The Role of Saikosaponins in Therapeutic Strategies for Age-Related Diseases
Natural products, such as herbal medicines, represent monotherapies or adjunctive therapies in the treatment of age-related diseases. Because conventional drugs have limitations and adverse side effects, the development of alternative medicines is necessary. Owing to the advantages of natural products, additional pharmaceutical agents will be discovered. Saikosaponins, which we have been studying for a long time, can be developed as novel potential drugs for future therapeutic strategies. Naturally occurring saikosaponins have been studied by different research groups and found to be very promising drug candidates for the prevention and treatment of various age-related diseases due to their multiple actions in inflammation, oxidant/antioxidant balance, and damage response.
However, despite its usefulness and potential for growth, natural product-derived medicine has not yet been widely applied in age-related diseases. As shown above, a significant portion of the research on natural products, including saikosaponins, has focused on cancer. It is still unknown whether saikosaponins exert therapeutic activity against other chronic disorders such as the forms of dementia other than AD and cardiovascular diseases other than atherosclerosis. Likewise, the therapeutic relevance of saikosaponins in the aging process remains unclear. Moreover, despite the extensive literature on the anticancer activities of saikosaponins, the cytotoxicity of saikosaponins has not been well investigated in normal cells. Therefore, it is necessary to evaluate the cytotoxic selectivity of saikosaponins for cancer cells versus normal cells. For research purposes, the accumulation of scientific data through cell culture, molecular biology, and in vivo mouse experiments will be necessary for an understanding of the underlying mechanisms of the therapeutic action and toxicity of natural products like saikosaponins in the body. Further studies of the possibly superior outcome of saikosaponin treatment over other components of Bupleuri Radix and the probable advantage of combined treatment with saikosaponin monomers and other components of Bupleuri Radix in the treatment of various age-related diseases are also required.
Saikosaponins are minimally soluble in water. Saikosaponins contain a rigid hydrophobic group and are dissolved in DMSO. Since DMSO may be toxic to normal cells, there are safety concerns regarding the use of DMSO as a solvent. However, given that less than 0.1% DMSO is generally noninfluential and that the final concentration of DMSO as a solvent of saikosaponins can be adjusted to be no greater than 0.1%, the possibility of DMSO toxicity in saikosaponin solution seems very slight. Nonetheless, the poor solubility of saikosaponins may be a major problem in future drug development. Therefore, various approaches to improve the solubility and bioavailability of saikosaponins should be considered. The application of pharmaceutical particle technologies, such as particle size reduction technologies and bioavailability enhancement technologies to saikosaponins may improve their solubility and pharmacokinetics for clinical development.
