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1.
Molecules ; 27(8)2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35458604

RESUMO

Cultivation location, maturity levels, and extraction solvents could affect the bioactive compounds and biological activities of mulberry (Morus alba Linnaeus). The lack of study on Malaysia-grown mulberry causes its underutilization. This study investigated the bioactive compound content and the antioxidant activity of Sabah-grown mulberry at two different maturity stages (fruits: red mature and black fully ripe; leaves: young and mature) extracted using 70% (v/v) methanol, 60% (v/v) ethanol, and 65% (v/v) acetone. Analyses showed that mulberry fruits demonstrated maturity-dependent increment (except UHPLC-DAD quantification), while the leaves revealed maturity-dependent reduction. Principal component analysis (PCA) displayed 65% (v/v) acetone black fully ripe fruits as the best phenolics and antioxidant sources. However, the 60% (v/v) ethanol black fully ripe fruits contained 20.08-68.43% higher total anthocyanins. Meanwhile, the 65% (v/v) acetone and 70% (v/v) methanol red mature fruits were higher in chlorogenic acid (27.53-47.12%) and rutin (31.42-35.92%) than other fruit extracts, respectively. For leaves, 65% (v/v) acetone young leaves were the best phenolics and antioxidant sources. However, the 60% (v/v) ethanol young leaves possessed greater chlorogenic acid (19.56-74.11%) than other leaf extracts. Overall, Malaysia-grown mulberry is rich in phenolics and antioxidants, suggesting its potential application in food and pharmaceutical products.


Assuntos
Morus , Acetona , Antocianinas , Antioxidantes/análise , Antioxidantes/farmacologia , Ácido Clorogênico , Etanol , Frutas/química , Metanol , Fenóis/análise , Extratos Vegetais , Folhas de Planta/química , Solventes
2.
Molecules ; 27(8)2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35458650

RESUMO

Marine fish collagen has attracted considerable attention due to its characteristics, including its biodegradability, biocompatibility, and weak antigenicity, and is considered a safer material compared to collagen from terrestrial animals. The aim of this study was to extract and characterize collagen from the skin of lizardfish (Saurida tumbil Bloch, 1795) with three different acids. The yields of acetic acid-extracted collagen (AESkC), lactic acid-extracted collagen (LESkC), and citric acid-extracted collagen (CESkC) were 11.73 ± 1.14%, 11.63 ± 1.10%, and 11.39 ± 1.05% (based on wet weight), respectively. All extracted collagens were categorized as type I collagen with mainly alpha chains (α1 and α2) detected and γ and ß chains to some extent. Fourier transform infrared (FTIR) spectra showed an intact triple-helical structure in the AESkC, LESkC, and CESkC. UV-vis spectra and X-ray diffraction further demonstrated the similarity of the extracted collagens to previously reported fish skin collagens. AESkC (Tmax = 40.24 °C) had higher thermostability compared to LESkC (Tmax = 38.72 °C) and CESkC (Tmax = 36.74 °C). All samples were highly soluble in acidic pH and low concentrations of NaCl (0-20 g/L). Under field emission scanning electron microscopy (FESEM) observation, we noted the loose, fibrous, and porous structures of the collagens. The results suggest that the lizardfish skin collagens could be a potential alternative source of collagen, especially the AESkC due to its greater thermostability characteristic.


Assuntos
Colágeno , Proteínas de Peixes , Ácidos/química , Animais , Colágeno/química , Proteínas de Peixes/química , Peixes , Pele/química , Solubilidade
3.
Molecules ; 27(12)2022 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-35744912

RESUMO

The caseinolytic protease (Clp) system plays an essential role in the protein homeostasis of the malaria parasite, particularly at the stage of apicoplast development. The inhibition of this protein is known to have a lethal effect on the parasite and is therefore considered an interesting avenue for antimalaria drugs discovery. The catalytic activity of the Clp system is modulated by its proteolytic subunit (ClpP), which belongs to the serine protease family member and is therefore extensively studied for further inhibitors development. Among many inhibitors, the group of ß-lactone is known to be a specific inhibitor for ClpP. Nevertheless, other groups of lactones have never been studied. This study aims to characterize the catalytic properties of ClpP of Plasmodium knowlesi (Pk-ClpP) and the inhibition properties of a δ-lactone hyptolide against this protein. Accordingly, a codon-optimized synthetic gene encoding Pk-ClpP was expressed in Escherichia coli BL21(DE3) and purified under a single step of Ni2+-affinity chromatography, yielding a 2.20 mg from 1 L culture. Meanwhile, size-exclusion chromatography indicated that Pk-ClpP migrated primarily as homoheptameric with a size of 205 kDa. The specific activity of pure Pk-ClpP was 0.73 U µg-1, with a catalytic efficiency kcat/KM of 0.05 µM-1 s-1, with optimum temperature and pH of 50 °C and 7.0-7.5, respectively. Interestingly, hyptolide, a member of δ-lactone, was shown to inhibit Pk-ClpP with an IC50 value of 17.36 ± 1.44 nM. Structural homology modelling, secondary structure prediction, and far-UV CD spectra revealed that helical structures dominate this protein. In addition, the structural homology modeling showed that this protein forms a barrel-shaped homoheptamer. Docking simulation revealed that the inhibition was found to be a competitive inhibition in which hyptolide was able to dock into the catalytic site and block the substrate. The competitiveness of hyptolide is due to the higher binding affinity of this molecule than the substrate.


Assuntos
Plasmodium knowlesi , Domínio Catalítico , Escherichia coli , Lactonas/farmacologia , Serina Proteases
4.
Molecules ; 26(21)2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34770879

RESUMO

Haematococcus pluvialis, a green microalga, appears to be a rich source of valuable bioactive compounds, such as astaxanthin, carotenoids, proteins, lutein, and fatty acids (FAs). Astaxanthin has a variety of health benefits and is used in the nutraceutical and pharmaceutical industries. Astaxanthin, for example, preserves the redox state and functional integrity of mitochondria and shows advantages despite a low dietary intake. Because of its antioxidant capacity, astaxanthin has recently piqued the interest of researchers due to its potential pharmacological effects, which include anti-diabetic, anti-inflammatory, and antioxidant activities, as well as neuro-, cardiovascular-, ocular, and skin-protective properties. Astaxanthin is a popular nutritional ingredient and a significant component in animal and aquaculture feed. Extensive studies over the last two decades have established the mechanism by which persistent oxidative stress leads to chronic inflammation, which then mediates the majority of serious diseases. This mini-review provides an overview of contemporary research that makes use of the astaxanthin pigment. This mini-review provides insight into the potential of H. pluvialis as a potent antioxidant in the industry, as well as the broad range of applications for astaxanthin molecules as a potent antioxidant in the industrial sector.


Assuntos
Produtos Biológicos , Suplementos Nutricionais , Fibrinolíticos/metabolismo , Microalgas/fisiologia , Biotecnologia , Desenvolvimento de Medicamentos , Fibrinolíticos/farmacologia , Indústria Alimentícia , Microalgas/química , Espécies Reativas de Oxigênio/metabolismo , Xantofilas/metabolismo , Xantofilas/farmacologia
5.
J Ethnopharmacol ; 330: 118239, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-38657877

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetes mellitus, a widespread chronic illness, affects millions worldwide, and its incidence is increasing alarmingly, especially in developing nations. Current pharmacological treatments can be costly and have undesirable side effects. To address this, medicinal plants with antidiabetic effects, particularly targeting α-glucosidase for controlling hyperglycaemia in type-2 diabetes mellitus (T2DM), hold promise for drug development with reduced toxicity and adverse reactions. AIM OF THIS REVIEW: This review aims to succinctly collect information about medicinal plant extracts that exhibit antidiabetic potential through α-glucosidase inhibition using acarbose as a standard reference in Southeast Asia. The characteristics of this inhibition are based on in vitro studies. MATERIALS AND METHODS: Relevant information on medicinal plants in Southeast Asia, along with α-glucosidase inhibition studies using acarbose as a positive control, was gathered from various scientific databases, including Scopus, PubMed, Web of Science, and Google Scholar. RESULTS: About 49 papers were found from specific counties in Southeast Asia demonstrated notable α-glucosidase inhibitory potential of their medicinal plants, with several plant extracts showcasing activity comparable to or surpassing that of acarbose. Notably, 19 active constituents were identified for their α-glucosidase inhibitory effects. CONCLUSIONS: The findings underscore the antidiabetic potential of the tested medicinal plant extracts, indicating their promise as alternative treatments for T2DM. This review can aid in the development of potent therapeutic medicines with increased effectiveness and safety for the treatment of T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores de Glicosídeo Hidrolases , Hipoglicemiantes , Extratos Vegetais , Plantas Medicinais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/uso terapêutico , Plantas Medicinais/química , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Sudeste Asiático , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Animais , alfa-Glucosidases/metabolismo , Fitoterapia
6.
Int J Biomater ; 2023: 7312447, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37151379

RESUMO

Waste from marine fish processing is an important source of valuable products. Fish collagen is considered a alternative biomaterial due to its excellent properties, and it is widely used for industrial purposes. Thus, this present study aimed to characterize acid and pepsin-soluble collagens from the waste of parrotfish (Scarus sordidus Forsskål, 1775) scales. The yields (p > 0.05) of acid-soluble collagen (ASC-PFS) and pepsin-soluble collagen (PSC-PFS) were 1.17 g/100 g and 1.00 g/100 g, respectively. Both collagen samples were categorized as type I owing to the presence of two alpha chain subunits (α1 and α1) after being confirmed by a sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Under the fourier transform infrared (FTIR) test, the triple helical structure of type I collagens from the ASC-PFS and PSC-PFS was maintained. Moreover, the study of UV visible spectra and X-ray diffraction (XRD) showed the similarity of collagens derived from different fish species, and the thermostability (T max) evaluation of all extracted collagens was in the range of 36.22-37.78°C, and their values were comparable to previous research on the fish scale collagens. The effect of various pH and sodium chloride (NaCl) treatments on solubility exhibited that the ASC-PFS and PSC-PFS were highly soluble in an acidic condition (pH < 5.0) and low concentration of sodium chloride (<30 g/L). Taken together, collagens extracted from parrotfish scale waste can be an alternative source for industries.

7.
Polymers (Basel) ; 15(4)2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36850337

RESUMO

Biopolymer-like collagen has great industrial potential in terms of its excellent properties, such as strong biocompatibility, high degradability, and low antigenicity. Collagen derived from fish by-products is preferable as it is safer (free from transmittable diseases) and acceptable to most religious beliefs. This study aimed to characterize the unicornfish (Naso reticulatus Randall, 2001) bone collagens prepared with different type of acids, i.e., acetic acid, lactic acid, and citric acid. A higher yield (Y) (p < 0.05) was obtained in the citric-acid-soluble collagen (CASC) (Y = 1.36%), followed by the lactic-acid-soluble collagen (LASC) (Y = 1.08%) and acetic-acid-soluble collagen (AASC) (Y = 0.40%). All extracted collagens were classified as type I due to the presence of 2-alpha chains (α1 and α2). Their prominent absorption spectra were located at the wavelengths of 229.83 nm to 231.17 nm. This is similar to wavelengths reported for other fish collagens. The X-ray diffraction (XRD) and infrared (IR) data demonstrated that the triple-helical structure of type I collagens was still preserved after the acid-extraction process. In terms of thermal stability, all samples had similar maximum transition temperatures (Tmax = 33.34-33.51 °C). A higher relative solubility (RS) of the unicornfish bone collagens was observed at low salt concentration (0-10 g/L) (RS > 80%) and at acidic condition (pH 1.0 to pH 3.0) (RS > 75%). The extracted collagen samples had an irregular and dense flake structure with random coiled filaments. Overall, bones of unicornfish may be used as a substitute source of collagen.

8.
J Funct Biomater ; 14(2)2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36826886

RESUMO

This study was carried out to compare the extractability and characteristics of barracuda (Sphyraena sp.) skin collagen using various organic acids. Acetic-solubilized collagen (ASBS), lactic-solubilized collagen (LSBS) and citric-solubilized collagen (CSBS) yielded 6.77 g/100 g, 10.06 g/100 g and 8.35 g/100 g, respectively, and those yields were significantly different (p < 0.05). All acid-solubilized collagens were considered as type I because of their two alpha chains (α1 and α2) detected in acrylamide gel after electrophoresis. Ultraviolet-visible (UV-vis) analysis confirmed that ASBS, LSBS and CSBS had similar absorption peaks (230.5 nm) and the results were in accordance with other fish collagens. Under infrared (IR) and X-ray diffraction (XRD) analysis, the triple helical structure of type I collagens extracted from barracuda skin was maintained. From a thermostability study, all type I collagens showed a higher maximum transition temperature (Tmax = 40.16 to 41.29 °C) compared to other fish skin collagens. In addition, the functional properties of the extracted collagens revealed the ASBS had higher water and oil absorption capacities than the CSBS and LSBS samples. The highest level of the emulsion ability index (EAI) (>200 m2/g) was detected under acidic conditions (pH 4), while lower EAIs were recorded under the alkaline (pH 10) and neutral treatments (pH 7). All type I collagens had a higher relative solubility (>60%) at a low pH test but the solubility level sharply decreased at a neutral pH. In addition to this, a lower concentration of NaCl (0-20 g/L) showed the higher percentage of solubility (>60%) while adding over 30 g/L of NaCl decreased solubility (>40%). From a microstructural test, all type I samples had an irregular and dense flake structure with random coiled filaments. Overall, collagen extracted from the barracuda skin may be applied as an alternative collagen from an industry perspective.

9.
Gels ; 8(5)2022 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-35621564

RESUMO

The purpose of this research was to extract collagen from the scales of lizardfish (Saurida tumbil) using various acids. Acetic acid-extracted collagen (AScC) produced a higher yield (1.8 mg/g) than lactic acid-extracted collagen (LScC) and citric acid-extracted collagen (CScC) although not significantly different (p > 0.05). All extracted collagens were categorized as type I collagens with the presence of alpha chains (α1 and α2) based on the SDS-PAGE profiles. The triple-helical structure of the collagen was maintained in the AScC, LScC, and CScC as confirmed by the FTIR spectra. The UV-vis and X-ray diffraction spectra observed in all collagens were in agreement with previous work on fish scale and calfskin (commercial) collagens. The thermal stability of AScC (Tmax = 31.61 °C) was greater than LScC (Tmax = 30.86 °C) and CScC (Tmax = 30.88 °C). The microstructure of acid-extracted collagens was characterized as complex, fibrous, and multilayered, with irregular sheet-like structures. All samples were highly soluble in acidic pH (1.0−4.0) and in low concentrations of NaCl (0−20 g/L). In conclusion, the lizardfish scale collagen, particularly AScC, may be used as an alternative to terrestrial animal collagen.

10.
Gels ; 8(8)2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-36005071

RESUMO

Reducing food waste is critical for sustainability. In the case of fish processing, more than sixty percent of by-products are generated as waste. Lizardfish (Saurida tumbil Bloch, 1795) is an economically important species for surimi production. To address waste disposal and maximize income, an effective utilization of fish by-products is essential. This study aims to isolate and characterize pepsin-soluble collagens from the skin, bone and scales of lizardfish. Significant differences (p < 0.05) in the yields of collagen were noted with the highest yield recorded in pepsin-soluble skin collagen (PSSC) (3.50 ± 0.11%), followed by pepsin-soluble bone collagen (PSBC) (3.26 ± 0.10%) and pepsin-soluble scales collagen (PSCC) (0.60 ± 0.65%). Through SDS−polyacrylamide gel electrophoresis, the presence of two alpha chains were noted and classified as type I. From Fourier transform infrared spectroscopy (FTIR) analysis, the triple-helix structure of the collagen was maintained. The X-ray diffraction and UV visible spectra characteristics of the lizardfish collagens in this study are similar to the previously reported fish collagens. In terms of thermostability, PSSC (Tmax = 43.89 °C) had higher thermostability in comparison to PSBC (Tmax = 31.75 °C) and PSCC (Tmax = 30.54 °C). All pepsin-soluble collagens were highly soluble (>70%) in acidic conditions (particularly at pH 4.0) and at low sodium chloride concentrations (0−30 g/L). Microstructural analysis depicted that all extracted collagens were multi-layered, irregular, dense, sheet-like films linked by random coiled filaments. Overall, pepsin-soluble collagens from lizardfish skin, bone and scales could serve as potential alternative sources of collagens.

11.
Gels ; 8(10)2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36286166

RESUMO

Fish processing waste is a prospective source of collagen and a cost-effective environmental pollutant. The skin of the purple-spotted bigeye snapper (Priacanthus tayenus) was extracted utilising various acid soluble collagens (ASC) including acetic acid (AAC), lactic acid (LAC), citric acid (CAC) and pepsin soluble collagens (PSC). In this study, PSC (6.65%) had the highest collagen yield, followed by AAC (5.79%), CAC (4.15%), and LAC (3.19%). The maximum temperatures (Tmax) denaturation of AAC, LAC, CAC, and PSC were 31.4, 31.7, 31.5, and 33.2 °C, respectively. UV-VIS absorption spectra showed all extracted collagens had a range of absorbance at 230 nm, due to the presence of glycine, proline, hydroxyproline, and triple-helical collagen. Additionally, they exhibited amide A, B, amide I, II, and III peaks. SDS−PAGE identified all extracted collagens as type I. The PSC had a significantly higher (p < 0.05) hydroxyproline content than acidic extraction 66.3 ± 1.03 (mg/g sample). Furthermore, all samples were extremely soluble in acetic conditions at pH 5, and all collagen was soluble in NaCl up to 3% (w/v). Therefore, PSC was the best treatment since it did not impact collagen triple helical and acetic acid yielded the most collagen in ASC extraction. Overall, the analysis revealed that fish skin waste might be used as an alternate source of collagen in diverse applications, particularly in food applications.

12.
PeerJ ; 10: e13103, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35310170

RESUMO

Background: Lizardfish (Saurida tumbil Bloch, 1795) bone is a fish by-product generated during industrial surimi processing. This by-product is an important source of collagen production since the use of terrestrial animal-based collagens no longer sought due to concern regarding the transfer of infectious diseases and religious issues. Hence, this study was carried out to determine the biochemical analysis of collagens from the bone of lizardfish extracted with different acids. Methods: Lizardfish bone collagens were extracted with various acids (i.e., acetic, lactic and citric acids). All extraction processes were conducted in a chiller room (4 °C). The extracted collagens were biochemically characterized, such as hydroxyproline content, Ultraviolet (UV) absorption, X-ray diffraction (XRD), Fourier transform infrared spectroscopy spectra (FTIR), Differential scanning calorimetry (DSC) and solubility in different pH values and NaCl concentrations. Results: The yield of extracted collagens ranged between 1.73% and 2.59%, with the highest (p < 0.05) observed in citric acid-extracted collagen (CaEC). Protein patterns confirmed that all-collagen samples had two identical subunits, α1 and α2, representing type I collagen. The highest whiteness value was found in acetic acid-extracted collagen (AaEC), but there was no significant difference (p ≥ 0.05) compared to lactic acid-extracted collagen (LaEC). UV absorption and XRD analysis reflected the characteristics of the collagen, as reported in the literature. For the FTIR, all acid-extracted collagen samples presented a triple helical structure. The thermal transition temperature (T max = 77.92-89.04 °C) was in accordance with collagen extracted from other fish species. All extracted collagens were highly soluble in acidic pH and low concentrations of NaCl (0-20 g/L). In conclusion, collagens extracted from lizardfish bone may be used as alternative sources of collagen in industrial settings, and AaEC would be considered superior in terms of the characteristics evaluated in this study.


Assuntos
Proteínas de Peixes , Cloreto de Sódio , Animais , Proteínas de Peixes/química , Colágeno/química , Colágeno Tipo I/química , Peixes/metabolismo , Ácidos/química , Ácido Acético/química
13.
Int J Food Sci ; 2022: 9437878, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35573824

RESUMO

Collagen is a structural protein naturally found in mammals. Vertebrates and other connective tissues comprise about 30% of an animal's overall protein. Collagen is used in a variety of applications including cosmetics, biomedical, biomaterials, food, and pharmaceuticals. The use of marine-based collagen as a substitute source is rapidly increasing due to its unique properties, which include the absence of religious restrictions, a low molecular weight, no risk of disease transmission, biocompatibility, and ease of absorption by the body system. This review discusses recent research on collagen extraction from marine-based raw material, specifically fish by-products. Furthermore, pretreatment on various sources of fish materials, followed by extraction methods, was described. The extraction procedures for acid soluble collagen (ASC) and pepsin soluble collagen (PSC) for fish collagen isolation are specifically discussed and compared. As a result, the efficacy of collagen yield was also demonstrated. The recent trend of extracting fish collagen from marine biomaterials has been summarized, with the potential to be exploited as a wound healing agent in pharmaceutical applications. Furthermore, background information on collagen and characterization techniques primarily related to the composition, properties, and structure of fish collagen are discussed.

14.
Data Brief ; 39: 107588, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34877373

RESUMO

Proteolytic subunit of the caseinolytic protease system of Plasmodium knowlesi (Pk-ClpP; EC 3.4.21.92) is considered a viable target for antimalarial drug development to eradicate P. knowlesi malaria infection in Malaysia and Southeast Asian region. Inhibition of this system leads to a disruption in the protein homeostasis molecular machinery and therefore be lethal for the parasite. While plants are considered excellent sources of bioactive compounds exhibiting inhibition activity towards Pk-ClpP, many local medicinal plants remain unexplored. This article expands the data collected from the inhibition properties of the methanolic extract of Asystasia gangetica (Chinese Violet), Alstonia scholaris (Pulai Tree), Piper retrofractum (Javanese Long Pepper) and Smallanthus sonchifolius (Yacon) towards Pk-ClpP. These plants are widely found in Malaysia and Indonesia and have been traditionally used in various medical treatments. The present dataset showed that the extracts contained phenolic and flavonoid compounds in various concentrations, whereby S. sonchifolius was found to have the lowest content of phenolic and flavonoid contents, while A. gangetica and A. scholaris were statistically comparable, yet higher than P. retrofactum and S. sonchifolus. Further inhibition data assay towards Pk-ClpP revealed that A. gangetica, A. scholaris and P. retrofactum demonstrated remarkable inhibition activity with IC50 values of 39.06 ± 1.98, 48.92 ± 1.52, and 87.63 ± 3.55, respectively. However, the inhibition activity of these extracts was significantly lower than a serine protease inhibitor of phenylmethylsulfonyl fluoridenone (PMSF). Meanwhile, S. sonchifolus did not exhibit significant inhibition activity towards Pk-ClpP. In addition, Pk-ClpP was not inhibited by a cysteine protease inhibitor of E64.

15.
Diabetes ; 67(4): 594-606, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29378767

RESUMO

Lipid droplets (LDs) are critical for the regulation of lipid metabolism, and dysregulated lipid metabolism contributes to the pathogenesis of several diseases, including type 2 diabetes. We generated mice with muscle-specific deletion of the LD-associated protein perilipin 5 (PLIN5, Plin5MKO ) and investigated PLIN5's role in regulating skeletal muscle lipid metabolism, intracellular signaling, and whole-body metabolic homeostasis. High-fat feeding induced changes in muscle lipid metabolism of Plin5MKO mice, which included increased fatty acid oxidation and oxidative stress but, surprisingly, a reduction in inflammation and endoplasmic reticulum (ER) stress. These muscle-specific effects were accompanied by whole-body glucose intolerance, adipose tissue insulin resistance, and reduced circulating insulin and C-peptide levels in Plin5MKO mice. This coincided with reduced secretion of fibroblast growth factor 21 (FGF21) from skeletal muscle and liver, resulting in reduced circulating FGF21. Intriguingly, muscle-secreted factors from Plin5MKO , but not wild-type mice, reduced hepatocyte FGF21 secretion. Exogenous correction of FGF21 levels restored glycemic control and insulin secretion in Plin5MKO mice. These results show that changes in lipid metabolism resulting from PLIN5 deletion reduce ER stress in muscle, decrease FGF21 production by muscle and liver, and impair glycemic control. Further, these studies highlight the importance for muscle-liver cross talk in metabolic regulation.


Assuntos
Estresse do Retículo Endoplasmático/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Gotículas Lipídicas/metabolismo , Fígado/metabolismo , Proteínas Musculares/genética , Músculo Esquelético/metabolismo , Animais , Glicemia/metabolismo , Dieta Hiperlipídica , Metabolismo Energético , Ácidos Graxos , Teste de Tolerância a Glucose , Homeostase , Metabolismo dos Lipídeos , Camundongos , Camundongos Knockout , Oxirredução , Estresse Oxidativo , Transdução de Sinais
16.
Mol Metab ; 3(6): 652-63, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25161888

RESUMO

Defective control of lipid metabolism leading to lipotoxicity causes insulin resistance in skeletal muscle, a major factor leading to diabetes. Here, we demonstrate that perilipin (PLIN) 5 is required to couple intramyocellular triacylglycerol lipolysis with the metabolic demand for fatty acids. PLIN5 ablation depleted triacylglycerol stores but increased sphingolipids including ceramide, hydroxylceramides and sphingomyelin. We generated perilipin 5 (Plin5)(-/-) mice to determine the functional significance of PLIN5 in metabolic control and insulin action. Loss of PLIN5 had no effect on body weight, feeding or adiposity but increased whole-body carbohydrate oxidation. Plin5 (-/-) mice developed skeletal muscle insulin resistance, which was associated with ceramide accumulation. Liver insulin sensitivity was improved in Plin5 (-/-) mice, indicating tissue-specific effects of PLIN5 on insulin action. We conclude that PLIN5 plays a critical role in coordinating skeletal muscle triacylglycerol metabolism, which impacts sphingolipid metabolism, and is requisite for the maintenance of skeletal muscle insulin action.

17.
Hum Exp Toxicol ; 31(1): 81-91, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21508074

RESUMO

This study was aimed to evaluate the effect of Cymbopogon citratus against carbon tetrachloride (CCl(4))-mediated hepatic oxidative damage in rats. Rats were administrated with C. citratus extract (100, 200 and 300 mg/kg b.w.) for 14 days before the challenge of CCl(4) (1.2 ml/kg b.w. p.o) on 13th and 14th days. Hepatic damage was evaluated by employing serum biochemical parameters (alanine aminotransferase-ALT, aspartate aminotransferase-AST and lactate dehydrogenase-LDH), malondialdehye (MDA) level, reduced GSH and antioxidant enzymes (catalase: CAT, glutathione peroxidase: GPX, quinone reductase: QR, glutathione S-transferase: GST, glutathione reductase: GR, glucose-6-phosphate dehyrogenase: G6PD). In addition, CCl(4)-mediated hepatic damage was further evaluated by histopathological examination. However, most of these changes were alleviated by prophylactic treatment of animals with C. citratus dose dependently (p < 0.05). The protection was further evident through decreased histopathological alterations in liver. The results of the present study indicated that the hepatoprotective effect of C. citratus might be ascribable to its antioxidant and free radical scavenging property.


Assuntos
Antioxidantes/uso terapêutico , Intoxicação por Tetracloreto de Carbono/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Cymbopogon , Fenóis/uso terapêutico , Extratos Vegetais/uso terapêutico , Animais , Antioxidantes/análise , Intoxicação por Tetracloreto de Carbono/metabolismo , Intoxicação por Tetracloreto de Carbono/patologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Glutationa/metabolismo , Glutationa Transferase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Oxirredutases/metabolismo , Fenóis/análise , Extratos Vegetais/química , Caules de Planta , Ratos , Ratos Sprague-Dawley , gama-Glutamiltransferase/metabolismo
18.
Redox Rep ; 16(3): 134-43, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21801496

RESUMO

Andrographis paniculata (hempedu bumi) is a plant that possesses many medicinal values in treating several diseases and for health care maintenance. However, its hepatoprotective activity and mechanism of action have not been fully investigated. Therefore, this study aimed to evaluate the hepatoprotective effects of A. paniculata and its mechanism of action in rats. Carbon tetrachloride (CCl(4)) challenge of rats at a dose of 1.2 ml/kg body weight-induced oxidative stress in the liver. This was evidenced by augmentation in lipid peroxidation, which was accompanied by a decrease in the activities of antioxidant enzymes and depletion in the level of reduced glutathione (P < 0.05). Parrallel to these changes, CCl(4) challenge too, enhanced hepatic damage as evidenced by sharp increase in serum transaminases (e.g. alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase) (P < 0.05). Additionally, the impairment of liver function corresponded to histolopathological changes. However, most of these changes were reversed in a dose-dependent fashion by pre-treatment of animals with A. paniculata (P < 0.05). The ability of A. paniculata to scavenge the 2,2-Diphenyl-2-picrylhydrazyl radical was determined through its EC(50) value. The EC(50) value of A. paniculata was 583.60 ± 4.25 µg/ml. In addition, A. paniculata was found to contain 65.37 ± 1.20 mg/g total phenolics expressed as gallic acid equivalent. From these studies, it is concluded that A. paniculata could be used as a hepatoprotective agent and possesses the potential to treat or prevent degenerative diseases where oxidative stress is implicated.


Assuntos
Andrographis/química , Intoxicação por Tetracloreto de Carbono/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Fígado/efeitos dos fármacos , Estresse Oxidativo , Animais , Antioxidantes/metabolismo , Compostos de Bifenilo/metabolismo , Tetracloreto de Carbono/toxicidade , Relação Dose-Resposta a Droga , Glutationa/metabolismo , Peroxidação de Lipídeos , Masculino , Picratos/metabolismo , Componentes Aéreos da Planta/química , Extratos Vegetais/uso terapêutico , Substâncias Protetoras/uso terapêutico , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
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