RATIONALE: Alteration of the NAD metabolic pathway is proposed to be implicated in lipopolysaccharide (LPS)-induced neurotoxicity and mitochondrial dysfunction in neurodegenerative diseases. Apigenin, a naturally-occurring flavonoid, has been reported to maintain NAD levels and to preserve various metabolic functions.

OBJECTIVES: This study aimed to explore the effect of apigenin on mitochondrial SIRT3 activity as a mediator through which it could modulate mitochondrial quality control and to protect against intracerebrovascular ICV/LPS-induced neurotoxicity.

METHODS: Mice received apigenin (40 mg/kg; p.o) for 7 consecutive days. One hour after the last dose, LPS (12 µg/kg, icv) was administered.

RESULTS: Apigenin robustly guarded against neuronal degenerative changes and maintained a normal count of intact neurons in mice hippocampi. Consequently, it inhibited the deleterious effect of LPS on cognitive functions. Apigenin was effective in preserving the NAD/NADH ratio to boost mitochondrial sirtuin-3 (SIRT3), activity, and ATP production. It conserved normal mitochondrial features via induction of the master regulator of mitochondrial biogenesis, peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α), along with mitochondrial transcription factor A (TFAM) and the fusion proteins, mitofusin 2 (MFN2), and optic atrophy-1 (OPA1). Furthermore, it increased phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1) and parkin expression as well as the microtubule-associated protein 1 light chain 3 II/I ratio (LC3II/I) to induce degradation of unhealthy mitochondria via mitophagy.

CONCLUSIONS: These observations reveal the marked neuroprotective potential of apigenin against LPS-induced neurotoxicity through inhibition of NAD depletion and activation of SIRT3 to maintain adequate mitochondrial homeostasis and function.

Nowadays, integrating large scale renewable energy sources, like solar PV parks, raises challenges for Load Frequency Controllers (LFC). The output of PV varies continuously, which requires a robust LFC deals
logically without continuous tuning and parameters optimization. In this paper, a fuzzy logic controller (FLC) is proposed to act as the main LFC instead of the traditional proportional–integral–derivative (PID) controller. The dynamic performance of FLC is enhanced by optimizing its parameters for different cost functions using particle swarm optimization technique (PSO). Another two FLCs will be added to PV system to act as an output controller instead of maximum power point tracker (MPPT) to enhance the overall system performance. To increase system reliability, a fast active power source called redox flow battery (RFB) is added in the proposed model as a frequency stabilizer. RFB can deeply discharge up to 90% with theoretically limitless number of duty cycles and has fast time response for severe load changes. The
importance of these proposed controllers side by side with RFB is to avoid disconnecting solar parks during
heavy cloudy days while preserving on maximizing its output during these periods. The superiority of the proposed FLC is examined by evaluating its performance compared to another control approach called PID-P (PID controller with P controller in the inner feedback loop). Finally, a comprehensive sensitivity analysis is also presented to investigate the controller robustness for extensive changes in power system parameters and loading.