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Nonalcoholic fatty liver disease (NAFLD) has become one of the most prominent causes of chronic liver diseases and malignancies. However, few therapy has been approved. Radix Bupleuri (RB) is the most frequently used herbal medicine for the treatment of liver diseases. In the current study, we aim to systemically evaluate the therapeutic effects of saikosaponin A (SSa) and saikosaponin D (SSd), the major bioactive monomers in RB, against NAFLD and to investigate the underlying mechanisms. Our results demonstrated that both SSa and SSd improved diet-induced NAFLD. Integrative lipidomic and transcriptomic analysis revealed that SSa and SSd modulated glycerolipid metabolism by regulating related genes, like Lipe and Lipg . SSd profoundly suppressed the fatty acid biosynthesis by downregulating Fasn and Acaca expression and promoted fatty acid degradation by inducing Acox1 and Cpt1a expression. Bioinformatic analysis further predicted the implication of master transcription factors, including peroxisome proliferator-activated receptor alpha (PPAR α ), in the protective effects of SSa and SSd. These results were further confirmed in vitro in mouse primary hepatocytes. In summary, our study uncoded the complicated mechanisms underlying the promising anti-steatosis activities of saikosaponins (SSs), and provided critical evidence inspiring the discovery of innovative therapies based on SSa and SSd for the treatment of NAFLD and related complications.

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Pheromones are a kind of signal produced by an animal that evoke innate responses in conspecifics. In moth, pheromone components can be detected by specialized olfactory receptor neurons (OSNs) housed in long sensilla trichoids on the male antennae. The pheromone receptors (PRs) located in the dendrite membrane of OSNs are responsible for pheromone sensing in most Lepidopteran insects. The potato tuber moth Phthorimaea operculella is a destructive pest of Solanaceae crops. Although sex attractant is widely used in fields to monitor the population of P. operculella, no study has been reported on the mechanism the male moth of P. operculella uses to recognize sex pheromone components. In the present study, we cloned two pheromone receptor genes PopeOR1 and PopeOR3 in P. operculella. The transcripts of them were highly accumulated in the antennae of male adults. Functional analysis using the heterologous expression system of Xenopus oocyte demonstrated that these two PR proteins both responded to (E, Z)-4,7–13: OAc and (E, Z, Z)-4,7,10–13: OAc, the key sex pheromone components of P. operculella, whilst they responded differentially to these two ligands. Our findings for the first time characterized the function of pheromone receptors in gelechiid moth and could promote the olfactory based pest management of P. operculella in the field.