. Liver and spleen coefficient, Serum ALT and AST activities, SOD, GSH-Px activities and MDA content in hepatic homogenate were measured and the hepatic histological changes were observed by optical microscope. Serum activities of ALT (P<0.01) and AST (P<0.05) in Alcohol extraction group was decreased; Activity of hepatic homogenate SOD increased in Alcohol extraction group and Water extraction group significantly (P<0.05). Content of MDA was decreased in Alcohol extraction group (P<0.01). Water extracts of SNF have obvious protective effects on hepatic injury induced by CCl4 in mice.

Anti-tumor effects of Abnormal Savda Munziq on the transplanted cervical cancer (U27) mouse model.

BACKGROUND: Abnormal Savda Munziq (ASMq), a traditional uyghur medicine, has shown anti-tumour properties in vitro. it was showed that total flavonoids of ASMq could inhibit the proliferation and enhance the antioxidant ability of human cervix cancer HeLa cell. This study attempts to confirm these effects on the transplanted cervical cancer (U27) mouse model in vivo. METHODS: Forty eight Kunming mice were randomly divided in to six groups: normal control group (Control group), U27 tumor model group (Model group), cyclophosphamide administration group (CTX group),low-dose ASMq group (ASMq.L group), medium-dose ASMq group (ASMq.M group), and high-dose ASMq group (ASMq.H group). The five groups except normal control group transplanted with cervical cancer (U27) cells. We observed mice tumor inhibition rate and conducted the histopathological analysisUsing the western blot assay, the expression of TGF-ß1 and TNF-α protein in transplanted cervical cancer U27 tumor tissue were detected. RESULTS: The tumor inhibition rates of CTX group, ASMq.L group, ASMq.M group, and ASMq.H group were 72.21, 31.27, 60.53 and 51.94% respectively, has obvious antitumor effect. ASMq significantly promote the spleen tlymphocyte proliferation of transplanted cervical cancer U27 mice. Invasive growth and diffusion rate in tumor tissue were accelerate in the transplanted cervical cancer U27 model group. Tumor tissue necrosis of tumor cells are smaller in the medium, high dosage group. Compared with the U27 model group, the expression levels of TGF-ß1 protein and TNF-α protein expression exhibited statistically significant decreased in the mice tumor tissues in the CTX administration group and the ASMq administration group. CONCLUSIONS: ASMq has some antitumor effects on U27 model mice in vivo, The effects are achieved not only by improving the immune function of U27 model mice, but also by inhibiting the expression levels of TGF-ß1 protein while promoting the expression levels of TNF-α protein.

Genetic polymorphisms of pharmacogenomic VIP variants in the Uygur population from northwestern China.

BACKGROUND: Drug response variability observed amongst patients is caused by the interaction of both genetic and non-genetic factors, and frequencies of functional genetic variants are known to vary amongst populations. Pharmacogenomic research has the potential to help with individualized treatments. We have not found any pharmacogenomics information regarding Uygur ethnic group in northwest China. In the present study, we genotyped 85 very important pharmacogenetic (VIP) variants (selected from the PharmGKB database) in the Uygur population and compared our data with other eleven populations from the HapMap data set. RESULTS: Through statistical analysis, we found that CYP3A5 rs776746, VKORC1 rs9934438, and VKORC1 rs7294 were most different in Uygur compared with most of the eleven populations from the HapMap data set. Compared with East Asia populations, allele A of rs776746 is less frequent and allele A of rs7294 is more frequent in the Uygur population. The analysis of F-statistics (Fst) and population structure shows that the genetic background of Uygur is relatively close to that of MEX. CONCLUSIONS: Our results show significant differences amongst Chinese populations that will help clinicians triage patients for better individualized treatments.

Investigation of the Hepato-Protective Effects of Imdur in a Rat Model of Chronic Mountain Sickness.

BACKGROUND: The objective of this study was to determine if the clinical nitrate, Imdur, has a hepato-protective effect in chronic mountain sickness (CMS). METHODS: A total of 60 SD rats were included in the study. Fifty rats were used to model CMS and were randomly divided into the following groups (10 rats per group): 1) plateau, 2) nifedipine, 3) low dose imdur, 4) moderate dose imdur, and 5) high dose imdur. The remaining 10 rats were used for the control group. Thirty days after the CMS model was established, according to the appropriate body weight of the rats, intragastric administration of the treatment groups commenced. After 15 days, changes in pulmonary artery pressure (PAP) and pathology of liver tissues were observed. Homocysteine (Hcy), interleukin-6 (IL-6), C-reactive protein (CRP), superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-PX) levels were also measured. RESULTS: Compared with the control group, the levels of PAP, Hcy, IL-6, CRP, and MDA of the rats in the plateau model group, nifedipine group, and imdur groups were elevated. The levels of SOD and GSH-PX in these groups decreased relative to the control group. The injured rat livers were observed under the light microscope, revealing that hypoxia had caused tissue damage. Compared with that of the plateau model group, the levels of PAP, Hcy, IL-6, CRP, and MDA of the rats in the high dose imdur group were decreased (p < 0.05), and the levels of SOD and GSH-PX were increased (p < 0.05). Except for IL-6, the other parameters were comparable to normal values and better than those of the nifedipine group. Liver tissue from the high dose imdur group demonstrated less tissue damage from pathological sections. CONCLUSIONS: High dose imdur has hepato-protective effects in CMS rat models.

Genetic Polymorphisms Analysis of Pharmacogenomic VIP Variants in Miao Ethnic Group of Southwest China.

BACKGROUND Genetic polymorphisms have a potential clinical role in determining both inter-individual and inter-ethnic differences in drug efficacy, but we have not found any pharmacogenomics information regarding minorities, such as the Miao ethnic group. Our study aimed to screen numbers of the Miao ethnic group for genotype frequencies of VIP variants and to determine differences between the Miao and other human populations worldwide. MATERIAL AND METHODS In this study, we genotyped 66 Very Important Pharmacogene (VIP) variants selected from PharmGKB in 98 unrelated, healthy Miao individuals from the Guizhou province and compared our data with 12 other populations, including 11 populations from the HapMap data set and Xi'an Han Chinese. RESULTS Using the χ2 test, we found that the allele frequencies of the VDR rs1544410 and VKORC1 (rs9934438) variants in the Miao population are quite different from that in other ethnic groups. Furthermore, we found that genotype frequencies of rs1801133 (MTHFR) in the 13 selected populations are significantly different. Population structure and F-statistics (Fst) analysis show that the genetic background of the Miao is relatively close to that of Chinese in metropolitan Denver, CO, USA (CHD). CONCLUSIONS Our results help complete the information provided by the pharmacogenomics database of the Miao ethnic group and provide a theoretical basis for safer drug administration, which may be useful for diagnosing and treating diseases in this population.

Effects and mechanisms of acetyl-L-cysteine in rats with chronic mountain sickness with H1-NMR metabolomics methods.

BACKGROUND: We established a rat model of chronic mountain sickness using acetyl-L-cysteine. Then we studied the effects and mechanisms of acetyl-L-cysteine (Da) in rats with chronic mountain sickness using nuclear magnetic resonance (H1-NMR) metabolomics methods. MATERIAL AND METHODS: Using NMR spectroscopy combined with pattern recognition and orthogonal partial least squares discriminant analysis, we analyzed the impact of Da on blood metabolism in rats with chronic mountain sickness by determining different metabolites and changes in metabolic network in the blood of rats with mountain sickness after the intragastric administration of different doses of Da suspension. RESULTS: Increased levels of amino acids (valine, tyrosine, 1-methyl-histidine, leucine, phenylalanine, and methionine) were detected in the blood of rats in the chronic mountain sickness group, yet significantly decreased levels were detected in control rats. At the same time, ß-glucose and α-glucose levels were markedly elevated in the blood of rats in the model group but decreased in the chronic mountain sickness group, which indicated a statistically significant difference compared with the chronic altitude sickness model group (P<0.05). CONCLUSIONS: Da has a significant impact on the metabolism of rats with chronic mountain sickness. Da may act on the disturbed glucose metabolism and amino acid metabolism in rats triggered by chronic mountain sickness, resulting in the treatment and prevention of this disease.

Effects of the ACE2-Ang-(1-7)-Mas axis on gut flora diversity and intestinal metabolites in SuHx mice.

Objective: Pulmonary artery hypertension (PAH) poses a significant challenge due to its limited therapeutic options and high mortality rates. The ACE2-Ang-(1-7)-Mas axis plays a pivotal role in regulating blood pressure and inhibiting myocardial remodeling. However, the precise mechanistic links between the ACE2-Ang-(1-7)-Mas axis and PAH remain poorly understood. This study aimed to elucidate the involvement of the ACE2-Ang-(1-7)-Mas axis in the development of PAH. Methods: PAH was induced in mice using Sugen5416/hypoxia, PAAT/PET ratio and PA were detected using cardiac ultrasound; inflammation related factors such as MCP-1, TNF, IL-10and IL-12p70 were detected in intestines using cytometric bead array (CBA) kits; histopathological and morphological changes in lung and intestinal tissues were assessed via HE staining and Masson staining to evaluate the progression of PAH. Immunohistochemistry and western blotting were employed to determine the expression levels of two tight junction proteins, occludin and ZO-1, in intestinal tissues. Additionally, 16rRNA sequencing and non-targeted metabolomics by LC-MS/MS techniques were utilized to investigate the impact of the ACE2-Ang-(1-7)-Mas axis on microbial diversity and metabolomics of intestinal contents. Results: Activation of the ACE2-Ang-(1-7)-Mas axis improves heart function, reduces intestines inflammatory factors and ameliorates pathological and histological alterations in SuHx mice. This activation notably upregulated the expression of occludin and ZO-1 proteins in intestinal tissues and promoted the proliferation of SCFA-producing bacteria genera, such as g_Candidatus_Saccharimonas. Furthermore, it enhanced the abundance of beneficial metabolites, including tryptophan and butyric acid. Conclusion: The findings suggest that modulation of the ACE2-Ang-(1-7)-Mas axis can alleviate PAH by regulating intestinal microbes and metabolites. These results highlight the potential of the ACE2-Ang-(1-7)-Mas axis as a promising therapeutic target for clinical management of PAH.

Brown adipose Vanin-1 is required for the maintenance of mitochondrial homeostasis and prevents diet-induced metabolic dysfunction.

BACKGROUND: Energy-dissipating brown adipocytes have significant potential for improving systemic metabolism. Vanin-1, a membrane-bound pantetheinase, is involved in various biological processes in mice. However, its role in BAT mitochondrial function is still unclear. In this study, we aimed to elucidate the impact of Vanin-1 on BAT function and contribution during overnutrition-induced obesity. METHODS: Vanin-1 expression was analyzed in different adipose depots in mice. The cellular localization of Vanin-1 was analyzed by confocal microscopy and western blots. Mice lacking Vanin-1 (Vanin-1-/-) were continuously fed either a chow diet or a high-fat diet (HFD) to establish an obesity model. RNA-seq analysis was performed to identify the molecular changes associated with Vanin-1 deficiency during obesity. BAT-specific Vanin-1 overexpression mice were established to determine the effects of Vanin-1 in vivo. Cysteamine treatment was used to examine the effect of enzymatic reaction products of Vanin-1 on BAT mitochondria function in Vanin-1-/- mice. RESULTS: The results indicate that the expression of Vanin-1 is reduced in BAT from both diet-induced and leptin-deficient obese mice. Study on the subcellular location of Vanin-1 shows that it has a mitochondrial localization. Vanin-1 deficiency results in increased adiposity, BAT dysfunction, aberrant mitochondrial structure, and promotes HFD induced-BAT whitening. This is attributed to the impairment of the electron transport chain (ETC) in mitochondria due to Vanin-1 deficiency, resulting in reduced mitochondrial respiration. Overexpression of Vanin-1 significantly enhances energy expenditure and thermogenesis in BAT, renders mice resistant to diet-induced obesity. Furthermore, treatment with cysteamine rescue the mitochondrial dysfunction in Vanin-1-/- mice. CONCLUSIONS: Collectively, these findings suggest that Vanin-1 plays a crucial role in promoting mitochondrial respiration to counteract diet-induced obesity, making it a potential therapeutic target for obesity.

Phenolic Constituents with Glucose Uptake and GLUT4 Translocation Bioactivities from the Fruits of Cordia dichotoma.

From the fruits of Cordia dichotoma, 11 new phenolic compounds, dichotomins A-K, were isolated, together with 19 known compounds. Through the analysis of detailed NMR data and HRESIMS data, the planar structures of all compounds were confirmed. Using NMR calculations, the absolute configuration of dichotomins A-K was elucidated by comparing their observed and computed electronic circular dichroism (ECD) spectra. Dichotomin H (8) and dichotomin I (9) were determined as two pairs of enantiomers. The enantiomers of compounds 8 and 9 were separated using chiral-phase high-performance liquid chromatography (HPLC), and the stereostructure of each enantiomer was determined by similarly calculating the ECD. Compounds 3, 5, 7, 17, 18, 23-25, and 27-30 increased glucose uptake by 1.04- to 2.85-folds at concentrations of 30 µg/mL. Further studies revealed that compounds 3 and 5 had a moderate effect on glucose transporter 4 (GLUT4) translocation activity in L6 cells. At 30 µg/mL, compound 3 significantly enhanced AMPK phosphorylation and GLUT4 expression. As a whole, compound 3 has the potential to be a drug candidate for the treatment of type 2 diabetes mellitus (T2DM).

Characterization of the distinct immune microenvironments between hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

As two major types of primary liver cancers, the tumor immune microenvironment (TIME) of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) have been well studied separately. However, a systemic assessment of the similarities and differences between the TIME of HCC and ICC is still lacking. In this study, we pictured a landscape of combined TIME of HCC and ICC by sequencing and integrating 41 single-cell RNA-seq samples from four different tissue types of both malignancies. We found that T cells in HCC tumors generally exhibit higher levels of immunosuppression and exhaustion than those in ICC tumors. Myeloid cells in HCC and ICC tumors also exhibit distinct phenotypes and may serve as a key factor driving the differences between their TIMEs. Besides, we identified a cluster of EGR1+ macrophages specifically enriched in HCC tumors. Together, our study provides new insights into cellular composition, states and interactions in the TIMEs of HCC and ICC, which could pave the way for the development of future therapeutic targets for liver cancers.

Oral delivery of sodium alginate/chitosan bilayer microgels loaded with Lactobacillus rhamnosus GG for targeted therapy of ulcerative colitis.

Probiotics regulate intestinal flora balance and enhance the intestinal barrier, which is useful in preventing and treating colitis. However, they have strict storage requirements. In addition, they degrade in a strongly acidic environment, resulting in a significant decrease in their activity when used as microbial agents. Lactobacillus rhamnosus GG (LGG) was loaded into acid-resistant and colon-targeting double-layer microgels. The inner layer consists of guar gum (GG) and low methoxyl pectin (LMP), which can achieve retention and degradation in the colon. To achieve colon localization, the outer layer was composed of chitosan (CS) and sodium alginate (SA). The formulation demonstrated favorable bio-responses across various pH conditions in vitro and sustained release of LGG in the colon lesions. Bare LGG survival decreased by 52.2 % in simulated gastric juice (pH 1.2) for 2 h, whereas that of encapsulated LGG decreased by 18.5 %. In the DSS-induced inflammatory model, LGG-loaded microgel significantly alleviated UC symptoms in mice and reduced inflammatory factor levels in the colon. Encapsulation of LGG improved its stability in acidic conditions, thus increasing its content at the colon lesions and reducing pathogenic bacteria. These findings provide an experimental basis and a technical reference for developing and applying probiotic microgel preparations.

Protective effects of the Terminalia bellirica tannin-induced Nrf2/HO-1 signaling pathway in rats with high-altitude pulmonary hypertension.

BACKGROUND: Oxidative stress and endothelial cell dysfunction induced by high-altitude hypoxia have important roles in the pathological process of high-altitude pulmonary hypertension (HAPH). Tannins present in Terminalia bellirica (Gaertn.) Roxb. (TTR) have pharmacological activities that produce oxidation resistance and exert anti-inflammatory effects. Whether TTR exerts a protective effect on HAPH remains unknown. METHODS: A rat model of HAPH was established. The mean pulmonary arterial pressure (mPAP) of the animals was measured, the serum levels of SOD, MDA, and GSH-Px were measured using ELISA, and the expression of Bax, Bcl-2, Nrf2, and HO-1 proteins in the lung tissue of each group of rats was measured using Western blotting. Pathological changes in the lung tissue were also observed. A model of damage to H2O2-induced pulmonary artery endothelial cells (PAECs) was generated, and cell proliferation was measured using CCK-8 assays. Flow cytometry was used to measure ROS levels in PAECs. Western blotting was used to detect the expression of Bax, Bcl-2, Nrf2, and HO-1 proteins in PAECs. RESULTS: The hemodynamic and pathologic findings showed that the mPAP of HAPH rats increased markedly, and the vascular wall thickness increased (P < 0.05). TTR reduced mPAP, alleviated or slowed pulmonary arterial remodeling, increased GSH-Px and SOD activity, lowered the level of MDA (P < 0.05), and downregulated the expression of Bax in the lung tissues of HAPH rats, while the expression of Bcl-2, Nrf2, and HO-1 was upregulated (P < 0.05). The results of the cell experiments showed that TTR inhibited H2O2-induced PAEC apoptosis and ROS production (P < 0.05), downregulated the expression of Bax in PAECs, and upregulated the expression of Bcl-2, Nrf2, and HO-1 (P < 0.05). CONCLUSION: The results suggest that TTR reduces pulmonary arterial pressure, decreases oxidative stress during HAPH, and exerts protective effects in rats with HAPH and that its mechanism of action is related to regulation of the Nrf2/HO-1 signaling pathway.

Immunomodulatory and antitumour effects of abnormal Savda Munziq on S180 tumour-bearing mice.

BACKGROUND: Abnormal Savda Munziq (ASMq), a traditional uyghur medicine, has shown anti-tumour properties in vitro. This study attempts to confirm these effects in vivo and measure effects on the immune system. METHODS: Kunming mice transplanted with Sarcoma 180 cells were treated with ASMq (2-8 g/kg/day) by intra-gastric administration compared to model and cyclophosphamide (20 mg/kg/day). After the 14th day post tumour implant, thymus, liver, spleen and tumours were removed, weighed, and processed for histopathological analysis. Blood samples were also taken for haematological and biochemical analyses including TNF-α , IL-1 ß and IL-2. Splenic lymphocyte function was measured with MTT; lymphocyte subpopulations were measured by flow cytometry. RESULTS: ASMq treated animals had reduced tumour volume compared to model and increased concentrations of TNF-α, IL-1ß and IL-2 compared to untreated and to cyclophosphamide-treated animals. No histopathological alterations were observed. The absence of viable S180 cells and the presence of necrotic cells and granulation tissue were observed in tumour tissue of treated animals. The effect on T lymphocytes was unclear. CONCLUSIONS: ASMq confirmed in vivo anti-tumour effects observed in vitro, which may be at least in part mediated by increased immune activity.

A 1H NMR spectroscopic metabolomic study of the protective effects of irbesartan in a rat model of chronic mountain sickness.

Chronic mountain sickness (CMS) is a significant pathology in most high-altitude regions globally, affecting the cardiopulmonary system and its mechanism is largely unknown. A metabonomic approach using 1H nuclear magnetic resonance spectroscopy allows for detecting differential metabolites, which provides a global view and mechanisms during CMS development. In this study, we simulated a high-altitude environment to establish a rat model of CMS. Irbesartan was administered to CMS rats at three doses (6.75, 13.5, and 27 mg/kg) once a day for 15 days. HE staining and transmission electron microscopy were used to evaluate the effect of changes on the lung. Based on 1H NMR spectra obtained from serum samples, partial least squares-discriminant analysis (PLS-DA) and its variant orthogonal PLS-DA (OPLS-DA) models were applied to distinguish the different groups. Histopathological sections showed that the alveolar structure was abnormal, inflammatory infiltration occurred in CMS rats, and CMS induced notable metabolic disorder according to the 1H NMR result. However, irbesartan reversed the imbalanced metabolites via energy metabolism, amino acid metabolism, and taurine metabolism pathways, and its effect was also confirmed by the general signs and morphology of the lung. The results revealed that irbesartan as an effective therapeutic agent to improve CMS is warranted.

Irbesartan ameliorates chronic mountain sickness in a rat model via the cholesterol metabolism: An iTRAQ -based proteomics analysis.

OBJECTIVE: To study the effects of irbesartan on pulmonary artery lesions in a rat model with chronic mountain sickness (CMS) and identify the biomarkers involved. METHODS: In this study, we used a rat model of CMS to evaluate the therapeutic effect of irbesartan by measuring pulmonary artery pressure and evaluating the histopathology of the pulmonary artery. We also used proteomics technology to identify differentially expressed proteins (DEPs) in the serum and performed bioinformatics analysis. Results were then verified by enzyme linked immunosorbent assay (ELISA) and immunohistochemistry (IHC). RESULTS: Irbesartan treatment induced a significant decrease (P < 0.05) in the pulmonary artery pressure of CMS rats. Histopathological and electron microscope further confirmed that high altitude hypoxia induced changes in the structure of the pulmonary artery tissue and caused ultrastructural lesions. Proteomics analysis identified 40 DEPs; bioinformatics analysis further revealed that the cholesterol metabolism pathway plays a crucial role in the occurrence of CMS. ELISA and IHC verified that several DEPs (Apo-A1, Apo-C1, Apo-E, IGF-1, Profilin1, and Col1a1) represent critical biological markers in pulmonary artery disease caused by CMS. CONCLUSIONS: Irbesartan significantly improved pulmonary artery damage in a rat model of CMS possibly by impacting on the cholesterol metabolism pathway and by reducing damage to vascular endothelial cells. Irbesartan also inhibited the expression levels of IGF-1, Profilin1 and Col1a1 to relieve pulmonary artery pressure and improve lung function by inhibiting vascular remodeling. Several proteins were identified as potential biomarkers of CMS, including Apo-A1, Apo-C1, Apo-E, IGF-1, Profilin1, and Col1a1.

iTRAQ-based quantitative proteomic analysis of the improved effects of total flavones of Dracocephalum Moldavica L. in chronic mountain sickness.

To use isobaric tags for relative and absolute quantification (iTRAQ) technology to study the pathogenesis of chronic mountain sickness (CMS), identify biomarkers for CMS, and investigate the effect of total flavones of Dracocephalum moldavica L. (TFDM) on a rat model of CMS. We simulated high altitude hypobaric hypoxia conditions and generated a rat model of CMS. Following the administration of TFDM, we measured the pulmonary artery pressure and serum levels of hemoglobin (Hb), the hematocrit (Hct), and observed the structure of the pulmonary artery in experimental rats. Furthermore, we applied iTRAQ-labeled quantitative proteomics technology to identify differentially expressed proteins (DEPs) in the serum, performed bioinformatics analysis, and verified the DEPs by immunohistochemistry. Analysis showed that the pulmonary artery pressure, serum levels of Hb, and the Hct, were significantly increased in a rat model of CMS (P < 0.05). Pathological analysis of lung tissue and pulmonary artery tissue showed that the alveolar compartment had obvious hyperplasia and the pulmonary artery degree of muscularization was enhanced. Both pulmonary artery pressure and tissue morphology were improved following the administration of TFDM. We identified 532 DEPs by quantitative proteomics; gene ontology (GO)and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis further revealed that metabolic pathways associated with coagulation and complement play crucial roles in the occurrence of CMS. Immunohistochemistry verified that several DEPs (α-1-acid glycoprotein, collagen, fibulin, haptoglobin, PLTP, and TAGLN2) are important biological markers for CMS. Our analyses demonstrated that TFDM can improve CMS and exert action by influencing the metabolic pathways associated with coagulation and complement. This process relieves pulmonary artery pressure and improves lung function. We also identified that α-1-acid glycoprotein, collagen, fibulin, haptoglobin, PLTP, and TAGLN2 may represent potential biomarkers for CMS.

Improvement of Total Flavonoids from Dracocephalum moldavica L. in Rats with Chronic Mountain Sickness through 1H-NMR Metabonomics.

BACKGROUND: We analyzed the effects of total flavonoids from Dracocephalum moldavica L. (D. moldavica L.) on improving chronic mountain sickness (CMS) in rats using the NMR hydrogen spectrum (1H-NMR) metabonomics technology. METHOD: We extracted the total flavonoids of D. moldavica L with 60% ethanol reflux. A CMS model was established with 48 Sprague-Dawley (SD) rats, which were then randomly divided into six groups (n = 8): control group (normal saline, 0.4 mL/100 g/d, ig); model group (normal saline, 0.4 mL/100 g/d, ig); nifedipine group (nifedipine tablets, 2.7 mg/kg/d, ig); and high-, middle-, and low-dose groups of total flavonoids from D. moldavica L. (DML.H, DML.M, and DML.L, receiving total flavonoids from D. moldavica L. at 400, 200, and 100 mg/kg/d, ig, respectively). The sera of the rats in all the groups were determined, and NMR hydrogen spectrum metabolomics was analyzed. The serum contents of apolipoproteins A1 (Apo-A1) and E (Apo-E) were determined, and histopathological changes in the brain tissue of each group were observed. RESULTS: Serum tests showed that total flavonoids from D. moldavica L. significantly increased the Apo-A1 and Apo-E levels in rats with CMS (P < 0.05). The results of serum metabonomics showed that total flavonoids from D. moldavica L can alleviate amino acid, energy, and lipid metabolism disorders in rats with CMS. Pathohistological examination of brain tissue showed that these flavonoids improved pathological changes, such as meningeal vasodilation, hyperemia, edema of brain parenchyma, inflammatory cell infiltration, increase in perivascular space, and increase in pyramidal cells. CONCLUSION: Total flavonoids from D. moldavica L. have potential therapeutic effects on CMS. The possible mechanism is the reduction of oxidative damage through the alleviation of metabolism disorder.

Enhanced antitumor efficacy and reduced toxicity of Abnormal Savda Munziq on tumor bearing mice treated with chemotherapy.

Previous research has demonstrated the anti-tumor properties of Abnormal Savda Munziq (ASMq), a traditional Uyghur compound herbal medicine. The effects of ASMq on cervical carcinomas in U27 tumor-bearing mice is investigated, the effect of adding Fluorouracil (5-FU) is also assessed in this paper. The results demonstrate that ASMq and 5-FU significantly inhibited the proliferation of U27 cells in a time-dependent and dose-dependent manner. Evaluating the interactions between ASMq and 5-FU on U27 cell growth yields a combination index (CI) < 1 in different time periods, suggesting a synergistic effect between the two drugs in vitro. Nuclear magnetic resonance (NMR) analysis demonstrates that ASMq can inhibit enhanced lipid metabolism in tumor mice, enhance the glutamine content, promote lymphocyte and macrophage proliferation, and increase tumor necrosis factor(TNF-α) and interleukin(IL) production, which can enhance the effect of 5-FU on the inhibition of tumors. Also ASMq can reduce the content of ALT and AST in serum. Increased SOD, GSH-Px, and decreased the content of MDA in liver tissue. ASMq has a synergistic effect on liver and tumor pathology, as well as tumor inhibition rate. In addition, ASMq can also enhance the body's antioxidant capacity and improve the body's metabolism, and reduce 5-FU's toxic side effects.