, Volume 26, Issue 5, pp 1207–1217 | Cite as

Labisia pumila prevented osteoarthritis cartilage degeneration by attenuating joint inflammation and collagen breakdown in postmenopausal rat model

  • Iffah Nadhira Madzuki
  • Seng Fong Lau
  • Nur Adeelah Che Ahmad Tantowi
  • Nur Iliyani Mohd Ishak
  • Suhaila MohamedEmail author
Original Article


The tropical herb Labisia pumila is traditionally used in facilitating childbirth and post-partum care. The effects of L. pumila leaf extract (LP) in explant cartilage culture and on postmenopausal osteoarthritis (OA) rat model were assessed. The LP (10, 25 and 50 µg/ml) or diclofenac (10 µg/ml) was added to the cartilage explants containing bovine IL-1β (20 ng/ml), to evaluate their direct effects on cartilage degradation. In the preclinical study, rats were grouped (n = 8) into: non-treated OA; OA + diclofenac (5 mg/kg); OA + LP extract (150 and 300 mg/kg); and healthy control. To induce OA, monosodium iodoacetate was injected into the ovariectomised female rats’ intra-articular knee joints and evaluated for OA severity after 8 weeks via physical (radiological, macroscopic and histological observations), biochemical, ELISA and mRNA expression analysis (for inflammation and cartilage degradation biomarkers). The LP reduced the nitric oxide and proteoglycan release from the cartilage explants under IL-1β induction. The radiological, macroscopic, microscopic and histological images showed the OA rats treated with LP and diclofenac had significantly reduced osteophytes and cartilage erosions compared to non-treated OA rats. The extract significantly up-regulated the anti-inflammatory interleukin-10, collagen type II and down-regulated pro-inflammatory PTGS2 (prostaglandin-endoperoxide synthase 2) mRNA expressions compared to non-treated control. The LP treatment significantly reduced serum collagenases (MMP-1 and MMP-3) and collagen type II degradation biomarker (CTX-II) levels in OA rats. The LP containing myricetin and gallic acid suppressed inflammation, collagenases and cartilage degradation, and helped cartilage matrix synthesis, to prevent OA at the dose equivalent to 30–60 mg/kg daily for humans.


Labisia pumila Osteoarthritis Inflammation Articular cartilage 



We thank the Ministry of Agriculture, Herbal development Division for the research Grant, Universiti Malaysia Perlis for the studentship, Universiti Putra Malaysia for the facilities and Comparative Medicine and Technology (CoMeT) Unit, Institute of Bioscience, Universiti Putra Malaysia for the assistance in performing all-animal related procedures.

Financial support

This work was supported by the Herbal Development Division, Ministry of Agriculture, Malaysia (Grant no. NH1014D052).

Compliance with ethical standards

Conflict of interests



Part of this work was poster presented at World Congress of Bone, Muscle and Joint Disease 2017. Institutional Animal Care and Use Committee (IACUC), Universiti Putra Malaysia Approval (UPM/IACUC/AUP-R050/2015).

Supplementary material

10787_2018_452_MOESM1_ESM.docx (145 kb)
Supplementary material 1 (DOCX 143 kb)


  1. Bellido M et al (2010) Subchondral bone microstructural damage by increased remodelling aggravates experimental osteoarthritis preceded by osteoporosis. Arthritis Res Ther 12(4):R152. CrossRefPubMedPubMedCentralGoogle Scholar
  2. BenSaad LA et al (2017) Anti-inflammatory potential of ellagic acid, gallic acid and punicalagin A&B isolated from Punica granatum. BMC Complement Altern Med 17(1):47. CrossRefPubMedPubMedCentralGoogle Scholar
  3. Burr DB, Gallant MA (2012) Bone remodelling in osteoarthritis. Nat Rev Rheumatol 8(11):665–673. CrossRefPubMedGoogle Scholar
  4. Che Ahmad Tantowi NA et al (2017) Mistletoe fig (Ficus deltoidea Jack) leaf extract prevented postmenopausal osteoarthritis by attenuating inflammation and cartilage degradation in rat model. Menopause 24(9):1071–1080. CrossRefPubMedGoogle Scholar
  5. Christgau S et al (2004) Suppression of elevated cartilage turnover in postmenopausal women and in ovariectomized rats by estrogen and a selective estrogen-receptor modulator (SERM). Menopause 11(5):508–518CrossRefGoogle Scholar
  6. Chua LS et al (2011) Flavonoids and phenolic acids from Labisia pumila (Kacip Fatimah). Food Chem 127(3):1186–1192. CrossRefPubMedGoogle Scholar
  7. Cibere J et al (2009) Association of biomarkers with pre-radiographically defined and radiographically defined knee osteoarthritis in a population-based study. Arthritis Rheum 60(5):1372–1380CrossRefGoogle Scholar
  8. Fathilah SN et al (2012) Labisia pumila protects the bone of estrogen-deficient rat model: a histomorphometric study. J Ethnopharmacol 142(1):294–299. CrossRefPubMedGoogle Scholar
  9. Fathilah SN et al (2013) Labisia pumila regulates bone-related genes expressions in postmenopausal osteoporosis model. BMC Complement Altern Med 13:217. CrossRefPubMedPubMedCentralGoogle Scholar
  10. FDA Center for Drug Evaluation and Research (2005) Guidance for industry: estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers. US Department of Health and Human Services, (July), pp 1–27Google Scholar
  11. Guzman RE et al (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. CrossRefPubMedGoogle Scholar
  12. Høegh-Andersen P et al (2004) Ovariectomized rats as a model of postmenopausal osteoarthritis: validation and application. Arthritis Res Ther 6(2):R169–R180CrossRefGoogle Scholar
  13. Karimi E, Jaafar HZE, Ahmad S (2011) Phenolics and flavonoids profiling and antioxidant activity of three varieties of Malaysian indigenous medicinal herb Labisia pumila benth. J Med Plants Res 5(7):1200–1206Google Scholar
  14. Karimi E, Jaafar HZE, Ahmad S (2013) Antifungal, anti-inflammatory and cytotoxicity activities of three varieties of Labisia pumila benth: from microwave obtained extracts. BMC Complement Altern Med 13:20. CrossRefPubMedPubMedCentralGoogle Scholar
  15. Kawano M et al (2015) Assessment of quality of life in patients with knee osteoarthritis. Acta Ortopedica Brasileira 23(5):307–310. CrossRefPubMedPubMedCentralGoogle Scholar
  16. Kowalski ML et al (2013) Classification and practical approach to the diagnosis and management of hypersensitivity to nonsteroidal anti-inflammatory drugs. Allergy 68(10):1219–1232. CrossRefPubMedGoogle Scholar
  17. Lappas M (2002) Nuclear factor kappa B regulation of proinflammatory cytokines in human gestational tissues in vitro. Biol Reprod 67(2):668–673CrossRefGoogle Scholar
  18. Li X et al (2009) Prostaglandin E2 and its cognate EP receptors control human adult articular cartilage homeostasis and are linked to the pathophysiology of osteoarthritis. Arthritis Rheum 60(2):513–523CrossRefGoogle Scholar
  19. Martín-Millán M, Castã Neda S (2013) Estrogens, osteoarthritis and inflammation. Jt Bone Spine 80:368–373CrossRefGoogle Scholar
  20. Mobasheri A et al (2015) Chondrosenescence: definition, hallmarks and potential role in the pathogenesis of osteoarthritis. Maturitas 80:237–244CrossRefGoogle Scholar
  21. Nagase H, Kashiwagi M (2003) Aggrecanases and cartilage matrix degradation. Arthritis Res Ther 5(2):94–103CrossRefGoogle Scholar
  22. Naito K et al (2010) Evaluation of the effect of glucosamine on an experimental rat osteoarthritis model. Life Sci 86(13–14):538–543CrossRefGoogle Scholar
  23. Neogi T (2012) Clinical significance of bone changes in osteoarthritis. Ther Adv Musculoskelet Dis 4(4):259–267CrossRefGoogle Scholar
  24. Pulsatelli L et al (2012) New findings in osteoarthritis pathogenesis: therapeutic implications. Ther Adv Chronic Dis 4(1):23–43. CrossRefGoogle Scholar
  25. Rigoglou S, Papavassiliou AG (2013) The NFkB signalling pathway in osteoarthritis. Int J Biochem Cell Biol 45(11):2580–2584CrossRefGoogle Scholar
  26. Rout R et al (2011) The histological features of anteromedial gonarthrosis—the comparison of two grading systems in a human phenotype of osteoarthritis. Knee 18(3):172–176. CrossRefPubMedGoogle Scholar
  27. Shahrzad S et al (2001) Pharmacokinetics of gallic acid and its relative bioavailability from tea in healthy humans. J Nutr 131(4):1207–1210CrossRefGoogle Scholar
  28. Sharma AR et al (2013) Interplay between cartilage and subchondral bone contributing to pathogenesis of osteoarthritis. Int J Mol Sci 14(10):19805–19830. CrossRefPubMedPubMedCentralGoogle Scholar
  29. Singh GD et al (2009) Sub-acute toxicity evaluation of an aqueous extract of Labisia pumila, a Malaysian herb. Food Chem Toxicol 47(10):2661–2665. CrossRefPubMedGoogle Scholar
  30. Traversa G et al (1995) Gastroduodenal toxicity of different nonsteroidal antiinflammatory drugs. Epidemiology 6(1):49–54CrossRefGoogle Scholar
  31. Trelle S et al (2011) Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ 342:c7086. CrossRefPubMedPubMedCentralGoogle Scholar
  32. Uhl M et al (2004) Detection of posttraumatic cartilage lesions using magnetic resonance imaging (MRI): an experimental study on canines. Internet J Radiol 4(1):1–8Google Scholar
  33. Wang P, Li S, Wang X (2016) Myricetin exerts anti-osteoarthritic effects in IL-1β stimulated SW1353 cells via regulating matrix metalloproteinases and modulating JNK/P38MAPK/Ap-1/c-Fos and JAK/STAT signalling. Int J Pharmacol 12(4):440–450. CrossRefGoogle Scholar
  34. Wu H, Du J, Zheng Q (2008) Expression of MMP-1 in cartilage and synovium of experimentally induced rabbit ACLT traumatic osteoarthritis: immunohistochemical study. Rheumatol Int 29(1):31–36CrossRefGoogle Scholar
  35. Yao Y et al (2014) Preformulation studies of myricetin: a natural antioxidant flavonoid. Pharmazie 69(1):19–26. CrossRefPubMedGoogle Scholar
  36. Yoon TJ, Koppula S, Lee KH (2013) The effects of β-glucans on cancer metastasis. Anticancer Agents Med Chem 13(5):699–708. CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.UPM-MAKNA Laboratory of Cancer Research, Institute of BioscienceUniversiti Putra Malaysia UPMSerdangMalaysia
  2. 2.Faculty of Veterinary MedicineUniversiti Putra Malaysia UPMSerdangMalaysia
  3. 3.Faculty of Engineering TechnologyUniversiti Malaysia Perlis, UniMAPPadang BesarMalaysia

Personalised recommendations