Natural Products as Tools for Defining How Cellular Metabolism Influences Cellular Immune and Inflammatory Function during Chronic Infection

Abstract

Chronic viral infections like those caused by hepatitis C virus (HCV) and human immunodeficiency virus (HIV) cause disease that establishes an ongoing state of chronic inflammation. While there have been tremendous improvements towards curing HCV with directly acting antiviral agents (DAA) and keeping HIV viral loads below detection with antiretroviral therapy (ART), there is still a need to control inflammation in these diseases. Recent studies indicate that many natural products like curcumin, resveratrol and silymarin alter cellular metabolism and signal transduction pathways via enzymes such as adenosine monophosphate kinase (AMPK) and mechanistic target of rapamycin (mTOR), and these pathways directly influence cellular inflammatory status (such as NF-κB) and immune function. Natural products represent a vast toolkit to dissect and define how cellular metabolism controls cellular immune and inflammatory function.

Identification of resveratrol analogs as potent anti‐dengue agents using a cell‐based assay

“…Data represent mean AE SD calculated from three independent experiments with duplicate samples. activity [Uchide and Toyoda, 2011;Komaravelli et al, 2015] and also regulates multiple cellular events, such as signal transduction pathways [De Leo et al, 2012;Lovelace and Polyak, 2015;Yang et al, 2015]. Thus, we propose that both compounds may also target unknown cellular factors in host cells that are essential for DENV2 replication.…”

“…A number of studies have shown that resveratrol and its derivatives inhibit the replication of different viruses such as herpes simplex [Docherty et al, ], varicella‐zoster [Docherty et al, ], and influenza A [Palamara et al, ; Li et al, ]. It is known that resveratrol exhibits anti‐oxidant activity [Uchide and Toyoda, ; Komaravelli et al, ] and also regulates multiple cellular events, such as signal transduction pathways [De Leo et al, ; Lovelace and Polyak, ; Yang et al, ]. Thus, we propose that both compounds may also target unknown cellular factors in host cells that are essential for DENV2 replication.…”

Impact of curcumin on energy metabolism in HIV infection: A case study

“…Curcumin modulates the expression of adiponectin, which suppresses the gluconeogenesis and increases the glucose absorption, by negative regulation of inflammatory cytokines such as TNF-α, IL-6, NF-kB, and COX-2 (Prasad & Tyagi, 2015). Furthermore, curcumin alters the cell metabolism and signal transduction pathways through AMPK and mTOR enzymes that mediate inflammatory and immunological processes (Lovelace & Polyak, 2015). FIGURE 1 Respiratory quotient (R) during the indirect calorimetry realized before and after oral curcumin supplementation.…”

Beneficial Effects of Resveratrol-Mediated Inhibition of the mTOR Pathway in Spinal Cord Injury

“…Both PI3K and Akt are mTOR upstream activators. Furthermore, resveratrol, in high concentration, has been evidenced to inhibit the mitochondrial function, decrease cellular ATP levels, and activate AMPK [ 80 ]. Moreover, the mTOR pathway could be inhibited by the activation of AMPK, as depicted in Figure 1 .…”