Screening of herbal extracts for rapid effect on activity-induced knee joint discomfort: a randomized and placebo-controlled pilot study

Authors

  • Shalini Srivastava Department of Clinical Development, Enovate Biolife, Wilmington DE, USA
  • Robert N. Girandola Department of Human Biology, University of South California, Los Angeles, CA, USA

DOI:

https://doi.org/10.18203/2349-3259.ijct20240400

Keywords:

Zingiber officinale, Vitex negundo, Joint discomfort, Acute pain, MPR, Physical activity

Abstract

Background: A feasibility study was conducted to investigate the effect of different proprietary extracts on joint discomfort associated with repeated episodes of physical activity.

Methods: A single-dose randomized, double-blind, placebo-controlled cross-over study was conducted in three phases with different extract combinations. Seventeen individuals aged 40-60 years with a history of knee joint pain aggravation on physical stress were randomized to receive the investigational product or the placebo in a 1:1 ratio. The primary outcome was the time taken to achieve meaningful pain relief (MPR) from baseline using a pain visual analog scale (VAS) compared to the placebo. The secondary outcomes were the pain intensity difference (PID) and joint discomfort at 1-, 2-, 3-, and 4-hours post-product administration and the time-weighted sum of pain intensity difference (SPID) over 4 hours compared to placebo.

Results: Participants in two out of eight investigational product groups achieved MPR successfully. The proprietary combination ZV-E (consisting of Z. officinale and V. negundo) showed the fastest pain reduction with more than 50% of the participants achieving meaningful relief. The BS-ZP (consisting of B. serrata + Z. officinale + P. lanceolata) group also had more than 50% of participants reporting MPR at 4 hours post-IP administration. Subsequently, the SPID was found to be lowest in the participants of above stated groups.

Conclusions: The proprietary combination of Z. officinale and V. negundo extracts, 200 mg could be a promising lead to conduct a further trial to investigate its effect on joint pain.

References

Varga Z, Syed RAS, Veronika V. Cardiovascular Risk of Nonsteroidal Anti-Inflammatory Drugs: An Under-Recognized Public Health Issue. Cureus. 2017;9(4):e1144.

Coxib and traditional NSAID Trialists’ (CNT) Collaboration, Coxib and traditional NSAID Trialists’ (CNT), Bhala N, Emberson J, Merhi A, Abramson S, et al. Vascular and Upper Gastrointestinal Effects of Non-Steroidal Anti-Inflammatory Drugs: Meta-Analyses of Individual Participant Data from Randomised Trials. Lancet (London, England). 2013;382(9894).

Grando RL, Iolanda FM. Medicinal Plants Used on Arthritis Treatment: An Overview through Patent Analysis. J Pharmacognosy Phytochem. 2017;6(66):1999-2003.

Yang L, David S, Jon A. A Critical Review of Complementary and Alternative Medicine Use among People with Arthritis: A Focus upon Prevalence, Cost, User Profiles, Motivation, Decision-Making, Perceived Benefits and Communication. Rheumatol Int. 2017;37(3):337-51.

Yatoo MI, Arumugam G, Archana S, Oveas RP, Noore AT, Sandip C, et al. Anti-Inflammatory Drugs and Herbs with Special Emphasis on Herbal Medicines for Countering Inflammatory Diseases and Disorders-A Review. Recent Patents Inflammation Allergy Drug Discovery. 2018;12(1):39-58.

Lü S, Qiushi W, Guoyu L, Shuang S, Yuyan G, Haixue K. The Treatment of Rheumatoid Arthritis Using Chinese Medicinal Plants: From Pharmacology to Potential Molecular Mechanisms. J Ethnopharmacol. Elsevier. 2015;176:177-206.

Jahromi B, Pirvulescu I, Candido KD, Knezevic NN. Herbal Medicine for Pain Management: Efficacy and Drug Interactions. Pharmaceutics. 2021;13(2):251.

Zheng CJ, Li HQ, Ren SC, Chuan-Liang X, Khalid R, Lu-Ping Q, et al. Phytochemical and pharmacological profile of vitex negundo. Phyther Res. 2015;29(5):633-47.

Wilson PB. Ginger (Zingiber officinale) as an Analgesic and Ergogenic Aid in Sport: A Systemic Review. J Strength Cond Res. 2015;29(10):2980-95.

Rondanelli M, Fossari F, Vecchio V, Clara G, Gabriella P, Daniele S, et al. Clinical trials on pain lowering effect of ginger: A narrative review. Phytother Res. 2020;34(11):2843-56.

Matsumura MD, Zavorsky GS, Smoliga JM. The Effects of Pre-Exercise Ginger Supplementation on Muscle Damage and Delayed Onset Muscle Soreness. Phytother Res. 2015;29(6):887-93.

Mashhadi NS, Ghiasvand R, Askari G, Awat F, Mitra H, Leila D, et al. Influence of ginger and cinnamon intake on inflammation and muscle soreness endued by exercise in Iranian female athletes. Int J Prev Med. 2013;4(1):S11-5.

Manimmanakorn N, Manimmanakorn A, Boobphachart D, Thuwakum W, Laupattarakasem W, Hamlin MJ. Effects of Zingiber cassumunar (Plai cream) in the treatment of delayed onset muscle soreness. J Integr Med. 2016;14(2):114-20.

Black CD, O’Connor PJ. Acute effects of dietary ginger on muscle pain induced by eccentric exercise. Phyther Res. 2010;24(11):1620-26.

Gill BS, Mehra R, Navgeet, Kumar S. Vitex negundo and its medicinal value. Mol Biol Rep. 2018;45(6):2925-34.

Dharmasiri MG, Jayakody JR, Galhena G, Liyanage SS, Ratnasooriya WD. Anti-inflammatory and analgesic activities of mature fresh leaves of Vitex negundo. J Ethnopharmacol. 2003;87(2-3):199-206.

Khatavkar P. S, Dawane J. S, Sarak A. Study of Multifaceted Effect of Vitex negundo Leaves Aqueous Extract and Decoction for Pain Relief in Experimental Models. Biomed Pharmacol J. 2021;14(3).

Abdel-Tawab M, Werz O, Schubert-Zsilavecz M. Boswellia serrata: an overall assessment of in vitro, preclinical, pharmacokinetic and clinical data. Clin Pharmacokinet. 2011;50(6):349-69.

Ojewole JAO. Anti-inflammatory and analgesic effects of Psidium guajava Linn. (Myrtaceae) leaf aqueous extract in rats and mice. Methods Find Exp Clin Pharmacol. 2006;28(7):440-46.

Kakuo S, Fushimi T, Kawasaki K, Nakamura J, Ota N. 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. 2018;30(11):1391-8.

Horigome S, Yoshida I, Tsuda A, Teppei H, Akihiro Y, Kumiko Y, et al. Identification and evaluation of anti-inflammatory compounds from Kaempferia parviflora. Biosci Biotechnol Biochem. 2014;78(5):851-60.

Mangione KK, Axen K, Haas F. Mechanical Unweighting Effects on Treadmill Exercise and Pain in Elderly People with Osteoarthritis of the Knee. Phys Ther. 1996;76(4):387-94.

Elinoff JM, Rame JE, Forfia PR, Hall MK, Sun J, Gharib AM, et al. A pilot study of the effect of spironolactone therapy on exercise capacity and endothelial dysfunction in pulmonary arterial hypertension: Study protocol for a randomized controlled trial. Trials. 2013;14:91.

Da Silva FAN, De Farias Freire SM, Da Rocha Borges MO, et al. Antinociceptive and Anti-inflammatory Effects of Triterpenes from Pluchea quitoc DC. Aerial Parts. Pharmacognosy Res. 2017;9(1):S1.

Kobayashi H, Suzuki R, Sato K, Takatoshi O, Hiroshi T, Masahito T, et al. Effect of Kaempferia parviflora extract on knee osteoarthritis. J Nat Med. 2018;72(1):136-44.

Moore RA, Moore OA, Derry S, McQuay HJ. Numbers needed to treat calculated from responder rates give a better indication of efficacy in osteoarthritis trials than mean pain scores. Arthritis Res Ther. 2008;10(2):R39.

Withee ED, Tippens KM, Dehen R, Hanes D. Effects of MSM on exercise-induced muscle and joint pain: a pilot study. J Int Soc Sports Nutr. 2015;12(1):P8.

Withee ED, Tippens KM, Dehen R, Tibbitts D, Hanes D, Zwickey H. Effects of Methylsulfonylmethane (MSM) on exercise-induced oxidative stress, muscle damage, and pain following a half-marathon: a double-blind, randomized, placebo-controlled trial. J Int Soc Sports Nutr. 2017;14(1):24.

Ruff KJ, Morrison D, Duncan SA, Back M, Aydogan C, Theodosakis J. Beneficial effects of natural eggshell membrane versus placebo in exercise-induced joint pain, stiffness, and cartilage turnover in healthy, postmenopausal women. Clin Interv Aging. 2018;13:285.

Zdzieblik D, Brame J, Oesser S, Gollhofer A, König D. The Influence of Specific Bioactive Collagen Peptides on Knee Joint Discomfort in Young Physically Active Adults: A Randomized Controlled Trial. Nutrients. 2021;13(2):1-13.

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Published

2024-02-23

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Original Research Articles