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Proceedings of the National Academy of Sciences of Belarus, Biological Series

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Anti-inflammatory properties of extracts from plants of the Rubiaceae family

https://doi.org/10.29235/1029-8940-2026-71-2-116-124

Abstract

Rubiaceae species are widely distributed, mainly concentrated in tropical regions. They contain various alkaloids, flavonoids, and other active compounds that have significant therapeutic effects on many diseases. In this study a meta-analysis of the existing experimental data on the therapeutic effects of Rubiaceae was conducted using Cochrane, PubMed, Google Scholar, and Web of Science databases for report retrieval. The search contained “Gardenia”, “Hedyotis”, “Morinda”, “Nauclea”, and “Paederia” species of Rubiaceae, which were used in animal inflammation models. A total of 348 papers were analyzed, duplicate studies were removed, data reliability and adequate sample sizes were filtered. Proinflammatory cytokines (PCs), and the expression of inflammatory gene NF-κB were used to evaluate the inflammatory levels in two animal models, the Rubiaceae-treated (RT) and Inflammation Model (IM). Subgroup analysis was used to explore: 1) the anti-inflammatory effects of different genera; 2) the anti-inflammatory effects of different extracts. The results from meta-analysis show that Rubiaceae extracts exert significant anti-inflammatory effects in animal models, with the RT group exhibiting lower levels of PCs (IL-1β, IL-6, TNF-α) and NF-κB expression than the IM group (p < 0.05). Subgroup analysis found that Gardenia, Hedyotis, and Morinda all significantly reduced IL-1β and TNF-α levels, while only Morinda had a notable inhibitory effect on IL-6; aqueous, ethanol, and terpenoid extracts all showed significant anti-inflammatory activity. Substantial heterogeneity was observed, which subgroup and meta-regression analyses identified as being primarily due to intergeneric differences. Begg’s and Egger’s tests indicated the presence of publication bias across the included studies. Further in vivo and in vitro experiments are therefore required to verify the anti-inflammatory effects of various medicinal plants of the Rubiaceae family.

About the Authors

Yuxuan Peng
Belarusian State University
Belarus

Yuxuan Peng – Postgraduate Student. Department of Plant Cell Biology and Bioengineering, Faculty of Biology

10, Kurchatova Str., 220030, Minsk



A. F. Bakhmetava
V. F. Kuprevich Institute of Experimental Botany of the National Academy of Sciences of Belarus
Belarus

Aryna F. Bakhmetava – Junior Researcher

27, Akademicheskaya Str., 220072, Minsk



M. A. Mysleika
Университет Национальной академии наук Беларуси
Belarus

Marharyta A. Mysleika – Master’s Student

10, per. Kalinina, 220049, Minsk



V. V. Demidchik
V. F. Kuprevich Institute of Experimental Botany of the National Academy of Sciences of Belarus
Belarus

Vadim V. Demidchik – Corresponding Member, D. Sc. (Biol.), Professor, Chief Researcher

27, Akademicheskaya Str., 220072, Minsk



References

1. Martins D., Nunez C. V. Secondary Metabolites from Rubiaceae Species. Molecules, 2015, vol. 20, no. 7, pp. 13422–13495. http://doi.org/10.3390/molecules200713422

2. Jaafar A., Zulkipli M. A., Hatta F. H. M., Jahidin A. H., Nasir N. A. A., Hasan M. H. Therapeutic potentials of iridoids derived from Rubiaceae against in vitro and in vivo inflammation: A scoping review. Saudi Pharmaceutical Journal, 2024, vol. 32, no. 1, art. 101876. http://doi.org/10.1016/j.jsps.2023.101876

3. Chen R., He J., Tong X., Tang L., Liu M. The Hedyotis diffusa Willd. (Rubiaceae): A Review on Phytochemistry, Pharmacology, Quality Control and Pharmacokinetics. Molecules, 2016, vol. 21, no. 6, art. 710. http://doi.org/10.3390/molecules21060710

4. Kou Y., Li Z., Yang T., Shen X., Wang X., Li H., Zhou K., Li L., Xia Z., Zheng X., Zhao Y. Therapeutic potential of plant iridoids in depression: a review. Pharmaceutical Biology, 2022, vol. 60, no. 1, pp. 2167–2181. http://doi.org/10.1080/13880209.2022.2136206

5. Wang C., Gong X., Bo A., Zhang L., Zhang M., Zang E., Zhang Ch., Li M. Iridoids: Research Advances in Their Phytochemistry, Biological Activities, and Pharmacokinetics. Molecules, 2020, vol. 25, no. 2, art. 287. http://doi.org/10.3390/molecules25020287

6. Deng R., Li F., Wu H., Wang W.-Y., Dai L., Zhang Z.-R., Fu J. Anti-inflammatory mechanism of geniposide: inhibiting the hyperpermeability of fibroblast-like synoviocytes via the RhoA/p38MAPK/NF-κB/F-actin signal pathway. Frontiers in Pharmacology, 2018, vol. 9, no. 1, art. 105. http://doi.org/10.3389/fphar.2018.00105

7. Gao S., Feng Q. The Beneficial Effects of Geniposide on Glucose and Lipid Metabolism: A Review. Drug Design, Development and Therapy, 2022, vol. 16, no. 1, pp. 3365–3383. http://doi.org/10.2147/dddt.S378976

8. Li N., Li L., Wu H., Zhou H., Antioxidative Property and Molecular Mechanisms Underlying Geniposide‐Mediated Therapeutic Effects in Diabetes Mellitus and Cardiovascular Disease. Oxidative Medicine and Cellular Longevity, 2019, no. 1, art. 7480512. http://doi.org/10.1155/2019/7480512

9. Shen B., Feng H., Cheng J., Li Z., Jin M., Zhao L., Wang Q., Qin H., Liu G. Geniposide alleviates non‐alcohol fatty liver disease via regulating Nrf2/AMPK/mTOR signalling pathways. Journal of Cellular and Molecular Medicine, 2020, vol. 24, no. 9, pp. 5097–5108. http://doi.org/10.1111/jcmm.15139

10. Zhuge X., Jin X., Ji T., Li R., Xue L., Yu W., Quan Z., Tong H., Xu F. Geniposide ameliorates dextran sulfate sodium-induced ulcerative colitis via KEAP1-Nrf2 signaling pathway. Journal of Ethnopharmacology, 2023, vol. 314, no. 1, art. 116626. http://doi.org/10.1016/j.jep.2023.116626

11. Xu Y., Zeng J., Wang L., Xu J., He X., Wang Y. Anti-inflammatory iridoid glycosides from Paederia scandens (Lour.) Merrill. Phytochemistry, 2023, vol. 212, no. 1, art. 113705. http://doi.org/10.1016/j.phytochem.2023.113705

12. Chen X., Jiang W., Liu Y. Anti-inflammatory action of geniposide promotes wound healing in diabetic rats. Pharmaceutical Biology, 2022, vol. 60, no. 1, pp. 294–299. https://doi.org/10.1080/13880209.2022.2030760

13. Carvalho-Silva J. M., dos Reis A. C. Anti-inflammatory action of silver nanoparticles in vivo: systematic review and meta-analysis. Heliyon, 2024, vol. 10, no. 14, p. e34564. https://doi.org/10.1016/j.heliyon.2024.e34564

14. Shamsudin N. F., Ahmed Q. U., Mahmood S., Shah S. A. A., Sarian M. N., Khattak M. M. A. K., Khatib A., Sabere A. S. M., Yusoff Y. M., Latip J. Flavonoids as Antidiabetic and Anti-Inflammatory Agents: A Review on Structural Activity Relationship-Based Studies and Meta-Analysis. International Journal of Molecular Sciences, 2022, vol. 23, no. 20, art. 12605. https://doi.org/10.3390/ijms232012605

15. Chen X.-Y., Jiang W.-W., Liu Y.-L. Ma Zh.-X., Dai J.-Q. Anti-inflammatory action of geniposide promotes wound healing in diabetic rats. Pharmaceutical Biology, 2022, vol. 60, no. 1, pp. 294–299. http://doi.org/10.1080/13880209.2022.2030760

16. Cheng S., Zhou F., Xu Y., Liu X., Zhang Y., Gu M., Su Z., Zhao D., Zhang L., Jia Y. Geniposide regulates the miR101/MKP-1/p38 pathway and alleviates atherosclerosis inflammatory injury in ApoE-/- mice. Immunobiology, 2019, vol. 224, no. 2, pp. 296–306. http://doi.org/10.1016/j.imbio.2018.12.005

17. Cui Y., Wang Q., Wang M., Jia J., Wu R. Gardenia Decoction Prevent Intestinal Mucosal Injury by Inhibiting Pro-inflammatory Cytokines and NF-κB Signaling. Frontiers in Pharmacology, 2019, vol. 10, no. 1, art. 180. http://doi.org/10.3389/fphar.2019.00180

18. Li H., Yang D.-H., Zhang Y., Zheng F., Gao F., Sun J., Shi G. Geniposide suppresses NLRP3 inflammasome-mediated pyroptosis via the AMPK signaling pathway to mitigate myocardial ischemia/reperfusion injury. Chinese Medicine, 2022, vol. 17, no. 1, art. 73. http://doi.org/10.1186/s13020-022-00616-5

19. Sun Q., Zhang X., Fan J., Zhang L., Ji H., Xue J., Zhang C., Chen R., Zhao J., Chen J., Liu X., Song D. Geniposide protected against cerebral ischemic injury through the anti-inflammatory effect via the NF-κB signaling pathway. Translational Neuroscience, 2023, vol. 14, no. 1, art. 20220273. http://doi.org/10.1515/tnsci-2022-0273

20. Dai M., Wang F., Zou Z., Xiao G., Chen H., Yang H. Metabolic regulations of a decoction of Hedyotis diffusa in acute liver injury of mouse models. Chinese Medicine, 2017, vol. 12, no. 1, art. 35. http://doi.org/10.1186/s13020-017-0159-4

21. Li Y., Ding T., Chen J., Ji J., Wang W., Ding B., Ge W., Fan, Y., Xu, L. The protective capability of Hedyotis diffusa Willd on lupus nephritis by attenuating the IL-17 expression in MRL/lpr mice. Frontiers in Immunology, 2022, vol. 13, no. 1, art. 943827. http://doi.org/10.3389/fimmu.2022.943827

22. Liu R., Wang P., Wu C., Chen J., Li Ch., Xie Y., Wang Q., Liu J., He H., Zhu J. Therapeutic effects of Hedyotis diffusa Willd in a COPD mouse model challenged with LPS and smoke. Experimental and Therapeutic Medicine, 2018, vol. 15, no. 4, pp. 3385–3391. http://doi.org/10.3892/etm.2018.5851

23. Wang L.-F., OuYang F., Ma Y., Sun R., Tan S.-W., Xiao L., Yang Q.-W. Effect of Hedyotis diffusa Willd extract on gouty arthritis in rats. Tropical Journal of Pharmaceutical Research, 2021, vol. 20, no. 1, pp. 129–134. http://doi.org/10.4314/tjpr.v20i1.19

24. Ye J.-H., Liu M.-H., Zhang X.-L., He J.-Y. Chemical Profiles and Protective Effect of Hedyotis diffusa Willd in Lipo polysaccharide-Induced Renal Inflammation Mice. International Journal of Molecular Sciences, 2015, vol. 16, no. 11, pp. 27252–27269. http://doi.org/10.3390/ijms161126021

25. Krishnakumar N. M., Manikantan K., Suja S. N. R., Latha P. G., Ceasar S. A. Morinda umbellata active fraction inhibits lipopolysaccharide induced proinflammatory cytokines by downregulating NF-κB activation. Toxicology Research, 2022, vol. 11, no. 5, pp. 841–851. http://doi.org/10.1093/toxres/tfac063

26. Liang J., Liang J., Hao H., Lin H., Wang P., Wu Y., Jiang X., Fu Ch., Li Q., Ding P., Liu H., Xiong Q., Lai X., Zhou L., Chan Sh., Hou Sh. The Extracts of Morinda officinalis and Its Hairy Roots Attenuate Dextran Sodium Sulfate- Induced Chronic Ulcerative Colitis in Mice by Regulating Inflammation and Lymphocyte Apoptosis. Frontiers in Immunology, 2020, vol. 11, no. 1, art. 2092. http://doi.org/10.3389/fimmu.2020.02092

27. Wan Osman W. N., Lau S. F., Mohamed S. Scopoletin-standardized Morinda elliptica leaf extract suppressed inflammation and cartilage degradation to alleviate osteoarthritis: A preclinical study. Phytotherapy Research, 2017, vol. 31, no. 12, pp. 1954–1961. http://doi.org/10.1002/ptr.5949

28. Zhang Q., Zhang J.-H., He Y.-Q., Zhang Q.-L., Zhu B., Shen Y., Liu M.-Q., Zhu L.-L., Xin H.-L., Qin L.-P., Zhang Q.-Y. Iridoid glycosides from Morinda officinalis How. exert anti-inflammatory and anti-arthritic effects through inacti vating MAPK and NF-κB signaling pathways. BMC Complementary Medicine and Therapies, 2020, vol. 20, no. 1, art. 172. http://doi.org/10.1186/s12906-020-02895-7

29. Xu H., Xu S., Li L., Wu Y., Mai Sh., Xie Y., Tan Y., Li A., Xue F., He X., Li Y. Integrated metabolomics, network pharmacology and biological verification to reveal the mechanisms of Nauclea officinalis treatment of LPS-induced acute lung injury. Chinese Medicine, 2022, vol. 17, no. 1, art. 131. http://doi.org/10.1186/s13020-022-00685-6

30. Borgohain M. P., Chowdhury L., Ahmed S., Bolshette N., Devasani K., Das T. J., Mohapatra A., Lahkar M. Renoprotective and antioxidative effects of methanolic Paederia foetida leaf extract on experimental diabetic nephropathy in rats. Journal of Ethnopharmacology, 2017, vol. 198, no. 1, pp. 451–459. http://doi.org/10.1016/j.jep.2017.01.035

31. Hou Sh.-X., Zhu W.-J., Pang M.-Q., Jeffry J., Zhou L.-L. Protective effect of iridoid glycosides from Paederia scandens (LOUR.) MERRILL (Rubiaceae) on uric acid nephropathy rats induced by yeast and potassium oxonate. Food and Chemical Toxicology, 2014, vol. 64, no. 1, pp. 57–64. http://doi.org/10.1016/j.fct.2013.11.022

32. Zhu W., Pang M., Dong L., Huang X., Wang S., Zhou L. Anti-inflammatory and immunomodulatory effects of iridoid glycosides from Paederia scandens (LOUR.) MERRILL (Rubiaceae) on uric acid nephropathy rats. Life Sciences, 2012, vol. 91, no. 11–12, pp. 369–376. http://doi.org/10.1016/j.lfs.2012.08.013

33. Dinarello Ch. A. Proinflammatory cytokines. Chest, 2000, vol. 118, no. 2, pp. 503–508. https://doi.org/10.1378/chest.118.2.503

34. Dinarello Ch. A., van der Meer J. W. M. Treating inflammation by blocking interleukin-1 in humans. Semin Immunol, 2013, vol. 25, no. 6, pp. 469–484. http://doi.org/10.1016/j.smim.2013.10.008

35. Kim E. Y., Moudgil K. D. Regulation of autoimmune inflammation by pro-inflammatory cytokines. Immunology letters, 2008, vol. 120, no. 1–2, pp. 1–5. https://doi.org/10.1016/j.imlet.2008.07.008

36. Nennig S. E., Schank J. R. The role of NFkB in drug addiction: beyond inflammation. Alcohol and Alcoholism, 2017, vol. 25, no. 2, pp.172–179. https://doi.org/10.1093/alcalc/agw098


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ISSN 1029-8940 (Print)
ISSN 2524-230X (Online)