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1.
Food Funct ; 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32667370

RESUMO

BACKGROUND: Samsoeum (SSE), a Korean medicine, has been used to treat upper respiratory infection including residual coughs after catching a cold, and colds in patients with gastrointestinal disorder. In this study, we investigated the inhibitory effect of SSE against lipopolysaccharide (LPS)-induced bronchitis and characterized its optimal dosing range based on the improvement of SSE concentrations. MATERIALS AND METHODS: Male Sprague Dawley rats were intra-nasally administered LPS on day 0, 3 and 6. 2 g kg-1 dose of SSE for rat was determined by the human equivalent dose formula and orally administered once a day from day 3 to day 6. To clarify the optimal administration dose of SSE, various doses including 0.5 (1/4 fold), 1 (1/2 fold), 6 (3 fold), 12 (6 fold), 24 (12 fold) and 36 g kg-1 (18 fold) were also orally administered. In addition, the molecular mechanism of SSE in mucin hyperproduction was investigated in LPS-sensitized A549 cells. RESULTS: Oral administration of SSE ameliorated alveolar wall thickening and inflammatory cell infiltration of lung tissues in LPS-induced bronchitis at doses of 1/4 fold, 1/2 fold and 1 fold. The total cell and neutrophil numbers in bronchoalveolar lavage fluid (BALF) were reduced in the SSE-treated groups compared with the LPS group. In addition, 0.5, 1 and 2 g kg-1 of SSE suppressed LPS-induced mucin glycoprotein 5AC (MUC5AC) production in BALF. Furthermore, SSE treatment significantly inhibited the pro-inflammatory cytokines, resulting in the decrease of MUC5AC production by the JAK1/STAT6 signaling pathway. CONCLUSIONS: 1, 2 and 6 g kg-1 of SSE ameliorated chronic bronchitis by inhibiting LPS-induced neutrophil infiltration and MUC5AC release in BALF. These findings suggested that SSE with 0.5-3-fold of general daily intake dose would be a therapeutic agent for chronic bronchitis.

2.
BMC Complement Med Ther ; 20(1): 230, 2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32689985

RESUMO

BACKGROUND: The human placenta (HP) is a complex organ used to alleviate tiredness and promote wound healing. Previous research showed the hair growth-promoting effect of HP. However, no reports have addressed the effects of HP on hair regrowth in chemotherapy-induced alopecia. In this study, we investigated the effects of HP on the apoptosis and proliferation of hair follicles in chemotherapy-induced alopecia. METHODS: Male C57BL/6 mice in telogen were depilated to enter anagen. After 9 days, dystrophic catagen was induced by the intraperitoneal injection of 150 mg/kg cyclophosphamide. During 9 to 16 days, 0.1 and 1 mg/mL HP were topically applied to depilated dorsal skin. RESULTS: Dystrophic hair follicles by cyclophosphamide were recovered by HP treatment. New hair shafts containing hair fibers appeared to be straight after HP treatment. Immunohistological staining revealed a significant increase of Ki67-positive cells in hair follicles treated with 1 mg/mL HP. Topical HP treatment increased the ratio of Bcl-2/Bax, while it attenuated the expression of pro-apoptotic Bax, p53, and cytochrome c with caspase-9 and -3. In addition, the expression of KGF and the phosphorylation of AKT were upregulated by HP treatment. CONCLUSION: These results suggest that HP treatment induced hair growth by inhibiting apoptosis and promoting the proliferation of hair follicles. HP may be useful for treating chemotherapy-induced alopecia.

3.
J Ethnopharmacol ; 261: 113074, 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32534115

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Kyung-Bang Gumiganghwal-tang tablet (GMGHT) is a standardized Korean Medicine that could treat a cold, headache, arthralgia and fever. Although GMGHT has been used for arthritis-related diseases including a sprain, arthralgia, unspecified arthritis and knee arthritis, there is no pre-clinical evidence to treat osteoarthritis (OA). This study determined the drug dosage and the mechanisms of GMGHT for OA. METHODS: OA was induced by intra-articular monoiodoacetic acid (MIA) injection in Sprague-Dawley rats. As calculated from the human equivalent dose formula, GMGHT was orally administered at the doses of 9.86, 98.6 and 986 mg/kg for 4 weeks. The arthritis score was performed by a blind test, and histological changes in articular cartilage were indicated by hematoxylin and eosin, Safranin O and toluidine blue staining. SW1353 chondrocytes were stimulated by interleukin (IL)-1ß recombinant to analyze the expressions of Type II collagen, matrix metalloproteinases (MMPs) and nuclear factor (NF)-κB. RESULTS: Rough and punctate surfaces of the femoral condyle induced by MIA, were recovered by the GMGHT treatment. The arthritis score was significantly improved in the 968 mg/kg of GMGHT-treated cartilage. Loss of chondrocytes and proteoglycan were ameliorated at the deep zone of the subchondral bone plate by the GMGHT administration in OA rats. The expression of Type II collagen was increased, while MMP-1, -3 and -13 levels were decreased in the GMGHT-treated SW1353 chondrocytes. In addition, the GMGHT treatment regulated NF-κB activation along with IL-6, transforming growth factor-ß and IL-12 production. CONCLUSIONS: GMGHT promoted the recovery of articular cartilage damage by inhibiting MMPs, accompanied with its anti-inflammatory effects in OA. GMGHT might be an alternative therapeutic treatment for OA.

4.
J Nat Med ; 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32533386

RESUMO

Soshiho-tang (SSHT) has traditionally been used to treat gastrointestinal disorders. In this experiment, we investigated the protective effect of SSHT on inflammatory liver injury in lipopolysaccharide (LPS)-sensitized mice. Male C57BL/6J mice aged 6 weeks were randomly placed in 6 groups (n = 5): normal mice (CTR), LPS-sensitized mice (LPS), LPS-sensitized mice treated with dexamethasone (DEX) and LPS-sensitized mice treated with 0.05, 0.55, and 5.55 g/kg of SSHT (SSHT 0.05, SSHT 0.55, and SSHT 5.55). Various doses of SSHT was given once a day for 7 days. After 2 h of LPS injection, the liver tissue was collected. SSHT pretreatment recovered hemorrhage of liver tissues in LPS-induced acute liver injury. The expressions of MAP Kinase, NF-κB, IκBα, p-IκBα, COX-2, and iNOS protein levels were markedly decreased by SSHT-treated liver tissues. Additionally, SSHT pretreatment significantly regulated the expressions of MCP-1, TNF-α, and IL-6 cytokines. These results suggest the potential of SSHT on the protection of acute liver injury.

5.
Molecules ; 25(9)2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32397290

RESUMO

Exposure to particulate matter (PM) has been known to be one of the risk factors to cause allergic asthma, leading to development of respiratory disease. Banhahubak-tang tablet (BHT), a standardized Korean Medicine, is prescribed for neurasthenia, laryngopharyngitis and asthma. In this study, we investigated therapeutic effects of BHT on airway inflammation in ovalbumin (OVA) and PM smaller than 10 µm (PM10)-induced allergic asthma mice. To establish allergic asthma with airway hyper-responsiveness by PM10, BALB/c mice were sensitized and challenged with OVA and PM10, and orally administered BHT. Histological staining was performed to assess airway remodeling. Serum and bronchoalveolar lavage fluid (BALF) was collected for measuring immunoglobulin levels and counting inflammatory cells, respectively. Expression levels of Janus kinase 1 (JAK1)/signal transducer and activator of transcription 6 (STAT6), pro-inflammatory cytokines and type 2 T-helper (Th2)-related cytokines were analyzed in vivo and in vitro models. Histopathological analysis demonstrated that BHT suppressed inflammatory cell infiltration, mucus hypersecretion and collagen deposition in the airway. BHT administration effectively decreased number of inflammatory cells in BALF. BHT reduced total serum Immunoglobulin E (IgE) and Immunoglobulin G (IgG) levels. In addition, BHT significantly inhibited the phosphorylation of JAK1 and STAT6 expressions. Release of pro-inflammatory cytokines and Th2-related cytokines were down-regulated by BHT. In conclusion, BHT mitigated airway inflammation by down-regulating pro-inflammatory and Th2-related cytokines via JAK1/STAT6 signaling. BHT might be a promising herbal medicine for preventing airway inflammation. Moreover, an intervention study among humans is needed to further evaluate the possible beneficial effects of BHT in allergic asthma.

6.
Int J Oncol ; 56(6): 1540-1550, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32236607

RESUMO

The epidermal growth factor receptor (EGFR)­tyrosine kinase inhibitor (TKI), gefitinib, is an effective therapeutic drug used in the treatment of non­small cell lung cancers (NSCLCs) harboring EGFR mutations. However, acquired resistance significantly limits the efficacy of EGFR­TKIs and consequently, the current chemotherapeutic strategies for NSCLCs. It is, therefore, necessary to overcome this resistance. In the present study, the anticancer potential of natural extracts of Coptis chinensis (ECC) against gefitinib­resistant (GR) NSCLC cells were investigated in vitro and in vivo. ECC inhibited the viability, migration and invasion, and effectively induced the apoptosis of GR cells. These effects were associated with the suppression of EGFR/AKT signaling and the expression of anti­apoptotic proteins, Mcl­1 and Bcl­2, which were overexpressed in GR NSCLC cells. Combination treatment with ECC and gefitinib enhanced the sensitivity of GR cells to gefitinib in vitro, but not in vivo. However, ECC increased the survival of individual zebrafish without affecting the anticancer effect to cancer cells in vivo, which indicated a specific cytotoxic effect of ECC on cancer cells, but not on normal cells; this is an important property for the development of novel anticancer drugs. On the whole, the findings of the present study indicate the potential of ECC for use in the treatment of NSCLC, particularly in combination with EGFR­TKI therapy, in EGFR­TKI­resistant cancers.

7.
J Cell Physiol ; 234(10): 18249-18261, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30851074

RESUMO

Epidemiological evidence suggests that obesity can significantly increase the risk of various cancers, although the mechanisms underlying this link are completely unknown. Here, we analyzed the effect of adipocytes on melanoma and colon cancer cells proliferation, migration, and invasion. The potential effects of conditioned media (CM) obtained from differentiated mouse 3T3-L1 cells and human adipose tissue-derived mesenchymal stem cells (hAMSC) on the proliferation, migration, and invasion of B16BL6 melanoma and colon 26-L5 cancer cells were investigated. The 3T3-L1 and hAMSC CM increased cell proliferation, migration, and invasion in both the cell lines. In addition, adipocytes CM increased matrix metalloproteinase 9 (MMP-9) and MMP-2 activity in both B16BL6 and colon 26-L5 cells. These effects were found to be associated with an increased expression of various oncogenic proteins in B16BL6 and colon 26-L5 cells. Also, adipocyte CM induced Akt and mTOR activation in both tumor cell lines, and the pharmacological inhibition of Akt and mTOR blocked the CM induced Akt as well as mTOR activation and CM-stimulated melanoma and colon cancer cell proliferation, migration, and invasion. These data suggest that adipocyte promotes melanoma and colon cancer progression through modulating the expression of diverse proteins associated with cancer growth and metastasis as well as modulation of the Akt/mTOR signaling.

8.
Biomed Rep ; 10(1): 17-22, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30588298

RESUMO

Phlomis umbrosa Turcz (labiatae) has been suggested to promote bone growth. However, the anti-osteoporotic effects of P. umbrosa have not yet been elucidated. In the present study, the osteogenic effects of P. umbrosa were investigated in an osteoporosis model. ICR female mice were ovariectomized (OVX) to induce osteoporosis for 7 weeks. Treatment with 1, 10 and 100 mg/kg P. umbrosa was administrated orally to the OVX mice for 6 weeks. At the end of experiment, the microstructure of the capital femoral epiphysis was investigated. The levels of bone mineral density (BMD), bone mineral content (BMC) and serum osteocalcin concentration were evaluated. In addition, mineralized Saos-2 osteoblast cells were treated with 0.01, 0.1 and 1 µg/ml P. umbrosa to analyze the expression of osteoblast differentiation-associated factors. Hyperplasia of the growth plate in the femur was recovered by P. umbrosa treatment. BMD and BMC were significantly increased in P. umbrosa-treated femurs. Serum calcium concentration was increased following P. umbrosa treatment. In addition, the ratio of mineralization was markedly increased in P. umbrosa-treated differentiated osteoblasts along with increases in Runx2 levels. P. umbrosa conferred its osteogenic effects by upregulating Runx2 in osteoporosis. P. umbrosa may be a potential therapeutic material for the treatment of osteoporosis.

9.
BMC Complement Altern Med ; 18(1): 270, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30285722

RESUMO

BACKGROUND: Schisandra chinenesis (SC) has been reported to have ameliorative effect on osteoporosis. However, the mechanisms underlying the anti-osteoporosis activity of SC have not been clearly elucidated. In the present study, we determined the effects of SC on The receptor activator of NF-kB ligand (RANKL)-induced osteoclastogenesis and its potential mechanism. METHODS: Raw 264.7 cells were treated with 0.6, 6 and 60 µg/mL SC in the presence of 100 ng/mL RANKL for 7 days. RANKL-induced osteoclast formation was analyzed by tartrate resistant acid phosphatase (TRAP) staining. The osteoclast differentiation-related factors were confirmed along with TNF-α. RESULTS: SC inhibits the RANKL-induced osteoclast differentiation in dose-dependent manner within non-toxic concentrations. The supernatant concentrations of TNF-α were significantly decreased by SC treatment. In addition, osteoclastogenesis-related factors, TRAP6 and NF-κB, were markedly decreased by SC in RANKL-induced osteoclasts. Mechanistically, SC reduced the RANKL-triggered NFATc1 and c-fos expressions. CONCLUSIONS: Taken together, our data suggest that SC can modulate bone metabolism by suppressing RANKL-induced osteoclast differentiation.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Fatores de Transcrição NFATC/genética , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/genética , Ligante RANK/metabolismo , Schisandra/química , Animais , Regulação para Baixo/efeitos dos fármacos , Camundongos , NF-kappa B/genética , NF-kappa B/metabolismo , Fatores de Transcrição NFATC/metabolismo , Oligopeptídeos/metabolismo , Osteoclastos/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Células RAW 264.7 , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
10.
J Dermatol Sci ; 91(3): 292-300, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29933898

RESUMO

BACKGROUND: (R)-(+)-pulegone (PLG), a biotransformation of monoterpene ketones, is one of essential oils of Labiatae family. Although PLG was reported to have anti-inflammatory and anti-histamine effects, the therapeutic effects of PLG on atopic dermatitis (AD) have not been reported yet. OBJECTIVE: This study investigated the anti-AD effects and underlying mechanisms of PLG in AD-induced mice. METHODS: BALB/c male mice were challenged with 2, 4-dinitrochlorobenzene (DNCB, 1%) to induce AD. After 4 days of rest, PLG (0.1, 1 and 10 µM) were topically applied to dorsal skin for 2 weeks with secondary elicitation using 0.5% DNCB. Histological changes were identified by H&E staining and mast cells were evaluated by toluidine blue staining. Pro-inflammatory cytokines and serum IgE levels were analyzed by ELISA. Inflammatory mediators were measured by western blotting assay. RESULTS: Topical treatment with PLG significantly suppressed skin thickness and scratching behavior compared with control group. Expression of nerve growth factor was also decreased by PLG treatment. PLG administration decreased serum IgE levels and the number of mast cells in mice model of DNCB-induced AD. The levels of IL-4, IFN-γ, IL-6, TNF-α and IL-1ß in dorsal skin of PLG-treated group were lower than those in the control group. PLG inhibited the phosphorylation of MAPKs, as well as IκBα degradation and NF-κB activation. CONCLUSIONS: PLG attenuated the symptoms of AD by suppressing cytokines production, the phosphorylation of MAPKs and the activation of NF-κB signaling. These data suggest that PLG may be an effective natural compound for the treatment of inflammatory skin diseases.


Assuntos
Antialérgicos/farmacologia , Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Dermatite Alérgica de Contato/prevenção & controle , Dermatite Atópica/prevenção & controle , Dinitroclorobenzeno , Mediadores da Inflamação/metabolismo , Monoterpenos/farmacologia , Pele/efeitos dos fármacos , Animais , Monoterpenos Cicloexânicos , Citocinas/imunologia , Dermatite Alérgica de Contato/imunologia , Dermatite Alérgica de Contato/metabolismo , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/imunologia , Dermatite Atópica/metabolismo , Modelos Animais de Doenças , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Mediadores da Inflamação/imunologia , Masculino , Camundongos Endogâmicos BALB C , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Fosforilação , Proteólise , Prurido/induzido quimicamente , Prurido/imunologia , Prurido/metabolismo , Prurido/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Pele/imunologia , Pele/metabolismo , Pele/patologia , Equilíbrio Th1-Th2/efeitos dos fármacos
11.
Cancer Lett ; 431: 123-141, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29857127

RESUMO

Aberrant reactions of signal transducer and transcriptional activator (STAT) are frequently detected in multiple myeloma (MM) cancers and can upregulate the expression of multiple genes related to cell proliferation, survival, metastasis, and angiogenesis. Therefore, agents capable of inhibiting STAT activation can form the basis of novel therapies for MM patients. In the present study, we investigated whether the potential anti-cancer effects of Formononetin (FT), a naturally occurring isoflavone derived from Astragalus membranaceus, Trifolium pratense, Glycyrrhiza glabra, and Pueraria lobata, against MM cell lines and human multiple myeloma xenograft tumors in athymic nu/nu mice model are mediated through the negative regulation of STAT3 and STAT5 pathways. Data from the in vitro studies indicated that FT could significantly inhibit cell viability, and induce apoptosis. Interestingly, FT also suppressed constitutive STAT3 (tyrosine residue 705 and serine residue 727) and STAT5 (tyrosine residue 694/699) activation, which correlated with the suppression of the upstream kinases (JAK1, JAK2, and c-Src) in MM cells, and this effect was found to be mediated via an increased production of reactive oxygen species (ROS) due to GSH/GSSG imbalance. Also, FT abrogated STAT3 and STAT5 DNA binding capacity and nuclear translocation. FT induced cell cycle arrest, downregulated the expression of STAT3-regulated anti-apoptotic, angiogenetic, and proliferative gene products; and this correlated with induction of caspase-3 activation and cleavage of PARP. Intraperitoneal administration of FT significantly suppressed the tumor growth in the multiple myeloma xenograft mouse model without exhibiting any significant adverse effects. Overall, our findings indicate that FT exhibits significant anti-cancer effects in MM that may be primarily mediated through the ROS-regulated inhibition of the STAT3 and STAT5 signaling cascade.


Assuntos
Isoflavonas/farmacologia , Mieloma Múltiplo/metabolismo , Estresse Oxidativo , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT5/metabolismo , Animais , Apoptose , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Glutationa/metabolismo , Humanos , Leucócitos Mononucleares/citologia , Camundongos , Camundongos Nus , Transplante de Neoplasias , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
12.
Phytomedicine ; 40: 165-175, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29496169

RESUMO

BACKGROUND: Ophiopogonin D (OP-D), a steroidal glycoside obtained from the Chinese medicinal plant Ophiopogonin japonicas (the root portion), has been traditionally used to treat fever, inflammation, cough, sputum etc. However, the detailed molecular mechanism(s) underlying its therapeutic actions is still unknown. HYPOTHESIS: Because nuclear factor-κB (NF-κB), PI3K/AKT, and activator protein-1 (AP-1) signaling cascades have significant functions in cell proliferation, inflammation, and angiogenesis in tumor cells, we hypothesized that OP-D may disrupt these signaling cascades to exert its anticancer effects in human lung-cancer cells. METHODS: We evaluated the effect of OP-D on multiple signaling cascades and its regulated functional responses in lung cancer cells. RESULTS: OP-D blocked both basal and cytokine-induced proliferation of human lung-cancer cells and caused down-regulation of the expression of diverse oncogenic gene products through the suppression of NF-κB, PI3K/AKT, and AP-1 pathways; but did not affect JNK, p38 and ERK MAP kinases. Interestingly, OP-D suppressed constitutive NF-κB activation in lung cancer cells via interfering with the IκB kinase activation, which inhibited phosphorylation and caused degradation of IκB-α. OP-D also blocked phosphorylation and the nuclear translocation of p65, thereby suppressing NF-κB reporter activity in lung cancer cells. Besides, OP-D could augment cell death induced by paclitaxel in lung-cancer cells. CONCLUSION: Overall, the data indicates that OP-D may abrogate diverse signaling cascades linked to tumorigenesis, and can be used in combination with chemotherapeutic agents for cancer therapy.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Saponinas/farmacologia , Espirostanos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição AP-1/metabolismo
13.
Molecules ; 23(3)2018 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-29522451

RESUMO

Embelin is a naturally-occurring benzoquinone compound that has been shown to possess many biological properties relevant to human cancer prevention and treatment, and increasing evidence indicates that embelin may modulate various characteristic hallmarks of tumor cells. This review summarizes the information related to the various oncogenic pathways that mediate embelin-induced cell death in multiple cancer cells. The mechanisms of the action of embelin are numerous, and most of them induce apoptotic cell death that may be intrinsic or extrinsic, and modulate the NF-κB, p53, PI3K/AKT, and STAT3 signaling pathways. Embelin also induces autophagy in cancer cells; however, these autophagic cell-death mechanisms of embelin have been less reported than the apoptotic ones. Recently, several autophagy-inducing agents have been used in the treatment of different human cancers, although they require further exploration before being transferred from the bench to the clinic. Therefore, embelin could be used as a potential agent for cancer therapy.


Assuntos
Benzoquinonas/farmacologia , Benzoquinonas/uso terapêutico , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/prevenção & controle , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Autofagia , Benzoquinonas/química , Produtos Biológicos/química , Sinergismo Farmacológico , Humanos , Neoplasias/metabolismo , Oxirredução/efeitos dos fármacos , Transdução de Sinais
14.
J Chin Med Assoc ; 81(2): 141-146, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29287702

RESUMO

BACKGROUND: Scutellaria baicalensis (SB) is widely used as a medicinal plant to treat various inflammatory diseases. In the present study, we investigated the effects of SB on periodontitis in ligature-induced experimental rat model. METHODS: Rats were subjected to a ligature placement around the first molar of the mandible to induce periodontitis. 100 mg/kg SB extracts were orally administered for 14 days. The molar tissues were stained with 1% methylene blue. Histopathological changes of the periodontium were observed by hematoxylin and eosin staining. The levels of cytokines were measured in the gingival tissue. RESULTS: Alveolar bone resorption was statistically lower in the SB group compared to the ligatured group. SB inhibited the mineralization of cementum. In addition, SB reduced the production of IL-1ß, 6, -8 and TNF-α cytokine mRNA expression in gingival tissues. CONCLUSION: These results suggest that SB showed ameliorative effects in the ligature-induced periodontitis by inhibition of inflammatory cytokine expression.


Assuntos
Citocinas/antagonistas & inibidores , Ligamento Periodontal/patologia , Periodontite/tratamento farmacológico , Extratos Vegetais/farmacologia , Perda do Osso Alveolar/prevenção & controle , Animais , Citocinas/genética , Gengiva/efeitos dos fármacos , Gengiva/imunologia , Masculino , Periodontite/patologia , Extratos Vegetais/uso terapêutico , RNA Mensageiro/análise , Ratos , Ratos Sprague-Dawley
15.
Mol Med Rep ; 17(3): 3758-3762, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29257324

RESUMO

Cynanchum wilfordii Hemsley has been used for the treatment of musculoskeletal diseases in traditional Republic of Korean medicine. The present study investigated the effects of C. wilfordii water extract (CW) on postmenopausal osteoporosis. Female mice were used and randomly assigned into a normal group and three ovariectomized (OVX) groups: OVX with vehicle (OVX + vehicle); OVX with 17ß­estradiol (E2; 10 µg/kg/day); and OVX with CW (1 mg/kg/day). Oral administration of CW or E2 intraperitoneal injection began 9 weeks after OVX and continued for 3 weeks. Following sacrifice, bone histology, bone mineral density (BMD) and bone mineral content (BMC) of the femur were observed. Serum osteocalcin concentration was analyzed. In addition, the expression levels of osteoprotegerin (OPG) and osterix were evaluated in human osteoblast­like Saos­2 cells. In the lateral and medial epicondyles of the CW­administrated group, dense and well­formed bone marrow cells with reduced bone marrow pores were observed. CW decreased the number of tartrate resistant acid phosphatase­positive multinucleated osteoclasts. BMD and BMC were increased following increased serum osteocalcin levels by CW treatment. The expression levels of OPG and osterix were upregulated by CW treatment in vitro. The results suggested that C. wilfordii has an advantageous effect on osteoporosis and possesses the potential to be used in osteoporosis treatment.


Assuntos
Reabsorção Óssea/patologia , Osso e Ossos/efeitos dos fármacos , Cynanchum/química , Extratos Vegetais/farmacologia , Administração Oral , Animais , Densidade Óssea/efeitos dos fármacos , Reabsorção Óssea/prevenção & controle , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Cynanchum/metabolismo , Estradiol/farmacologia , Feminino , Camundongos , Camundongos Endogâmicos ICR , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteocalcina/sangue , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Osteoporose/patologia , Osteoprotegerina/metabolismo , Ovariectomia , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Fator de Transcrição Sp7/metabolismo , Fosfatase Ácida Resistente a Tartarato/farmacologia , Regulação para Cima/efeitos dos fármacos
16.
J Ethnopharmacol ; 213: 328-339, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29051115

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis (Turcz.) Baill (SC), Lycium chinense Mill (LC) and Eucommia ulmoides Oliv (EU) are representative tonic herbal medicines that help to strengthen body muscles and bones making them stronger according to the Donguibogam, a tradition medical book of the Joseon Dynasty in Korea. AIM OF THE STUDY: To evaluate effects of an herbal formula consisting of SC, LC and EU on muscle atrophy in C2C12 myotubes and in a rat model of immobilization-induced muscle atrophy. MATERIALS AND METHODS: Muscle atrophy was developed by cast immobilization of unilateral hindlimb on rats for 3 weeks. Treatments were administered orally 14 times over 3 weeks. After treatments, we compared the change of body weight, muscle weight, grip strength, muscle fiber size, muscle fiber type shift by Grip strength meter, H&E stain and ATPase stain. And western blot was used for evaluating molecular mechanism in muscle atrophy on C2C12 cells. RESULTS: When taken individually, SC was the most effective of the three in inhibiting tumor necrosis factor alpha (TNF-α)-induced degeneration of C2C12 myogenesis. The formulation with a mass ratio of 2:1:1 SC: LC: EU (SSLE) was more effective against TNF-α-induced muscle atrophy than was a 1:1:1 SC: LC: EU (SLE) formula or any of the single herbal extracts. In a rat model of disuse muscle atrophy, the SSLE formula significantly inhibited reductions in muscle weight, grip strength and muscle fiber size induced by hindlimb immobilization, in a dose-dependent manner. The formula also inhibited immobilization-induced shifting of the muscle fiber type in soleus muscle. Treatment with SSLE inhibited TNF-α-induced expression of the atrogenes atrogin-1 and muscle RING-finger protein 1 in C2C12 cells. The SSLE formula also increased myoblast differentiation markers (myoD and myogenin) and activation of the Akt and mammalian target of rapamycin (mTOR) signaling pathway. CONCLUSION: These findings suggest that the SSLE formula prevents muscle atrophy through inhibition of the ubiquitin-proteasome system as well as upregulation of myoblast differentiation and muscle protein synthesis in C2C12 cells. Taken together, we conclude that the SSLE formula is invaluable for the development of therapeutic medicines to prevent disuse muscle atrophy and its accompanying muscle weakness.


Assuntos
Eucommiaceae , Lycium , Atrofia Muscular/tratamento farmacológico , Fitoterapia , Schisandra , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Força da Mão , Elevação dos Membros Posteriores , Masculino , Camundongos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Proteínas Musculares/biossíntese , Músculo Esquelético/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Complexo Repressor Polycomb 1/biossíntese , Ratos , Proteínas Ligases SKP Culina F-Box/biossíntese , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Ubiquitina-Proteína Ligases/biossíntese
17.
FASEB J ; 32(3): 1388-1402, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29141998

RESUMO

Energy expenditure is a target gaining recent interest for obesity treatment. The antiobesity effect of vanillic acid (VA), a well-known flavoring agent, was investigated in vivo and in vitro. High-fat diet (HFD)-induced obese mice and genetically obese db/db mice showed significantly decreased body weights after VA administration. Two major adipogenic markers, peroxisome proliferator activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), were reduced while the key factor of energy metabolism, AMPKα, was increased in the white adipose tissue and liver tissue of VA-treated mice. Furthermore, VA inhibited lipid accumulation and reduced hepatotoxic/inflammatory markers in liver tissues of mice and HepG2 hepatocytes. VA treatment also decreased differentiation of 3T3-L1 adipocytes by regulating adipogenic factors including PPARγ and C/EBPα. AMPKα small interfering RNA was used to examine whether AMPK was associated with the actions of VA. In AMPKα-nulled 3T3-L1 cells, the inhibitory action of VA on PPARγ and C/EBPα was attenuated. Furthermore, in brown adipose tissues of mice and primary cultured brown adipocytes, VA increased mitochondria- and thermogenesis-related factors such as uncoupling protein 1 and PPARγ-coactivator 1-α. Taken together, our results suggest that VA has potential as an AMPKα- and thermogenesis-activating antiobesity agent.-Jung, Y., Park, J., Kim, H.-L., Sim, J.-E., Youn, D.-H., Kang, J., Lim, S., Jeong, M.-Y., Yang, W. M., Lee, S.-G., Ahn, K. S., Um, J.-Y. Vanillic acid attenuates obesity via activation of the AMPK pathway and thermogenic factors in vivo and in vitro.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adipogenia/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Obesidade/tratamento farmacológico , Termogênese/efeitos dos fármacos , Ácido Vanílico/farmacologia , Células 3T3-L1 , Tecido Adiposo Marrom/patologia , Animais , Proteínas Estimuladoras de Ligação a CCAAT , Ativação Enzimática/efeitos dos fármacos , Masculino , Camundongos , Obesidade/metabolismo , Obesidade/patologia , PPAR gama/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo
18.
Chin J Integr Med ; 2017 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-28762131

RESUMO

OBJECTIVE: To investigate the phytoestrogenic effects of Schizandra chinensis (SC) extract by regulating the activation of estrogen receptor. METHODS: Western blotting assay was performed to investigate the effect of SC extract (1, 10, 100 µg/mL) on the expression of estrogen receptor (ER)-α and -ß in MCF-7 human breast cancer cells. Cell viability and the levels of c-fos and c-Jun were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Western blot analysis, respectively, to further confirm the anti-cancer effect of SC extract. RESULTS: SC extract increased the expressions of ER-α and -ß (P<0.001), whereas cell viability and the expressions of growth factors (c-fos and c-Jun) were inhibited (P< and <0.001, respectively) following treatment. CONCLUSIONS: SC extract has phytoestrogenic effects, and its biological action includes ER binding ability with low cancer risk. Therefore, SC might be a potential source for the development of a new alternative to hormone therapy in menopause.

19.
Molecules ; 22(7)2017 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-28696369

RESUMO

2,5-Dihydroxyacetophenone (DHAP) is an active compound obtained from Radix rehmanniae preparata, which is widely used as a herbal medicine in many Asian countries. DHAP has been found to possess anti-inflammatory, anti-anxiety, and neuroprotective qualities. For the present study, we evaluated the anti-cancer effects of DHAP on multiple myeloma cells. It was discovered that DHAP downregulated the expression of oncogenic gene products like Bcl-xl, Bcl-2, Mcl-1, Survivin, Cyclin D1, IAP-1, Cyclin E, COX-2, and MMP-9, and upregulated the expression of Bax and p21 proteins, consistent with the induction of G2/M phase cell cycle arrest and apoptosis in U266 cells. DHAP inhibited cell proliferation and induced apoptosis, as characterized by the cleavage of PARP and the activation of caspase-3, caspase-8, and caspase-9. Mitogen-activated protein kinase (MAPK) pathways have been linked to the modulation of the angiogenesis, proliferation, metastasis, and invasion of tumors. We therefore attempted to determine the effect of DHAP on MAPK signaling pathways, and discovered that DHAP treatment induced a sustained activation of JNK, ERK1/2, and p38 MAPKs. DHAP also potentiated the pro-apoptotic and anti-proliferative effects of bortezomib in U266 cells. Our results suggest that DHAP can be an effective therapeutic agent to target multiple myeloma.


Assuntos
Acetofenonas/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Mieloma Múltiplo/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Expressão Gênica , Humanos , Pontos de Checagem da Fase M do Ciclo Celular , Sistema de Sinalização das MAP Quinases , Proteínas Quinases Ativadas por Mitógeno/metabolismo
20.
Int J Mol Sci ; 18(5)2017 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-28534824

RESUMO

Isorhynchophylline (Rhy) is an active pharmacological component of Uncaria rhynchophylla that has been reported previously to exert significant antihypertensive and neuroprotective effects. However, very little is known about its potential anti-cancer activities. This study was carried out to evaluate the anticancer effects of Rhy against various human carcinoma cell lines. We found that Rhy exhibited substantial cytotoxic effect against human hepatocellular carcinoma HepG2 cells when compared with other human carcinoma cell lines including those of lung, pancreas, prostate, head and neck, breast, multiple myeloma, brain and renal cell carcinoma. Rhy induced apoptosis as characterized by accumulation of cells in sub G1 phase; positive Annexin V binding; activation of caspase-8, -9, and -3; and cleavage of PARP (poly-ADP ribose polymerase). This effect of Rhy correlated with the down-regulation of various proteins that mediated cell proliferation, cell survival, metastasis, and angiogenesis. Moreover, cell proliferation, migration, and constitutive CXCR4 (C-X-C chemokine receptor type 4), MMP-9 (Matrix metallopeptidase-9), and MMP-2 expression were inhibited upon Rhy treatment. We further investigated the effect of Rhy on the oncogenic cell signaling cascades through phospho-kinase array profiling assay. Rhy was found to abrogate phospho-p38, ERK, JNK, CREB, c-Jun, Akt, and STAT3 signals, but interestingly enhanced phospho-p53 signal. Overall, our results indicate, for the first time, that Rhy could exert anticancer and anti-metastatic effects through regulation of multiple signaling cascades in hepatocellular carcinoma cells.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Alcaloides Indólicos/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos Fitogênicos/química , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Hep G2 , Humanos , Alcaloides Indólicos/química , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Metástase Neoplásica/patologia , Metástase Neoplásica/prevenção & controle , Oxindois , Uncaria/química
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