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1.
Nutrients ; 16(13)2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38999871

ABSTRACT

IL-17A drives inflammation and oxidative stress, affecting the progression of chronic lung diseases (asthma, chronic obstructive pulmonary disease (COPD), lung cancer, and cystic fibrosis). Oleuropein (OLP) is a polyphenolic compound present in olive oil and widely included in the Mediterranean diet. It exerts antioxidant and anti-inflammatory activities, oxidative stress resistance, and anticarcinogenic effects with a conceivable positive impact on human health. We hypothesized that OLP positively affects the mechanisms of oxidative stress, apoptosis, DNA damage, cell viability during proliferation, and cell growth in alveolar epithelial cells and tested its effect in a human alveolar epithelial cell line (A549) in the presence of IL-17A. Our results show that OLP decreases the levels of oxidative stress (Reactive Oxygen Species, Mitochondrial membrane potential) and DNA damage (H2AX phosphorylation-ser139, Olive Tail Moment data) and increases cell apoptosis in A549 cells exposed to IL-17A. Furthermore, OLP decreases the number of viable cells during proliferation, the migratory potential (Scratch test), and the single cell capacity to grow within colonies as a cancer phenotype in A549 cells exposed to IL-17A. In conclusion, we suggest that OLP might be useful to protect lung epithelial cells from oxidative stress, DNA damage, cell growth, and cell apoptosis. This effect might be exerted in lung diseases by the downregulation of IL-17A activities. Our results suggest a positive effect of the components of olive oil on human lung health.


Subject(s)
Apoptosis , Cell Proliferation , DNA Damage , Interleukin-17 , Iridoid Glucosides , Iridoids , Oxidative Stress , Humans , Oxidative Stress/drug effects , Interleukin-17/metabolism , Iridoid Glucosides/pharmacology , Cell Proliferation/drug effects , A549 Cells , DNA Damage/drug effects , Apoptosis/drug effects , Iridoids/pharmacology , Reactive Oxygen Species/metabolism , Antioxidants/pharmacology , Cell Survival/drug effects , Lung/drug effects , Lung/metabolism , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Membrane Potential, Mitochondrial/drug effects , Olive Oil/pharmacology , Alveolar Epithelial Cells/drug effects , Alveolar Epithelial Cells/metabolism
2.
Nutrients ; 16(13)2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38999733

ABSTRACT

Natural and synthetic colorants present in food can modulate hemostasis, which includes the coagulation process and blood platelet activation. Some colorants have cardioprotective activity as well. However, the effect of genipin (a natural blue colorant) and synthetic blue colorants (including patent blue V and brilliant blue FCF) on hemostasis is not clear. In this study, we aimed to investigate the effects of three blue colorants-genipin, patent blue V, and brilliant blue FCF-on selected parameters of hemostasis in vitro. The anti- or pro-coagulant potential was assessed in human plasma by measuring the following coagulation times: thrombin time (TT), prothrombin time (PT), and activated partial thromboplastin time (APTT). Moreover, we used the Total Thrombus formation Analysis System (T-TAS, PL-chip) to evaluate the anti-platelet potential of the colorants in whole blood. We also measured their effect on the adhesion of washed blood platelets to fibrinogen and collagen. Lastly, the cytotoxicity of the colorants against blood platelets was assessed based on the activity of extracellular lactate dehydrogenase (LDH). We observed that genipin (at all concentrations (1-200 µM)) did not have a significant effect on the coagulation times (PT, APTT, and TT). However, genipin at the highest concentration (200 µM) and patent blue V at the concentrations of 1 and 10 µM significantly prolonged the time of occlusion measured using the T-TAS, which demonstrated their anti-platelet activity. We also observed that genipin decreased the adhesion of platelets to fibrinogen and collagen. Only patent blue V and brilliant blue FCF significantly shortened the APTT (at the concentration of 10 µM) and TT (at concentrations of 1 and 10 µM), demonstrating pro-coagulant activity. These synthetic blue colorants also modulated the process of human blood platelet adhesion, stimulating the adhesion to fibrinogen and inhibiting the adhesion to collagen. The results demonstrate that genipin is not toxic. In addition, because of its ability to reduce blood platelet activation, genipin holds promise as a novel and valuable agent that improves the health of the cardiovascular system and reduces the risk of cardiovascular diseases. However, the mechanism of its anti-platelet activity remains unclear and requires further studies. Its in vivo activity and interaction with various anti-coagulant and anti-thrombotic drugs, including aspirin and its derivatives, should be examined as well.


Subject(s)
Blood Coagulation , Blood Platelets , Food Coloring Agents , Iridoids , Humans , Iridoids/pharmacology , Blood Coagulation/drug effects , Food Coloring Agents/pharmacology , Blood Platelets/drug effects , Blood Platelets/metabolism , Hemostasis/drug effects , Partial Thromboplastin Time , Platelet Adhesiveness/drug effects , Fibrinogen/metabolism , Benzenesulfonates/pharmacology , Prothrombin Time , Rosaniline Dyes/pharmacology , Hemostatics/pharmacology , Platelet Activation/drug effects , Thrombin Time
3.
J Nutr Sci Vitaminol (Tokyo) ; 70(3): 193-202, 2024.
Article in English | MEDLINE | ID: mdl-38945884

ABSTRACT

Oleuropein aglycone (OA), which is the absorbed form of oleuropein, is a major phenolic compound in extra virgin olive oil. We analyzed the anti-obesity effect of OA intake combined with mild treadmill walking (MTW, 4 m/min for 20 min/d, 5-6 d/wk, without electric shocks and slope) in rats under a high-fat diet (HF). Four-week-old male Sprague-Dawley rats (n=28) were equally divided into four groups: control (HF), 0.08% oleuropein-supplemented HF (HFO), HF with MTW (HF+W), and HFO with MTW (HFO+W) groups. After 28 d, the inguinal subcutaneous fat content and weight gain were significantly lower in the HFO+W group than in the control group. The HFO+W group also had significantly higher levels of urinary noradrenaline secretion, interscapular brown adipose tissue, uncoupling protein 1, brain transient receptor potential ankyrin subtype 1 (TRPA1), vanilloid subtype 1 (TRPV1), and brain-derived neurotrophic factor (BDNF) than the control group. Especially, the HFO+W group showed a synergistic effect on noradrenaline secretion. Therefore, OA combined with MTW may accelerate the enhancement of UCP1 and BDNF levels in rats with HF-induced obesity by increasing noradrenaline secretion after TRPA1 and TRPV1 activation.


Subject(s)
Adipose Tissue, Brown , Brain-Derived Neurotrophic Factor , Diet, High-Fat , Iridoid Glucosides , Iridoids , Norepinephrine , Obesity , Rats, Sprague-Dawley , TRPA1 Cation Channel , Uncoupling Protein 1 , Animals , Male , Uncoupling Protein 1/metabolism , Iridoid Glucosides/pharmacology , Obesity/metabolism , Adipose Tissue, Brown/metabolism , Adipose Tissue, Brown/drug effects , Iridoids/pharmacology , Norepinephrine/metabolism , TRPA1 Cation Channel/metabolism , Brain-Derived Neurotrophic Factor/metabolism , Rats , Anti-Obesity Agents/pharmacology , Walking , Weight Gain/drug effects , Physical Conditioning, Animal , TRPV Cation Channels
4.
Int J Mol Sci ; 25(11)2024 May 21.
Article in English | MEDLINE | ID: mdl-38891768

ABSTRACT

Gut-dysbiosis-induced lipopolysaccharides (LPS) translocation into systemic circulation has been suggested to be implicated in nonalcoholic fatty liver disease (NAFLD) pathogenesis. This study aimed to assess if oleuropein (OLE), a component of extra virgin olive oil, lowers high-fat-diet (HFD)-induced endotoxemia and, eventually, liver steatosis. An immunohistochemistry analysis of the intestine and liver was performed in (i) control mice (CTR; n = 15), (ii) high-fat-diet fed (HFD) mice (HFD; n = 16), and (iii) HFD mice treated with 6 µg/day of OLE for 30 days (HFD + OLE, n = 13). The HFD mice developed significant liver steatosis compared to the controls, an effect that was significantly reduced in the HFD + OLE-treated mice. The amount of hepatocyte LPS localization and the number of TLR4+ macrophages were higher in the HFD mice in the than controls and were lowered in the HFD + OLE-treated mice. The number of CD42b+ platelets was increased in the liver sinusoids of the HFD mice compared to the controls and decreased in the HFD + OLE-treated mice. Compared to the controls, the HFD-treated mice showed a high percentage of intestine PAS+ goblet cells, an increased length of intestinal crypts, LPS localization and TLR4+ expression, and occludin downregulation, an effect counteracted in the HFD + OLE-treated mice. The HFD-fed animals displayed increased systemic levels of LPS and zonulin, but they were reduced in the HFD + OLE-treated animals. It can be seen that OLE administration improves liver steatosis and inflammation in association with decreased LPS translocation into the systemic circulation, hepatocyte localization of LPS and TLR4 downregulation in HFD-induced mouse model of NAFLD.


Subject(s)
Iridoid Glucosides , Iridoids , Lipopolysaccharides , Non-alcoholic Fatty Liver Disease , Olive Oil , Toll-Like Receptor 4 , Animals , Toll-Like Receptor 4/metabolism , Iridoid Glucosides/pharmacology , Mice , Olive Oil/pharmacology , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/etiology , Non-alcoholic Fatty Liver Disease/pathology , Male , Iridoids/pharmacology , Down-Regulation/drug effects , Diet, High-Fat/adverse effects , Liver/metabolism , Liver/drug effects , Liver/pathology , Mice, Inbred C57BL , Inflammation/metabolism , Fatty Liver/metabolism , Fatty Liver/drug therapy , Fatty Liver/etiology , Fatty Liver/pathology
5.
Nanotechnology ; 35(36)2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38861966

ABSTRACT

Synergistic cancer therapies have attracted wide attention owing to their multi-mode tumor inhibition properties. Especially, photo-responsive photoimmunotherapy demonstrates an emerging cancer treatment paradigm that significantly improved treatment efficiency. Herein, near-infrared-II responsive ovalbumin functionalized Gold-Genipin nanosystem (Au-G-OVA NRs) was designed for immunotherapy and deep photothermal therapy of breast cancer. A facile synthesis method was employed to prepare the homogeneous Au nanorods (Au NRs) with good dispersion. The nanovaccine was developed further by the chemical cross-linking of Au-NRs, genipin and ovalbumin. The Au-G-OVA NRs outstanding aqueous solubility, and biocompatibility against normal and cancer cells. The designed NRs possessed enhanced localized surface plasmon resonance (LSPR) effect, which extended the NIR absorption in the second window, enabling promising photothermal properties. Moreover, genipin coating provided complimentary red fluorescent and prepared Au-G-OVA NRs showed significant intracellular encapsulation for efficient photoimmunotherapy outcomes. The designed nanosystem possessed deep photothermal therapy of breast cancer and 90% 4T1 cells were ablated by Au-G-OVA NRs (80µg ml-1concentration) after 1064 nm laser irradiation. In addition, Au-G-OVA NRs demonstrated outstanding vaccination phenomena by facilitating OVA delivery, antigen uptake, maturation of bone marrow dendritic cells, and cytokine IFN-γsecretion for tumor immunosurveillance. The aforementioned advantages permit the utilization of fluorescence imaging-guided photo-immunotherapy for cancers, demonstrating a straightforward approach for developing nanovaccines tailored to precise tumor treatment.


Subject(s)
Gold , Immunotherapy , Infrared Rays , Iridoids , Nanotubes , Ovalbumin , Gold/chemistry , Iridoids/chemistry , Iridoids/pharmacology , Animals , Ovalbumin/chemistry , Ovalbumin/immunology , Mice , Immunotherapy/methods , Cell Line, Tumor , Female , Nanotubes/chemistry , Photothermal Therapy/methods , Phototherapy/methods , Mice, Inbred BALB C , Humans , Breast Neoplasms/therapy , Breast Neoplasms/pathology , Dendritic Cells/immunology , Surface Plasmon Resonance
6.
BMC Complement Med Ther ; 24(1): 224, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38858704

ABSTRACT

In the past few decades, there has been a notable rise in the occurrence of several types of candidiasis. Candida albicans is the most common cause of superficial fungal infections in humans. In this study, plumieride, one of the major iridoids from Plumeria obtusa L. leaves, was isolated and investigated for its potential against Candida albicans (CA)-induced dermatitis in mice. qRT-PCR was done to assess the impact of plumieride on the expression of the major virulence genes of CA. Five groups (n = 7) of adult male BALB/c mice were categorized into: group I: non-infected mice; group II: mice infected intradermally with 107-108 CFU/mL of CA; group III: CA-infected mice treated with standard fluconazole (50 mg/kg bwt.); group IV and V: CA-infected mice treated with plumieride (25- and 50 mg/kg. bwt., respectively). All the treatments were subcutaneously injected once a day for 3 days. Skin samples were collected on the 4th day post-inoculation to perform pathological, microbial, and molecular studies. The results of the in vitro study proved that plumieride has better antifungal activity than fluconazole, manifested by a wider zone of inhibition and a lower MIC. Plumieride also downregulated the expression of CA virulence genes (ALS1, Plb1, and Hyr1). CA-infected mice showed extensive dermatitis, confirmed by strong iNOS, TNF-α, IL-1ß, and NF-κB genes or immune expressions. Whereas the treatment of CA-infected mice with plumieride significantly reduced the microscopic skin lesions and modulated the expression of all measured proinflammatory cytokines and inflammatory markers in a dose-dependent manner. Plumieride interfered with the expression of C. albicans virulence factors and modulated the inflammatory response in the skin of mice infected with CA.


Subject(s)
Anti-Inflammatory Agents , Antifungal Agents , Candida albicans , Iridoids , Mice, Inbred BALB C , Animals , Mice , Male , Candida albicans/drug effects , Candida albicans/pathogenicity , Antifungal Agents/pharmacology , Iridoids/pharmacology , Anti-Inflammatory Agents/pharmacology , Candidiasis/drug therapy , Disease Models, Animal
7.
Med Oncol ; 41(8): 186, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38918260

ABSTRACT

This comprehensive review delves into the multifaceted aspects of genipin, a bioactive compound derived from medicinal plants, focusing on its anti-cancer potential. The review begins by detailing the sources and phytochemical properties of genipin, underscoring its significance in traditional medicine and its transition into contemporary cancer research. It then explores the intricate relationship between genipin's chemical structure and its observed anti-cancer activity, highlighting the molecular underpinnings contributing to its therapeutic potential. This is complemented by a thorough analysis of preclinical studies, which investigates genipin's efficacy against various cancer cell lines and its mechanisms of action at the cellular level. A crucial component of the review is the examination of genipin's bioavailability and pharmacokinetics, providing insights into how the compound is absorbed, distributed, metabolized, and excreted in the body. Then, this review offers a general and updated overview of the anti-cancer studies of genipin and its derivatives based on its basic molecular mechanisms, induction of apoptosis, inhibition of cell proliferation, and disruption of cancer cell signaling pathways. We include information that complements the genipin study, such as toxicity data, and we differentiate this review by including commercial status, disposition, and regulation. Also, this review of genipin stands out for incorporating information on proposals for a technological approach through its load in nanotechnology to improve its bioavailability. The culmination of this information positions genipin as a promising candidate for developing novel anti-cancer drugs capable of supplementing or enhancing current cancer therapies.


Subject(s)
Iridoids , Neoplasms , Humans , Iridoids/pharmacology , Iridoids/chemistry , Iridoids/therapeutic use , Neoplasms/drug therapy , Phytochemicals/therapeutic use , Phytochemicals/pharmacology , Phytochemicals/chemistry , Animals , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/therapeutic use , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/chemistry , Apoptosis/drug effects
8.
Chem Pharm Bull (Tokyo) ; 72(6): 547-558, 2024.
Article in English | MEDLINE | ID: mdl-38866476

ABSTRACT

Iridoids, which are a class of monoterpenoids, are attractive synthetic targets due to their diversely substituted cis-fused cyclopenta[c]pyran skeletons. Additionally, various biological activities of iridoids raise the value of synthetic studies on this class of compounds. Here, our synthetic efforts toward 11-noriridoids; (±)-umbellatolide B (6), (±)-10-O-benzoylglobularigenin (9) and 1-O-pentenylaucubigenin (34) are described. For the efficient synthesis of target compounds, common synthetic intermediates (tricyclic enones 17 and 26) were prepared by the Pauson-Khand reaction. The cleavage of the acetal bond on the tricyclic enones and 1,2-reduction introduced the two hydroxy groups on the cyclopentane ring of the core scaffold. Furthermore, the C3-C4 olefin part was constructed by the syn-elimination of a thiocarbonate moiety to obtain 34. The developed synthetic routes for 6, 9, and 34 will be useful for the preparation of iridoid analogs that have a polyfunctionalized core skeleton.


Subject(s)
Iridoids , Iridoids/chemical synthesis , Iridoids/chemistry , Molecular Structure , Stereoisomerism
9.
BMC Plant Biol ; 24(1): 526, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38858643

ABSTRACT

Light intensity is a key factor affecting the synthesis of secondary metabolites in plants. However, the response mechanisms of metabolites and genes in Gentiana macrophylla under different light intensities have not been determined. In the present study, G. macrophylla seedlings were treated with LED light intensities of 15 µmol/m2/s (low light, LL), 90 µmol/m2/s (medium light, ML), and 200 µmol/m2/s (high light, HL), and leaves were collected on the 5th day for further investigation. A total of 2162 metabolites were detected, in which, the most abundant metabolites were identified as flavonoids, carbohydrates, terpenoids and amino acids. A total of 3313 and 613 differentially expressed genes (DEGs) were identified in the LL and HL groups compared with the ML group, respectively, mainly enriched in KEGG pathways such as carotenoid biosynthesis, carbon metabolism, glycolysis/gluconeogenesis, amino acids biosynthesis, plant MAPK pathway and plant hormone signaling. Besides, the transcription factors of GmMYB5 and GmbHLH20 were determined to be significantly correlated with loganic acid biosynthesis; the expression of photosystem-related enzyme genes was altered under different light intensities, regulating the expression of enzyme genes involved in the carotenoid, chlorophyll, glycolysis and amino acids pathway, then affecting their metabolic biosynthesis. As a result, low light inhibited photosynthesis, delayed glycolysis, thus, increased certain amino acids and decreased loganic acid production, while high light got an opposite trend. Our research contributed significantly to understand the molecular mechanism of light intensity in controlling metabolic accumulation in G. macrophylla.


Subject(s)
Gentiana , Iridoids , Light , Metabolome , Transcriptome , Gentiana/genetics , Gentiana/metabolism , Iridoids/metabolism , Metabolome/radiation effects , Gene Expression Regulation, Plant , Plant Leaves/metabolism , Plant Leaves/genetics , Plant Leaves/radiation effects , Gene Expression Profiling
10.
Biomed Pharmacother ; 176: 116911, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38861857

ABSTRACT

Atopic dermatitis (AD) is a globally increasing chronic inflammatory skin disease with limited and potentially side-effect-prone treatment options. Monotropein is the predominant iridoid glycoside in Morinda officinalis How roots, which has previously shown promise in alleviating AD symptoms. This study aimed to systematically investigate the pharmacological effects of monotropein on AD using a 2, 4-dinitrochlorobenzene (DNCB)/Dermatophagoides farinae extract (DFE)-induced AD mice and tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated keratinocytes. Oral administration of monotropein demonstrated a significant reduction in AD phenotypes, including scaling, erythema, and increased skin thickness in AD-induced mice. Histological analysis revealed a marked decrease in immune cell infiltration in skin lesions. Additionally, monotropein effectively downregulated inflammatory markers, encompassing pro-inflammatory cytokines, T helper (Th)1 and Th2 cytokines, and pro-inflammatory chemokines in skin tissues. Notably, monotropein also led to a considerable decrease in serum immunoglobulin (Ig)E and IgG2a levels. At a mechanistic level, monotropein exerted its anti-inflammatory effects by suppressing the phosphorylation of Janus kinase / signal transducer and activator of transcription proteins in both skin tissues of AD-induced mice and TNF-α/IFN-γ-stimulated keratinocytes. In conclusion, monotropein exhibited a pronounced alleviation of AD symptoms in the experimental models used. These findings underscore the potential application of monotropein as a therapeutic agent in the context of AD, providing a scientific basis for further exploration and development.


Subject(s)
Dermatitis, Atopic , Janus Kinases , Keratinocytes , Signal Transduction , Skin , Animals , Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/pathology , Dermatitis, Atopic/chemically induced , Signal Transduction/drug effects , Mice , Janus Kinases/metabolism , Skin/drug effects , Skin/pathology , Skin/metabolism , Keratinocytes/drug effects , Keratinocytes/metabolism , Cytokines/metabolism , Mice, Inbred BALB C , STAT Transcription Factors/metabolism , Humans , Dinitrochlorobenzene , Anti-Inflammatory Agents/pharmacology , Female , Disease Models, Animal , Inflammation/drug therapy , Inflammation/pathology , Immunoglobulin E/blood , Dermatophagoides farinae/immunology , Iridoids/pharmacology
11.
Carbohydr Polym ; 339: 122174, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38823938

ABSTRACT

Segmental bone defects can arise from trauma, infection, metabolic bone disorders, or tumor removal. Hydrogels have gained attention in the field of bone regeneration due to their unique hydrophilic properties and the ability to customize their physical and chemical characteristics to serve as scaffolds and carriers for growth factors. However, the limited mechanical strength of hydrogels and the rapid release of active substances have hindered their clinical utility and therapeutic effectiveness. With ongoing advancements in material science, the development of injectable and biofunctionalized hydrogels holds great promise for addressing the challenges associated with segmental bone defects. In this study, we incorporated lyophilized platelet-rich fibrin (LPRF), which contains a multitude of growth factors, into a genipin-crosslinked gelatin/hyaluronic acid (GLT/HA-0.5 % GP) hydrogel to create an injectable and biofunctionalized composite material. Our findings demonstrate that this biofunctionalized hydrogel possesses optimal attributes for bone tissue engineering. Furthermore, results obtained from rabbit model with segmental tibial bone defects, indicate that the treatment with this biofunctionalized hydrogel resulted in increased new bone formation, as confirmed by imaging and histological analysis. From a translational perspective, this biofunctionalized hydrogel provides innovative and bioinspired capabilities that have the potential to enhance bone repair and regeneration in future clinical applications.


Subject(s)
Bone Regeneration , Freeze Drying , Gelatin , Hyaluronic Acid , Hydrogels , Iridoids , Platelet-Rich Fibrin , Animals , Iridoids/chemistry , Iridoids/pharmacology , Gelatin/chemistry , Rabbits , Hydrogels/chemistry , Hydrogels/pharmacology , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacology , Bone Regeneration/drug effects , Platelet-Rich Fibrin/chemistry , Tissue Engineering/methods , Cross-Linking Reagents/chemistry , Tissue Scaffolds/chemistry , Tibia/drug effects , Tibia/surgery
12.
J Pharm Pharmacol ; 76(7): 897-907, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38727186

ABSTRACT

OBJECTIVES: Bile acids (BAs), as signaling molecules to regulate metabolism, have received considerable attention. Genipin is an iridoid compound extracted from Fructus Gradeniae, which has been shown to relieve adiposity and metabolic syndrome. Here, we investigated the mechanism of genipin counteracting obesity and its relationship with BAs signals in diet-induced obese (DIO) rats. METHODS: The DIO rats were received intraperitoneal injections of genipin for 10 days. The body weight, visceral fat, lipid metabolism in the liver, thermogenic genes expressions in brown fat, BAs metabolism and signals, and key enzymes for BAs synthesis were determined. KEY FINDINGS: Genipin inhibited fat synthesis and promoted lipolysis in the liver, and upregulated thermogenic gene expressions in brown adipose tissue of DIO rats. Genipin increased bile flow rate and upregulated the expressions of aquaporin 8 and the transporters of BAs in liver. Furthermore, genipin changed BAs composition by promoting alternative pathways and inhibiting classical pathways for BAs synthesis and upregulated the expressions of bile acid receptors synchronously. CONCLUSIONS: These results suggest that genipin ameliorate obesity through BAs-mediated signaling pathways.


Subject(s)
Bile Acids and Salts , Iridoids , Liver , Obesity , Rats, Sprague-Dawley , Animals , Obesity/drug therapy , Obesity/metabolism , Iridoids/pharmacology , Bile Acids and Salts/metabolism , Male , Rats , Liver/metabolism , Liver/drug effects , Lipid Metabolism/drug effects , Diet, High-Fat/adverse effects , Bile/metabolism , Signal Transduction/drug effects , Lipolysis/drug effects , Intra-Abdominal Fat/drug effects , Intra-Abdominal Fat/metabolism
13.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2654-2665, 2024 May.
Article in Chinese | MEDLINE | ID: mdl-38812166

ABSTRACT

This study established an ultrasound-assisted extraction-high performance liquid chromatography method for simulta-neously determinining the content of 11 bioactive compounds including iridoids, phenolic acids, and flavonoids in Lonicera japonica flowers. The flowers at six stages from the rice bud stage(ML) to the golden flower stage(JH) of L. japonica varieties 'Sijuhua' and 'Beihua No.1' in two planting bases in Shandong province were collected. The established method was employed to determine the content of 11 target compounds, on the basis of which the dynamics of active components in L. japonica sampels during different development stages was investigated. The correlation analysis was carried out to reveal the correlations of the content of iridoids, phenolic acids, and flavonoids. Furthermore, the antioxidant activities of samples at different developmental stages were determined, and the relationship between antioxidant activity and chemical components was analyzed by the correlation analysis. The results showed that the total content of the 11 components in 'Sijihua' changed in a "W" pattern from the ML to JH, being the highest at the ML and the second at the slight white stage(EB). The total content of 11 compounds in 'Beihua No.1' was the highest at the ML and decreased gra-dually from the ML to JH. The samples of 'Sijihua' had higher content of iridoids and lower content of phenolic acids than those of 'Beihua No.1'. The content of flavonoids and phenolic acids showed a positive correlation(R~2=0.90, P<0.05) in 'Sijihua' but no obvious correlation in 'Beihua No.1'. The antioxidant activity and phenolic acid content showed positive correlations, with the determination coefficients(R~2) of 0.84(P<0.05) in 'Beihua No.1' and 0.73(P<0.05) in 'Sijihua'. The antioxidant activity of both varieties was the strongest at the ML and the second at the EB. This study revealed that the content dynamics of iridoids, phenolic acids, and flavonoids in 'Sijihua' and 'Beihua No.1' cultivated in Shandong province during different developmental stages. The results indicated that the antioxidant activity of L. japonica flowers was significantly correlated with the content of phenolic acids at different deve-lopmental stages, which provided a basis for determining the optimum harvest time of L. japonica flowers.


Subject(s)
Antioxidants , Flavonoids , Flowers , Lonicera , Lonicera/chemistry , Lonicera/growth & development , Lonicera/metabolism , Flowers/chemistry , Flowers/growth & development , Flowers/metabolism , Antioxidants/metabolism , Antioxidants/analysis , Antioxidants/chemistry , China , Flavonoids/analysis , Flavonoids/chemistry , Flavonoids/metabolism , Hydroxybenzoates/analysis , Hydroxybenzoates/metabolism , Secondary Metabolism , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/chemistry , Iridoids/metabolism , Iridoids/analysis , Iridoids/chemistry
14.
Biomed Mater ; 19(4)2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38815598

ABSTRACT

Bacterial infection can lead to various complications, such as inflammations on surrounding tissues, which can prolong wound healing and thus represent a significant clinical and public healthcare problem. Herein, a report on the fabrication of a novel genipin/quaternized chitosan (CS) hydrogel for wound dressing is presented. The hydrogel was prepared by mixing quaternized CS and genipin under 35 °C bath. The hydrogels showed porous structure (250-500 µm) and mechanical properties (3000-6000 Pa). In addition, the hydrogels displayed self-healing ability and adhesion performance on different substrates. Genipin crosslinked quaternized CS hydrogels showed antibacterial activities againstE. coliandS. aureus. The CCK-8 and fluorescent images confirmed the cytocompatibility of hydrogels by seeding with NIH-3T3 cells. The present study showed that the prepared hydrogel has the potential to be used as wound dressing.


Subject(s)
Anti-Bacterial Agents , Bandages , Chitosan , Cross-Linking Reagents , Escherichia coli , Hydrogels , Iridoids , Quaternary Ammonium Compounds , Staphylococcus aureus , Wound Healing , Chitosan/chemistry , Iridoids/chemistry , Animals , Mice , Hydrogels/chemistry , Wound Healing/drug effects , NIH 3T3 Cells , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Staphylococcus aureus/drug effects , Escherichia coli/drug effects , Cross-Linking Reagents/chemistry , Quaternary Ammonium Compounds/chemistry , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Materials Testing , Porosity
15.
Biomacromolecules ; 25(6): 3566-3582, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38780026

ABSTRACT

Diabetic foot ulcers (DFUs), a prevalent complication of diabetes mellitus, may result in an amputation. Natural and renewable hydrogels are desirable materials for DFU dressings due to their outstanding biosafety and degradability. However, most hydrogels are usually only used for wound repair and cannot be employed to monitor motion because of their inherent poor mechanical properties and electrical conductivity. Given that proper wound stretching is beneficial for wound healing, the development of natural hydrogel patches integrated with wound repair properties and motion monitoring was expected to achieve efficient and accurate wound healing. Here, we designed a dual-network (chitosan and sodium alginate) hydrogel embedded with lignin-Ag and quercetin-melanin nanoparticles to achieve efficient wound healing and motion monitoring. The double network formed by the covalent bond and electrostatic interaction confers the hydrogel with superior mechanical properties. Instead of the usual chemical reagents, genipin extracted from Gardenia was used as a cross-linking agent for the hydrogel and consequently improved its biosafety. Furthermore, the incorporation of lignin-Ag nanoparticles greatly enhanced the mechanical strength, antibacterial efficacy, and conductivity of the hydrogel. The electrical conductivity of hydrogels gives them the capability of motion monitoring. The motion sensing mechanism is that stretching of the hydrogel induced by motion changes the conductivity of the hydrogel, thus converting the motion into an electrical signal. Meanwhile, quercetin-melanin nanoparticles confer exceptional adhesion, antioxidant, and anti-inflammatory properties to the hydrogels. The system ultimately achieved excellent wound repair and motion monitoring performance and was expected to be used for stretch-assisted safe and accurate wound repair in the future.


Subject(s)
Chitosan , Electric Conductivity , Hydrogels , Wound Healing , Hydrogels/chemistry , Wound Healing/drug effects , Chitosan/chemistry , Animals , Quercetin/chemistry , Quercetin/pharmacology , Melanins/chemistry , Silver/chemistry , Diabetic Foot/therapy , Diabetic Foot/drug therapy , Mice , Alginates/chemistry , Metal Nanoparticles/chemistry , Humans , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Iridoids
16.
Food Res Int ; 186: 114161, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38729685

ABSTRACT

In this article, the synthesis of antioxidant peptides in the enzymatic hydrolysis of caprine casein was analyzed at three different time points (60 min, 90 min, and 120 min) using immobilized pepsin on activated and modified carbon (AC, ACF, ACG 50, ACG 100). The immobilization assays revealed a reduction in the biocatalysts' activity compared to the free enzyme. Among the modified ones, ACG 50 exhibited greater activity and better efficiency for reuse cycles, with superior values after 60 min and 90 min. Peptide synthesis was observed under all studied conditions. Analyses (DPPH, ß-carotene/linoleic acid, FRAP) confirmed the antioxidant potential of the peptides generated by the immobilized enzyme. However, the immobilized enzyme in ACG 50 and ACG 100, combined with longer hydrolysis times, allowed the formation of peptides with an antioxidant capacity greater than or equivalent to those generated by the free enzyme, despite reduced enzymatic activity.


Subject(s)
Antioxidants , Caseins , Enzymes, Immobilized , Glutaral , Goats , Iridoids , Pepsin A , Peptides , Antioxidants/chemistry , Enzymes, Immobilized/chemistry , Enzymes, Immobilized/metabolism , Caseins/chemistry , Animals , Pepsin A/metabolism , Pepsin A/chemistry , Glutaral/chemistry , Peptides/chemistry , Iridoids/chemistry , Hydrolysis , Charcoal/chemistry
17.
Biomacromolecules ; 25(6): 3519-3531, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38742604

ABSTRACT

Elastic fibers provide critical elasticity to the arteries, lungs, and other organs. Elastic fiber assembly is a process where soluble tropoelastin is coacervated into liquid droplets, cross-linked, and deposited onto and into microfibrils. While much progress has been made in understanding the biology of this process, questions remain regarding the timing of interactions during assembly. Furthermore, it is unclear to what extent fibrous templates are needed to guide coacervate droplets into the correct architecture. The organization and shaping of coacervate droplets onto a fiber template have never been previously modeled or employed as a strategy for shaping elastin fiber materials. Using an in vitro system consisting of elastin-like polypeptides (ELPs), genipin cross-linker, electrospun polylactic-co-glycolic acid (PLGA) fibers, and tannic acid surface coatings for fibers, we explored ELP coacervation, cross-linking, and deposition onto fiber templates. We demonstrate that integration of coacervate droplets into a fibrous template is primarily influenced by two factors: (1) the balance of coacervation and cross-linking and (2) the surface energy of the fiber templates. The success of this integration affects the mechanical properties of the final fiber network. Our resulting membrane materials exhibit highly tunable morphologies and a range of elastic moduli (0.8-1.6 MPa) comparable to native elastic fibers.


Subject(s)
Elastin , Polylactic Acid-Polyglycolic Acid Copolymer , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Elastin/chemistry , Lactic Acid/chemistry , Polyglycolic Acid/chemistry , Iridoids/chemistry , Tropoelastin/chemistry , Cross-Linking Reagents/chemistry , Tannins/chemistry , Peptides/chemistry , Elasticity
18.
Int J Biol Macromol ; 270(Pt 1): 132329, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38744362

ABSTRACT

The present work develops an effective bioadsorbent of cross-linked chitosan-genipin/SiO2 adsorbent (CHI-GNP/SiO2). The developed CHI-GNP/SiO2 was employed for the removal of organic dye (reactive orange 16, RO16) from simulated wastewater. The optimization of the fundamental adsorption variables (CHI-GNP/SiO2 dose, time, and pH) via the Box-Behnken design (BBD) was attained for achieving maximal adsorption capacity and high removal efficiency. The good agreement between the Freundlich isotherms and empirical data of RO16 adsorption by CHI-GNP/SiO2 indicates that the adsorption process follows a multilayer adsorption mechanism. The reasonable agreement between the pseudo-second-order model and the kinetic data of RO16 adsorption by CHI-GNP/SiO2 was obtained. The maximum RO16 adsorption capacity (qmax) of CHI-GNP/SiO2 was identified to be 57.1 mg/g. The adsorption capacity of CHI-GNP/SiO2 is attributed to its unique surface properties, including its highly porous structure and the presence of functional groups such as amino and hydroxyl groups. According to the results of this investigation, CHI-GNP/SiO2 has the potential to be an adsorbent for the removal of acidic dyes from wastewater.


Subject(s)
Azo Compounds , Chitosan , Silicon Dioxide , Water Pollutants, Chemical , Water Purification , Chitosan/chemistry , Silicon Dioxide/chemistry , Adsorption , Azo Compounds/chemistry , Azo Compounds/isolation & purification , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/isolation & purification , Kinetics , Water Purification/methods , Hydrogen-Ion Concentration , Models, Statistical , Wastewater/chemistry , Coloring Agents/chemistry , Coloring Agents/isolation & purification , Iridoids
19.
Ultrason Sonochem ; 106: 106899, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38733852

ABSTRACT

Chitosan nanoparticles (NPs) possess great potential in biomedical fields. Orifice-induced hydrodynamic cavitation (HC) has been used for the enhancement of fabrication of size-controllable genipin-crosslinked chitosan (chitosan-genipin) NPs based on the emulsion cross-linking (ECLK). Experiments have been performed using various plate geometries, chitosan molecular weight and under different operational parameters such as inlet pressure (1-3.5 bar), outlet pressure (0-1.5 bar) and cross-linking temperature (40-70 °C). Orifice plate geometry was a crucial factor affecting the properties of NPs, and the optimized geometry of orifice plate was with single hole of 3.0 mm diameter. The size of NPs with polydispersity index of 0.359 was 312.6 nm at an optimized inlet pressure of 3.0 bar, and the maximum production yield reached 84.82 %. Chitosan with too high or too low initial molecular weight (e.g., chitosan oligosaccharide) was not applicable for producing ultra-fine and narrow-distributed NPs. There existed a non-linear monotonically-increasing relationship between cavitation number (Cv) and chitosan NP size. Scanning electron microscopy (SEM) test indicated that the prepared NPs were discrete with spherical shape. The study demonstrated the superiority of HC in reducing particle size and size distribution of NPs, and the energy efficiency of orifice type HC-processed ECLK was two orders of magnitude than that of ultrasonic horn or high shear homogenization-processed ECLK. In vitro drug-release studies showed that the fabricated NPs had great potential as a drug delivery system. The observations of this study can offer strong support for HC to enhance the fabrication of size-controllable chitosan-genipin NPs.


Subject(s)
Chitosan , Hydrodynamics , Iridoids , Nanoparticles , Particle Size , Chitosan/chemistry , Nanoparticles/chemistry , Iridoids/chemistry , Pressure , Temperature , Molecular Weight
20.
J Agric Food Chem ; 72(27): 15190-15197, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38807430

ABSTRACT

Cultured meat technology is expected to solve problems such as resource shortages and environmental pollution, but the muscle fiber differentiation efficiency of cultured meat is low. Genipin is the active compound derived from Gardenia jasminoides Ellis, which has a variety of activities. Additionally, genipin serves as a noncytotoxic agent for cross-linking, which is suitable as a foundational scaffold for in vitro tissue regeneration. However, the impact of genipin on myoblast differentiation remains to be studied. The research revealed that genipin was found to improve the differentiation efficiency of myoblasts. Genipin improved mitochondrial membrane potential by activating the AMPK signaling pathway of myoblasts, promoting mitochondrial biogenesis, and mitochondrial network remodeling. Genipin activated autophagy in myoblasts and maintained cellular homeostasis. Autophagy inhibitors blocked the pro-differentiation effect of genipin. These results showed that genipin improved the differentiation efficiency of myoblasts, which provided a theoretical basis for the development of cultured meat technology.


Subject(s)
AMP-Activated Protein Kinases , Autophagy , Cell Differentiation , Iridoids , Myoblasts , Signal Transduction , Iridoids/pharmacology , Iridoids/chemistry , Cell Differentiation/drug effects , Myoblasts/drug effects , Myoblasts/cytology , Myoblasts/metabolism , Autophagy/drug effects , AMP-Activated Protein Kinases/metabolism , AMP-Activated Protein Kinases/genetics , Animals , Mice , Signal Transduction/drug effects , Cell Line , Humans
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