Anti-inflammatory Activity of Nanoemulgel formulated from Ageratum conyzoides (L.) L. and Oldenlandia corymbosa L. Extracts in Rats


  • Department of Pharmacology, Faculty of Pharmacy, Universitas Indonesia, Kampus UI Depok
  • Department of Pharmaceutics, Faculty of Pharmacy, Universitas Indonesia, Kampus UI Depok
  • Department of Medicinal Chemistry, Faculty of Medicine, Universitas Indonesia, Kampus UI Salemba No 6
  • Department of Pharmacology, Faculty of Pharmacy, Universitas Indonesia, Kampus UI Depok



Aggrecan Core Protein, Collagen Type II, Monosodium Iodoacetate, Osteoarthritis


The use of traditional medicine in the treatment of disease has increased globally due to its safety and efficacy. Ageratum conyzoides (L.) L. and Oldenlandia corymbosa L. have been used traditionally as a topical preparation for joint disease in Indonesia. Hence, the study was planned to scientifically study the existing empirical data. A nanoemulgel of combined Ageratum conyzoides (L.) L. (ACE) and Oldenlandia corymbosa L. Extract (OCE) as a new drug focused on plant-based natural products with a good physical characteristic that inhibits inflammatory process in managing osteoarthritis (OA) was formulated. Thirty animals were randomly designated to the 6 groups (n=5) as follows: (1) The normal control group (Normal), (2) negative control groups of Monosodium Iodoacetate (MIA), (3) combination ACE-OCE, (4) single ACE, (5) single OCE, (6) positive control group (Diclofenac). Rats received intraarticular MIA injection dose 3mg/0.05 mL on day zero excluding normal control group. All groups were administered topical preparations allotted to each dose group on day 29. Knee edema profile (every 7 days) and serum cytokine level (on day 57) was evaluated with Enzyme-Linked Immunoabsorbent Assay (ELISA). Till day 42, knee edema profile of all group treatment have been similar with normal control group (p>0.05). Serum cytokines level for some biomarkers, such as S100A8 Protein, Interleukin-1β, Inducible Nitric Oxide Synthase (iNOS), matrix metalloproteinase-13 (MMP-13), a disintegrin and metalloproteinase thrombospondin-like motifs-5 (ADAMTS-5), Collagen Type II and Aggrecan Core Protein were decreased. A significant difference compared with MIA group showed for all group treatment on measurement of S100A8 Protein, IL-1β, and iNOS as a biomarker of inflammatory process (#P<0.05). The developed nanoemulgel ACE-OCE either in single or in combination has good physical characteristic and promising effect of anti-inflammatory activity to enhance MIA induced cartilage damage as potential therapeutic agent for OA and encouraging to conduct further studies.


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Cush JJ, Lipsky PE, Brandt KD. Harrison's rheumatology. Fauci AS, editor. Philadelphia: Mc-Graw-Hill; 2006. p. 227–57.

Martel-pelletier J, Barr AJ, Cicuttini FM, Conaghan PG, Cooper C, Goldring MB, et al. Osteoarthritis. Nature Reviews Disease Primers. 2016; 2. nrdp.2016.73. PMid:27734844

Chikanza IC, Fernandes L. Novel strategies for the treatment of osteoarthritis. Expert Opinion on Investigational Drugs. 2000; 9(7):1499–510. PMid:11060755

Kienzler JL, Gold M, Nollevaux F. Systemic bioavailability of topical diclofenac sodium gel 1% versus oral diclofenac sodium in healthy volunteers. The Journal of Clinical Pharmacology. 2010; 50(1):50–61. https://doi. org/10.1177/0091270009336234. PMid:19841157

de Padua LS, Bogor PF, Lemmens RHM, Bunyapraphatsara N. Plant resources of South East Asia No 12(1) medicinal and poisonous plants 1. Bogor Indonesia: Backhuys Publishers; 1999. p. 711.

EISAI. Medicinal herbs index in Indonesia. Second Edi. PT EISAI Indonesia; 1995.

Bahtiar A, Nurazizah M, Roselina T, Tambunan AP, Arsianti A. Ethanolic extracts of babandotan leaves (Ageratum conyzoides L.) prevents inflammation and proteoglycan degradation by inhibiting TNF-a and MMP-9 on osteoarthritis rats induced by monosodium iodoacetate. Asian Pacific Journal of Tropical Medicine. 2017; 10(3):270–7. Available from: science/article/pii/S1995764516304436?via%3Dihub. https://doi. org/10.1016/j.apjtm.2017.03.006. PMid:28442110

Moura ACA, Silva ELF, Fraga MCA, Wanderley AG, Afiatpour P, Maia MBS. Antiinflammatory and chronic toxicity study of the leaves of Ageratum conyzoides L. in rats. Phytomedicine. 2005; 12(1-2):138–42. PMid:15693721

Vigil de Mello SVG, da Rosa JS, Facchin BM, Luz ABG, Vicente G, Faqueti LG, et al. Beneficial effect of Ageratum conyzoides Linn (Asteraceae) upon inflammatory response induced by carrageenan into the mice pleural cavity. Journal of Ethnopharmacology. [Internet]. 2016; 194:337–47. Available from: S0378874116306535?via%3Dihub. jep.2016.09.003. PMid:27596330

Permatasari DA, Karliana D, Arsianti A. Quercetin prevent proteoglycan destruction by inhibits matrix metalloproteinase - 9 , matrix metalloproteinase - 13, a disintegrin and metalloproteinase with thrombospondin motifs - 5 expressions on osteoarthritis model rats. Journal of Advanced Pharmaceutical Technology & Research. 2019; 10:2–8. PMid:30815381 PMCid:PMC6383352

Wang Y, Wang C, Lin H, Liu Y, Li Y, Zhao Y, et al. Discovery of the potential biomarkers for discrimination between hedyotis diffusa and hedyotis corymbosa by UPLC-QTOF / MS Metabolome Analysis. Molecules. 2018; 23(1525). molecules23071525. PMid:29941819. PMCid:PMC6100407

Bahtiar A, Sari FA, Audina M, Datunsolang NLC, Arsianti A. Ethanolic extracts of Hedyotis corymbosa L . Improves monosodium iodoacetate-induce osteoarthritis in rat. Asian Journal of Pharmaceutical and Clinical Research. 2017; 10(3).

David AA, Arulmoli R, Parasuraman S. Overviews of biological importance of quercetin: A bioactive flavonoid. Pharmacogn Reviews. 2016; 10(20):84. 7847.194044. PMid:28082789 PMCid:PMC5214562

Kuyinu EL, Narayanan G, Nair LS, Laurencin CT. Animal models of osteoarthritis: Classification, update, and measurement of outcomes. Journal of Orthopaedic Surgery and Research. 2016; 11(1):1–27. s13018-016-0346-5. PMid:26837951. PMCid:PMC4738796

Zhang Q, Jiang X, Jiang W, Lu W, Su L, Shi Z. Preparation of nimodipine-loaded microemulsion for intranasal delivery and evaluation on the targeting efficiency to the brain. International Journal of Pharmaceutics. 2004; 275:85–96. PMid:15081140

Shafiq S, Shakeel F, Talegaonkar S, Ahmad FJ, Khar RK, Ali M. Development and bioavailability assessment of ramipril nanoemulsion formulation. European Journal of Pharmaceutics and Biopharmaceutics. 2007; 66:227–43. PMid:17127045

Samia O, Hanan R, Kamal ET. Carbamazepine Mucoadhesive Nanoemulgel (MNEG) as brain targeting delivery system via the olfactory mucosa. Drug Delivery. 2012; (November 2011):1–10. PMid:22191715

Aithal G, Nayak UY, Mehta C, Narayan R, Gopalkrishna P, Pandiyan S, et al. Localized in situ nanoemulgel drug delivery system of quercetin for periodontitis : Development and computational simulations. Molecules. 2018; 23(1363). molecules23061363. PMid:29882751. PMCid:PMC6099597

Jaiswal M, Dudhe R, Sharma PK. Nanoemulsion: An advanced mode of drug delivery system. 3 Biotech. 2015; 5(2):123–7. PMid:28324579. PMCid:PMC4362737

Ramadon D, Anwar E, Harahap Y. In vitro penetration and bioavailability of novel transdermal Quercetin-loaded ethosomal gel. Indian Journal of Pharmaceutical Sciences. 2017; 79(September):948–56. 1000312

Guo CY, Yang CF, Li QL, Tan Q, Xi YW, Liu WN, et al. Development of a Quercetin-loaded nanostructured lipid carrier formulation for topical delivery. International Journal of Pharmaceutics. 2012; 430(1–2):292–8. https://doi. org/10.1016/j.ijpharm.2012.03.042. PMid:22486962

Vijayakumar A, Baskaran R, Jang YS, Oh SH, Yoo BK. Quercetinloaded solid lipid nanoparticle dispersion with improved physicochemical properties and cellular uptake. American Association of Pharmaceutical Scientists. 2017; 18(3):875–83. PMid:27368922

Barry BW. Novel mechanisms and devices to enable successful transdermal drug delivery. European Journal of Pharmaceutical Sciences. 2001; 14:101–14.

Rocha-Filho P, Ferrari M, Maruno M, Souza O, Gumiero V. In vitro and in vivo evaluation of nanoemulsion containing vegetable extracts. Cosmetics. 2017; 4(3):32. https://doi. org/10.3390/cosmetics4030032

Hatahet T, Morille M, Hommoss A, Devoisselle JM, Müller RH, Bégu S. Quercetin topical application, from conventional dosage forms to nanodosage forms. European Journal of Pharmaceutics and Biopharmaceutics. 2016; 108:41–53. PMid:27565033

Elsayed MMA, Abdallah OY, Naggar VF, Khalafallah NM. Lipid vesicles for skin delivery of drugs : Reviewing three decades of research. InternationalJournalofPharmaceutics. 2007; 332:1–16. PMid:17222523

Tran TH, Guo YI, Song D, Bruno RS, Lu X. Quercetin-containing self-nanoemulsifying drug delivery system for improving oral bioavailability. Journal of Pharmaceutical Sciences. 2014; 103:840–52. PMid:24464737

Guingamp C, Gegout-pottie P, Philippe L, Terlain B, Netter P, Gillet P. mono-iodoacetate-induced experimental osteoarthritis a dose-response study of loss of mobility , morphology , and biochemistry. Arthritis & Rheumatology. 1997; 40(9):1670–9. PMid:9324022

McCoy AM. Animal models of osteoarthritis: Comparisons and key considerations. Veterinary Pathology. 2015; 52(5):803–18. PMid:26063173

Teeple E, Jay GD, Elsaid KA, Fleming BC. Animal models of osteoarthritis: Challenges of model selection and analysis. AAPS Journal. 2013; 15(2):438–46. s12248-013-9454-x. PMid:23329424 PMCid:PMC3675748

Ziaei A, Sahranavard S, Gharagozlou MJ, Faizi M. Preliminary investigation of the effects of topical mixture of Lawsonia inermis L. and Ricinus communis L. leaves extract in treatment of osteoarthritis using MIA model in rats. DARU Journal of Pharmaceutical Sciences. 2016; 24(12):1–10. PMid:27142000. PMCid:PMC4855329

Janusz MJ, Hookfin EB, Heitmeyer SA, Woessner JF, Freemont AJ, Hoyland JA, et al. Moderation of iodoacetateinduced experimental osteoarthritis in rats by matrix metalloproteinase inhibitors. Osteoarthritis and Cartilage. 2001; 9:751–60. PMid:11795995

Pickarski M, Hayami T, Zhuo Y, Duong LT. Molecular changes in articular cartilage and subchondral bone in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis. BMC Musculoskelet Disord. 2011; 12(1):197. PMid:21864409. PMCid:PMC3176489

Kato J, Svensson CI. Role of extracellular Damage- Associated Molecular Pattern Molecules ( DAMPs ) as mediators of persistent pain. 1st ed. Vol. 131, Molecular and Cell Biology of Pain; 2015. p. 51–279. bs.pmbts.2014.11.014. PMid:25744676

Roughley PJ, Mort JS. The role of aggrecan in normal and osteoarthritic cartilage. Journal of Experimental Orthopaedics. 2014; 1(8):1–11. s40634-014-0008-7. PMid:26914753. PMCid:PMC4648834

Balmaceda CM. Clinical trial data in support of changing guidelines in osteoarthritis treatment. Journal of Pain Research. 2014; 7:211–8. PMid:24748817. PMCid:PMC3990388

Li Y, Yao J, Han C, Yang J, Chaudhry MT, Wang S, et al. Quercetin, inflammation and immunity. Nutrients. 2016; 8(3):1–14. PMid:26999194. PMCid:PMC4808895




How to Cite

Permawati, M., Anwar, E., Arsianti, A., & Bahtiar, A. (2019). Anti-inflammatory Activity of Nanoemulgel formulated from <i>Ageratum conyzoides</i> (L.) L. and <i>Oldenlandia corymbosa</i> L. Extracts in Rats. Journal of Natural Remedies, 19(3), 124–134.



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