Exploring a novel class tryptophan hydroxylase 1 inhibitor derived from Sambucus williamsii Hance for the osteoporosis treatment

Objective:Gut-derived serotonin strongly inhibits bone formation by inhibiting osteoblast proliferation.Our previous study demonstrated that the lignan-rich fraction prepared from Sambucus willimasii Hance,a folk herbal medicine used to treat bone fractures and joint diseases in China,exerted bone-protective effects,and its actions were modulated by suppressing the synthesis of gut-derived serotonin via the inhibition of intestinal tryptophan hydroxylase 1(TPH-1).However,there is no direct evidence for the action of lignans on TPH-1.This study aimed to verify the direct action of lignans on the TPH-1 and its influence on serotonin synthesis and bone properties.Methods:Molecular docking and surface plasmon resonance were performed to determine the affinities of lignans to TPH-1.The cell viability and the protein activity and expression of TPH-1 were measured in RBL2H3 cells.The serum serotonin level and bone mineral density upon lignan treatment in ovariectomized mice were determined.Result:The lignans showed high binding scores and binding affinities to TPH-1,inhibited the activity and protein expression of TPH-1,suppressed the serum serotonin levels in ovariectomized mice as well as promoted bone mineral density.Conclusion:This is the first study to report that lignans are novel TPH-1 inhibitors and that these lignans could be potential agents for the management of serotonin-related diseases,including osteoporosis.

Novel anti-AD dimeric leads:from relieving symptoms to modifying diseases via multi-targets

Alzheimer disease(AD) has now become the most common brain disorder among the older population. In addition, the currently existing therapeutics only offer temporary symptomatic relieves. Therefore, further research and development of more efficacious and disease-modifying agents for the prevention, treatment and restoration of AD will have tremendous value from both scientific, and economic standpoints. Over the past few years, our series of studies have identified several highly promising anti-AD dimeric leads, with disease-modifying potentials. In this presentation, the latest progress on the neuroprotective and disease modifying effects and the underlying mechanisms of those candidates will be comprehensively illustrated and discussed.

Recent advances in natural compounds inducing non-apoptotic cell death for anticancer drug resistance

The induction of cell death is recognized as a potent strategy for cancer treatment.Apoptosis is an extensively studied form of cell death,and multiple anticancer drugs exert their therapeutic effects by inducing it.Nonetheless,apoptosis evasion is a hallmark of cancer,rendering cancer cells resistant to chemotherapy drugs.Consequently,there is a growing interest in exploring novel non-apoptotic forms of cell death,such as ferroptosis,necroptosis,pyroptosis,and paraptosis.Natural compounds with anticancer properties have garnered significant attention due to their advantages,including a reduced risk of drug resistance.Over the past two decades,numerous natural compounds have been discovered to exert anticancer and anti-resistance effects by triggering these four non-apoptotic cell death mechanisms.This review primarily focuses on these four non-apoptotic cell death mechanisms and their recent advancements in overcoming drug resistance in cancer treatment.Meanwhile,it highlights the role of natural compounds in effectively addressing cancer drug resistance through the induction of these forms of non-apoptoticcell death.