Curcumin: an orally bioavailable blocker of TNF and other pro‐inflammatory biomarkers

Abstract

TNFs are major mediators of inflammation and inflammation-related diseases, hence, the United States Food and Drug Administration (FDA) has approved the use of blockers of the cytokine, TNF-a, for the treatment of osteoarthritis, inflammatory bowel disease, psoriasis and ankylosis. These drugs include the chimeric TNF antibody (infliximab), humanized TNF-a antibody (Humira) and soluble TNF receptor-II (Enbrel) and are associated with a total cumulative market value of more than $20 billion a year. As well as being expensive ($15 000-20 000 per person per year), these drugs have to be injected and have enough adverse effects to be given a black label warning by the FDA. In the current report, we describe an alternative, curcumin (diferuloylmethane), a component of turmeric (Curcuma longa) that is very inexpensive, orally bioavailable and highly safe in humans, yet can block TNF-a action and production in in vitro models, in animal models and in humans. In addition, we provide evidence for curcumin's activities against all of the diseases for which TNF blockers are currently being used. Mechanisms by which curcumin inhibits the production and the cell signalling pathways activated by this cytokine are also discussed. With health-care costs and safety being major issues today, this golden spice may help provide the solution. LINKED ARTICLESThis article is part of a themed section on Emerging Therapeutic Aspects in Oncology. To view the other articles in this section visit http://dx

Curcumin for the treatment of major depression: A randomised, double-blind, placebo controlled study

“…In a recent meta-analysis on clinical trials it was concluded that curcumin lowers CRP levels (Sahebkar, 2014). It can also lower IL-6 (Belcaro et al, 2010, Zhou et al, 2011 and TNF-Į levels (Aggarwal et al, 2013).…”

Kurkumin Menurunkan Ekspresi Tumor Necrosis Factor (TNF)-α Kompleks Oosit-Kumulus Sapi pada Kultur dengan Zalir Peritoneum Penderita Infertil Terkait Endometriosis

“…TNF-α merupakan mediator utama dalam proses inflamasi dan kadar TNF-α dalam zalir perito-neum wanita dengan endometriosis telah terbukti terjadi peningkatan secara signifikan. 10,11 Infertilitas adalah salah satu keluhan penderita dengan endometriosis yang tatalaksananya hingga kini masih belum juga memberikan hasil yang memuaskan. Sebuah konsep umum yang penting adalah bahwa pada endometriosis terjadi proses inflamasi lokal pada pelvis dengan perubahan fungsi sel-sel terkait sistem imun di lingkungan peritoneum.…”

Current paradigms of cancer chemoprevention

“…Selectively identifying chemopreventive agents that would specifically block or enhance the target genes or proteins can serve as ideal chemopreventive agents. For example, in inflammation mediated carcinogenesis the inflammation stimulus releases TNFa, which can activate the NFkB pathway in epithelial cells (Aggarwal et al, 2013). The signaling cascade then would activate production of BcL-X L and IAP-1 (Szliszka and Krol, 2011) and cell cycle regulatory cyclins, such as cyclin D. During the inflammation induced carcinogenesis, expression of Cox-2 is also upregulated, resulting in increased prostaglandin E2, which is responsible for loss of contact inhibition, increased cell proliferation, and loss of E-cadherin.…”

“…The signaling cascade then would activate production of BcL-X L and IAP-1 (Szliszka and Krol, 2011) and cell cycle regulatory cyclins, such as cyclin D. During the inflammation induced carcinogenesis, expression of Cox-2 is also upregulated, resulting in increased prostaglandin E2, which is responsible for loss of contact inhibition, increased cell proliferation, and loss of E-cadherin. Therefore, compounds that would block TNFa, NFkB, or Cox-2 may serve as possible chemopreventive agents against inflammation induced cell transformation (Aggarwal et al, 2013;Wang et al, 2013). There are several chemopreventive agents that have targeted Cox-2 expression, which include resveratrol, indol-3-carbinol, epigalocatechin gallate (EGCG), curcumin, sulforaphan etc.…”