The Effect Components and Mechanisms of Action of Cimicifugae Rhizoma in the Treatment of Acute Pneumonia

Overview

Journal J Inflamm Res

Publisher Dove Medical Press

Date 2025 Jan 3

PMID 39749001

Authors

Jing Zhu

Yiming Huang

Chao Ye

Xiaoxia Deng

Yuxuan Zou

En Yuan

Qi Chen

Affiliations

Soon will be listed here.

Abstract

Objective: The main objective of this study was to elucidate the effector material basis of Cimicifugae Rhizoma (CR) for the treatment of acute pneumonia (AP) and to explore the potential mechanisms underlying the anti-AP effects of these active components in a lipopolysaccharide (LPS)-induced inflammation model of lung epithelial cells.

Methods: Chemical components were identified using ultra-performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UPLC-TOF-MS), and a CR component library was subsequently established based on a combination of databases and available literature. Bioinformatics techniques were used to construct "component-target" and "protein-protein interaction (PPI)" networks, and the potential active components and core targets screened according to degree value, followed by molecular docking and in vitro experiments for verification. Inflammation was induced in normal human lung epithelial cells using lipopolysaccharide (LPS) to mimic the occurrence of AP.

Results: In total, 122 CR components were identified. The therapeutic effects of potential active components against AP were associated with 147 targets involving 165 signaling pathways. Molecular docking experiments revealed the strong affinity of N-cis- feruloyltyramine, ferulic acid, cimifugin, and isoferulic acid for core AP-associated targets. In vitro cellular experiments showed that the above compounds and CR alcoholic extracts inhibited the expression of inflammatory factors in the following order: isoferulic acid > cimifugin > CR alcoholic extract > N-cis-feruloyltyramine > ferulic acid.

Conclusion: N-cis- feruloyltyramine, ferulic acid, cimifugin, and isoferulic acid were the effector components of CR with activity against AP. These compounds potentially co-regulate the IL-6/JAK/STAT3 and TLR4/IL-1β-IRAK pathways through the inhibition of cytokines such as IL-6, TNF-α, and IL-1β, and downregulation of P-STAT3, TLR4, PIK3CA, and NF-κB involved in TLR4/IL-1β-IRAK/NF-κB and PI3K-Akt signaling pathways to exert therapeutic effects on AP.

References

Hirabayashi T, Ochiai H, Sakai S, Nakajima K, Terasawa K . Inhibitory effect of ferulic acid and isoferulic acid on murine interleukin-8 production in response to influenza virus infections in vitro and in vivo. Planta Med. 1995; 61(3):221-6. DOI: 10.1055/s-2006-958060. View

Hu L, Song X, Nagai T, Yamamoto M, Dai Y, He L . Chemical profile of Cimicifuga heracleifolia Kom. And immunomodulatory effect of its representative bioavailable component, cimigenoside on Poly(I:C)-induced airway inflammation. J Ethnopharmacol. 2020; 267:113615. DOI: 10.1016/j.jep.2020.113615. View

Lu Y, Wu Y, Huang M, Chen J, Zhang Z, Li J . Fuzhengjiedu formula exerts protective effect against LPS-induced acute lung injury via gut-lung axis. Phytomedicine. 2023; 123:155190. DOI: 10.1016/j.phymed.2023.155190. View

Lipinski C, Lombardo F, Dominy B, Feeney P . Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2001; 46(1-3):3-26. DOI: 10.1016/s0169-409x(00)00129-0. View

Wang Z, Cai R, Wang G, Guo Z, Liu X, Guan Y . Combination Therapy of Phage vB_KpnM_P-KP2 and Gentamicin Combats Acute Pneumonia Caused by K47 Serotype . Front Microbiol. 2021; 12:674068. PMC: 8100603. DOI: 10.3389/fmicb.2021.674068. View

Yu Y, Zhang G, Han T, Huang H . Analysis of the pharmacological mechanism of Banxia Xiexin decoction in treating depression and ulcerative colitis based on a biological network module. BMC Complement Med Ther. 2020; 20(1):199. PMC: 7325019. DOI: 10.1186/s12906-020-02988-3. View

Lei Y, Zhu Y, Mallah M, Lu P, Yang L, He X . The activation of SIRT1 ameliorates BPDE-induced inflammatory damage in BEAS-2B cells via HMGB1/TLR4/NF-κB pathway. Environ Toxicol. 2023; 38(10):2429-2439. DOI: 10.1002/tox.23878. View

Long M, Mallampalli R, Horowitz J . Pathogenesis of pneumonia and acute lung injury. Clin Sci (Lond). 2022; 136(10):747-769. PMC: 9429452. DOI: 10.1042/CS20210879. View

Gu D, Dong N, Zheng Z, Lin D, Huang M, Wang L . A fatal outbreak of ST11 carbapenem-resistant hypervirulent Klebsiella pneumoniae in a Chinese hospital: a molecular epidemiological study. Lancet Infect Dis. 2017; 18(1):37-46. DOI: 10.1016/S1473-3099(17)30489-9. View

10.

Hwang J, Kim Y, Jang H, Oh H, Lim C, Lee S . Study of the UV Light Conversion of Feruloyl Amides from Portulaca oleracea and Their Inhibitory Effect on IL-6-Induced STAT3 Activation. Molecules. 2016; 21(7). PMC: 6273636. DOI: 10.3390/molecules21070865. View

11.

Rocha D, Caldas A, Oliveira L, Bressan J, Hermsdorff H . Saturated fatty acids trigger TLR4-mediated inflammatory response. Atherosclerosis. 2015; 244:211-5. DOI: 10.1016/j.atherosclerosis.2015.11.015. View

12.

Zhu N, Hou J . Exploring the mechanism of action Xianlingubao Prescription in the treatment of osteoporosis by network pharmacology. Comput Biol Chem. 2020; 85:107240. DOI: 10.1016/j.compbiolchem.2020.107240. View

13.

Zeng Z, Fu Y, Li M, Shi Y, Ding Q, Chen S . Guben Qingfei decoction attenuates LPS-induced acute lung injury by modulating the TLR4/NF-κB and Keap1/Nrf2 signaling pathways. J Ethnopharmacol. 2023; 323:117674. DOI: 10.1016/j.jep.2023.117674. View

14.

Stelzer G, Rosen N, Plaschkes I, Zimmerman S, Twik M, Fishilevich S . The GeneCards Suite: From Gene Data Mining to Disease Genome Sequence Analyses. Curr Protoc Bioinformatics. 2016; 54:1.30.1-1.30.33. DOI: 10.1002/cpbi.5. View

15.

Zhang W, Xue K, Gao Y, Huai Y, Wang W, Miao Z . Systems pharmacology dissection of action mechanisms of Dipsaci Radix for osteoporosis. Life Sci. 2019; 235:116820. DOI: 10.1016/j.lfs.2019.116820. View

16.

Yang X, Liu Y, Gan J, Xiao Z, Cao Y . FitDock: protein-ligand docking by template fitting. Brief Bioinform. 2022; 23(3). DOI: 10.1093/bib/bbac087. View

17.

Li W, Han J, Ren P, Xie Y, Jiang D . Exploration of the mechanism of Zisheng Shenqi decoction against gout arthritis using network pharmacology. Comput Biol Chem. 2020; 90:107358. DOI: 10.1016/j.compbiolchem.2020.107358. View

18.

Han Y, Ge C, Ye J, Li R, Zhang Y . Demethyleneberberine alleviates Pseudomonas aeruginosa-induced acute pneumonia by inhibiting the AIM2 inflammasome and oxidative stress. Pulm Pharmacol Ther. 2023; 83:102259. DOI: 10.1016/j.pupt.2023.102259. View

19.

Sakai S, Kawamata H, Kogure T, Mantani N, Terasawa K, Umatake M . Inhibitory effect of ferulic acid and isoferulic acid on the production of macrophage inflammatory protein-2 in response to respiratory syncytial virus infection in RAW264.7 cells. Mediators Inflamm. 2000; 8(3):173-5. PMC: 1781798. DOI: 10.1080/09629359990513. View

20.

Chen K, Iribarren P, Gong W, Wang J . The essential role of phosphoinositide 3-kinases (PI3Ks) in regulating pro-inflammatory responses and the progression of cancer. Cell Mol Immunol. 2005; 2(4):241-52. View