Abstract
The effect of Orthosiphon stamineus aqueous (OSA) extract against osteoarthritis (OA) was investigated in explant cartilage culture and in postmenopausal OA rat model. Female rats were bilaterally ovariectomized (OVX). Osteoarthritis was induced after surgical recovery, by intra-articular injection of monosodium iodoacetate (MIA) into the right knee. Rats were grouped (n = 8) into: healthy sham control; non-treated OA; OA + diclofenac (positive control 5 mg/kg); and two doses OSA (150–300 mg/kg). After 4 weeks’ treatment, rats were evaluated for OA-related parameters and biomarkers. The OSA reduced proteoglycan and ROS release from the cartilage explants under inflammatory (IL-1b) conditions. In the OA-induced rats’ cartilages, the OSA downregulated the mRNA expressions for IL-1β, IL-6, IL-10, TNF-α, NF-κβ, NOS2, PTGS2, PTGER2, ACAN, COL2A1, MMP1, MMP13, ADAMTS4, ADAMTS5 and TIMP1, mostly dose-dependently. The OSA reduced the OA rats’ serum levels for PGE2, CTX-II, TNF-α, MMP1, MMP13, PIINP, OPG, RANKL, OC and BALP, but not dose-dependently. The OSA contained polyphenols and flavonoids (tetramethoxyflavone). The OSA alleviated articular cartilage degradation, inflammation, collagenase/aggrecanase activities, to improve joint and subchondral bone structure. O. stamineus mitigated osteoarthritis by downregulating inflammation, peptidases and aggrecanases, at a dose equivalent to about 30 mg/kg for humans.
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Acknowledgements
We thank the Ministry of Agriculture, Herbal development Division for the research Grant, 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.
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This work was supported by the Herbal Development Division, Ministry of Agriculture, Malaysia (Grant no. NH1014D052).
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Institutional Animal Care and Use Committee (IACUC), Universiti Putra Malaysia approval (UPM/IACUC/AUP-R083/2014).
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Bokhari, R.A., Tantowi, N.A.C.A., Lau, S.F. et al. Java Tea (Orthosiphon stamineus) protected against osteoarthritis by mitigating inflammation and cartilage degradation: a preclinical study. Inflammopharmacol 26, 939–949 (2018). https://doi.org/10.1007/s10787-017-0432-2
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DOI: https://doi.org/10.1007/s10787-017-0432-2