Pharmacological Potential of the Genus Chloranthus as Antioxidant, Cytotoxic, and Anti-inflammatory Agents: A Systematic Review
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Abstract
The Chloranthus genus (Chloranthaceae family) has been traditionally used in Asian medicine as an anti-inflammatory agent, but recent scientific exploration reveals broader pharmacological potential. This systematic review aims to evaluate the latest experimental evidence on the antioxidant, cytotoxic, and anti-inflammatory activities of Chloranthus-derived compounds and elucidate their molecular mechanisms. Studies were selected through structured database searches using specific keyword combinations and screened using rigorous inclusion-exclusion criteria. The findings highlight a predominance of sesquiterpenoids, particularly lindenane-type (monomers, dimers, and trimers), which consistently exhibit anti-inflammatory effects via inhibition of NF-κB and MAPK pathways and modulation of the NLRP3 inflammasome. Antioxidant activity through the Nrf2/Keap1 pathway and cytotoxic effects against cancer cells were also frequently reported. Notably, several compounds demonstrated dual actions, suppressing both ROS (Reactive Oxygen Species) production and proinflammatory cytokines, emphasizing their relevance in treating diseases involving oxidative stress and inflammation. These results support Chloranthus as a promising natural source of multitarget bioactive compounds. Future research should adopt a multidisciplinary approach to further elucidate molecular targets, validate in vivo efficacy, and explore novel biological resources.
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References
Musayyaf AF, Haryoto. Determination of Antidiabetic Activity of Ethanolic Extract of Karas Tulang Leaves (Chloranthus Erectus) In Alloxan-Induced Wistar Rats. Int J Med Sci Clin Res Stud 2024;04:2418–22. DOI: https://doi.org/10.47191/ijmscrs/v4-i12-39
Prastanti RF, Haryoto. Aktivitas Antioksidan dan Sitotoksik Ekstak Etanol Daun Karas Tulang (Chlorantus erectus) Terhadap Sl Hela. J Insa Farm Indones 2024;7:410–20. https://doi.org/10.36387/jifi.v7i3.2294.
Ye S, Zheng Q, Zhou Y, Bai B, Yang D, Zhao Z. Chlojaponilactone B attenuates lipopolysaccharide-induced inflammatory responses by suppressing TLR4-mediated ROS generation and NF-κB signaling pathway. Molecules 2019;24. https://doi.org/10.3390/molecules24203731. DOI: https://doi.org/10.3390/molecules24203731
Wen Q, Zhan B, Jin L, Peng Z, Liu J, Zhu L, et al. Chlojaponilactone B Attenuates THP-1 Macrophage Pyroptosis by Inhibiting the TLR/MyD88/NF-κB Pathway. Pharmaceuticals 2024;17:1–19. https://doi.org/10.3390/ph17030402. DOI: https://doi.org/10.3390/ph17030402
Li Y, Liu W, Xu J, Guo Y. Chlorahololide D, a Lindenane-Type Sesquiterpenoid Dimer from Chloranthus holostegius Suppressing Breast Cancer Progression. Molecules 2023;28. https://doi.org/10.3390/molecules28207070. DOI: https://doi.org/10.3390/molecules28207070
Zhan ZC, Xia YP, Tang Q, Zhu HH, Du JY, Cai JX, et al. Lindenane sesquiterpenoid dimers from Chloranthus holostegius with anti-neuroinflammatory activities in BV-2 microglia. Phytochemistry 2023;215:113859. https://doi.org/10.1016/J.PHYTOCHEM.2023.113859. DOI: https://doi.org/10.1016/j.phytochem.2023.113859
Yin XW, Hu JJ, Ren FC, Pu XD, Yang MY, Yang BY, et al. Anti-inflammatory Lindenane Sesquiterpene Dimers from the Roots of Chloranthus fortunei. ACS Omega 2024;9:34869–79. https://doi.org/10.1021/acsomega.4c04403. DOI: https://doi.org/10.1021/acsomega.4c04403
Wang S, Sun Y, Li Y, Xu W, Li Q, Mu Y, et al. Rearranged Lindenane Sesquiterpenoid Trimers from Chloranthus fortunei: Target Discovery and Biomimetic Conversion. J Org Chem 2023;88:347–54. https://doi.org/10.1021/ACS.JOC.2C02372/SUPPL_FILE/JO2C02372_SI_002.ZIP. DOI: https://doi.org/10.1021/acs.joc.2c02372
Park JH, Choi JW, Ju EJ, Pae AN, Park KD. Antioxidant and anti-inflammatory activities of a natural compound, shizukahenriol, through Nrf2 activation. Molecules 2015;20:15989–6003. https://doi.org/10.3390/molecules200915989. DOI: https://doi.org/10.3390/molecules200915989
Yan H, Xu LL, Zheng XF, Zou XF, Xiao LG, Zhou YS, et al. Sesquiterpenes from Chloranthus holostegius with anti-inflammatory activities. Fitoterapia 2024;172:105766. https://doi.org/10.1016/J.FITOTE.2023.105766. DOI: https://doi.org/10.1016/j.fitote.2023.105766
Chiu LC, Wang JY, Lin CH, Hsu CH, Lin LC, Fu SL. Diterpenoid compounds isolated from chloranthus oldhamii solms exert anti-inflammatory effects by inhibiting the ikk/nf-κb pathway. Molecules 2021;26. https://doi.org/10.3390/molecules26216540. DOI: https://doi.org/10.3390/molecules26216540
Nursoleha E, Utami W. ORIGINAL ARTICLE Effectiveness of Combination Glutathione Depletion Agent ( GSH ) and Glutathione S- Transferase ( GST ) Inhibitors of Cisplatin Resistance on Cancer Cells : Systematic Literature Review Efektivitas Kombinasi Agen Pendeplesi Glutathione ( 2025:694–705. DOI: https://doi.org/10.36490/journal-jps.com.v8i2.777
Huang W ming, Bian Y ting, Chen F you, Ning T jiao, Zhu Z ying, Chen Z chao, et al. Chlomultiols A-L, sesquiterpenoids from Chloranthus multistachys and their anti-inflammatory activities. Phytochemistry 2022;193:113001. https://doi.org/10.1016/J.PHYTOCHEM.2021.113001. DOI: https://doi.org/10.1016/j.phytochem.2021.113001
Wu XJ, Cao D, Chen FL, Shen RS, Gao J, Bai LP, et al. Chlorfortunones A and B, Two Sesquiterpenoid Dimers, Possessing Dispiro[4,2,5,2]pentadecane-6,10,14-tren Moiety from Chloranthus fortunei. ACS Omega 2022;7:35063–8. https://doi.org/10.1021/acsomega.2c03927. DOI: https://doi.org/10.1021/acsomega.2c03927
Wang X, Zan Z, Chi J, Huang A, Zhang D, Jiang H, et al. Anti-inflammatory lindenane sesquiterpenoid dimers from the roots of Chloranthus holostegius var. trichoneurus. J Nat Med 2024;78:995–1002. https://doi.org/10.1007/S11418-024-01817-Y/METRICS. DOI: https://doi.org/10.1007/s11418-024-01817-y
Wang XJ, Yu SZ, Xin JL, Pan LL, Xiong J, Hu JF. Further terpenoids from the Chloranthaceae plant Chloranthus multistachys and their anti-neuroinflammatory activities. Fitoterapia 2022;156:105068. https://doi.org/10.1016/J.FITOTE.2021.105068. DOI: https://doi.org/10.1016/j.fitote.2021.105068
Gong X, Zhou Y, Wu P, He L, Ou C, Xiao X, et al. The petroleum ether extracts of Chloranthus fortunei(A. Gray) Solms-Laub.with bioactivities: A rising source in HCC drug treatment. J Ethnopharmacol 2024;333:118414. https://doi.org/10.1016/J.JEP.2024.118414. DOI: https://doi.org/10.1016/j.jep.2024.118414
Liu S, Wang XX, Wang J, Yang H, Zhang ZM, Zhuang PY, et al. Discovery of sesquiterpenoids from the roots of Chloranthus henryi Hemsl. var. hupehensis (Pamp.) K. F. Wu and their anti-inflammatory activity by IKBα/NF-κB p65 signaling pathway suppression. Bioorg Chem 2024;147:107420. https://doi.org/10.1016/J.BIOORG.2024.107420. DOI: https://doi.org/10.1016/j.bioorg.2024.107420
Kietrungruang K, Sookkree S, Sangboonruang S, Semakul N, Poomanee W, Kitidee K, et al. Ethanolic Extract Propolis-Loaded Niosomes Diminish Phospholipase B1, Biofilm Formation, and Intracellular Replication of Cryptococcus neoformans in Macrophages. Molecules 2023;28. https://doi.org/10.3390/molecules28176224. DOI: https://doi.org/10.3390/molecules28176224
Feng WJ, Huang PZ, Zhang LM, Ma Q, Hu HY, Gu Y, et al. Anti-inflammatory sesquiterpenoids from Chloranthus japonicus. Phytochemistry 2025;234:114433. https://doi.org/10.1016/J.PHYTOCHEM.2025.114433. DOI: https://doi.org/10.1016/j.phytochem.2025.114433
Feng WJ, Gu Y, Huang PZ, Yang HY, Zhang R, He YL, et al. Chlorajaponins A—Q, Lindenane-Related Sesquiterpenoid Dimers from Chloranthus japonicus and Their Biological Activities. Chinese J Chem 2024;42:1247–59. https://doi.org/10.1002/CJOC.202300731. DOI: https://doi.org/10.1002/cjoc.202300731
Dong X, Qu L, Xiong J, Wang B, Sha X, Wu B, et al. Shizukaol C alleviates trimethylamine oxide-induced inflammation through activating Keap1-Nrf2-GSTpi pathway in vascular smooth muscle cell. Phytomedicine 2024;128:155403. https://doi.org/10.1016/J.PHYMED.2024.155403. DOI: https://doi.org/10.1016/j.phymed.2024.155403
Xiao LG, Huang JX, Yan H, Li YX, Yang XY, Ni W, et al. Highly Fused Lindenane Sesquiterpenoid Dimers with Apoptosis-Inducing Properties from Chloranthus holostegius var. shimianensis. J Org Chem 2025. https://doi.org/10.1021/ACS.JOC.5C00070/SUPPL_FILE/JO5C00070_SI_001.PDF. DOI: https://doi.org/10.1021/acs.joc.5c00070
Yang Y, Li Y, Hou Y, Qin M, Gong P, Liu J, et al. Design, synthesis, and biological evaluation of 4-phenoxyquinoline derivatives as potent c-Met kinase inhibitor. Bioorganic Med Chem Lett 2019;29:126666. https://doi.org/10.1016/j.bmcl.2019.126666. DOI: https://doi.org/10.1016/j.bmcl.2019.126666
Bian X xiang, Zhao X, Liu S shan, Wu L, Yin X wen, Shen C pu. Sesquiterpene dimers from Chloranthus fortunei and their protection activity against acute lung injury. Fitoterapia 2022;159:105191. https://doi.org/10.1016/J.FITOTE.2022.105191. DOI: https://doi.org/10.1016/j.fitote.2022.105191
Chen F, He M, Xu L, Liu Y, Yang B, Luo Y. Lindenane sesquiterpenoid monomers and oligomers: Chemistry and pharmacological activities. Phytochemistry 2023;215:113866. https://doi.org/10.1016/J.PHYTOCHEM.2023.113866. DOI: https://doi.org/10.1016/j.phytochem.2023.113866
Wang S, Li Y, Wang X, Zhang X, Xu F, Ying P, et al. Fortunilides M-O, anti-inflammatory lindenane sesquiterpenoid dimers from Chloranthus fortunei. Fitoterapia 2023;168:105547. https://doi.org/10.1016/J.FITOTE.2023.105547. DOI: https://doi.org/10.1016/j.fitote.2023.105547
Zhou B, Liu QF, Dalal S, Cassera MB, Yue JM. Fortunoids A-C, Three Sesquiterpenoid Dimers with Different Carbon Skeletons from Chloranthus fortunei. Org Lett 2017;19:734–7. https://doi.org/10.1021/acs.orglett.7b00066. DOI: https://doi.org/10.1021/acs.orglett.7b00066
Ye S, Wen Q, Zhu L, Qian C, Yang D, Zhao Z. Neuroprotective Effects of a New Derivative of Chlojaponilactone B against Oxidative Damaged Induced by Hydrogen Peroxide in PC12 Cells. Molecules 2022;27. https://doi.org/10.3390/molecules27186049. DOI: https://doi.org/10.3390/molecules27186049