The effect of a multi-herbal product, C. autumnale, W. somnifera, and P. lentiscus, on knee osteoarthritis: a triple-blind randomized clinical trial
Abstract
Background and purpose: Osteoarthritis (OA) is a common joint disease that affects millions of people worldwide and is characterized by cartilage degeneration, stiffness, and limited mobility.
This clinical trial aimed to investigate the efficacy and safety of a herbal combination of Colchicum autumnale root, Withania somnifera root, and Pistacia lentiscus gum in the relief of knee OA symptoms.
Experimental approach: Seventy patients diagnosed with knee OA were randomized to receive the herbal product or a placebo for 6 weeks. Pain and functional outcomes were measured using the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and Visual Analogue Scale (VAS). The heel-to-thigh distance parameter was also assessed by measuring the distance between the thigh and heel at maximum knee flexion in the prone position.
Findings/Results: Significant improvements were observed in WOMAC scores for pain, stiffness, and physical function in the herbal product group compared to placebo at 3 and 6 weeks. VAS scores confirmed these results and showed lower pain intensity in the herbal product group. Heel-to-thigh distance decreased significantly within all groups during the study.
Conclusion and implications: This study provided evidence for the efficacy of the herbal combination in the management of knee OA symptoms and was well tolerated by all patients with no severe adverse effects. The observed benefits emphasized the potential of herbal medicines as a complementary approach in the management of knee OA. Further research is needed to fully elucidate the therapeutic mechanisms and optimize the clinical application of this herbal combination.
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GBD 2021 osteoarthritis collaborators; Steinmetz JD, Culbreth GT, Haile LM, Rafferty Q, Lo J, Fukutaki KG, et al. Global, regional, and national burden of osteoarthritis, 1990-2020 and projections to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet Rheumatol. 2023;5(9): e508-e522.DOI: 10.1016/S2665-9913(23)00163-7.
Erol Aksekili MA, Fidan F, Alkan BM, Alemdar A, Aksekili H, Ardıçoğlu Ö. Quality of life in knee osteoarthritis: correlation with clinical measures and the knee injury and osteoarthritis outcome score. Acta Med Anatol. 2016;4(1):1-7.DOI: 10.5505/actamedica.2016.41636.
Sharma L. Osteoarthritis of the knee. N Engl J Med. 2021;384(1):51-59.DOI: 10.1056/NEJMcp1903768.
Alsharif IA, Abd-Elsalam RM, Amer MS, El-Desoky AH, Abdel-Rahman RF. Crataegus sinaica defatted methanolic extract ameliorated monosodium iodoacetate-induced oxidative stress and inhibited inflammation in a rat model of osteoarthritis. Res Pharm Sci. 2022;17(5):493-507.DOI: 10.4103/1735-5362.355209.
Addissouky TA, El Sayed IET, Ali MMA. Conservative and emerging rehabilitative approaches for knee osteoarthritis management. J Clinical Orthopaedics and Trauma Care. 2024;6(2): 1-11.DOI: 10.31579/2694-0248/082.
Fuggle NR, Cooper C, Oreffo ROC, Price AJ, Kaux JF, Maheu E, et al. Alternative and complementary therapies in osteoarthritis and cartilage repair. Aging Clin Exp Res. 2020;32(4):547-560.DOI: 10.1007/s40520-020-01515-1.
Kongkwamcharoen C, Itharat A, Ketjinda W, Lee HY, Moon GS, Davies NM. Formulation design and physicochemical evaluation of an anti-inflammatory hydrogel patch containing Crinum asiaticum L. extract. Res Pharm Sci. 2023;18(3):244-261.DOI: 10.4103/1735-5362.371581.
Baig M, Saleem M. The effects of herbal products in cartilage healing and reducing the progression of osteoarthritis. Mako: NSU Undergraduate Student Journal. 2023;2023(2):2,1-19.
Abbasifard M, Moosavi Z, Azimi M, Kamiab Z, Bazmandegan G, Madahian A, et al. Effect of topical hemp (Cannabis sativa L.) seed oil on knee osteoarthritis: a randomized double-blind controlled trial. Pain Manag Nurs. 2025;26(1):e74-e81.DOI: 10.1016/j.pmn.2024.08.001.
Itharat A, Thongmee P, Piwngam K, Inprasit J, Makchuchit S, Kuropakornpong P, et al. In vitro and in vivo evaluation of anti-inflammatory activities of ethanol extract from Lom-Am-Ma-Pruek remedy for pain relief. Res Pharm Sci. 2024;19(6):683-697.DOI: 10.4103/RPS.RPS-26-24.
Azam Khan M. Exir Azam (Persian). Tehran: Institute of Medical History Studies, Islamic Medicine and Complementary Medicine of Iran Medical University. 2008. pp. 575-584.
Thakur S, Chaudhary G, Kaurav H. Colchicum autumnale (Suranjan): a cytotoxic plant with anti-arthritis properties. Adv Pharm J. 2021;6(3):80-86.DOI: 10.31024/apj.2021.6.3.4.
Ramakanth GSH, Kumar CU, Kishan PV, Usharani P. A randomized, double blind placebo controlled study of efficacy and tolerability of Withaina somnifera extracts in knee joint pain. J Ayurveda Integr Med. 2016;7(3):151-157.DOI: 10.1016/j.jaim.2016.05.003.
Mohtashami R, Hashem-Dabaghian F, Nabati F, Qaderi A, Kianbakht S. Efficacy of topical oleoresin of Pistacia atlantica L. subspecies kurdica for symptomatic relief of knee osteoarthritis: a randomized double-blinded controlled trial. J Herb Med. 2023;38:100638.DOI: 10.1016/j.hermed.2023.100638.
Heidari‐Beni M, Moravejolahkami AR, Gorgian P, Askari G, Tarrahi MJ, Bahreini‐Esfahani N. Herbal formulation "turmeric extract, black pepper, and ginger" versus Naproxen for chronic knee osteoarthritis: a randomized, double‐blind, controlled clinical trial. Phytother Res. 2020;34(8):2067-2073.DOI: 10.1002/ptr.6671.
Gerayeli Malek V, Parvari S, Rouhani Y, Jafari F, Rahimi R, Abbassian A. Efficacy of a traditional herbal formula based on Colchicum autumnale L. (Rhazes tablet) in low back pain: a randomized controlled clinical trial. Int J Ayurvedic Med. 2019;10(1):27-33.DOI: 10.47552/ijam.v10i1.1178.
Wang Z, Efferth T, Hua X, Zhang XA. Medicinal plants and their secondary metabolites in alleviating knee osteoarthritis: a systematic review. Phytomedicine. 2022;105:154347.DOI: 10.1016/j.phymed.2022.154347.
Zhang P, Li K, Kamali A, Ziadlou R, Ahmad P, Wang X, et al. Small molecules of herbal origin for osteoarthritis treatment: in vitro and in vivo evidence. Arthritis Res Ther. 2022;24(1):105,1-19.DOI: 10.1186/s13075-022-02785-y.
Akram M, Alam O, Usmanghani K, Naveed A, Asif M. Colchicum autumnale: A review. J Med Plant Res. 2012;6(29):1489-1491.DOI: 10.5897/JMPR11.323.
Romani A, Pinelli P, Galardi C, Mulinacci N, Tattini M. Identification and quantification of galloyl derivatives, flavonoid glycosides and anthocyanins in leaves of Pistacia lentiscus L. Phytochem Anal. 2002;13(2): 79-86.DOI: 10.1002/pca.627.
Gajbhiye NA, Makasana J, Kumar S. Accumulation of three important bioactive compounds in different plant parts of Withania somnifera and its determination by the LC-ESI-MS-MS (MRM) method. J Chromatogr Sci. 2015;53(10):1749-1756.DOI: 10.1093/chromsci/bmv088.
Mehrabani M, Lotfian Sargazi M, Amirkhosravi A, Farhadi S, Vasei S, Raeiszadeh M, et al. The influence of harvest time on total phenolic and flavonoid contents, antioxidant, antibacterial and cytotoxicity of Rheum khorasanicum root extract. Ann Pharm Fr; 2023: 81(3):475-483.DOI: 10.1016/j.pharma.2022.11.010.
Sealed Envelope Ltd. Create a blocked randomisation list. 2022. [Online] Available from: https://www.sealedenvelope.com/simple-randomiser/v1/lists.
Boonstra AM, Preuper HRS, Balk GA, Stewart RE. Cut-off points for mild, moderate, and severe pain on the visual analogue scale for pain in patients with chronic musculoskeletal pain. Pain. 2014;155(12):2545-2550.DOI: 10.1016/j.pain.2014.09.014.
Eftekhar-Sadat B, Niknejad-Hosseyni SH, Babaei-Ghazani A, Toopchizadeh V, Sadeghi H. Reliability and validity of Persian version of Western Ontario and McMaster Universities Osteoarthritis index in knee osteoarthritis. J Anal Res Clin Med. 2015;3(3):170-177.DOI: 10.15171/jarcm.2015.027.
Al-Mahmood MR, Uddin MT, Islam MT, Fuad SM, Shah TR. Correlation between goniometric measurements of range of motion and radiographic scores in osteoarthritis knee: an observational study among females. Medicine (Baltimore). 2022;101(32):e29995,1-6.DOI: 10.1097/MD.0000000000029995.
Adham-Foumani E, Irani S, Shokoohinia Y, Mostafaie A. Colchicine of Colchicum autumnale, a traditional anti-inflammatory medicine, induces apoptosis by activation of apoptotic genes and proteins expression in human breast (MCF-7) and mouse breast (4T1) cell lines. Cell J. 2022;24(11):647-656.DOI: 10.22074/cellj.2022.8290.
Milia E, Bullitta SM, Mastandrea G, Szotáková B, Schoubben A, Langhansová L, et al. Leaves and fruits preparations of Pistacia lentiscus L.: a review on the ethnopharmacological uses and implications in inflammation and infection. Antibiotics (Basel). 2021;10(4):425,1-21.DOI: 10.3390/antibiotics10040425.
Goel P, Bhuria M, Kaushal M. Efficacy of medicinal plants in combating COVID-19. J Pharmacogn Phytochem. 2021;10(5):147-157.
Palliyaguru DL, Chartoumpekis DV, Wakabayashi N, Skoko JJ, Yagishita Y, Singh SV, et al. Withaferin A induces Nrf2-dependent protection against liver injury: role of Keap1-independent mechanisms. Free Radic Biol Med. 2016;101:116-128.DOI: 10.1016/j.freeradbiomed.2016.10.003.
Lim DW, Kim JG, Lim EY, Kim YT. Antihyperalgesic effects of ashwagandha (Withania somnifera root extract) in rat models of postoperative and neuropathic pain. Inflammopharmacology. 2018;26(1):207-215.
pain. Inflammopharmacology. 2018;26(1):207-215.DOI: 10.1007/s10787-017-0389-1.
Singh A, Molina-Garcia P, Hussain S, Paul A, Das SK, Leung YY, et al. Efficacy and safety of colchicine for the treatment of osteoarthritis: a systematic review and meta-analysis of intervention trials. Clin Rheumatol. 2023;42(3): 889-902.DOI: 10.1007/s10067-022-06402-w.
Bhatwal V, Patil M, Chaudhari N. A prospective, open-label, non-randomised clinical trial to evaluate the safety and efficacy of Rymanyl Tablets in the treatment of osteoarthritis. J Ayurveda Integr Med Sci. 2024;9(7):28-35.DOI: 10.21760/jaims.9.7.4.
Lindler BN, Long KE, Taylor NA, Lei W. Use of herbal medications for treatment of osteoarthritis and rheumatoid arthritis. Medicines (Basel). 2020;7(11):67,1-18.DOI: 10.3390/medicines7110067.
Kessler CS, Dhiman KS, Kumar A, Ostermann T, Gupta S, Morandi A, et al. Effectiveness of an Ayurveda treatment approach in knee osteoarthritis- a randomized controlled trial. Osteoarthritis Cartilage. 2018;26(5):620-630.DOI: 10.1016/j.joca.2018.01.022.
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