Treatment ideas of acupuncture and moxibustion for adenomyosis based on "etiology, location, nature and development of disease". / 基于"ç— å› ã€ç— ä½ã€ç— æ€§ã€ç— åŠ¿"æµ æžå­å®«è ºè‚Œç—‡çš„é’ˆç¸æ²»ç–—æ€è·¯.

Focusing on the syndrome/pattern differentiation to determine treatment, the approaches to the diagnosis and treatment of acupuncture and moxibustion for adenomyosis are explored by identifying the etiology, location, nature and development of disease. The syndromes/patterns of adenomyosis are differentiated in view of both zangfu and meridian theories. The treatment is delivered complying with the menstrual cycle and the basic rule of treatment, "treating the symptoms in the acute stage, while the root causes in the recovery stage". During menstrual period, stopping pain and eliminating stasis are dominant; while during the other days of menstrual cycle, regulating zangfu dysfunction (excess or deficiency) is emphasized. In general, the functions of the thoroughfare vessel and the conception vessel should be specially considered and adjusted, and the principles of treatment include strengthening the spleen, regulating the kidney and soothing the liver. Acupoints are selected mainly from the spleen meridian of foot-taiyin, the kidney meridian of foot-shaoyin and the conception vessel. Ciliao (BL 32), Shiqizhui (EX-B 8), Zigong (EX-CA 1), Diji (SP 8) and four-gate points (bilateral Hegu [LI 4] and Taichong [LR 3]) are used in menstrual period; Zusanli (ST 36), Sanyinjiao (SP 6) and Taixi (KI 3) in postmenstrual phase; Guanyuan (CV 4), Luanchao (Ovary, Extra) and Qihai (CV 6) in intermenstrual phase; while, Guanyuan (CV 4), Qihai (CV 6) and Shenque (CV 8), combined with Gongsun (SP 4), Neiguan (PC 6) and Jianshi (PC 5) in premenstrual phase. According to the dynamic development of patient's conditions, the reinforcing or reducing techniques of acupuncture and moxibustion are feasibly applied in treatment of adenomyosis.

Mechanisms of electroacupuncture relieves uterine smooth muscle spasm in dysmenorrhea rats based on Rho/ROCK signaling pathway. / 基于Rho/ROCKä¿¡å·é€šè·¯æŽ¢è®¨ç”µé’ˆä»»è„‰ã€ç£è„‰ç»ç©´ç¼“è§£ç±»ç—›ç»æ¨¡åž‹å¤§é¼ å­å®«å¹³æ»‘è‚Œç—‰æŒ›çš„æœºåˆ¶.

OBJECTIVES: To investigate the effect of electroacupuncture (EA) on Rho/Rho-associated coiled-coil-forming kinases (ROCK) signaling pathway of uterus tissue in rats with dysmenorrhea, so as to explore the underlying mechanism of EA treating primary dysmenorrhea (PD) and uterine smooth muscle spasm, and to observe whether there is a difference in the effect of meridian acupoints in Conception Vessel (CV) and Governer Vessel (GV). METHODS: Sixty female SD rats were randomly divided into saline, model, CV, GV, and non-acupoint groups, with 12 rats in each group. The dysmenorrhea model was established by subcutaneous injection of estradiol diphenhydrate combined with intraperitoneal injection of oxytocin (OT). EA (2 Hz) was applied to "Qihai" (CV6) and "Zhongji" (CV3) for CV group, "Mingmen" (GV4) and "Yaoshu" (GV2) for GV group, "non-acupoint 1" and "non-acupoint 3" on the left side for non-acupoint group, and manual acupuncture was applied to "Guanyuan" (CV4) for CV group, "Yaoyangguan" (GV3) for GV group, "non-acupoint 2" on the left side for non-acupoint group. The treatment was conducted for 20 min each time, once daily for 10 days. The writhing score was evaluated. The smooth myoelectric signals of rats' uterus in vivo were recorded by multi-channel physiological recorder. The uterine histopathological changes were observed by HE staining. The contents of prostaglandin F2α (PGF2α), OT and calcium ion (Ca2+) in uterine tissue of rats were detected by ELISA. The protein and mRNA expression levels of smooth muscle 22-α (SM22-α), RhoA and ROCKⅡ in uterine tissue were detected by Western blot and fluorescence quantitative PCR, respectively. RESULTS: Compared with the saline group, the writhing score of rats in the model group was increased (P<0.01), the amplitude voltage of uterine smooth muscle in vivo was elevated (P<0.01), the contents of PGF2α, OT and Ca2+, the protein and mRNA expression of SM22-α, RhoA and ROCK Ⅱ in uterine tissue were all increased (P<0.01). Compared with the model and the non-acupoint groups, the writhing scores of the CV and the GV groups were decreased (P<0.01, P<0.05), the amplitude voltage of uterine smooth muscle was decreased (P<0.01), the contents of PGF2α, OT and Ca2+ in uterine tissue were decreased (P<0.01, P<0.05), and the protein expression and mRNA expression of SM22-α, RhoA and ROCKⅡ in uterine tissue were decreased (P<0.01, P<0.05). HE staining showed extensive exfoliation of uterine intima with severe edema and increased glandular secretion in the model group, which was alleviated in the CV and GV groups. CONCLUSIONS: EA at acupoints of CV and GV can significantly reduce the writhing score, uterine smooth muscle amplitude voltage, pathological injury degree of uterus, and relieve spasm of uterine smooth muscle in dysmenorrhea rats, which may be related to its effect in regulating PGF2α and OT contents, inhibiting the Rho/ROCK signaling pathway, and reducing the SM22-α, RhoA, ROCKⅡ protein and mRNA expression, and Ca2+ content in uterine tissue.

Ayurvedic Herbal Medicines: A Literature Review of Their Applications in Female Reproductive Health.

Ayurveda, an ancient holistic and personalized healing system originating from the Indian subcontinent, has been gaining increasing attention as a complementary and alternative medical practice for treating various health conditions, including those related to women's reproductive well-being. This comprehensive literature review examines a wide array of experimental and clinical studies exploring the diverse facets of Ayurvedic interventions in addressing issues such as menstrual irregularities, polycystic ovary syndrome (PCOS), infertility, and menopausal symptoms. The paper specifically focuses on discussing the available data regarding the efficacy of Tulsi (Ocimum tenuiflorum), ashwagandha (Withania somnifera), ginger (Zingiber officinale), cardamom (Elettaria cardamomum), turmeric (Curcuma longa), and Shatavari (Asparagus racemosus), which have traditionally been used in Ayurvedic medicine for centuries. The synthesis of literature not only highlights the potential benefits of these Ayurvedic interventions, but also critically assesses the methodological rigor of existing studies, identifying research gaps, and proposing directions for future investigations. While acknowledging the need for further rigorous research and clinical trials, the review emphasizes the benefits of collaborative and integrative healthcare. This review aims to serve as a valuable resource for healthcare practitioners, researchers, and individuals seeking holistic and natural alternatives for female reproductive health management.

Acupuncture for pain and pain-related disability in deep infiltrating endometriosis.

Objectives: To evaluate the efficacy of acupuncture in relieving symptoms (dysmenorrhea, dyspareunia, pelvic pain and dyschezia) intensity, improving functional disability, reducing the number of days per months of dysmenorrhea, the frequency and the efficacy of analgesic use in deep infiltrating endometriosis (DIE). The safety profile was also evaluated. Methods: The study sample was 34 patients with DIE; for 2 months (T-2, T-1) the women recorded diary notes on the numbers of days of menstruation, the presence, intensity, and disability related to dysmenorrhea, dyspareunia, pelvic pain, and dyschezia. They then received a total of 15 acupuncture treatments over 6 months (T1-T6; once a week for 12 weeks, then once a month for 3 months). Results: Dysmenorrhea intensity was decreased during treatment. A decrease of at least 50% in number of days of dysmenorrhea, and a decrease in moderate-to-severe disability starting from T1 to T6 was recorded for 58.6% of patients. Dyspareunia intensity steadily decreased starting at T2; the percentage of women with moderate-to-severe disability declined from 73.3% at T-2, to 36.9% at T3, T4, and T5. A decrease in pelvic pain score was noted starting at T1; the percentage of disability decreased from 83.3% at T-2 to 33.3% at T3 and T6. The intensity of dyschezia decreased from T-2 to T3 and T4 and then increased slightly. Analgesic drug use was lower during treatment and its efficacy appeared to be greater. Conclusions: The limitations notwithstanding our study-findings show that acupuncture was safe and effective in reducing pain intensity and symptoms-related disability. Larger-scale studies are needed to compare acupuncture and pharmacotherapy for endometriosis-related pain.

Plants in Menstrual Diseases: A Systematic Study from Italian Folk Medicine on Current Approaches.

Background: Plant-based remedies have been used since antiquity to treat menstrual-related diseases (MD). From the late nineteenth to the early to mid-twentieth century, Italian folk remedies to treat "women's diseases" were documented in a vast corpus of literature sources. Aim: The purpose of this paper is to bring to light the plant-based treatments utilized by Italian folk medicine to heal clinical manifestations of premenstrual syndrome (PMS), dysmenorrhea, amenorrhea and menstrual disorders in an attempt to discuss these remedies from a modern pharmacological point of view. Moreover, we compare the medical applications described by Hippocrates with those utilized by Italian folk medicine to check if they result from a sort of continuity of use by over two thousand years. Results: Out of the 54 plants employed in Italian folk medicine, 25 (46.3%) were already documented in the pharmacopoeia of the Corpus Hippocraticum for treating MD. Subsequently, a detailed search of scientific data banks such as Medline and Scopus was undertaken to uncover recent results concerning bioactivities of the plant extracts to treat MD. About 26% of the plants used by Italian folk medicine, nowadays, have undergone human trials to assess their actual efficacy. At the same time, about 41% of these herbal remedies come back to in different countries. Conclusions: Active principles extracted from plants used by Italian folk healers could be a promising source of knowledge and represent strength candidates for future drug discovery for the management of MD.

Treatment of Women With Primary Dysmenorrhea With Manual Therapy and Electrotherapy Techniques: A Systematic Review and Meta-Analysis.

OBJECTIVE: The objective of this study was to evaluate the efficacy of electrotherapy and manual therapy for the treatment of women with primary dysmenorrhea. METHODS: Systematic searches were conducted in Scopus, Web of Science, PubMed, CINAHL, and MEDLINE. The articles must have been published in the last 10 years, had a sample exclusively of women with primary dysmenorrhea, had a randomized controlled trial design, and used interventions that included some form of manual therapy and/or electrotherapy techniques. Two reviewers independently screened articles for eligibility and extracted data. Difference in mean differences and their 95% CIs were calculated as the between-group difference in means divided by the pooled standard deviation. The I2 statistic was used to determine the degree of heterogeneity. RESULTS: Twelve selected studies evaluated interventions, with 5 evaluating electrotherapy techniques and 7 evaluating manual therapy techniques. All studies analyzed identified improvements in pain intensity and meta-analysis confirmed their strong effect. CONCLUSIONS: Manual therapy and electrotherapy are effective for the treatment of women with primary dysmenorrhea. Transcutaneous electrical nerve stimulation combined with thermotherapy and effleurage massage stands out for its effects on the intensity and duration of pain with the application of a few sessions and their long-term effects. IMPACT: Manual therapy techniques and electrotherapy methods reduce the pain intensity of women with primary dysmenorrhea. Quality of life and degree of anxiety improved significantly with manual therapy interventions. Transcutaneous electrical nerve stimulation combined with thermotherapy and effleurage massage are the interventions with which positive effects were achieved with fewer sessions.

Association of the Verbal Rating Scale-Measured Dysmenorrhea with Nausea and Vomiting in Pregnancy: A Retrospective Cohort Study.

OBJECTIVES: Nausea and vomiting in pregnancy (NVP) is a common condition that reduces the quality of life by negatively affecting work and family life, physical and mental health, and economic well-being. However, its risk factors remain unclear. This study aimed to explore the association between NVP and verbal rating scale (VRS)-measured dysmenorrhea and to explore potential protective factors. METHODS: This retrospective cohort study was conducted from June 2018 to December 2020 at Tongji Hospital in Wuhan. Information on baseline characteristics, pregnancy-related history, periconceptional micronutrient supplementation, and obstetric outcomes were collected. The severity of dysmenorrhea was assessed using VRS. RESULTS: A total of 443 pregnant women were recruited and divided into the NVP group (n = 76) and the control group (n = 367). A significant association was observed between NVP and VRS-measured dysmenorrhea (c2=10.038, P = 0.007). After adjusting for covariates, the association between moderate/severe dysmenorrhea and NVP remained significant (OR 2.384; 95% CI 1.104-5.148, P = 0.004). First-trimester docosahexaenoic acid supplement (OR 0.443; 95% CI 0.205-0.960, P = 0.039) may be beneficial in reducing the risk of NVP. CONCLUSIONS: Women with moderate to severe dysmenorrhea have a higher risk of experiencing NVP during the first trimester. Periconceptional docosahexaenoic acid supplementation may play a protective role.

Auricular Acupuncture Prior to Menstruation Can Reduce Primary Dysmenorrhea: A Randomized Controlled Trial.

Objective: Primary dysmenorrhea is a common condition that impacts quality of life significantly. Auricular therapies have shown promise for treating primary dysmenorrhea, but there is a lack of evidence specifically for auricular acupuncture (AA). This study evaluated the safety and efficacy of AA for managing primary dysmenorrhea. Materials and Methods: A randomized, double-blinded controlled trial was conducted on 90 females with primary dysmenorrhea: an AA group; n = 45) and a sham-AA (SA) group; n = 45. Specific ear acupoints (i.e., Uterus, Endocrine, Shenmen, Subcortex, Liver, and Kidney) were used for the intervention, which was 1 or 2 days prior to the expected menstruation onset. Outcomes were visual analogue scale (VAS) scores, ibuprofen needs, and adverse events (AEs). Results: The AA group had significantly lower VAS scores, compared to the SA group at menstruation onset and for up to 12 hours (mean differences [MDs] and 95% confidence intervals [CIs]: -1.08 [-1.96, -0.21] and -1.17 [-2.16, -0.18], respectively). Both groups had reductions in pain levels, compared to the prior menstrual cycle; the AA group had a significantly greater improvement. The AA group needed fewer ibuprofen tablets (MD: -0.28; 95% CI: -0.58, 0.00]). AEs were mild pain and irritation at insertion sites, all resolved spontaneously with no lasting effects. Conclusions: AA is safe. It may be effective for managing primary dysmenorrhea. Further studies are warranted on AA's effectiveness in diverse populations and extended times.

Metabolomics study of graphene nuangong acupoint plaster for primary dysmenorrhea.

Primary dysmenorrhea is a common gynecological disease with typical clinical symptoms and diverse treatment methods. Acupoint patch therapy is one of the traditional external treatments of traditional Chinese medicine, with a long history, and has been widely used in the treatment of many diseases in China. Graphene nuangong acupoint plaster (GNGAP) developed based on traditional acupoints and new materials have been used in the clinical treatment of primary dysmenorrhea, and satisfactory therapeutic effects have been achieved. However, the underlying mechanisms of GNGAP still need further investigation. In this study, we used estradiol benzoate combined with oxytocin intraperitoneally to establish dysmenorrhea model rats, and observed the torsion response, uterine organ coefficients, prostaglandin levels and metabolite changes of rats with dysmenorrhea model after the intervention of GNGAP, to elucidate the mechanism of the effect of GNGAP. Compared with normal rats, the dysmenorrhea model rats exhibited increased writhing response and latency time, increased uterine organ coefficient, and significant changes in 79 metabolites. Twenty-three significantly enriched pathways were discovered, including amino acid metabolism, arachidonic acid metabolism, pyrimidine metabolism, and ovarian steroidogenesis, which may be involved in the pathogenesis of primary dysmenorrhea. Compared with the model group, the torsion response, latency time and uterine organ coefficient of rats in the acupoint patch group were significantly improved, and nine uterine metabolites were significantly altered, among which metabolites such as 4-pyridoxic acid, d-glucarate and Phenol were identified as potential biomarkers for the therapeutic effects of GNGAP. Vitamin B6 metabolism, Ascorbate and aldarate metabolism and Tyrosine metabolism were enriched in nine metabolic pathways. These findings contribute to the screening study of potential pathological metabolic pathways in primary dysmenorrhea. Additionally, they reveal the biological effects of GNGAP in the treatment of primary dysmenorrhea at the metabolite level.

Osteopathic Manipulative Treatment in Dysmenorrhea: A Systematic Review.

The majority of women experience dysmenorrhea during their lifetime. The current standard-of-care treatment consists of nonsteroidal anti-inflammatory drugs, oral contraceptive pills, or intrauterine devices. Osteopathic manipulative treatment (OMT) is a beneficial tool for improving non-musculoskeletal (non-MSK) conditions such as migraines, gastroesophageal reflux disease (GERD), and anxiety. OMT should be utilized to improve other non-MSK conditions, such as dysmenorrhea. The current review aims to evaluate the effects of OMT in women with dysmenorrhea. An extensive search was conducted in Cumulative Index to Nursing and Allied Health Literature (CINAHL), MEDLINE, Biomedical Reference Collection: Comprehensive, and Nursing & Allied Health Collection: Comprehensive from inception to June 2022. Studies evaluating the use of OMT in patients with dysmenorrhea were included, while editorial/opinion articles were excluded. Three independent reviewers evaluated the studies. Ten studies evaluating the use of OMT in patients with dysmenorrhea were included. Overall, OMT was shown to provide relief of symptoms, including back and menstrual pain; however, there was no guideline on which OMT techniques are the most successful. Numerous positive effects were found, including a reduction in the duration of pain, reduction of pain intensity, and reduction of analgesic use. However, the low number of studies supports the need for further investigations. Dysmenorrhea patients could benefit from a prospective randomized controlled trial targeting spinal facilitation and viscerosomatic reflexes to decrease pain duration, pain intensity, and analgesic use. Non-MSK-focused OMT has a large body of mostly anecdotal evidence for relief of conditions such as migraine, GERD, and anxiety. It has helped when traditional standards of care have failed. Non-MSK-focused OMT research represents a relatively untouched field of research that can have a profound and positive global impact, particularly in areas with poor income/healthcare access.

Head-to-Head Comparison of Electroacupuncture and Laser Acupuncture Effects on Autonomic Regulation and Clinical Effects in Dysmenorrhea: A Randomized Crossover Clinical Trial.

Introduction: Electroacupuncture (EA) has been applied in dysmenorrhea and has shown good efficacy. The mechanisms of EA are associated with autonomic nervous system adjustments and neuroendocrine regulation. Laser acupuncture (LA), however, has been widely investigated for its noninvasiveness. However, it remains uncertain whether LA is as effective as EA. This study aimed to compare EA and LA head to head in dysmenorrhea. Methods: A crossover, randomized clinical trial was conducted. EA or LA was applied to selected acupuncture points. Participants were randomized into two sequence treatment groups who received either EA or LA twice per week in luteal phase for 3 months followed by 2-month washout, then shifted to other groups (sequence 1: EA > LA; sequence 2: LA > EA). Outcome measures were heart rate variability (HRV), prostaglandins (PGs), pain, and quality-of-life (QoL) assessment (QoL-SF12). We also compared the effect of EA and LA in low and high LF/HF (low frequency/high frequency) status. Results: Totally, 43 participants completed all treatments. Both EA and LA significantly improved HRV activity and were effective in reducing pain (Visual Analog Scale [VAS]; EA: p < 0.001 and LA: p = 0.010) and improving QoL (SF12: EA: p < 0.001, LA, p = 0.017); although without intergroup difference. EA reduced PGs significantly (p < 0.001; δ p = 0.068). In low LF/HF, EA had stronger effects than LA in increasing parasympathetic tone in respect of percentage of successive RR intervals that differ by more than 50 ms (pNN50; p = 0.053) and very low-frequency band (VLF; p = 0.035). Conclusion: There is no significant difference between EA and LA in improving autonomic nervous system dysfunction, pain, and QoL in dysmenorrhea. EA is prominent in PGs changing and preserving vagus tone in low LF/HF; yet LA is noninvasive for those who have needle phobia. Whether LA is equivalent with EA and the mechanism warrants further study. Clinical trial identification number: NCT04178226.

Clinical observation on 90 cases of primary dysmenorrhea treated by buccal acupuncture therapy: a randomized controlled study.

OBJECTIVE: To explore the short-term and long-term efficacy of buccal acupuncture therapy in the treatment of patients with primary dysmenorrhea (PD). METHODS: A total of 90 patients with PD who were admitted to the Second Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine from January 2020 to December 2021 were included in this study and randomly divided into three groups, including the observation group, the control group, and the placebo group, with 30 patients in each group. Patients in the observation group were treated according to the syndrome types of Traditional Chinese Medicine, those in the control group were treated with Saridon, and those in the placebo group received a placebo. The visual analog scale (VAS) scores of these patients were evaluated at different time points (before treatment, 5 min after needle retention, 30 min after needle retention, 1 h after treatment, 2 h after treatment, 1 d after treatment, and 2 d after treatment). The Cox Menstrual Symptom Scale (CMSS) scores were assessed before the treatment and after three courses of treatment. Besides, these two scales were also evaluated during follow-up. Moreover, the pain score and adverse reactions of these patients were assessed during treatment. RESULTS: After treatment, the VAS and CMSS scores in the observation group decreased significantly (P < 0.05) 5 and 30 min after needle retention and after treatment. CONCLUSION: Buccal acupuncture therapy is verified to have short-term efficacy in the treatment of PD. In addition, this therapy has an immediate analgesic effect and long-term efficacy in reducing the severity and frequency of PD.

Synergistic mechanism of stir-baked curcumae radix with vinegar in dysmenorrhea rats based on UPLC-Q-TOF/MS metabolomics.

Curcumae Radix (i.e. Huangsiyujin: HSYJ), a well-known traditional Chinese medicine (TCM), has been widely used in clinical practice for many years to treat depression and primary dysmenorrhea. Modern pharmacological researches have demonstrated its anti-inflammatory, antidepressant, and dysmenorrhea relief effects. According to the processing theory of TCM, it is believed that stir-baked HSYJ with vinegar may enhance the ability to disperse stagnant hepatoqi and alleviate pain. However, whether the vinegar concoction of HSYJ can enhance the therapeutic effect on the Qi stagnation due to liver depression (LDQS) type of dysmenorrhea and what its mechanism has not been well explained. Based on the processing drugs theory of "stir-baked with vinegar into liver", a metabolomic approach was used to investigate the therapeutic effect and mechanism of stir-baked HSYJ with vinegar to enhance the treatment of dysmenorrhea in rats. By establishing a rat model of dysmenorrhea of the "LDQS" type, observation of hemorheology, uterine pathological sections, COX-2 and OTR protein expression and other indicators; analysis of urinary metabolic changes in rats by UPLC-Q-TOF-MS technique, to compare the differential biomarkers and metabolic pathways in the treatment of dysmenorrhea due to "liver stagnation and qi stagnation" before and after stir-baked HSYJ with vinegar. Stir-baked HSYJ with vinegar significantly inhibited the writhing response of rats, improved hemorheology, repaired damaged diseased uterus and inhibited high expression of COX-2 and OTR proteins in uterus; 68 differential metabolites were screened from the urine of rats, compared with the raw HSYJ, the levels of 14 metabolites were significantly changed in stir-baked HSYJ with vinegar, involving the pathways of phenylalanine, tyrosine and tryptophan metabolism, cysteine and methionine metabolism, aspartate and glutamate metabolism. The potentiating effect of stir-baked HSYJ with vinegar may be related to the regulation of multiple amino acid metabolic pathways.

Acupoint application therapy alleviates pain by regulating immune function through inhibiting TLR4/MyD88/NF-κB p65 signaling in a primary dysmenorrhea rat model. / 穴位贴敷通过TLR4/MyD88/NF-κBé€šè·¯è°ƒèŠ‚åŽŸå‘æ€§ç—›ç»å¤§é¼ çš„å ç–«åŠŸèƒ½.

OBJECTIVES: To investigate the effects of graphene-based warm uterus acupoint paste on uterine Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear transcription factor-kappa B p65 (NF-κB p65) signaling pathway and Th1/Th2 immune balance in primary dysmenorrhea ( PD ) model rats, so as to reveal its immunological mechanisms of relieving dysmenorrhea. METHODS: Thirty SD female rats were randomly divided into 3 groups：normal group, model group and acupoint paste group, with 10 rats in each group. PD rat model was established by subcutaneous injection of estradiol benzoate for 10 consecutive days. At the same time of modeling, graphene-based warm uterus acupoint paste was applied to the acupoints of "Guanyuan" (CV4), bilateral "Zigong" (EX-CA1) and "Sanyinjiao" (SP6) of rats in the acupoint paste group. The application was continuously applied once daily for 10 d, 5 h each time. On the 11th day, oxytocin was injected intraperitoneally to observe the writhing latency, writhing times within 30 min and writhing score of rats in each group. The spleen and thymus indexes were calculated. The pathological changes of spleen and thymus tissue were observed after HE staining. The contents of serum immunoglobulin (Ig) A, IgG, tumor necrosis factor-α (TNF-α), interleukin (IL)-2, interferon-γ (IFN-γ), IL-4 and IL-10 were detected by ELISA . The protein and mRNA expression levels of TLR4, MyD88 and NF-κB p65 in rat uterine tissue were detected by Western blot and real-time quantitative PCR, respectively. RESULTS: Compared with the normal group, the writhing times and writhing scores within 30 min of rats in the model group were significantly increased(P<0.001), and the rats showed writhing reaction (P<0.01). The spleen index and thymus index were significantly decreased(P<0.01, P<0.05). The spleen and thymus had obvious pathological changes. The contents of IgA, IgG, TNF-α, IL-2 and IFN-γ in serum were significantly increased, while the contents of serum IL-4 and IL-10 were significantly decreased(P<0.001, P<0.01). The expression levels of TLR4, MyD88, NF-κB p65 protein and corresponding mRNA in uterine tissue were significantly increased(P<0.001). Following intervention, compared with the model group, the writhing latency time of rats in the acupoint paste group was prolonged, and the writhing times and writhing scores within 30 min were significantly decreased (P<0.001). The spleen index and thymus index were significantly increased(P<0.01, P<0.05). The pathological changes of spleen and thymus were improved. The contents of serum IgA, IgG, TNF-α, IL-2 and IFN-γ were significantly decreased, while the contents of IL-4 and IL-10 were significantly increased(P<0.001, P<0.05, P<0.01). The expression of TLR4, MyD88, NF-κB p65 protein and the corresponding mRNA levels in uterine tissue were decreased(P<0.001, P<0.01). CONCLUSIONS: Graphene-based warm uterus acupoint paste can regulate the immune balance of Th1/ Th2 by regulating TLR4/ MyD88/ NF-κB p65 signaling pathway, repair the pathological damage of immune tissue, improve immune function, and effectively relieve the pain symptoms of PD rats.

The effect of antioxidant supplementation on dysmenorrhea and endometriosis-associated painful symptoms: a systematic review and meta-analysis of randomized clinical trials.

This study aimed to review randomized controlled trials (RCTs) investigating the effects of dietary antioxidant supplements on the severity of endometriosis-related pain symptoms. The PubMed/Medline, Scopus, and Web of Science databases were searched until April 2022. Additionally, we manually searched the reference lists. Endpoints were summarized as standardized mean difference (SMD) with 95% confidence intervals (CIs) in a random-effects model. The I2 statistic was used to assess heterogeneity. Ten RCTs were included in this meta-analysis. Overall, 10 studies were related to dysmenorrhea, four to dyspareunia, and four to pelvic pain. Antioxidants significantly reduced dysmenorrhea (SMD, -0.48; 95% CI, -0.82 to -0.13; I2=75.14%). In a subgroup analysis, a significant reduction of dysmenorrhea was observed only in a subset of trials that administered vitamin D (SMD, -0.59; 95% CI, -1.13 to -0.06; I2=69.59%) and melatonin (SMD, -1.40; 95% CI, -2.47 to -0.32; I2=79.15%). Meta-analysis results also suggested that antioxidant supplementation significantly improved pelvic pain (SMD, -1.51; 95% CI, -2.74 to -0.29; I2=93.96%), although they seem not to have a significant beneficial impact on the severity of dyspareunia. Dietary antioxidant supplementation seems to beneficially impact the severity of endometriosis-related dysmenorrhea (with an emphasis on vitamin D and melatonin) and pelvic pain. However, due to the relatively small sample size and high heterogeneity, the findings should be interpreted cautiously, and the importance of further well-designed clinical studies cannot be overstated.

Unraveling the anti-primary dysmenorrhea mechanism of Ainsliaea fragrans Champ. extract by the integrative approach of network pharmacology and experimental verification.

BACKGROUND: The plant Ainsliaea fragrans Champ. (A. fragrans) named "Xingxiang Tuerfeng", is a traditional herb with a long history of therapeutic practice in southern China in the treatment of gynecological diseases. PURPOSE: The anti-inflammatory extract of Ainsliaea fragrans Champ. (AF-ext) exhibited anti-primary dysmenorrhea (PD) activity in oxytocin-induced mice. This study aimed to unravel the underlying mechanisms of AF-ext on PD by the integrative approach of network pharmacology and experimental verification. METHODS: First, the therapeutic targets of AF-ext are predicted using network pharmacology and molecular docking methods. Second, activity screening and immunoblotting methods were used for target validation. Then, the therapeutic effect of AF-ext on PD was evaluated using oxytocin-induced mice and uterine strips model. RESULTS: AF-p1, and AF-p2, the active ingredients of AF-ext, showed inhibitory effects on COX1/2 and EGFR, and all five active components showed antagonistic activity on TRPV1. AF-ext (25, 50, 100 mg/kg) could significantly reduce the number of writhing times and prolong writhing latencies in a dose-dependent manner. AF-ext inhibited spasmolytic activity in uterine strips induced by oxytocin and Ca2+ stimulation. AF-ext inhibited NF-κB/COX-2/PG pathway and activation of the NLRP3 inflammasome in PD mice. It significantly downregulated the PD-induced overexpression of p-p65/p65, p-IκBα, and COX-2 by inhibiting the NF-κB pathway. Moreover, the overexpression of NLRP3, p20/pro-Caspase 1, and p17/pro-IL-1ß was greatly downregulated. CONCLUSIONS: AF-ext demonstrated anti-inflammatory, analgesic, and spasmolytic activity in the treatment of PD. It inhibited the NF-κB/COX-2/PG pathway and NLRP3 inflammasome activation in PD mice with a multi-target approach.

Effect of Tuina Combined with Chinese Herbal Compress on Primary Dysmenorrhea with Cold Coagulation and Blood Stasis Syndrome: A Study Protocol for a Randomized Controlled Trial.

INDRODUCTION: Primary dysmenorrhea (PD) is a very common issue in young women that reduces the quality of women's lives. Both Western medicine and traditional Chinese medicine (TCM) provide several ways to treat PD; however, TCM treatment exhibits fewer side effects for the patient. Tuina massage and Chinese herbal compresses are considered forms of external TCM therapy that have been widely used to treat PD, especially in China. Therefore, to provide the most effective and safe treatment for PD, we combined Tuina and Chinese herbal compresses together in this observational study. METHODS: A randomized controlled trial (RCT) consisting of 114 participants from the Shanghai University of Traditional Chinese Medicine who meet inclusion criteria will be divided into two groups in a 1:1 allocation ratio. The intervention group will receive Tuina combined with Chinese herbal compress therapy, while the control group will only receive Chinese herbal compress therapy. The treatment will be given 3 days before menstruation (once per day, 3 times per menstrual cycle). The primary outcome will be measured with the Visual Analog Scale (VAS). The secondary outcomes will be measured by the Dysmenorrhea Symptom Score, the Chinese Medical Dysmenorrhea Symptom Score, the Self-Rating Anxiety Scale (SAS), the Self-Rating Depression Scale (SDS), and the pain threshold at Guanyuan (CV4). CONCLUSION: This study will be the first RCT that will entail the combination of Tuina and Chinese herbal compresses to treat PD in the category of cold coagulation and blood stasis syndrome. If the results demonstrate that Tuina combined with a Chinese herbal compress is effective, we posit that this study will provide evidence-based references for a potential alternative treatment to treat PD in the future.Die primäre Dysmenorrhoe (PD) ist ein Problem, das bei jungen Frauen sehr häufig auftritt und ihre Lebensqualität beeinträchtigt. Sowohl die westliche Medizin als auch die traditionelle chinesische Medizin (TCM) bieten verschiedene Therapiemöglichkeiten zur Behandlung der PD, allerdings ist die TCM mit weniger Nebenwirkungen für die Patientin verbunden. Tuina-Massage und chinesische Kräuterkompressen gelten als Formen der äußerlichen TCM-Therapie, die besonders in China zur Behandlung der PD weit verbreitet sind. Daher haben wir in dieser Beobachtungsstudie Tuina und chinesische Kräuterkompressen kombiniert, um eine möglichst wirksame und sichere Behandlung der PD bereitzustellen.Es handelt sich um eine randomisierte kontrollierte Studie (randomized controlled trial, RCT), bei der 114 Teilnehmerinnen der Shanghai University of Traditional Chinese Medicine, die die Einschlusskriterien erfüllen, im Verhältnis 1:1 in zwei Gruppen aufgeteilt werden. Die Interventionsgruppe erhält Tuina in Kombination mit chinesischen Kräuterkompressen, während die Kontrollgruppe nur eine Behandlung mit chinesischen Kräuterkompressen erhält. Die Behandlung erfolgt drei Tage vor der Menstruation (einmal täglich, dreimal pro Menstruationszyklus). Das primäre Zielkriterium wird anhand der visuellen Analogskala (VAS) gemessen. Die sekundären Zielkriterien werden mithilfe des Dysmenorrhoe-Symptom-Scores, des chinesischen medizinischen Dysmenorrhoe-Symptom-Scores, der Self-rating Anxiety Scale (SAS), der Self-rating Depression Scale (SDS) und der Schmerzschwelle am Guanyuan-Akupunkturpunkt (CV4) ermittelt.Diese Studie ist die erste randomisierte kontrollierte Studie, die die Kombination von Tuina und chinesischen Kräuterkompressen zur Behandlung von PD in der Kategorie Kältekoagulation und Blutstauungssyndrom untersucht. Sollten die Ergebnisse zeigen, dass Tuina in Kombination mit chinesischen Kräuterkompressen wirksam ist, erwarten wir, dass diese Studie evidenzbasierte Belege für eine mögliche alternative Behandlung von PD in der Zukunft liefern wird.

Peony Pollen Protects against Primary Dysmenorrhea in Mice by Inhibiting Inflammatory Response and Regulating the COX2/PGE2 Pathway.

Peony pollen contains multiple nutrients and components and has been used as a traditional Chinese medicine with a long history, but the effect of the treatment of primary dysmenorrhea remains to be clarified. The aim of this study is to investigate the therapeutic effect of peony pollen on primary dysmenorrhea mice and the potential mechanism. A uterus contraction model in vitro and primary dysmenorrhea mice were used to evaluate the treatment effect of peony pollen on primary dysmenorrhea. The primary dysmenorrhea mice were treated with 62.5 mg/kg, 125 mg/kg, or 250 mg/kg of peony pollen, and the writhing response, latency period, histopathological changes in the uterus, prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α) levels, and infiltration of neutrophils and macrophages were investigated. Protein expression of interleukin 1 ß (IL-1ß), interleukin 6 (IL-6), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), cyclooxygenase-2 (COX-2), microsomal prostaglandin-E synthase 1 (mPGEs-1), BCL2-Associated X (Bax), B-cell lymphoma-2 (BCL-2), caspase-3, and cleaved caspase-3 were detected by Western blot, and the oxidative stress related marker malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and reactive oxygen species (ROS) were evaluated. Peony pollen could attenuate spontaneous or oxytocin-induced uterus contractions in vitro. Moreover, peony pollen decreased the writhing times, prolonged the writhing latency, and reduced the pathological damage of uterine tissues. Furthermore, the inflammatory cell infiltration and the protein expression of IL-1ß, IL-6, and NLRP3 were decreased. The COX-2/PGE2 pathway was inhibited; oxidative stress and apoptosis in the uterus also improved in the uterus of primary dysmenorrhea mice. Peony pollen exerts a positive effect on primary dysmenorrhea by inhibiting the inflammatory response and modulating oxidative stress and apoptosis by regulating the COX-2/PGE2 pathway.

Repurposing of Bryophyllum pinnatum for dysmenorrhea treatment: a systematic scoping review and case series.

Dysmenorrhea affects women throughout their reproductive years but there has been a lack of effective and well-tolerated treatment options. Pain symptoms mainly result from inflammatory processes and increased contractile activity in the myometrium. The reported use of Bryophyllum pinnatum preparations against inflammation and pain in ethnomedicine as well as current pharmacological data on their inhibition of myometrial contractility led us to hypothesize that this medicinal plant might be a new treatment option for dysmenorrhea. In the first part of the present work, clinical, in vivo, and in vitro studies on the anti-nociceptive and anti-inflammatory, as well as on myometrium relaxing properties of B. pinnatum are reviewed. In the second part, cases of five women with dysmenorrhea who were tentatively treated with a B. pinnatum product are described. The review revealed thirty-three experimental in vivo and in vitro studies, but no clinical study, reporting anti-nociceptive and anti-inflammatory effects of B. pinnatum extracts and compounds in a wide range of conditions. Moreover, sixteen publications on smooth muscle contractility revealed relaxing effects. The latter consisted of clinical evidence, as well as of in vivo and in vitro data. The evidence reviewed therefore provided a rational basis for the use of B. pinnatum in the treatment of dysmenorrhea. We subsequently set out to tentatively treat patients with a well-tolerated B. pinnatum product that is registered (without indication) and commonly used in obstetrics and gynecology in Switzerland. All five treated patients reported a reduction in pain symptoms and 4 out of 5 indicated a reduced intake of painkillers during menstruation. Taken together, the reviewed information on the pharmacological properties and clinical evidence of B. pinnatum extracts and compounds as well as the outcomes of all five patients in the case series support our hypothesis in favor of B. pinnatum as a new, well-tolerated therapeutic approach for dysmenorrhea. Prospective clinical studies are urgently needed.

[Therapeutic effect of Leonuri Herba aqueous decoction on primary dysmenorrhea in rats and its metabolomic analysis].

This study aimed to investigate the therapeutic effect of Leonuri Herba aqueous decoction on primary dysmenorrhea(PD) and explore the underlying mechanism in conjunction with untargeted metabolomics. Forty adult female rats were randomly divi-ded into a normal group, a model control group, ibuprofen(0.12 g·kg~(-1)) group, and high-and low-dose Leonuri Herba aqueous decoction(5 and 2.5 g·kg~(-1)) groups, with eight rats in each group. The PD rat model was prepared using intramuscular injection of estradiol benzoate combined with intraperitoneal injection of pitocin. Drugs were administered by gavage from the 4th day of modeling for 7 d. After the last administration, pitocin was injected intraperitoneally, and the writhing latency and writhing times within 30 min were recorded. The uterine and ovarian coefficients were determined. Estradiol(E_2), progesterone(Prog), oxytocin(OT), cyclooxyge-nase 2(COX-2), prostaglandin E_2(PGE_2), prostaglandin F_(2α)(PGF_(2α)), and Ca~(2+) levels in uterine tissues were measured by ELISA and biochemical kits. Morphological changes in uterine and ovarian tissues were observed by hematoxylin-eosin(HE) staining. The protein expression of oxytocin receptor(OTR), prostaglandin E_2 receptor 3(EP3), and estrogen receptor alpha(ERα) in uterine tissues was detected by immunohistochemistry. The mRNA expression of OTR, PGE_2 receptors 1-4(EP1, EP2, EP3, and EP4), and PGF_(2α) receptor(FP) in uterine tissues was detected by quantitative real-time PCR. Untargeted metabolomics analysis was performed by ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(LC-QTOF-MS) technology to screen potential biomarkers and enrich metabolic pathways. The results showed that Leonuri Herba was able to significantly reduce the writhing times in PD rats(P<0.05 or P<0.01), significantly reduce the uterine and ovarian coefficients(P<0.01), and improve their histomorphology. After treatment with Leonuri Herba, PGE_2 content was significantly increased(P<0.05), COX-2, PGF_(2α) and Ca~(2+) content, and PGF_(2α)/PGE_2 was significantly decreased(P<0.05 or P<0.01), and OT content was decreased, while E_2 and Prog content tended to further increase in uterine tissues of PD rats. Correspondingly, OTR and EP3 protein expression was significantly downregulated(P<0.05 or P<0.01) and ERα protein expression was upregulated(P<0.05) in uterine tissues. The mRNA expression of FP and EP4 in uterine tissues was significantly downregulated(P<0.01), and the mRNA expression of EP1, EP3, and OTR showed a decreasing trend. The untargeted metabolomics results showed that 10 differential metabolites were restored in the plasma of PD rats after Leonuri Herba treatment. The results indicate that Leonuri Herba is effective in the prevention and treatment of PD, and the underlying mechanism may be attributed to the regulation of PGs synthesis and corresponding receptor binding.