Anti-inflammatory effects of rhein and crude extracts from Cassia alata L. in HaCaT cells

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Nushjira Pongnimitprasert
Kwanchanok Wadkhien
Chatchai Chinpaisal
Malai Satiraphan
Penpan Wetwitayaklung


Cassia alata L. is a medicinal plant and is in the Thai traditional household herbal drug list. Furthermore, C. alata leaves extract has been reported to have anti-inflammatory activities. The rhein, an active component, can inhibit inflammation via suppressing reactive oxygen species (ROS) production, leading to decreased cytokines (TNF-α, IL-8). However, the role of anti-inflammation on skin has been investigated only in a few research. The rhein in C. alata leaves extract was determined by HPLC. The anti-inflammatory effects of rhein and C. alata leaves extract on tert-butyl hydroperoxide-induced oxidative stress in HaCaT cells were evaluated. Anti-inflammatory activities of C. alata leaves extract were compared with rhein standard via inhibition of ROS generation and production of TNF-α and IL-8. The results showed that rhein content in C. alata leaves extract was 0.1225% w/w. Rhein (1-50 μM) significantly reduced ROS generation in a concentration-dependent manner, and paralleled the decrease in TNF-α and IL-8 production. C. alata leaves extract exhibited stronger anti-inflammatory effect than rhein at same concentration. These findings indicate that rhein and C. alata leaves extract may reduce inflammation by decreasing TNF-α and IL-8 as a result of ROS reduction. These results indicate that C. alata leaves may have the possibility of role as an anti-inflammatory agent. Therefore, further studies need to be performed.


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Bito, T., and Nishigori, C. (2012). Impact of reactive Oxygen species on keratinocyte signaling pathways. Journal of Dermatological Science, 68(1), 3-8.

Borderie, D., Hernvann, A., Lemarechal, H., Menkes, C. J., and Ekindjian, O. (2001). Inhibition of the nitrosothiol production of cultured osteoarthritic chondrocytes by rhein, cortisol and diclofenac. Osteoarthritis and Cartilage, 9(1), 1-6.

Cong, X. D., Ding, M. J., Dai, D. Z., Wu, Y., Zhang, Y., and Dai, Y. (2012). ER stress, p66shc, and p-Akt/Akt mediate adjuvant-induced inflammation, which is blunted by argirein, a supermolecule and rhein in rats. Inflammation, 35(3), 1031-1040.

Fernand, V. E., Dinh, D. T., Washington, S. J., Fakayode, S. O., Losso, J. N., van Ravenswaay, R. O., and Warner, I. M. (2008). Determination of pharmacologically active compounds in root extracts of Cassia alata L. by use of high performance liquid chromatography. Talanta, 74(4), 896-902.

Gritsanapan, W., and Mangmeesri, P. (2009). Standardized Senna alata. leaf extract. Journal of Health Research, 23(2), 59-64.

Heo, S. K., Yun, H. J., Noh, E. K., and Park, S. D. (2010). Emodin and rhein inhibit light-induced monocytes migration by blocking of ROS production. Vascular Pharmacology, 53(1-2), 28-37.

Hu, G., Liu, J., Zhen, Y. Z., Wei, J., Qiao, Y., Lin, Y. J., and Tu, P. (2013). Rhein inhibits the expression of vascular cell adhesion molecule 1 in human umbilical vein endothelial cells with or without lipopolysaccharide stimulation. American Journal of Chinese Medicine, 41(3), 473-485.

Idu, M., Omonigho, S. E., and Igeleke, C. L. (2007). Preliminary investigation on the photochemistry an antimicrobial activity of Senna alata L. flower. Pakistan Journal of Biological Sciences, 10(5), 806-809.

Jayashree, G. V., Kumar, K. H., Krupashree, K., Rachitha, P., and Khanum, F. (2015). LC–ESI–MS/MS analysis of Asparagus racemosus Willd. roots and its protective effects against t-BHP induced oxidative stress in rats. Industrial Crops and Products, 78, 102-109.

Kalyanaraman, B., Darley-Usmar, V., Davies, K. J., Dennery, P. A., Forman, H. J., Grisham, M. B., Mann, G. E., Moore, K., Roberts, L. J., and Ischiropoulos, H. (2012). Measuring reactive oxygen and nitrogen species with fluorescent probes: challenges and limitations. Free Radical Biology & Medicine, 52(1), 1-6.

Kim, Y. S., Lee, S. J., Hwang, J. W., Kim, E. K., Kim, S. E., Kim, E. H., Moond, S. H., Jeon, B. T., and Park, P. J. (2012). In vitro protective effects of Thymus quinquecostatus Celak extracts on t-BHP-induced cell damage through antioxidant activity. Food and Chemical Toxicology, 50(11), 4191-4198.

Liu, A., Xu, L., Zou, Z., and Yang, S. (2009). Studies on chemical constituents from leaves of Cassia alata. Zhongguo Zhong Yao Za Zhi, 34(7), 861-863.

Liu, J., Chen, Z., Zhang, Y., Zhang, M., Zhu, X., Fan,Y., Shi, S., Zen, K., and Liu, Z. (2013). Rhein protects pancreatic β-cells from dynamin-related protein-1-mediated mitochondrial fission and cell apoptosis under hyperglycemia. Diabetes, 62(11), 3927-3935.

Muller, K., and Meineke, V. (2007). Radiation-induced alterations in cytokine production by skin cells. Experimental Hematology, 35(4 supplement 1), 96-104.

Nestle, F. O., Meglio, P. D., Qin, J. Z., and Nickoloff, B. J. (2009). Skin immune sentinels in health and disease. Nature Reviews Immunology, 9(10), 679-691.

Panichayupakaranant, P., Sakunpak, A., and Sakunphueak, A. (2009). Quantitative HPLC determination and extraction of anthraquinones in Senna alata leaves. Journal of Chromatographic Science, 47(3), 197-200.

Promgool, T., Pancharoen, O., and Deachathail, S. (2014). Antibacterial and antioxidative compounds from Cassia alata Linn. Songklanakarin Journal of Science and Technology, 36(4), 459-463.

Ramsay, A., and Mueller-Harvey, I. (2016). Senna alata leaves are a good source of propelargonidins. Natural Product Research, 30(13), 1-10.

Riss, T. L., Moravec, R. A., Niles, A. L., Duellman, S., Benink, H. A., Worzella, T. J., and Minor, L. (2016). Cell Viability Assays. In Assay Guidance Manual, 262-291.

Sagnia, B., Fedeli, D., Casetti, R., Montesano, C., Falcioni, G., and Colizzi, V. (2014). Antioxidant and anti-inflammatory activities of extracts from Cassia alata, Eleusine indica, Eremomastax speciosa, Carica papaya and Polyscias fulva medicinal plants collected in cameroon. Public Library of Science, 9(8), 1-10.

Sanchez, C., Mathy-Hartert, M., Deberg, M. A., Ficheux, H., Reginster, J. Y., and Henrotin, Y. E. (2003). Effects of rhein on human articular chondrocytes in alginate beads. Biochemical Pharmacology, 65(3), 377-388.

Sheng, X., Wang, M., Lu, M., Xi, B., Sheng, H., and Zang, Y. Q. (2011). Rhein ameliorates fatty liver disease through negative energy balance, hepatic lipogenic regulation, and immunomodulation in diet-induced obese mice. American Journal of Physiology Endocrinology and Metabolism, 300(5), E886-E893.

Singh, B., Nadkarni J. R., Vishwakarma, R. A., Bharate, S. B., Nivsarkar, M., and Anandjiwala, S. (2012). The hydroalcoholic extract of Cassia alata (Linn.) leaves and its major compound rhein exhibits antiallergic activity via mast cell stabilization and lipoxygenase inhibition. Journal of Ethnopharmacology, 141(1), 469-473.

Turner, M. D., Nedjai, B., Hurst, T., and Pennington D. J. (2014). Cytokines and chemokines: At the crossroads of cell signaling and inflammatory disease. Biochimica et Biophysica Acta-Molecular Cell Research, 1843(11), 2563-2582.

Twentymam, P. R., and Luscombe, M. (1987). A study of some variables in a tetrazolium dye (MTT) based assay for cell growth and chemosensitivity. British Journal of Cancer, 56(3), 279-285.

Wagener, F. A., Carels, C. E., and Lundvig, D. M. (2013). Targeting the redox balance in inflammatory skin conditions. International Journal of Molecular Sciences, 14(5), 9126–9167.

Wuthi-udomlert, M., Kupittayanant, P., and Gritsanapan, W. (2010). In vitro evaluation of antifungal activity of anthraquinone derivatives of Senna alata. Journal of Health Research, 24(3), 117-122.

Yaron, M., Shirazi, I., and Yaron, I. (1999). Anti-interleukin-1 effects of diacerein and rhein in human osteoarthritic synovial tissue and cartilage cultures. Osteoarthritis Cartilage, 7(3), 272-280.

Zhao, Y. L., Zhou, G. D., Yang, H. B., Wang, J. B., Shan, L. M., Li, R. S., and Xiao, X. H. (2011). Rhein protects against acetaminophen-induced hepatic and renal toxicity. Food and Chemical Toxicology, 49(8), 1705-1710.