A polymeric nanoparticle formulation of curcumin (NanoCurc™) ameliorates CCl4-induced hepatic injury and fibrosis through reduction of pro-inflammatory cytokines and stellate cell activation

Bisht, Savita; Khan, Mojammel A.; Bekhit, Mena; Bai, Haibo; Cornish, Toby C.; Mizuma, Masamichi; Rudek, Michelle A.; Zhao, Ming; Maitra, Amarnath; Ray, Balmiki; Lahiri, Debomoy K.; Maitra, Anirban; Anders, Robert A.

doi:10.1038/labinvest.2011.86

Cited by 99 publications

(74 citation statements)

References 61 publications

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“…This includes novel mechanisms of targeting the liver, such as the use of siRNA 139, 140 or specific targeting systems 69, 141 . For example, TGF-β is well known to play a central role in the fibrogenic cascade and therefore is an important therapeutic target.…”

Section: Novel Approachesmentioning

confidence: 99%

Translating an Understanding of the Pathogenesis of Hepatic Fibrosis to Novel Therapies

Rockey

2013

Clinical Gastroenterology and Hepatology

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The response to injury is one of wound healing and fibrogenesis, which ultimately leads to fibrosis. The fibrogenic response to injury is a generalized one across virtually all organ systems. In the liver, the injury response, typically occuring over a prolonged period of time, leads to cirrhosis (although it should be pointed out that not all patients with liver injury develop cirrhosis). The fact that many different diseases result in cirrhosis suggests a common pathogenesis. The study of hepatic fibrogenesis over the past 2 decades has been remarkably active, leading to a considerable understanding of this process. It has been clearly demonstrated that the hepatic stellate cell is a central component in the fibrogenic process. It has also been recognized that other “effector” cells are important in the fibrogenic process, including resident fibroblasts, bone marrow derived cells, fibrocytes, and even perhaps cells derived from epithelial cells (i.e., through epithelial to mesenchymal transition or EMT). A key aspect of the biology of fibrogenesis is that the fibrogenic process is dynamic; thus, even advanced fibrosis (or cirrhosis) is reversible. Together, an understanding of the cellular basis for liver fibrogenesis, along with multiple aspects of the basic pathogenesis of fibrosis, have highlighted many exciting potential therapeutic opportunities. Thus, while the most effective “anti-fibrotic” therapy is treatment of the underlying disease, in situations in which this not possible, specific anti-fibrotic therapy is likely to not only become feasible, but will soon become a reality. The goal of this review is to highlight the mechanisms underlying fibrogenesis that may be translated into future anti-fibrotic therapies and to review the current state of clinical development.

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Section: Novel Approachesmentioning

confidence: 99%

Translating an Understanding of the Pathogenesis of Hepatic Fibrosis to Novel Therapies

Rockey

2013

Clinical Gastroenterology and Hepatology

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“…Injection with CCl 4 significantly enhances oxidative stress, hepatic inflammation, cellular apoptosis, necrosis, fibrosis, and even liver cancer in mice2. A great number of researchers have demonstrated the mechanisms of CCl 4 toxicity in the liver.…”

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confidence: 99%

Inhibition of caspase-9 aggravates acute liver injury through suppression of cytoprotective autophagy

Guo

Lin

Pan

et al. 2016

Sci Rep

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Acute liver disease is characterized by inflammation, oxidative stress and necrosis, which can greatly influence the long term clinical outcome and lead to liver failure or cancer. Here, we initially demonstrated the beneficial role of caspase-9-dependent autophagy in acute liver injury. Treatment with caspase-9 inhibitor z-LEHD-FMK in HepG2 cells, AML12 cells and C57BL/b6N mice exacerbated CCl4-induced acute hepatocellular damage, and also down-regulated autophagy markers expression levels, indicating that caspase-9 inhibition may aggravate acute liver damage by suppressing cytoprotective autophagy. CCl4 was used as an acute liver injury inducer which caused oxidative stress and apoptosis through up-regulation of HIF-1α, as well as triggered hepatic inflammation and necroptosis via TLR4/NF-κB pathway. Caspase-9 Thr125 site was firstly phosphorylated by ERK1/2 which subsequently activated the cytoprotective autophagy process to attenuate acute CCl4 injury. Caspase-9 inhibition further aggravated hepatic necroptosis through NF-κB expression, leading to increased pro-inflammatory mediators levels, suggesting a protective role of caspase-9-dependent autophagy in the inflammatory process as well as its possibility being a new therapeutic target for the treatment of acute liver injury.

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“…The ability to amplify these beneficial effects of herbs or nutriceuticals for treatment of infectious diseases by attaching them to nanoparticle carriers [64, 90] and delivering them directly into infected cells throughout the body is a significant advantage. NPs also have other potential public health applications.…”

Section: Resultsmentioning

confidence: 99%

Advances in integrative nanomedicine for improving infectious disease treatment in public health

Bell

Schwartz

Boyer³

et al. 2013

European Journal of Integrative Medicine

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Introduction Infectious diseases present public health challenges worldwide. An emerging integrative approach to treating infectious diseases is using nanoparticle (NP) forms of traditional and alternative medicines. Advantages of nanomedicine delivery methods include better disease targeting, especially for intracellular pathogens, ability to cross membranes and enter cells, longer duration drug action, reduced side effects, and cost savings from lower doses. Methods We searched Pubmed articles in English with keywords related to nanoparticles and nanomedicine. Nanotechnology terms were also combined with keywords for drug delivery, infectious diseases, herbs, antioxidants, homeopathy, and adaptation. Results NPs are very small forms of material substances, measuring 1–100 nanometers along at least one dimension. Compared with bulk forms, NPs’ large ratio of surface-area-to-volume confers increased reactivity and adsorptive capacity, with unique electromagnetic, chemical, biological, and quantum properties. Nanotechnology uses natural botanical agents for green manufacturing of less toxic NPs. Discussion Nanoparticle herbs and nutriceuticals can treat infections via improved bioavailability and antiinflammatory, antioxidant, and immunomodulatory effects. Recent studies demonstrate that homeopathic medicines may contain source and/or silica nanoparticles because of their traditional manufacturing processes. Homeopathy, as a form of nanomedicine, has a promising history of treating epidemic infectious diseases, including malaria, leptospirosis and HIV/AIDS, in addition to acute upper respiratory infections. Adaptive changes in the host’s complex networks underlie effects. Conclusions Nanomedicine is integrative, blending modern technology with natural products to reduce toxicity and support immune function. Nanomedicine using traditional agents from alternative systems of medicine can facilitate progress in integrative public health approaches to infectious diseases.

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A polymeric nanoparticle formulation of curcumin (NanoCurc™) ameliorates CCl4-induced hepatic injury and fibrosis through reduction of pro-inflammatory cytokines and stellate cell activation

Cited by 99 publications

References 61 publications

Translating an Understanding of the Pathogenesis of Hepatic Fibrosis to Novel Therapies

Translating an Understanding of the Pathogenesis of Hepatic Fibrosis to Novel Therapies

Inhibition of caspase-9 aggravates acute liver injury through suppression of cytoprotective autophagy

Advances in integrative nanomedicine for improving infectious disease treatment in public health

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