Efficacy of Phytotherapeutic Protocol for the Risk Factor of Elevated Level of Serum C-Reactive Protein in Knee-Osteoarthritis: Part I. A Systematic Meta - Analysis

  • Apurba Ganguly Founder and Head Researcher, OPTM Research Institute, 145 Rashbehari Avenue, Kolkata – 700029, India
Keywords: Topical phytotherapy, Knee-osteoarthritis, Phytoextracts, Medicinal plants, Knee-symmetry


Background: Knee-osteoarthritis (KOA) is a common disease worldwide. C-reactive protein (CRP) in serum is a marker enzyme for inflammation and elevated in KOA. The present study was aiming to normalize the elevated level of CRP by topical phytotherapeutic protocol correlated with anatomical measurements, body mass index and radiological images in KOA.

Materials & Methods: Baseline data from153 patients (101 females and 52 males) with KOA aged 40-70 years old were recruited in this cross-sectional study. Bilateral anatomical measurements included the gap at the knee between the short head of the biceps femoris and the surface of the bed, diameter of muscles 4cm above and below the patella and calf, and flexion and extension in supine, prone and standing positions and body mass index (BMI) were measured using appropriate instruments. The elevated level of serum CRP and pain under visual analogue scale (VAS) and WOMAC osteoarthritis index were also evaluated at the baseline and after 42nd sessions by topically applied specialized phytotherapeutic treatment protocol.

Results: All the bilateral leg anatomical measurements were symmetry at the end of the 42nd sessions (P<0.0001). The significant changes were observed in pain under VAS (P<0.0001) and WOMAC scales (P<0.0001), CRP level (P<0.0001) and BMI (P<0.0001). The radiological features of the knee-joints were also revealed the improvement in KOA.

 Conclusion: The improvements of inflammation and normalization of elevated serum CRP level confirmed by anatomical measurements, BMI, VAS and WOMAC index and radiological images in KOA by topical phytotherapy. This study revealed that combinations of phytochemicals during topical application may be synergistic effect.



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1. Felson DT. Epidemiology of hip and knee osteoarthritis. Epidemiol. Rev. 1988;10:1-28.
2. Thompson D, Pepys MB, Wood SP. The physiological structure of human C-reactive protein and its complex with phosphocholine. Structure 1999;7:169-177.
3. Morley JJ, Kushner I.Serum C-reactive protein levels in disease. Annals of the New York Academyof Sciences1982;389:406-418.
4. Pepys MB, Baltz ML. Acute phase proteins with special reference to C-reactive protein and related proteins (pentaxins) and serum amyloid A protein. Adv. Immunol.1983;34:141-212.
5. Pepys MB. The acute phase response and C-reactive protein. In: Weatherall DJ, Ledingham JGG, Warrell DA. (eds.), Oxford Textbook of Medicine. 3rd edition. Oxford: Oxford University Press 1995;pp.1527-1533.
6. Shrivastava AK, Singh HV, Raizada A, Singh SK. C-reactive protein, inflammation and coronary heart disease. The Egyptian Heart Journal 2015;67:89-97.
7. Tillet WS, Francis T. Serological reactions in pneumonia with a non-protein somatic fraction of the Pneumococcus. J. Exp. Med.1930;52:561-71.
8. Hashemi R, Majidi A, Motamed H, Amini A, Najari F, Tabatabaey A. Erythrocyte sedimentation rate measurement using as a rapid alternative to the westergren method. Emergency 2015;3(2):50-53.

9. Pagana K, Pagana TJ. (eds.). Mosby's Manual of Diagnostic and Laboratory Tests. 5th Ed. St. Louis, Missouri. 2014.
10. Kaysen GA. Biochemistry and biomarkers of inflamed patients: Why look, What to assess. Clin. J. Am. Soc. Nephrol. 2009;4:S56-S63.
11. Otterness IG, Swindell AC, Zimmerer RO, Poole AR, Ionescu M, Weiner E. Ananalysis of 14 molecular markers for monitoring osteoarthritis: segregation of the markers into clusters and distinguishing osteoarthritis at baseline. Osteoarthr. Cartil. 2000;8:180-185.
12. Pearle AD, Scanzello CR, George S, Mandl LA, DiCarlo EF, Peterson M, et al. Elevated high-sensitivity C-reactive protein levels are associated with local inflammatory findings inpatients with osteoarthritis. Osteoarthr. Cartil. 2007;15:516-523.
13. GangulyA. Diagnosis, Prevention & Phytotherapy for Osteoarthritic Disorders, (ISBN: 978-3-330-65274-3), Scholars Press Book 2017a; pp:13,14,46-48.
14. GangulyA. Tropical phytotherapeutic treatment for achieving knee symmetry in osteoarthritis – A sustainable approach. International Journal of Phytomedicine.2014;6(4): 489-509.
15. Ganguly A. Tropical phytotherapeutic treatment for achieving knee symmetry in osteoarthritis – A sustainable approach. Int. J. Phytomed. 2015a;6(4):489-509.
16. GarneroP, PipernoM, GineytsE, ChristgauS, DelmasPD, VignonE. Cross sectional evaluation of biochemical markers of bone, cartilage, and synovial tissue metabolism in patients with knee osteoarthritis: relations with disease activity and joint damage. Ann. Rheum. Dis. 2001;60:619-626.
17. Parsons S, Alesci S, Feuerstein G, Wang J. Biomarkers in the development of novel disease-modifying therapies for osteoarthritis. Biomarkers Med. 2008;2(6):587-602.
18. Liu J, Shikhman AR, Lotz MK, Wong C-H. Hexosaminidase inhibitors as new drug candidates for the therapy of osteoarthritis. Chem. Biol. 2001;8(7):701-711.
19. Dam EB, Loog M, Christiansen C, Byrjalsen I, Folkesson J, Nielsen M, et al. Identification of progressors in osteoarthritis by combining biochemical and MRI-based markers. Arthritis Res. Ther. 2009;11(4):R115 doi: 10.1186/ar2774.
20. Chantia A. Traditional Knowledge of ethno medicine in Jaunsarbawar, Dehradun district. Indian J. Tradit. Know. 2003;2(4):397-399.
21. Haslam E. Natural polyphenols (vegetable tannins) as drugs: possible modes of action. J. Nat. Prod. 1996;59:205-215.
22. Kurian JC. Ethno-medicinal plants of India, Thailand and Vietnam. J. Biodiversity 2012;3(1):61-75.
23. Singh GB, Atal CK. Pharmacology of an extract of salaiguggal ex-Boswellia serrata, a new non-steroidal anti-inflammatory agent. Agents Actions 1986;18:407-412.
24. Lalithakumari K, Krishnaraju AV, Sengupta K, Subbaraju GV, Chatterjee A. Safety and toxicological evaluation of a novel, standardized 3-O-acetyl-11-keto-β-boswellic acid (AKBA)-enriched Boswellia serrata extract (5-Loxin). Toxicol. Mechanisms Methods2006; 16:199-226.
25. Sengupta K, Alluri KV, Satish AR, Mishra S, Golakoti T, Sarma, KVS, et al. A double blind, randomized, placebo controlled study of the efficacy and safety of 5-Loxin® for treatment of osteoarthritis of the knee. Arthritis Res. Therp. 2008;10(4):R85 (doi:10.1186/ar2461).
26. Schumacher HR, Pullman-Mooar S, Gupta SR, Dinnella JE, Kim R, McHugh MP. Randomized double-blind crossover study of the efficacy of a tart cherry juice blend in treatment of osteoarthritis (OA) of the knee. Osteoarthr. Cartil. 2013;21(8):1035-1041.
27. Schneider CM, Dennehy CA, Roderarmel SJ, Hayward JR. Effects of physical activity on creatine phosphokinase and the isoenzyme creatine kinase-MB. Ann. Emerg. Med. 1995;25(4):520-524.
28. Miller VM, Redfield MM, McConnel JP. Use of BNP and CRP as biomarkers in assessing cardiovascular disease: Diagnosis versus risk. Current Vascular Pharmacology 2007;5: 15-25.
29. Sugiyama M, Hong Z, Liang P-H, Dean SM, Whalen LJ, Greenberg WA,et al. D-fructose-6-phosphate aldolase-catalyzed one-pot synthesis of iminocyclitols. J. Am. Chem. Soc. 2007;129:14811-14817.
30. Talapatra SN, Talukdar P, Swarnakar S. Interaction between C-reactive protein and phytochemical(s)from Calotropisprocera: An approach on molecular docking. International Letters of Natural Sciences 2017;61:43-55.
31. Wang Q, Pan X, Wong HH, Wagner CA, Lahey LJ, Robinson WH, et al.Oral and topical boswellic acid attenuates mouse osteoarthritis. Osteoarthr. Cartil. 2014;22(1):128-132.
32. Ganguly A. Tropical phytotherapeutic treatment for achieving knee symmetry in osteoarthritis – A sustainable approach. International Archives of Biomedical and clinical Research2017b (in press).
33. American Academy of Orthopaedic Surgeons (AAOS). Joint motion: method of measuring and recording. 4th reprint 1965; E. & S. Livingstone Ltd., Edinburgh.
34. Zeigenhagen G, Drahovshy D, Klinishe Bedeutung des C-reactive protein. Med Klin. 1983;78:45-50.
35. Rifai N, Tracy RP, Ridker PM. Clinical efficacy of an automated highsensitivity C-reactive protein assay. ClinChem. 1999;45:2136-2141.
36. Scott J, Huskisson EC. Graphic representation of pain. Pain 1976;2:175-184.
37. Haefeli M, Elfering A. Pain assessment. Eur Spine J. 2006;15:S17-S24.
38. Bellamy N, Buchnan WW, Goldsmith CH, Campbell J, Stitt LW. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to anti-rheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol.1988; 15:1833-1840.
39. Ganguly A. Degenerative changes in lumbar region always lead to bilateral degenerative changes in knee-joints and vice-versa: Sensation of pain cannot only be the parameter of degeneration. Anat Physol. 2015b;S4-005, doi:10/41722161-0940.S4-005.
40. Bhargava S, Dhabhai K, Batra A, Sharma A, Malhotra B. Zingiber officinale: Chemical and phytochemical screening and evaluation of its antimicrobial activities. Journal of Chemical and Pharmaceutical Research 2012;4(1):360-364.
41. Boukhatem MN, Ferhat MA, Kameli A, Saidi F, Kebir HT. Lemon grass (Cymbopogon citratus) essential oil as a potent anti-inflammatory and antifungal drugs. Libyan J. Med.2014;9:25431 (doi.org/10.3402/ljm.v9.25431).
42. Balazs EA. Viscosupplementation for treatment of osteoarthritis: from initial discovery to current status and results. Surgical Technology International 2004;12:278-289.
43. Tugwell PS, Wells GA, Shainhouse JZ. Equivalence study of a topical diclofenac solution (pennsaid) compared with oral diclofenac in symptomatic. treatment of osteoarthritis of the knee: a randomized controlled trial. The Journal of Rheumatology 2004;31(10):2002-2012.
44. Wiltrud R. Cell based cartilage repair: illution and solution for osteoarthritis. Current Opinion in Rheumatology 2007;19(5):451-456.
45. Rosenwald K, Ertl K, Fletcher KE, Whittle J. Patterns of arthritis medication use in a community sample. Journal of Primary Care and Community Health 2012;3(4):272-277.
46. Dnyaneshwar JT, Maruti GW, Rajendra SB, Ravindra YP. Antinociceptive activity of Ricinus communis L. Leaves. Asian Pacific Journal of Tropical Biomedicine 2011;1(2):139-141.
47. Ganguly A. Degenerative changes in lumbar-region occur simultaneously with bilateral-osteoarthritic changes in knee-joints and vice versa: Normalization with topical application of phytoconstituents by specialized techniques involving possible cartilage-regeneration. International Journal of Recent Scientific Research2015c;6(9):6331-6346.
48. 48. Ganguly A. Obtaining normal flexion and extension of knee joints on supine, prone and standing positions in osteoarthritis by topical phytotherapeutic treatment irrespective of age and sex. International Journal of Phytomedicine 2015d;7(3):290-301.
How to Cite
Ganguly A. Efficacy of Phytotherapeutic Protocol for the Risk Factor of Elevated Level of Serum C-Reactive Protein in Knee-Osteoarthritis: Part I. A Systematic Meta - Analysis. IABCR [Internet]. 29Jun.2018 [cited 22Jul.2018];4(2):59-7. Available from: https://iabcr.org/index.php/iabcr/article/view/341