FITOTERAPIA
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2025
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IF 2.6
Xuan Zhang,Jie Weng,Yi Luo,Hongcun Liu,Jing Yan,Zhiqiang Gong,Chaonan Kong,Xue Li,Lifang Yang,Mingguo Jiang
To elucidate the efficacy and potential molecular mechanisms underlying the therapeutic effects of Spatholobi Caulis flavonoids (SCF) in the treatment of primary dysmenorrhea (PD). The present study established oxytocin-induced uterine contractions in vitro and a model of PD in rats evoked by estradiol benzoate and oxytocin. The uterine contraction experiments demonstrated that SCF significantly inhibited uterine smooth muscle tone by 62.07 %. SCF effectively attenuated the torsional response in PD rats, normalised the PGF2α/PGE2 ratio, and reduced NO and Ca 2+ levels. The constituents of SCF were evaluated by using a Liquid Chromatograph Mass Spectrometer(LC-MS) method, and 11 flavonoid components were preliminarily deduced. Network pharmacology and molecular docking (MD) techniques were used to predict therapeutic targets, with the former suggesting key targets such as RhoA, VEGFA, and PIK3CA, while the latter indicated that 10 compounds had a strong binding affinity for RhoA. The expression of CALM, RhoA, ROCK1, PIK3CA, and AKT was down-regulated at both the protein and mRNA levels. Additionally, the expression levels of genes associated with VEGFA, IP3R, MLCK and NOS3 were found to be regulated. The collective evidence from this study suggests that SCF may attenuate uterine spasm by inhibiting the RhoA/ROCK signaling pathway, decreasing the levels of PGF2α, NO and Ca 2+ , and increasing the content of PGE2. This study provides a theoretical basis for the application of SCF in the treatment of PD.
研究领域:
药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2021
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IF 5.811
Zhang Yu,Su Na,Liu Weiyi,Wang Qingqing,Sun Jianguo,Peng Ying
Dysmenorrhea refers to a kind of uterine cramping pain that occurs in women during the period of menstrual. Guizhi Fuling Capsules are mainly used for the treatment of various pain syndromes and especially effective in treating primary dysmenorrhea. However, the research on its modern pharmacology and mechanism of action have not been thoroughly carried out. It is not clear about the main active ingredients, potential targets and metabolic pathways involved in its efficacy. Therefore, this research project employed estradiol benzoate sensitization combined with oxytocin pain to construct the cold coagulation syndrome dysmenorrhea model, observed the anti-dysmenorrhea effect of Guizhi Fuling Capsules, and used the metabolomics to explore its mechanism. The results showed that Guizhi Fuling Capsules could considerably reduce the number of writhing times in dysmenorrhea rats, increasing the level of PGE2 and β-EP and reducing the contents of PGF2α in rat serum. Pathological sections of uterus and ovaries also showed that Guizhi Fuling Capsules could significantly relieve endometrial hyperplasia and improve ovarian function. The LC/MS-based metabolomics of rat uterine indicated that the model group has a great deviation from the control group. Compared with the model group, the Guizhi Fuling Capsules group had a tendency to shift to the control group, and the main metabolic changes was mainly concentrated on saturated and unsaturated fatty acids. Among them, arachidonic acid is in a pivotal position, and the expression of its rate-limiting enzyme (COX-2) involved in its cyclooxygenase metabolic pathway was significantly up-regulated in the model group, but significantly decreased after the intervention of Guizhi Fuling Capsules. In conclusion, Guizhi Fuling Capsules can effectively relieve primary dysmenorrhea, and this effect may be attributed to the regulation effects of Guizhi Fuling Capsules on endogenous metabolism, such as inhibiting arachidonic acid converted to prostaglandins through downregulate the expression of COX-2, which plays an anti-inflammatory effect.
研究领域:
药理学
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中医药学
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代谢组学
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妇科学
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产品关联
DOI
PubMed
高影响因子
COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING
·
2024
·Vol. 28
·期 6
·1011-1025
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IF 1.6
Xiaotian Yang,Yajie Qin,Huifang Zhou
BackgroundPrimary dysmenorrhea (PDM) is a prevalent menstrual disorder among women, often underreported and undertreated. Wen-Jing-Zhi-Tong Decoction (WJZTD), a patented Traditional Chinese Medicine (TCM) herbal decoction, has shown efficacy in treating PDM. However, the underlying therapeutic mechanism of WJZTD in PDM treatment remains to be elucidated.ObjectiveThis study aimed to employ integrative pharmacology and experimental validation to investigate the potential therapeutic mechanisms of WJZTD in treating PDM.MethodsThe bioactive compounds of WJZTD were identified by UPLC-Q-Exactive-Orbitrap MS/MS and GC-MS. Putative targets of WJZTD were obtained from Swiss Target Prediction, STITCH, and BATMAN-TCM databases. Known targets of PDM were retrieved from Gene Cards and Drug Bank databases. Protein-to-protein interactions were constructed to screen key targets using the STRING database. Subsequently, GO and KEGG pathway enrichment analyses were performed based on Metascape. Finally, a PDM rat model was established to validate the potential therapeutic mechanisms of WJZTD using Western Blot, PCR, and ELISA.Results390 bioactive compounds in WJZTD were identified through UPLC-Q-Exactive-Orbitrap MS/MS and GC-MS. Network pharmacology revealed 7 key compounds with 20 targets and pathways that are crucial for WJZTD in treating PDM. Behavioral tests confirmed that WJZTD can effectively ameliorate menstrual pain in PDM. WJZTD also inhibited prostaglandin production, thereby relieving uterine smooth muscle contraction. The downregulation of the BDNF/TrkB/ERK/CREB signaling pathway, identified as the key target and pathway through network pharmacology, may be crucial to the anti-nociceptive and anti-inflammatory effects of WJZTD in treating PDM.ConclusionThis study provides the first comprehensive analysis of the key compounds, targets, and pathways of WJZTD, laying a solid foundation for future pharmacological studies on PDM. The anti-nociceptive and anti-inflammatory effect may be attributed to the downregulation of the BDNF/TrkB/ERK/CREB signaling pathway.
研究领域:
中药学
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药理学
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分子生物学
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DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Yongfang Sun,Jinmei Xie,Canzheng Wang,Shaoxue Qin,Kun Ren,Dongmei Wang,Yingni Pan,Shumeng Ren,Xiaoqiu Liu
Curcumae wenyujin Rhizoma (CWR) is extensively implemented in clinical practice for treating primary dysmenorrhea (PD) resulting from qi stagnation and blood stasis. However, the development of CWR-derived polysaccharides remains poorly investigated. In this study, the polysaccharide CWP-3 was isolated from CWR, and structurally characterized through FT-IR, HPLC, GC–MS, and NMR, which identified it as an RG-I-type pectin polysaccharide with a molecular weight of 423.6 kDa. CWP-3 consists of the monosaccharides Rha, GalA, Gal, and Ara (25.7: 28.6:42.8:2.9). The main backbone consisted of alternating 1,2-linked Rha p and 1,4-linked GalA p residues, with Gal and Ara forming the side chains, respectively. SEM revealed a porous, sheet-like morphology, while Congo Red staining and AFM analyses confirmed a triple helix structure with a height of 3.37 nm, and TG-DSC analysis indicated good thermal stability. In a mouse model of PD, 160 mg/kg CWP-3 reduced writhing by 70.3 %, prolonged coagulation time by 37.5 %, restored uterine and hepatic indices, and decreased AST, ALT, D2D, TXB2, IL-6, IL-1β, and TNF-α, while normalizing PGF₂α/PGE₂ levels. These results indicate that CWP-3 exerts blood-activating and analgesic effects through cytokine-mediated COX-2 suppression, suggesting its potential as a therapeutic candidate for PD with qi stagnation and blood stasis.
研究领域:
药理学
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生物化学
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药物化学
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妇科学
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结构生物学
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多糖研究
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产品关联
DOI
PubMed
高影响因子
FOOD HYDROCOLLOIDS
·
2023
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IF 10.7
Xiaolin Hou,Meng Long,Nianping Feng,Yongtai Zhang
Low solubility, poor physicochemical stability and unpleasant odor are the main limitations for the application of some essential oils in the pharmaceutical and food industries. In this work, cinnamon oil (CIO) was encapsulated as oil phase with soya phospholipids as emulsifiers in sodium alginate-formed nanocapsules (NCs), which were further reinforced with acid-processed gelatin by electrostatic adsorption, and then incorporated into hyaluronic acid (HA)-fabricated microneedles (MNs) to construct a new transdermal drug delivery system (HAMNs-CIO@NCs). The obtained CIO-loaded nanocapsules (CIO@NCs) with optimized formulation showed 246.5 ± 4.2 nm in diameter, −24.5 ± 1.7 mV in zeta potential , 22.60% in drug loading, and kept physical stability. In HAMNs-CIO@NCs, the CIO@NCs were homogeneously distributed, and the HAMNs-CIO@NCs with sufficient mechanical hardness were successfully pierced into skin. Compared with the free CIO application, the transdermal fluxes of cinnamaldehyde and cinnamic acid in HAMNs-CIO@NCs group were increased to 8.5 and 6.3 times, and the application was completed within 1 min with no essential oil residue on skin, which improved patient compliance. Further more, HAMNs-CIO@NCs effectively alleviated the symptoms of primary dysmenorrhea in rats and reduced the expression ratio of PGF 2α /PGE 2 in uterus. This newly designed drug delivery system is formulated with natural food-derived materials, and CIO is served as drug and carrier excipient for self-assembling nanocapsules in a green manufacturing process, thus providing a new strategy for efficiently using essential oils and contributing to a simple and safe treatment for relieving pain of primary dysmenorrhoea.
研究领域:
药学
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药物递送系统
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透皮技术
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天然产物化学
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疼痛管理
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2018
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IF 3.115
Yue Wei,Tingyun Ma,Hanxue Wang,Jianguo Xing,Yuwen Wang,Zhengyi Gu,Dandan Mu,Qiang Yin,Xuemei Cheng,Changhong Wang
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 F 1α (6-k-PGF 1α ), prostaglandin F 2α (PGF 2α ), thromboxane B2 (TXB 2 ), and nitric oxide (NO) levels in uterine tissues and PGF 2α 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 PGF 2α , 6-k-PGF 1α , TXB 2 , NO and MDA in uterine tissues and PGF 2α 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.
研究领域:
药理学
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传统医学
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民族药理学
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生殖健康
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2024
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IF 3.1
Yufang Huang,Xikang Ren,Yonghui Li,Junqing Zhang,Na Wei,Hailong Li,Yinfeng Tan
The Liangfu formula, as described in 'Liangfang Jiye', is well-known for its efficacy in treating stomach pain, abdominal pain, and dysmenorrhea. This research aimed to investigate the pharmacokinetics and tissue distribution of 5-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-phenyl-3-heptanone (DPHA), Galangin, Kaempferide, 5-Hydroxy-1,7-diphenyl-3-heptanone (DPHC), α-Cyperone, and Nootkatone in vivo using an LC-MS/MS method. The method successfully separated the six active components and internal standards (Chrysin and Yakuchinone-A) on an XB-C18 column with a mobile phase of 0.2 ‰ formic acid water-acetonitrile. It demonstrated good linearity with a correlation coefficient (r 2 ) ≥ 0.9911 and a lower limit of quantification (LLOQ) of 5–80 ng/mL for the different components. Precision, accuracy, matrix effects, and recovery rates were within acceptable ranges. Pharmacokinetic analysis revealed significant differences in parameters between primary dysmenorrhea (PD) and normal rats (especially AUC, T max, and CL z /F). Tissue distribution showed that the six active components of the herbal pair Alpinia officinarum Hance- Cyperus rotundus L. (HPAC) extract was primarily distributed in the liver, lung, and kidney. This study offers valuable insights into the potential mechanisms of action and drug development for treating PD.
研究领域:
药理学
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中医
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分析化学
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药物动力学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2020
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IF 3.69
Baolian Ma,Shilin Yang,Ting Tan,Junmao Li,Xiaoyong Zhang,Hui Ouyang,Mingzhen He,Yulin Feng
Ethnopharmacological relevance Akebiae Fructus, a Tujia minority folk medicine and a well-known traditional Chinese medicine for soothing the liver, regulating Qi, promoting blood circulation and relieving pain, is widely used in the treatment of primary dysmenorrhea . However, little is known about its underlying mechanism. Aim of the study To explore the effect of Akebiae Fructus on primary dysmenorrhea model induced by estradiol benzoate and oxytocin, and to provide better understanding of the mechanism of Akebiae Fructus for primary dysmenorrhea treatment. Materials and methods The primary dysmenorrhea mouse model was used in this study. Except for the control group and the normal administration group, the mice of other groups were subcutaneously injected with estradiol benzoate (10 mg/kg/d) for 10 consecutive days. From the 5th day of the ten-day model period, the positive control groups were given 0.075 g/kg ibuprofen and 7.5 g/kg Leonurus granule, the drug groups were given 0.2 g/kg, 0.4 g/kg, 0.8 g/kg Akebiae Fructus extract, the normal administration group was given 0.8 g/kg Akebiae Fructus extract, and the same volume saline was given in the control group. On the tenth day, oxytocin (10 U/kg) was peritoneally injected after estradiol benzoate injected 1 h. After the oxytocin injection, writhing behavior was observed for 30 min. Then the uterine tissue was collected to measure the level of PGF 2α and PGE 2 , and for histological analysis and transcriptomics analysis. Meanwhile, plasma and urine samples were collected for metabolomic analysis. Results Akebiae Fructus inhibited the writhing, decreased the PGF 2α level and ameliorated the morphological changes. 32 potential metabolic biomarkers in plasma and 17 in urine were found for primary dysmenorrhea, and after Akebiae Fructus treatment, 25 metabolites in plasma and 14 in urine were restored. These altered metabolites were mainly involved in lipid, amino acid and organic acid metabolism. For the transcriptomic study, a total of 2244 differentially expressed genes (1346 up-regulated and 898 down-regulated) were obtained between the control and model group, and 148 differentially expressed genes (DEGs) were found related with Akebiae Fructus treatment of primary dysmenorrhea. Correlation analysis was carried out based on the transcriptomic and metabolomic data. 5 differentially expressed genes (Plpp3, Sgpp2, Arg1, Adcy8, Ak5) were found related with the enrichment metabolic pathways. The mechanism by which Akebiae Fructus ameliorates primary dysmenorrhea may account for the regulation of the gene expression to control the key enzymes in the sphingolipid metabolism, arginine and proline metabolism, glycerophospholipid metabolism and purine metabolism, inhibiting the abnormal secretion of PGF 2α , alleviating the uterine contraction and reducing inflammation and pain. Conclusions Akebiae Fructus could effectively alleviate the symptoms of primary dysmenorrhea, regulate metabolic disorders , and control the related gene expression in primary dysmenorrhea. The study may provide clues for further study of Akebiae Fructus treatment on primary dysmenorrhea.
研究领域:
药理学
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中药学
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分子生物学
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代谢组学
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转录组学
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疼痛管理
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Junling Ren,Xia Wang,Yuran Sun,Le Yang,Hui Sun,Ye Sun,Ling Kong,Guangli Yan,Ying Han,Xijun Wang
Background Danggui Sini Decoction (DGSND) is a classic prescription for treating primary dysmenorrhea (PD), while, the ameliorating effects of DGSND on PD and its mechanisms are not yet fully understood. Purpose The present study is devoted to investigate the protective effect of DGSND against PD and the possible mechanism from the perspective of metabolomics as well as lipidomics. Methods DGSND was characterized by UPLC-Q-TOF/MS. The PD rat model was induced by estradiol benzoate and oxytocin, and traditional pharmacology, including writhing times, latency time, biochemical index, organ index, and histopathology were performed to evaluated the efficacy of DGSND on PD. Urine metabolomics strategy combined with functional analysis was adopted to delineate the therapeutic effect of DGSND on PD rats and anchor the crucial pathway, and lipidomics analysis was further performed with the uterine tissue as the research object to elucidate the protective mechanism of DGSND from the perspective of lipid homeostasis. Finally, western blot analysis was used to validate the expression of key metabolic enzymes in lipid metabolism. Results DGSND was effective in ameliorating writhing times, latency time, the value of prostaglandin F 2α (PGF 2α )/PGE 2 , uterus index, and morphological changes of PD rats. Metabolic signature of PD rats was primarily characterized by the disturbance of steroid hormone metabolism, amino acid metabolism, and lipid metabolism. Functional analysis revealed the urine biomarkers of PD were most related with lipid abnormality. Further lipidomics analysis indicated DGSND exerted anti-PD effects by remodeling lipid homeostasis, which might be due to the significant correlations between different kinds of lipids, especially the extremely high correlation of phosphatidylethanolamine, phosphatidylcholine, and fatty acids. Moreover, the key metabolic enzymes expression of CK, PLA 2 , LPCAT3, COX-2, and 5-LOX can be greatly downregulated by DGSND. Conclusion Our findings demonstrated a novel protective mechanism of DGSND against PD by regulating lipid homeostasis.
研究领域:
药理学
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代谢组学
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脂质组学
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中医
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动物模型
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）