Plasma metabolic profiling of normal and dysmenorrhea syndrome rats and the effects of Xiang–Fu–Si–Wu Decoction intervention

Abstract

Context: Primary dysmenorrhea (PDM), a common, clinically heterogeneous endocrine disorder affecting young women, is associated with endocrinopathy and metabolic abnormalities. The Xiang–Fu–Si–Wu Decoction (XFSWD) is a traditional Chinese medicine preparation used to treat PDM.

Objective: In the current study, a plasma metabonomics method based on the ultra-high-performance liquid chromatography-quantitative time-of-flight-mass spectrometry (UHPLC-Q-TOF-MS) system was employed to examine the mechanism of XFSWD action in PDM.

Materials and methods: Estradiol benzoate (0.01 g/kg/d) and oxytocin (5 mL/kg) were used to create the dysmenorrhea rat model. Based on the chromatographic data of plasma samples at different time-points following oral administration of XFSWD mixed in water (37.8 g crude herbs/kg) on day 7, partial least square (PLS) and discriminate analysis (DA) were applied to visualize group differentiation and marker selection.

Results: Systemic changes occurring in PDM reflect alterations in not only uterus function but also whole-body metabolism. The XFSWD was effective as a therapeutic agent for PDM by reflect metabolic pathway. Prostaglandins and lysophospholipids were identified as two marker types for oxytocin-induced dysmenorrhea syndrome, including LysoPC(18:4), LysoPE(22:2/0:0), LysoPC(17:0), PGJ₂, 11-deoxy-11-methylene-PGD₂, 15-deoxy-δ-12,14-PGJ₂, LysoPC(20:3), etc. Specifically, the concentrations of prostaglandins compounds (PGJ₂, 11-deoxy-11-methylene-PGD₂, 15-deoxy-δ-12,14-PGJ₂) were increased while those of lysophospholipid compounds [lysoPC(18:4), LysoPE(22:2/0:0), LysoPC(17:0)] were decreased to a significant extent (p < 0.05) in dysmenorrheal rats. Upon treatment with the XFSWD at 12 h, the concentrations of lysophospholipids showed no significant differences (P > 0.05) between the model and normal groups. The lysophospholipid levels were restored. Lysophospholipids were the key factors in phospholipid metabolism. Thus, disruption of phospholipids metabolism appears critical for the development of dysmenorrhea. The XFSWD exerted its effects by interfering with the sphingolipid metabolic pathway.

Discussion and conclusions: The metabonomics method presents a promising tool to treat PDM in animal models, and may be applicable for clinical treatment of the human disease in the future.

• Lysophospholipid
• metabonomics
• primary dysmenorrhea
• prostanoid
• UHPLC-Q-TOF-MS

Acknowledgements

We are grateful to Waters China Ltd. for technical support.