<i>In Silico</i>, <i>In Vitro</i> and <i>In Vivo</i> Assessment of Safety and Anti-inflammatory Activity of Curcumin

Abstract

Problem statement: Curcumin the active component of turmeric is known for its wide biological actions. Extensive studies on curcumin highlighted its anti-inflammatory, anti-oxidant, antimicrobial, anti-carcinogenic and anti-coagulant activity. The anti-inflammatory activities of curcumin have been demonstrated both in vitro and in vivo. Though curcumin and its anti-inflammatory properties are well documented, the exact mechanism of action and effective in vivo dosage required for potential anti-inflammatory activity of curcumin are yet to be determined. The current work reflects in identfying the the role curcumin in the inflmmatory cascade and arriving at an optimal effective dose (ED 50 ). Approach: The objective of the current study is to understand and establish the role of curcumin in the treatment of inflammatory condition, through in-silico, in-vitro and in-vivo studies. The specificity and binding affinity of curcumin to major inflammatory mediators such as, cytokines/chemokines, signaling proteins and transcription factors were evaluated using molecular docking. Subsequently, in-vitro experiments were conducted to establish the role of curcumin in reducing the release of histamine and β-hexosaminidase form U937 human monocytes cell lines. Further, the Effective Dose (ED 50 ) of curcumin was established for its potent in vivo anti-inflammatory activity. Results: Our study confirmed a strong affinity of curcumin to various inflammatory mediators (ERK, PKC, P38 MAP Kinase, NFkB and Lipoxygenase). Curcumin when studied for its affinity towards chemokines/cytokines and TNF-α was found to be ineffective. Proportionate reduction in histamine and β-hexosaminidase release in U937 cells in vitro and inhibition of paw edema in carrageenan induced inflammation in rats affirmed the dose dependent anti-inflammatory activity of curcumin. This in vivo study elucidated the ED 50 value to be 570.6 mg kg −1 body weight for curcumin, which apparently shall be the potent dose to screen its anti-inflammatory activity. Conclusion: Overall results suggest that, curcumin mediates its anti-inflammatory activity by its direct effect on multitarget inflammatory mediators while others were mediated by the downstream effects of curcumin. Curcumin can be a potent molecule in treatment of various diseases associated with inflammation, with its multi-target potency and high safety profile.

Molecular docking and ADME-toxicity studies of potential compounds of medicinal plants grown in Indonesia as an anti-rheumatoid arthritis

“…IL-6 has an activity on neutrophils that secretes reactive oxygen intermediates and proteolytic enzymes, which lead to inflammation and joint destruction [4]. In the previous study, the activation of TNF-α and IL-1β receptor has been found related to the production of pro-inflammatory cytokines that were regulated by the activity of p38 Mitogen Activated Protein Kinase (MAPK), Extracellular signal-Regulated Kinases (ERK), Protein Kinase C (PKC), Nuclear Factor Kappa B (NF-kB), and the other enzymes [9].…”

Conversion of Curcumin into Heterocyclic Compounds as Potent Anti-diabetic and Anti-histamine Agents

“…Analysis of 7 C 32 H 26 Determination of α-Amylase Inhibitory Activity We used the assay of colorimetric microplate to determined the activity of α-amylase inhibitory by utilizing a well-established protocol. 24) The reaction of enzyme consisted of 4 mg α-amylase of porcine pancreatic (type VI-B, ≥10 units/mg solid), 1.25 mM p-nitrophenyl-α-D-maltopentaoside (PNPG-5) and 1 mg of samples in the 96-well plate. The microplate reader was using to monitor the reaction of enzyme at 405 nm.…”

“…α-Amylase Inhibitory Effect of Control (Acarbose), Newly Prepared Curcumin Derivatives 2-7 of 20 nM phorbol myristate acetate (PMA) (Sigma-Aldrich) for 1 h. The cell culture supernatants collected from either untreated control or treated cultures were clarified at 10000 g for 5 min at 4°C and assessed for released histamine by a commercially available EIA kit (SPI-Bio, France). 25)…”

“…Curcumin when treated at different concentration 10, 250 and 1000 ng mL −1 showed decrease in the percentage rise in histamine levels by 82.70, 67.51 and 55.69% from U937 cells. 25) Curcumin also suppressed the immunoglobulin E (IgE)-dependent PSA reaction in a mast cell-dependent in vivo model of systemic allergic reaction 29) with a potency equivalent to that of the H1 histamine antagonist. 30) CONCLUSION From this study we have synthesized new pyrimidine, pyranone, cyclohexanone derivatives from curcumin and proved its structure by different spectral data.…”

Potential of Curcumin to Reduce Serum Nuclear Factor-Kappa B (NF-kB) Levels After High-Intensity Exercise

“…Curcumin is known for its active compounds that have anti-inflammatory activity (Boarescu et al 2022). Curcumin is able to inhibit inflammation by modulating NF-κB signals and blocking TNFα signals by activating protein responses in muscles (Srivastava et al 2017;Venkata et al 2012). The anti-inflammatory activity of curcumin also inhibits the production of pro-inflammatory eicosanoids which include prostaglandins and leukotrienes (Han, Zhang, and Li 2021;Petrone-Garcia et al 2021;Zhu et al 2019).…”