The inflammatory response is the body’s natural response to tissue injury of any kind. It results in increased vascular permeability by the release of vasoactive and chemotactic factors to begin the repair and healing process, the emigration of leukocytes to clear debris and phagocytosis of collagen and extracellular matrix degradation. Oxidation is a necessary, yet a destructive element of the inflammatory process and can lead to oxidative stress resulting in chronic inflammation as the body struggles to repair itself. Many natural herbs have been clinically shown to be effective antioxidants and anti-inflammatory agents. We will discuss the inflammatory process and provide current research on the anti-inflammatory effects of Turmeric (Curcumin longa) and Ginger (Zingiber officinale).
Inflammation and Oxidative Stress
Inflammation occurs when cells are injured by either endogenous (internal) or exogenous (external) injuries (Banasik, 2013). Endogenous injuries from surgeries and physical trauma damage tissue and interfere with cell signaling communication and cellular metabolism. Exogenous sources from infections including pathogens (viruses, bacteria, yeast, mold, fungi and parasites) or foreign substances from environmental toxins also result in inflammation. Inflammation stimulates the body’s immune system which is designed to defend and eliminate these stressors by neutralizing and destroying harmful agents, limiting their proliferation to neighboring tissues and repairing damaged tissue (Banasik, 2013).
Oxidizing agents are destructive byproducts of the inflammatory response because they attack cell membranes and can cause permeability releasing nitric oxide which reacts with oxygen to attack microbial molecules (Banasik, 2013). Oxidative stress is defines as a disturbance in the balance between the production of reactive oxygen species (free radical and reactive metabolites) and the antioxidant defenses of the system to detoxify the reactive intermediates and repair the resulting damage (Wikepedia, 2015). Oxidative stress can lead to chronic inflammation, disruptions in normal mechanisms of cellular signaling and DNA damage (Wikepedia, 2015) resulting in many diseases including pulmonary, neurological, diabetes, cardiovascular, and cancers (He, Yue, Zheng et al 2015) and many others.
Ginger (Zingiber officinale)
Ginger (Zingiber officinale) (root) has been used for thousands of years in China for medicinal purposes (Murray, 2013). Its therapeutic actions include anti-emetic, gastrointestinal support, choloagogue, spasmolytic, anti-inflammatory, antibiotic, antioxidant, and anti-inflammatory (Murray, 2013). We will discuss current research on the anti-oxidant and anti-inflammatory and anti-allergenic effects. The active constituents that appear to demonstrate the antioxidant and anti-inflammatory activities are the phenolic compounds gingerol, shogaol, paradol, zingerone, zerumbone (Tahir, Sani, Murad et al 2015). The anti-inflammatory effects of ginger are due to the inhibitory effect to reduce prostaglandin synthesis, leukotriene biosynthesis (Al-Nahain, Jahan and Rahmatullah 2014) thromboxanes and its other antioxidant activities (Murray, 2013).
Gingerols are phenolic substances found in the rhizome shown to have anti-inflammatory, anti-oxidant and anticancer properties (Wang, Zhang, and Yang et al 2014). Inappropriate T lymphocyte function is implicated in the inflammatory process. Gingerol extracts were shown to inhibit DNA synthesis by T lymphocytes and interferon-y synthesis (Bernard, Furlong and Power et al. (2015). Gingerol (8) and gingerol (10) impaired IL-2 induced proliferation of CLL-2 cells through the inhibition of IL-2 receptor signaling. The anticancer activities of 6-Gingerol are via a variety of biological pathways involved in apoptosis, cell cycle regulation, cytotoxic activity and inhibition of angiogenesis (Wang et al 2014) the growth of new blood vessels.
Zingerone from ginger is an anti-inflammatory agent shown to suppress acute systemic lipopolysaccharide (LPS) inflammation via nuclear factor (NF-kB) and proinflammatory cytokines in mice (Hsiang, Cheng, Lo, et al. 2015). Zerumbone a sesquiterpene from wild ginger rhizome has been shown to contain ant carcinogenic, anti-inflammatory, antioxidant and antiallergenic properties (Shieh, Huang, Wang et al. 2015). The antiallergenic properties are due to reducing allergen specific immunoglobulin E (lgE) and increasing lgG2a antibodies, preventing eosinophilic pulmonary infiltration and ameliorating mucus hypersecretion suggesting the anti-allergic effects result from modulation of Th1/Th2 cytokines (Shieh et al 2015).
Zingiber officinale and Gelam honey was shown to be have anti-inflammatory and anti-tumor effects against colorectal cancer by stimulation of apoptosis (upregulation of caspase 9 and lkB genes) and downregulation of the KRAS,ERK, AKT, Bclxl and NFkB (p65) genes (Tahir, Sani, Murad et al. 2015). It has also been shown to ameliorate Rheumatoid arthritis by stopping RA-induced bone destruction (Al-Nahain, Jahan, and Rahmatullah 2014).
Curcumin longa (Turmeric) (root) has been used for 4,000 years as an herbal remedy in medicine. It contains therapeutic action as an anti-arthritic, anti-asthmatic, antibacterial, anticarcinogenic, antifungal, antihyperlipidemic, anti-inflammatory, antioxidant, antiulcer, antiviral, cholagogue, expectorant, hepatic and hypoglycemic (Peterson, 2015). We will discuss the anti-inflammatory and antioxidant effects in cardiovascular disease and rheumatoid arthritis.
Curcumin has been shown to display anti-inflammatory activity and alleviate oxidative stress in chronic diseases through the Nrf2-keap1 pathway and through its natural chemical structure as a free radical scavenger (He et al., 2015). Curcumin suppresses pro-inflammatory pathways and blocks the product of TNF by binding to TNF directly remediating TNF cell signaling in various cells (He et al., 2015). As an antioxidant, curcumin is known to bind amyloids, stabilizing protein homeostasis networks (He et al., 2015).
Cardiovascular diseases have been shown to develop from oxidative stress, inflammation and activation of proinflammatory cytokines (He et al., 2015). Curcumin was shown to protect against inflammation, cardiac hypertrophy and fibrosis by inhibiting p200-HAT activity and other signaling pathways (He et al., 2015). Curcumin suppressed lipopolysaccharide (LPS) induced inflammation in vascular smooth muscle cells of rats by inhibition of TLR4-MAPK/NF-kB pathways (He et al., 2015). Parodi et al. found mice treated with curcumin exhibited decreases in aortic tissue activator protein – and NF-kB DHA binding lowering concentrations of IL1B, IL-6, MCP-1 and MMP-9 (He et al. 2015). Curcumin was shown to stimulate apoptosis of H9c2 cells by upregulating reverse oxygen species (ROS) and triggering the activation of JNK’s (He et al., 2015).
Rheumatoid arthritis (RA) is an autoimmune condition resulting in inflammation of the synovial joints. ROS mediates many transcription factors that regulate gene expression, growth factors, chemokines and inflammatory cytokines suspected to play a role in RA. Curcumin has raised a great deal of interest as a therapy for RA and clinical trials are under way. Curcumin activated caspase-3 and -9, up regulated Bax, down-regulated Bcl-2 and Bcl-xL, degraded poly (ADP-ribose) polymerase in RA patients (He et al. 2015). Curcumin showed anti-inflammatory response in synovial fibroblasts by suppression of COX-2 and inhibition of prostaglandin E2 synthesis (He et al. 2015). Lee et al also found in vitro that curcumin abolished the p65 NF-kB nuclear translocation and binding activity of NF-kB DNA by inhibition of COX-2 and MMP-9 and reduction of IkBa phosphorylation in IL-1B and TNF –a-articular chondrocytes (He et al., 2015).
Al-Nahain, A., Jahan, R., & Rahmatullah, M. (2014). Zingiber officinale: A potential Plant against Rheumatoid Arthritis. [Abstract]. Arthritis. doi:10.1155/2014/159089
Banasik, J. (2013). Inflammation and immunity. In Pathophysiology (5th, pp. 157-193). St. Louis, Missouri: Elsevier Saunders.
Bernard, M., Furlong, S. J., Power Coombs, M. R., & Hoskin, D. W. (2015). Differential Inhibition of T Lymphocyte Proliferation and Cytokine Synthesis by -Gingerol, -Gingerol, and -Gingerol. [Abstract]. Phytotherapy Research. doi:10.1002/ptr.5414
He, Y., Yue, Y., Zheng, X., Zhang, K., Chen, S., & Du, Z. (2015). Curcumin, inflammation, and chronic diseases: how are they linked? Molecules, 9183-213. doi:10.3390/molecules20059183
Hsiang, C. Y., Cheng, H. M., Lo, H. Y., Li, C. C., Chou, P. C., Lee, Y. C., & Ho, T. Y. (2015). Ginger and Zingerone ameliorate lipopolysaccharide-induced acute systemic inflammation in Mice, assessed by nuclear factor-?B bioluminescent imaging. [Abstract]. Journal of Agricultural and Food Chemistry, 63, 6051-8. doi:10.1021/acs.jafc.5b01801
Murray, M. T. (2013). Zingiber officinale (Ginger). In Tectbook of Natural Medicine (4th ed., pp. 1147-1153). St. Louis, Missouri: Elsevier, Churchill Livingstone.
Oxidative stress. (2015, October 31). In Wikipedia. Retrieved November 3, 2015, from Wikepedia Foundation Inc website: https://en.wikipedia.org/wiki/Oxidative_stress
Peterson, D. (2015). Essential oil of Turmeric. In http//www.achs.edu. Retrieved November 4, 2015, from American College of Healthcare Sciences website: http://myachsclass.org/re/DotNextLaunch.asp?courseid=11632021&userid
Shieh, Y. H., Huang, H. M., Wang, C. C., Lee, C. C., Fan, C. K., & Lee, Y. L. (2015). Zerumbone enhances the Th1 response and ameliorates ovalbumin-induced Th2 responses and airway inflammation in mice. [Abstract]. International Immunopharmacology, 383-91. doi:10.1016/j.intimp.2014.12.027
Tahir, A. A., Sani, N. F., Murad, N. A., Makpol, S., Ngah, W. Z., & Yusof, Y. A. (2015). Combined ginger extract & Gelam honey modulate Ras/ERK and P13K/AKT pathway genes in colon cancer HT 29 cells. Nutrition Journal. doi:10.1186/s12937-015-0015-2.
Wang, S., Zhang, C., Yang, G., & Yang, Y. (2014). Biological properties of 6-gingerol: a brief review. Natural Product Communications, 1027-30. Abstract retrieved from PMID: 25230520