Structure and hemolytic activity relationships of triterpenoid saponins and sapogenins

We evaluated the hemolytic activity of 41 commercially available triterpenoid saponins and sapogenins derived from three types of structural skeletons. Structure–activity relationships were established by comparing the structural characteristics of both the aglycone and sugar moieties among the tested compounds. The majority of oleanane-type sapogenins had stronger hemolytic effects than those of the ursane and dammarane types. The presence of polar regions on sapogenins, such as a carboxyl (COOH) at position 28, an α-hydroxyl (α-OH) at position 16, and/or a β-hydroxyl (β-OH) at position 2, significantly enhanced hemolysis. Meanwhile, the introduction of an α-OH at position 2 or a methyl hydroxyl (CH₂OH) at positions 23 or 24 was closely associated with reduced activity. Our findings suggest that not only the complexity of sugar moieties but also the types and stereochemical configurations of functional groups at different positions, as well as the skeleton types, are important structural features affecting hemolytic potential. Our results provide a baseline in terms of the toxicity of saponins and sapogenins to erythrocytes, which holds promise for drug development.     

Chemosensitizing Effect of Saikosaponin B on B16F10 Melanoma Cells

Cancer cell resistance to chemotherapy is one of the obstacles for better cancer treatment, and inflammatory signaling pathways, such as NF-κB signaling pathway, have been recognized to be involved in such chemoresistance. In this study, we aim to identify a new approach for overcoming cancer chemoresistance by using natural compounds. As a result of screening by using Murine B16F10 melanoma cell line constitutively expressing NF-κB luciferase reporter gene, we identified Saikosaponin B2 as an effective inhibitor for etoposide-induced NF-κB activation in B16F10NFkB cells. Saikosaponin B2 sensitized etoposide-induced cell death in B16F10 melanoma cells through the induction of apoptosis. Along with apoptosis induction, we observed an induction of γ-H2AX expression, which is a molecular signature for DNA damage, upon the combination treatment of etoposide and Saikosaponin B2. Among Saikosaponin family compounds, we found that Saikosaponin B1, but not Saikosaponin A, sensitized etoposide-induced cytotoxicity implicating the structural requirement of Saikosaponin B for such chemosensitization. By testing the combination of Saikosaponin B1 and B2 with 9 clinical anticancer drugs, Saikosaponin B showed a certain preference in the combination with those tested anticancer drugs. Collectively, we conclude Saikosaponin B can be an attractive adjuvant for enhancing the clinical effect of cancer chemotherapy.     

Recurrent infarctions due to a dome-shaped pannus above the mitral valve prosthesis

This report describes a unique case of a 56-year-old female who suffered from recurrent stroke after double mechanical valve replacement. During the four years after the surgery, she remained in normal sinus rhythm, received adequate anticoagulation therapy, and no apparent left atrial thrombus was detected. She underwent redo surgery to prevent further stroke after fourth instance of cerebral infarction. Intraoperative findings revealed a ‘dome-shaped’ pannus formation covering the sewing ring of the mitral prosthesis circumferentially, probably leading to clot formation and repeated infarctions. She has been stroke free for three years after pannus resection.