Cirsimaritin

Cirsimaritin, a lung squamous carcinoma cells (NCIH-520) proliferation inhibitor

Cirsimaritin is a dimethoxy flavone, which is present in Ocimum sanctum, Microtea debilis, Artemisia judaica, Cirsium japonicum, and Lithocarpus dealbatus. Its antiproliferative potential has been explored in breast and gall bladder cancer cell lines. However, no reports are available on skin and squamous lung carcinoma. Also, the complete mode of action is unknown. Therefore, in the present study, the anticancer potential of cirsimaritin is explored in organ-specific cell lines by using MTT assay. Further, the inhibitory potential and binding interaction with the selected targets were analyzed through in vitro and in-silico analysis. Cirsimaritin showed selective anticancer activity against NCIH-520 cell-line (IC50 23.29 ?M), also inhibited the proliferation of other cell-lines up to 48% at 100 ?M. In NCIH-520 cell-line, cirsimaritin significantly increased the apoptosis of the cells at both the tested concentrations (10 and 100 ?M), which was confirmed by Annexin-V signifying the induction of late apoptosis. Besides, an increase in the ROS levels of 1.6 fold (10 ?M) and 1.8 fold (100 ?M), circimaritin also inhibits the activity of ODC and CATD with the IC50 57.30 and 68.22 ?M respectively. It exhibited a good binding score with the selected targets, follow Lipinski's rule of five and non-mutagenic. Hence, cirsimaritin is a potent molecule, which inhibits the proliferation of lung squamous cell lines by inducing apoptosis. It also inhibited the activity of ODC and CATD responsible for the progression phase in the cancer cells. Communicated by Ramaswamy H. Sarma.

The Current State of Knowledge in Biological Properties of Cirsimaritin

The search for natural plant-based products as new pharmacological alternatives to treat various human pathologies has taken on great importance for researchers and research laboratories. In this context, research has intensified to extract and identify natural molecules endowed with biological effects. The objective of this study is to review the source and pharmacological properties of cirsimaritin. The identification and isolation of this flavonoid from various natural sources, including medicinal plants such as Artemisia judaica, Cirsium japonicum, Lithocarpus dealbatus, Microtea debilis, and Ocimum sanctum, has been carried out and verified using different spectral techniques. Biological effect investigations are carried out with a wide variety of experimental models in vitro and in vivo and laboratory techniques. The results of these research works showed the biological properties of cirsimaritin including anticancer, antimicrobial, antidiabetic, antiparasitic, antioxidant, and anti-inflammatory effects. The mechanisms involved in the multiple activities of this molecule are diverse and include sub-cellular, cellular, and molecular levels. Indeed, this bioactive induces anti-inflammatory and antiproliferative effects by inhibiting cell membrane receptors, interference with signaling pathways, and inhibiting transcriptional factors such as Nf-百B involved in cell promotion and proliferation. In the light of these results, cirsimaritin appears as a promising and viable alternative natural bioactive drug to treat many pathological conditions.

Melanogenesis-inducing effect of cirsimaritin through increases in microphthalmia-associated transcription factor and tyrosinase expression

The melanin-inducing properties of cirsimaritin were investigated in murine B16F10 cells. Cirsimaritin is an active flavone with methoxy groups, which is isolated from the branches of Lithocarpus dealbatus. Tyrosinase activity and melanin content in murine B16F10 melanoma cells were increased by cirsimaritin in a dose-dependent manner. Western blot analysis revealed that tyrosinase, tyrosinase-related protein (TRP) 1, TRP2 protein levels were enhanced after treatment with cirsimaritin for 48 h. Cirsimaritin also upregulated the expression of microphthalmia-associated transcription factor (MITF) after 24 h of treatment. Furthermore, cirsimaritin induced phosphorylation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) in a dose-dependent manner after treatment for 15 min. The cirsimaritin-mediated increase of tyrosinase activity was significantly attenuated by H89, a cAMP-dependent protein kinase A inhibitor. These findings indicate that cirsimaritin stimulates melanogenesis in B16F10 cells by activation of CREB as well as upregulation of MITF and tyrosinase expression, which was activated by cAMP signaling. Finally, the melanogenic effect of cirsimaritin was confirmed in human epidermal melanocytes. These results support the putative application of cirsimaritin in ultraviolet photoprotection and hair coloration treatments.

Protective effect of cirsimaritin against streptozotocin-induced apoptosis in pancreatic beta cells

Objectives: Maintaining glucose homoeostasis is essential for the survival of cells. Despite the various health benefits of Korean thistle (Cirsium japonicum var. maackii), their effects on pancreatic 汕-cell apoptosis in type 1 diabetes mellitus and the underlying mechanisms remain unclear, and experimentally investigated in this study.
Methods: The effects of C. japonicum var. maackii and its active component cirsimaritin against streptozotocin (STZ)-induced cytotoxicity were assessed in INS-1 cells. By Western blotting analysis, protein expressions related to apoptosis were evaluated. The involvement of apoptosis was also confirmed with image-based cytometric assay and caspase activity tests.
Key findings: Cirsium japonicum var. maackii extract and cirsimaritin in non-toxic concentrations improved cell viability to near normal levels and protected INS-1 cells against STZ-induced damage. In addition, cirsimaritin reduced the intracellular oxidative stress induced by STZ. Cirsimaritin effectively suppressed apoptosis in pancreatic 汕 cells by decreasing the activation of caspase-8 and caspase-3, BID and the DNA repair protein poly (ADP-ribose) polymerase (PARP) and increasing anti-apoptotic BCL-2 protein expression.
Conclusions: This study demonstrates the therapeutic potential and action mechanism of cirsimaritin for the prevention and treatment of type 1 diabetes mellitus.

Santin and cirsimaritin from Betula pubescens and Betula pendula buds induce apoptosis in human digestive system cancer cells

Flavonoids are bioactive secondary metabolites of plants, which exert anti-cancer effects. However, metabolism in enterocytes and the liver can influence the biological activity of flavonoids contained in the diet. Therefore, results from in vitro studies on cancer cells from the digestive tract and liver may reflect the real effects in the human body. Previously, we have found that the extract from birch buds exerts antiproliferative activity in a panel of cancer cells. In the present study, the anti-cancer activity of ten flavonoids isolated from the buds of Betula pubescens and Betula pendula was characterized. Among them, santin and cirsimaritin significantly reduced viability, proliferation and clonogenicity of gastric (AGS), colon (DLD-1) and liver (HepG2) cancer cells. Both flavonoids induced apoptosis, accompanied by activation of caspase-3, caspase-7, caspase-8 and caspase-9. Moreover, upregulation of p53 was detected only in wild-type p53 harbouring cells. Together, our results suggest that santin and cirsimaritin exhibit promising anti-cancer activity in cultures of digestive system cancer cells.