Gui Zhi Fu Ling Wan

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Chinese Medicine Research Hub

Randomised Controlled Trial

Gui Zhi Fu Ling Wan significantly reduced menstrual pain in primary dysmenorrhea patients with heat-burning blood-stasis syndrome, without notable adverse effects.

2023 Journal of Ethnopharmacology Effect of Guizhi Fuling Wan in primary dysmenorrhea: A randomized controlled trial
Luo Y, Mao P, Chen P, Li C, Fu X, Zhuang M

Chinese Medicine Research Hub

Network Pharmacology

Gui Zhi Fu Ling Wan can lessen the expression of certain proteins, which may be key to its ability to impede abnormal tissue invasion and metastasis in adenomyosis.

2022 Evidence-Based Complementary and Alternative Medicine Analysis of the Mechanism of GuizhiFuling Wan in Treating Adenomyosis Based on Network Pharmacology Combined with Molecular Docking and Experimental Verification
Shi Y, Zhang C, Wang X, Wang Z, Zhang Y, Liu Z, Wang X, Shi W

Chinese Medicine Research Hub

Cohort Study

The majority of reproductive age women with endometriosis in Taiwan use traditional Chinese medicine, specifically Gui Zhi Fu Ling Wan, to relieve related symptoms.

2022 Frontiers in Pharmacology The Traditional Chinese Medicine Prescription Pattern of Endometriosis Patients in Taiwan: A Population-Based Study
Ruei-Chi Fang, Yueh-Ting Tsai, Jung-Nien Lai, Chia-Hao Yeh, Chien-Tung Wu

Chinese Medicine Research Hub

Network Pharmacology

Gui Zhi Fu Ling Wan treats adenomyosis by intervening in local estrogen signalling pathways and affecting estrogen resistance via myometrium signalling pathways.

2021 Evidence-Based Complementary and Alternative Medicine Integrating Network Pharmacology and Experimental Validation Deciphers the Mechanism of Guizhi Fuling Wan against Adenomyosis
Wang H, Zhang J, Zhu Q, Fu X, Li C

Chinese Medicine Research Hub

Experimental Study

Gui Zhi Fu Ling Wan can potentially reduce and induce apoptosis in uterine leiomyomas cells.

2019 Frontiers in Pharmacology Gyejibongnyeong-Hwan (Gui Zhi Fu Ling Wan) Ameliorates Human Uterine Myomas via Apoptosis
Lee SM, Choi ES, Ha E, Ji KY, Shin SJ, Jung J

Chinese Medicine Research Hub

Systematic Review

Guizhi Fuling formula shows potential in treating uterine fibroids.

2014 BMC Complementary Medicine and Therapies Chinese herbal medicine Guizhi Fuling Formula for treatment of uterine fibroids: a systematic review of randomised clinical trials
Chen NN, Han M, Yang H, Yang GY, Wang YY, Wu XK, Liu JP

Executive Summary

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A Randomised Controlled Trial published in 2023 in the journal Journal of Ethnopharmacology found that Gui Zhi Fu Ling Wan significantly reduced menstrual pain in primary dysmenorrhea patients with heat-burning blood-stasis syndrome, without notable adverse effects. In the methodology, a randomized, double-blinded, placebo-controlled trial was conducted. Eligible patients suffering from primary dysmenorrhea with heat-burning blood-stasis syndrome were randomly placed into two groups – one received Guizhi Fuling Wan, the other a placebo, administered twice daily across three menstrual cycles, with a 3-month follow-up. The primary measurement was the change in pain intensity from the beginning to the 6th month, gauged by using a Visual Analog Scale. In the discussion of results, data showed that the pain intensity (measured using Visual Analog Scale) significantly decreased in the Guizhi Fuling Wan group compared to the placebo over the 6 month period. Secondary measurements also indicated a greater reduction in Cox Menstrual Symptom Scale, Self-rating Anxiety Scale, and traditional Chinese medicine syndrome scores in the Guizhi Fuling Wan group compared to the placebo. However, there was no significant difference between the two groups when measuring the Self-rating Depression Scale. Furthermore, no serious adverse events were observed during the trial.

A Network Pharmacology published in 2022 in the journal Evidence-Based Complementary and Alternative Medicine found that Gui Zhi Fu Ling Wan can lessen the expression of certain proteins, which may be key to its ability to impede abnormal tissue invasion and metastasis in adenomyosis. Firstly, an approach called network pharmacology was utilized which involved identifying active components of GuizhiFuling Wan (GFW), its drug targets and disease targets through public databases, and finding shared targets. The biological function and pathway of GFW in treating adenomyosis were analyzed. Then, the interaction and strength of binding between key components and targets of GFW were verified by a method known as molecular docking. In the animal part of the study, the impact of GFW on the expression of several proteins in mice with adenomyosis was observed using different staining, protein analysis, and immunohistochemical techniques. Through collecting and intersecting data, 26 common targets were identified, with the key active compounds being baicalein, sitosterol, and -sitosterol, and the key targets being certain proteins. Enrichment analyses showed that processes such as the positive regulation of vascular endothelial migration and signaling pathways were involved in regulating angiogenesis, invasion, and metastasis in adenomyosis. Furthermore, the molecular docking results suggested that the key active compounds had substantial binding potential with the key proteins. In vivo analysis suggested that GFW could decrease the serum content and protein expression of certain proteins in mice with adenomyosis. These findings reinforce the hypothesis that reducing the expression of these proteins might be a significant mechanism for GFW in inhibiting the invasion and metastasis of atypical tissues associated with adenomyosis.

A Cohort Study published in 2022 in the journal Frontiers in Pharmacology found that The majority of reproductive age women with endometriosis in Taiwan use traditional Chinese medicine, specifically Gui Zhi Fu Ling Wan, to relieve related symptoms. The methodology of this study involved analyzing the use of TCM among women with endometriosis in Taiwan. Researchers evaluated the usage, frequency of service, and the specific Chinese herbal products prescribed for endometriosis using a randomly sampled cohort of 1,000,000 beneficiaries from the National Health Insurance Research Database. In terms of results, it was found that most women with endometriosis used TCM in dealing with their symptoms. These women were more likely to seek out TCM treatment than those without symptoms. Gui-Zhi-Fu-Ling-Wan, a Cinnamon Twig and Poria Pill known for its sedative and anti-inflammatory properties, was the most commonly prescribed Chinese herbal formula. This specific TCM plays a significant role in treating the discomfort associated with endometriosis, showing a preference towards natural remedies over conventional ones.

A Network Pharmacology published in 2021 in the journal Evidence-Based Complementary and Alternative Medicine found that Gui Zhi Fu Ling Wan treats adenomyosis by intervening in local estrogen signalling pathways and affecting estrogen resistance via myometrium signalling pathways. This study utilized network pharmacology, molecular docking and animal experiments to understand the treatment mechanisms of Guizhi Fuling Wan on adenomyosis. Initially, key indices and target components of the traditional Chinese medicine were identified through various databases, which resulted in isolation of 55 active ingredients and 44 targets specifically related to adenomyosis treatment. These components were then subjected to protein interaction analysis and compound-hub target network constructions. Main active elements and hub targets were subsequently studied with molecular docking tech. The pathway enrichment analysis showed that the medicinal effects were primarily linked to estrogen signaling, endocrine resistance, and a specific tyrosine kinase signaling pathway. The molecular docking revealed that significant compounds of Guizhi Fuling Wan had a strong binding ability with a couple of cellular receptors. Animal trials indicated that this medicine could reduce abnormal infiltration of specific cells without interrupting normal sexual cycles. These results point towards the importance of the estrogen signaling pathway and cell receptors in the treatment capabilities of Guizhi Fuling Wan.

A Experimental Study published in 2019 in the journal Frontiers in Pharmacology found that Gui Zhi Fu Ling Wan can potentially reduce and induce apoptosis in uterine leiomyomas cells. In the study, human uterine myoma cells (hUtMCs) were collected from patients who had undergone surgery for this condition. The viability of these cells was tested when exposed to various doses of Gyejibongnyeong-hwan (GBH). Determination of adequate concentration for the treatment was also performed, ensuring that it did not affect normal cells adversely. Western blotting was employed to identify the expression levels of certain proteins that indicate cellular apoptosis, while the levels of reactive oxygen species were evaluated through fluorescence microscopy. Finally, the researchers looked into the time-dependent anti-neoplastic effect of GBH in order to establish an appropriate treatment duration under a non-harmful concentration of the medication. The results showed that Gyejibongnyeong-hwan (GBH) drastically reduced the viability and number of hUtMCs within 48 hours in a dose-dependent manner. It was identified that the ratio of certain proteins and the expression of other apoptosis-related ones increased, suggesting that GBH induced cellular self-destruction in uterine leiomyomas. Moreover, it was shown that GBH noticeably increased the mitochondrial concentration of reactive oxygen species. Conversely, by using certain inhibitors along with GBH, the apoptotic effect mediated by GBH was mitigated. This evidence suggests that GBH could potentially trigger apoptosis of leiomyomas and hence, presents a promising therapeutic agent in managing uterine leiomyomas.

A Systematic Review published in 2014 in the journal BMC Complementary Medicine and Therapies found that Guizhi Fuling formula shows potential in treating uterine fibroids. This comprehensive review analyzed 21 trials (including three meta-analyses and eight individual trials) regarding the effectiveness of Guizhi Fuling Formula combined with mifepristone in treating uterine fibroids. The results indicated potential benefits in reducing fibroid volume and uterine size compared to mifepristone alone. However, the overall methodological quality of the included trials was deemed poor, with issues such as unclear randomization procedures and lack of blinding. Further high-quality clinical trials with larger sample sizes are recommended to provide more conclusive evidence on the efficacy of this treatment approach for uterine fibroids.

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