Differential neuroprotective effect of curcuminoid formulations in aluminum chloride-induced Alzheimer's disease.

Alzheimer's disease (AD) is a slowly progressive brain degenerative disorder which gradually impairs memory, thinking, and ability to perform easy routine tasks. This degenerative disorder mainly targets the elderly people and has imposed an endemic burden on society. Hence, there is a crucial need to investigate the efficacious herbal pharmacotherapies that can effectively mitigate and prevent the pathological hallmarks of AD. The current study aims to explore the potential efficacy of curcuminoid-rich extract (CRE) and its ternary complex (TC). Experimental rodents were administered with AlCl3 (300 mg/kg) to induce AD and treated with rivastigmine, curcuminoid crude extract, CRE, and TC orally for three consecutive weeks. Neurobehavioral, biochemical, and histopathological studies were performed from the last week of the study period. The mRNA expression of different pathological biomarkers was estimated by RT-qPCR analysis. The results of the study suggested that CRE and TC significantly improved the behavioral, biochemical parameters and acetylcholinesterase inhibitory activity in treatment groups. Histological analysis was also carried out indicating that the neurodegenerative changes and neuronal loss were stabilized by CRE and TC supplementation. CRE and TC supplementation remarkably downregulated the interleukin-1α, tumor necrosis factor-α, interleukin-1ß, acetylcholinesterase, and ß-secretase pathological gene expression. Hence, it was concluded that CRE and TC may act as promising candidates in the prevention of AD via numerous underlying signaling pathways.

Cytokine preconditioning of engineered cartilage provides protection against interleukin-1 insult.

BACKGROUND: During osteoarthritis and following surgical procedures, the environment of the knee is rich in proinflammatory cytokines such as IL-1. Introduction of tissue-engineered cartilage constructs to a chemically harsh milieu may limit the functionality of the implanted tissue over long periods. A chemical preconditioning scheme (application of low doses of IL-1) was tested as a method to prepare developing engineered tissue to withstand exposure to a higher concentration of the cytokine, known to elicit proteolysis as well as rapid degeneration of cartilage. METHODS: Using an established juvenile bovine model system, engineered cartilage was preconditioned with low doses of IL-1α (0.1 ng/mL, 0.5 ng/mL, and 1.0 ng/mL) for 7 days before exposure to an insult dose (10 ng/mL). The time frame over which this protection is afforded was investigated by altering the amount of time between preconditioning and insult as well as the time following insult. To explore a potential mechanism for this protection, one set of constructs was preconditioned with CoCl2, a chemical inducer of hypoxia, before exposure to the IL-1α insult. Finally, we examined the translation of this preconditioning method to extend to clinically relevant adult, passaged chondrocytes from a preclinical canine model. RESULTS: Low doses of IL-1α (0.1 ng/mL and 0.5 ng/mL) protected against subsequent catabolic degradation by cytokine insult, preserving mechanical stiffness and biochemical composition. Regardless of amount of time between preconditioning scheme and insult, protection was afforded. In a similar manner, preconditioning with CoCl2 similarly allowed for mediation of catabolic damage by IL-1α. The effects of preconditioning on clinically relevant adult, passaged chondrocytes from a preclinical canine model followed the same trends with low-dose IL-1ß offering variable protection against insult. CONCLUSIONS: Chemical preconditioning schemes have the ability to protect engineered cartilage constructs from IL-1-induced catabolic degradation, offering potential modalities for therapeutic treatments.

A single injection of interleukin-1 induces reversible aqueous-tear deficiency, lacrimal gland inflammation, and acinar and ductal cell proliferation.

Emerging studies from our laboratory demonstrate that interleukin-1 (IL-1) family members play a major role in impairing lacrimal gland functions. Here we have extended our investigations to observe the effects of IL-1 on aqueous tear production, lacrimal gland secretion, lacrimal gland histology, and acinar and ductal cell proliferation. We demonstrate that a single injection of IL-1 into the lacrimal glands inhibited neurally- as well as agonist-induced protein secretion resulting in decreased tear output. Meanwhile, IL-1 injection induced a severe, but reversible (7-13 days), inflammatory response that led to destruction of lacrimal gland acinar epithelial cells. Finally, we demonstrate that as the inflammatory response subsided and lacrimal gland secretion and tear production returned to normal levels, there was increased proliferation of acinar and ductal epithelial cells. Our work uncovers novel effects of IL-1 on lacrimal gland functions and the potential regenerative capacity of the mouse lacrimal gland.

[The effect of interleukin-1alpha on intraocular pressure in rabbit eyes and its focal side effects].

OBJECTIVE: To investigate the efficiency of interleukin-1alpha on intraocular pressure reduction and its safety. METHODS: 35 New Zealand female rabbits were randomized into seven groups. In group-A, one eye was randomly selected to receive sub-conjunctival injection of 15 ng IL-1alpha, and in group B-D, one eye was injected intracamerally with IL-1alpha 1.5 ng, 15 ng and 40 ng respectively, and the other eye was injected intracamerally with equivalent volume of 0.1% PBS as control. In group-E, one eye was treated with 0.5% timolol eye drops and the other eye was given artificial tear. Groups F and G were treated as group D, and specifically in group-G, both eyes were given IL-1alpha. In group-A to D, the examination of tonometry, slit-lamp biomicroscopy and direct ophthalmoscope were taken before treatment and 24 hours after the treatment and were repeated everyday for 4 days. In group-E, tonometry was applied before treatment and 7 days after treatment. In group-F, aqueous humor of two eyes was aspirated for smear examination 24 and 48 hours after treatment, and corneal endothelium microscope and flash-ERG were done in group-G before and 30 to 40 hours after treatment, and then the eyes were enucleated for histology analysis. RESULTS: IOP of the eyes received IL-1alpha was decreased significantly compared with that of contralateral control eyes in group A to D (P < 0.05). Peaking time of IOP reduction was 72 - 96 hours after treatment, and IOP reduction was continued for over 96 hours. The IOP reduction efficiency in group C and D was more significant than those of group E (P < 0.05). No significant abnormal was found with the examinations of slit-lamp biomicroscopy, ophthalmoscope, corneal endothelium microscopy, flash-ERG, smear and histological observation, except for mild focal conjunctival congestion. CONCLUSION: Intraocular reduction were demonstrated with IL-1alpha treatment, charactered by its strong hypotensive effect, long duration and safety.