Inhibitory effect of cepharanthine on dendritic cell activation and function

Uto, Takuhiro; Nishi, Yosuke; Toyama, Masaaki; Yoshinaga, Keisuke; Baba, Masanori

doi:10.1016/j.intimp.2011.08.003

Cited by 22 publications

(19 citation statements)

References 32 publications

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“…It is shown to reduce IL-6 and TNF-α secretion in LPS-stimulated DCs, and inhibits LPS-stimulated DC maturation and antigen uptake by DCs [793]. CEP-treated DCs becomes a poor stimulator of allogeneic T cell activation and reduces IFN-γ production [793]. Therefore, it is suggested that CEP may have potential to be a cancer immunomodulatory agent.…”

Section: Cepharanthine (Cep)mentioning

confidence: 99%

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

et al. 2019

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Numerous natural products originated from Chinese herbal medicine exhibit anti-cancer activities, including antiproliferative, pro-apoptotic, anti-metastatic, anti-angiogenic effects, as well as regulate autophagy, reverse multidrug resistance, balance immunity, and enhance chemotherapy in vitro and in vivo. To provide new insights into the critical path ahead, we systemically reviewed the most recent advances (reported since 2011) on the key compounds with anti-cancer effects derived from Chinese herbal medicine (curcumin, epigallocatechin gallate, berberine, artemisinin, ginsenoside Rg3, ursolic acid, silibinin, emodin, triptolide, cucurbitacin B, tanshinone I, oridonin, shikonin, gambogic acid, artesunate, wogonin, β-elemene, and cepharanthine) in scientific databases (PubMed, Web of Science, Medline, Scopus, and Clinical Trials). With a broader perspective, we focused on their recently discovered and/or investigated pharmacological effects, novel mechanism of action, relevant clinical studies, and their innovative applications in combined therapy and immunomodulation. In addition, the present review has extended to describe other promising compounds including dihydroartemisinin, ginsenoside Rh2, compound K, cucurbitacins D, E, I, tanshinone IIA and cryptotanshinone in view of their potentials in cancer therapy. Up to now, the evidence about the immunomodulatory effects and clinical trials of natural anti-cancer compounds from Chinese herbal medicine is very limited, and further research is needed to monitor their immunoregulatory effects and explore their mechanisms of action as modulators of immune checkpoints.

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Section: Cepharanthine (Cep)mentioning

confidence: 99%

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

et al. 2019

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“…CEP can reduce the production of IL-6 and TNF-α in LPS-stimulated dendritic cells (Uto et al, 2011). The potent anti-inflammatory activity of CEP speaks for the potential use of the drug for treating systemic inflammatory response syndromes such as sepsis.…”

Section: Immuno-modulation -Treatment Of Sepsis Chronic Immune Thrommentioning

confidence: 99%

Cepharanthine: An update of its mode of action, pharmacological properties and medical applications

2019

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A B S T R A C TBackground: Cepharanthine (CEP) is a drug used in Japan since the 1950s to treat a number of acute and chronic diseases, including treatment of leukopenia, snake bites, xerostomia and alopecia. It is the only approved drug for Human use in the large class of bisbenzylisoquinoline alkaloids. This natural product, mainly isolated from the plant Stephania cephalantha Hayata, exhibits multiple pharmacological properties including anti-oxidative, anti-inflammatory, immuno-regulatory, anti-cancer, anti-viral and anti-parasitic properties. Purpose: The mechanism of action of CEP is multifactorial. The drug exerts membrane effects (modulation of efflux pumps, membrane rigidification) as well as different intracellular and nuclear effects. CEP interferes with several metabolic axes, primarily with the AMP-activated protein kinase (AMPK) and NFκB signaling pathways. In particular, the anti-inflammatory effects of CEP rely on AMPK activation and NFκB inhibition. Conclusion: In this review, the historical discovery and development of CEP are retraced, and the key mediators involved in its mode of action are presented. The past, present, and future of CEP are recapitulated. This review also suggests new opportunities to extend the clinical applications of this well-tolerated old Japanese drug.

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“…As we reported in our previous work, CEH could effectively reverse the MDR-mediated CDDP resistance of ESCC cells in vitro and in vivo (Zhou et al, 2017). Other studies have reported that CEH regulates immunity and possesses anti-inflammatory effects (Kondo et al, 1992; Murakami et al, 2003; Nagano et al, 2003; Seubwai et al, 2010; Rogosnitzky and Danks, 2011; Uto et al, 2011; Kao et al, 2015; Paudel et al, 2016). Nevertheless, there is no research on the effects of CEH on intestinal mucosal immunity or regulation of intestinal microbes.…”

Section: Introductionmentioning

confidence: 97%

Cepharanthine Hydrochloride Improves Cisplatin Chemotherapy and Enhances Immunity by Regulating Intestinal Microbes in Mice

Zhou

et al. 2019

Front. Cell. Infect. Microbiol.

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Chemotherapy is one of the major treatment strategies for esophageal squamous cell carcinoma (ESCC). Unfortunately, most chemotherapeutic drugs have significant impacts on the intestinal microbes, resulting in side effects and reduced efficiency. Therefore, new strategies capable of overcoming these disadvantages of current chemotherapies are in urgent need. The natural product, Cepharanthine hydrochloride (CEH), is known for its anticancer and immunoregulatory properties. By sequencing the V4 region of 16S rDNA, we characterized the microbes of tumor-bearing mice treated with different chemotherapy strategies, including with CEH. We found that CEH improved the therapeutic effect of CDDP by manipulating the gut microbiota. Through metagenomic analyses of the microbes community, we identified a severe compositional and functional imbalance in the gut microbes community after CDDP treatment. However, CEH improved the effect of chemotherapy and ameliorated CDDP treatment-induced imbalance in the intestinal microbes. Mechanically, CEH activated TLR4 and MYD88 innate immune signaling, which is advantageous for the activation of the host's innate immunity to exert a balanced intestinal environment as well as to trigger a better chemotherapeutic response to esophageal cancer. In addition, TNFR death receptors were activated to induce apoptosis. In summary, our findings suggest that chemotherapy of CDDP combined with CEH increased the effect of chemotherapy and reduced the side effects on the microbes and intestinal mucosal immunity. We believe that these findings provide a theoretical basis for new clinical treatment strategies.

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Inhibitory effect of cepharanthine on dendritic cell activation and function

Cited by 22 publications

References 32 publications

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

Cepharanthine: An update of its mode of action, pharmacological properties and medical applications

Cepharanthine Hydrochloride Improves Cisplatin Chemotherapy and Enhances Immunity by Regulating Intestinal Microbes in Mice

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