PMID: 

J Agric Food Chem. 2007 Dec 26 ;55(26):10671-7. Epub 2007 Nov 27. PMID: 18038978

Abstract Title: 

Hypolipidemic effects of Citrus bergamia Risso et Poiteau juice in rats fed a hypercholesterolemic diet.

Abstract: 

Citrus bergamia Risso et Poiteau fruits have been traditionally utilized, in Calabria (Italy), as a popular remedy for their hypolipidemic properties. C. bergamia juice total phenol content (2474.35+/-38 microg/mL) was evaluated by the Folin-Ciocalteu method; moreover, HPLC analysis led to the identification of naringin (520 ppm), neoeriocitrin (370 ppm), and neohesperidin (310 ppm). The present study was designed to investigate the hypolipidemic effects of C. bergamia juice and its protective effect on liver of hyperlipidemic rats. Chronic administration of C. bergamia (1 mL/rat/day) provoked a significant reduction in serum cholesterol, triglycerides, and low-density lipoprotein (LDL) levels and an increase in high-density lipoprotein (HDL) levels; moreover, histopathological observations showed, in rats submitted to C. bergamia treatment, a protection of hepatic parenchyma. In addition, fecal neutral sterols and fecal bile acid excretion was found to be increased after C. bergamia treatment. These results suggest that the hypocholesterolemic effect of C. bergamia may be mediated by the increase in fecal neutral sterols and total bile acids excretion. In addition to the hypolipidemic effect, the juice shows radical scavenging activity in the diphenylpicrylhydrazyl (DPPH) test; probably the two effects are related. These observations suggest that the positive intake of C. bergamia may reduce the risk of some cardiovascular diseases through its radical scavenging function and hypocholesterolemic action.

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PMID: 

Hepatol Res. 2019 Feb ;49(2):212-223. Epub 2018 Nov 19. PMID: 30338893

Abstract Title: 

Stevia prevents experimental cirrhosis by reducing hepatic myofibroblasts and modulating molecular profibrotic pathways.

Abstract: 

AIM: The aims of the present study were to investigate the capacity of stevia leaves to prevent experimental cirrhosis induced by chronic administration of carbon tetrachloride (CCl) in rats and to explore the action mechanism involved.METHODS: Liver cirrhosis was established by CCltreatment (400 mg/kg i.p. three times a week for 12 weeks); stevia powder was administered (100 mg/kg by gavage daily) during the CCltreatment. Serum markers of liver damage and hydroxyproline were evaluated and histopathological analyses were carried out. The profibrotic pathways were analyzed by western blot and immunohistochemistry.RESULTS: We found for the first time that stevia cotreatment prevented the elevation of serum markers of necrosis and cholestasis and the occurrence of liver fibrosis. It is worth noting that stevia downregulated several profibrogenic pathways, including the reduction of hepatic myofibroblasts and decreased matrix metalloproteinase (MMP)2 and MMP13 expression, thereby blocking the liberation of transforming growth factor-β from the extracellular matrix. Notably, stevia reduced the phosphorylation of pSmad3L, the most profibrogenic and mitogenic Smad, by inhibiting the activation of c-Jun N-terminal kinase and extracellular signal-regulated kinase. Interestingly, Smad7, an important antifibrotic molecule, was upregulated by stevia treatment in cirrhotic rats. These multitarget mechanisms led to the prevention of experimental cirrhosis.CONCLUSIONS: Because stevia possesses a reasonable safety profile, our results indicate that it could be useful in the clinical setting to treat chronic liver diseases.

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PMID: 

Biomed Pharmacother. 2020 Jan ;121:109586. Epub 2019 Nov 6. PMID: 31706104

Abstract Title: 

Tanshinone IIA attenuates silica-induced pulmonary fibrosis via inhibition of TGF-β1-Smad signaling pathway.

Abstract: 

Transforming growth factor-β 1 (TGF-β1) is a key mediator in fibrogenesis, and is upregulated and activated in fibrotic diseases. The exact role of TGF-β1-Smad signaling in the progression of silicosis fibrosis is yet to be conclusively determined. Using a Wistar rat silicosis model, we examined whether tanshinone IIA (TanIIA) could meliorate silicosis fibrosis. The pulmonary fibroblasts of rats from the normal control group and silicosis-induced model group were extracted and examined so as to further explore the disruption of TGF-β1-Smad signaling pathway in silicosis pathogenesis and the intervention of Tan IIAin this pathway. Using RT-PCR, immunohistochemical staining, and immunofluorescence analysis, we determined that Tan IIA could ameliorate silicosis fibrosis, downregulate collagen I, collagen III, and α-SMA expression both, in vivo and in vitro. In silicosis fibroblasts, TGF-β1 induced phosphorylation of Smad2, Smad3, and negative feedback Smad7 inhibition in a dose dependent manner, and the phosphorylation of Smad3 persisted when the upstream signal was blocked. Tan IIA treatment effectively inhibited the TGF-β1-induced phosphorylation of Smads, especially the persistent phosphorylation ofSmad3 in the nucleus, and upregulated the expression of Smad7 in silicosis fibroblasts, leading to a reduction in ECM deposition. Our findings indicate that dysregulation of the TGF-β1-Smad signaling pathway may play an important role in the pathological process of silicosis. Tan IIA thus ameliorates silicosis fibrosis partially by suppressing activation of TGF-β1-Smad signaling pathway, which may turn out to be a potential therapeutic approach to prevent silicosis fibrosis.

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PMID: 

Int J Pharm. 2019 Dec 9 ;574:118846. Epub 2019 Dec 9. PMID: 31821877

Abstract Title: 

A Tanshinone IIA loaded hybrid nanocomposite with enhanced therapeutic effect for otitis media.

Abstract: 

Otitis media, commonly known as middle ear inflammation, is among one of the most common maladies and results in significant morbidity such as loss of hearing. In view of the bacteria invasion such as Staphylococcus aureus causes the majority forms of otitis media, drug treatment generally uses antibacterial by topical or systematic approach. However, the effectiveness of antibacterial is diminishing because of the rapid emergence of antibiotic-resistant bacterial strains. Here, we designed and fabricated a silver nanoparticle (AgNPs)-based multicomponent hybrid nanocomposite termed as TSIIA @ CS/Lys @ AgNPs, which was comprised of a AgNPs core, a chitosan (CS) or lysozyme (Lys) middle layer, and a Tanshinone IIA (TSIIA) inclusion outlayer. Coating of CS or Lys to AgNPs through electrostatic interaction probably produced a core-shell nanocomplex resembling the endocarp of walnut. This design could reduce the dosage of AgNPs while maintaining antibacterial activity possibly due to the favorable interactions between nanocomplex and bacteria. The deposition of Chinese herb active component TSIIA by inclusion complexation formed the out layer of hybrid nanocomposite towards an improved antibacterial performance, which showed a therapeutic effect against acute otitis media of guinea pig comparable to the clinical commercial-used ofloxacin administrated by injection. The hybrid nanocomposite, when dispersed in poly (lactic-co-glycolic acid)/N-methyl-2-pyrrolidone (PLGA/NMP) solution as an in-situ organogel, not only maintained the therapeutic effectiveness, but also possessed the advantage of lower injection frequency compared with solution formulation. In addition, no obvious toxicity to the basilar membrane and epithelia tissue was observed after the healthy guinea pigs were treated with hybrid nanocomposite or organogel. This study provides a promising strategy to develop hybrid nanocomposite with enhanced antibacterial efficacy and also opens a new way for the establishment of efficient therapeutic systems with reduced administration frequency as substitute of antibiotics to treat otitis media.

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PMID: 

Coron Artery Dis. 2019 Dec 13. Epub 2019 Dec 13. PMID: 31842027

Abstract Title: 

Tanshinone IIA protects mice against atherosclerotic injury by activating the TGF-β/PI3K/Akt/eNOS pathway.

Abstract: 

OBJECTIVE: Explored the mechanism of action of tanshinone IIA (TIIA) against atherosclerosis.METHODS: ApoE mice were divided into two groups of 10: model and TIIA. A control group of 10 wild-type mice was created. ApoE mice were fed a high-fat diet for 12 weeks. The TIIA group received TIIA once daily. Mice were anesthetized, blood collected by cardiac puncture, and the aortic sinus/arch collected for histology and molecular studies, respectively.RESULTS: Mice intima in the model group had large areas of plaque formation, serum levels of total cholesterol (TC), triglycerides, and low-density lipoprotein-cholesterol (LDL-C) increased significantly, and high-density lipoprotein-cholesterol (HDL-C) levels decreased significantly in the model group after 12 weeks. Staining [hematoxylin and eosin (H&E), Oil-Red-O] showed that the aorta had lesions, a higher degree of plaque formation, and considerable lipid deposition in model-group mice. After TIIA treatment, expression of HDL-C was increased significantly and that of TC, triglycerides and LDL-C decreased significantly, and plaque size and lipid deposition improved obviously. Analyses of protein phosphorylation in aortic tissue suggested that the transforming growth factor (TGF)-β/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/endothelial nitric oxide synthase (eNOS) pathway was activated in TIIA-treated mice.CONCLUSION: TIIA can lower levels of serum lipids, stabilize atherosclerotic plaques, reduce endothelial injury, and inflammatory damage by activation of the TGF-β/PI3K/Akt/eNOS pathway.

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PMID: 

Vaccine. 2015 Apr 21 ;33(17):2004-8. Epub 2015 Mar 18. PMID: 25795257

Abstract Title: 

C-reactive protein response to influenza vaccination as a model of mild inflammatory stimulation in the Philippines.

Abstract: 

BACKGROUND: C-reactive protein (CRP) is increasingly measured as a marker of systemic inflammation that predicts elevated risk for cardiovascular disease. Influenza vaccination is a mild pro-inflammatory stimulus, and the CRP response to vaccination may provide additional information on individual differences in inflammatory response and risk for disease.AIM: To document the pattern of CRP response to influenza vaccination among a large sample of older women in the Philippines. The Philippines exemplifies current global trends toward increasing rates of overweight/obesity, but also maintains relatively high rates of infectious disease. The secondary aim of the study is to investigate the impact of infectious symptoms on the pattern of response to vaccination.METHODS: A community-based sample of 934 women (mean age=55.4 years) received the influenza vaccine. CRP was assessed at baseline and 72h post-vaccination. Descriptive, non-parametric, and parametric analyses were implemented to assess the magnitude of CRP response, and to investigate whether responses were associated with baseline CRP or the presence of infectious symptoms prior to vaccination.RESULTS: Influenza vaccination resulted in a statistically significant CRP response of 0.35mg/L (p

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PMID: 

J Lab Clin Med. 2005 Jun ;145(6):323-7. PMID: 15976761

Abstract Title: 

Effect of influenza vaccine on markers of inflammation and lipid profile.

Abstract: 

Despite wide use of the influenza vaccine, relatively little is known about its effect on the measurement of inflammatory markers. Because inflammatory markers such as C-reactive protein (CRP) are increasingly being used in conjunction with lipids for the clinical assessment of cardiovascular disease and in epidemiologic studies, we evaluated the effect of influenza vaccination on markers of inflammation and plasma lipid concentrations. We drew blood from 22 healthy individuals 1 to 6 hours before they were given an influenza vaccination and 1, 3, and 7 days after the vaccination. Plasma CRP, interleukin (IL)-6, monocyte chemotactic protein 1, tumor necrosis factor alpha, IL-2 soluble receptor alpha, and serum amyloid A were measured, and differences in mean concentrations of absolute and normalized values on days 1, 3, and 7 were compared with mean baseline values. There was a significant increase in mean IL-6 (P

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PMID: 

Ann Med. 2007 ;39(5):392-9. PMID: 17701480

Abstract Title: 

Residual adverse changes in arterial endothelial function and LDL oxidation after a mild systemic inflammation induced by influenza vaccination.

Abstract: 

BACKGROUND: Several clinical studies have suggested possible increase in cardiovascular risk during and in the first weeks after an acute inflammatory disease. Using influenza vaccine as inflammatory stimulus, we investigated whether arterial endothelial dysfunction could persist beyond the inflammatory state, and whether amplified oxidative modification of low-density lipoprotein (LDL) accompanies this vascular disturbance.METHODS AND SUBJECTS: The brachial artery responses to hyperemia (flow-mediated dilatation (FMD), and to sublingual glyceryl trinitrate (GTN), and the carotid intima-media thickness were assessed by external ultrasound in eight healthy male volunteers (age 17-30 y) before, and 2 and 14 days after intramuscular administration of influenza vaccine. Plasma levels of high-sensitivity C-reactive protein (CRP), fibrinogen, cyclic guanosine monophosphate (cGMP), and antibodies against oxidized LDL (oxLDL) were measured at each time point. Data are means+/-standard errors of the mean (SEM).RESULTS: Influenza vaccination caused a slight elevation in CRP (from 0.5+/-0.1 at baseline, to 2+/-0.6 mg/L, P = 0.01) and fibrinogen (from 2.3+/-0.1 to 2.7+/-0.1 g/L, P = 0.01) at 2 days, which completely resolved at 14 days (CRP: 0.6+/-0.2 mg/L, P = 0.9, and fibrinogen: 2.3+/-0.1 g/L, P = 0.8 versus baseline). OxLDL antibody levels rose significantly at 2 days (from 1+/-0.1 at baseline to 2+/-0.4, P = 0.04), and remained elevated at 14 days (1.7+/-0.3, P = 0.1 versus baseline). FMD of the brachial artery decreased at 2 days (from 8.3+/-1.2% at baseline, to 5.4+/-1%, P = 0.05) with a further decrease at 14 days (4.9+/-0.8%, P = 0.03 versus baseline). The dilatory responses to GTN and the carotid IMT remained unchanged throughout the study period (P>0.5).CONCLUSION: Abnormalities in arterial function and LDL oxidation may persist for at least 2 weeks after a slight inflammatory reaction induced by influenza vaccination. These could explain in part the earlier reported increase in cardiovascular risk during the first weeks after an acute inflammatory disorder.

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PMID: 

Immunology. 2007 Jun ;121(2):276-82. Epub 2007 Mar 20. PMID: 17371543

Abstract Title: 

BCG stimulated dendritic cells induce an interleukin-10 producing T-cell population with no T helper 1 or T helper 2 bias in vitro.

Abstract: 

Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine has been associated with beneficial effects on overall childhood mortality in low-income countries; this cannot be explained merely by the prevention of tuberculosis (TB) deaths. The beneficial effects of BCG vaccine could be the result of either strengthening of pro-inflammatorymechanisms, helping neonates to fight infections, or the induction of an immune-regulatory network restricting overt inflammation and intense pathology. We aimed to study the effect of live BCG on the ability of dendritic cells (DCs) to polarize T-cell responses. Monocyte-derived DCs were matured in the presence or absence of BCG. The DC phenotype was assessed by CD83 expression, interleukin-12 (IL-12) and IL-10 production, as well as for the ability to polarize T-cell responses. Following stimulation with CD40 ligand, DCs matured in the presence of BCG showed enhanced IL-10 and diminished IL-12 production. These DCs primed naive T cells to develop into IL-10-producing T cells, with no T helper 1 or T helper 2 bias. These results suggest that BCG vaccination might result in the development of IL-10-producing DCs as well as IL-10-producing T cells that could contribute to restricting overt inflammation in infants exposed to pathogens and thus lead to lower infant mortality.

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PMID: 

Vaccine. 2010 Mar 19 ;28(14):2648-52. Epub 2010 Jan 20. PMID: 20096390

Abstract Title: 

Th2-polarisation of cellular immune memory to neonatal pertussis vaccination.

Abstract: 

Current infant vaccination against pertussis in North America and Australia requires three doses of vaccines including diphtheria, tetanus and acellular pertussis antigens (DTaP) at 2, 4 and 6 months of age. Interest is growing in the possibility that vaccination at birth might provide earlier protection of infants, but early vaccination also gives rise to concerns over the potential for excessive Th2-polarisation of pertussis-specific T-cell memory profiles. We evaluated this issue as part of a small pilot study comparing infants receiving a monovalent acellular pertussis vaccine (aP) at birth or birth and at 1 month, followed by DTaP at 2, 4 and 6 months with infants receiving DTaP only from 2 months. We compared in vitro Th-memory responses at 8 months and pertussis-specific IgG in serum at 2, 4, 6 and 8 months. Neonatal vaccination elicited earlier IgG responses, but accompanying Th-memory profiles displayed a strong Th2 bias with high IL-5 and IL-13 production. The correlation between T-cell memory profiles and other clinical outcomes should be evaluated in larger trials of neonatal aP vaccine.

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