Hyaluronic Acid Modified Curcumin-Loaded Chitosan Nanoparticles Inhibit Chondrocyte Apoptosis to Attenuate Osteoarthritis via Upregulation of Activator Protein 1 and RUNX Family Transcription Factor 2

Hyaluronic acid (HA) and curcumin (CUR) have been previously utilized for osteoarthritis (OA) treatment. CUR-loaded chitosan nanoparticles (CUR@CS NPs) and HA CUR@CS NPs were synthesized in our research to ascertain the synergistic impacts of HA and CUR-loaded NPs on OA treatment. CUR@CS NPs and HA CUR@CS NPs were synthesized with evaluation of their particle size, potential, PDI, encapsulation efficiency, drug loading and surface coating as well as HA binding rate. The in vitro CUR release curve and stability of HA-CUR@CS NPs were measured. Chondrocytes were isolated from the cartilages of OA patients, followed by cell uptake assay.
The chondrocyte viability and apoptosis were determined. Subsequently, the knee OA model was established, followed by H&E, Safranin O/Fast green staining and micro-CT. HA CUR@CS NPs improved CUR stability and bioavailability. CUR@CS NPs and HA-CUR@CS NPs were successfully characterized and could further be internalized by chondrocytes. CUR@CS NPs promoted tBHP-induced chondrocyte viability and inhibited chondrocyte apoptosis. HA-CUR@CS NPs upregulated the AP-1 and RUNX2 transcription levels to activate Hedgehog pathway, which subsequently blocked the Notch pathway.
Mechanically, HA-CUR@CS NPs sustained release and long-lasting effect and long-term retention in the joint cavity and downregulated the expression of several pro-inflammatory cytokines in vivo. HA-CUR@CS NPs exhibited superior effects in the preceding experiments than CUR@CS NPs. Altogether, HA-CUR@CS NPs may restrict inflammation and chondrocyte apoptosis in OA through upregulation of AP-1 and RUNX2.

Curcumin Mitigates TNFα-Induced Caco-2 Cell Monolayer Permeabilization Through modulation of NF-κB, ERK1/2 and JNK Pathways

Scope: This work studied the capacity of curcumin to inhibit TNFα-induced inflammation, oxidative stress, and loss of intestinal barrier integrity, characterizing the underlying mechanisms.
Methods and results: Caco-2 cell monolayers were incubated with TNFα (10 ng/ml), in the absence or presence of curcumin. TNFα caused an increase in interleukin (IL)-6 and IL-8 release which was inhibited by curcumin in a dose-dependent manner (IC50 = 3.4 μM for IL-6). Moreover, TNFα led to: i) increased ICAM-1 and NLRP3 expression; ii) increased cell monolayer permeability and decreased levels of tight junction proteins; iii) increased cellular and mitochondrial oxidant production; iv) decreased mitochondrial membrane potential and complex I-III activity; v) activation of redox-sensitive pathways, i.e., NF-κB, ERK1/2 and JNK; and vi) increased MLCK expression and phosphorylation levels of MLC. Curcumin (2-8 μM) inhibited all these TNFα-triggered undesirable outcomes, mostly showing dose-dependent effects.
Conclusion: The inhibition of NF-κB, ERK1/2 and JNK activation could be in part involved in the capacity of curcumin to mitigate intestinal inflammation, oxidant production, activation of redox-sensitive pathways, and prevention of monolayer permeabilization. These results support an action of dietary curcumin in sustaining gastrointestinal tract physiology. This article is protected by copyright. All rights reserved.
Keywords: antioxidant; bioactives; inflammation; intestinal permeabilization; redox.

Curcumin in Combination with Other Adjunct Therapies for Brain Tumor Treatment: Existing Knowledge and Blueprint for Future Research

Malignant brain tumors proliferate aggressively and have a debilitating outcome. Surgery followed by chemo-radiotherapy has been the standard procedure of care since 2005 but issues of therapeutic toxicity and relapse still remain unaddressed.
Repurposing of drugs to develop novel combinations that can augment existing treatment regimens for brain tumors is the need of the hour. Herein, we discuss studies documenting the use of curcumin as an adjuvant to conventional and alternative therapies for brain tumors.
Comprehensive analysis of data suggests that curcumin together with available therapies can generate a synergistic action achieved through multiple molecular targeting, which results in simultaneous inhibition of tumor growth, and reduced treatment-induced toxicity as well as resistance.
The review also highlights approaches to increase bioavailability and bioaccumulation of drugs when co-delivered with curcumin using nano-cargos.
Despite substantial preclinical work on radio-chemo sensitizing effects of curcumin, to date, there is only a single clinical report on brain tumors. Based on available lab evidence, it is proposed that antibody-conjugated nano-curcumin in combination with sub-toxic doses of conventional or repurposed therapeutics should be designed and tested in clinical studies.
This will increase tumor targeting, the bioavailability of the drug combination, reduce therapy resistance, and tumor recurrence through modulation of aberrant signaling cascades; thus improving clinical outcomes in brain malignancies.

Curcumin suppresses TGF-β2-induced proliferation, migration, and invasion in lens epithelial cells by targeting KCNQ1OT1/miR-377-3p/COL1A2 axis in posterior capsule opacification

Background: Posterior capsule opacification (PCO) is a common complication after cataract surgery, which can lead to secondary loss of vision. Curcumin has been reported to play a suppressive role in PCO progression, and the potential molecular mechanism was explored in this study.
Methods: Cell viability and proliferation were analyzed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and 5-Ethynyl-2′-deoxyuridine (EdU) assay. Transwell assay and wound healing assay were performed to assess cell invasion and migration abilities. Western blot assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were conducted to measure the expression of proteins and RNAs. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were conducted to confirm the interaction between microRNA-377-3p (miR-377-3p) and KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) or collagen type I alpha 2 chain (COL1A2).
Results: Curcumin dose-dependently alleviated transforming growth factor-β2 (TGF-β2)-induced proliferation, migration, and invasion in SRA01/04 cells. KCNQ1OT1 was up-regulated in PCO patients and TGF-β2-induced SRA01/04 cells. Curcumin-induced protective effects in TGF-β2-induced SRA01/04 cells were largely overturned by KCNQ1OT1 overexpression. KCNQ1OT1 directly interacted with miR-377-3p and negatively regulated its expression. miR-377-3p silencing overturned Curcumin-mediated protective effects in SRA01/04 cells upon TGF-β2 treatment. miR-377-3p directly interacted with the 3′ untranslated region (3’UTR) of COL1A2. COL1A2 overexpression largely counteracted KCNQ1OT1 silencing-induced effects in TGF-β2-stimulated SRA01/04 cells. KCNQ1OT1 could up-regulate COL1A2 expression by sponging miR-377-3p in SRA01/04 cells.
Conclusion: In conclusion, Curcumin suppressed TGF-β2-induced malignant changes in lens epithelial cells by targeting KCNQ1OT1/miR-377-3p/COL1A2 axis.
Keywords: COL1A2; Curcumin; KCNQ1OT1; TGF-β2; miR-377-3p; posterior capsule opacification.

A new perspective on the treatment of Alzheimer’s disease and sleep deprivation-related conse-quences: Curcumin

Sleep problems and Alzheimer’s Disease (AD) are two disorders often seen together. Age-related structural and physiological changes in certain parts of the brain lead to changes in sleep patterns. Conditions such as AD also affect these areas of the brain, thus changing the sleep-wake cycle.
Sleep disorders likewise adversely affect the course of the disease. Sleep quality is important for the proper functioning of the memory. Impaired sleep is also associated with problems in some areas of the brain that play a key role in learning and memory functions.
Changes in the brain seen in aging and AD disrupt sleep and memory processes, leading increased cognitive impairment. In addition to synthetic drugs, treatment with plants has also become a preferred factor in the treatment.
Curcuminoids, which are in the structure of diarylheptanoid, are the main components of turmeric. Curcumin has multiple applications in treatment regimes of various diseases such as cardiovascular diseases, obesity, cancer, inflammatory diseases, and aging.

Curcumin

M35000 EpiGentek 1 g 109.45 EUR

Curcumin

HY-N0005 MedChemExpress 100mg 119 EUR

Curcumin

GP8291-100G Glentham Life Sciences 100 g 146 EUR

Curcumin

GP8291-1G Glentham Life Sciences 1 g 41 EUR

Curcumin

GP8291-25G Glentham Life Sciences 25 g 74 EUR

Curcumin

GP8291-50G Glentham Life Sciences 50 g 102 EUR

Curcumin

GP8291-5G Glentham Life Sciences 5 g 54 EUR

Curcumin

CB0346 Bio Basic 5g 58.7 EUR

Curcumin

A3335-100 ApexBio 100 mg 108 EUR

Curcumin

A3335-5.1 ApexBio 10 mM (in 1mL DMSO) 113 EUR

Curcumin

TB0283-0500 ChemNorm 4X25mg 268 EUR

Demethoxy curcumin

TBW00424 ChemNorm 20mg 186 EUR

Curcumin, pure, 98%

GP7022-10MG Glentham Life Sciences 10 mg 103 EUR

Curcumin, pure, 98%

GP7022-250MG Glentham Life Sciences 250 mg 390 EUR

Curcumin, pure, 98%

GP7022-50MG Glentham Life Sciences 50 mg 160 EUR

Curcumin, Curcuma longa (High Purity)

1850-10 Biovision 115 EUR

Curcumin, Curcuma longa (High Purity)

1850-50 Biovision 251 EUR
Besides these applications and activities, curcumin has been reported to be effective in many neurodegenerative diseases.
There are plenty of studies show-ing that curcumin can lead significant improvements in the pathological process of AD.
Despite many important positive effects, the therapeutic limitation of curcumin is its low solubility and bioavailabil-ity. New approaches are needed to solve this problem and many studies have focused different types of advanced nanoformulations.
This review summarizes the available scientific data, as reported by the most recent studies describing the treatment of Alzheimer’s Disease and sleep deprivation-related consequences.

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