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Cimicifugae Rhizoma, generally known as “Sheng Ma” in China, has great medicinal and dietary values. Cimicifugae Rhizoma is the dried rhizome of Cimicifuga foetida L., Cimicifuga dahurica (Turcz.) Maxim. and Cimicifuga heracleifolia Kom., which has been used to treat wind-heat headache, tooth pain, aphtha, sore throat, prolapse of anus and uterine prolapse in traditional Chinese medicine. This review systematically presents the traditional uses, phytochemistry, pharmacology, clinical studies, quality control and toxicity of Cimicifugae Rhizoma in order to propose scientific evidence for its rational utilization and product development. Herein, 348 compounds isolated or identified from the herb are summarized in this review, mainly including triterpenoid saponins, phenylpropanoids, chromones, alkaloids, terpenoids and flavonoids. The crude extracts and its constituents had various pharmacological properties such as anti-inflammatory, antitumor, antiviral, antioxidant, neuroprotective, anti-osteoporosis and relieving menopausal symptoms. The recent research progress of Cimicifugae Rhizoma in ethnopharmacology, phytochemistry and pharmacological effects demonstrates the effectiveness of its utilization and supplies valuable guidance for further research. This review will provide a basis for the future development and utilization of Cimicifugae Rhizoma.

Background and Objectives: Cimicifugae Rhizoma, also known as ‘Sheng ma’ in Madeiran, is a widely used Chinese herbal medicine that has several pharmacological qualities, one of which is its antioxidant activity. Isoferulic acid, a prominent phenolic compound found in Cimicifugae Rhizoma, has potent antioxidant properties. This study was aimed to comprehensively analyze the components in Cimicifugae Rhizoma and rat plasma to evaluate the in vitro antioxidant and anti-inflammatory properties of Cimicifugae Rhizoma extract and Isoferulic acid as potential candidates for developing herbal formulations targeting podocyte injury in diabetic nephropathy for further clinical utilization. Materials and Methods: UPLC/Q-TOF-MS and HPLC were utilized as analytical tools to identify components of Cimicifugae Rhizoma extract or rat plasma after administrating it. MPC5 cells were cultured with H2O2 and high glucose and subjected to oxidative stress injury. The CXCL12/CXCR4 system plays a crucial role at certain stages of multiple kidney diseases’ injury. Apoptosis-related and target CXCL12/CXCR4/mTOR/Caspase-3 and Cask protein levels were assessed, and the levels of inflammatory-related factors, motility, morphology, ROS level, and apoptosis in podocytes were tested. Results: A total of 82 and 39 components were identified in the Cimicifugae Rhizoma extract and plasma, and Isoferulic acid content was determined as 6.52 mg/g in the Cimicifugae Rhizoma extract. The Cimicifugae Rhizoma extract (1 μg/mL) and Isoferulic acid (10, 25, 50 μM) considerably decreased high glucose and oxidative-stress-mediated toxicity, impaired mobility and adhesion and apoptotic changes in MPC5 cells, and reversed inflammation response. Moreover, the Cimicifugae Rhizoma extract and Isoferulic acid down-regulated Cask, mTOR, and Caspase-3, while significantly blocking the overactivation of CXCL12/CXCR4 in podocytes stimulated by oxidative stress and high glucose. Conclusions: These results indicate that the renal protective mechanism of the Cimicifugae Rhizoma extract and Isoferulic acid on simulating H2O2-induced podocyte injury involves mainly the of CXCL12/CXCR4 pathways and the inactivation of oxidative-stress-mediated apoptotic pathways after comprehensive qualitative and quantitative research by UPLC/Q-TOF-MS and HPLC. These findings provide an important efficacy and ingredient basis for further study on the clinical utilities of Cimicifugae Rhizoma and Isoferulic acid on podocyte and kidney impairment.

Cimicifugae is a commonly used treatment for breast cancer, but the specific molecular mechanisms underlying its effectiveness remain unclear. In this research, we employ a combination of network pharmacology, molecular docking, and molecular dynamics simulations to uncover the most potent phytochemical within Cimicifugae rhizoma in order to delve into its interaction with the target protein in breast cancer treatment. We identified 18 active compounds and 89 associated targets, primarily associated to various biological processes such as lipid metabolism, the signaling pathway in diabetes, viral infections, and cancer-related pathways. Molecular docking analysis revealed that the two most active compounds, Formononetin and Cimigenol, exhibit strong binding to the target protein AKT1. Through molecular dynamics simulations, we found that the Cimigenol-AKT1 complex exhibits greater structural stability and lower interaction energy compared to the stigmasterol-AKT1 complex. Our study demonstrates that Cimicifugae rhizoma exerts its effects in breast cancer treatment through a multi-component, multi-target synergistic approach. Furthermore, we propose that Cimigenol, targeting AKT-1, represents the most effective compound, offering valuable insights into the molecular mechanisms underpinning its role in breast cancer therapy.

BackgroundAs a typical Chinese herbal medicine, rhizoma Cimicifugae (RC, 升麻 in Chinese) possesses various pharmacological effects involved in antioxidant activity. However, its antioxidant activity has not been reported so far. The aim of the present study was to systematically evaluate the antioxidant ability of RC in vitro, then discuss the mechanism.MethodsFirstly, five RC extracts (i.e. petroleum ether extract PERC, ethyl acetate extract EARC, absolute ethanol extract AERC, 95% ethanol extract 95ERC, and water extract WRC) were prepared and determined by various antioxidant methods, including anti-lipidperoxidation, protection against DNA damage, ·OH scavenging, ·O2- scavenging, DPPH· (1,1-diphenyl-2-picryl-hydrazl radical) scavenging, ABTS+· (2,2’-azino-bis (3-ethylbenzo- thiazoline-6-sulfonic acid radical ion) scavenging, Cu2+-chelating, and Fe3+ reducing assays. Subsequently, we measured the chemical contents of five RC extracts, including total phenolics, total saponins, total sugars, caffeic acid, ferulic acid and isoferulic acid. Finally, we quantitatively analyzed the correlations between antioxidant levels (1/IC50 values) and chemical contents.ResultsIn the study, the antioxidant levels and chemical contents (including total phenolics, total saponins, total sugars, caffeic acid, ferulic acid and isoferulic acid) of five RC extracts were determined by various methods. In all antioxidant assays, five RC extracts increased the antioxidant levels in a dose-dependent manner. However, their antioxidant levels (IC50 values) and chemical contents significantly differed from each other. Quantitative analysis of the correlation showed that total phenolic was of significant positive correlations (average R value was 0.56) with antioxidant levels; In contrast, total sugars and total saponins had no positive correlation with antioxidant (the average R values were −0.20 and −0.26, for total sugars and total saponins, respectively); Among total phenolics, three phenolic acids (caffeic acid, ferulic acid and isoferulic acid) also displayed positive correlations (the average R values were 0.51, 0.50, and 0.51, for caffeic acid, ferulic acid and isoferulic acid, respectively).ConclusionsAs an effective antioxidant, Rhizoma Cimicifugae can protect DNA and lipids against oxidative damage. Its antioxidant ability can be responsible for its various pharmacological effects and may be mainly attributed to the existence of total phenolics, among which caffeic acid, ferulic acid and isoferulic acid are regarded as main bioactive components. Rhizoma Cimicifugae exerts its antioxidant effect through metal-chelating, and radical-scavenging which is via donating hydrogen atom (H·) and donating electron (e).

Cimicifugae Rhizoma has been used as a medicinal herb for fever, pain, and inflammation in East Asia. We conducted this study because the effect of Cimicifugae Rhizoma extract (CRE) on allergic asthma has not yet been evaluated. To induce allergic airway inflammation, we intraperitoneally injected ovalbumin (OVA) mixed with aluminum hydroxide into mice twice at intervals of 2 weeks (Days 0 and 14) and then inhaled them thrice with 1% OVA solution using a nebulizer (Days 21 to 23). CRE (30 and 100 mg/kg) was administered orally daily for 6 days (Days 18 to 23). The mice showed remarkable reduction in allergic inflammation at 100 mg/kg of CRE, as evidenced by decreased inflammatory cell counts, pro-inflammatory cytokine levels, OVA-specific immunoglobulin E level, airway hyperresponsiveness, and production of mucus. Additionally, these effects were involved with the enhancement of heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidoreductase (NQO1), and nuclear factor erythroid 2-related factor 2 (Nrf2) expression and reduction of nuclear factor-κB (NF-κB) phosphorylation and matrix metalloproteinase-9 expression. Our findings indicated that CRE effectively protected against OVA-induced inflammation and oxidative stress via upregulation of the Nrf2/HO-1/NQO1 signaling and downregulation of NF-κB phosphorylation in asthma caused by OVA.

Objective: A model of Near Infrared Diffuse Reflectance Spectroscopy (NIR-DRS) was established for the first time to determine the content of Shengmaxinside I in the honey-fried processing of Rhizoma Cimicifugae. Methods: Shengmaxinside I content was determined by high-performance liquid chromatography (HPLC), and the data of the honey-fried processing of Rhizoma Cimicifugae samples from different batches of different origins by NIR-DRS were collected by TQ Analyst 8.0. Partial Least Squares (PLS) analysis was used to establish a near-infrared quantitative model. Results: The determination coefficient R2 was 0.9878. The Cross-Validation Root Mean Square Error (RMSECV) was 0.0193%, validating the model with a validation set. The Root Mean Square Error of Prediction (RMSEP) was 0.1064%. The ratio of the standard deviation for the validation samples to the standard error of prediction (RPD) was 5.5130. Conclusion: This method is convenient and efficient, and the experimentally established model has good prediction ability, and can be used for the rapid determination of Shengmaxinside I content in the honey-fried processing of Rhizoma Cimicifugae.

Cimicifugae Rhizoma, mainly originated from C. acerina, C. dahurica, C. foetida, C. heracleifolia, C. racemosa and C. simplex, has long been used in traditional medicine system. During the past 45 years, a lot of efforts have been dedicated to the studies on their bioactive constituents, pharmacological effects and clinical uses, and a variety of biological activities including relief of hot flash, anti-osteoporosis, anti-human immunodeficiency virus (HIV), antiinflammatory, antidiabetes, antimalaria and vasoactive property have been discovered. Although C. racemosa is widely applied to relieve menopause symptoms in clinic for its hormonal-like action, meaningfully, no estrogenic effect was confirmed up to date. The purpose of this paper is to systematically highlight these achievements and the further therapeutic potential. The origins and distributions of the rhizome are simply listed and phytochemical aspects including over 200 compounds mainly belonging to cycloartane-type triterpenoids have been summarized. The pharmacological characterizations, especially, as a clinically effective phytomedicine, the effects of the rhizoma on menopause symptoms and the clinical applications including possible mechanism have been reviewed in detail. Various in vivo, in vitro studies on the anti-bone resorption effects of the triterpenoids, together with structure-activity relationships are also incorporated to explore the therapeutic potential on osteoporosis, a major public health threat for postmenopausal women.