Traditional Chinese Medicine (TCM) is characterized by the wide use of herbal formulae, which are capable of systematically treating diseases determined by interactions among various herbs. However, the combination rule of TCM herbal formulae remains a mystery due to the lack of appropriate methods.

Background: Drug combination therapy is commonly used in clinical practice. Many methods including Bliss independence method have been proposed for drug combination design based on simulations models or experiments. Although Bliss independence method can help to solve the drug combination design problem when there are only a small number of combinations, as the number of combinations increases, it may not be scalable. Exploration of system structure becomes important to reduce the complexity of the design problem.Results: In this paper, we deduced a mathematical model which can simplify the serial structure and parallel structure of biological pathway for synergy evaluation of drug combinations. We demonstrated in steady state the sign of the synergism assessment factor derivative of the original system can be predicted by the sign of its simplified system. In addition, we analyzed the influence of feedback structure on survival ratio of the serial structure. We provided a sufficient condition under which the combination effect could be maintained. Furthermore, we applied our method to find three synergistic drug combinations on tumor necrosis factor α-induced NFκB pathway and subsequently verified by the cell experiment.Conclusions: We identified several structural properties underlying the Bliss independence criterion, and developed a systematic simplification framework for drug combiation desgin by combining simulation and system reaction network topology analysis. We hope that this work can provide insights to tackle the challenging problem of assessment of combinational drug therapy effect in a large scale signaling pathway. And hopefully in the future our method could be expanded to more general criteria.

Skin photoaging, driven primarily by ultraviolet radiation, remains a critical dermatological concern. Carotenoids, a class of natural pigments with potent antioxidant properties, have emerged as promising agents for preventing and mitigating photoaging. This review comprehensively integrates current understanding regarding the triggers of skin photoaging, oxidative stress and their associated signal pathways, the photoprotective roles and mechanisms of carotenoids, as well as their bioavailability. Common C₄₀ carotenoids, such as β-carotene, lycopene, astaxanthin, lutein, and zeaxanthin demonstrate remarkable antioxidant activity, primarily attributed to their conjugated double bond structures. Many studies have demonstrated that both oral and topical administration of these C₄₀ carotenoids can effectively alleviate skin photoaging. Specifically, they play a crucial role in promoting the formation of a new skin barrier and enhancing the production of collagen and elastin, key structural proteins essential for maintaining skin integrity and elasticity. Mechanistically, these carotenoids combat photoaging by effectively scavenging reactive oxygen species and modulating oxidative stress responsive signal pathways, including MAPK, Nrf2, and NF-κB. Notably, we also anticipate the anti-photoaging potential of novel carotenoids, with a particular emphasis on bacterioruberin, a C₅₀ carotenoid derived from halophilic archaea. Bacterioruberin exhibits a superior radical scavenging capacity, outperforming the conventional C₄₀ carotenoids. Furthermore, when considering the application of carotenoids, aspects such as safe dosage, bioavailability, and possible long term usage issues, including allergies and pigmentation disorders, must be taken into account. This review underscores the anti-photoaging mechanism of carotenoids, providing strategies and theoretical basis for the prevention and treatment of photoaging.