scholarly journals Rikkunshito Ameliorates Cancer Cachexia Partly through Elevation of Glucarate in Plasma

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Katsuya Ohbuchi ◽  
Shin Nishiumi ◽  
Naoki Fujitsuka ◽  
Tomohisa Hattori ◽  
Masahiro Yamamoto ◽  
...  
Keyword(s):  
Weight Loss ◽  
Herbal Medicine ◽  
Rat Model ◽  
Cancer Cachexia ◽  
Host Cells ◽  
Metabolome Analysis ◽  
Traditional Herbal Medicine ◽  
Delayed Onset ◽  
Tumor Bearing

Cancer cachexia, which is characterized by decreased food intake, weight loss and systemic inflammation, increases patient’s morbidity and mortality. We previously showed that rikkunshito (RKT), a Japanese traditional herbal medicine (Kampo), ameliorated the symptoms of cancer cachexia through ghrelin signaling-dependent and independent pathways. To investigate other mechanisms of RKT action in cancer cachexia, we performed metabolome analysis of plasma in a rat model bearing the Yoshida AH-130 hepatoma. A total of 110 metabolites were detected in plasma and RKT treatment significantly altered levels of 23 of those metabolites in cachexia model rats. Among them, glucarate, which is known to have anticarcinogenic activity through detoxification of carcinogens via inhibition ofβ-glucuronidase, was increased in plasma following administration of RKT. In our AH-130 ascites-induced cachexia rat model, administration of glucarate delayed onset of weight loss, improved muscle atrophy, and reduced ascites content. Additionally, glucarate reduced levels of plasma interferon-γ(IFN-γ) in tumor-bearing rats and was also found to suppress LPS-induced IFN-γexpression in splenocytesin vitro. These results suggest that glucarate has anti-inflammatory activity via a direct effect on immune host cells and suggest that RKT may also ameliorate inflammation partly through the elevation of glucarate in plasma.

scholarly journals The Extract of Arctium lappa L. Fruit (Arctii Fructus) Improves Cancer-Induced Cachexia by Inhibiting Weight Loss of Skeletal Muscle and Adipose Tissue

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3195
Author(s):  
Yo-Han Han ◽  
Jeong-Geon Mun ◽  
Hee Dong Jeon ◽  
Dae Hwan Yoon ◽  
Byung-Min Choi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Weight Loss ◽  
Adipose Tissue ◽  
Cancer Cachexia ◽  
Uncoupling Protein ◽  
Body Weight Loss ◽  
In Vivo Experiments ◽  
Wasting Syndrome

Background: Cachexia induced by cancer is a systemic wasting syndrome and it accompanies continuous body weight loss with the exhaustion of skeletal muscle and adipose tissue. Cancer cachexia is not only a problem in itself, but it also reduces the effectiveness of treatments and deteriorates quality of life. However, effective treatments have not been found yet. Although Arctii Fructus (AF) has been studied about several pharmacological effects, there were no reports on its use in cancer cachexia. Methods: To induce cancer cachexia in mice, we inoculated CT-26 cells to BALB/c mice through subcutaneous injection and intraperitoneal injection. To mimic cancer cachexia in vitro, we used conditioned media (CM), which was CT-26 colon cancer cells cultured medium. Results: In in vivo experiments, AF suppressed expression of interleukin (IL)-6 and atrophy of skeletal muscle and adipose tissue. As a result, the administration of AF decreased mortality by preventing weight loss. In adipose tissue, AF decreased expression of uncoupling protein 1 (UCP1) by restoring AMP-activated protein kinase (AMPK) activation. In in vitro model, CM increased muscle degradation factors and decreased adipocytes differentiation factors. However, these tendencies were ameliorated by AF treatment in C2C12 myoblasts and 3T3-L1 cells. Conclusion: Taken together, our study demonstrated that AF could be a therapeutic supplement for patients suffering from cancer cachexia.

scholarly journals Dual roles of a novel oncolytic viral vector-based SARS-CoV-2 vaccine: preventing COVID-19 and treating tumor progression

2021 ◽  
Author(s):  
Michael A. Caligiuri ◽  
Jianhua Yu ◽  
Yaping Sun ◽  
Wenjuan Dong ◽  
Lei Tian ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Viral Vector ◽  
Protein A ◽  
Surface Protein ◽  
T Cell Response ◽  
Host Cells ◽  
Serious Adverse Events ◽  
S Protein ◽  
Tumor Bearing

The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cancer patients are usually immunocompromised and thus are particularly susceptible to SARS-CoV-2 infection resulting in COVID-19. Although many vaccines against COVID-19 are being preclinically or clinically tested or approved, none have yet been specifically developed for cancer patients or reported as having potential dual functions to prevent COVID-19 and treat cancer. Here, we confirmed that COVID-19 patients with cancer have low levels of antibodies against the spike (S) protein, a viral surface protein mediating the entry of SARS-CoV-2 into host cells, compared with COVID-19 patients without cancer. We developed an oncolytic herpes simplex virus-1 vector-based vaccine named oncolytic virus (OV)-spike. OV-spike induced abundant anti-S protein neutralization antibodies in both tumor-free and tumor-bearing mice, which inhibit infection of VSV-SARS-CoV-2 and wild-type (WT) live SARS-CoV-2 as well as the B.1.1.7 variant in vitro. In the tumor-bearing mice, OV-spike also inhibited tumor growth, leading to better survival in multiple preclinical tumor models than the untreated control. Furthermore, OV-spike induced anti-tumor immune response and SARS-CoV-2-specific T cell response without causing serious adverse events. Thus, OV-spike is a promising vaccine candidate for both preventing COVID-19 and enhancing the anti-tumor response.

scholarly journals Traditional Herbal Medicine, Rikkunshito, Induces HSP60 and Enhances Cytoprotection of Small Intestinal Mucosal Cells as a Nontoxic Chaperone Inducer

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Kumiko Tamaki ◽  
Michiro Otaka ◽  
Tomoyoshi Shibuya ◽  
Naoto Sakamoto ◽  
Soh Yamamoto ◽  
...  
Keyword(s):  
Herbal Medicine ◽  
Immunoblot Analysis ◽  
Intestinal Cell ◽  
Traditional Herbal Medicine ◽  
Intestinal Cell Line ◽  
Mucosal Cells ◽  
Hsp60 Expression ◽  
Small Intestinal ◽  
Intestinal Ulcers

Increasing incidence of small intestinal ulcers associated with nonsteroidal anti-inflammatory drugs (NSAIDs) has become a topic with recent advances of endoscopic technology. However, the pathogenesis and therapy are not fully understood. The aim of this study is to examine the effect of Rikkunshito (TJ-43), a traditional herbal medicine, on expression of HSP60 and cytoprotective ability in small intestinal cell line (IEC-6). Effect of TJ-43 on HSP60 expression in IEC-6 cells was evaluated by immunoblot analysis. The effect of TJ-43 on cytoprotective abilities of IEC-6 cells against hydrogen peroxide or indomethacin was studied by MTT assay, LDH-release assay, caspase-8 activity, and TUNEL. HSP60 was significantly induced by TJ-43. Cell necrosis and apoptosis were significantly suppressed in IEC-6 cells pretreated by TJ-43 with overexpression of HSP60. Our results suggested that HSP60 induced by TJ-43 might play an important role in protecting small intestinal epithelial cells from apoptosis and necrosis in vitro.

New cancer cachexia rat model generated by implantation of a peritoneal dissemination-derived human stomach cancer cell line

2014 ◽  
Vol 306 (4) ◽  
pp. E373-E387 ◽  
Author(s):  
Kiyoshi Terawaki ◽  
Yumi Sawada ◽  
Yohei Kashiwase ◽  
Hirofumi Hashimoto ◽  
Mitsuhiro Yoshimura ◽  
...  
Keyword(s):  
Weight Loss ◽  
Cell Line ◽  
Stomach Cancer ◽  
Rat Model ◽  
Cancer Cachexia ◽  
Peritoneal Dissemination ◽  
Cancer Cell Line ◽  
Human Stomach ◽  
Mrna Levels ◽  
Human Stomach Cancer

Cancer cachexia (CC), a syndrome characterized by anorexia and body weight loss due to low fat-free mass levels, including reduced musculature, markedly worsens patient quality of life. Although stomach cancer patients have the highest incidence of cachexia, few experimental models for the study of stomach CC have been established. Herein, we developed stomach CC animal models using nude rats subcutaneously implanted with two novel cell lines, i.e., MKN45c185, established from the human stomach cancer cell line MKN-45, and 85As2, derived from peritoneal dissemination of orthotopically implanted MKN45c185 cells in mice. Both CC models showed marked weight loss, anorexia, reduced musculature and muscle strength, increased inflammatory markers, and low plasma albumin levels; however, CC developed earlier and was more severe in rats implanted with 85As2 than in those implanted with MKN45cl85. Moreover, human leukemia inhibitory factor (LIF), a known cachectic factor, and hypothalamic orexigenic peptide mRNA levels increased in the models, whereas hypothalamic anorexigenic peptide mRNA levels decreased. Surgical removal of the tumor not only abolished cachexia symptoms but also reduced plasma LIF levels to below detectable limits. Importantly, oral administration of rikkunshito, a traditional Japanese medicine, substantially ameliorated CC-related anorexia and body composition changes. In summary, our novel peritoneal dissemination-derived 85As2 rat model developed severe cachexia, possibly caused by LIF from cancer cells, that was ameliorated by rikkunshito. This model should provide a useful tool for further study into the mechanisms and treatment of stomach CC.

scholarly journals Effects of Syo-seiryu-to and Its Constituent Crude Drugs on Phorbol Ester-Induced Up-Regulation of IL-33 and Histamine H1 Receptor mRNAs in Swiss 3T3 and HeLa Cells

Allergies ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 163-175
Author(s):  
Seiichi Nakano ◽  
Sayaka Yamamoto ◽  
Takako Esu ◽  
Shiho Naniwa ◽  
Yuki Konishi ◽  
...  
Keyword(s):  
Herbal Medicine ◽  
Nasal Congestion ◽  
Eosinophil Infiltration ◽  
High Concentration ◽  
H1 Receptor ◽  
Traditional Herbal Medicine ◽  
Signal Molecule ◽  
Histamine H1 Receptor ◽  
Crude Drugs

Syo-seiryu-to (SST) is a traditional herbal medicine that has been used clinically to treat allergic rhinitis (AR) in Japan. SST improves acute symptoms, such as sneezing and rhinorrhea, as well as chronic symptoms, such as nasal obstruction, in patients with AR. However, its therapeutic mechanisms remain unknown. We examined the effects of SST and eight constituent crude drugs on phorbol 12-myristate-13-acetate (PMA)-induced gene up-regulation of IL-33 and histamine H1 receptor (H1R), which are responsible for the pathogenesis of AR. We found that SST and its crude drugs, except for Pinellia tuber, significantly and dose-dependently suppressed PMA-induced both IL-33 and H1R mRNA up-regulation in vitro. The half-maximal inhibitory concentration values of the seven crude drugs to inhibit PMA-induced IL-33 mRNA up-regulation were correlated with those related to H1R mRNA up-regulation, suggesting that they act on a common signal molecule. These results suggest that SST improves nasal congestion that is induced by IL-33-related eosinophil infiltration and inhibits sneezing and rhinorrhea that are induced by H1R-mediated histamine signaling in the nasal mucosa of AR patients through its inhibition of a common molecule in the gene expression pathways of IL-33 and H1R. The results could explain the advantages of traditional herbal medicine, in which mixing various crude drugs not only acts on a common target to enhance its pharmacological action, similar to the effect of a high concentration of a single crude extract but also has the benefit of reducing the side effects of each crude drug.

Paljung-San, a traditional herbal medicine, attenuates benign prostatic hyperplasia in vitro and in vivo

2018 ◽  
Vol 218 ◽  
pp. 109-115 ◽  
Author(s):  
Eunsook Park ◽  
Mee-Young Lee ◽  
Woo-Young Jeon ◽  
Chang-Seob Seo ◽  
Sooseong You ◽  
...  
Keyword(s):  
Benign Prostatic Hyperplasia ◽  
Herbal Medicine ◽  
Prostatic Hyperplasia ◽  
Traditional Herbal Medicine

scholarly journals IGF-1 treatment reduces weight loss and improves outcome in a rat model of cancer cachexia

2011 ◽  
Vol 2 (2) ◽  
pp. 105-109 ◽  
Author(s):  
Katja Schmidt ◽  
Stephan von Haehling ◽  
Wolfram Doehner ◽  
Sandra Palus ◽  
Stefan D. Anker ◽  
...  
Keyword(s):  
Weight Loss ◽  
Rat Model ◽  
Cancer Cachexia

scholarly journals Antitumor Efficacy and Mechanism in Hepatoma H22-Bearing Mice ofBrucea javanicaOil

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Wen-Rong Shi ◽  
Yan Liu ◽  
Xiao-Ting Wang ◽  
Qiong-Ying Huang ◽  
Xue-Rong Cai ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Herbal Medicine ◽  
Antitumor Effect ◽  
Antitumor Activities ◽  
Traditional Herbal Medicine ◽  
Brucea Javanica ◽  
Protein Levels ◽  
Tumor Bearing ◽  
Tumor Tissues ◽  
Wbc Count

Brucea javanicais a traditional herbal medicine in China, and its antitumor activities are of research interest.Brucea javanicaoil, extracted with ether and refined with 10% ethyl alcohol fromBrucea javanicaseed, was used to treat hepatoma H22-bearing mice in this study. The antitumor effect and probable mechanisms of the extractedBrucea javanicaoil were studied in H22-bearing mice by WBC count, GOT, GPT levels, and western blotting. The H22 tumor inhibition ratio of 0.5, 1, and 1.5 g/kg bwBrucea javanicaoil were 15.64%, 23.87%, and 38.27%.Brucea javanicaoil could inhibit the involution of thymus induced by H22 tumor-bearing, but it could not inhibit the augmentation of spleen and liver.Brucea javanicaoil could decrease the levels of WBC count and GOT and GPT in H22-bearing mice. The protein levels of GAPDH, Akt, TGF-β1, andα-SMA in tumor tissues decreased after being treated withBrucea javanicaoil. Disturbing energy metabolism and neoplastic hyperplasia controlled by Akt and immunoregulation activity were its probable antitumor mechanisms in hepatoma H22-bearing mice.

scholarly journals Streptococcus iniae Virulence Is Associated with a Distinct Genetic Profile

2001 ◽  
Vol 69 (4) ◽  
pp. 1994-2000 ◽  
Author(s):  
Jeffrey D. Fuller ◽  
Darrin J. Bast ◽  
Victor Nizet ◽  
Donald E. Low ◽  
Joyce C. S. de Azavedo
Keyword(s):  
Weight Loss ◽  
Endothelial Cells ◽  
In Vitro Models ◽  
Host Cells ◽  
Streptococcus Iniae ◽  
Genetic Profile ◽  
Commercial Fish ◽  
Lactate Dehydrogenase Release

ABSTRACT Streptococcus iniae causes meningoencephalitis and death in commercial fish species and has recently been identified as an emerging human pathogen producing fulminant soft tissue infection. As identified by pulsed-field gel electrophoresis (PFGE), strains causing disease in either fish or humans belong to a single clone, whereas isolates from nondiseased fish are genetically diverse. In this study, we used in vivo and in vitro models to examine the pathogenicity of disease-associated isolates. Strains with the clonal (disease-associated) PFGE profile were found to cause significant weight loss and bacteremia in a mouse model of subcutaneous infection. As little as 102 CFU of a disease-associated strain was sufficient to establish bacteremia, with higher inocula (107) resulting in increased mortality. In contrast, non-disease-associated (commensal) strains failed to cause bacteremia and weight loss, even at inocula of 108 CFU. In addition, disease-associated strains were more resistant to phagocytic clearance in a human whole blood killing assay compared to commensal strains, which were almost entirely eradicated. Disease-associated strains were also cytotoxic to human endothelial cells as measured by lactate dehydrogenase release from host cells. However, both disease-associated and commensal strains adhered to and invaded cultured human epithelial and endothelial cells equally well. While cellular invasion may still contribute to the pathogenesis of invasive S. iniaedisease, resistance to phagocytic clearance and direct cytotoxicity appear to be discriminating virulence attributes of the disease-associated clone.

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