Danggui Shaoyao Granules Jia Fuzi

The escalating prevalence of hyperlipidemia has a profound impact on individuals' daily physiological well-being. The traditional Chinese medicine (TCM) prescription Danggui Shaoyao San (DSS) has demonstrated significant clinical efficacy and promising prospects for clinical application. Leveraging network pharmacology and bioinformatics, we hypothesize that DSS can ameliorate lipid metabolic disorders in hyperlipidemia by modulating the PPAR signaling pathway. In this study, we employed a zebrafish model to investigate the impact of DSS on lipid metabolism in hyperlipidemia. Body weight alterations were monitored by pre- and postmodeling weight measurements. Behavioral assessments and quantification of liver biochemical markers were conducted using relevant assay kits. Pathways associated with lipid metabolism were identified through network pharmacology and GEO analysis, while PCR was utilized to assess genes linked to lipid metabolism. Western blotting was employed to analyze protein expression levels, and liver tissue underwent Oil Red O and immunofluorescence staining to evaluate liver lipid deposition. Our findings demonstrate that DSS effectively impedes weight gain and reduces liver lipid accumulation in zebrafish models with elevated lipid levels. The therapeutic effects of DSS on lipid metabolism are mediated through its modulation of the PPAR signaling pathway, resulting in a significant reduction in lipid accumulation within the body and alleviation of certain hyperlipidemia-associated symptoms.

The traditional Chinese medicine formula Danggui-Shaoyao-San (DSS) has been reported to have estrogen-like effects and therapeutic effects on the symptoms of Alzheimer's disease (AD).

To explore whether the central oxytocin and neuroendocrine system is involved in the modulating effects of DSS on the cognition and neuropsychiatric hebaviors in female AD rats, and to investigate the pharmacokinetics of paeoniflorin and ferulic acid in female AD rats with DSS treatment.

DSS (1.2, 3.2, 8.6 g/kg/day) was orally administered to ovariectomized (OVX) rats, and saline was orally administered to sham operation rats as control group. The Morris water maze test, novel object recognition test, and passive avoidance test were conducted for evaluation of learning and memory abilities, while elevated plus maze test and forced swim test were performed to assess anxiety- and depressive-like behaviors. ELISA kits were used to detect the levels of estrogen (E), estrogen receptor α (ERα), oxytocin (OT), oxytocin receptor (OTR), acetylcholine (Ach), acetylcholin esterase (AchE), and choline acetyl transferase (ChAT) in the cortex. The concentrations of Ach, glutamate (Glu), γ-aminobutyric acid (GABA), 5-hydroxytryptamine (5-HT), norepinephrine (NE) and dopamine (DA) in the hippocampus were assessed by HPLC-MS. The changes of neuronal morphology in the hippocampus were observed by Nissl staining. The pharmacokinetics of paeoniflorin and ferulic acid in OVX rats with DSS treatment were studied by HPLC.

In the Morris water maze test, novel object recognition test, and passive avoidance test, OVX rats showed cognitive impairment. In the elevated plus maze test and forced swim test, the anxiety- and depressive-like behaviors of OVX rats were significant as compared to the control group. Treatment of DSS significantly imporved the cognitive deficits, and ameliorated anxiety- and depressive-like behaviors of OVX rats. The expression of E, ERα, OT, OTR, AchE and ChAT in the cortex of model group were significantly decreased, and DSS significantly reversed these changes. The concentrations of Ach, Glu, GABA, 5-HT and NE in the hippocampus of OVX rats were significantly decreased, whereas DSS significantly increased the levels of Ach, Glu, GABA, 5-HT and NE. There was no significant difference in the concentration of DA in the hippocampus among groups. Degenerating neurons in the hippocampal CA3 region were observed in OVX rats, and the number of neurons was decreased. DSS treatment reduced the degenerating neurons, and incresed the number of neurons. The MRT (0 - ∞), AUC (0 - ∞), Cmax and t1/2z values of paeoniflorin, and the AUC _0-∞ and C_max value of ferulic acid were higher in DSS-treated OVX rats than those in the DSS-treated control rats.

DSS improves the learning and memory ability, and attenuates anxiety- and depressive-like behaviors of OVX rats. The mechanism may be through increasing estrogen, reducing cholinergic damage, and modulating neurotransmitters. The increase in absorption and elimination time of paeoniflorin and ferulic acid in OVX rats may enhance the efficacy of DSS.