“A COMPARATIVE STUDY OF ANTI- INFLAMMATORY AND ANALGESIC PROPERTIES OF PLANT RUTA GRAVEOLENS AND ALLOPATHIC MEDICINE”
Main Article Content
Keywords
Analgesic agents, Anti- inflammatory agents, Ruta graveolens, NSAIDs, Comparative study
Abstract
Inflammation is a complex biological response to pathogens and tissue damage, involving various immune cells and inflammatory mediators. Non-steroidal anti-inflammatory drugs (NSAIDs) have been widely used to mitigate inflammation and pain by inhibiting prostaglandin production through COX-1 and COX-2 enzyme inhibition. However, NSAIDs are associated with potential side effects, including gastrointestinal and renal issues. In contrast, Ruta graveolens, a plant from the Rutaceae family, has a long history of use in Ayurveda, Homeopathy, and Unani medicine. It contains a diverse array of compounds, including acridone alkaloids, coumarins, essential oils, flavonoids, and fluoroquinolones, which contribute to its anti-inflammatory and analgesic properties. This review article delves into the anti-inflammatory and analgesic properties of Ruta graveolens and compares them with those of allopathic medicines, particularly NSAIDs. We explore the mechanisms of action, clinical evidence, and safety profiles of both approaches. NSAIDs are effective at reducing inflammation and pain but come with notable side effects, including gastrointestinal and cardiovascular risks. In contrast, Ruta graveolens demonstrates potential as a safer alternative with fewer side effects, though more research is needed to establish its safety profile fully. We present the results of our comparative analysis, highlighting the strengths and limitations of each treatment option. Additionally, we discuss the chemical composition of Ruta graveolens and its traditional uses, shedding light on its diverse array of constituents, such as acridone alkaloids, coumarins, limonoids, and flavonoids. Furthermore, we provide insights into the methodology used for extracting Ruta graveolens, including aqueous, methanolic, and ethanolic extracts, and describe animal models used to assess anti-inflammatory and analgesic effects. Our analysis incorporates data from studies exploring the inhibition of sPLA2 enzyme, carrageenan-induced inflammation in rats, and the analgesic potential of Ruta graveolens.
References
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29. Fong SY, Efferth TH, Zuo Z. Modulation of the pharmacokinetics, therapeutic and adverse effects of NSAIDs by Chinese herbal medicines. Expert opinion on drug metabolism & toxicology. 2014 Dec;10(12):1711-39.
30. Sostres C, Gargallo CJ, Arroyo MT, Lanas A. Adverse effects of non-steroidal antiinflammatory drugs (NSAIDs, aspirin and Coxibs) on upper gastrointestinal tract. Best practice & research. Clinical gastroenterology. 2010 Apr;24(2):121-32.
31. Hatt KM, Vijapura A, Maitin IB, Cruz E. Safety considerations in prescription of NSAIDs for musculoskeletal pain: a narrative review. PM&R. 2018 Dec 1;10(12):1404-11.
32. Glover DD, Amonkar M, Rybeck BF, Tracy TS. Prescription, over-the-counter, and herbal medicine use in a rural, obstetric population. American journal of obstetrics and gynecology. 2003 Apr 1;188(4):1039-45.
33. Saxena A, Balaramnavar VM, Hohlfeld T, Saxena AK. Drug/drug interaction of common NSAIDs with antiplatelet effect of aspirin in human platelets. European journal of pharmacology. 2013 Dec 5;721(1-3):215-24.
34. Brantley SJ, Argikar AA, Lin YS, Nagar S, Paine MF. Herb–drug interactions: challenges and opportunities for improved predictions. Drug Metabolism and Disposition. 2014 Mar 1;42(3):301-17.
35. Klueglich M, Ring A, Scheuerer S, Trommeshauser D, Schuijt C, Liepold B, Berndl G. “Ibuprofen Extrudate, a Novel, Rapidly Dissolving Ibuprofen Formulation: Relative Bioavailability Compared to Ibuprofen Lysinate and Regular Ibuprofen, and Food Effect on All Formulations.” The Journal of Clinical Pharmacology. 2005 Sep;45(9):1055-61.
36. Saino V, Monti D, Burgalassi S, Tampucci S, Palma S, Allemandi D, Chetoni P. Optimization of skin permeation and distribution of ibuprofen by using nanostructures (coagels) based on alkyl vitamin C derivatives. European Journal of Pharmaceutics and Biopharmaceutics: Official Journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik eV. 2010 Sep 9;76(3):443-9.
37. Kumar Lalit, Verma Shivani, Singh Mehakjot, Chalotra Tammana and Utreja Puneet, Advanced Drug Delivery Systems for Transdermal Delivery of Non-Steroidal AntiInflammatory Drugs: A Review, Current Drug Delivery 2018; 15(8). https://dx.doi.org/10.2174/1567201815666180605114131
38. Bookstaver PB, Miller AD, Rudisill CN, Norris LB. Intravenous ibuprofen: the first injectable product for the treatment of pain and fever. Journal of pain research. 2010 May 25:67-79.
39. Vilenchik R, Berkovitch M, Jossifoff A, Ben-Zvi Z, Kozer E. Oral versus rectal ibuprofen in healthy volunteers. Journal of Population Therapeutics and Clinical Pharmacology. 2012;19(2).
40. Karp JC, Sanchez C, Guilbert P, Mina W, Demonceaux A, Curé H. Treatment with Ruta graveolens 5CH and Rhus Toxicodendron 9CH may reduce joint pain and stiffness linked to aromatase inhibitors in women with early breast cancer: results of a pilot observational study. Homeopathy. 2016 Nov 1;105(4):299-308.
41. Ratheesh M, Sindhu G, Helen A. Anti-inflammatory effect of quinoline alkaloid skimmianine isolated from Ruta graveolens L. Inflammation research: official journal of the European Histamine Research Society...[et al.]. 2013 Apr;62(4):367-76.
42. Ziesenitz VC, Welzel T, van Dyk M, Saur P, Gorenflo M, van den Anker JN. Efficacy and Safety of NSAIDs in Infants: A Comprehensive Review of the Literature of the Past 20 Years. Pediatric Drugs. 2022 Sep 2;24(6):603-55.
43. Hao H, Wang G, Sun J. Enantioselective pharmacokinetics of ibuprofen and involved mechanisms. Drug metabolism reviews. 2005;37(1):215-34.
44. Radi ZA, Khan KN. Cardio-renal safety of non-steroidal anti-inflammatory drugs. The Journal of Toxicological Sciences (J. Toxicol. Sci.). 2019;44(6):373-91.
45. Ulinski T, Guigonis V, Dunan O, Bensman A. Acute renal failure after treatment with non-steroidal anti-inflammatory drugs. European journal of pediatrics. 2004 Mar;163(3):148-50.
46. Bianciotto M, Chiappini E, Raffaldi I, Gabiano C, Tovo PA, Sollai S, de Martino M, Mannelli F, Tipo V, Da Cas R, Traversa G. Drug use and upper gastrointestinal complications in children: a case–control study. Arch Dis Child. 2013; 98:218-21.
47. Seak CJ, Lin CC. Ruta Graveolens intoxication. Clinical toxicology (Philadelphia, Pa.). 2007;45(2):173-5.
48. Mirghazanfari SM, Abbassian A, Kamalinejad M, Karimian SM, Massoud A. The Effect of Methanolic and Ethanolic Extracts of Ruta graveolens L. Leaves on FormalinInduced Inflammation in Rats. Trad Integr Med. 2016;1(4):136-41.
49. jalali Moghadam MA, Honarmand H, Falah-Delavar S, Saeidinia A. Study on antibacterial effect of Ruta graveolens extracts on pathogenic bacteria. Annals of Biological Research. 2012;3(9):4542-5.
50. Oliva A, Meepagala KM, Wedge DE, Harries D, Hale AL, Aliotta G, Duke SO. Natural fungicides from Ruta graveolens L. leaves, including a new quinolone alkaloid. Journal of agricultural and food chemistry. 2003 Feb 12;51(4):890-6.
2. Day RO, Graham GG. Non-steroidal anti-inflammatory drugs (NSAIDs). Bmj. 2013 Jun 27;346.
3. Tranquilli WJ, Grimm KA. Introduction: use, definitions, history, concepts, classification, and considerations for anesthesia and analgesia. Veterinary Anesthesia and Analgesia: The Fifth Edition of Lumb and Jones. 2015 Apr 29:1-0.
4. Kannan R, Babu UV. Identity and pharmacognosy of Ruta graveolens Linn. Ancient Science of Life. 2012 Jul;32(1):17.
5. Cashman JN. The mechanisms of action of NSAIDs in analgesia. Drugs.1996;52:1323.
6. Bindu S, Mazumder S, Bandyopadhyay U. Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: A current perspective. Biochemical pharmacology. 2020 Oct 1;180 :114147.
7. Rainsford KD. Anti-inflammatory drugs in the 21st century. Inflammation in the pathogenesis of chronic diseases: the COX-2 controversy. 2007 Jan 1:3-27.
8. Kowalski ML, Makowska JS. Seven Steps to the Diagnosis of NSAIDs Hypersensitivity: How to Apply a New Classification in Real Practice? Allergy, Asthma & Immunology Research. 2015 Jul;7(4):312.
9. Sharma D. A brief review of Ruta graveolens plant in homoeopathic system of medicine. Indian Journal of Integrative Medicine. 2022:1-5.
10. https://www.istockphoto.com/search/2/image?phrase=ruta+graveolens(04-09-2023)
11. Réthy B, Zupkó I, Minorics R, Hohmann J, Ocsovszki I, Falkay G. Investigation of cytotoxic activity on human cancer cell lines of arborinine and furanoacridones isolated from Ruta graveolens. Planta medica. 2007 Jan;73(1):41-8.
12. Asgarpanah J, Khoshkam R. Phytochemistry and pharmacological properties of Ruta graveolens L. J Med Plants Res. 2012 Jun 21;6(23):3942-9.
13. Gravot A, Larbat R, Hehn A, Lievre K, Gontier E, Goergen JL, Bourgaud F. Cinnamic acid 4-hydroxylase mechanism-based inactivation by psoralen derivatives: cloning and characterization of a C4H from a psoralen producing plant—Ruta graveolens— exhibiting low sensitivity to psoralen inactivation. Archives of Biochemistry and Biophysics. 2004 Feb 1;422(1):71-80.
14. Meepagala KM, Schrader KK, Wedge DE, Duke SO. Algicidal and antifungal compounds from the roots of Ruta graveolens and synthesis of their analogs. Phytochemistry. 2005 Nov 1;66(22):2689-95.
15. Hale AL, Meepagala KM, Oliva A, Aliotta G, Duke SO. Phytotoxins from the leaves of Ruta graveolens. Journal of agricultural and food chemistry. 2004 Jun 2;52(11):33459.
16. Ratheesh M, Helen A. Anti-inflammatory activity of Ruta graveolens Linn on carrageenan induced paw edema in wistar male rats. African journal of Biotechnology. 2007;6(10).
17. Benazir JF, Suganthi R, Renjini Devi MR, Suganya K, Monisha K, Nizar Ahamed KP, Santhi R. Phytochemical profiling, antimicrobial and cytotoxicity studies of methanolic extracts from Ruta graveolens. Journal of Pharmacy Research. 2011 May;4(5):1407-9.
18. Ratheesh M, Shyni GL, Helen A. Methanolic extract of Ruta graveolens L. inhibits inflammation and oxidative stress in adjuvant induced model of arthritis in rats. Inflammopharmacology. 2009 Apr 1;17(2):100-5.
19. Öztürk A, Özbek H. THE ANTI-INFLAMMATORY ACTIVITY OF EUGENIA CARYOPHYLLATA ESSENTIAL OIL: AN ANIMAL MODEL OF ANTI-INFLAMMATORY ACTIVITY. Eur J Gen Med. 2005;2(4):159-63.
20. Cryer B, Barnett MA, Wagner J, Wilcox CM. Overuse and misperceptions of nonsteroidal anti-inflammatory drugs in the United States. The American journal of the medical sciences. 2016 Nov 1;352(5):472-80.
21. Vuilleumier PH, Schliessbach J, Curatolo M. Current evidence for central analgesic effects of NSAIDs: an overview of the literature. Minerva anesthesiologic. 2018 Jul;84(7):865-70.
22. Cunha MR, Melo TS, Magri FM, Delorenzi JC. Analgesic activity of Ruta graveolens L. (Rue) extracts. African J. of Pharmacy and Pharmacol. 2015; 9:1-5.
23. Nissen SE, Yeomans ND, Solomon DH, Lüscher TF, Libby P, Husni ME, Graham DY, Borer JS, Wisniewski LM, Wolski KE, Wang Q. Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis.
24. Kizhakkedath R. Clinical evaluation of a formulation containing Curcuma longa and Boswellia serrata extracts in the management of knee osteoarthritis. Molecular medicine reports. 2013 Nov 1;8(5):1542-8.
25. Osafo N, Agyare C, Obiri DD, Antwi AO. Mechanism of Action of Nonsteroidal Anti-Inflammatory Drugs. NONSTEROIDAL ANTI-INFLAMMATORY DRUGS. 2017:2.
26. Bannuru RR, Osani MC, Al-Eid F, Wang C. Efficacy of curcumin and Boswellia for knee osteoarthritis: systematic review and meta-analysis. InSeminars in arthritis and rheumatism 2018 Dec 1 (Vol. 48, No. 3, pp. 416-429). WB Saunders.
27. Bhagat BV, Rachh PR, Pawar AR. Evaluation of anti-inflammatory and analgesic activity of optimized lipid based non-aqueous nano emulsion of naproxen in experimental animals. Int J Health Sci. 2022;6(S1):5963-72.
28. Harirforoosh S, Asghar W, Jamali F. Adverse Effects of Nonsteroidal Antiinflammatory Drugs: An Update of Gastrointestinal, Cardiovascular and Renal Complications. J Pharm Ph Ulinski T, Guigonis V, Dunan O, Bensman A. Acute renal failure after treatment with non-steroidal anti-inflammatory drugs. European journal of pediatrics. 2004 Mar;163(3):148-50. arm Sci (www. cspsCanada. org). 2013;16(5):82147.
29. Fong SY, Efferth TH, Zuo Z. Modulation of the pharmacokinetics, therapeutic and adverse effects of NSAIDs by Chinese herbal medicines. Expert opinion on drug metabolism & toxicology. 2014 Dec;10(12):1711-39.
30. Sostres C, Gargallo CJ, Arroyo MT, Lanas A. Adverse effects of non-steroidal antiinflammatory drugs (NSAIDs, aspirin and Coxibs) on upper gastrointestinal tract. Best practice & research. Clinical gastroenterology. 2010 Apr;24(2):121-32.
31. Hatt KM, Vijapura A, Maitin IB, Cruz E. Safety considerations in prescription of NSAIDs for musculoskeletal pain: a narrative review. PM&R. 2018 Dec 1;10(12):1404-11.
32. Glover DD, Amonkar M, Rybeck BF, Tracy TS. Prescription, over-the-counter, and herbal medicine use in a rural, obstetric population. American journal of obstetrics and gynecology. 2003 Apr 1;188(4):1039-45.
33. Saxena A, Balaramnavar VM, Hohlfeld T, Saxena AK. Drug/drug interaction of common NSAIDs with antiplatelet effect of aspirin in human platelets. European journal of pharmacology. 2013 Dec 5;721(1-3):215-24.
34. Brantley SJ, Argikar AA, Lin YS, Nagar S, Paine MF. Herb–drug interactions: challenges and opportunities for improved predictions. Drug Metabolism and Disposition. 2014 Mar 1;42(3):301-17.
35. Klueglich M, Ring A, Scheuerer S, Trommeshauser D, Schuijt C, Liepold B, Berndl G. “Ibuprofen Extrudate, a Novel, Rapidly Dissolving Ibuprofen Formulation: Relative Bioavailability Compared to Ibuprofen Lysinate and Regular Ibuprofen, and Food Effect on All Formulations.” The Journal of Clinical Pharmacology. 2005 Sep;45(9):1055-61.
36. Saino V, Monti D, Burgalassi S, Tampucci S, Palma S, Allemandi D, Chetoni P. Optimization of skin permeation and distribution of ibuprofen by using nanostructures (coagels) based on alkyl vitamin C derivatives. European Journal of Pharmaceutics and Biopharmaceutics: Official Journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik eV. 2010 Sep 9;76(3):443-9.
37. Kumar Lalit, Verma Shivani, Singh Mehakjot, Chalotra Tammana and Utreja Puneet, Advanced Drug Delivery Systems for Transdermal Delivery of Non-Steroidal AntiInflammatory Drugs: A Review, Current Drug Delivery 2018; 15(8). https://dx.doi.org/10.2174/1567201815666180605114131
38. Bookstaver PB, Miller AD, Rudisill CN, Norris LB. Intravenous ibuprofen: the first injectable product for the treatment of pain and fever. Journal of pain research. 2010 May 25:67-79.
39. Vilenchik R, Berkovitch M, Jossifoff A, Ben-Zvi Z, Kozer E. Oral versus rectal ibuprofen in healthy volunteers. Journal of Population Therapeutics and Clinical Pharmacology. 2012;19(2).
40. Karp JC, Sanchez C, Guilbert P, Mina W, Demonceaux A, Curé H. Treatment with Ruta graveolens 5CH and Rhus Toxicodendron 9CH may reduce joint pain and stiffness linked to aromatase inhibitors in women with early breast cancer: results of a pilot observational study. Homeopathy. 2016 Nov 1;105(4):299-308.
41. Ratheesh M, Sindhu G, Helen A. Anti-inflammatory effect of quinoline alkaloid skimmianine isolated from Ruta graveolens L. Inflammation research: official journal of the European Histamine Research Society...[et al.]. 2013 Apr;62(4):367-76.
42. Ziesenitz VC, Welzel T, van Dyk M, Saur P, Gorenflo M, van den Anker JN. Efficacy and Safety of NSAIDs in Infants: A Comprehensive Review of the Literature of the Past 20 Years. Pediatric Drugs. 2022 Sep 2;24(6):603-55.
43. Hao H, Wang G, Sun J. Enantioselective pharmacokinetics of ibuprofen and involved mechanisms. Drug metabolism reviews. 2005;37(1):215-34.
44. Radi ZA, Khan KN. Cardio-renal safety of non-steroidal anti-inflammatory drugs. The Journal of Toxicological Sciences (J. Toxicol. Sci.). 2019;44(6):373-91.
45. Ulinski T, Guigonis V, Dunan O, Bensman A. Acute renal failure after treatment with non-steroidal anti-inflammatory drugs. European journal of pediatrics. 2004 Mar;163(3):148-50.
46. Bianciotto M, Chiappini E, Raffaldi I, Gabiano C, Tovo PA, Sollai S, de Martino M, Mannelli F, Tipo V, Da Cas R, Traversa G. Drug use and upper gastrointestinal complications in children: a case–control study. Arch Dis Child. 2013; 98:218-21.
47. Seak CJ, Lin CC. Ruta Graveolens intoxication. Clinical toxicology (Philadelphia, Pa.). 2007;45(2):173-5.
48. Mirghazanfari SM, Abbassian A, Kamalinejad M, Karimian SM, Massoud A. The Effect of Methanolic and Ethanolic Extracts of Ruta graveolens L. Leaves on FormalinInduced Inflammation in Rats. Trad Integr Med. 2016;1(4):136-41.
49. jalali Moghadam MA, Honarmand H, Falah-Delavar S, Saeidinia A. Study on antibacterial effect of Ruta graveolens extracts on pathogenic bacteria. Annals of Biological Research. 2012;3(9):4542-5.
50. Oliva A, Meepagala KM, Wedge DE, Harries D, Hale AL, Aliotta G, Duke SO. Natural fungicides from Ruta graveolens L. leaves, including a new quinolone alkaloid. Journal of agricultural and food chemistry. 2003 Feb 12;51(4):890-6.
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Dec 16, 2023
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Vismruti Rathod, Ms. Krupa Vyas, & Dr. Pragnesh Patani. (2023). “A COMPARATIVE STUDY OF ANTI- INFLAMMATORY AND ANALGESIC PROPERTIES OF PLANT RUTA GRAVEOLENS AND ALLOPATHIC MEDICINE”. Journal of Population Therapeutics and Clinical Pharmacology, 30(19), 2012–2022. https://doi.org/10.53555/jptcp.v30i19.4126
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Author Biographies
Vismruti Rathod
Khyati college of Pharmacy, Palodia, Ahmedabad
Ms. Krupa Vyas
Khyati college of Pharmacy, Palodia, Ahmedabad
Dr. Pragnesh Patani
Khyati college of Pharmacy, Palodia, Ahmedabad