Pre-clinical in vitro and in vivo safety evaluation of Cimicifuga heracleifolia

Yun, Jun Won; You, Ji Ran; Kim, Yun Soon; Cho, Eun Young; Kim, Seung Hyun; Yoon, Jung Hee; Kwon, Euna; Chung, Doo Hyun; Kim, Young Tae; Jang, Ja June; Hwan, Jeong; Kang, Byeong Cheol

doi:10.1016/j.yrtph.2015.07.006

Cited by 12 publications

(4 citation statements)

References 32 publications

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“…Compared with the control group, there was no significant difference in the biochemical indicators of the RC groups ( p > 0.05). Yun [ 21 ] selected the crude extract of the rhizome of Cimicifuga heracleifolia Kom. for 13 weeks of safety evaluation, and the biochemical test results showed that the changes in various indicators are sporadic and within physiologically acceptable ranges.…”

Section: Resultsmentioning

confidence: 99%

Fibrous Roots of Cimicifuga Are at Risk of Hepatotoxicity

et al. 2022

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The cause of liver damage by using black cohosh preparation has been concerned but remains unclear. After a preliminary investigation, the black cohosh medicinal materials sold in the market were adulterated with Asian cohosh (Cimicifuga) without removing the fibrous roots. The safety of Cimicifuga rhizome and fibrous roots is unknown and has not been reported. Therefore, in this paper, the rhizome and fibrous roots of Cimicifuga dahurica (Turcz.) Maxim (C. dahurica) were completely separated, extracted with 70% ethanol, and freeze-dried to obtain crude rhizome extract (RC) and fibrous roots extract (FRC). UHPLC-Q-TOF-MS was used to identify 39 compounds in the rhizome and fibrous roots of Cimicifuga, mainly saponins and phenolic acids. In the L-02 cytotoxicity experiment, the IC50 of fibrous roots (1.26 mg/mL) was slightly lower than that of rhizomes (1.417 mg/mL). In the 90-day sub-chronic toxicity study, the FRC group significantly increased the level of white blood cells, ALP, ALT, AST, BILI and CHOL (p < 0.05); large area of granular degeneration and balloon degeneration occurred in liver tissue; and the expression of p-NF-kB in the nucleus increased in a dose-dependent manner. Overall, Fibrous roots of Cimicifuga are at risk of hepatotoxicity and should be strictly controlled and removed during the processing.

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Section: Resultsmentioning

confidence: 99%

Fibrous Roots of Cimicifuga Are at Risk of Hepatotoxicity

et al. 2022

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“…It was proven that long-term use of fibrous root could lead to serious liver damage, especially in women [ 143 ]. In a 13-week subchronic toxicity and genotoxicity study, C. heracleifolia extract (667, 2000 mg/kg) increased serum alanine transaminase activity and liver weights in female rats without effects on male [ 144 ]. Overall findings indicated that Cimicifugae Rhizoma extract may be prone to hepatotoxicity in female rats.…”

Section: Toxicologymentioning

confidence: 99%

Traditional uses, phytochemistry, pharmacology, quality control and clinical studies of Cimicifugae Rhizoma: a comprehensive review

Zhang,

Wei,

Jin

et al. 2024

Chin Med

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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.

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“…Cimicifugae Rhizoma is a traditional herbal medicine that has been taken as an analgesic, anti-inflammatory, antipyretic, and antiviral in East Asia [8][9][10][11]. It demonstrated an antioxidant effect via its metal-chelating and radical-scavenging activities in in vitro experiments [12].…”

Section: Introductionmentioning

confidence: 99%

Cimicifugae Rhizoma Extract Attenuates Oxidative Stress and Airway Inflammation via the Upregulation of Nrf2/HO-1/NQO1 and Downregulation of NF-κB Phosphorylation in Ovalbumin-Induced Asthma

et al. 2021

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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.

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Pre-clinical in vitro and in vivo safety evaluation of Cimicifuga heracleifolia

Cited by 12 publications

References 32 publications

Fibrous Roots of Cimicifuga Are at Risk of Hepatotoxicity

Fibrous Roots of Cimicifuga Are at Risk of Hepatotoxicity

Traditional uses, phytochemistry, pharmacology, quality control and clinical studies of Cimicifugae Rhizoma: a comprehensive review

Cimicifugae Rhizoma Extract Attenuates Oxidative Stress and Airway Inflammation via the Upregulation of Nrf2/HO-1/NQO1 and Downregulation of NF-κB Phosphorylation in Ovalbumin-Induced Asthma

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