Abstract
Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome (PMS), a common mental health disturbance associated with several periodic psychological symptoms in women. Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for PMS/PMDD patients; however, side effects are inevitable, especially in long-term treatment. In previous studies, the natural compound paeonol in Moutan Cortex was found to play effective roles in central nervous system disorders with its anti-inflammatory, anti-oxidant, and neuroprotective effects. Consequently, we assume that paeonol might produce positive effects in the treatment of PMS/PMDD. In this study, the open-field test (OFT) and elevated plus maze (EPM) and light dark box (LDB) tests were performed in mice to determine the optimal dose of paeonol for treating anxiety. Then, paeonol was used to treat the progesterone withdrawal (PWD) and resident intruder paradigm (RIP) rat models of PMDD. Using these two reliable models, the OFT and EPM, LDB, and composite aggressive tests were performed to evaluate the effect of the drug on behavioural symptoms of PMDD. From the dosage screening results, the optimal anti-anxiety dose of paeonol was identified as 17.5 mg/kg/d for 7 days. With regard to the effect of paeonol on PMDD rat models, a significantly improvement was found in the behavioural symptoms, but the effective dose varied in different models. For the PWD model rats, treatment with 6.05 mg/kg paeonol could significantly improve anxiety and irritability, while that with 24.23 mg/kg paeonol resulted in anxiety-like effects in behavioural tests. In RIP model rats, treatment with 12.11 mg/kg paeonol demonstrated excellent effects in improving anxiety, particularly irritable emotional behaviour. In conclusion, our study indicates that paeonol is a potential therapeutic compound for PMS/PMDD; it is a drug option that helps establish dosage guidance for treatment of this condition.
Highlights
Women experiencing premenstrual syndrome (PMS), one of the most common mental health disturbances, have several characteristic psychological symptoms including anger, irritability, depressed mood, and anxiety [1]
In the light dark box (LDB) test (Figures 3H–K), diazepam increased the light entries (p=0.0248), light distance (p=0.0048), and total distance (p=0.0064), which confirmed its anti-anxiety effect; 17.5 mg/kg/d paeonol increased the time in the light box (p=0.0450), light entries (p=0.0442), and light distance (p=0.0483)
We found that 6.05 mg/kg paeonol could significantly improve the anxiety and irritability in premenstrual dysphoric disorder (PMDD)-progesterone withdrawal (PWD) model rats, while a dosage of 24.23 mg/kg demonstrated anxiety-like effects in the behavioural tests
Summary
Women experiencing premenstrual syndrome (PMS), one of the most common mental health disturbances, have several characteristic psychological symptoms including anger, irritability, depressed mood, and anxiety [1]. A recent report [8] indicated that short-term low dose fluoxetine could prevent anxiety-like behaviour related to the oestrous cycle in female rats; evaluation of its effect on depression and irritability is lacking. It has been reported that paeonol has a neuroprotective effect by the inflammatory processes mediated by microglial activation [10, 11] and plays a role in central nervous system disorders including depression [12, 13]. Based on this evidence, we assume that paeonol might produce positive effects in the treatment of PMS/PMDD
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