The steroidal alkaloids α-tomatine and tomatidine: Panorama of their mode of action and pharmacological properties

The steroidal glycoalkaloid alpha-tomatine (alpha TM) and its aglycone tomatidine (TD) are abundant in the skin of unripe green tomato and present in tomato leaves and flowers. They mainly serve as defensive agents to protect the plant against infections by insects, bacteria, parasites, viruses, and fungi. In addition, the two products display a range of pharmacological properties potentially useful to treat various human diseases. We have analyzed all known pharmacological activities of alpha TM and TD, and the corresponding molecular targets and pathways impacted by these two steroidal alkaloids. In experimental models, alpha TM displays anticancer effects, particularly strong against androgen-independent prostate cancer, as well as robust antifungal effects. alpha TM is a potent cholesterol binder, useful as a vaccine adjuvant to improve delivery of protein antigens or therapeutic oligonucleotides. TD is a much less cytotoxic compound, able to restrict the spread of certain viruses (such as dengue, chikungunya and porcine epidemic diarrhea viruses) and to provide cardio and neuro-protective effects toward human cells. Both alpha TM and TD exhibit marked anti-inflammatory activities. They proceed through multiple signaling pathways and protein targets, including the sterol C24 methyltransferase Erg6 and vitamin D receptor, both directly targeted by TD. alpha TM is a powerful regulator of the NFkB/ERK signaling pathway implicated in various diseases. Collectively, the analysis shed light on the multitargeted action of alpha TM/TD and their usefulness as chemo-preventive or chemotherapeutic agents. A novel medicinal application for alpha TM is proposed.