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Illuminating the Biological Mechanism of Curcumin Use

Illuminating the Biological Mechanism of Curcumin Use

Curcumin is a small-molecular weight compound isolated from the plant source Curcuma longa L. used for medicinal use. Several research studies include in vitro and in vivo studies representing potent antioxidant, anticarcinogenic, anti-inflammatory, antiangiogenic, antispasmodic, antimicrobial, antiparasitic and other activities. Curcumin shows inhibition in the progression stage of carcinogenesis by inducing apoptosis and arresting the cancer cells in the S phase, G2/M phase of the cell cycle. It also shows inhibition in the activities of growth factor receptors. The anti-inflammatory properties of curcumin mediate through their effects on cytokines, lipid mediators, eicosanoids and proteolytic enzymes. It acts as scavengers and searches for superoxide radicals, hydrogen peroxide and nitric oxide that inhibit lipid peroxidation. These biological mechanisms evolve different pharmacological and therapeutic use of curcumin. The biological mechanism of curcumin shows efficacy towards human health.

It is a nutraceutical with low toxicity, representing successful use in various medical conditions such as cataracts, cystic fibrosis, and prostate and colon cancers. Some of the significant biological activities of curcumin are described below:

Anti-inflammatory activity: Curcumin and its derivatives are considered the potent inhibitor of inflammation. It modulates several inflammatory mediators involved both in vitro and in vivo through complex reactions on cytokines, lipid mediators and proteolytic enzymes (Joe et al., 2004). It mainly inhibits IL-1βstimulated gene expression of a neutrophil chemotactic peptide, interleukin–8 (IL–8), and inhibits lipopolysaccharide-induced production of IL -1 and TNFα by a human monocyte protein macrophage cell line. It also inhibits the proinflammatory l Th1 cytokine profile and NF-kappaB activation pathway. Curcumin has also shown inhibition of the cellular uptake of arachidonic acid (AA), known to be an essential proinflammatory eicosanoid. 

Antioxidant activity: Curcumin has a strong capability of searching superoxide radicals, hydrogen peroxide and nitric oxide (NO) from activated macrophages while reducing iron complex and inhibiting lipid peroxidation. These activities show a central mechanism as curcumin exhibits pharmacological and therapeutic activities (Balasubramanyam et al., 2003). The use of curcumin has shown protection to the renal cells and neural glial cells from oxidative stress. It also enhances the activities of other antioxidants, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase. It shows protection against oxidative stress in endothelial cells by induction of haem oxygenase-1. Also, the antioxidant properties of curcumin are represented by protecting tissues from the effects of oxidative stress induced by radiation (REF), metals, and severe injury to skeletal muscles.

Anti-viral activities: Several in vivo and in vitro studies have shown that curcumin constitutes moderate to high inhibitory activity regarding some viruses involving human simple-virus-2 and type I HIV. Curcumin shows efficacy in inhibiting P24 antigen production in cells infected chronically or acutely with HIV-1 and inhibiting enzymatic reactions linked with HIK 1 integrase, but no other virus and cells.

Anti-tumour activity: Curcumin is capable of preventing cancer by suppressing tumour promotion. It shows inhibition and induction of apoptosis in different cell types and arrests the cancer cells at the S and G2 phases of the cell cycle. It remains active in various signalling pathways through NF-қB and reduces the expression of COX-2. Curcumin also interacts with cell regulatory proteins such as the mitogen-activated protein (MAP) cascade. It shows solid inhibitory actions on various cytochrome P-450s, phenol sulphotransferase, and glutathione S-transferases evolving anticarcinogenic activity. Curcumin possesses antiangiogenic action, which is mediated, at the molecular level, by inhibiting vascular endothelial growth factor (VEGF), angiopoietins (Ang 1 and Ang 2), and fibroblast growth factors (bFGF)– induced angiogenesis.

Antiparasitic and Antimalarial activity: Curumin has shown actions against different types of parasites under in vitro and in vivo conditions. It has demonstrated antiprotozoal activity against Leishmania major, Leishmania donovani, Trichomonas vaginalis, Entamoeba histolytica, etc. Anthelmintic activity has also shown on the nematode Ascaridia galli and the cestode Raillietina cesticillus

Effect on immunity: Curcumin has shown immune regulation. It enhances the immunosuppressive activity of cyclosporine in the animal model (Chueh et al., 2003). The effect of curcumin on mitogen or antigen-induced proliferation of splenic lymphocytes, induction of cytotoxic T lymphocytes, lymphokine-activated killer cells, and the production of cytokines by T lymphocytes and macrophages have also been determined (Gao et al., 2004). 

Wound healing activity: Curcumin is capable of inducing apoptosis of inflammatory cells during the early phase of wound healing, inhibiting the movement of the transcription factor NF-κB, reducing the production of cytokines (TNF-α and IL-1), removal of ROS, affecting the production of antioxidant enzymes and thus reducing inflammation and shortening the inflammatory phase in the wound healing process.

Other activities: Anti-inflammatory activity is exhibited in arragenin and caoline-induced edema due to curcumin and salt. The protection of gastric mucosa against irritants is determined by turmeric powder. Curcumin can decrease high cholesterol levels like statine and have antimutagenic activity.  

References

  1. Joe, B., Vijaykumar, M., & Lokesh, B. R. (2004). Biological properties of curcumin-cellular and molecular mechanisms of action. Critical reviews in food science and nutrition, 44(2), 97-111. https://doi.org/10.1080/10408690490424702
  2. Balasubramanyam, M., Koteswari, A. A., Kumar, R. S., Monickaraj, S. F., Maheswari, J. U., & Mohan, V. (2003). Curcumin-induced inhibition of cellular reactive oxygen species generation: novel therapeutic implications. Journal of Biosciences, 28(6), 715-721. https://doi.org/10.1007/BF02708432
  3. Chueh, S. C., Lai, M. K., Liu, I. S., Teng, F. C., & Chen, J. (2003, June). Curcumin enhances the immunosuppressive activity of cyclosporine in rat cardiac allografts and in mixed lymphocyte reactions. In Transplantation proceedings (Vol. 35, No. 4, pp. 1603-1605). Elsevier. https://doi.org/10.1016/S0041-1345(03)00377-4

Gao, X., Kuo, J., Jiang, H., Deeb, D., Liu, Y., Divine, G., … & Gautam, S. C. (2004). Immunomodulatory activity of curcumin: suppression of lymphocyte proliferation, development of cell-mediated cytotoxicity, and cytokine production in vitro. Biochemical pharmacology, 68(1), 51-61. https://doi.org/10.1016/j.bcp.2004.03.015

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