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1.
Biomol Ther (Seoul) ; 31(6): 682-691, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37899745

RESUMO

Cell transformation induced by epidermal growth factor (EGF) and 12-O-tetradecanoylphorbol-13-acetate (TPA) is a critical event in cancer initiation and progression, and understanding the underlying mechanisms is essential for the development of new therapeutic strategies. Licorice extract contains various bioactive compounds, which have been reported to have anticancer and anti-inflammatory effects. This study investigated the cancer preventive efficacy of licochalcone D (LicoD), a chalcone derivative in licorice extract, in EGF and TPA-induced transformed skin keratinocyte cells. LicoD effectively suppressed EGF-induced cell proliferation and anchorage-independent colony growth. EGF and TPA promoted the S phase of cell cycle, while LicoD treatment caused G1 phase arrest and down-regulated cyclin D1 and up-regulated p21 expression associated with the G1 phase. LicoD also induced apoptosis and increased apoptosis-related proteins such as cleaved-caspase-3, cleaved-caspase-7, and Bax (Bcl-2-associated X protein). We further investigated the effect of LicoD on the AKT signaling pathway involved in various cellular processes and found decreased p-AKT, p-GSK3ß, and p-NFκB expression. Treatment with MK-2206, an AKT pharmacological inhibitor, suppressed EGF-induced cell proliferation and transformed colony growth. In conclusion, this study demonstrated the potential of LicoD as a preventive agent for skin carcinogenesis.

2.
Dose Response ; 19(4): 15593258211044329, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34690616

RESUMO

PURPOSE: Previously, we demonstrated that the specific ratio of Korean multi-herbal formula (SR-5) exhibits hepatoprotective properties against ethanol-induced hepatic damage in rats. Chronic and excessive alcohol consumption is a major etiological factor involved in gastric disease and ulcer development induced by the inflammatory response and oxidative stress. METHODS: The present study evaluated the gastroprotective effects of SR-5 (100, 150, and 200 mg/kg) against hydrochloride acid/ethanol (HCl/EtOH)-induced and indomethacin/hydrochloride acid (INDO/HCl)-induced gastritis in a mouse model and the mechanisms involved. RESULTS: All the tested doses of SR-5 significantly inhibited gastric lesions in the HCl/EtOH-induced ulcer model mice. Similarly, all the tested doses of SR-5 significantly inhibited gastric lesions in the INDO/HCl-induced ulcer model mice. Furthermore, mice pretreated with SR-5 had significantly increased gastric levels of enzymatic and nonenzymatic antioxidants, namely, catalase (CAT) and glutathione (GSH), with concomitant reductions in malondialdehyde (MDA) and reactive oxygen species (ROS) levels compared with those in the HCl/EtOH or INDO/HCl group. SR-5 suppressed the expression of nuclear factor-kappa B (NF-κB)/p65, inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), and cyclooxygenase-2 (COX-2) to their normal values. CONCLUSION: These findings are the first to demonstrate the powerful protective effect of SR-5 against gastric injury development and provide hope for clinical application.

3.
Int J Mol Sci ; 22(4)2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33670808

RESUMO

Hepatic fibrosis occurs when liver tissue becomes scarred from repetitive liver injury and inflammatory responses; it can progress to cirrhosis and eventually to hepatocellular carcinoma. Previously, we reported that neoagarooligosaccharides (NAOs), produced by the hydrolysis of agar by ß-agarases, have hepatoprotective effects against acetaminophen overdose-induced acute liver injury. However, the effect of NAOs on chronic liver injury, including hepatic fibrosis, has not yet been elucidated. Therefore, we examined whether NAOs protect against fibrogenesis in vitro and in vivo. NAOs ameliorated PAI-1, α-SMA, CTGF and fibronectin protein expression and decreased mRNA levels of fibrogenic genes in TGF-ß-treated LX-2 cells. Furthermore, downstream of TGF-ß, the Smad signaling pathway was inhibited by NAOs in LX-2 cells. Treatment with NAOs diminished the severity of hepatic injury, as evidenced by reduction in serum alanine aminotransferase and aspartate aminotransferase levels, in carbon tetrachloride (CCl4)-induced liver fibrosis mouse models. Moreover, NAOs markedly blocked histopathological changes and collagen accumulation, as shown by H&E and Sirius red staining, respectively. Finally, NAOs antagonized the CCl4-induced upregulation of the protein and mRNA levels of fibrogenic genes in the liver. In conclusion, our findings suggest that NAOs may be a promising candidate for the prevention and treatment of chronic liver injury via inhibition of the TGF-ß/Smad signaling pathway.


Assuntos
Cirrose Hepática/metabolismo , Cirrose Hepática/prevenção & controle , Oligossacarídeos/farmacologia , Substâncias Protetoras/farmacologia , Transdução de Sinais , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Tetracloreto de Carbono , Linhagem Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Humanos , Cirrose Hepática/patologia , Masculino , Camundongos Endogâmicos ICR
4.
Int J Mol Sci ; 21(14)2020 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32674521

RESUMO

We investigated the time-dependent deleterious ocular changes induced by urban particulate matter (UPM) in vitro and in vivo. UPM treatment decreased human corneal epithelial cell migration and survival. Fluorescein scores were consistently increased by UPM application for 16 weeks. One week of rest at 2 or 4 weeks led to a recovery trend, whereas two weeks of rest at 8 weeks induced no change. UPM treatment decreased the tear film break-up time at 2 weeks, which was thereafter maintained until 16 weeks. No changes were found after periods of rest. UPM-treated eyes exhibited greater corneal epithelium thickness than normal eyes at 2 weeks, which recovered to normal at 4 and 8 weeks and was significantly decreased at 16 weeks. Apoptotic cell number in the epithelium was increased at 2 weeks, which remained constant except at 8 weeks. IL-6 expression in the cornea of the right eye continually increased for 16 weeks, and significant recovery was only observed at 8 weeks after 2 weeks of rest. Ocular pressure was significantly increased in the right eye at 12 and 16 weeks. Topical UPM application to the eye induced deleterious changes to various closely related parts of the eye.


Assuntos
Túnica Conjuntiva/efeitos dos fármacos , Córnea/efeitos dos fármacos , Epitélio Corneano/efeitos dos fármacos , Material Particulado/efeitos adversos , Retina/efeitos dos fármacos , Animais , Linhagem Celular , Túnica Conjuntiva/metabolismo , Córnea/metabolismo , Modelos Animais de Doenças , Síndromes do Olho Seco/induzido quimicamente , Epitélio Corneano/metabolismo , Fluoresceína/farmacologia , Humanos , Incidência , Interleucina-6/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Retina/metabolismo , Lágrimas/efeitos dos fármacos , Lágrimas/metabolismo
5.
Biol Pharm Bull ; 43(4): 619-628, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32009027

RESUMO

Neoagarooligosaccharides (NAOS) are generated by ß-agarases, which cleave the ß-1,4 linkage in agarose. Previously, we reported that NAOS inhibited fat accumulation in the liver and decreased serum cholesterol levels. However, the hepatoprotective effect of NAOS on acute liver injury has not yet been investigated. Thus, we examined whether NAOS could activate nuclear factor (NF)-E2-related factor 2 (Nrf2)-antioxidant response element (ARE) and upregulates its target gene, and has hepatoprotective effect in vivo. In hepatocytes, phosphorylation and subsequent nuclear translocation of Nrf2 are increased by treatment with NAOS, in a manner dependent on p38 and c-Jun N-terminal kinase (JNK). Consistently, NAOS augmented ARE reporter gene activity and the antioxidant protein levels, resulting in increased intracellular glutathione levels. NAOS antagonized tert-butylhydroperoxide-induced reactive oxygen species (ROS) generation. Moreover, NAOS inhibited acetaminophen (APAP)-induced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and significantly decreased hepatocyte degeneration and inflammatory cell infiltration. Moreover, ROS production and glutathione depletion by APAP were reversed by NAOS. APAP-mediated apoptotic signaling pathways were also inhibited in NAOS-treated mice. Upregulalted hepatic expression of genes related to inflammation by APAP were consistently diminished by NAOS. Collectively, our results demonstrate that NAOS exhibited a hepatoprotective effect against APAP-mediated acute liver damage through its antioxidant capacity.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , Oligossacarídeos/uso terapêutico , Substâncias Protetoras/uso terapêutico , Acetaminofen , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Glutationa/metabolismo , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Masculino , Camundongos Endogâmicos ICR , Oligossacarídeos/farmacologia , Substâncias Protetoras/farmacologia , Espécies Reativas de Oxigênio/metabolismo
6.
BMC Complement Altern Med ; 19(1): 319, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31747910

RESUMO

BACKGROUND: ChondroT is a complex herbal medicine consisting of water extracts of Ostericum koreanum (Maxim.) Kitag., Lonicera japonica Thunb., Angelica gigas Nakai, Clematis manshurica Rupr., and Phellodendron amurense Rupr. (6:4:4:4:3). Previous studies have reported that ChondroT possesses chondroprotective and anti-inflammatory, anti-osteoarthritic, and anti-hyperuricemic activities. The study is aim to demonstrate the effects of ChondroT and its five constituent herbs on receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and the underlying mechanisms. METHODS: Osteoclastogenesis was identified in bone marrow-derived macrophages (BMDMs) by tartrate-resistant acid phosphatase (TRAP) staining assay, actin ring formation assay and the bone resorption assay. For the molecular mechanisms, activation of RANKL-induced NF-κB and MAPK signaling pathways and the expression levels of osteoclast-specific proteins were investigated by Western blotting. Cell viability was assessed by MTT assay. Actin ring formation and NF-κB translocation were evaluated by immunostaining. RESULTS: ChondroT and each of its constituent herbs significantly suppressed osteoclast differentiation dose dependently, and decreased actin ring formation as well as bone-resorbing capacity. Mechanistically, ChondroT and its constituent herbs downregulated the expressional levels of osteoclast-specific proteins such as NFATc1, c-Fos, Cathepsin K, and matrix metalloproteinase 9 (MMP9) by suppressing NF-κB translocation to nucleus and MAPKs phosphorylation at different levels. Compared to its five constituent herbs, ChondroT exhibited the best inhibitory efficiency against osteoclastogenesis. CONCLUSIONS: Taken together, ChondroT has anti-osteoclastogenesis properties by inhibiting NF-κB and MAPKs pathways. It could be considered as a potential therapeutic candidate for the treatment of osteoclast-related bone diseases.


Assuntos
Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Preparações de Plantas/farmacologia , Ligante RANK/farmacologia , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL
7.
Antioxid Redox Signal ; 31(3): 243-259, 2019 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-30909713

RESUMO

Aims: Hepatic fibrosis results from chronic liver injury and inflammatory responses. Sestrin 2 (Sesn2), an evolutionarily conserved antioxidant enzyme, reduces the severities of acute hepatitis and metabolic liver diseases. However, the role of Sesn2 in the pathogenesis of liver fibrosis remains obscure. Here, we used cultured hepatic stellate cells (HSCs) and chronic carbon tetrachloride (CCl4) and bile duct ligation (BDL) murine models to investigate the effects of Sesn2 on fibrogenesis. Results: Sesn2 protein and mRNA levels were upregulated in activated primary HSCs, and by increasing transcription, transforming growth factor-ß (TGF-ß) also increased Sesn2 expression in HSCs. Furthermore, Smad activation was primarily initiated by TGF-ß signaling, and Smad3 activation increased Sesn2 luciferase activity. In silico analysis of the 5' upstream region of the Sesn2 gene revealed a putative Smad-binding element (SBE), and its deletion demonstrated that the SBE between -964 and -956 bp within human Sesn2 promoter was critically required for TGF-ß-mediated response. Moreover, ectopic expression of Sesn2 reduced gene expressions associated with HSC activation, and this was accompanied by marked decreases in SBE luciferase activity and Smad phosphorylation. Infection of recombinant adenovirus Sesn2 reduced hepatic injury severity, as evidenced by reductions in CCl4- or BDL-induced alanine aminotransferase and aspartate aminotransferase, and inhibited collagen accumulation. Furthermore, HSC-specific lentiviral delivery of Sesn2 prevented CCl4-induced liver fibrosis. Finally, Sesn2 expression was downregulated in the livers of patients with liver cirrhosis and in mouse models of hepatic fibrosis. Innovation and Conclusion: Our findings suggest that Sesn2 has the potential to inhibit HSC activation and hepatic fibrosis.


Assuntos
Células Estreladas do Fígado/citologia , Cirrose Hepática/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteína Smad3/metabolismo , Animais , Sítios de Ligação , Tetracloreto de Carbono/efeitos adversos , Células Cultivadas , Modelos Animais de Doenças , Regulação para Baixo , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Humanos , Cirrose Hepática/genética , Masculino , Camundongos , Proteínas Nucleares/química , Regiões Promotoras Genéticas , Fator de Crescimento Transformador beta/farmacologia
8.
Phytomedicine ; 57: 84-94, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30668326

RESUMO

BACKGROUND: In December 2016, WHO released a report stating that in 2015 there were 383,000 deaths caused by asthma and 235 million people suffering from asthma. As there are many adverse effects associated with the currently-used asthma drugs, new anti-asthmatic drugs need to be developed. PURPOSE: In order to find new drug candidates with safe and low side effects, the anti-asthmatic function and mechanism of C. japonica oil were evaluated, and its active ingredients were analyzed for use in an ovalbumin asthma murine model. STUDY DESIGN AND METHODS: The study consisted of six groups: control; ovalbumin group; and dexamethasone group as a positive control; and 10, 100, and 500 mg/kg C. japonica oil treatment groups. In order to measure the anti-asthmatic effect of C. japonica oil, WBC and differential cell count in BALF, IgE in serum, morphological changes in pulmonary system, and gene and protein levels such as IFN-γ, IL-12p40, IL-4, IL-5, IL-6, TNF-α, and IL-6 were all evaluated. RESULTS: C. japonica oil had an anti-asthmatic effect and significantly controlled eosinophil in BALF, Th2-related factors such as GATA-3 that is Th2 cell transcription factor, IL-4, IL-5, and IL-13, and TNF-α in the lung. It also dose-dependently modulated inflammatory cells, T-bet, IL-12p40, and IL-6. Oleci acid was the major gradient (52.89%) in C. japonica oil and also had anti-asthmatic effects such as the downregulation of inflammatory cells, WBC, and eosinophil in BALF, IgE in serum, and morphological changes in the lung. CONCLUSION: We concluded that C. japonica oil is a new anti-asthmatic drug candidate and that oleic acid is the major anti-asthmatic ingredient in C. japonica oil.


Assuntos
Antiasmáticos/farmacologia , Asma/tratamento farmacológico , Camellia/química , Óleos de Plantas/farmacologia , Animais , Antiasmáticos/química , Asma/metabolismo , Líquido da Lavagem Broncoalveolar , Citocinas/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Eosinófilos/efeitos dos fármacos , Feminino , Fator de Transcrição GATA3/metabolismo , Interleucina-4/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Camundongos Endogâmicos BALB C , Ácido Oleico/análise , Óleos de Plantas/administração & dosagem , Óleos de Plantas/química
9.
Nutrients ; 11(1)2019 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-30626086

RESUMO

This study was designed to investigate the hepatoprotective effect of bamboo stems using in vitro and in vivo experimental liver damage models. Ethyl acetate fraction of 80% ethanol extract of Phyllostachys nigra stem (PN3) containing polyphenols had a higher NQO1-ARE reporter gene activity as monitored by the activity of the NF-E2-related factor (Nrf2) antioxidant pathway in cells in comparison to extracts from other species and under other conditions. The Nrf2 was translocated from the cytosol to the nucleus in response to PN3, followed by induction of the Nrf2 target gene expression, including HO-1, GCL, and NQO-1 in HepG2 cells. Phosphorylation of Nrf2 in HepG2 cells was enhanced in PN3, which was mediated by PKCδ, ERK, and p38 MAPK. Consequently, PN3 inhibited arachidonic acid (AA) + iron-induced reactive oxygen species generation and glutathione depletion, and, thus, highlighted their role in cytotoxicity. Treatment with major polyphenols of PN3, including catechin, chlorogenic acid, caffeic acid, and p-coumaric acid, also improved AA + iron-mediated oxidative stress and, thus, improved cell viability. Treatment with phenylhydrazine in mice, i.e., the iron overload liver injury model, increased plasma alanine aminotransferase and aspartate aminotransferase levels and changed histological features in mice-a response that was almost completely blocked by PN3 administration. Moreover, PN3 extract mitigated phenylhydrazine-induced oxidative stress and inflammatory responses. Conclusively, PN3 can exert a hepatoprotective effect against iron overload-induced acute liver damage due to its antioxidant properties.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Fígado/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Poaceae/química , Polifenóis/farmacologia , Alanina Transaminase/sangue , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Aspartato Aminotransferases/sangue , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Glutationa/metabolismo , Heme Oxigenase-1/metabolismo , Células Hep G2 , Humanos , Ferro/metabolismo , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos Endogâmicos ICR , NAD(P)H Desidrogenase (Quinona)/metabolismo , Fenil-Hidrazinas , Fitoterapia , Extratos Vegetais/uso terapêutico , Caules de Planta/química , Fatores de Transcrição/metabolismo
10.
BMC Complement Altern Med ; 19(1): 10, 2019 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-30621705

RESUMO

BACKGROUND: ChondroT, a new herbal medication, consists of the water extracts of Osterici Radix, Lonicerae Folium, Angelicae Gigantis Radix, Clematidis Radix, and Phellodendri Cortex (6:4:4:4:3). We previously reported that ChondroT showed significant anti-arthritis and anti-inflammatory effects. METHODS: This study was designed to evaluate the effect of ChondroT on hyperuricemia. First, the effect of ChondroT was evaluated on xanthine oxidase (XOD) activity in vitro. The anti-hyperuricemic effect of ChondroT was also studied in potassium oxonate (PO)-induced hyperuricemic model mice. Uric acid (UA) and XOD were evaluated in the serum, urine, and liver of the mice. In addition, we measured serum creatinine (Cr) and blood urea nitrogen (BUN) levels as well as mRNA expression of the mouse urate transporter 1 (mURAT1) to evaluate kidney function and urate excretion in hyperuricemic mice. RESULTS: ChondroT showed in vitro XOD inhibitory activity in a dose-dependent manner (P < 0.05). We demonstrated that ChondroT (37.5, 75 and 150 mg/kg) significantly reduced serum UA (P < 0.01 and P < 0.001, respectively), and upregulated urinary UA (P < 0.001, respectively) in PO-induced hyperuricemic mice. In addition, ChondroT (75 and 150 mg/kg) significantly reduced Cr (P < 0.05 and P < 0.01, respectively), BUN (P < 0.05 and P < 0.001, respectively), GOT (P < 0.05 and P < 0.01, respectively), and GPT (P > 0.05 and P < 0.05, respectively) levels in PO-induced hyperuricemic mice. ChondroT (75 and 150 mg/kg) also significantly downregulated serum (P < 0.05) and liver (P < 0.05) XOD activity. Compared to the hyperuricemic mice, the ChondroT (37.5, 75, and 150 mg/kg)-treated mice showed decreased mURAT1 protein expression level. CONCLUSION: ChondroT displayed anti-hyperuricemic effects by regulating XOD activity and kidney mURAT1.


Assuntos
Regulação para Baixo/efeitos dos fármacos , Medicamentos de Ervas Chinesas/administração & dosagem , Hiperuricemia/tratamento farmacológico , Transportadores de Ânions Orgânicos/genética , Ácido Oxônico/efeitos adversos , Xantina Oxidase/genética , Animais , Creatinina/sangue , Avaliação Pré-Clínica de Medicamentos , Humanos , Hiperuricemia/induzido quimicamente , Hiperuricemia/genética , Hiperuricemia/metabolismo , Rim/efeitos dos fármacos , Rim/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Transportadores de Ânions Orgânicos/metabolismo , Ácido Úrico/sangue , Xantina Oxidase/sangue
11.
BMC Complement Altern Med ; 18(1): 131, 2018 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-29673343

RESUMO

BACKGROUND: Previously, we reported that ChondorT showed significant anti-arthritis and anti-inflammatory effects. ChondroT, a new herbal medication, consists of the water extracts of Osterici Radix, Lonicerae Folium, Angelicae Gigantis Radix, Clematidis Radix, and Phellodendri Cortex (6:4:4:4:3). The objective of this study was to investigate the effects of ChondroT in collagenase-induced osteoarthritis rat model. METHODS: Osteoarthritis was induced by the injection of collagenase into the right knee joint cavity of rats. The samples were divided into seven groups [intact (n = 6), control (n = 6), indomethacin (n = 6), Joins tab (n = 6), ChondroT50 (n = 6), ChondroT100 (n = 6), and ChondroT200 (n = 6)]. The control group was administered normal saline, indomethacin group was administered indomethacin (2 mg/kg), and Joins tab group was administered Joins Tab (20 mg/kg). The ChondroT50, ChondroT100, and ChondroT200 groups were administered 50, 100, and 200 mg/kg of ChondroT, respectively. All oral administrations were initiated 7 days after the induction of arthritis and were continued for a total of 12 days. At the end of the experiment, serum aminotransferase, albumin, blood urea nitrogen, creatinine, leukocyte, and inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6] were analyzed. Hematoxylin and eosin (H&E) and safranin O-fast green staining of the articular structures of the knee joint were performed. RESULTS: TNF-α and IL-1ß decreased in the ChondroT100 and ChondroT200 groups compared with those in the control group. IL-6 and aspartate aminotransferase decreased in the ChondroT50, ChondroT100, and ChondroT200 groups compared with that in the control group. Albumin, WBC and lymphocytes decreased in the ChondroT100 and ChondroT200 groups compared with those in the control group. In H&E stain, synoviocytes, cartilage lacunae, and chondrocytes were well preserved in the ChondroT100 and ChondroT200 groups, and safranin O-fast staining showed a clear reaction of proteoglycans in the ChondroT100 and ChondroT200 groups. CONCLUSIONS: Based on these results, it can be proposed that ChondroT has anti-osteoarthritic effects on collagenase-induced rat model.


Assuntos
Anti-Inflamatórios , Osteoartrite , Extratos Vegetais , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Colagenases/efeitos adversos , Modelos Animais de Doenças , Interleucina-1beta/metabolismo , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/metabolismo , Masculino , Osteoartrite/induzido quimicamente , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo
12.
Artigo em Inglês | MEDLINE | ID: mdl-29576802

RESUMO

Ganghwaljetongyeum is a traditional Korean herbal medicine used to treat joint pain, limited motion, fever, and swelling; it also inhibits inflammatory processes associated with arthritis. ChondroT, a water extract of Ganghwaljetongyeum, is a new complex herbal medicine. This study investigated the effects of ChondroT using a rat model of monosodium iodoacetate- (MIA-) induced osteoarthritis. Thirty-six rats were randomly divided into three ChondroT groups and a normal, control, and positive control group. Changes in paw edema volume, histopathology, and plantar withdrawal response were analyzed. Further, inflammatory cytokines, arachidonic acids, liver and kidney function, and hematological features were measured. ChondroT significantly decreased paw edema by the 5th day and notably improved articular cartilage damage; it also significantly improved the plantar withdrawal response in terms of both reaction time and force intensity. Moreover, treatment with ChondroT significantly decreased the serum levels of tumor necrosis factor alpha, interleukin-1ß, interleukin-6, and prostaglandin E2 and significantly increased serum aspartate aminotransferase and alanine aminotransferase levels. This study demonstrates that ChondroT has anti-inflammatory and analgesic effects in a MIA-induced osteoarthritis rat model. These results support the clinical relevance of ChondroT for future use in patients with osteoarthritis. However, further studies are required to elucidate the corresponding mechanisms.

13.
J Ginseng Res ; 42(1): 57-67, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29348723

RESUMO

BACKGROUND: Ginseng contains many small metabolites such as amino acids, fatty acids, carbohydrates, and ginsenosides. However, little is known about the relationships between microorganisms and metabolites during the entire ginseng fermentation process. We investigated metabolic changes during ginseng fermentation according to the inoculation of food-compatible microorganisms. METHODS: Gas chromatography mass spectrometry (GC-MS) datasets coupled with the multivariate statistical method for the purpose of latent-information extraction and sample classification were used for the evaluation of ginseng fermentation. Four different starter cultures (Saccharomyces bayanus, Bacillus subtilis, Lactobacillus plantarum, and Leuconostoc mesenteroide) were used for the ginseng extract fermentation. RESULTS: The principal component analysis score plot and heat map showed a clear separation between ginseng extracts fermented with S. bayanus and other strains. The highest levels of fructose, maltose, and galactose in the ginseng extracts were found in ginseng extracts fermented with B. subtilis. The levels of succinic acid and malic acid in the ginseng extract fermented with S. bayanus as well as the levels of lactic acid, malonic acid, and hydroxypruvic acid in the ginseng extract fermented with lactic acid bacteria (L. plantarum and L. mesenteroide) were the highest. In the results of taste features analysis using an electronic tongue, the ginseng extracts fermented with lactic acid bacteria were significantly distinguished from other groups by a high index of sour taste probably due to high lactic acid contents. CONCLUSION: These results suggest that a metabolomics approach based on GC-MS can be a useful tool to understand ginseng fermentation and evaluate the fermentative characteristics of starter cultures.

14.
Food Nutr Res ; 61(1): 1393307, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29151835

RESUMO

Asthma is a chronic pulmonary disease that affects an estimated 235 million people worldwide, but asthma drugs have many adverse effects. Opuntia humifusa (eastern prickly pear) has been used as a food and traditional medicine worldwide; however, its anti-asthmatic effects have not been reported. We evaluated O. humifusa as a potential therapeutic or preventive component of anti-asthmatic drugs. We divided ovalbumin-sensitized mice into the following groups: normal control, asthma-induced control, dexamethasone-treated group (positive control), 50 mg/kg O. humifusa-treated group, 100 mg/kg O. humifusa-treated group, and 500 mg/kg O. humifusa-treated group. Levels of Th1/Th2/Th17-related cytokines were evaluated using RT-PCR, ELISA, and immunohistochemistry. O. humifusa dose-dependently suppressed the morphological changes typically observed in asthma, such as goblet cell hyperplasia, inflammatory cell infiltration, mucous hypersecretion, and relative basement membrane thickening in the respiratory system. These results may be attributable to regulation of Th1-/Th2-/Th17-related factors, especially interleukin (IL)-4 and IL-13. We conclude that O. humifusa is a potential anti-asthmatic functional food. Abbreviations: O. humifusa: Opuntia humifusa; Th: helper T; RT-PCR: real-time polymerase chain reaction; ELISA: enzyme-linked immunosorbent assay; IL: interleukin; WHO: World Health Organization; IFN-γ: interferon gamma; TNF-α: tumor necrosis factor-alpha; IgE: immunoglobulin E; CD: cluster of differentiation; OVA: ovalbumin; DEX: dexamethasone; BALF: bronchoalveolar fluid; H&E: hematoxylin and eosin; PAS: periodic acid-schiff; PBS: phosphate-buffered saline; BM: basement membrane; cDNA: complementary deoxyribonucleic acid; RNA: ribo nucleic acid; RIPA: radioimmunoprecipitation assay; IHC: immunohistochemistry; HPLC: high-performance liquid chromatography; SD: standard deviation; WBC: white blood cells; APCs: antigen-presenting cells.

15.
BMC Complement Altern Med ; 13: 47, 2013 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-23442977

RESUMO

BACKGROUND: Ganghwaljetongyeum (GHJTY), a complex herbal decoction, is used to treat rheumatoid arthritis. However, the action mechanism of GHJTY is not still unclear on rheumatoid arthritis. In this study, we examined the beneficial effects and the action mechanisms of GHJTY on synoviocyte proliferation and inflammatory mediators. METHODS: To test the effect of GHJTY on synoviocyte proliferation, HIG-82 cells, rabbit knee synovial membrane cells, were treated with GHJTY under IL-1ß. To evaluate the effects of GHJTY on proinflammatory mediators, we tested cytokine levels in RAW264.7 cells. RESULTS: Proliferation of HIG-82 cells was significantly inhibited by GHJTY treatment. We found that GHJTY caused cytoskeleton damage to HIG-82 cells. In contrast, treatment of GHJTY did not show any cytotoxicity to other different origin cell lines, HeLa and RAW264.7 cells. GHJTY inhibited IL-1ß-mediated NF-κB activation in HIG-82 cells and reduced the LPS-mediated production of proinflammatory cytokines, TNF-α, IL-12, and NO in RAW264.7 cells. In addition, the expression of cyclooxygenase in LPS-activated RAW264.7 cells was also decreased by GHJTY treatment. CONCLUSIONS: These results suggest that GHJTY might effectively attenuate rheumatoid arthritis by inhibiting the production of proinflammatory mediators and the proliferation of synoviocytes.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Mediadores da Inflamação/metabolismo , Magnoliopsida , Fitoterapia , Extratos Vegetais/uso terapêutico , Membrana Sinovial/efeitos dos fármacos , Animais , Antirreumáticos/farmacologia , Artrite Reumatoide/metabolismo , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase/farmacologia , Inibidores de Ciclo-Oxigenase/uso terapêutico , Citocinas/metabolismo , Citoesqueleto/efeitos dos fármacos , Humanos , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Medicina Tradicional Coreana , Camundongos , Óxido Nítrico/metabolismo , Extratos Vegetais/farmacologia , Coelhos , Membrana Sinovial/citologia
16.
Am J Chin Med ; 34(6): 989-1003, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17163588

RESUMO

Clinically, acupuncture therapy is useful for the control of acute or chronic pain. This study was designed to elucidate the antinociceptive mechanism of acupuncture and the mechanisms underlying cardiovascular reflex elicited by toothache. Expression of c-Fos, a neuronal activation marker, and the phenylethanalamine-N-methyltransferase (PNMT) were examined 1.5 hours after noxious intrapulpal tooth stimulation. Manual acupuncture was performed 20 min before noxious intrapulpal stimulation by 2 M KCl injection into upper or lower anterior tooth pulp. The acupuncture points were Li4 (Hegu) between the 1st and 2nd metacarpal bones or St36 (Zusanli) between the anterior crest of the tibial tuberosity and the fibula head below the patella. After noxious intrapulpal tooth stimulation, Fos-immunoreactive (IR) neurons were identified in the trigeminal subnucleus caudalis (Vc) and the transitional region between the subnucleus caudalis and the subnucleus interpolaris (Vi), in the inferior olivory nucleus (IO) connecting the cerebellum and other brain regions, and also the thalamic ventral posteromedial (VPM) nucleus and centrolateral (CL) nucleus, respectively. In addition, Fos-IR neurons were found in the central cardiovasuclar regulation centers, such as the hypothalamus supraoptic nucleus (SON) and paraventricular nucleus (PVN), and nucleus tractus solitarius (NTS) and rostral ventromedulla (RVLM). All acupuncture at St36 or Li4 significantly suppressed Fos-IR neurons in all Fos-expressed brain areas except the IO nucleus and attenuated the increases in arterial blood pressure (BP) and heart rate (HR) after noxious intrapulpal stimulation. Its Fos-suppressive effects were mostly blocked by naloxone, an opioid antagonist. In addition, acupuncture at St36 or Li4 significantly decreased Fos-containing PNMT, and this effect was also reversed by naloxone. These results suggest that: 1) tooth pulpal noxious signals transmit to the Vc and Vc/Vi transitional region and the 2nd afferent neuron synapse in the thalamic VPM and CL, 2) tooth pulpal pain elicits cardiovascular reflex mediated by NTS, VLM, hypothalamic SON and PVN, and 3) acupuncture reduces cardiovascular reflex elicited by toothache, is associated with the adrenergic system.


Assuntos
Terapia por Acupuntura , Encéfalo/metabolismo , Polpa Dentária/metabolismo , Estimulação Física , Proteínas Proto-Oncogênicas c-fos/metabolismo , Pontos de Acupuntura , Animais , Pressão Sanguínea/fisiologia , Frequência Cardíaca/fisiologia , Masculino , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Agulhas , Neurônios/metabolismo , Nociceptores/metabolismo , Feniletanolamina N-Metiltransferase/metabolismo , Cloreto de Potássio/farmacologia , Ratos , Ratos Sprague-Dawley , Estimulação Química , Odontalgia/prevenção & controle
17.
Am J Chin Med ; 31(6): 885-95, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-14992541

RESUMO

A type of polycystic ovary resembling some aspects of human polycystic ovarian syndrome (PCOS) can be induced in the rat with a single injection of long-acting estradiol valerate. Among several theories behind the development of polycystic ovaries (PCO), the involvement of the sympathetic nervous system draws much attention, and herbal medicine is known to relieve the abnormal symptoms of PCO. Two herbal formulas, Changbudodam-Tang (cang fu dao tan tang) and Yongdamsagan-Tang (long dan xie gan tang), were used in the present study. The administration of herbal medicine was done every other day for 60 days. The morphological changes of ovaries from herbal medicine treatment were compared to those from an oil-treated control group and an estradiol valerate-injected group. This study also examined the possible hypothesis of neurogenic participation in terms of nerve growth factor (NGF) in the pathology of ovarian dysfunction. The nerve growth factor was analyzed in the central nervous system and ovaries by immunohistochemistry. The main findings of the present study were: (1) PCO were fully developed in rats with a single intramuscular injection of estradiol valerate, (2) PCO resulted in the expression of NGF in the ovaries and the brain tissues, and (3) herbal medicine administration significantly decreased the elevated NGF staining in the ovaries without affecting the brain tissues significantly.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Estradiol/análogos & derivados , Fator de Crescimento Neural/metabolismo , Síndrome do Ovário Policístico/tratamento farmacológico , Animais , Peso Corporal , Encéfalo/metabolismo , Feminino , Imuno-Histoquímica , Tamanho do Órgão , Ovário/metabolismo , Ovário/patologia , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/metabolismo , Ratos , Ratos Sprague-Dawley
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