Alpha-pine self-emulsifying nano formulation attenuates rotenone and trichloroethylene-induced dopaminergic loss.

AIM: The current investigation's goals are to pharmacologically evaluate the neurotherapeutic role of the bioactive compound Alpha Pinene (ALP)-loaded Self-emulsifying nano-formulation (SENF) in neurotoxin (Rotenone and the Industrial Solvent Trichloroethylene)- induced dopaminergic loss. It is believed that these models simulate important aspects of the molecular pathogenesis of Parkinson's disease. MATERIAL AND METHODS: The ALP-nano-formulation's anti-Parkinson's activity was compared to ALP suspension in Wistar rats after rotenone and trichloro ethylene-induced dopaminergic loss. Neurobehavioral and motor performances were measured on the 14th, 21st, and 28th day in the rotenone model. However, in the trichloroethylene model, it was measured from the 4th to the 8th week. RESULTS: Significant neurobehavioral improvement has been found in ALP-SENF treated animals then untreated and animals treated with plain ALP suspension. Furthermore, biochemical tests reveal marked expression of catalase, glutathione, and superoxide dismutase, which significantly combat the (Oxidative stress) OS-induced neurodegeneration. CONCLUSION: The antioxidant effect of ALP-SENF likely includes free radicals neutralization and the activation of enzymes associated with antioxidant activity, leading to the enhancement of neurobehavioral abnormalities caused by rotenone and trichloroethylene.

Formulation and Evaluation of α-Pinene Loaded Self-emulsifying Nanoformulation for In-Vivo Anti-Parkinson's Activity.

AIM: The present study was aimed to developed and optimize the self-nano emulsifying drug delivery system of α-pinene (ALP-SNEDDS) and evaluate its in-vivo anti-Parkinson's activity. BACKGROUND: Different lipid-based drug delivery technologies have been researched to upgrade drug bioavailability and expand their clinical adequacy upon oral administration. Self-emulsifying drug delivery systems (SEDDS) have pulled in developing the interest specifically for self nano emulsifying drug delivery systems (SNEDDS). OBJECTIVE: The present work was attempted to improve the bioavailability of the ALP by defining the role of self-nano emulsifying formulations for its neuroprotective effect. METHODS: Miscibility of the ALP was estimated in various excipient components to select the optimized combination. Self-nano emulsification, thermodynamic stability, the effect of dilution on robustness, optical clarity, viscosity, and conductivity tests were performed. The in-vivo anti-Parkinson's activity of the ALP-SNEDDS formulations were done using Pilocarpine antagonism induced Parkinsonism in rodents. Behavioral tests like tremulous jaw movements, body temperature, salivation, and lacrimation are performed. RESULTS: Two optimized formulations, composed of Anise oil, Tween 80, and Transcutol-HP of Oil: Smix ratio (4:6 and 3:7) were selected. The Smix ratio for both the formulation was 2:1. The particle size was found to consistent with the increase in dilution. The mean negative zeta potential of the formulations was found to be increased with an increase in dilution. The TEM images of the formulations revealed spherical shape of the droplet. The in-vitro drug release profile was found to be significant as compared to plain ALP suspension. CONCLUSION: The results of in-vivo studies indicate that nanosizing and enhanced solubilization of oral ALP-SNEDDS formulations significantly improved the behavioral activities compared to plain ALP suspension.

Neuroprotective effect of α-pinene self-emulsifying nanoformulation against 6-OHDA induced neurotoxicity on human SH-SY5Y cells and its in vivo validation for anti-Parkinson's effect.

Oxidative stress (OS) is involved in the multifaceted pathogenic paradigm of neurodegenerative diseases like Parkinson's disease (PD). Monoterpenes like α-pinene (ALP) is considered to be a therapeutically potent antioxidant agent able to attenuate and scavenge various reactive oxygen species and reactive nitrogen species. The present study aimed to evaluate the in vitro and in vivo neuroprotective effect of α-pinene self-emulsifying nanoformulation (ALP-SENF) for PD. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay was done to evaluate the neurotoxic dose of the ALP-SENF; however, the neuroprotective effect was assessed by 6-hydroxydopamine (6-OHDA) induced neurotoxicity model on SH-SY5Y taking NAC (N-acetyl-l-cysteine) as standard. The in vivo anti-Parkinson's activity of the ALP-SENF was compared with that of the plain ALP suspension by using reserpine antagonism and haloperidol-induced Parkinsonism model in rats. Various behavioral tests and biochemical antioxidant enzymes were estimated. The in vitro results revealed that treatment with ALP-SENF at a concentration of 100 and 200 µM was found to show significant neuronal SH-SY5Y cell viability against 50 µM 6-OHDA. ALP-SENF treated animals have seen significant neurobehavioral improvement. Furthermore, the levels of antioxidative enzymes in biochemical test reveals a marked enhancement in the expression of antioxidant enzymes that significantly attenuated the OS induced neurodegeneration. Due to the mechanisms of their antioxidant action, it was probably due to the scavenging of free radicals and the expression of antioxidant enzymes. It also improved neurobehavioral changes induced by reserpine and haloperidol.

Bioactive Loaded Lipid-based Nanostructures: A Novel Insight for Age-related Neurodegeneration.

Substantial affirmation suggested that oxidative stress remains an impelling target, contributing to initiate and exacerbate the multiple neurological complications in age-related neurodegeneration (ARN). Factors including gene and environmental toxins are now becoming the most threatening cause of oxidative stress, which leads to mitochondrial dysfunction of the neurons that ultimately causes permanent loss of their functionality. Clinical trials on antioxidants are still in the pipeline to access them as a potential therapeutic class. But this raised the generosity for not only to investigate the module of the antioxidant mechanism but also to justify the drug delivery and dose regimen. Biological barriers, predominantly, Blood-brain barrier (BBB) and rapid firstpass metabolism, are some of the potential obstacles for the effective targeting of the therapeutic agent. Bioactive drugs with antioxidant capacity, loaded with lipid-based Nano career system have revealed to be a novel therapeutic intervention for ARN. The review will deal with the comprehensive state-of-art methodology for the delivery of bioactive loaded lipid Nanocarriers to treat neurodegeneration. A systematic analysis of published reports will help the researchers to understand the role of natural compound loaded Nanoengineered system in the field of ARN as a potential Nano therapeutic intervention.