Pharmacological Activity of Cepharanthine

Liu, Ke; Hong, Bixia; Wang, Shuqi; Lou, Fuxing; You, Yecheng; Hu, Ruolan; Shafqat, Amna; Fan, Huahao; Tong, Yigang

doi:10.3390/molecules28135019

Cited by 7 publications

(3 citation statements)

References 220 publications

(647 reference statements)

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“…The inhibitory effects of bis-BIAs on SARS-CoV-2 and other coronaviruses have been attributed to various mechanisms 33 – 35 , with the blockade of calcium ion (Ca 2+ )-dependent membrane fusion by BIAs emerging as a plausible explanation. Bis-BIAs are known as hindering calcium inward flow through the physical alteration of lipid properties 36 , thereby suppressing calcium-induced responses and inhibiting membrane permeability transition (MPT) 37 , 38 . This cascade results in inhibiting Ca 2+ -mediated fusion and suppressing virus entry 34 .…”

Section: Resultsmentioning

confidence: 99%

Cepharanthine analogs mining and genomes of Stephania accelerate anti-coronavirus drug discovery

Leng,

Xu,

Hong

et al. 2024

Nat Commun

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Cepharanthine is a secondary metabolite isolated from Stephania. It has been reported that it has anti-conronaviruses activities including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Here, we assemble three Stephania genomes (S. japonica, S. yunnanensis, and S. cepharantha), propose the cepharanthine biosynthetic pathway, and assess the antiviral potential of compounds involved in the pathway. Among the three genomes, S. japonica has a near telomere-to-telomere assembly with one remaining gap, and S. cepharantha and S. yunnanensis have chromosome-level assemblies. Following by biosynthetic gene mining and metabolomics analysis, we identify seven cepharanthine analogs that have broad-spectrum anti-coronavirus activities, including SARS-CoV-2, Guangxi pangolin-CoV (GX_P2V), swine acute diarrhoea syndrome coronavirus (SADS-CoV), and porcine epidemic diarrhea virus (PEDV). We also show that two other genera, Nelumbo and Thalictrum, can produce cepharanthine analogs, and thus have the potential for antiviral compound discovery. Results generated from this study could accelerate broad-spectrum anti-coronavirus drug discovery.

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Section: Resultsmentioning

confidence: 99%

Cepharanthine analogs mining and genomes of Stephania accelerate anti-coronavirus drug discovery

Leng,

Xu,

Hong

et al. 2024

Nat Commun

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“…CEP, a natural bisbenzylisoquinoline alkaloid, has been used in the clinic for more than 70 years [ 23 ]. It has a variety of medicinal properties, including antioxidant, anti-inflammatory, immunomodulatory, antitumoral, and antiviral effects [ 23 , 24 ]. Recently, CEP and its analogues were reported to show broad-spectrum anti-coronavirus activities [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Cepharanthine synergistically promotes methylprednisolone pharmacodynamics against human peripheral blood mononuclear cells possibly via regulation of P-glycoprotein/glucocorticoid receptor translocation

Xu,

Chen,

Wang

et al. 2024

BMC Complement Med Ther

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Background Cepharanthin® alone or in combination with glucocorticoid (GC) has been used to treat chronic immune thrombocytopenia (ITP) since the 1990s. Cepharanthine (CEP) is one of the main active components of Cepharanthin®. The purpose of this study was to investigate the effects of CEP on GC pharmacodynamics on immune cells and analyse the possible action mechanism of their interactions. Methods Peripheral blood mononuclear cells (PBMCs), T lymphocytic leukemia MOLT-4 cells and daunorubicin resistant MOLT-4 cells (MOLT-4/DNR) were used to evaluate the pharmacodynamics and molecular mechanisms. Drug pharmacodynamics was evaluated by WST-8 assay. P-glycoprotein function was examined by rhodamine 123 assay. CD4+CD25+Foxp3+ regulatory T cells and Th1/Th2/Th17 cytokines were detected by flow cytometry. P-glycoprotein expression and GC receptor translocation were examined by Western blot. Results CEP synergistically increased methylprednisolone (MP) efficacy with the suppressive effect on the cell viability of PBMCs. 0.3 and 1 μM of CEP significantly inhibited P-glycoprotein efflux function of CD4+ cells, CD8+ cells, and lymphocytes (P<0.05). 0.03~3 μM of CEP also inhibited the P-glycoprotein efflux function in MOLT-4/DNR cells in a concentration-dependent manner (P<0.001). However, 0.03~3 μM of CEP did not influence P-glycoprotein expression. 0.03~0.3 μM of CEP significantly increased the GC receptor distribution from the cytoplasm to the nucleus in a concentration-dependent manner in MOLT-4/DNR cells. The combination did not influence the frequency of CD4+, CD4+CD25+ and CD4+CD25+Foxp3+ T cells or the secretion of Th1/Th2/Th17 cytokines from PBMCs. In contrast, CEP alone at 1 μM decreased the percentage of CD4+ T cell significantly (P<0.01). It also inhibited the secretion of IL-6, IL-10, IL-17, TNF-α, and IFN-γ. Conclusions CEP synergistically promoted MP pharmacodynamics to decrease the cell viability of the mitogen-activated PBMCs, possibly via inhibiting P-glycoprotein function and potentiating GC receptor translocation. The present study provides new evidence of the therapeutic effect of Cepharanthin® alone or in combination with GC for the management of chronic ITP.

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“…This appears to be harmful for cancer patients’ long-term use. The assessment of CEP localization in the management of gastric cancer is challenging and necessitates our extra focus [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Cepharanthine, a regulator of keap1-Nrf2, inhibits gastric cancer growth through oxidative stress and energy metabolism pathway

Lu,

Zhu,

Ding

et al. 2023

Cell Death Discov.

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Cepharanthine (CEP), a bioactive compound derived from Stephania Cephalantha Hayata, is cytotoxic to various malignancies. However, the underlying mechanism of gastric cancer is unknown. CEP inhibited the cellular activity of gastric cancer AGS, HGC27 and MFC cell lines in this study. CEP-induced apoptosis reduced Bcl-2 expression and increased cleaved caspase 3, cleaved caspase 9, Bax, and Bad expression. CEP caused a G2 cell cycle arrest and reduced cyclin D1 and cyclin-dependent kinases 2 (CDK2) expression. Meanwhile, it increased oxidative stress, decreased mitochondrial membrane potential, and enhanced reactive oxygen species (ROS) accumulation in gastric cancer cell lines. Mechanistically, CEP inhibited Kelch-like ECH-associated protein (Keap1) expression while activating NF-E2 related factor 2 (Nrf2) nuclear translocations, increasing transcription of Nrf2 target genes quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), and glutamate-cysteine ligase modifier subunit (GCLM). Furthermore, a combined analysis of targeted energy metabolism and RNA sequencing revealed that CEP could alter the levels of metabolic substances such as D (+) - Glucose, D-Fructose 6-phosphate, citric acid, succinic acid, and pyruvic acid, thereby altering energy metabolism in AGS cells. In addition, CEP significantly inhibited tumor growth in MFC BALB/c nude mice in vivo, consistent with the in vitro findings. Overall, CEP can induce oxidative stress by regulating Nrf2/Keap1 and alter energy metabolism, resulting in anti-gastric cancer effects. Our findings suggest a potential application of CEP in gastric cancer treatment.

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Pharmacological Activity of Cepharanthine

Cited by 7 publications

References 220 publications

Cepharanthine analogs mining and genomes of Stephania accelerate anti-coronavirus drug discovery

Cepharanthine analogs mining and genomes of Stephania accelerate anti-coronavirus drug discovery

Cepharanthine synergistically promotes methylprednisolone pharmacodynamics against human peripheral blood mononuclear cells possibly via regulation of P-glycoprotein/glucocorticoid receptor translocation

Cepharanthine, a regulator of keap1-Nrf2, inhibits gastric cancer growth through oxidative stress and energy metabolism pathway

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