Jatrorrhizine ameliorates Schwann cell myelination via inhibiting HDAC3 ability to recruit Atxn2l for regulating the NRG1-ErbB2-PI3K-AKT pathway in diabetic peripheral neuropathy mice.

Diabetic peripheral neuropathy (DPN) is a chronic complication associated with nerve dysfunction and uncontrolled hyperglycemia. Unfortunately, due to its complicated etiology, there has been no successful therapy for DPN. Our research recently revealed that jatrorrhizine (JAT), one of the active constituents of Rhizoma Coptidis, remarkably ameliorated DPN. This work highlighted the potential mechanism through which JAT relieves DPN using db/db mice. The results indicated that JAT treatment significantly decreased the threshold for thermal and mechanical stimuli and increased nerve conduction velocity. Histopathological analysis revealed that JAT significantly increased the number of sciatic nerve fibers and axons, myelin thickness, and axonal diameters. Additionally, JAT markedly elevated the expression of myelination-associated proteins (MBP, MPZ, and Pmp22). The screening of histone deacetylases (HDAC) determined that histone deacetylase 3 (HDAC3) is an excellent target for JAT-induced myelination enhancement. Liquid chromatography-mass spectrometry-(MS)/MS and coimmunoprecipitation analyses further confirmed that HDAC3 antagonizes the NRG1-ErbB2-PI3K-AKT signaling axis by interacting with Atxn2l to augment SCs myelination. Thus, JAT ameliorates SCs myelination in DPN mice via inhibiting the recruitment of Atxn2l by HDAC3 to regulate the NRG1-ErbB2-PI3K-AKT pathway.

Risk factors analysis of surgical site infections in postoperative colorectal cancer: a nine-year retrospective study.

BACKGROUND: Colorectal cancer (CRC) patients undergoing surgery are at a high risk of developing surgical site infections (SSIs), which contribute to increased morbidity, prolonged hospitalization, and escalated healthcare costs. Understanding the incidence, risk factors, and impact of SSIs is crucial for effective preventive strategies and improved patient outcomes. METHODS: This retrospective study analyzed data from 431 CRC patients who underwent surgery at Huangshan Shoukang Hospital between 2014 and 2022. The clinical characteristics and demographic information were collected. The incidence and impact of SSIs were evaluated, and independent risk factors associated with SSIs were identified using multivariable logistic regresison. A nomogram plot was constructed to predict the likelihood of SSIs occurrence. RESULTS: The overall incidence rate of SSIs was 7.65% (33/431). Patients with SSIs had significantly longer hospital stays and higher healthcare costs. Risk factors for SSIs included elevated Body Mass Index (BMI) levels (odds ratio, 1.12; 95% CI, 1.02-1.23; P = 0.017), the presence of diabetes (odds ratio, 3.88; 95% CI, 1.42 - 9.48; P = 0.01), as well as specific surgical factors such as open surgical procedures (odds ratio, 2.39; 95% CI [1.09; 5.02]; P = 0.031), longer surgical duration (odds ratio, 1.36; 95% CI [1.01; 1.84]; P = 0.046), and the presence of a colostomy/ileostomy (odds ratio, 3.17; 95% CI [1.53; 6.62]; P = 0.002). Utilizing multivariable regression analysis, which encompassed factors such as open surgical procedures, the presence of diabetes and colostomy/ileostom, the nomogram plot functions as a visual aid in estimating the individual risk of SSIs for patients. CONCLUSIONS: Risk factors for SSIs included higher BMI levels, the presence of diabetes, open surgical procedures, longer surgical duration, and the presence of colostomy/ileostomy. The nomogram plot serves as a valuable tool for risk assessment and clinical decision-making.

Resilience and intention of healthcare workers in China to receive a COVID-19 vaccination: The mediating role of life satisfaction and stigma.

AIMS: The present study investigated the association between resilience, stigma, life satisfaction and the intention to receive a COVID-19 vaccination among Chinese HCWs. It also explored the mediating role of stigma and life satisfaction on the association between resilience and intention to receive a COVID-19 vaccination. DESIGN: An anonymous cross-sectional survey. METHODS: 1733 HCWs from five hospitals in four provinces of mainland China completed a cross-sectional online survey in October and November 2020. RESULTS: Among the HCWs, the rate of intention to receive a COVID-19 vaccination was 73.1%. Results from structural equation modelling showed that resilience was associated both directly, and indirectly with greater intent to receive a COVID-19 vaccination through two pathways: first by increasing life satisfaction, and second by reducing stigma and increasing life satisfaction. CONCLUSION: Promoting the resilience of HCWs has the potential to increase the COVID-19 vaccination uptake rate among HCWs in China. IMPACT: This study tested the relationship between several psychological factors and the COVID-19 vaccination intention of HCWs in China, finding that resilience played a significant role in improving COVID-19 vaccination intention rates by reducing stigma and increasing life satisfaction.

Borneol-modified tanshinone IIA liposome improves cerebral ischemia reperfusion injury by suppressing NF-κB and ICAM-1 expression.

OBJECTIVE: To investigate the metabolism and brain tissue distribution of borneol-modified tanshinone IIA liposome (BO-TA-Lip) and its effect on NF-κB and ICAM-1 in cerebral ischemia reperfusion rats, thereby exploring the ameliorative mechanism of BO-TA-Lip on ischemic encephalopathy. METHODS: Particle size, entrapment efficiency, drug loading were measured to evaluate the preparation comprehensively. Metabolism and brain tissue distributions in vivo were measured by HPLC, and the pharmacokinetic parameters were calculated. In addition, 24 SD rats were randomly divided into sham, model, STS (sodium tanshinone IIA sulfonate, 30 mg/kg) and BO-TA-Lip groups (44 mg/kg). The middle cerebral artery occlusion (MCAO) rats were constructed with thread embolism method. Neurological deficits were scored using Zea Longa scoring standard. TTC and HE staining were used for the cerebral infarction and histopathological examination, respectively. The protein expression was examined by immunohistochemistry and Western blot. RESULTS: The average particle size, encapsulation efficiency and drug loading of BO-TA-Lip were (135.33 ± 7.25) nm, (85.95 ± 3.20)% and (4.06 ± 0.31)%, respectively. Both in the pharmacokinetic analysis of plasma and brain tissue, in BO-TA-Lip group, the peak concentration and the area under the curve increased, and the clearance rate decreased. The neurological deficit scores and infarct area of the BO-TA-Lip group were significantly lower than that of the model and STS groups. Besides, BO-TA-Lip reduced the protein expression of NF-κB, ICAM-1, IL-1ß, TNF-α and IL-6 in the brain tissue. CONCLUSION: BO-TA-Lip had higher bioavailability and better absorption in brain tissue, and could improve cerebral ischemia reperfusion injury, which might be related to the inhibitory effect of BO-TA-Lip in expression of NF-κB and ICAM-1.

Preparation, characterization, and anti-colon cancer activity of oridonin-loaded long-circulating liposomes.

In this study, oridonin-loaded long-circulating liposomes (LC-lipo@ORI) were prepared with the ethanol injection method. Its physicochemical properties and the morphology were characterized, and its stability and release profiles were evaluated. Furthermore, its antitumor effects were studied using two in vitro cell models of colon cancer and two tumor-bearing models in nude mice. The prepared LC-lipo@ORI was quasi-spherical, with a mean particle size of 109.55 ± 2.30 nm. The zeta potential was -1.38 ± 0.21 mV, the encapsulation efficiency was 85.79%±3.25%, and the drug loading was 5.87%±0.21%. In vitro release results showed that the cumulative release rate of LC-lipo@ORI at 12 h was 63.83%. However, ORI dispersion was almost completely released after 12 h. In vitro cytotoxicity results showed that, the inhibiting effects of LC-lipo@ORI on the proliferation of two types of colon cancer cells were apparently higher than those of ORI dispersion, whereas those of the blank carrier were not noticeable. In vivo studies confirmed that, the encapsulation of LC-lipo enhanced the inhibitory effects of ORI on tumor growth. These results indicated that LC-lipo@ORI a promising formulations for colon cancer treatment.

Magnoflorine from Coptis chinese has the potential to treat DNCB-induced Atopic dermatits by inhibiting apoptosis of keratinocyte.

AIMS: In Sheng Nong's herbal classic in China, Rhizoma coptidisa(RC) could be used to treat Atopic dermatitsb(AD), but its core ingredient(s) and mechanism remains unknown. The present study aimed to find out the ingredients against AD and expound its mechanisms. MATERIALS AND METHODS: Seven alkaloids were isolated from RC to compare the inhibition against HaCaT cells by MTT assays and apoptosis of cells stimulated with TNF-α/IFN-γ by flow cytometry. The effects of target alkaloids against AD were evaluated on DNCBc (2,4-dinitrochlorobenzene)-induced atopic dermatitis in mice. KEY FINDINGS: Seven alkaloids were isolated from RC successfully. The results from MTT and flow cytometry indicated that among these alkaloids, only magnoflorine d(MAG) had no obvious toxicity on cells, but could inhibit the apoptosis of the cells stimulated with TNF-α/IFN-γ. Further animal experiments confirmed that MAG significantly attenuated the AD-like symptom and inhibited the AD-induced increases in IgE/IL-4, as compared with control (P < 0.01). Moreover, MAG reduced the low Δψme(mitochondrial membrane potential) in HaCaT cells. The results of western blotting proved that MAG inhibited apoptosis of keratinocytes through decreasing the expressions of CTSBf (cathepsin B), Cyte Cg (cytochrome C), Bid and caspase-3/7/8/9. SIGNIFICANCE: Overall, MAG inhibited apoptosis by decreasing the expression of apoptotic pathway-related proteins, and laid a foundation for the study of AD mechanisms.

Daucosterol linolenate from Sweet Potato Suppresses MCF7-Xenograft-Tumor Growth through Regulating PI3K/AKT Pathway.

Sweet potato is a functional food with potential antitumor properties, but the bioactive constituents and biological mechanisms remain unclear. In this study, we investigated the antitumor effect of daucosterol linolenate extracted from sweet potato and its potential mechanism. An MTT assay indicated that DLA inhibited the proliferation of breast cancer MCF-7 cells but had only weak effects on the proliferation of MDA-MB-231, 4T1, and MCF-10A cells. Flow cytometry analysis revealed that daucosterol linolenate induced apoptosis of MCF-7 cells. Experiments with MCF-7 xenograft in nude mice further confirmed that DLA inhibited tumor growth dose-dependently. After DLA treatment, the expressions of B-cell lymphoma 2 and vascular endothelial growth factor were decreased and that of cleaved caspase 3 was increased as compared to the TC group. DLA also down-regulated the expression of phosphoinositide 3-kinase/protein kinase B and repressed insulin-induced phosphoinositide 3-kinase/protein kinase B activation. Our findings suggest that DLA suppresses breast tumor growth through inactivating the phosphoinositide 3-kinase/protein kinase B pathway.

Anti-inflammatory effects of vinpocetine in LPS-stimulated microglia via activation of AMPK.

Microglia are the resident immune cells in the central nervous system (CNS), which play important roles in the repair of neuroinflammatory injury. The present study investigated the anti-neuroinflammatory effects of vinpocetine induced by lipopolysaccharide (LPS) in BV2 microglia. BV2 microglia were pretreated with vinpocetine, and then stimulated with LPS (100 ng/mL). The cytotoxicity of BV2 microglia was assessed by MTT assay. The expression levels of nitrite oxide were measured by Griess assay. Proinflammatory cytokines and mediators were determined by Western blot, ELISA, or quantitative real-time PCR. Vinpocetine significantly decreased the generation of nitric oxide-inducible nitric oxide synthase (iNOS), cyclooxygenase- (COX-) 2 in a dose-dependent manner. In addition, vinpocetine decreased the production of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin (IL)-6 and IL-1ß. Furthermore, it was observed that phosphorylation levels of AMPK (Thr-172) decreased in LPS-stimulated BV2 microglia. Vinpocetine treatment increased AMPK phosphorylation in LPS-stimulated BV2 microglia. AMPK inhibition by siRNA blocked the anti-inflammatory effects of vinpocetine induced by LPS in BV2 microglia. The overall results demonstrate that vinpocetine has anti-inflammatory effects on LPS-stimulated BV2 microglia via inducing phosphorylation of AMPK, suggesting that vinpocetine is a potential therapeutic agent in neuroinflammatory injury.

Aluminum relieves fluoride stress through stimulation of organic acid production in Camellia sinensis.

Tea plants (Camellia sinensis O. Kuntze) can hyperaccumulate fluoride (F) in leaves. Although, aluminum (Al) can alleviate F toxicity in C. sinensis, the mechanisms driving this process remain unclear. Here, we measured root length, root activity, soluble proteins content, and levels of peroxidase, superoxide dismutase, catalase, malondialdehyde (MDA), and chlorophyll in tea leaves after treatment with different F concentrations. In addition, we focused on the content of organic acids, the gene transcription of malate dehydrogenase (MDH), glycolate oxidase (GO) and citrate synthase (CS) and the relative enzyme activity involved in the tolerance to F in C. sinensis. We also examined the role of Al in this process by analyzing the content of these physiological indicators in tea leaves treated with F and Al. Our results demonstrate that increased MDA content, together with decreased chlorophyll content and soluble proteins are responsible for oxidative damage and metabolism inhibition at high F concentration. Moreover, increased antioxidant enzymes activity regulates ROS damage to protect tea leaves during F stress. Furthermore, exogenous Al alleviated F stress in tea leaves through the regulation of MDA content and antioxidant enzymes activity. In addition, organic acids in exudate stimulated root growth in tea plants exposed to low F concentrations are regulated by MDH, GO, and CS. In addition, Al can stimulate the exudation of organic acids, and may participate in regulating rhizosphere pH of the roots through the interaction with F, eventually leading to the response to F stress in C. sinensis.

Correlation between microbes and colorectal cancer: tumor apoptosis is induced by sitosterols through promoting gut microbiota to produce short-chain fatty acids.

The diversity of the bacterial community in the gut is closely related to human health. Gut microbes accomplish multiple physiological and biochemical functions. Sitosterols are a series of phytochemicals that have multiple pharmacological activities and are used as cholesterol-lowering drugs in clinical practice. In this study, we investigated the roles of bacteria and short-chain fatty acids (SCFAs) to the anti-colorectal cancer (anti-CRC) effects of sitosterols in BALB/c nude mice. Sitosterols were administered orally and gut microbiota composition and intestinal SCFAs changes were analyzed. The correlation between gut microbiota, SCFAs, and tumor apoptosis was assessed by a series of in vivo and in vitro experiments. Tumor growth in the mice was inhibited by sitosterol-treatment. Mechanistic studies revealed that sitosterol-treatment reduced the expression of PI3K/Akt, promoted the activation of Bad, decreased Bcl-xl, and enhanced cyto-c release, leading to caspase-9 and caspase-3 activation, PARP cleavage, and apoptosis. 16S rDNA analysis revealed that the diversity of microbiota, particularly phyla Bacteroidetes and Firmicutes, reduced dramatically in the gut of tumor-bearing mice, whilst treatment with sitosterols reversed these changes. The levels of SCFAs in the fecal samples of sitosterol-treated mice increased, leading to cancer cell apoptosis in vitro. Moreover, tumor apoptosis was induced after mice received a daily dose of 2 × 108 CFU/0.2 mL Lactobacillus pentosus or 20 mM/0.2 mL SCFAs. Taken together, these results demonstrate that sitosterols maintain a diverse microbial environment and enrich the content of L. pentosus in the gut, leading to the production of beneficial metabolites including SCFAs that promote tumor apoptosis.

S-equol inhibits proliferation and promotes apoptosis of human breast cancer MCF-7 cells via regulating miR-10a-5p and PI3K/AKT pathway.

S-equol is the exclusive enantiomeric form of the soy isoflavone metabolite produced by human intestinal bacterial flora, which has strong anti-cancer activity. Based on this, the purpose of this study was to investigate the anti-breast cancer mechanism of S-equol. We examined the effects of S-equol on proliferation and apoptosis of MCF-7 cells by cell counting kit-8 assay and flow cytometry. Screening for microRNAs and predicting their target genes using the starBase and Targetscan website, respectively. Protein expression was detected by Western blot. The microRNA level were quantified by real-time PCR. The results showed that S-equol inhibited the proliferation of breast cancer MCF-7 cells in a time- and dose-dependent manner and promoted apoptosis of MCF-7 cells. The expression of miR-10a-5p was significantly decreased in breast cancer tissues and breast cancer cell lines, and the expression of miR-10a-5p was negatively correlated with the proliferation of MCF-7 cells. Luciferase reporter experiments demonstrated that miR-10a-5p directly targets PIK3CA 3'UTR to function. It was further found that S-equol exerts an anti-breast cancer effect by up-regulating miR-10a-5p and inhibiting the PI3K/AKT pathway. Our study revealed the mechanism of S-equol against breast cancer, and miR-10a-5p may be a potential target for the treatment of breast cancer.

Antibacterial Nanorods Made of Carbon Quantum Dots-ZnO Under Visible Light Irradiation.

Due to secondary pollution from bactericidal substances, the importance of eliminating microbial contamination has become a controversial topic. Three antibacterial nanorod materials of carbon quantum dots-zinc oxide (1/3CQDs-ZnO, CQDs-ZnO, and 2CQDs-ZnO), in which ZnO nanorods are surrounded by carbon quantum dots (CQDs), were successful prepared via in-situ sol-gel chemistry. Antibacterial nanorods of CQDs-ZnO had strong antibacterial activity under visible light irradiation, and a concentration of 0.1 mg/L was able to kill more than 96% of bacteria. The photocatalytic antibacterial mechanism was also studied. CQDs-ZnO produced more than three times the free radicals than pure ZnO under visible light irradiation. These free radicals destroyed the bacterial matrix of the cell wall and released cell proteins and nucleic acids. Moreover, CQDs-ZnO showed low cytotoxicity and can be used in medical applications.

[Total alkaloids of Coptidis Rhizoma combined with exercise inhibits tumor growth of orthotopically transplanted 4T1 breast cancer mice by blocking cell cycle G_1/S transformation].

Breast cancer is one of the leading causes for cancer-related death among women worldwide. Coptidis Rhizoma has antibacterial,anti-inflammatory,anti-tumor and other pharmacological activities,but whether exercise could synergistically promote the role of RC in the treatment of breast cancer has not been reported. In this experiment,the effects and mechanism of total alkaloids of Coptidis Rhizoma combined with exercise on the tumor growth of orthotopically transplanted 4 T1 breast cancer were systemically studied in mice. Balb/C mice transplanted with 4 T1 cells in situ were used as models. The total alkaloids of RC(145 mg·kg-1·d-1) alone or in combination with exercise(10 m·min-1,30 min/time,5 times/week) were given for 28 days,and then the changes in body weight and tumor volume,tumor weight,interleukin-1ß(IL-1ß),serum estradiol(E2) content,and expression levels of estrogen receptor α(ERα),cell cycle related proteins CDK4,CDK6,cyclin D1,CDK2,and cyclin E in tumor tissues. The results showed that total alkaloids of Coptidis Rhizoma could significantly inhibit the growth of 4 T1 breast cancer in mice(P< 0. 01),and exercise significantly promoted the anti-tumor activity of total alkaloids of Coptidis Rhizoma(P<0. 01),and reduced E2 and IL-1ß levels in mice. Western blot and flow cytometry showed that the total alkaloids of Coptidis Rhizoma combined with exercise could down-regulate the protein expression levels of ERα,CDK4,CDK6,cyclin D1,CDK2 and cyclin E in cancer cells,block the transformation of G1/S in 4 T1 cell cycle,and inhibit DNA synthesis in breast cancer cells. The total alkaloids of Coptidis Rhizoma combined with exercise showed synergistic effect in inhibition of tumor growth in mice with orthotopically transplanted 4 T1 breast cancer.

Rhizoma Coptidis alkaloids alleviate hyperlipidemia in B6 mice by modulating gut microbiota and bile acid pathways.

It is hypothesized that Rhizoma Coptidis (RC) alkaloids exert their hypolipidemic effects primarily by targeting the gastrointestinal tract and liver. Thus, this study was conducted to evaluate the antihyperlipidemic mechanisms of RC alkaloids (at a daily dose of 140mg/kg for 35days) in high-fat and high-cholesterol induced hyperlipidemic B6 mice. After treatment, serum lipid parameters were determined, the expression of lipid metabolism related genes and pathways such as the sterol regulatory element binding proteins (SREBPs) and bile acid signaling in mice were also investigated. Meanwhile, Illumina sequencing was used to investigate the differences in gut microbiota of B6 mice. The results indicated that RC alkaloids reduced the body weight gain and serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), total bile acids (TBA) and lipopolysaccharide of B6 mice. Liver fat deposition and epididymal adipose cell size were also deceased in therapy group. RC alkaloids feeding significantly promoted the abundance of Sporobacter termitidis, Alcaligenes faecalis, Akkermansia muciniphila in the gut of mice, whereas, the abundance of Escherichia coli, Desulfovibrio C21_c20, Parabacteroides distasonis was suppressed. The observed antihyperlipidemic effects of RC alkaloids can also be attributed to their action as agonists of FXR and TGR5, activators for SREBP2, LDLR, UCP2 and CYP7A1, inhibitors of HMGCR, TXNIP, TLR4 and JNK. Therefore, this study expands current knowledge on hypolipidemic mechanisms of RC alkaloids and presents new evidence supporting a key role for RC alkaloids as regulators of lipid homeostasis by modulation gut microbiota and hepatic lipid metabolism.

Gene expression profile indicates involvement of NO in Camellia sinensis pollen tube growth at low temperature.

BACKGROUND: Nitric oxide (NO) functions as a critical signaling molecule in the low-temperature stress responses in plants, including polarized pollen tube growth in Camellia sinensis. Despite this, the potential mechanisms underlying the participation of NO in pollen tube responses to low temperature remain unclear. Here, we investigate alterations to gene expression in C. sinensis pollen tubes exposed to low-temperature stress and NO using RNA-Seq technology, in order to find the potential candidate genes related to the regulation of pollen tube elongation by NO under low-temperature stress. RESULTS: Three libraries were generated from C. sinensis cv. 'Longjingchangye' pollen tubes cultured at 25 °C (CsPT-CK) and 4 °C (CsPT-LT) or with 25 µM DEA NONOate (CsPT-NO). The number of unigenes found for the three biological replications were 39,726, 40,440 and 41,626 for CsPT-CK; 36,993, 39,070 and 39,439 for CsPT-LT; and 39,514, 38,298 and 39,061 for CsPT-NO. A total of 36,097 unique assembled and annotated sequences from C. sinensis pollen tube reads were found in a BLAST search of the following databases: NCBI non-redundant nucleotide, Swiss-prot protein, Kyoto Encyclopedia of Genes and Genomes, Cluster of Orthologous Groups of proteins, and Gene Ontology. The absolute values of log2Ratio > 1 and probability > 0.7 were used as the thresholds for significantly differential gene expression, and 766, 497 and 929 differentially expressed genes (DEGs) were found from the comparison analyses of the CK-VS-LT, CK-VS-NO and LT-VS-NO libraries, respectively. Genes related to metabolism and signaling pathways of plant hormones, transcription factors (TFs), vesicle polarized trafficking, cell wall biosynthesis, the ubiquitination machinery of the ubiquitin system and species-specific secondary metabolite pathways were mainly observed in the CK-VS-LT and CK-VS-NO libraries. CONCLUSION: Differentially expressed unigenes related to the inhibition of C. sinensis pollen tube growth under low temperature and NO are identified in this study. The transcriptomic gene expression profiles present a valuable genomic tool to improve studying the molecular mechanisms underlying low-temperature tolerance in pollen tube.

Purification of α-glucosidase from mouse intestine by countercurrent chromatography coupled with a reverse micelle solvent system.

Countercurrent chromatography coupled with a reverse micelle solvent was applied to separate α-glucosidase, which is stable at pH 6.0-8.8, 15-50°C. The separation conditions are as follows: stationary phase: pH 4.0 Tris-HCl buffer phase containing 50 mM Tris-HCl and 50 mM KCl; mobile phase A: isooctane containing 50 mM anionic surfactant sodium di(2-ethylhexyl)sulfosuccinate; mobile phase B: 50 mM Tris-HCl buffer containing 500 mM KCl (pH 8.0); In total, 25 mL (23.9 mg) crude enzyme was injected through the injection valve, the enzymatic reaction and sodium dodecylsulfate polyacrylamide gel electrophoresis results imply that the activity of purified α-glucosidase is 6.63-fold higher than that of the crude enzyme. Therefore, countercurrent chromatography coupled with a reverse micelle solvent is capable for protein separation and enrichment.

Hypolipidemic Effects of Alkaloids from Rhizoma Coptidis in Diet-Induced Hyperlipidemic Hamsters.

This study was conducted to evaluate the antihyperlipidemic activity of five major alkaloids in Rhizoma Coptidis using high-fat- and high-cholesterol-induced hyperlipidemic hamsters. Hyperlipidemic hamsters were treated with coptisine, berberine, jatrorrhizine, palmatine, epiberberine, and total Rhizoma Coptidis alkaloids with a dose of 46.7 mg/kg × day for 140 days. Serum total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total bile acids were examined after alkaloid treatment. The results showed that all therapy agents prevented body weight gain, reduced the serum total cholesterol, and increased the high-density lipoprotein cholesterol of hamsters. Berberine, jatrorrhizine, and total Rhizoma Coptidis alkaloids decreased the triglyceride level in hyperlipidemic hamsters, while coptisine, jatrorrhizine, palmatine, and total Rhizoma Coptidis alkaloids significantly suppressed the elevation of the low-density lipoprotein cholesterol level. The fecal excretion of bile acids was significantly elevated by berberine, coptisine, jatrorrhizine, palmatine, total Rhizoma Coptidis alkaloids, and orlistat. Notably, total Rhizoma Coptidis alkaloids possess a much stronger lipid-lowering effect than the pure Rhizoma Coptidis alkaloids. Quantitative reverse transcription-polymerase chain reaction analyses revealed that Rhizoma Coptidis alkaloids could retard the synthesis of cholesterol by downregulating the mRNA expression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase and accelerate the clearance of lipids by upregulating the low-density lipoprotein receptor, cholesterol 7α-hydroxylase, and uncoupling protein-2 expression. These findings highlight the critical role of Rhizoma Coptidis alkaloids in hyperlipidemia treatment. Thus, they need to be considered in future therapeutic approaches.

The Hypoglycemic and Synergistic Effect of Loganin, Morroniside, and Ursolic Acid Isolated from the Fruits of Cornus officinalis.

Hypoglycemic activity-guided separation of ethanol extracts from the fruits of Cornus officinalis Sieb. et Zucc (CO) led to the isolation of loganin, morroniside, and ursolic acid. The antidiabetic capacity of CO extracts and related compounds was further investigated in diabetes mellitus mice. The results suggested that both CO extracts and pure compounds could ameliorate diabetes-associated damages and complications. Oral administration of loganin and morroniside decreased fasting blood glucose levels in diabetes mellitus mice. Ursolic acid exhibited the highest reactive oxygen species scavenging activity and α-glucosidase inhibitory activity. Notably, we noticed an interesting synergistic effect between loganin and ursolic acid. Given these favorable hypoglycemic properties, C. officinalis, a food and medicinal plant in China, may be used as a valuable food supplement for the treatment of diabetes mellitus.

Antihyperglycemia and Antihyperlipidemia Effect of Protoberberine Alkaloids From Rhizoma Coptidis in HepG2 Cell and Diabetic KK-Ay Mice.

Preclinical Research Rhizoma Coptidis (RC), the root of Coptis chinensis Franch, a species in the genus Coptis (family Ranunculaceae), has been commonly prescribed for the treatment of diabetes in Chinese traditional herbal medicine applications. The present study is focused on the assessment of the antihyperglycemia and antidiabetic hyperlipidemia effect of five protoberberine alkaloids, berberine (BBR), coptisine (COP), palmatine (PAL), epiberberine (EPI), and jatrorrhizine (JAT), separated from R. Coptidis in hepatocellular carcinoma HepG2 cells and diabetic KK-Ay mice. Protoberberine alkaloids are effective in modulating hyperglycemia and hyperlipidemia. After adding BBR and COP to culture medium, glucose consumption of HepG2 cells was increased. In KK-Ay mice assays, suppressed fasting blood glucose level and ameliorated glucose tolerance were observed after BBR/COP administration. After treated with berberine and coptisine, in the same dose of 5 µg/mL, the glucose consumption of HepG2 cells were promoted and, respectively, reached 96.1% and 17.6%. Body weight, food consumption, water intake, and urinary output of KK-Ay mice were reduced after treated with EPI. Serum total cholesterol and triglyceride of mice were decreased after treated with palmatine and jatrorrhizine. Serum high-density lipoprotein cholesterol of mice was increased after palmatine, jatrorrhizine, and berberine administrated. Moreover, hepatomegaly was attenuated in JTR-treated mice. Suggested that these protoberberine alkaloids from R. Coptidis have potential curative effect for diabetes. Drug Dev Res 77 : 163-170, 2016. © 2016 Wiley Periodicals, Inc.

Hypolipidemic Effect and Mechanism of Palmatine from Coptis chinensis in Hamsters Fed High-Fat diet.

Palmatine (PAL) is one of the main alkaloids in Coptis chinensis. The present aim was to investigate the hypolipidemic effect and mechanism of palmatine in hamsters fed with high-fat diet (HFD). PAL treatment decreased serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels, as well as increased fecal excretion of TC and total bile acids (TBA) in hyperlipidemic hamsters. Furthermore, PAL treatment up-regulated low-density lipoprotein receptor (LDLR) and cholesterol 7α-hydroxylase (CYP7A1) mRNA and protein expression and down-regulated apical sodium-dependent bile salt transporter (ASBT) mRNA and protein expression. These results demonstrated that PAL as a potential natural cholesterol lowering agent works by up-regulating LDLR and CYP7A1 mRNA and protein expression, down-regulating ASBT mRNA and protein expression, as well as enhancing fecal excretion of TC and TBA. The findings in our study suggest that palmatine could be a potential natural agent for treating hyperlipidemia.