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Ting Liu - One of the best experts on this subject based on the ideXlab platform.

  • the plant alkaloid tetrandrine inhibits metastasis via autophagy dependent wnt β catenin and metastatic tumor antigen 1 signaling in human liver cancer cells
    Journal of Experimental & Clinical Cancer Research, 2018
    Co-Authors: Zhenxing Zhang, Ting Liu
    Abstract:

    Tetrandrine is a bisbenzylisoquinoline alkaloid isolated from the Chinese medicinal herb Stephania tetrandra S. Moore. We previously demonstrated that tetrandrine exhibits potent antitumor effects in many types of cancer cells. In this study, we investigated the effects of tetrandrine on human hepatocellular carcinoma (HCC) metastasis. The invasion and migration effects were evaluated via wound healing and transwell assays. Immunofluorescence and western blotting analyses were used to investigate the levels of epithelial-mesenchymal transition (EMT)-related protein. A metastasis model was established to investigate the inhibitory effect of tetrandrine on hepatocellular carcinoma metastasis in vivo. Tetrandrine inhibits HCC invasion and migration by preventing cell EMT. The underlying mechanism was closely associated with tetrandrine-induced human liver cell autophagy, which inhibits Wnt/β-catenin pathway activity and decreases metastatic tumor antigen 1 (MTA1) expression to modulate cancer cell metastasis. Our findings demonstrate, for the first time, that tetrandrine plays a significant role in the inhibition of human hepatocellular carcinoma metastasis and provide novel insights into the application of tetrandrine in clinical HCC treatment.

  • The plant alkaloid tetrandrine inhibits metastasis via autophagy-dependent Wnt/β-catenin and metastatic tumor antigen 1 signaling in human liver cancer cells
    BMC, 2018
    Co-Authors: Zhenxing Zhang, Ting Liu
    Abstract:

    Abstract Background Tetrandrine is a bisbenzylisoquinoline alkaloid isolated from the Chinese medicinal herb Stephania tetrandra S. Moore. We previously demonstrated that tetrandrine exhibits potent antitumor effects in many types of cancer cells. In this study, we investigated the effects of tetrandrine on human hepatocellular carcinoma (HCC) metastasis. Methods The invasion and migration effects were evaluated via wound healing and transwell assays. Immunofluorescence and western blotting analyses were used to investigate the levels of epithelial-mesenchymal transition (EMT)-related protein. A metastasis model was established to investigate the inhibitory effect of tetrandrine on hepatocellular carcinoma metastasis in vivo. Results Tetrandrine inhibits HCC invasion and migration by preventing cell EMT. The underlying mechanism was closely associated with tetrandrine-induced human liver cell autophagy, which inhibits Wnt/β-catenin pathway activity and decreases metastatic tumor antigen 1 (MTA1) expression to modulate cancer cell metastasis. Conclusion Our findings demonstrate, for the first time, that tetrandrine plays a significant role in the inhibition of human hepatocellular carcinoma metastasis and provide novel insights into the application of tetrandrine in clinical HCC treatment

  • tetrandrine a chinese plant derived alkaloid is a potential candidate for cancer chemotherapy
    Oncotarget, 2016
    Co-Authors: Ting Liu, Xin Liu
    Abstract:

    Cancer is a disease caused by the abnormal proliferation and differentiation of cells governed by tumorigenic factors. Chemotherapy is one of the major cancer treatment strategies, and it functions by targeting the physiological capabilities of cancer cells, including sustained proliferation and angiogenesis, the evasion of programmed cell death, tissue invasion and metastasis. Remarkably, natural products have garnered increased attention in the chemotherapy drug discovery field because they are biologically friendly and have high therapeutic effects. Tetrandrine, isolated from the root of Stephania tetrandra S Moore, is a traditional Chinese clinical agent for silicosis, autoimmune disorders, inflammatory pulmonary diseases, cardiovascular diseases and hypertension. Recently, the novel anti-tumor effects of tetrandrine have been widely investigated. More impressive is that tetrandrine affects multiple biological activities of cancer cells, including the inhibition of proliferation, angiogenesis, migration, and invasion; the induction of apoptosis and autophagy; the reversal of multidrug resistance (MDR); and the enhancement of radiation sensitization. This review focuses on introducing the latest information about the anti-tumor effects of tetrandrine on various cancers and its underlying mechanism. Moreover, we discuss the nanoparticle delivery system being developed for tetrandrine and the anti-tumor effects of other bisbenzylisoquinoline alkaloid derivatives on cancer cells. All current evidence demonstrates that tetrandrine is a promising candidate as a cancer chemotherapeutic.

Shinjiro Kobayashi - One of the best experts on this subject based on the ideXlab platform.

  • tetrandrine prevents bone loss in sciatic neurectomized mice and inhibits receptor activator of nuclear factor κb ligand induced osteoclast differentiation
    Biological & Pharmaceutical Bulletin, 2012
    Co-Authors: Tatsuo Takahashi, Masaaki Nomura, Yusuke Tonami, Mami Tachibana, Tsutomu Shimada, Masaki Aburada, Shinjiro Kobayashi
    Abstract:

    One of the mediators of osteoclast differentiation is receptor activator of nuclear factor κB ligand (RANKL), which is produced by osteoblasts. Binding of RANKL to its receptor, RANK, activates several signaling pathways, including those involving mitogen-activated protein kinases (MAPKs), nuclear factor κB (NF-κB), nuclear factor of activated T cells c1 (NFATc1) and Ca(2+)-calcineurin. In the present study, we found that tetrandrine, a bisbenzylisoquinoline alkaloid extracted from the root of Stephania tetrandra S. MOORE, significantly ameliorated the decrease of bone mass in sciatic-neurectomized osteoporosis model mice. It appears that tetrandrine acts directly on osteoclast precursors, since tetrandrine inhibited osteoclast differentiation not only in mouse bone marrow cells, but also in monocultures of murine macrophage RAW 264.7 cells without osteoblasts. Tetrandrine suppressed RANKL-induced amplification of NFATc1, a master regulator of osteoclast differentiation. However, it did not affect other signaling molecules such as MAPKs and NF-κB. These results suggest that tetrandrine is a candidate for the treatment of bone-destructive diseases, or at least a suitable lead compound for further development.

  • effects of oral administration of Stephania tetrandra s moore on neovascularization of retinal and choroidal capillaries of diabetes in rats
    Phytotherapy Research, 2008
    Co-Authors: Taiki Tsutsumi, Nobuyoshi Hagino, Xiaochun Liang, Saishan Guo, Shinjiro Kobayashi
    Abstract:

    In rats, an injection of streptozotocin (STZ) elevated blood levels of glucose 4 weeks later (STZ-induced diabetes) and an over-production of microvessels of retinal and choroidal capillaries of eyes developed. A previous study has shown that administration of Stephania tetrandra S. Moore (STSM) in culture prevented the over-production of microvessels of those capillaries of STZ-induced diabetes in vitro. Therefore, the study investigated whether or not orally administered STSM could inhibit over-production of microvessels of those capillaries of STZ injected rats in vivo. When STSM was given at the same time as the STZ injection and continued daily for 7 weeks, STSM prevented the elevation of blood glucose level and over-production of microvessels of those capillaries. When STSM was given after elevation of blood glucose level of glucose (4 weeks after STZ injection) and continued daily for 4 weeks, STSM lowered the elevated blood glucose level but had no effect on the over-production of microvessels of those capillaries. It was inferred that deposition of N(epsilon)(carboxymethyl) lysine in retinal and choroidal tissues, which is induced by STZ-induced diabetes may deteriorate the blood-retinal barrier and the blood-choroidal barrier. One might, therefore, speculate that advanced STZ-induced diabetes may deteriorate the blood-retinal barrier and blood-choroidal barrier. Therefore, STSM may not reach the retinal and choroidal tissues in the posterior ocular region in vivo.

  • Combined effects of fangchinoline from Stephania tetrandra Radix and formononetin and calycosin from Astragalus membranaceus Radix on hyperglycemia and hypoinsulinemia in streptozotocin-diabetic mice.
    Biological & pharmaceutical bulletin, 2007
    Co-Authors: Masaaki Nomura, Tatsuo Takahashi-nishioka, Shinjiro Kobayashi
    Abstract:

    The anti-hyperglycemic action of Stephania tetrandra Radix (Stephania) is potentiated by Astragalus membranaceus BUNGE Radix (Astragali) in streptozotocin (STZ)-diabetic ddY mice (Tsutsumi et al., Biol. Pharm. Bull., 26, 313 (2003)). Fangchinoline (0.3-3 mg/kg), a main constituent of Stephania, decreased the high level of blood glucose and increased the low level of blood insulin in STZ-diabetic mice. Here, we investigated the combined effects of fangchinoline with isoflavone or isoflavonoid components (formononetin, calycosin and ononin) of Astragali on the hyperglycemia and hypoinsulinemia of STZ-diabetic mice. Formononetin, calycosin and ononin (0.03-0.1 mg/kg) alone did not affect the blood glucose or blood insulin level of the diabetic mice. Formononetin and calycosin (0.03-0.1 mg/kg) potentiated the anti-hyperglycemic action of fangchinoline (0.3 mg/kg), but ononin did not. Formononetin (0.1 mg/kg) facilitated the fangchinoline-induced insulin release, and calycosin (0.1 mg/kg) also facilitated it, though without statistical significance. In conclusion, the combined effect of fangchinoline with formononetin and calycosin on hyperglycemia in the diabetic mice accounted well for the therapeutic effect of the combination of Stephania with Astragali in Boi-ogi-to. The anti-hyperglycemic action of formononetin appeared to be due to its potentiating action on insulin release. Our strategy for studying combinations of crude drugs and their components in Kampo medicine has uncovered new potentiating effects of formononetin and calycosin on the anti-hyperglycemic action of fangchinoline in STZ-diabetic mice.

  • Anti-hyperglycemic Effect of Fangchinoline Isolated from Stephania tetrandra Radix in Streptozotocin-Diabetic Mice
    Biological & pharmaceutical bulletin, 2003
    Co-Authors: Taiki Tsutsumi, Shinjiro Kobayashi, Yuan Ying Liu, Hitoshi Kontani
    Abstract:

    Kampo medicine, Stephania tetrandra Radix (Stephania) in Boi-ogi-to increases the blood insulin level and falls the blood glucose level in streptozotocin (STZ)-diabetic ddY mice. These actions of Stephania are potentiated by Astragalus membranaceus Bunge Radix (Astragali) in Boi-ogi-to (Liu et al., J. Traditional Med., 17, 253-260, 2000). In the present study, actions of bis-benzylisoquinoline alkaloids isolated from Stephania were investigated in the hyperglycemia of STZ-diabetic mice. A main bis-benzylisoquinoline alkaloid, fangchinoline (0.3-3 mg/kg) significantly fell the blood glucose level of the diabetic mice in a dose-dependent manner. The effect of fangchinoline was 3.9-fold greater than that of water extract of Stephania. However, another main compound, tetrandrine (1-100 mg/kg) did not have any effect. The water extract of Astragali did not affect singly but potentiated the anti-hyperglycemic action of fangchinoline (0.3 mg/kg). Out of used compounds (1 mg/kg) isolated from Stephania, fangchinoline, fangchinoline 2'-N-alpha-oxide and 2'-N-norfangchinoline, which are substituted with 7-hydroxy side chain for 7-O-methyl side chain, decreased to near 50% of high blood glucose level. In addition, tetrandrine 2'-N-beta-oxide, tetrandrine 2'-N-alpha-oxide, tetrandrine 2-N-beta-oxide, fangchinoline 2'-N-alpha-oxide, which are added to 2- or 2'-N-oxide side chain, also decreased to near 50% of the high blood glucose level. In conclusion, fangchinoline but not tetrandrine from Stephania shows the anti-hyperglycemic action in the STZ-diabetic mice. The demethylation of 7-O-position and/or addition of 2- or 2'-N-oxide side chain in bis-benzylisoquinoline compounds in Stephania have a role for the induction of the anti-hyperglycemic actions.

  • therapeutic efficacy of Stephania tetrandra s moore for treatment of neovascularization of retinal capillary retinopathy in diabetes in vitro study
    Phytomedicine, 2002
    Co-Authors: Xiaochun Liang, Taiki Tsutsumi, Nobuyoshi Hagino, Saishan Guo, Shinjiro Kobayashi
    Abstract:

    Summary The present study was designed to examine therapeutic efficacy of the root extract of Stephania tetrandra S. Moore (STMS) (traditional Chinese medicine; Han Fang Ji) for treatment of neovascularization of the retinal capillary (retinopathy) in streptozotocin (STZ)-induced diabetic rats (STZ diabetic rats) in culture. Recently we have established the culture system in which fetal bovine serum (FBS) in Dulbecco modified Eagle medium (DMEM) induced neovascularization of the retinal capillary and choroidal capillary in normal rats in culture. STZ diabetic rats showed more neovascularization of the retinal capillary and choroidal capillary than did normal rats in culture. In this study, the retinal tissue was removed for the posterior ocular region and cultured in DMEM containing FBS. The choroidal tissue of the posterior ocular region was also removed and cultured as an internal reference. Administration of STSM (0.91, 9.1 and 91 μg/ml) significantly suppressed neovascularization of the retinal capillary in both STZ diabetic rats and normal rats in a dose-dependent manner. Similar results were obtained with the choroidal capillary; administration of STSM suppressed neovascularization of the choroidal capillary in both STZ diabetic rats and normal rats. In order to determine the component of STSM inhibiting neovascularization of the retinal capillary, tetrandrine (a major chemical constituent of STSM) was administered and neovascularization of the retinal capillary was examined in culture. The effect of tetrandrine on the choroidal capillary was also examined as an internal reference. Administration of tetrandrine (0.1, 1.0 and 10 μM) suppressed neovascularization of the retinal capillary in both STZ diabetic rats and normal rats in a dose-dependent manner. Similar results were obtained with the choroidal capillary of both STZ diabetic rats and normal rats. We infer, therefore, that STSM has a direct effect on the retinal capillary of posterior ocular region and suppresses neovascularization of retinal capillary in STZ diabetic rats through the activation of tetrandrine. These results suggest that STSM may prevent for delay the progression of retinopathy in diabetic patients.

Kwang Ho Pyun - One of the best experts on this subject based on the ideXlab platform.

  • anti inflammatory effects of Stephania tetrandra s moore on interleukin 6 production and experimental inflammatory disease models
    Mediators of Inflammation, 1996
    Co-Authors: Hyung Sik Kang, Young Ho Kim, Chulsung Lee, Jung Joon Lee, In Pyo Choi, Kwang Ho Pyun
    Abstract:

    Deregulation of interleukin-6 (IL-6) expression caused the synthesis and release of many inflammatory mediators. It is involved in chronic inflammation, autoimmune diseases, and malignancy. Stephania tetrandra S. Moore is a Chinese medicinal herb which has been used traditionary as a remedy for neuralgia and arthritis in China. To investigate the anti-inflammatory effects of S. tetrandra S. Moore in vitro and in vivo, its effects on the production of IL-6 and inflammatory mediators were analysed. When human monocytes/macrophages stimulated with silica were treated with 0.1–10 μg/ml S. tetranda S. Moore, the production of IL-6 was inhibited up to 50%. At these concentrations, it had no cytotoxicity effect on these cells. It also suppressed the production of IL-6 by alveolar macrophages stimulated with silica. In addition, it inhibited the release of superoxide anion and hydrogen peroxide from human monocytes/macrophages. To assess the anti-fibrosis effects of S. tetrandra S. Moore, its effects on in vivo experimental inflammatory models were evaluated. In the experimental silicosis model, IL-6 activities in the sera and in the culture supernatants of pulmonary fibroblasts were also inhibited by it. In vitro and in vivo treatment of S. tetrandra S. Moore reduced collagen production by rat lung fibroblasts and lung tissue. Also, S. tetrandra S. Moore reduced the levels of serum GOT and GPT in the rat cirrhosis model induced by CCL4, and it was effective in reducing hepatic fibrosis and nodular formation. Taken together, these data indicate that it has a potent anti-inflammatory and antifibrosis effect by reducing IL-6 production.

  • Anti-inflammatory effects of Stephania tetrandra S. moore on interleukin-6 production and experimental inflammatory disease models
    Taylor & Francis, 1996
    Co-Authors: Hyung Sik Kang, Young Ho Kim, Jung Joon Lee, In Pyo Choi, C S Lee, Kwang Ho Pyun
    Abstract:

    Deregulation of interleukin-6 (IL-6) expression caused the synthesis and release of many inflammatory mediators. It is involved in chronic inflammation, autoimmune diseases, and malignancy. Stephania tetrandra S. Moore is a Chinese medicinal herb which has been used traditionally as a remedy for neuralgia and arthritis in China. To investigate the anti-inflammatory effects of S. tetrandra S. Moore in vitro and in vivo, its effects on the production of IL-6 and inflammatory mediators were analysed. When human monocytes/macrophages stimulated with silica were treated with 0.1-10 μg/ml S. tetranda S. Moore, the production of IL-6 was inhibited up to 50%. At these concentrations, it had no cytotoxicity effect on these cells. It also suppressed the production of IL-6 by alveolar macrophages stimulated with silica. In addition, it inhibited the release of superoxide anion and hydrogen peroxide from human monocytes/macrophages. To assess the anti-fibrosis effects of S. tetrandra S. Moore, its effects on in vivo experimental inflammatory models were evaluated. In the experimental silicosis model, IL-6 activities in the sera and in the culture supernatants of pulmonary fibroblasts were also inhibited by it. In vitro and in vivo treatment of S. tetrandra S. Moore reduced collagen production by rat lung fibroblasts and lung tissue. Also, S. tetrandra S. Moore reduced the levels of serum GOT and GPT in the rat cirrhosis model induced by CCl4, and it was effective in reducing hepatic fibrosis and nodular formation. Taken together, these data indicate that it has a potent anti-inflammatory and antifibrosis effect by reducing IL-6 production.ope

Zhenxing Zhang - One of the best experts on this subject based on the ideXlab platform.

Hyeong Kyu Lee - One of the best experts on this subject based on the ideXlab platform.

  • effects of tetrandrine and fangchinoline on human platelet aggregation and thromboxane b2 formation
    Journal of Ethnopharmacology, 1999
    Co-Authors: Hack Seang Kim, Yong He Zhang, Lian Hua Fang, Yeo Pyo Yun, Hyeong Kyu Lee
    Abstract:

    Abstract Tetrandrine (TET) and fangchinoline (FAN) are two major components of the radix of Stephania tetrandra . The effects of TET and FAN on human platelet aggregation and formation of thromboxane (TX) B 2 , a stable metabolite of TXA 2 , were examined in the aspect of platelet aggregation. TET and FAN inhibited platelet-activating factor (PAF)-induced human platelet aggregation. IC 50 values for TET and FAN were 28.6±3.24 μM and 21.7±2.61 μM, respectively. In the PAF-receptor binding assay, neither TET nor FAN showed any inhibitory effects on the specific bindings of PAF to its receptor. TET and FAN also inhibited PAF-, thrombin- and arachidonic acid-induced thromboxane B 2 formation in human washed platelet. These results indicate that TET and FAN inhibit the platelet aggregation by interfering with the intracellular messengers system, but not by inhibiting the binding of PAF to PAF-receptor on the platelet membrane directly, and the suppression of TXA 2 formation by TET and FAN may be responsible for their inhibitory activities on the platelet aggregation and further on the thrombosis.

  • Effects of tetrandrine and fangchinoline on human platelet aggregation and thromboxane B₂formation
    Elsevier, 1999
    Co-Authors: Hack Seang Kim, Yong He Zhang, Lian Hua Fang, Yeo Pyo Yun, Hyeong Kyu Lee
    Abstract:

    Tetrandrine (TET) and fangchinoline (FAN) are two major components of the radix of Stephania tetrandra. The effects of TET and FAN on human platelet aggregation and formation of thromboxane (TX) B2, a stable metabolite of TXA2, were examined in the aspect of platelet aggregation. TET and FAN inhibited platelet-activating factor (PAF)-induced human platelet aggregation. IC50 values for TET and FAN were 28.6 ± 3.24 μM and 21.7 ± 2.61 μM, respectively. In the PAF-receptor binding assay, neither TET nor FAN showed any inhibitory effects on the specific bindings of PAF to its receptor. TET and FAN also inhibited PAF-, thrombin- and arachidonic acid- induced thromboxane B2 formation in human washed platelet. These results indicate that TET and FAN inhibit the platelet aggregation by interfering with the intracellular messengers system, but not by inhibiting the binding of PAF to PAF-receptor on the platelet membrane directly, and the suppression of TXA2 formation by TET and FAN may be responsible for their inhibitory activities on the platelet aggregation and further on the thrombosis.ope