THE BENEFITS OF ACTIVE COMPOUNDS IN KALANCHOE PINNATA (LMK) PERS ETHYL ACETATE FRACTION ON LUPUS ARTHRITIS MICE


Niken Indriyanti, Joewono Soeroso, Junaidi Khotib

Abstract


Ethyl acetate fraction of Kalanchoe pinnata (Lmk) Pers leaves (EF-KP) is a potential material to be developed for lupus treatment. The aim of this research was to measure the effects of the EF-KP on lupus arthritis mice.  The research was performed by testing of CD123+IFN-α+ dendritic cells and CD68+IL-6+ macrophages as the main biomarkers by using flow cytometry methods, and then the outcomes were directly observed in the joint’s tissue structure. The results of the research were analyzed by using statistics. The EF-KP reduces the relative percentages of CD123+IFN-α+ dendritic cells significantly (p<0.05) with the percentage of 32.95±8.25% (negative control); 23.28±9.31%* (EF-KP); 22.98±10.39%* (positive control). It also reduces the relative percentages of CD68+IL-6+ macrophages but not significantly (p>0.05). Finally, the outcome to the grade of joint damage was scored by using Pritzker method. The treated groups have one grade lower, and the joint spaces were narrower than the untreated group. The results show the ability of the active compounds in EF-KP, which are comparable to 0.042 mg/Kg quercetin, to inhibit the progress of lupus arthritis pathogenesis in mice. It reveals the effectiveness of the EF-KP in human with lupus arthritis. However, the further clinical research is necessary.


Keywords


Kalanchoe pinnata (Lmk) Pers, Flavonoids, Lupus arthritis, CD123+ interferon-α dendritic cells, CD68+ interleukin 6 macrophages.

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References


Crow MK, Olferiev M, Kirou KA. Targeting of Type I interferon in systemic autoimmune diseases. Transl Res 2015;165(2):296-305.

Golding A, Rosen A, Petri M, Akhter E, Andrade F. Interferon-alpha regulates the dynamic balance between human activated regulatory and effector T cells: Implications for antiviral and autoimmune responses. Immunology 2010;131(1):107-7.

Jego G, Palucka AK, Blanck JP, Chalouni C, Pascual V, Banchereau J. Plasmacytoid dendritic cells induce plasma cell differentiation through Type I interferon and interleukin 6. Immunity 2003;19(2):225-34.

Rottman JB, Willis CR. Mouse models of systemic lupus erythematosus reveal a complex pathogenesis. Vet Pathol 2010;47(4):664-76.

Fonseca JE, Santos MJ, Canhão H, Choy E. Interleukin-6 as a key player in systemic inflammation and joint destruction. Autoimmun Rev 2009;8(7):538-42.

Ortiz MA, Diaz-Torné C, Hernández MV, Reina D, de la Fuente D, Castellví I, et al. IL-6 blockade reverses the abnormal STAT activation of peripheral blood leukocytes from rheumatoid arthritis patients. Clin Immunol 2015;158(2):174-82.

Venkatesha SH, Astry B, Nanjundaiah SM, Kim HR, Rajaiah R, Yang Y, et al. Control of autoimmune arthritis by herbal extracts and their bioactive components. Asian J Pharm Sci 2016;11:301-7.

Liu CY, Wu WH, Huang TP, Lee TY, Chang HH. A novel model for exploring the correlation between patterns and prescriptions in clinical practice of traditional Chinese medicine for systemic lupus erythematosus. Complement Ther Med 2014;22(3):481-8.

Borchers AT, Sakai S, Henderson GL, Harkey MR, Keen CL, Stern JS, et al. Shosaiko-to and other Kampo (Japanese herbal) medicines: A review of their immunomodulatory activities. J Ethnopharmacol 2000;73:1-13.

Lee J, Shin JS, Kim MR, Byun JH, Lee SY, Shin YS, et al. Liver enzyme abnormalities in taking traditional herbal medicine in Korea: A retrospective large sample cohort study of musculoskeletal disorder patients. J Ethnopharmacol 2015;169:407-12.

Cruz EA, Reuter S, Martin H, Dehzad N, Muzitano MF, Costa SS, et al. Kalanchoe pinnata inhibits mast cell activation and prevents allergic

airway disease. Phytomedicine 2012;19(2):115-21.

Cruz EA, Da-Silva SA, Muzitano MF, Silva PM, Costa SS, Rossi-Bergmann B. Immunomodulatory pretreatment with Kalanchoe pinnata extract and its quercitrin flavonoid effectively protects mice against fatal anaphylactic shock. Int Immunopharmacol 2008;8(12):1616-21.

Ferreira RT, Coutinho MA, Malvar Ddo C, Costa EA, Florentino IF, Costa SS, et al. Mechanisms underlying the antinociceptive, antiedematogenic, and anti-Inflammatory activity of the main flavonoid from Kalanchoe pinnata. Evid Based Complement Alternat Med 2014;2014:429256.

El Abdellaoui S, Destandau E, Toribio A, Elfakir C, Lafosse M, Renimel I, et al. Bioactive molecules in Kalanchoe pinnata leaves: Extraction, purification, and identification. Anal Bioanal Chem 2010;398(3):1329-8.

Darmawan A, Megawati M, Fajriah S. 3’, 4’-Dimethoxy quercetin, a flavonol compound isolated from Kalanchoe pinnata. J Appl Pharm Sci 2013;3(1):88-90.

Indriyanti N, Garmana AN. Ekstrak daun cocor bebek (Kalanchoe pinnata) untuk terapi preventif lupus pada mencit yang diinduksi dengan 2,6,10,14-tetramethylpentadecane. J Trop Pharm Chem 2011;1(3):224-9.

Ozolua RI, Idogun SE, Tamafel GE. Acute and sub-acute toxicological assessment of aqueous leaf extract of Bryophyllum Pinnatum (Lam.) in sprague-dawley rats. Am J Pharmacol Toxicol 2010;5(3):145-51.

Gwehenberger B, Rist L, Huch R, von Mandach U. Effect of Bryophyllum pinnatum versus fenoterol on uterine contractility. Eur J Obstet Gynecol Reprod Biol 2004;113(2):164-71.

Hahn BH, McMahon MA, Wilkinson A, Wallace WD, Daikh DI, Fitzgerald JD, et al. American college of rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res (Hoboken) 2012;64(6):797-808.

Kasjmir Y, Handono K, Wijaya LK, Hamijoyo L, Albar Z, Kalim H, et al. Rekomendasi Perhimpunan Reumatologi Indonesia Untuk Diagnosis Dan Pengelolaan Lupus Eritematosus Sistemik. Indonesia: Performance Review Institute; 2011.

Fiechtner JJ, Montroy T. Treatment of moderately to severely active systemic lupus erythematosus with adrenocorticotropic hormone: A single-site, open-label trial. Lupus 2014;23(9):905-12.

Velo-García A, Castro SG, Isenberg DA. The diagnosis and management of the haematologic manifestations of lupus. J Autoimmun 2016;74:139-60.

Aoki C, Hartati S, Santi MR, Firdaus RL, Hanafi M, Kardono L, et al. Isolation and identification of substances with anti-hepatitis C virus activities from Kalanchoe pinnata. Int J Pharm Pharm Sci 2014;6(2):211-5.

Asiedu-Gyekye IJ, Antwi DA, Awortwe C, N’guessan BB, Nyarko AK. Short-term administration of an aqueous extract of kalanchoe integra var. crenata (Andr.) Cuf leaves produces no major organ damage in Sprague-Dawley rats. J Ethnopharmacol 2014;151(2):891-6.

Pritzker KP, Gay S, Jimenez SA, Ostergaard K, Pelletier JP, Revell PA, et al. Osteoarthritis cartilage histopathology: Grading and staging. Osteoarthritis Cartilage 2006;14(1):13-29.

Leiss H, Niederreiter B, Bandur T, Schwarzecker B, Blüml S, Steiner G, et al. Pristane-induced lupus as a model of human lupus arthritis: Evolvement of autoantibodies, internal organ and joint inflammation. Lupus 2013;22(8):778-92.

Zhu W, Xu J, Jiang C, Wang B, Geng M, Wu X, et al. Pristane induces autophagy in macrophages, promoting a STAT1-IRF1-TLR3 pathway and arthritis. Clin Immunol 2017;175:56-68.

Nascimento LB, Leal-Costa MV, Menezes EA, Lopes VR, Muzitano MF, Costa SS, et al. Ultraviolet-B radiation effects on phenolic profile and flavonoid content of Kalanchoe pinnata. J Photochem Photobiol B 2015;148:73-81.

Asiedu-Gyekye IJ, Antwi DA, Bugyei KA, Awortwe C. Comparative study of two Kalanchoe species: Total flavonoid, phenolic contents and antioxidant properties. Afr J Pure Appl Chem 2012;6(5):65-73.

Jackson JK, Higo T, Hunter WL, Burt HM. The antioxidants curcumin and quercetin inhibit inflammatory processes associated with arthritis. Inflamm Res 2006;55(4):168-75.

Almatar M, Ekal H, Rahmat Z. A glance on medical applications of Orthosiphon stamineus and some of its oxidative compounds. Int J Pharm Sci Rev Res 2014;24(2):83-8.

Huang RY, Yu YL, Cheng WC, OuYang CN, Fu E, Chu CL. Immunosuppressive effect of quercetin on dendritic cell activation and function. J Immunol 2010;184(12):6815-21.

Banchereau J, Pascual V. Type I interferon in systemic lupus erythematosus and other autoimmune diseases. Immunity 2006;25(3):383-92.

Lu R, Munroe ME, Guthridge JM, Bean KM, Fife DA, et al. Dysregulation of innate and adaptive serum mediators precedes systemic lupus erythematosus classification and improves prognostic accuracy of autoantibodies. J Autoimmun 2016;74:182-93.

Pan Q, Gao C, Chen Y, Feng Y, Liu WJ, Liu HF. Update on the role of autophagy in systemic lupus erythematosus: A novel therapeutic target. Biomed Pharmacother 2015;71:190-3.

Mello BS, Monte AS, McIntyre RS, Soczynska JK, Custódio CS, Cordeiro RC, et al. Effects of doxycycline on depressive-like behavior in mice after lipopolysaccharide (LPS) administration. J Psychiatr Res 2013;47(10):1521-9.

Simões-Wüst AP, Hassani TA, Müller-Hübenthal B, Pittl S, Kuck A, Meden H, et al. Sleep quality improves during treatment with Bryophyllum pinnatum: An observational study on cancer patients. Integr Cancer Ther 2015;14(5):452-9.

Stone RC, Feng D, Deng J, Singh S, Yang L, Fitzgerald-Bocarsly P, et al. Interferon regulatory factor 5 activation in monocytes of systemic lupus erythematosus patients is triggered by circulating autoantigens independent of Type I interferons. Arthritis Rheum 2012;64(3):788-98.

Banchereau J, Pascual V, Palucka AK. Autoimmunity through cytokine-induced dendritic cell activation. Immunity 2004;20(5):539-50.

Urbonaviciute V, Starke C, Pirschel W, Pohle S, Frey S, Daniel C, et al. Toll-like receptor 2 is required for autoantibody production and development of renal disease in pristane-induced lupus. Arthritis Rheum 2013;65(6):1612-23.

Dzulkifli S, Kumolosasi E. Study on effectiveness and side effect of my cophenolate mofetil versus azathioprine in maintenance treatment of lupus nephritis. Int J Pharm Pharm Sci 2013;5(4):360-2.

Sharma A, Bhot M, Chandra N. In vitro antibacterial and antioxidant activity of Bryophyllum pinnatum (Lam.) Kurz. Int J Pharm Pharm Sci 2014;6(1):558-60.

Palanishwamy R, Padma PR. Comparison of three herbal plants for best free radical scavenging activity. Int J Curr Pharm Res 2017;9(3):62-4.

Rapeshkumar M, Kavitha K, Haldar PK. Role of herbal plants in the diabetes mellitus therapy: An overview. Int J Appl Pharm 2014;6(3):1-3.

Hsieh CC, Lin BF. Dietary factors regulate cytokines in murine models of systemic lupus erythematosus. Autoimmun Rev 2011;11(1):22-7.

Maurya H, Kumar T. A review on comprehensive overview in the management on nephritic disorders. J Crit Rev 2016;3(2):34-43.




About this article

Title

THE BENEFITS OF ACTIVE COMPOUNDS IN KALANCHOE PINNATA (LMK) PERS ETHYL ACETATE FRACTION ON LUPUS ARTHRITIS MICE

Topics

Pharmacy; Pharmacology

Keywords

Kalanchoe pinnata (Lmk) Pers, Flavonoids, Lupus arthritis, CD123+ interferon-α dendritic cells, CD68+ interleukin 6 macrophages.

DOI

10.22159/ajpcr.2017.v10i11.20766

Date

01-11-2017

Additional Links

Manuscript Submission

Journal

Asian Journal of Pharmaceutical and Clinical Research
Vol 10 Issue 11 November 2017 Page: 199-203

Print ISSN

0974-2441

Online ISSN

2455-3891

Statistics

24 Views | 62 Downloads

Authors & Affiliations

Niken Indriyanti
Department of Pharmacology, Faculty of Pharmacy, Mulawarman University, Samarinda, East Kalimantan, Indonesia.
Indonesia

Joewono Soeroso
Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Jl. Prof. Dr. Moestopo Surabaya, East Java, Indonesia.
Indonesia

Junaidi Khotib
Department of Clinical Pharmacy, Faculty of Pharmacy, Universitas Airlangga, Jl. Dharmawangsa Surabaya, East Java, Indonesia
Indonesia


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