Yue Wei1, Tingyun Ma1, Hanxue Wang1, Jianguo Xing2, Yuwen Wang1, Zhengyi Gu2, Dandan Mu3, Qiang Yin3, Xuemei Cheng4, Changhong Wang5. 1. Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine; The MOE Key Laboratory for Standardization of Chinese Medicines; Shanghai Key Laboratory of Compound Chinese Medicines; Shanghai R&D Centre for Standardization of Chinese Medicines, 1200 Cailun Rood, Shanghai 201203, China. 2. The Xinjiang Institute of Materia Medica, Urumqi, Xinjiang 830002, China. 3. Xinjiang Uighur Pharmaceutical Limited Company, Urumqi, Xinjiang 830001, China. 4. Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine; The MOE Key Laboratory for Standardization of Chinese Medicines; Shanghai Key Laboratory of Compound Chinese Medicines; Shanghai R&D Centre for Standardization of Chinese Medicines, 1200 Cailun Rood, Shanghai 201203, China. Electronic address: chengxuemei1963@163.com. 5. Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine; The MOE Key Laboratory for Standardization of Chinese Medicines; Shanghai Key Laboratory of Compound Chinese Medicines; Shanghai R&D Centre for Standardization of Chinese Medicines, 1200 Cailun Rood, Shanghai 201203, China; The Xinjiang Institute of Materia Medica, Urumqi, Xinjiang 830002, China. Electronic address: wchcxm@hotmail.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Compound Muniziqi granule (CMG) is usually used as a traditional Uighur medicine to treat acne, chloasma, skin inflammation, primary dysmenorrhea (PDM), and menopausal syndrome. However, there are no sufficient data to support the clinic uses of CMG in PDM. AIM OF THE STUDY: This work aims to examine the effect of CMG as a treatment for PDM and reveal its possible therapeutic mechanism. MATERIALS AND METHODS: In vivo and in vitro mouse PDM models were utilized in this study. The mouse uterine contraction was induced by oxytocin after progynova or estradiol benzoate pretreatment. CMG, alkaloid extracts from seeds of Peganum harmala (AEP), and 10% and 95% ethanol extracts from seeds of Nigella glandulifera (EEN10 and EEN95) were given to mice in three doses by gavage. The writhing times within 30 min after oxytocin treatment were recorded to evaluate the analgesic effect, and the glutathione peroxidase (GSH-Px), malondialdehyde (MDA), 6-keto-prostaglandin F1α (6-k-PGF1α), prostaglandin F2α (PGF2α), thromboxane B2 (TXB2), and nitric oxide (NO) levels in uterine tissues and PGF2α and MDA in serum were determined. The effects (contractile curve) of CMG, AEP, EEN10, and EEN95 on uterus contraction induced by oxytocin in isolated mouse uterus were recorded. RESULTS: In contrast to the control group, CMG, AEP, N10, and N95 could display analgesic activities dose dependently by reducing the writhing response of the PDM model mice. CMG, AEP, EEN10, and EEN95 could also remarkably decrease the level of PGF2α, 6-k-PGF1α, TXB2, NO and MDA in uterine tissues and PGF2α and MDA in serum, whereas the activity of GSH-Px in uterine tissues was increased. Furthermore, CMG, AEP, EEN10, and EEN95 could significantly inhibit the frequency and amplitude of isolated uterus induced by oxytocin in a concentration-dependent manner. CONCLUSIONS: CMG exhibited a significant protective effect on experimental PDM. The mechanisms are probably associated with abating lipid peroxidation and over-inflammatory reaction, and alleviating the contraction of isolated mouse uterus. The seeds of P. harmala and N. glandulifera in the CMG may play an important role in exerting protective effects on PDM. This study provides pre-clinic proof to the use of CMG in clinical practice of PDM.
ETHNOPHARMACOLOGICAL RELEVANCE: Compound Muniziqi granule (CMG) is usually used as a traditional Uighur medicine to treat acne, chloasma, skin inflammation, primary dysmenorrhea (PDM), and menopausal syndrome. However, there are no sufficient data to support the clinic uses of CMG in PDM. AIM OF THE STUDY: This work aims to examine the effect of CMG as a treatment for PDM and reveal its possible therapeutic mechanism. MATERIALS AND METHODS: In vivo and in vitro mouse PDM models were utilized in this study. The mouse uterine contraction was induced by oxytocin after progynova or estradiol benzoate pretreatment. CMG, alkaloid extracts from seeds of Peganum harmala (AEP), and 10% and 95% ethanol extracts from seeds of Nigella glandulifera (EEN10 and EEN95) were given to mice in three doses by gavage. The writhing times within 30 min after oxytocin treatment were recorded to evaluate the analgesic effect, and the glutathione peroxidase (GSH-Px), malondialdehyde (MDA), 6-keto-prostaglandin F1α (6-k-PGF1α), prostaglandin F2α (PGF2α), thromboxane B2 (TXB2), and nitric oxide (NO) levels in uterine tissues and PGF2α and MDA in serum were determined. The effects (contractile curve) of CMG, AEP, EEN10, and EEN95 on uterus contraction induced by oxytocin in isolated mouse uterus were recorded. RESULTS: In contrast to the control group, CMG, AEP, N10, and N95 could display analgesic activities dose dependently by reducing the writhing response of the PDM model mice. CMG, AEP, EEN10, and EEN95 could also remarkably decrease the level of PGF2α, 6-k-PGF1α, TXB2, NO and MDA in uterine tissues and PGF2α and MDA in serum, whereas the activity of GSH-Px in uterine tissues was increased. Furthermore, CMG, AEP, EEN10, and EEN95 could significantly inhibit the frequency and amplitude of isolated uterus induced by oxytocin in a concentration-dependent manner. CONCLUSIONS:CMG exhibited a significant protective effect on experimental PDM. The mechanisms are probably associated with abating lipid peroxidation and over-inflammatory reaction, and alleviating the contraction of isolated mouse uterus. The seeds of P. harmala and N. glandulifera in the CMG may play an important role in exerting protective effects on PDM. This study provides pre-clinic proof to the use of CMG in clinical practice of PDM.