Aegle Marmelos Suppresses Inflammation and Cartilage

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RD, 2011; Vol 3(4): June 2011 (38 - 45) International Standard Serial Number 0974 – 944

ailable online on www.ijprd.com 38

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AEGLE MARMELOS SUPPRESSES INFLAMMATION AND CARTILAGE

DESTRUCTION IN COLLAGEN-INDUCED ARTHRITIC RAT.

Hardik P. Trivedi1*, Nimish L. Pathak1, Mahendra G. Gavaniya1,

Anjana K. Patel1, Dr. Harshkant D. Trivedi1, Nitin. M Panchal1

1C.U. Shah College of Pharmacy and Research Wadhwan,Gujarat-363030

ABSTRACT

Aegle marmelos has multiple applications in Indian traditional medicinebecause of its anti-pyretic, anti-inflammatory, antidiabetic andantimicrobial activities and also have immunosuppressive activity.However, no study on the anti-arthritic activity of Aegle mamrmelos hasbeen reported in vivo. Rheumatoid arthritis (RA) is a systemicautoimmune disease with chronic inflammation characterized byhyperplasia of synovial cells in affected joints, which ultimately leads to

the destruction of cartilage and bone. We investigated therapeuticefficacy of Aegle marmelos in treating Rheumatoid Arthritis (RA) usingcollagen-induced arthritis (CIA) animal model. Arthritis was induced inwistar rats by immunization with bovine type II collagen. CIA rats weretreated daily with oral administration of different doses of Methanolicextract of A.marmelos (MAM) beginning on the day after the onset of arthritis (day 21st, the therapeutic treatment) until day 45. The resultsshowed that treatment with MAM markedly reduced paw swelling andarthritic index even in the established CIA. Radiologic andhistopathologic changes in the arthritic joints were also significantlyreduced in the MAM-treated versus vehicle-treated rats. Moreover,

Rheumatoid factor was significantly reduced in MAM treated group incompared to disease control group. Hence, our studies demonstratesafety, and effectiveness of A.marmemlos as an anti-arthritic agent,which makes A.marmelos a strong candidate for further research onrheumatoid arthritis (RA).

Correspondence to Author

Hardik P. Trivedi

C.U. Shah College of Pharmaand Research Wadhwan,

Gujarat-363030

Email [email protected]

Key Words

Arthritis, Collagen Inducedarthritis, Aegle Marmelos,Cartilage destruction



ernational Journal of Pharmaceutical Research & Development ISSN: 0974 – 9


TRODUCTION

eumatoid arthritis (RA) is a chronic inflammatoryease involving multiple joints. The main pathology of

e affected synovial tissue consists of hyperplasia andbintimal infiltration of T and B lymphocytes. Synovialsue hyperplasia forms the pannus tissue thateversibly destroys the cartilage and bone in theected joint. Collagen-induced arthritis (CIA) rat is adely studied animal model of inflammatorylyarthritis with similarities to RA. CIA is induced aftermunization of susceptible strains of rat with bovine

pe II collagen (CII) in Incomplete Freund’s adjuvantA), and the resulting disease is primarily mediated byautoimmune response. [1,2] The significance of the

odel lies in the fact that CII is the major constituentotein of the cartilage in the diarthrodial joints—themary site affected in RA.[2]

Drug therapy for RA is

sed on two principal approaches: symptomaticatment with non-steroidal anti-inflammatory drugsSAIDs) and disease-modifying antirheumatic drugsMARDs).[3] However, most of the currently availableugs are primarily directed towards the control of paind/or the inflammation associated with joint synovitis,t do little to interfere with the underlying immune-lammatory events, and consequently also do little to

ock the disease progression and reduce cartilage andne destruction of joints. A systematic review of ndomized placebo-controlled trials conductedcently demonstrates that the published evidencepports only the efficacies of nine agents in Westernedicine, i.e., infliximab, cyclosporin, sulphasalzine,unomide, methotrexate, parenteral gold,

rticosteroids, auranofin and IL-1 receptor antagonist,decreasing radiological progression in RA.[4]

vertheless, a variety of problems exist with theseugs. For example, the use of methotrexate andunomide is impeded by their long-term side-effects

d toxicity,[5] while cytokines antagonists, despite

bstantial efficacy and clinical improvement, entail highst and incur hypersensitivity to medications andections.[6] Consequently, there is dramatically

owing interest in herbal medicines among personsth RA and in the RA research community.[7] In fact,rbal medicine is being widely used virtually arounde world for treatment of rheumatic and arthritic

diseases.[7,8,9,10,11] Thus, herbal medicines constitupotentially important avenue leading to ntherapeutic agents for RA that may not only prestructural damage of arthritic joints caused by tissuebone breakdown, but also be safe, relatinexpensive, highly tolerated, and convenient for mpatients. Aegle marmelos (AM) a highly repayurvedic medicinal tree commonly known as baeltree is found all over India . The tree is endowed various medicinal properties. Several studiesdifferent parts of AM showed the plant poantidiarrhoel [12], antidiabetic [13], anticancer [14], protective [15], antifungal [16], antimicrobial

antimicrofilarial [18], and anti-inflammatory, anti-pyand analgesic activities [19]. AM has been usenervous disorder and as tonic for brain [20

Phytochemical analysis of AM leaves have showcontain several bioactive compounds including esseoil (e.g marmenol, β- caryophyllene, α- humultriterpenoids (e.g. lupeol, β & α- sitostrelo), flavo(e.g rutin), alkaloids (rutacin, aegeline, aegelicoumarins (e.g- marmesinin, umbeliferone), condetannins, anthocyanins and flavoinds glycosides [19, 22

MATERIAL AND METHODS

Plant Material

The disease free fresh plant material (Leaves) collected in the month of September 2009 surrounding area of Wadhwan, Gujarat authenticated at Botany Department of GuUniversity. After authentication, fresh leaves collected in bulk from the tree, shade dried, pulveand passed through sieve no.40 to obtain copowder.Preparation of the Extract The powdered leaves (400 gm.) were subjectecontinuous hot extraction with methanol in Soextractor for 48 hrs, followed by concentrating ex

under vacuum. The extracts were stored in airbottle until use.Animals The study was carried out with adult female Wistarweighing 180–250 g. Animals were acclimatized toexperimental conditions in cages and kept ustandard environmental conditions (22 ± 3◦C; 12/





ht/dark cycle). Rats were allowed to feed and waterlibitum.

duction of CIA and MAM treatment

thritis was induced in female Wistar rats using theethod described previously.[25] Collagen was dissolvedernight at 4°C in 0.1M Acetic acid to preparencentration 2mg/ml. This solution was added dropse to an equal volume of chilled incomplete Freund’sjuvant (IFA). On day first, animals (five groups, eachntaining six animals) receive total 0.5 ml collagen in5 ml, equally divided in 5 sites. All injections areradermal, one at the base of each appendages ande in the nape of neck. Seven days post-immunization,e animals receive identical booster injections. Controlmals receive only the incomplete Freund’s adjuvant

uted with 0.1 M acetic acid. In the therapeuticatment protocol for the established CIA, treatment

th MAM, Dexamethazone, and vehicle were initiated

the day after the onset of arthritis (day 21) andntinued once daily until day 45 of the experiment.ts were treated orally with different dose of MAM00, 400, 600 mg/kg of body weight), Dexamethasonemg/kg) and vehicle until day 45 of experiment.aluation of the development of arthritis ts were inspected daily for the onset of arthritisaracterized by edema and/or erythema in the paws.e incidence and severity of arthritis were evaluatedng a system of arthritic scoring, and measurement of hind paw volumes every 2 or 3 days beginning on they when arthritic signs were first visible. Animals wereserved for presence or absence of nodules in differentgans like ear, fore paw, hind paw, nose and tail.imal were score 0 for absence and 1 for presence of dules. 5 was the potential maximum of combinedhritic score per animal. Hind paw volume was

easured using plethysmometer. Paw volumes of bothnd limbs were recorded from 21st day to 45th day atur day interval

using mercury column

ethysmometer. [26]

eumatoid factore latex turbidimetry method was used in the presentdy using RF turbilatex kit of SPINREACT Company.ibration was carried out for linear range up to 100

/ml. The reading of RF factor of all the groupstained was compared with the control animals and

s expressed as IU/ml RF.[27]

Radiography

Female wistar rats were sacrificed on 45th

dacollagen administration and legs were removedplaced on formalin containing plastic bag. This pbag was kept at a distance of 90 cm from the Xsource was and Radiographic analysis of arthritictreated animal hind paw were performed by

machine with a 300-mA exposition for 0.01 sinvestigator blinded for the treatment regperformed radiograph score. The following radiogcriteria were considered: These scores (destroyeintact joint) were used as a quantal test for necrosis. Radiographs were carefully examined usstereo microscope and abnormalities were gradefollows:(i) Periosteaic reaction, 0 - 3 (None, Slight, ModeMarked);(ii) Erosions, 0 - 3 (None, Few, Many Small, Many La

(iii) Joint space narrowing, 0 - 3 (None, MinModerate, Marked);(iv) Joint space destruction, 0 - 3 (None, MinExtensive, Ankylosis).Bone destruction was scored on the patella as desc

previously.[26]

Histological processing and assessment of art

damage

Rats were killed by ether anesthesia. Knee joints removed and fixed for 4 days in 4% formaldehyde. A

decalcification in 5 % formic acid, the specimens processed for paraffin embedding tissue sections (7thick) and were stained with haematoxylin and eossafranin. An experienced pathologist, unaware odifferent drug treatments scored the conditiotibiotarsal joints. Histopathological changes were scusing the following parameters. Infiltration of cellsscored on a scale from 0 to 3, depending on the amof inflammatory cells in the synovial tisInflammatory cells in the joint cavity were graded

scale from 0 to 3 and expressed as exudatcharacteristic parameter in arthritis is the progreloss of articular cartilage. This destruction separately graded on a scale from 0 to 3, ranging the appearance of dead chondrocytes (empty lacuto complete loss of the articular cartilage. Bone erowas scored on a scale ranging from 0 to 3, ranging no abnormalities to complete loss of cortical





becular bone of the femoral head. Cartilage and bonestruction by pannus formation was scored rangingm 0, no change; 1, mild change (pannus invasion

thin cartilage); 2, moderate change (pannus invasiono cartilage/subchondral bone); 3, severe change

annus invasion into the subchondral bone); andscularity (0, almost no blood vessels; 1, a few bloodssels; 2, some blood vessels; 3, many blood vessels).stopathological changes in the knee joints wereored in the femur region on 5 semiserial sections of e joint, spaced 70 μm apart. Scoring was performed

decoded slides by two observers, as described

rlier.[28-31]

SULTS lowing the primary and booster injections of CII/IFA,s developed arthritis from day 21st onwards, andatment with MAM, Dexamethazone(1 mg/kg), and

hicle were initiated on day 21st after the primary

munization and continued until day 45th of theperiment. As shown in Fig. 1, even after the onset of hritis, MAM at high doses (200, 400 and 600 mg/kg)

d markedly reduce hind paw volume of the arthritics in a dose-dependent manner as compared to thehicle-treated arthritic rats.

thritic index and rheumatoid factor were significantlycreased in treatment with MAM (200 mg/kg, 400g/kg and 600mg/kg) and dexamethasone (1 mg/kg)

ated animal as compare to disease control treatment.ne destruction, which is a common feature of hritis, was examined by radiological analysis. Collagenministered rats had developed definite joint spacerrowing of the intertarsal joints, diffuse soft tissueelling that included the digits, diffusemineralization of bone, marked periosteal thickening,d cystic enlargement of bone and extensive erosionsoduced narrowing or pseudo widening of all jointaces. In contrast, in rats treated with MAM attenuatenormalities consisted of asymmetric soft tissueelling and small erosions, periosteal thickening, andnimal joint space narrowing, predominantly localizedthe proximal areas of the paws.shown in Fig 5 a [NC]: Histology of synovial joint of

rmal control rat with intact morphology of synoviumd synovial lining Fig 5 b [DC]: CA induced diseasentrol rat showed plenty of lymphocytic infiltration

[↓]in synovial lining with severe inflammation marked angiogenesis [↕] studied with proliferatiosynovial cells [↓↓]Fig 5 c [DEXA]: Dexamethasonmg/kg] treated rats showed significant protection mild lymphocytic infiltration [↓] with no evidencthickening of synovial lining and angiogenesis FigMAM200: MAM 200 treated rats showed mangiogenesis [↕], lymphocytic infiltration [↓] synovial lining thickening[↓↓]. Fig 5 e MAMMAM400 treated rats showed milder angiogenesissynovial lining thickening [↓↓] with no evidenclymphocytic infiltration. Fig 5 f MAM600: MAMtreated rats showed milder lymphocytic infiltrationand synovial-lining thickening [↓↓] with no evidenangiogenesis.DISCUSSION RA is a complicated refractory autoimmune discharacterized by a number of the inflammatory

destructive events such as joint pain and swesynovial hyperplasia, pannus formation, cartilagebone erosions, joint malformation.[32] Although vatherapeutic approaches, such as cytokine-, recepsignal-transduction- or cell-type directed intervenhave been done, the inflammatory and destruprocesses of RA are impeded partly, but rarely blofully, which reflects both the complexity and multipof the pathogenesis. These findings indicate treatment targeting individual molecules mightsuffice to stop the ongoing events, while combintherapy, which interferes with multiple targets, migmore effective for the treatment of RA. [33] Inregard, herbal medicines, comprising multiple acomponents with broad ranging pharmacoloactivities, represent an ancient model of combintherapy that could serve us well today.Evaluation of the inflammatory stratus in RA is refleby inflammation in the hind paw. Progression of disin MAM treated group shows reduction in edemdose dependent manner as compare to tissues co

animals. Symmetric involvement of small hand j(especially proximal interphalangeal metacarpophalangeal), foot j(metatarsophalangeal), wrists, elbows, and ankltypical, but initial manifestations may occur in any jInflammation and / or nodules are observed on nose, and tail, fore paws and hind paws. Arthritic i





the average of the score given to severity of theions in these places. This gives full picture of theease. [34] MAM treated animal showed significantser arthritic index as compared with disease controlmals.

ominent immunological abnormalities that may beportant in pathogenesis of RA include immunemplexes are found in joint fluid cells and in vasculitis.sma cells produce antibodies e.g., rheumatoid factor

F) that contribute to these complexes. Serumeumatoid factor (RF) is the immunological expression

an individual's immune system reaction to theesence of an immunoglobulin molecule that iscognized as "non-self." This response to the "non-self"munoglobulin results in the presence of immunemplexes. These, in turn, bind complement and mayentually lead to synovium, cartilage, and bonestruction. Higher the levels of serum rheumatoid

tor, higher are the development of inflammation.[35]

rum rheumatoid factor (RF) measures the amount of tibody IgM titer present in the serum.[36] MAMated animal showed significantly lesser serum RFen compared to disease control animals.ne destruction, which is a common feature of hritis, was examined by radiological analysis. CAated rats had developed definite joint spacerrowing of the intertarsal joints, diffuse soft tissueelling that included the digits, diffusemineralization of bone, marked periosteal thickening,d cystic enlargement of bone and extensive erosionsoduced narrowing or pseudowidening of all jointaces. Despite a similar clinical course of arthritis,ease control rats suffered from more pronouncedne destruction than MAM treated group.is characterized by synovial tissue leukocyte ingress

d angiogenesis. [37] The disease is thought to occur asimmunological response to as yet unidentified

tigen. Even in early RA, some of the earliesttological observations are blood vessels. [38] A

ononuclear infiltrate characterizes the synovial tissueong with a luxuriant vasculature. Angiogenesis isegral to formation of the inflammatory pannus andthout angiogenesis, leukocyte ingress could not occur.anges in the density of blood vessels in the synoviumd alterations in endothelial proliferative responses inhave been shown in a range of studies. The number

of synovial blood vessels has been found to corrwith hyperplasia of synovial cells, infiltrationmononuclear cells, and indices of joint tenderneHistopathology study of synovial joint showed treatment with Aegle marmelos Group decrevascularity, lymphocytic infiltration with less rheuminflammation and angiogenesis, with no thickeninsynovial membrane and absence of lymphoid follAs compared to disease control and orally treanimals.Our data suggested that Aegle marmelos posssignificant antiarthritic activity. The possible modanti- arthritic activity of Methanolic extract of Amarmelos appears to be, Possessing anti–inflammaactivity showed in arthritic parameters like Paw edArthritic index, Rheumatoid factor, improving erosion.Acknowledgements

The authors are thankful to the Director, Principamanagement of C U Shah College of PharmacyResearch, Wadhwan for providing necessary faciliticarry out this work. Our Acknowledgement to Dr.Solanki for their technical assistance in the collection and Identification.

References:

1. Haqqi TM, David CS. T-cell receptor V beta grepertoire in mice: Possible role in resistancesusceptibility to type II collagen-induced arthJ. Autoimmun. 1990, 3, 113–121.

2. Myers LK, Rosloniec EF, Cremer MA, KangCollagen induced arthritis, an animal modautoimmunity. Life Sci. 1997, 61, 1861–1878

3. Smolen JS, Steiner G. Therapeutic strategierheumatoid arthritis. Nature Reviews. Discovery 2003, 2, 473–488.

4. Jones G, Halbert J, Crotty M, Shanahan Batterham M, Ahern M. The effect of treat

on radiological progression in rheumarthritis: a systematic review of randomplacebo-controlled trials. Rheumatology 242, 6–13.

5. Kremer JM, Methotrexate and leflunombiochemical basis for combination





therapy in the treatment of rheumatoid arthritis.Seminars in Arthritis and Rheumatism 1999, 29,14–26.

6. Feldmann M, Maini RN. Anti-TNF alpha therapyof rheumatoid arthritis: what have we learned?Annual Review of Immunology 2001, 19, 163–196.

7. Rao JK, Mihaliak K, Kroenke K, Bradley J, TierneyWM, Weinberger M, Use of complementarytherapies for arthritis among patients of rheumatologists. Annals of Intern Medicine1999, 131, 409–416.

8. Shin SS, Jin M, Jung HJ, Kim B, Jeon H, Choi JJ,Kim JM, etal. Suppressive effects of PG201, anethanol extract from herbs, on collagen-inducedarthritis in mice. Rheumatology 2003, 42, 665–672.

9. Soeken KL, Miller SA, Ernst E. Herbal medicines

for the treatment of rheumatoid arthritis: asystematic review. Rheumatology 2003, 42, 652–659.

10. Chang SH, Sung HC, Choi Y, Ko SY, Lee BE, BaekDH, etal. Suppressive effect of AIF, a waterextract from three herbs, on collagen-inducedarthritis in mice. InternationalImmunopharmacology 2005, 5, 1365–1372.

11. Park KC, Park EJ, Kim ER, Kim Y, Chung SH, ChoBW, etal. Therapeutic effects of PG201, anethanol extract from herbs, through cartilageprotection on collagenase-induced arthritis inrabbits. Biochemical and Biophysical ResearchCommunications 2005, 331, 1469–1477.

12. Shobha FG, Thomas M. Study of antidiarrhoealactivity of four medicinal plants in castor-oiinduced diarrhea. J. Ethnopharmacol 2001, 76,73-76.

13. Kamalakkannan N. Prince PS. Hypoglycaemiceffect of water extracts of Aegle marmelos fruitsin streptozotocin diabetic rats. J.Ethnopharmacol

2003, 87, 207-210.14. Lotufu LV, Khan MT, Ather A, et al. Studies of the

anticancer potential of plants used inBangladeshi folk medicines. J. Ethnopharmacol2005, 99, 21-23.

15. jagetia GC, Venkatesh P, Balinga MS. Evaluationof radio protective effect of bael leaf (Aegle

marmelos) extract in mice. Int J Radiat Biol 280, 231-290.

16. Rana BK, Jain AK. Evaluation of anti fuactivity of essential oil isolated from leavethe A.marmelos. J. Ethnopharmacol 1997, 5737.

17. Mazmudar S, Bhattacharya A, MajmudarPattnaik P, Tiwari M, Chaudhary S. Anti bactevolution of Aegle marmelos (Correa) Linn. extract. Phytother Res 2006, 20, 82-84.

18. Sahare KN, Anandhraman V, Meshram VG, Antimicrofilarial activity of methanol extravitex negudndo and Aegle marmelos and phytochemical analysis. Indian J Exp. Biol 13, 245-249.

19. Veerappan A, Shigeru M, Rengnathan D. Stuon the anti inflammatory, antipyretic analgesic properties of the leaves of A

marmelos Corr. J. Ethnopharmacol 2005159-163.

20. Raj KPS, Patel MR, Some medicinal planCamby and its immediate vicinity and theirin Indian Indigenous system of medicine InDrugs 1978, 15, 145-152.

21. Maheshwari JK, Singh JP. Plants used inethno-medicine by the Koles of Allahabad diUttar Pradesh. Bull Med Ethnobot Res 15,105-121.

22. Garg SN, Siddiqui MS, Agarwal SK.P- Meth

3β, 5β diol, a new constituent of Amarmelos. Indian J Chem 1980, 19, 162.

23. Chakravorty RN, Dasgupta B. γ-Sitosterol the leaves of Aegle marmelos Correa. J InChem Soc 1958, 35, 194-196.

24. Ali MS, Pervez M. Marmenol: ageranylozycoumarin from the leaves of Amarmelos Nat Prod Res 2004, 14, 141-146.

25. Wang C, Dai Y, Yang J, Chou G, Wang C, WaTreatment with total alkaloids from R

linderae reduces inflammation and destruction in type II collagen-induced modrheumatoid arthritis. J Ethnopharmacol 2111,322-8.

26. Pearson CM, Wood FD. Studies on polyartand other lesions induced in rats by injectiomycobacterium adjuvant. I. General clinic





pathological characteristics and some modifyingfactors. Arth rheum. 1959, 2, 440-459.

27. Van de Berg WB, Joosten LAB, Helsen MMA, vande Loo FAJ. Amelioration of established murinecollagen-induced arthritis with anti-IL-1treatment. Clin Exp Immunol. 1994, 95, 237–243.

28. Joosten LAB, Helsen MMA, Van de Loo FAJ, vanden Berg WB. Anticytokine treatment of established collagen type II arthritis in DBA/1mice: a comparative study using anti-TNF alpha,anti-IL-1 alpha, beta and IL-1Ra. Arthritis Rheum.1996, 39, 797–809.

29. Joosten LAB, Lubberts E, Helsen MMA, van denBerg WB. Dual role of IL-12 in early and latestages of murine collagen type II arthritis. JImmunol. 1997, 159, 4094–4102.

30. Taniguchi K, Kohsaka H, Inoue N, Terada Y, Ito H,Hirokawa K, Miyasaka N: Induction of the

p16INK4a senescence gene as a new therapeuticstrategy for the treatment of rheumatoidarthritis.Nat Med. 1999, 5, 760-767.

31. Robert H, Shmerling, et al. The Americn Journalof Medicine. 1991, 91, 528-534.

32. Weyand CM. New insights into the pathogenesisof rheumatoid arthritis. Rheumatology 2000, 39(1), 3–8.

33. Smolen JS, Steiner G. Therapeutic strategies forrheumatoid arthritis.Nature Reviews. Drug Discovery 2, 2003, 473–488.

34. Colpert KM. Evidence that adjuvant arthritis inthe rat is associated with chronic pain: Pain.1987, 28, 201-222

35. Koopman W, et al. Rheumatoid factor andhuman disease. Clin Immunol News.1990,10,137-141.

36. Szekanecz Z, Szegedi G, Koch A. Angiogenesis inrheumatoid arthritis: pathogenic and clinicalsignificance. J Invest Med. 1998, 46, 27-41.

37. Walsh D. Angiogenesis and arthritis.Rheumatology. 1999, 38, 103-112.

38. Rooney M, Condell D, Quinlan W, Daly L, WhelanA, Feighery C, Bresnihan B. Analysis of thehistologic variation of synovitis in rheumatoidarthritis. Arthritis Rheum. 1988, 31,956-963.

39. Simon G. Alterations in joint space (arthritisassociated bone change, in: Principles of Boray Diagnosis, 2nd ed., Butlerworth & Co. Great Britain, 1965, 157- 163.

Fig. 1: Effect of Methanolic extract of Aegle marm

on paw edema in collagen induced arthritis in rat.

are presented as Mean ± SEM (n=6), * P < 0.05, w

compared with Disease control. (One Way ANOVA)

Fig. 2: A & B Effect of Methanolic extract of A

marmelos on arthritic index and rheumatoid facto

collagen induced arthritis in rat. Data are presente

Mean ± SEM (n=6), @ P < 0.0001, when comparednormal control, # P < 0.001, when compared with di

control. (One Way ANOVA)





g. 3: Effect of Methanolic extract of Aegle marmelos

radiographic score in collagen induced arthritis in rat.

ta are presented as Mean ± SEM (n=6), @ P < 0.001,

P < 0.05 when compared with disease control, (Oneay ANOVA)

Fig. 4: Effect of Methanolic extract of Aegle marm

on Radiographs of tibiotarsal joints

Fig. 5: Describe histopathology of joints indtreatment with methanolic extract of Aegle marm

prevent bone erosion.

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Aegle Marmelos Suppresses Inflammation and Cartilage

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