skip to main content

Effects of Andrographis paniculata Leaf Extract on C-Reactive Protein and Serum Ferritin in Lipopolysaccharide-Induced Sepsis Model Rat

Rezya Salsabela  -  Faculty of Medicine, Diponegoro University, Semarang, Indonesia
*Nyoman Suci Widyastiti orcid scopus  -  Department of Clinical Pathology, Faculty of Medicine, Universitas Diponegoro, Semarang, Indonesia
Dwi Retnoningrum  -  Department of Clinical Pathology, Faculty of Medicine, Universitas Diponegoro, Semarang, Indonesia
Ariosta Ariosta  -  Department of Clinical Pathology, Faculty of Medicine, Universitas Diponegoro, Semarang, Indonesia
Neni Susilaningsih  -  Department of Anatomy-Histology, Faculty of Medicine, Universitas Diponegoro, Semarang, Indonesia

Citation Format:

Background: C-reactive protein (CRP) and ferritin are acute-phase reactants that have demonstrated association with the severity of a variety of inflammation-mediated illnesses, including infection and sepsis. Sambiloto (Andrographis paniculata) leaf is traditionally used as an anti-inflammation and anti-bacterial herb. Sambiloto leaf extract possesses anti-inflammatory, antiallergenic, immuno-stimulatory, antiviral, and antioxidant activities

Objective: To evaluate the effect of Sambiloto leaf extract (Andrographis paniculata) on inflammation biomarker (CRP and serum ferritin) in a rat model of sepsis-induced by lipopolysaccharide (LPS).

Methods: This research was a true experimental study with a post-test-only control group design. Twenty five male Wistar rats were randomly divided into 5 groups consisting of a healthy control (HC), Negative control (NC), Treatment 1 (T1) Sambiloto 200mg/kgBW, T2 Sambiloto 400mg/kgBW, T3 Sambiloto 500mg/kgBW). Sambiloto leaf extract was given on days 8-21 and LPS 5mg/kgBW was injected intraperitoneal on day 22. On the 25th day, blood was drawn and  CRP and serum ferritin levels were analyzed using ELISA method. The data were analyzed using One-Way ANOVA and Kruskal Wallis test.

Results: The mean CRP levels of HC, NC, T1, T2,T3 were 7.72 ± 2.53; 8.12 ± 1.08; 5.22 ± 1.71; 6.40 ± 1.19; 5.14 ± 1.37 ng/dl respectively. The mean serum ferritin level of HC, NC, T1, T2, T3 were 293.60 ± 66.53; 601.20 ± 100.17; 433.40 ± 194.65; 331.60 ± 75.97; 318.00 ± 69.64 ng/dl respectively. There were differences in CRP levels in groups T1(p=0.012) and T3(p=0.010), serum ferritin levels in groups T2(p=0.014) and T3(p=0.008) to the control group.

Conclusion: Sambiloto (Andrographis paniculata) leaf extract  has anti-inflammatory effects in the rat model of sepsis.
Fulltext View|Download
Keywords: Andrographis paniculata; CRP; serum ferritin; lipopolysaccharide; sepsis
Funding: This research is funded by Faculty of Medicine, Diponegoro University, grant No: 1664/UN7.5.4.2/PP2021)

Article Metrics:

  1. Gargano LM, Hughes JM. Microbial Origins of Chronic Diseases. Annu Rev Public Health. 2014 Mar 18;35(1):65–82
  2. van der Poll T, van de Veerdonk FL, Scicluna BP, Netea MG. The immunopathology of sepsis and potential therapeutic targets. Nat Rev Immunol. 2017 Jul 24;17(7):407–20
  3. Kell DB, Pretorius E. On the translocation of bacteria and their lipopolysaccharides between blood and peripheral locations in chronic, inflammatory diseases: the central roles of LPS and LPS-induced cell death. Integrative Biology. 2015 Nov 2;7(11):1339–77
  4. Bauer M, Gerlach H, Vogelmann T, Preissing F, Stiefel J, Adam D. Mortality in sepsis and septic shock in Europe, North America and Australia between 2009 and 2019— results from a systematic review and meta-analysis. Crit Care. 2020 Dec 19;24(1):239
  5. WHO calls for global action on sepsis - cause of 1 in 5 deaths worldwide [Internet]. [cited 2023 Jan 19]. Available from:
  6. Luo X pan, Wang H hong, Hu S fei, Wu S jing, Xie G hao, Cheng B li, et al. [Comparison of three different organ failure assessment score systems in predicting outcome of severe sepsis]. Zhonghua Wai Ke Za Zhi. 2009 Jan 1;47(1):48–50
  7. Kim MH, Choi JH. An Update on Sepsis Biomarkers. Infect Chemother. 2020;52(1):1
  8. Horvat CM, Fabio A, Nagin DS, Banks RK, Qin Y, Park HJ, et al. Mortality Risk in Pediatric Sepsis Based on C-reactive Protein and Ferritin Levels. Pediatric Critical Care Medicine. 2022 Dec 30;23(12):968–79
  9. Horvat CM, Bell J, Kantawala S, Au AK, Clark RSB, Carcillo JA. C-Reactive Protein and Ferritin Are Associated With Organ Dysfunction and Mortality in Hospitalized Children. Clin Pediatr (Phila). 2019 Jun 31;58(7):752–60
  10. Zhang L, Bao M, Liu B, Zhao H, Zhang Y, Ji X, et al. Effect of Andrographolide and Its Analogs on Bacterial Infection: A Review. Pharmacology. 2020;105(3–4):123–34
  11. Sumiyati S, Prajoko YW, Karlowee V, Setyawan NA, Susilaningsih N, Widyastiti NS. The Potential Role Of Andrographis Paniculata Against Sepsis By Inhibiting Nf-Kb P65 And Inos In Lipopolysaccharide-Induced Rat Model. 2022;62(07)
  12. Kopp F, Kupsch S, Schromm AB. Lipopolysaccharide-binding protein is bound and internalized by host cells and colocalizes with LPS in the cytoplasm: Implications for a role of LBP in intracellular LPS-signaling. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 2016 Apr;1863(4):660–72
  13. Chen J, Wei H. Immune Intervention in Sepsis. Front Pharmacol. 2021 Jul 14;12
  14. Shi J, Zhao Y, Wang Y, Gao W, Ding J, Li P, et al. Inflammatory caspases are innate immune receptors for intracellular LPS. Nature. 2014 Oct 6;514(7521):187–92
  15. Delano MJ, Ward PA. The immune system’s role in sepsis progression, resolution, and long-term outcome. Immunol Rev. 2016 Nov;274(1):330–53
  16. Cohen LA, Gutierrez L, Weiss A, Leichtmann-Bardoogo Y, Zhang D liang, Crooks DR, et al. Serum ferritin is derived primarily from macrophages through a nonclassical secretory pathway. Blood. 2010 Sep 2;116(9):1574–84
  17. Wen Y, Lambrecht J, Ju C, Tacke F. Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities. Cell Mol Immunol. 2021 Jan 12;18(1):45–56
  18. Ruddell RG, Hoang-Le D, Barwood JM, Rutherford PS, Piva TJ, Watters DJ, et al. Ferritin functions as a proinflammatory cytokine via iron-independent protein kinase C zeta/nuclear factor kappaB-regulated signaling in rat hepatic stellate cells. Hepatology. 2009 Mar;49(3):887–900
  19. Saito H. Metabolism Of Iron Stores. Nagoya J Med Sci. 2014 Aug;76(3–4):235–54
  20. Yunita E. Mekanisme Kerja Andrografolida Dari Sambiloto Sebagai Senyawa Antioksidan. Herb-Medicine Journal. 2021 Mar 27;4(1):43
  21. Fu S, Chen J, Liu B, Liang P, Zeng Y, Feng M, et al. Systemic inflammation modulates the ability of serum ferritin to predict all-cause and cardiovascular mortality in peritoneal dialysis patients. BMC Nephrol. 2020 Dec 23;21(1):237
  22. Mussard E, Jousselin S, Cesaro A, Legrain B, Lespessailles E, Esteve E, et al. Andrographis paniculata and Its Bioactive Diterpenoids Protect Dermal Fibroblasts against Inflammation and Oxidative Stress. Antioxidants. 2020 May 15;9(5):432
  23. Xu LB, Yue JK, Korley F, Puccio AM, Yuh EL, Sun X, et al. High-Sensitivity C-Reactive Protein is a Prognostic Biomarker of Six-Month Disability after Traumatic Brain Injury: Results from the TRACK-TBI Study. J Neurotrauma. 2021 Apr 1;38(7):918–27
  24. Ngwa DN, Pathak A, Agrawal A. IL-6 regulates induction of C-reactive protein gene expression by activating STAT3 isoforms. Mol Immunol. 2022 Jun;146:50–6
  25. Mohamed GA, Abd-Elrahman MZ, Bahriz R, Albehairy A. Inflammatory cytokine and plasma C-reactive protein response to ketoacidosis in adults with type 1 diabetes: Egyptian multicenter study. Egypt J Intern Med. 2020 Dec 15;32(1):10
  26. Nedeva C, Menassa J, Puthalakath H. Sepsis: Inflammation Is a Necessary Evil. Front Cell Dev Biol. 2019 Jun 20;7
  27. Burgos RA, Alarcón P, Quiroga J, Manosalva C, Hancke J. Andrographolide, an Anti-Inflammatory Multitarget Drug: All Roads Lead to Cellular Metabolism. Molecules. 2020 Dec 22;26(1):5
  28. Zhu N, Hou J, Yang N. Network pharmacology integrated with experimental validation revealed the anti-inflammatory effects of Andrographis paniculata. Sci Rep. 2021 May 7;11(1):9752
  29. Potempa LA, Rajab IM, Hart PC, Bordon J, Fernandez-Botran R. Insights into the Use of C-Reactive Protein as a Diagnostic Index of Disease Severity in COVID-19 Infections. Am J Trop Med Hyg. 2020 Aug 5;103(2):561–3
  30. Fu K, Chen H, Wang Z, Cao R. Andrographolide attenuates inflammatory response induced by LPS via activating Nrf2 signaling pathway in bovine endometrial epithelial cells. Res Vet Sci. 2021 Jan;134:36–41

Last update:

No citation recorded.

Last update:

No citation recorded.