scholarly journals Anti-HBV Activities of Polysaccharides from Thais clavigera (Küster) by In Vitro and In Vivo Study

Marine Drugs ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. 195
Author(s):  
Fei Tang ◽  
Guanghua Huang ◽  
Liping Lin ◽  
Hong Yin ◽  
Lili Shao ◽  
...  

Hepatitis B virus (HBV) infection remains a major global health problem. It is therefore imperative to develop drugs for anti-hepatitis B with high-efficiency and low toxicity. Attracted by the observations and evidence that the symptoms of some patients from the Southern Fujian, China, suffering from hepatitis B were alleviated after daily eating an edible marine mollusk, Thais clavigera (Küster 1860) (TCK). Water-soluble polysaccharide from TCK (TCKP1) was isolated and characterized. The anti-HBV activity of TCKP1 and its regulatory pathway were investigated on both HepG2.2.15 cell line and HBV transgenic mice. The data obtained from in vitro studies showed that TCKP1 significantly enhanced the production of IFN-α, and reduced the level of HBV antigens and HBV DNA in the supernatants of HepG2.2.15 cells in a dose-dependent manner with low cytotoxicity. The result of the study on the HBV transgenic mice further revealed that TCKP1 significantly decreased the level of transaminases, HBsAg, HBeAg, and HBV DNA in the serum, as well as HBsAg, HBeAg, HBV DNA, and HBV RNA in the liver of HBV transgenic (HBV-Tg) mice. Furthermore, TCKP1 exhibited equivalent inhibitory effect with the positive control tenofovir alafenamide (TAF) on the markers above except for HBV DNA even in low dosage in a mouse model. However, the TCKP1 high-dose group displayed stronger inhibition of transaminases and liver HBsAg, HBeAg, and HBV RNA when compared with those of TAF. Meanwhile, inflammation of the liver was, by pathological observation, relieved in a dose-dependent manner after being treated with TCKP1. In addition, elevated levels of interleukin-12 (IL-12) and interferon γ (IFN-γ), and reduced level of interleukin-4 (IL-4) in the serum were observed, indicating that the anti-HBV effect of TCKP1 was achieved by potentiating immunocyte function and regulating the balance of Th1/Th2 cytokines.

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 386
Author(s):  
Tung-Hu Tsai ◽  
Yu-Jen Chen ◽  
Li-Ying Wang ◽  
Chen-Hsi Hsieh

This study was performed to evaluate the interaction between conventional or high-dose radiotherapy (RT) and the pharmacokinetics (PK) of regorafenib in concurrent or sequential regimens for the treatment of hepatocellular carcinoma. Concurrent and sequential in vitro and in vivo studies of irradiation and regorafenib were designed. The interactions of RT and regorafenib in vitro were examined in the human hepatoma Huh-7, HA22T and Hep G2 cell lines. The RT–PK phenomenon and biodistribution of regorafenib under RT were confirmed in a free-moving rat model. Regorafenib inhibited the viability of Huh-7 cells in a dose-dependent manner. Apoptosis in Huh-7 cells was enhanced by RT followed by regorafenib treatment. In the concurrent regimen, RT decreased the area under the concentration versus time curve (AUC)regorafenib by 74% (p = 0.001) in the RT2 Gy × 3 fraction (f’x) group and by 69% (p = 0.001) in the RT9 Gy × 3 f’x group. The AUCregorafenib was increased by 182.8% (p = 0.011) in the sequential RT2Gy × 1 f’x group and by 213.2% (p = 0.016) in the sequential RT9Gy × 1 f’x group. Both concurrent regimens, RT2Gy × 3 f’x and RT9Gy × 3 f’x, clearly decreased the biodistribution of regorafenib in the heart, liver, lung, spleen and kidneys, compared to the control (regorafenib × 3 d) group. The concurrent regimens, both RT2Gy × 3 f’x and RT9Gy × 3 f’x, significantly decreased the biodistribution of regorafenib, compared with the control group. The PK of regorafenib can be modulated both by off-target irradiation and stereotactic body radiation therapy (SBRT).


2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi6-vi6
Author(s):  
Takashi Fujii ◽  
Shun Yamamuro ◽  
Masamichi Takahashi ◽  
Akihide Kondo ◽  
Yoshitaka Narita ◽  
...  

Abstract The therapeutic outcome of glioblastomas (GBMs) is still very poor. Therefore, invention of novel therapeutic methods against GBM cases is considered urgent. The antitumor effects of naturally-derived compounds are attracting attention recently, and therapeutic efficacy of curcumin, a plant-derived compound previously used for multiple purpose, has been indicated in many cancer systems; however, clinical application of curcumin is considered difficult because of its poor bioavailability (under 1 %). Curcumin monoglucuronide (CMG), a water-soluble prodrug of curcumin recently developed for overcoming this weakness, has been demonstrated excellent antitumor effects for several malignancies in vitro and in vivo; therefore, we investigated the effects of CMG against GBM cells. CMG induced cell death of human GBM cells lines (T98G, U251MG, and U87MG) by dose dependent manner by triggering multiple forms of cell death such as apoptosis and perthanatos. Immunoblotting of CMG-treated GBM cell lysates demonstrated activation of multiple cell death signaling. Furthermore, immunodeficiency mice harboring intracerebral U87MG cell xenografts systemically treated by CMG showed significantly prolonged survival compared with control mice. These results suggest CMG would be a novel therapeutic agent against GBM cases.


2021 ◽  
Author(s):  
Tobias Schmidt ◽  
Robin Kahn ◽  
Fredrik Kahn

Objective To investigate the effects of high dose ascorbic acid (AA) on monocyte polarization and cytokine production in vitro Design Experimental in vitro study of cells from healthy subjects and patients with sepsis Setting University research laboratory and academic hospital Subjects Six healthy controls and three patients with sepsis Interventions Monocytes were isolated from whole blood of healthy donors (n=6) and polarized in vitro for 48hrs using LPS or LTA. Polarization was confirmed by surface marker expression using flow cytometry. As a comparison, monocytes were also isolated from septic patients (n=3) and analyzed for polarization markers. The effect of AA on monocyte polarization was evaluated. As a functional assay, AA-treated monocytes were analyzed for cytokine production of TNF and IL-8 by intracellular staining and flow cytometry following activation with LPS or LTA. Measurements and Main Results Both LPS and LTA induced polarization in healthy monocytes in vitro, with increased expression of both pro- (CD40 and PDL1, p<0.05) and anti-inflammatory (CD16 and CD163, p<0.05) polarization markers, with non-significant effects on CD86 and CD206. This pattern resembled, at least partly, that of monocytes from septic patients. Treatment with AA significantly inhibited the upregulation of surface expression of CD16 and CD163 (p<0.05) in a dose dependent manner, but not CD40 or PDL-1. Finally, AA attenuated LPS or LTA-induced cytokine production of IL-8 and TNF in a dose-dependent manner (both p<0.05). Conclusions AA inhibits upregulation of anti-, but not pro-inflammatory related markers in LPS or LTA polarized monocytes. Additionally, AA attenuates cytokine production from in vitro polarized monocytes, displaying functional involvement. This study provides important insight into the immunological effects of high dose AA on monocytes, and potential implications in sepsis.


2009 ◽  
Vol 77 (9) ◽  
pp. 3826-3837 ◽  
Author(s):  
Anna Martner ◽  
Susann Skovbjerg ◽  
James C. Paton ◽  
Agnes E. Wold

ABSTRACT Streptococcus pneumoniae is a major pathogen in humans. The pathogenicity of this organism is related to its many virulence factors, the most important of which is the thick pneumococcal capsule that minimizes phagocytosis. Another virulence-associated trait is the tendency of this bacterium to undergo autolysis in stationary phase through activation of the cell wall-bound amidase LytA, which breaks down peptidoglycan. The exact function of autolysis in pneumococcal pathogenesis is, however, unclear. Here, we show the selective and specific inefficiency of wild-type S. pneumoniae for inducing production of phagocyte-activating cytokines in human peripheral blood mononuclear cells (PBMC). Indeed, clinical pneumococcal strains induced production of 30-fold less tumor necrosis factor (TNF), 15-fold less gamma interferon (IFN-γ), and only negligible amounts of interleukin-12 (IL-12) compared with other closely related Streptococcus species, whereas the levels of induction of IL-6, IL-8, and IL-10 production were similar. If pneumococcal LytA was inactivated by mutation or by culture in a medium containing excess choline, the pneumococci induced production of significantly more TNF, IFN-γ, and IL-12 in PBMC, whereas the production of IL-6, IL-8, and IL-10 was unaffected. Further, adding autolyzed pneumococci to intact bacteria inhibited production of TNF, IFN-γ, and IL-12 in a dose-dependent manner but did not inhibit production of IL-6, IL-8, and IL-10 in response to the intact bacteria. Fragments from autolyzed bacteria inhibited phagocytosis of intact bacteria and reduced the in vitro elimination of pneumococci from human blood. Our results suggest that fragments generated by autolysis of bacteria with reduced viability interfere with phagocyte-mediated elimination of live pneumococci.


2003 ◽  
Vol 284 (2) ◽  
pp. R550-R557 ◽  
Author(s):  
Roy D. Goldfarb ◽  
Thomas S. Parker ◽  
Daniel M. Levine ◽  
Dana Glock ◽  
Imran Akhter ◽  
...  

Lipoprotein phospholipid (PL) plays a major role in neutralization of endotoxin. This study tested the hypothesis that prophylactic administration of a PL-enriched emulsion (PRE), which augments PL content of serum lipoproteins and neutralizes endotoxin in vitro, would preserve cardiovascular function and improve survival in porcine septic peritonitis. A control group was compared with low-, mid-, and high-dose treatment groups that received PRE by primed continuous infusion for 48 h. A fibrin clot containing live Escherichia coli 0111.B4 was implanted intraperitoneally 30 min after the priming dose. Survival increased in a dose-dependent manner and was correlated with serum PL. Infused PL was associated with high-density lipoprotein in the low-dose group and all serum lipoproteins at higher doses. Treatment significantly lowered serum endotoxin and tumor necrosis factor (TNF)-α, preserved cardiac output and ejection fraction, and attenuated increases in systemic and pulmonary vascular resistances. This study demonstrated that augmentation of lipoprotein PL via administration of PRE improved survival and offered a novel therapeutic approach to sepsis.


Author(s):  
Mengue Ngadena Yolande Sandrine ◽  
Essoh Etouke Adrien ◽  
Tchiedjo Marie Laure ◽  
Sulem Yong Nina Nindum ◽  
Fifen Ngapout Rodrigue ◽  
...  

Cameroonian farmers used Elaeis guineensis oil (EGO) named usually palm oil to reduce stress and mortality during the transportation of catfish fingerlings. The present study is aimed to evaluate the uses of EGO for stress management during the transportation of catfish fingerlings. Antioxidant activities of EGO were assessed in vitro. 1500 fingerlings were transported from Douala (Littoral Region, Cameroon) to Yaoundé (Centre Region Cameroon). The transportation was for 7 h 55 min in black tins of 10 L which contain 8 L of water and 100 fingerlings each. The following treatment was administrated: commercial anti-stress, 2, 4, and 6 drops of EGO. Control received no treatment and all groups were triplicated. After 10 fingerlings were sacrificed by decapitation. Total protein, total bilirubin (TB), triglycerides level, and lactate deshydrogenase (LDH) activity were assessed in the liver as well as oxidant stress parameters. Brain and gills were fixed for histopathological analysis. Results showed that transportation of catfish fingerlings induced a significant increase of TB level and LDH activity in the liver. Indeed, it induced cerebellar and gills necrosis. Moreover, EGO exhibits antioxidant activities in vitro against DPPH, ABTS radicals, and possesses a ferric reducing antioxidant power of 6.31 mEAG/g. This observation was confirmed in vivo by the increase in a dose-dependent manner of GSH and nitrites levels in the liver compared to control. However, the administration of 6 drops of EGO increased significantly (p < 0.05) the activity of LDH in the liver compared to control. Thus, high dose induced anaerobic respiration which was confirmed by alveolar necrosis in gills and neurodegeneration although low dose of EGO (2-4 drops) prevented those alterations compared to control. Hence, low doses of Elaeis guineensis oil can prevent liver, cerebellar and gills impairment during artisanal transportation to reduce the effects of stress.


Author(s):  
Cyril Ogbiko ◽  
Dickson Achimugu Musa ◽  
Musa Usman Dabai ◽  
Ibeabuchi Jude Ali ◽  
Abubakar Sani Yelwa ◽  
...  

Herbal medicine despite its increase usage globally is being plagued by inadequate research on their effectiveness. Stachytarpheta indica commonly known as snakeweed is used locally in the management of asthma, headache, alopecia, bronchitis, bruise, chest cold, constipation, itch, diarrhea, skin sore, vermifuge, dysentery, dysmenorrhea among others. This study investigated the phytochemical composition, quantitative proximate parameters and in vitro anti-inflammatory activity of the leaves of S. indica using established methods. Results confirmed the presence of alkaloids, saponins, carbohydrate, cardiac glycosides, terpenoid, tannin, anthraquinones, phenolics and flavonoid. Moisture content (9.16 ± 0.04%), total ash (19.42 ± 0.15%), water insoluble ash (7.17 ± 0.22%), acid insoluble ash (3.63 ± 0.26%), alcohol soluble extractive (0.99 ± 0.06%) and water-soluble extractive (0.36 ± 0.02%) values were obtained from the quantitative proximate analysis. An infusion of the methanol leaf extract of Stachytarpheta indica demonstrated significant anti-inflammatory activity in a dose dependent manner comparable to that of indomethacin standard.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 921-921
Author(s):  
Enriqueta Coll-Sangrona ◽  
Ali Amirkhosravi ◽  
Alshad S. Lalani ◽  
Liza Robles ◽  
Hina Desai ◽  
...  

Abstract Calcitriol, the hormonally-active metabolite of Vitamin D3, plays critical roles in calcium homeostasis, cell growth and differentiation, and immunoregulation. The anti-tumor activities of high-dose calcitriol have been demonstrated in a variety of preclinical models of solid tumors, leukemias and lymphomas. Recently, a new dose-intense formulation of calcitriol, termed DN-101 (Asentar™), was developed specifically for cancer therapy which allows for supraphysiological concentrations of calcitriol to be safely delivered in vivo to patients with cancer. In a recent Phase 2 clinical trial, DN-101 significantly increased overall survival and also reduced the incidence of thromboembolic events in men with androgen-independent prostate cancer receiving docetaxel-based chemotherapy. Based on previous observations we hypothesized that calcitriol’s anti-thrombotic effects in vivo may be due to the downregulation of Tissue Factor (TF) antigen and activity and/or upregulation of Thrombomodulin (TM). To test this hypothesis, we incubated A549 lung carcinoma, A375-C15 metastatic melanoma, THP-1 monocytic leukemia, and Eahy926 endothelial cells with increasing concentrations of calcitriol for 24 hrs. For TF induction, tumor cells were stimulated with TNFα for 5 hrs and activity was measured by a clotting assay and a thrombin generation assay (TGA). TM activity was measured by a chromogenic assay. TF and TM surface antigen were assessed by flow cytometry. Calcitriol prevented the induction of TF in TNFα-stimulated THP-1 cells in a dose-dependent manner (from 33% at 1 nM to 94% at 100 nM) as evidenced by a prolongation of plasma clotting time, a decrease in endogenous thrombin potential (ETP), and a reduction of surface TF antigen. In addition, the activity and surface expression of TM on THP-1 cells was increased significantly (40% and 3-fold respectively, P < 0.01) following 100 nM calcitriol treatment. Similarly, in TNFα-stimulated melanoma cells, calcitriol prevented the induction of TF activity (from 26% at 1 nM to 60% at 1 μM) and expression in a dose-dependent manner. High-dose calcitriol treatment also increased melanoma cell TM activity between 8% and 62%. In contrast, constitutively expressed TF activity and antigen were less affected by calcitriol in A549 lung carcinoma cells (12 to 28% reduction at concentrations between 1–100 nM) whilst TM activity and antigen were unaffected. In comparison to the tumor cells, calcitriol had no significant effect on TM or TF activity or antigen in TNFα-stimulated EAhy926 endothelial cells. In conclusion, we have demonstrated that high concentrations of calcitriol inhibit the induction of surface TF expression and upregulates TM in multiple tumor cell lines in vitro. The degree of the inhibition is proportional to the extent of TF induction by TNF-α. These in vitro results provide further support for the anticoagulant properties associated with high concentrations of calcitriol and may provide a rationale for understanding the lower incidence of thromboembolic complications observed in patients with metastatic prostate cancer treated with DN-101.


Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 681 ◽  
Author(s):  
Renuka V. Iyer ◽  
Orla Maguire ◽  
Minhyung Kim ◽  
Leslie I. Curtin ◽  
Sandra Sexton ◽  
...  

The multikinase inhibitor sorafenib is the only standard first-line therapy for hepatocellular carcinoma (HCC). Here, we report the dose-dependent effects of sorafenib on the immune response, which is related to nuclear factor of activated T cells 1 (NFAT1) activity. In vitro and in vivo experiments were performed with low and high doses of sorafenib using human T cells and spontaneous developed woodchuck HCC models. In vitro studies demonstrated that following exposure to a high dose of sorafenib the baseline activity of NFAT1 in T cells was significantly increased. In a parallel event, high dose sorafenib resulted in a significant decrease in T cell proliferation and increased the proportion of PD-1 expressing CD8+ T cells with NFAT1 activation. In the in vivo model, smaller tumors were detected in the low-dose sorafenib treated group compared to the placebo and high-dose treated groups. The low-dose sorafenib group showed a significant tumor growth delay with significantly more CD3+ cells in tumor. This study demonstrates that sorafenib has immunomodulatory effects in a dose- and time-dependent manner. Higher dose of sorafenib treatment was associated with immunosuppressive action. This observed effect of sorafenib should be taken into consideration in the selection of optimum starting dose for future trials.


2019 ◽  
Vol 9 (7) ◽  
pp. 1325 ◽  
Author(s):  
Chong Li ◽  
Chaomin Liu ◽  
Jing Zhang ◽  
Honggang Li ◽  
Yan Zhou ◽  
...  

As a traditional Chinese drink, tea is favored for its rich flavor and its medicinal functionality. In this study, the in vitro bioactivities of Wushanshencha (WST; a local tea from Chongqing, China), which is processed mainly from the leaves of the wild Malus hupehensis (Pamp.) Rehd.). We assessed the scavenging capacity of tea extracts on 1, 1-diphenyl-2-picrylhydrazyl (DPPH); 2, 2′-azino-bis (3-ethylbenzthiazoline-6- sulphonic acid) diammonium salt (ABTS); and hydroxyl (OH) free radicals, and demonstrate the high antioxidant activity and dose-dependent relationship of these extracts. We also detail the anti-mutagenic effect of these tea extracts against the Salmonella typhimurium TA98 strain induced by the 2, 7-diaminofluorene (2, 7-AF) mutagen and the TA100 strain induced by the N-methyl-N′-nitro- N- nitrosoguanidine (MNNG) mutagen at concentrations of 1.25 and 2.50 mg/plate, respectively, with the high-dose groups showing better results. We investigated the anticancer mechanisms of WST extracts (40, 100, and 160 μg/mL) in HepG2 human hepatoma cells via 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay and quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR). The results showed that the proliferation of HepG2 cells was significantly inhibited in a dose-dependent manner by the tea extracts. Moreover, apoptosis in HepG2 cells was induced via upregulation of Caspase-3, Caspase-7, Caspase-8, Caspase-9, p21, p53, and Bax as well as downregulation of Bcl-2 apoptosis-associated factors, as assessed via mRNA expression levels after treating with WST extracts. The expression of inflammation-related factors, e.g., NF-κB, and Cox-2, was significantly downregulated by the WST extracts, demonstrating its inflammatory properties. Together, these observations indicated that WST extracts have anti-inflammatory and anti-cancer properties. In addition, high-performance liquid chromatography (HPLC) analysis showed that WST extracts contained chlorogenic acid, 4-hydroxycinnamic acid, isoquercitrin, taxifolin, quercitrin, rosmarinic acid, myricetin, baicalin, neosperidin dihydrochalcone, and quercetin. As such, WST appears to be an effectively functional drink, due to its rich functional components and anti-cancer activity.


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