Artocarpus altilis and antiarthritic efficacy


J. Pharm. Pharmacogn. Res., vol. 12, no. 2, pp. 382-390, Mar-Apr 2024. DOI: Original Article Effectiveness of Artocarpus altilis (Parkinson ex F.A.Zorn) Fosberg ethanol extract in suppressing inflammation and cartilage degeneration in animal models of osteoarthritis [Eficacia del extracto etanólico de Artocarpus altilis (Parkinson ex F.A.Zorn) Fosberg en la supresión de la inflamación y … Continue reading Artocarpus altilis and antiarthritic efficacy

J. Pharm. Pharmacogn. Res., vol. 12, no. 2, pp. 382-390, Mar-Apr 2024.


Original Article

Effectiveness of Artocarpus altilis (Parkinson ex F.A.Zorn) Fosberg ethanol extract in suppressing inflammation and cartilage degeneration in animal models of osteoarthritis

[Eficacia del extracto etanólico de Artocarpus altilis (Parkinson ex F.A.Zorn) Fosberg en la supresión de la inflamación y la degeneración del cartílago en modelos animales de osteoartritis]

Fitrya1,2*, Muharni3, Fatma Sri Wahyuni4, Annisa Amriani1,2

1Doctoral Program, Faculty of Mathematics and Natural Science, Universitas Sriwijaya, South Sumatera, Indonesia.

2Department of Pharmacy, Faculty of Mathematics and Natural Science, Universitas Sriwijaya, South Sumatera, Indonesia.

3Department of Chemistry, Faculty of Mathematics and Natural Science, Universitas Sriwijaya, South Sumatera, Indonesia.

4Faculty of Pharmacy, Universitas Andalas, West Sumatera, Indonesia.



Context: Osteoarthritis (OA) is a degenerative joint disease characterized by an inflammatory reaction and cartilage degradation. Artocarpus altilis is a well-known traditional medicine with various phenolic and flavonoid content. Several pharmacological properties of A. altilis extract (AAE) have been reported, but its effectiveness in osteoarthritis is unknown.

Aims: To investigate the potential of AAE as an anti-osteoarthritis.

Methods: The Wistar rats induced OA with mono-iodoacetate (MIA). The OA model rats were treated with AAE with three dose levels (100, 200, and 400 mg/kg) for 28 days. As a positive control used Na-diclofenac (20 mg/kg). Serum IL-1β, IL-10, MMP-3, and MMP-13 levels and histopathological profiles were compared to the MIA group and normal control (5% Na-CMC).

Results: The experimental results showed that AAE could significantly suppress the production of inflammatory mediator factor IL-1β, matrix-degrading proteinase MMP-3, MMP-13, and cartilage degeneration. In addition, AAE increased the production of the anti-inflammatory mediator IL-10, improved synovial inflammation, and increased cartilage thickness.

Conclusions: A. altilis extract has the potential to be developed as an anti-osteoarthritis therapeutic agent from natural medicine.

Keywords: Artocarpus altilis; cartilage degeneration; inflammatory; mono-iodoacetate; osteoarthritis.



Contexto: La osteoartritis (OA) es una enfermedad degenerativa de las articulaciones caracterizada por una reacción inflamatoria y la degradación del cartílago. El Artocarpus altilis es una medicina tradicional muy conocida por su contenido en diversos fenoles y flavonoides. Se han descrito varias propiedades farmacológicas del extracto de A. altilis (AAE), pero se desconoce su eficacia en la osteoartritis.

Objetivos: Investigar el potencial del AAE como antiosteoartrítico.

Métodos: A las ratas Wistar se les indujo OA con mono-iodoacetato (MIA). Las ratas modelo de OA fueron tratadas con AAE con tres niveles de dosis (100, 200 y 400 mg/kg) durante 28 días. Como control positivo se utilizó Na-diclofenaco (20 mg/kg). Se compararon los niveles séricos de IL-1β, IL-10, MMP-3 y MMP-13 y los perfiles histopatológicos con el grupo MIA y el control normal (5% Na-CMC).

Resultados: Los resultados experimentales mostraron que AAE podría suprimir significativamente la producción del factor mediador inflamatorio IL-1β, la proteinasa degradadora de la matriz MMP-3, MMP-13, y la degeneración del cartílago. Además, la AAE aumentó la producción del mediador anti-inflamatorio IL-10, mejoró la inflamación sinovial y aumentó el grosor del cartílago.

Conclusiones: El extracto de A. altilis tiene potencial para ser desarrollado como agente terapéutico anti-osteoartritis desde la medicina natural.

Palabras Clave: Artocarpus altilis; degeneración del cartílago; inflamatorio; monoyodoacetato; osteoartritis.



Citation Format: Fitrya, Muharni, Wahyuni FS, Amriani A (2024) Effectiveness of Artocarpus altilis (Parkinson ex F.A.Zorn) Fosberg ethanol extract in suppressing inflammation and cartilage degeneration in animal models of osteoarthritis. J Pharm Pharmacogn Res 12(2): 382–390.

Ansari MY, Ahmad N, Haqqi TM (2020) Oxidative stress and inflammation in osteoarthritis pathogenesis: Role of polyphenols. Biomed Pharmacother 129: 110452.

Asante-Kwatia E, Mensah AY, Baidoo MF (2020) Analgesic and anti-inflammatory effect of Ghanaian medicinal plants. In: Medicinal Plants - Use in prevention and treatment of diseases. Hassan BAR. Ghana: Licensee IntechOpen. pp. 1–23.

Cadet C, Maheu E, Breville P, Cailleaux PE, Jeandel C, Le Quintrec JL (2021) Non-steroidal anti-inflammatory drugs in the pharmacological management of osteoarthritis in the very old: Prescribe or proscribe? Ther Adv Musculoskelet Dis 13: 1–13.

Choi B, Kang S, Kim J, Lee Y, Ku Sae-Kwang (2020) Anti-osteoarthritic effects of a mixture of dried pomegranate concentrate powder, Eucommiae cortex, and Achyranthis radix 5:4:1 (g/g) in a surgically induced osteoarthritic rabbit model. Nutriens 12(3): 852.

Chun JM, Kim HS, Lee AY, Kim SH, Kim HK (2016) Anti-inflammatory and antiosteoarthritis effects of Saposhnikovia divaricata ethanol extract: In vitro and in vivo studies. Evid Based Complement Altern Med 2016: 1984238.

Endrinaldi E, Ali H, Tofrizal T, Asterina A, Elmatris E, Yarni SD (2022) Optimization of the duration of the administration of mesenchymal stem cells Wharton’s Jelly to the level of matrix metalloproteinase-1 and transforming growth factor-Β in osteoarthritis rat model. Maced J Med Sci 10: 563–571.

Fakhrudin N, Hastuti S, Andriani A, Widyarini S, Nurrochmad A (2015) Study on the antiinflammatory activity of Artocarpus altilis leaves extract in mice. Int J Pharmacogn Phytochem Res 7(6): 1080–1085.

Fitrya, Muharni, Wahyuni FS, Amriani A (2023a) Cytotoxicity and anti-inflammatory activity of ethanol extract of Artocarpus altilis (Parkinson ex F.A. Zorn) Fosberg leaf in lipopolysaccharide-stimulated RAW 264.7 cells. J Pharm Pharmacogn Res 11(3): 517–522.

Fitrya F, Amriani A, Novita RP, Salsabila A, Siregar SM, Anafisya Y (2022) Evaluation of ethanol extracts from three species of Artocarpus as natural gastroprotective agents: In vivo and histopathological studies. J Complement Integr Med 19(4):  967–974.

Fitrya F, Amriani A, Novita RP, Gabriella R, Lestari SV, Agustina A (2023b) The diuretic effect of ethyl acetate fractions of Artocarpus altilis, Artocarpus champeden, and Artocarpus heterophyllus leaves in normotensive Wistar rats. J Ayurveda Integr Med 14(4): 100746.

Glasson SS, Chambers MG, Van Den Berg WB, Little CB (2010) The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the mouse. Osteoarthr Cartil 18: S17–S23.

Guzman RE, Evans MG, Bove S, Morenko B, Kilgore K (2003) Mono-iodoacetate-induced histologic changes in subchondral bone and articular cartilage of rat femorotibial joints: An animal model of osteoarthritis. Toxicol Pathol 31(6): 619–624.

Ho Y, Lu J, Ho L, Lai J, Huang H, Lee C (2019) Anti-inflammatory and anti-osteoarthritis effects of Cm-02 and Ck 02. Biochem Biophys Res 517: 155–163.

Huang T Le, Yang SH, Chen YR, Liao JY, Tang Y, Yang KC (2019) The therapeutic effect of aucubin-supplemented hyaluronic acid on interleukin-1beta-stimulated human articular chondrocytes. Phytomedicine 53: 1–8.

Imbawan IE, Putra TR, Kambayana G (2011) Korelasi Kadar Matrix Metalloproteinases 3 (MMP-3) Dengan Derajat Beratnya Oteoartritis Lutut. J Penyakit Dalam 12(3): 181–192.

Inoue M, Hitora Y, Kato H, Losung F, Remy EP, Mangindaan REP, Tsukamoto S (2018) New geranyl avonoids from the leaves of Artocarpus communis. J Nat Med 72(3): 632-640.

Ji X, Du W, Che W, Wang L, Zhao L (2023) Apigenin inhibits the progression of osteoarthritis by mediating macrophage polarization. Molecules 28(7): 2915.

Kakatum N, Pinsornsak P, Kanokkangsadal P, Ooraikul B, Itharat A (2021) Efficacy and safety of sahastara remedy extract capsule in primary knee osteoarthritis: A randomized double-blinded active-controlled trial. Evid Based Complement Altern Med 2021: 6635148.

Lee YM, Son E, Kim SH, Kim DS, Kim DS (2019a) Anti-inflammatory and anti-osteoarthritis effect of Mollugo pentaphylla extract. Pharm Biol 57(1): 73–80.

Lee YM, Son E, Kim SH, Kim DS (2019b) Effect of Alpinia oxyphylla extract in vitro and in a monosodium iodoacetate-induced osteoarthritis rat model. Phytomedicine 65: 153095.

Li X, Zhang S (2020) Recent advance in treatment of osteoarthritis by bioactive components from herbal medicine. Chin Med 15: 80.

Liu S, Deng Z, Chen K, Jian S, Zhou F, Yang Y (2022) Cartilage tissue engineering: From proinflammatory and anti-inflammatory cytokines to osteoarthritis treatments (Review). Mol Med Rep 25: 99.

Mohammadifar M, Aarabi MH, Aghighi F, Kazemi M, Vakili Z, Memarzadeh MR (2021) Anti-osteoarthritis potential of peppermint and rosemary essential oils in a nanoemulsion form: Behavioral, biochemical, and histopathological evidence. BMC Complement Med Ther 21: 57.

Nguyen MTH, Nguyen NT, Nguyen KDH, Dau HTT, Nguyen HX, Dang PH, Le TM, Phan THN, Tran AH, Nguyen BD, Ueda J, Awale S (2014) Geranyl dihydrochalcones from Artocarpus altilis and their antiausteric activity. Planta Med 80: 193–200.

Pal S, Dhobi M (2019) A comprehensive review: biomarker in the field of osteoartritis & potential of herbal medicinal plants used in the treatment. Sch Acad J Pharm 8(7): 313–326.

Palupi DHS, Retnoningrum DS, Iwo MI, Soemardji AA (2020) Leaf extract of Artocarpus altilis [Park.] Fosberg has potency as antiinflammatory, antioxidant, and immunosuppressant. Rasayan J Chem 13(1): 636–646.

Park JG, Yi YS, Hong YH, Yoo S, Han SY, Kim E (2017) TabetriTM (Tabebuia avellanedae ethanol extract) ameliorates osteoarthritis symptoms induced by monoiodoacetate through its anti-inflammatory and chondroprotective activities. Mediators Inflamm 2017: 3619879.

Park JS, Kim DK, Shin H, Lee HJ, Jo HS, Jeong JH (2016) Apigenin regulates interleukin-1β-induced production of matrix metalloproteinase both in the knee joint of rat and in primary cultured articular chondrocytes. Biomol Ther 24(2). 163–170.

Park MH, Jung JC, Hill S, Cartwright E, Dohnalek MH, Yu M, Jun HJ, Han SB, Hong JT, Son DJ (2020) FlexPro MD®, a combination of krill oil, astaxanthin and hyaluronic acid, reduces pain behavior and inhibits inflammatory response in monosodium iodoacetate-induced osteoarthritis in rats. Nutriens 12(4): 956.

Pérez-Lozano ML, Cesaro A, Mazor M, Esteve E, Berteina-Raboin S, Best TM, Lespessailles E, Toumi H (2021) Emerging natural-product-based treatments for the management of osteoarthritis. Antioxidants 10(2): 265.

Riasari H, Nurlalela S, Gumilang GC. (2019) Anti-Inflammatory activity of Artocarpus altilis (Parkinson) Fosberg in Wistar male rats. Pharmacol Clin Pharm Res 4(1): 22–26.

Seo BB, Kwon Y, Kim J, Hong KH, Kim SE, Song HR, Kim YM, Song SC (2022) Injectable polymeric nanoparticle hydrogel system for long-term anti-inflammatory effect to treat osteoarthritis. Bioact Mater 7: 14–25.

Shao Y, He J, Zhang X, Xie P, Lian H, Zhang M (2022) Mechanism of Astragali Radix for the treatment of osteoarthritis: A study based on network pharmacology and molecular docking. Medicine 101(28): e29885.

Shiomi T, Lemaître V, D’Armiento J, Okada Y (2010) Matrix metalloproteinases, a disintegrin and metalloproteinases, and a disintegrin and metalloproteinases with thrombospondin motifs in non-neoplastic diseases. Pathol Int 60(7): 477–496.

Sofia V, Bachri MS, Endrinaldi E (2019) The influence of mesenchymal stem cell wharton jelly toward prostaglandin E2 gene expression on synoviocyte cell osteoarthritis. Maced J Med Sci 7(5): 1252–1258.

Takahashi I, Matsuzaki T, Kuroki H, Hoso M (2018) Induction of osteoarthritis by injecting monosodium iodoacetate into the patellofemoral joint of an experimental rat model. PLoS One 13(4): e0196625.

Teng L, Shen Y, Qu Y, Yang L, Yang Y, Jian X (2023) Cyasterone inhibits IL-1β-mediated apoptosis and inflammation via the NF-kB and MAPK signaling pathways in rat chondrocytes and ameliorates osteoarthritis in vivo. Chin J Nat Med 21(2): 99–112.

Wang Y, Xu K, Lin L, Pan Y, Zheng X (2007) Geranyl flavonoids from the leaves of Artocarpus altilis. Phytochemistry 68: 1300–1306.

Xu J, Yan L, Yan B, Zhou L, Tong P, Shan L (2020) Osteoarthritis pain model induced by intra-articular injection of mono-iodoacetate in rats. J Vis Exp (159): e60649.

Yagi H, Ulici V, Tuan RS (2020) Polyphenols suppress inducible oxidative stress in human osteoarthritic and bovine chondrocytes. Osteoarthr Cartil Open 2(3): 100064.

Zhang W, Ouyang H, Dass CR, Xu J (2016) Current research on pharmacologic and regenerative therapies for osteoarthritis. Bone Res 4: 15040.

Zhao P, Cheng J, Geng J, Yang M, Zhang Y, Zhang Q (2018) Curcumin protects rabbit articular chondrocytes against sodium nitroprusside-induced apoptosis in vitro. Eur J Pharmacol 828: 146–153.

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