FOSTERED ANTIARTHRITIC UPSHOT OF MORINGA OLEIFERA LAM. STEM BARK EXTRACT IN DIVERSELY INDUCED ARTHRITIS IN WISTAR RATS WITH PLAUSIBLE MECHANISM

FOSTERED ANTIARTHRITIC UPSHOT OF MORINGA OLEIFERA LAM. STEM BARK EXTRACT IN DIVERSELY INDUCED ARTHRITIS IN WISTAR RATS WITH PLAUSIBLE MECHANISM

Vikas Kumar*¹, Amita Verma ¹, Danish Ahmed ¹, Nikhil Kumar Sachan ², Firoz Anwar ³ and Mohd. Mujeeb*⁴

Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom Institute of Agriculture, Technology & Sciences ¹, Allahabad, Uttar Pradesh, India – 211007.

University Institute of Pharmacy, Chhatrapati Shahu Ji Maharaj University ², Kanpur- 208 024, Uttar Pradesh, India

Siddhartha Institute of Pharmacy ³, Dehradun-248 001, Uttarakhand, India

Department of Phytochemisty & Pharmacognosy, Faculty of Pharmacy, Jamia Hamdard ⁴, New Delhi- 110 062, India

ABSTRACT: The present research exertion was undertaken to evaluate the antiarthritic effect of methanolic extract of Moringa oleifera Lam stem bark. The extract was subjected to preliminary phytochemical investigation and antiarthritic activity was evaluated with turpentine oil, formaldehyde and CFA induced arthritis. Other parameter like body weight and hematological estimation were carried out.The result indicated that the methanolic extract of Moringa oleifera has excellent antiarthritic activity against turpentine oil, formaldehyde and CFA induced arthritis. The all groups of animals showed increase in the body weight except arthritis control and hematological perturbations indued by CFA were maintained. The complete result indicated that Moringa oleifera methanolic extract possesses a potent protective effect against turpentine oil, formaldehyde and CFA induced arthritis. The consequences of the present investigation proved well thatMoringa oleifera methanolic extract is effective in the treatment of rheumatoid arthritis and that it support the common belief prevailing in traditional medicine world wide.

Moringa oleifera, CFA induced arthritis, arthritic index

INTRODUCTION:Rheumatoid arthritis (RA), one of the commonest autoimmune diseases, is a chronic, progressive, systemic inflammatory disorder affecting the synovial joints and typically producing symmetrical arthritis that leads to joint damage, which has accountability for the deformity and disability.

The consequences, morbidity and mortality have a potential socioeconomic impact¹.It is the most common cause of physical disability in developed countries, and the prevalence ranges between 0.3% and 1.50% with a female to male ratio of 3:1. The initiating factors for the inflammation, local tissue destruction and systemic responses seen in RA are unknown, and although a variety of infectious agents have been implicated, the causal agent of this disease has not been identified and therefore it had not been possible to treat in a rational manner ². Currently not even a single therapeutic agent, or combination of agents available for preventing disease progression or reversing joint destruction.

Moringa oleifera Lam. (Drumstick tree) a plant in a family of Moringaceae, is widely cultivated in India, used as food and active ingredient of the food preparation, medication and oil manufacturing ³. Moringa oleifera is mostly used in the preparation of sambhar and curry in India. Different parts of the plant used in traditional medicine system for the treatment of various diseases. It believed to be miracle herb, because it can be used as food as well as medicine for numerous ailments. The stem bark of M. oleifera used in a number of ailments, including asthma, gout, lumbago, enlarged spleen or liver, internal deep seated inflammation and calculous affections, antiulcer, diuretic, anti-inflammatory wound healing etc. ^4-6.

Moreover, it has been used to inhibit arthritic conditions too. Nowadays, numerous health products of M. oleifera is available in the market and claimed for the effect on arthritic condition is mentioned earlier, no scientific evidence of antiarthritic activity of M. oleifera documented till now.

Therefore, the investigation was designed to evaluate the antiarthritic effect of stem bark from Moringa oleifera on turpentine oil, formaldehyde and CFA induced arthritis in rats.

MATERIAL & METHODS:

Plant: The stem bark of Moringa oleifera Lam were collected from Herbal Garden, Department of Pharmaceutical Sciences, Sam Higginbottom Institute of Agriculture & Technology Sciences, Allahabad, India and authenticated by Dr. Imran Kajmi (Pharmacognosist) and a specimen voucher ( SIP/HD/054/13) of the plant sample respectively have been deposited in the herbarium of Sidharatha Institute of Pharmacy, Dehradun, Uttrakhand, India.

Chemicals: CFA (Sigma Aldrich, USA), Turpentine oil, formaldehyde (Merck Lab, Mumbai), Aspirin and diethyl ether (Merck Lab, Mumbai) were used for study. Other chemicals and reagents used for the study were of analytical grade.

Preparation of extraction: The dried leaf powder of Moringa oleifera (1 kg) was exhaustively extracted using methanol in Soxhlet apparatus for 5 days. The extracts concentrated under reduced pressure and low temperature to yield 17.5 % methanolic extract of Moringa oleifera stem bark. A suspension of extracts in distilled water, prepared using 0.2% sodium carboxymethyl cellulose, was used for experimental studies.

Preliminary phytochemical investigation: The extract subjected to preliminary phytochemical investigation employing standard procedures and tests to reveal the presence of phytoconstituents such as glycosides, saponins, tannins, fats and oils, steroids, triterpenoids, alkaloids, proteins and carbohydrates, etc. ^7-8.

Animals and experimental design: Swiss albino rats (Wistar strain, 150–200g) were used for the study. The animals were acclimatized in polyethylene plastic cages at 254 ± 2 ◦C with free access to standard pellet diet and water ad libitum. The experimental protocol was approved by the Institutional Animal Ethical Committee constituted as per the rules of the Committee for the Purpose of Control and Supervision of Experiments on Animals, India (CPCSEA). All the studies were conducted in accordance with the Animal Ethical Committee of the Institute and approved by the Sidharatha Institute of Pharmacy (1435/PO/a/ 11/CPCSEA).

Acute toxicity studies: Acute toxicity of Moringa oleifera was determined by OECD-425 guidelines. Swiss albino wistar rats were divided into different groups and administered with graded doses of Moringa oleifera and observed continuously for 6 hours detecting any change in behavior, locomotion, convulsion and motility. One group of animal treated with vehicle, served as control group ⁹.

Acute Model for Anti-arthritic activity:

Turpentine oil-induced joint edema in rats: Waster albino rats were fasted 24 h before experimentation with free excess of water. Animals were divided into five groups (n=6). Group I served as normal control and received vehicle only, group II-IV received different doses (125, 250, 500 mg/kg, p.o) of methanolic extracts of Moringa oleifera, respectively, and group V received a standard drug aspirin (100 mg/kg).

Acute inflammation in joint produced by injecting 0.02 ml of turpentine oil into the synovial cavity of the left knee joint, after 30 min of drug administration diameter of the joint was monitored at hourly interval for 6 h using micrometer screw gauge¹⁰. The percentage inhibition of left paw edema was calculated by following formula

Where VC= Paw edema of control group, VT= paw edema of the test group.

Formaldehyde-induced arthritis in rats: Formaldehyde used to induce arthritis using reported method with minor modification ¹¹. All wistar rats were divided into five groups, Group I served as normal control and received vehicle only, group II-IV received different doses (125, 250, 500 mg/kg, p.o) of methanolic extracts of Moringa oleifera respectively,  and group V received a standard drug aspirin (100 mg/kg p.o.). On day1, 30 min after the drug administration chronic non-immunological arthritis was induced by sub plantar injection of 0.1 ml of 2% formaldehyde solution and repeated on day 3. Arthritis was assessed by measuring the mean increase in paw diameter over a period of 10 days using a micrometer screw gauge ¹⁰.

The percentage inhibition of left paw edema calculated by following formula

Where VC= Paw edema of control group, VT= paw edema of the test group.

Chronic Model for Anti-arthritic activity

CFA-induced arthritis in rats: Experimental immunological arthritis was induced in rats with some modification in the previously documented method¹². 30 Wistar rats divided into the five groups (n=6). Group I served as normal control and administerd with vehicle only, group II-IV received different doses (125, 250, 500 mg/kg, p.o) of methanolic extracts of Moringa oleifera respectively, and group V received a standard drug aspirin (100 mg/kg p.o).

The left paw of each rat was injected subcutaneously with 0.01 ml of Complete Fruend Adjuvent (CFA - 0.1ml of 0.5% w/v suspension of heat killed Mycobacterium tuberculosis cells in liquid paraffin) except normal control group of rats. The edema of the left and right hind paw observed at 5, 7, 10, 13, 15, 18, 21 post injection of CFA using micrometer screw gauge ¹⁰. The percentage inhibition of left paw edema was calculated by following formula

Where VC= Paw edema of control group, VT= paw edema of the test group. The changes in body weight were recorded on regular interval. On the 21^th day, blood was withdrawn through retro-orbital vein puncture of all groups by anesthetizing the animals with diethyl ether and the heamatological parameters such as hemoglobin content, total WBC (white blood cells), ESR (erythrocyte sedimentation rate) and RBC (red blood cells) were evaluated.

Arthritis assessment in CFA rats: Determination of clinical symptoms in CFA induced arthritis was evaluated by a visual scoring system on scale 0-4, where 0: no change, 1: swelling and erythema of the limb, 2: mild swelling and erthyma of the limb, 3: gross swelling and erthema of the limb, 4: gross deformity and inability of the limb. A score of the 4 limb was counted and score more than 1 exhibit the arthritis whereas a maximum score of the arthritis is 16. The frequency and day of onset of arthritis also recorded ¹³.

Statistical analysis: The results are expressed as the Mean ± SEM. The significance of the difference was evaluated by one-way ANOVA. Data were considered statistically significant if P < 0.05.

RESULT:

Acute toxicity studies: Moringa oleifera, in acute toxicity studies did not produce any symptom of toxicity and was observed no lethality upto dose of 2000 mg/kg body weight in rats.

Hence, the extract was considered to be safe and non-toxic for further pharmacological screening.

In turpentine, formaldehyde and CFA induced arthritis model, rats developed a chronic swelling in multiple joints with the influence of inflammatory cells, erosion of joint cartilage, bone destruction and remodeling.

Preliminary phytochemical analysis: The methanolic extract of Moringa oleifera when tested chemically was found to have   presence of tannins, flavanoids, anthraquinones, and Saponins.

Effect on turpentine oil induced arthritis: Antiarthritic activity of Moringa oleifera (methanolic extract) was evaluated by the assessment made on the 6^thhr. The outcomes showed that treatment of different doses (125, 250, 500 mg/kg, p.o) of methanolic extract of Moringa oleifera inhibited swelling in the synovial cavity at dose dependent manner. After 6 h, percentage inhibition of paw edema in wistar rats at different doses of Moringa oleifera methanolic extract (125, 250, 500 mg/kg, p.o) were 70.25%, 90.46%, 97.33%, respectively; while Aspirin showed 95.55% of inhibition (Table 1).

Effect on formaldehyde induced arthritis: In formaldehyde induced arthritis model of wistar rats,  the assessment made on the 10^th day showed that, treatment with different doses of Moringa oleifera (125, 250, 500 mg/kg, p.o)methanolic extractsignificantly reduced (P<0.001) swelling in the injected (left) hind paw as compared to Aspirin treated group. On the 10th day the % inhibition of paw edema exhibited by different doses of Moringa oleifera were 62.88%, 66.87%, 90.91% respectively; while Aspirin treated animals showed maximum inhibition of paw edema 85.61% (Table 2).

Effect on CFA- induced arthritis: In Adjuvant induced animals, Different doses (125, 250, 500 mg/kg) of Moringa oleifera methanolic extract significantly (p < 0.001) inhibited arthritic swelling by 74.65% 79.26% and 90.90% as compared to the adjuvant control respectively, whereas the Aspirin treated group showed an inhibition of 94.89% (Table 3).

Effect on arthritis assessment: The occurrence of the arthritis recorded. On the day 5 injections of arthritis, the arthritis index of the different extract of Moringa oleifera and aspirin was recorded.

The Moringa oleifera stem bark extract and aspirin exhibit the lower arthritis score as compared to an arthritis model in Table 4.

Effect on body weight: The gain in body weight on day 21^st in each treatment group was observed in the rats under study (Table 5). The body weight of the disease control groups were significantly reduced as compared to the different doses (125, 250, 500 mg/kg) of Moringa oleifera methanolic extract and aspirin treated groups.

Effect on hematological parameters: The CFA-induced hematological perturbations, such as an increase in the ESR, WBC count and decrease in Hb, RBC count were also significantly (p < 0.001) altered at different doses (125, 250, 500 mg/kg p.o.) of Moringa oleifera methanolic extract and aspirin (100 mg/kg p.o.) (Table 6).

TABLE 1: EFFECT OF MORINGA OLEIFERA LEAVES EXTRACTS ON TURPENTINE OIL INDUCED RAT PAW EDEMA

The data are expressed in mean ± SEM) (n = number of animals in each group = 6). The comparisons were made by ANOVA followed by Dunnett’s test. .ns-non-significant; MO- Moringa oleifera. *P < 0.05 is considered as significant. **P < 0.01 is considered as very significant. ***P < 0.001 is considered as extremely significant.

TABLE 2: EFFECT OF MORINGA OLEIFERA LEAVES EXTRACTS ON FORMALDEHYDE INDUCED RAT PAW EDEMA

The data are expressed in mean ± SEM) (n = number of animals in each group = 6). The comparisons were made by ANOVA followed by Dunnett’s test. .ns-non-significant; MO- Moringa oleifera. *P < 0.05 is considered as significant. **P < 0.01 is considered as very significant. ***P < 0.001 is considered as extremely significant.

TABLE 3: EFFECT OF MORINGA OLEIFERA LEAVES EXTRACTS ON CFA INDUCED RAT PAW EDEMA

The data are expressed in mean ± SEM) (n = number of animals in each group = 6). The comparisons were made by ANOVA followed by Dunnett’s test. ns-non-significant; MO- Moringa oleifera, CFA- Complete Fruend’s Arthritic. *P < 0.05 is considered as significant. **P < 0.01 is considered as very significant.

***P < 0.001 is considered as extremely significant.

TABLE 4: EFFECT OF MORINGA OLEIFERA LEAVES EXTRACTS AND STANDARD DRUG ON THE DEVELOPMENT OF CFA ARTHRITIC INDEX

The data are expressed in mean ± SEM) (n = number of animals in each group = 6). The comparisons were made by ANOVA followed by Dunnett’s test. ns-non-significant; MO- Moringa oleifera, CFA- Complete Fruend’s Arthritic. *P < 0.05 is considered as significant. **P < 0.01 is considered as very significant. ***P < 0.001 is considered as extremely significant

   TABLE 5: EFFECT OF MORINGA OLEIFERA LEAVES EXTRACTON BODY WEIGHT OF CFA INDUCED RAT PAW EDEMA

The data are expressed in mean ± SEM) (n = number of animals in each group = 6). The comparisons were made by ANOVA followed by Dunnett’s test.ns-non-significant; MO- Moringa oleifera  CFA- Complete Fruend’s Arthritic. *P < 0.05 is considered as significant. **P < 0.01 is considered as very significant. ***P < 0.001 is considered as extremely significant.

TABLE 6: EFFECT ON HAEMATOLOGICAL PARAMETERS IN ADJUVANT-INDUCED ARTHRITIS IN RATS

The data are expressed in mean ± SEM) (n = number of animals in each group = 6). The comparisons were made by ANOVA followed by Dunnett’s test. ns-non-significant; MO- Moringa oleifera, WBC-White Blood Cell, RBC-Red Blood Cell, Hb-Hemoglobin, ESR-Erythrocytes Sedimentation Rates. *P < 0.05 is considered as significant. **P < 0.01 is considered as very significant. ***P < 0.001 is considered as extremely significant.

DISCUSSION: Alternative medicine for the treatment of various diseases is getting increasing popularity day by day. Because it shows fewer side effects as compared to other system of medicine, many medicinal plants have proven effects on arthritic symptoms as compared to that of conventional medicine agent ¹⁴. The anti-arthritic effect of methanolic extract of Moringa oleifera stem bark could be observed in acute (Turpentine oil and Formaldehyde induced arthritis) and chronic (Freund’s complete adjuvant induced polyarthritis in rat) model of inflammation.

Arthritis is a chronic inflammatory disease which affects several joints of the body like cartilage, synovium, tendon and muscle. Mostly researcher has claimed that inhibition of adjuvant – induced arthritis in rats, is the suitable test procedure to screen anti-arthritic activity. The rats develop chronic swelling in multiple joint with the influence of inflammatory cells, attrition of joint cartilage and bone damage. It closely resembles with human arthritis disease ⁹.

One of the reasons for wide utilization of the rat animal model method is due to the strong correlation between efficacy in the animal model and rheumatism condition in human.

Turpentine oil induced acute inflammation is due to release of mediator like histamine and serotonin in early phase; then kinin in intermediate phase and in a later phase releasing prostaglandin ¹⁵.

Different doses of Moringa oleifera significantly inhibit the turpentine oil induced joint edema, suggest that the possible mechanism of action inhibition the different phase of inflammation.

The Antiproliferative and antiarthritic activity was evaluated by using common method inhibition of formaldehyde induced edema. The injection of formaldehyde into animal paw produced localized inflammation (releasing of histamine, serotonin and kinin) and pain ¹⁶. Formaldehyde induced arthritis is biphasic in nature i.e. an untimely neurogenic element followed by a later tissue mediated response ¹⁷.

Three different doses of Moringa oleifera significantly inhibit the proliferative global oedematous response at dose dependent manner. The dose of the Moringa oleifera (500 mg/kg) is more effective than the standard aspirin.

In the Adjuvant induced arthritic method, it was observed that swelling and redness developed in rats after injecting the CFA over 24 hours. It seems that bacterial peptidoglycon and muramyl dipeptide are responsible for its induction ^18-19 and chronic inflammation reaction slowly developed next 8 – 10 days. Chronic inflammation occurs in multiple joints with the influence of inflammatory cells, erosion of joint cartilage and bone destruction. Cytokines, GM-CSF (Granulocyte-macrophage colony-stimulating factor), interferons like mediator are responsible for the chronic inflammation and pain, destruction of bone and cartilage ^20-21.

Another mechanism of chronic inflammation is leukocytes phagocytes forms a complex with the mediators (cytokines, GM-CSF, histamine, 5 hydroxytryptamine, bradykinin, various chemotactic factors, interferons and prostaglandin) and released the lysosomal enzymes, causing injury to cartilage and other tissue ^22-25. In the arthritis condition, arthritis changes the hematological parameters. Another condition of arthritis is a WBC increased in due to an lL-1B mediated rise in the respective colony stimulating factors. Moringa oleifera showed the effect in the arthritic rat at dose dependent manner.

The drug showing the effect on two ways – firstly it decreases the release of certain mediator like cytokines, histamine, 5-hydroxytryptamine, bradykinin, interference and prostaglandin. Secondly it may be stimulating the DTH response and increased phagocytic index and protection against chclophosphamide induced myelo-suppression by increasing total WBC count which are directly associated with the immunomodulatory activity.

As the level of WBC increases in arthritis rats, the migration of leukocytes to the inflamed area was significantly suppressed by different doses of Moringa oleifera stem bark (methanolic extract), which is associated with indicated that a significant decrease in the WBC count.

Another symptom of arthritic patient is common occurrence anemia ²⁶. In arthritic condition gastrointestinal blood loss occurred due to medication and in bone marrow changes in patients with inflammatory arthritis, which prevent the release of iron for incorporation into red blood cells ^27-28.

In the present investigation, arthritic control group rats showed reduction of RBC, Hb and increase the level of WBC and ESR (erythrocyte sedimentation rate). All of these symptoms indicated as anemia conditions. Our result suggests that different doses of Moringa oleifera showed significant recovery from the induced anemia with an increase in the level of RBC, Hb and decreases the level of WBC, ESR. During arthritis the body weight of the animals significantly decreases due to deficient absorption of nutrients through the internet and that treatment with the tested drug and standard drugs normalizes the process of absorption ²⁹.

The increase in the body weight in the Moringa oleifera and Aspirin treated groups may involve improvement of intestinal absorption of the nutrients and reduction in the distress caused by the severity of the arthritis.

CONCLUSION: In conclusion, Moringa oleifera, in a dose-dependent pattern, was effective in attenuating turpentine oil induced paw edema, formaldehyde-induced paw edema and CFA induced arthritis in rat models of acute and chronic inflammation, and therefore it could be investigated as a potential treatment for acute and chronic arthritis conditions in humans. The results obtained justify the use of the plant extract in traditional Indian medicine for the treatment of painful inflammatory and arthritic conditions.

Further work in our lab is in process to isolate, identify, characterize, and elucidate the structure of the phytoconstituents responsible for the observed pharmacological activities in this study. Explicate the exact mechanism of action of Moringa oleifera stem bark in curtailing the effect of arthritis.

Conflicts of interest: All authors have none to declare.

REFERENCE:

1. Bansod MS, Kagathara VG, Pujari R, patel VB, Ardeshna HH. Therapeutic effect of a poly­herbal preparation on adjuvant induced arthritis in wistar rats. International Journal of Pharmacy and Pharmaceutical Sciences 2011; 3(2): 186-192.
2. Rajendran R, krishnakumar E. Anti-Arthritic Activity of Premna serratifolia Linn. Wood against Adjuvant Induced Arthritis. Avicenna Journal of Medical Biotechnology. 2010; 2(2): 101-108.
3. Anwer F, Latif S, Ashraf M, Gilani AH. Moringa oleifera: a food plant with multiple medicinal uses. Phytother. Res. 2007; 21: 17–25.
4. Jaiswal D, Rai PK, Kumar A, Mehta S, Watal G.Effect of Moringa oleifera Lam. leaves aqueous extract therapy on hyperglycemic rats. Journal of Ethnopharmacology. 2009; 123: 392–396.
5. Mehta A, Agrawal B. Investigation into the mechanism of action of Moringa oleifera for its anti-asthmatic activity. Oriental Pharmacy and Experimental Medicine 2008; 8(1): 24-31.
6. Kumar V, Yadav PKS, Singh UP, Bhat HR, Zaman K. Pharmacognostical and phytochemical studies on the leaves of Paederia foetida Linn. International Journal of Pharm Tech Research 2009; 3: 918-920.
7. Kumar V, Yadav PKS, Singh UP, Bhat HR,  Rana A, Zaman K. Pharmacognostical evaluation of Cuscuta reflexa Roxb. Pharmcog J, 2011; 2(6): 74 – 82.
8. Fahad J, Vijayalakshmi, Kumar MCS, Kodancha GP, Adarsh B, Udupa AL, Rathnakar UP. Antiurolithiatic activity of aqueous extract of bark ofMoringa oleifera (lam.) in rats. Health. 2010, 2(4): 352-355.
9. Rajendran R, Krishnakumar E. Anti-Arthritic Activity of PremnaserratifoliaLinn., Wood against Adjuvant induced Arthritis. Avicenna J Med Biotech, 2010, 2(2): 101-106.
10. Kathwas G, Gautam R, Jachak SM, Saklani A. Antiarthritic effects of AjugabracteosaWall ex Benth. in acute and chronic models of arthritis in albino rats. Asian journal of Tropical Biomedicine 2012; 185 – 188.
11. Singh S, Nair V, Gupta YK. Antiarthritic activity of MajoonSuranjan (a polyherbal Unani formulation) in rat.Indian J Med Res 2011; 134: 384-388.
12. Mishra NK, Bstia S, Mishra G, Chowdary KA, Patra S. Anti-arthritic activity of Glycyrrhizaglabra, Boswellia serrata and their synergistic activity in combined formulation studied in freund’s adjuvant induced arthritic rats. Pharm Educ Res, 2011; 2(2): 92 – 98.
13. Kim KW, Shin YS, Kim KS, Chang YC, Park KK, Park JB, ChoeJY,Lee KG, Kang MS, Park YG, Kim CH. Suppressive effects of bee venom on the immune responses in collagen-induced arthritis in rats. Phytomedicine, 2008; 15: 1099-1107
14. Rogerio AP, Kanashiro A, Fontanari C, Da Silva EVD, Lucisano-Valim YM, Soates EG, Faccioli LH.  Anti-inflammatory activity of quercetin and isoquercitrin in experimental murine allergic asthma. Inflammation Research 2007; 56(10): 402-408.
15. Ilavarasan R, Mohideen S, Venkataraman S. Analgesic and anti-inflammatory properties of Thespesia populnea leaf extracts. Natural Product Research 2012; 26(17): 1616-1620.
16. Nair V, Singh S, Gupta YK. Evaluation of disease modifying activity of Colchicum luteum Baker in experimental arthritis. J Ethnopharmacol 2011; 133: 303-307.
17. Owoyele BV, Adenekan OT, Soladoye AO. Effects of honey on inflammation and nitric oxide production in Wistar rats. Jorunal of Chines Integrative medicine, 2011, 9(4): 447-452.
18. Xin HL, Zhai XF, Zheng X, Zhang L, Wang YL, Wang Z.Anti-Inflammatory and Analgesic Activity of Total Flavone of Cunninghamia lanceolata. Molecules 2012; 17(8): 8842-8850.
19. Amresh G, Singh PN, Rao ChV. Antinociceptive and antiarthritic activity of Cissampelos pareira roots. Journal of Ethnopharmacology, 2007; 111: 531–536
20. Simplice FH, Armand AB, Roger P, Emmanuel AA, Pierre K, Veronica N. Effects of Hibiscus asper leaves extracts on carrageenan induced oedema and complete Freund’s adjuvant-induced arthritis in rats. Journal of Cell and Animal Biology 2011; 5 (5):  69-75.
21. Rajendran R, Krishnakumar E. Anti-Arthritic Activity of Premna serratifolia Linn. Wood against Adjuvant Induced Arthritis. Avicenna J Med Biotech 2010; 2(2): 101-106
22. Foong CP, Hamid RA. Evaluation of anti-inflammatory activities of ethanolic extract of Annona muricata leaves. Brazilian Journal of Pharmacognosy 2012; 22(6): 1301-1307.
23. Mauriz JL, Collado PS, Veneroso C, Reiter RJ, Gallego JG. A review of the molecular aspects of melatonin’s anti-inflammatory actions: recent insights and new perspectives. Journal of Pineal Research 2013; 54(1): 1-14.
24. Tavares TG, Spindola H, Longato G, Pintado ME, Carvalho JE, Malcata FX. Antinociceptive and anti-inflammatory effects of novel dietary protein hydrolysate produced from whey by proteases of Cynara cardunculus. International Dairy Journal 2013; 32(2): 156-162.
25. Patil MVK, Kandhare AD, Bhise SD. Anti-arthritic and anti-inflammatory activity of Xanthium srtumarium L. ethanolic extract in Freund's complete adjuvant induced arthritis. Biomedicine & Aging Pathology 2012; 2(1): 6-15.
26. Renju GL, Kurup GM, Kumari CHS. Anti-inflammatory activity of lycopene isolated from Chlorella marina on Type II Collagen induced arthritis in Sprague Dawley rats. Immunopharmacology and Immunotoxicology 2013; 35(2): 282-291.
27.  Sindhu G, Ratheesh M, Shyni GL, Nambisan, Helen A. Anti-inflammatory and antioxidative effects of mucilage of Trigonella foenum graecum (Fenugreek) on adjuvant induced arthritic rats. International Immuno-pharmacology, 2012; 12(1): 205-211.
28. Patil KS, Suryavanshi J. Effect of Celastrus paniculatus Willd. seed on adjuvant induced arthritis in rats. Pharmacognosy Magazine 2007; 3: 177–181.
29. Anwar F, Latif S, Ashraf M, Gilani AH. Moringa oleifera: a food plant with multiple medicinal uses. Phytotherapy Research, 2007; 21(1): 17-25.
    

    ---

    How to cite this article:

    Kumar V,  Verma A, Ahmed D, Sachan NK, Anwar F and Mujeeb M: Fostered antiarthritic upshot of Moringa oleifera Lam. stem bark extract in diversely induced arthritis in Wistar rats with plausible mechanism. Int J Pharm Sci Res 2013; 4(10): 3894-01. doi: 10.13040/IJPSR. 0975-8232.4(10).3894-01

    ---

    All © 2013 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.

    ---