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Effects of Psidium guajava Linn. leaf extract in Japanese subjects with knee pain: a randomized, double-blind, placebo-controlled, parallel pilot study

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Abstract

The extract of Psidium guajava Linn. (guava) leaf was recently revealed to suppress the advance of osteoarthritis (OA) in rat anterior cruciate ligament-transection models. To investigate the efficacy of guava leaf extract in improving knee pain, which is a common symptom of OA, we conducted a double-blind parallel pilot clinical study in Japanese subjects with knee pain. The subjects, who had no medical history of knee treatment, were randomly assigned to two groups with similar total Japanese Knee Osteoarthritis Measure (JKOM) scores. During the 12-week intake period, the subjects in each group ingested 1 g of guava leaf extract (the guava group) or placebo (the placebo group) daily. At week 12, pain and stiffness in knees (one subcategory of JKOM score) in the guava group was significantly lower than that in the placebo group. Using the visual analogue scale (VAS) for knee pain, a significant association between treatment effect and test period was shown, and the guava group had a lower VAS score at week 12 than the placebo group. In conclusion, continuous intake of guava leaf extract might relieve knee pain, suggesting a potential preventive effect against OA symptoms.

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References

  1. Yoshimura N, Muraki S, Oka H et al (2009) Prevalence of knee osteoarthritis, lumbar spondylosis, and osteoporosis in Japanese men and women: the research on osteoarthritis/osteoporosis against disability study. J Bone Miner Metab 27:620–628. https://doi.org/10.1007/s00774-009-0080-8

    Article  PubMed  Google Scholar 

  2. Zhang W, Nuki G, Moskowitz RW et al (2010) OARSI recommendations for the management of hip and knee osteoarthritis Part III: changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthr Cartil 18:476–499. https://doi.org/10.1016/j.joca.2010.01.013

    Article  CAS  PubMed  Google Scholar 

  3. McAlindon TE, Bannuru RR, Sullivan MC et al (2014) OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthr Cartil 22:363–388. https://doi.org/10.1016/j.joca.2014.01.003

    Article  CAS  PubMed  Google Scholar 

  4. Glasson SS, Askew R, Sheppard B et al (2005) Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis. Nature 434:644–648. https://doi.org/10.1038/nature03369

    Article  CAS  PubMed  Google Scholar 

  5. Stanton H, Rogerson FM, East CJ et al (2005) ADAMTS5 is the major aggrecanase in mouse cartilage in vivo and in vitro. Nature 434:648–652. https://doi.org/10.1038/nature03417

    Article  CAS  PubMed  Google Scholar 

  6. Verma P, Dalal K (2011) ADAMTS-4 and ADAMTS-5: key enzymes in osteoarthritis. J Cell Biochem 112:3507–3514. https://doi.org/10.1002/jcb.23298

    Article  CAS  PubMed  Google Scholar 

  7. Yao W, Wasserman ZR, Chao M et al (2001) Design and synthesis of a series of (2R)-N 4-hydroxy-2-(3-hydroxybenzyl)-N 1-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]butanediamide derivatives as potent, selective, and orally bioavailable aggrecanase inhibitors. J Med Chem 44:3347–3350. https://doi.org/10.1021/jm015533c

    Article  CAS  PubMed  Google Scholar 

  8. Shiozaki M, Maeda K, Miura T et al (2011) 2 Discovery of (1S,2R,3R)-2,3-dimethyl-2-phenyl-1-sulfamidocyclopropanecarboxylates: novel and highly selective aggrecanase inhibitors. J Med Chem 54:2839–2863. https://doi.org/10.1021/jm101609j

    Article  CAS  PubMed  Google Scholar 

  9. Vankemmelbeke MN, Jones GC, Fowles C et al (2003) Selective inhibition of ADAMTS-1, -4 and -5 by catechin gallate esters. Eur J Biochem 270:2394–2403. https://doi.org/10.1046/j.1432-1033.2003.03607

    Article  CAS  PubMed  Google Scholar 

  10. Imada K, Lin N, Liu C et al (2008) Nobiletin, a citrus polymethoxy flavonoid, suppresses gene expression and production of aggrecanases-1 and – 2 in collagen-induced arthritic mice. Biochem Biophys Res Commun 373:181–185. https://doi.org/10.1016/j.bbrc.2008

    Article  CAS  PubMed  Google Scholar 

  11. Moncada-Pazos A, Obaya AJ, Viloria CG et al (2011) The nutraceutical flavonoid luteolin inhibits ADAMTS-4 and ADAMTS-5 aggrecanase activities. J Mol Med (Berl) 89:611–619. https://doi.org/10.1007/s00109-011-0741-7

    Article  CAS  Google Scholar 

  12. Lay E, Samiric T, Handley CJ et al (2012) Short- and long-term exposure of articular cartilage to curcumin or quercetin inhibits aggrecan loss. J Nutr Biochem 23:106–112. https://doi.org/10.1016/j.jnutbio.2010.11.004

    Article  CAS  PubMed  Google Scholar 

  13. Zhang Z, Leong DJ, Xu L et al (2016) Curcumin slows osteoarthritis progression and relieves osteoarthritis-associated pain symptoms in a post-traumatic osteoarthritis mouse model. Arthritis Res Ther 18:128. https://doi.org/10.1186/s13075-016-1025

    Article  PubMed  PubMed Central  Google Scholar 

  14. Perkins K, Sahy W, Beckett RD (2017) Efficacy of curcuma for treatment of osteoarthritis. J Evid Based Complement Altern Med 22:156–165. https://doi.org/10.1177/2156587216636747

    Article  CAS  Google Scholar 

  15. Yan C, Lee J, Kong F et al (2013) Anti-glycated activity prediction of polysaccharides from two guava fruits using artificial neural networks. Carbohydr Polym 98:116–121. https://doi.org/10.1016/j.carbpol.2013.05.071

    Article  CAS  PubMed  Google Scholar 

  16. McCook-Russell KP, Nair MG, Facey PC et al (2012) Nutritional and nutraceutical comparison of Jamaican Psidium cattleianum (strawberry guava) and Psidium guajava (common guava) fruits. Food Chem 134:1069–1073. https://doi.org/10.1016/j.foodchem.2012.03.018

    Article  CAS  PubMed  Google Scholar 

  17. Kawasaki K, Fushimi T, Nakamura J et al (2018) Guava leaf extract suppresses the advance of osteoarthritis in rat anterior cruciate ligament-transection model. Food Sci Nutr. https://doi.org/10.1002/fsn3.601

    Article  PubMed  PubMed Central  Google Scholar 

  18. Yoshimura N, Akune T, Fujiwara S et al (2014) Prevalence of knee pain, lumbar pain and its coexistence in Japanese men and women: The Longitudinal Cohorts of Motor System Organ (LOCOMO) study. J Bone Miner Metab 32:524–532. https://doi.org/10.1007/s00774-013-0522-1

    Article  PubMed  Google Scholar 

  19. Akai M, Doi T, Fujino K et al (2005) An outcome measure for Japanese people with knee osteoarthritis. J Rheumatol 32:1524–1532

    PubMed  Google Scholar 

  20. Kim H, Suzuki T, Saito K et al (2013) Effectiveness of exercise with or without thermal therapy for community-dwelling elderly Japanese women with non-specific knee pain: a randomized controlled trial. Arch Gerontol Geriatr 57:352–359. https://doi.org/10.1016/j.archger.2013.06.008

    Article  PubMed  Google Scholar 

  21. Tsuji T, Yoon J, Aiba T et al (2014) Effects of whole-body vibration exercise on muscular strength and power, functional mobility and self-reported knee function in middle-aged and older Japanese women with knee pain. Knee 21:1088–1095. https://doi.org/10.1016/j.knee.2014.07.015

    Article  PubMed  Google Scholar 

  22. Tsuji T, Yoon J, Kitano N et al (2016) Effects of N-acetyl glucosamine and chondroitin sulfate supplementation on knee pain and self-reported knee function in middle-aged and older Japanese adults: a randomized, double-blind, placebo-controlled trial. Aging Clin Exp Res 28:197–205. https://doi.org/10.1007/s40520-015-0412-6

    Article  PubMed  Google Scholar 

  23. National Cancer Institute (2009) Common terminology criteria for adverse events (CTCAE) v4.0. http://evs.nci.nih.gov/ftp1/CTCAE/About.html. Accessed 1 Dec 2017

  24. Kahan A, Uebelhart D, De Vathaire F et al (2009) Long-term effects of chondroitins 4 and 6 sulfate on knee osteoarthritis: the study on osteoarthritis progression prevention, a two-year, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 60:524–533. https://doi.org/10.1002/art.24255

    Article  CAS  PubMed  Google Scholar 

  25. Puopolo A, Boice JA, Fidelholtz JL et al (2007) A randomized placebo-controlled trial comparing the efficacy of etoricoxib 30 mg and ibuprofen 2400 mg for the treatment of patients with osteoarthritis. Osteoarthr Cartil 15:1348–1356. https://doi.org/10.1016/j.joca.2007.05.022

    Article  CAS  PubMed  Google Scholar 

  26. Umesalma S, Sudhandiran G (2010) Differential inhibitory effects of the polyphenol ellagic acid on inflammatory mediators NF-κB, iNOS, COX-2, TNF-a, and IL-6 in 1,2-dimethylhydrazine-induced rat colon carcinogenesis. Basic Clin Pharmacol Toxicol 107:650–655. https://doi.org/10.1111/j.1742-7843.2010.00565

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This study was funded by Kao Corporation. All authors; S. Kakuo, T. Fushimi, K. Kawasaki, J. Nakamura and N. Ota are employees of this company. We would like to thank Editage (http://www.editage.jp) for English language editing.

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Authors

Contributions

SK, JN and NO designed this study. SK and TF analyzed data. SK, TF and NO interpreted the results. KK prepared test samples. TF and NO drafted this manuscript.

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Correspondence to Noriyasu Ota.

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The authors declare no conflict of interest associated with this manuscript.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethics Committee of Kao Corporation and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The present study protocol was registered in the University Hospital Medical Information Network (UMIN), one of the ICMJE-accredited clinical trial sites (ID: UMIN 000031558). This article does not contain any studies with animals performed by any of the authors.

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Written informed consent for participation was obtained from all individual participants in the study.

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Kakuo, S., Fushimi, T., Kawasaki, K. et al. Effects of Psidium guajava Linn. leaf extract in Japanese subjects with knee pain: a randomized, double-blind, placebo-controlled, parallel pilot study. Aging Clin Exp Res 30, 1391–1398 (2018). https://doi.org/10.1007/s40520-018-0953-6

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  • DOI: https://doi.org/10.1007/s40520-018-0953-6

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