Jaleel Kizhakkayil

Background: Exercise training positively modulates myokine secretion and improves glucose metabolism. Herein, we analyzed the effect of moderate-intensity training, detraining, and Protocatechuic Acid (PCA) supplementation on myokine secretions and regulation of insulin-signaling pathways. Methods: A five-arm study was conducted on 47 healthy male Wistar rats, trained at a moderate intensity level for four weeks (T0-T4). Animals were randomly classified into groups according to PCA supplementation and exercise durations: four weeks of Aerobic Training with or without PCA (AT4, AT4-PCA), eight weeks of Aerobic Training with or without PCA (AT8, AT8-PCA), and PCA Vehicle Control (VC). The animals were followed up until week 12 (T12). We decapitated six rats at T0 and T4, four rats per group at T8, and three rats per group at T12. Myokines (IGF-1, IL-6, FGF-21, myostatin, and irisin) were analyzed with ELISA. Western blot analysis measured protein expression of insulin-signaling pathways and GLUT-4 in the gastrocnemius muscle. Results: The IL-6 levels increased significantly (p < 0.01) with 8-week training in AT8 by 34% and AT8-PCA by 32%, compared to groups trained for only 4 weeks (AT4 and AT4-PCA). Similarly, the PI3K, and GLUT-4 expression improved in AT8 and AT8-PCA at T8. Training for 4 weeks improved IGF-1 levels, but a further 14% improvement was observed with 8-week training in AT8 at T8. Myostatin level significantly dropped by 27% even with 4-week training (p < 0.001). However, detraining increased the myostatin levels in all groups, but in AT8-PCA with PCA dose, myostatin reduced by 11% compared to AT8 at T12. PCA supplementation reduced the FGF-21 levels by 54% during detraining at T12 in AT8-PCA compared to AT8. However, the irisin level did not change markedly in any group. Conclusions: Physical training (with and without PCA) modulates myokine production and improves glucose metabolism, but the benefits are lost after detraining.

Exercise training positively regulates glucose metabolism. This study investigated the impact of training and detraining on glucose metabolism, lipid profiles, and liver enzymes. Twenty-six rats completed an initial 4-week moderate-intense training (T0–T4). Then, the animals were randomly assigned to two groups at the end of week 4: AT4: detraining for 8 weeks; AT8: training for 8 weeks and 4-week detraining. Six animals were sacrificed at T0 and T4, four animals/group at T8, and three/group at T12. The study continued for 12 weeks, and all parameters were assessed at T0, T4, T8, and T12. IPGTT significantly improved after 4 weeks of training (p < 0.01) and was further reduced in AT8 at T8. In AT8, 8-week training significantly reduced total cholesterol at T4 and T12 vs. T0 (p < 0.05), LDL at T4, T8, and T12 vs. T0 (p < 0.01), ALP at T8, T12 vs. T0 (p < 0.01), and increased HDL at T8 and ALT at T8 and T12 vs. T0 (p < 0.05). Triglycerides and hexokinase activity increased significantly at T4 and T8 (p < 0.05) and then decreased at T12 in AT8. Pyruvate and glycogen increased at T12 in AT8 vs. AT4. Eight-week training improved LPL and ATGL expressions. Training positively modulated insulin, glucose metabolism, and lipid profiles, but detraining reduced the benefits associated with the initial training.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the selective degeneration of dopaminergic neurons in the substantia nigra pars compacta resulting in an irreversible and a debilitating motor dysfunction. Though both genetic and idiopathic factors are implicated in the disease etiology, idiopathic PD comprise the majority of clinical cases and is caused by exposure to environmental toxicants and oxidative stress. Fyn kinase activation has been identified as an early molecular signaling event that primes neuroinflammatory and neurodegenerative events associated with dopaminergic cell death. However, the upstream regulator of Fyn activation remains unidentified. We investigated whether the lipid and tyrosine phosphatase PTEN (Phosphatase and Tensin homolog deleted on chromosome 10) could be the upstream regulator of Fyn activation in PD models as PTEN has been previously reported to contribute to Parkinsonian pathology. Our findings, using bioluminescence resonance energy transfer (BRET) and immunoblotting, indicate for the first time that PTEN is a critical early stress sensor in response to oxidative stress and neurotoxicants in in vitro models of PD. Pharmacological attenuation of PTEN activity rescues dopaminergic neurons from neurotoxicant-induced cytotoxicity by modulating Fyn kinase activation. Our findings also identify PTEN’s novel roles in contributing to mitochondrial dysfunction which contribute to neurodegenerative processes. Interestingly, we found that PTEN positively regulates interleukin-1β (IL-1β) and the transcription of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Taken together, we have identified PTEN as a disease course altering pharmacological target that may be further validated for the development of novel therapeutic strategies targeting PD. Graphical Abstract

Diabetes mellitus is a public health concern, affecting 10.5% of the population. Protocatechuic acid (PCA), a polyphenol, exerts beneficial effects on insulin resistance and diabetes. This study investigated the role of PCA in improving insulin resistance and the crosstalk between muscle with liver and adipose tissue. C2C12 myotubes received four treatments: Control, PCA, insulin resistance (IR), and IR-PCA. Conditioned media from C2C12 was used to incubate HepG2 and 3T3-L1 adipocytes. The impact of PCA was analyzed on glucose uptake and signaling pathways. PCA (80 µM) significantly enhanced glucose uptake in C2C12, HepG2, and 3T3-L1 adipocytes (p < 0.05). In C2C12, PCA significantly elevated GLUT-4, IRS-1, IRS-2, PPAR-γ, P-AMPK, and P-Akt vs. Control (p ≤ 0.05), and modulated pathways in IR-PCA. In HepG2, PPAR-γ and P-Akt increased significantly in Control (CM) vs. No CM, and PCA dose upregulated PPAR-γ, P-AMPK, and P-AKT (p < 0.05). In the 3T3-L1 adipocytes, PI3K and GLUT-4 expression was elevated in PCA (CM) vs. No CM. A significant elevation of IRS-1, GLUT-4, and P-AMPK was observed in IR-PCA vs. IR (p ≤ 0.001). Herein, PCA strengthens insulin signaling by activating key proteins of that pathway and regulating glucose uptake. Further, conditioned media modulated crosstalk between muscle with liver and adipose tissue, thus regulating glucose metabolism.

Utilising major waste products from the food industry can have both a great environmental impact and be a means to improve consumer health. Date seed is a food industry byproduct that has been proven to have high nutritional value. The aim of this work was to measure the total polyphenolic content (TPC), flavonoids, and antioxidant activity of the seeds of six date fruit varieties, Fard, Khalas, Khinaizi, Sukkary, Shaham, and Zahidi, and to use those seeds to enhance the antioxidant value of cookies by partially substituting flour with ground date seed. Date seed powder (DSP) was extracted at three levels of sample to solvent ratio (5:1, 10:1 and 15:1 mg/mL). Cookies were prepared using three substitution levels of wheat flour (2.5, 5.0, and 7.5%, w/w) by DSP and two types of flour (white and whole wheat), and were baked at two different temperatures, 180 and 200 °C. The composite cookies were found to contain a significant amount of TPC and flavonoids, and showed increased antioxidant activity compared with the control samples.

Moringa peregrina (Forssk.) Fiori. is a native desert tree growing in United Arab Emirates (UAE). The plant is being cultivated in many parts of UAE, owing to its uses in traditional medicinal and food systems. In the present study bioactivities of cultivated M. peregrina species samples are evaluated with cytotoxic studies in the human breast cancer cell line (MCF-7) and human colon adenocarcinoma cell line (Caco-2). Different extracts with hexane, chloroform, acetone and methanol were prepared from tubers, leaves and stem of M. peregrina for estimating their antioxidant contents and anticancer activities. The study was performed at different concentrations and all the extracts showed dose-depended response on both the cell lines. Among the extracts tested, the chloroform extract of stem showed remarkable anti-proliferative/cell death activity (IC₅₀ = 45.53 µg/mL of 48 h incubation and 33.32 µg/mL of 72 h incubation) on MCF-7 cell lines. Whereas the same extract showed comparatively less activity (IC₅₀ = 93.75 µg/mL of 48 h incubation and 87.76 µg/mL of 72 h incubation) on Caco-2 cell lines. The anti-proliferative effect of leaf extract with chloroform showed a drastic change in cell viability from 48 to 72 h incubation, in MCF-7 cells 220 to 87.5 µg/mL and in Caco-2 cells 500.9 to 72.9 µg/mL, respectively. Moreover, less than 200 µg/mL of IC₅₀ values reported in hexane extracts of tubers (188.6 µg/mL for 48 h and 164.3 µg/mL for 72 h), acetone extracts of tubers (167.4 µg/mL for 72 h) and acetone extracts of stem (171.5 µg/mL for 48 h and 101.7 µg/mL for 72 h) on MCF-7 cells. PARP (Poly (ADP-ribose) polymerase) cleavage assay and DNA fragmentation assay performed to understand the cause of cell death. Treatment of extract on the normal fibroblast cell line required more concentration for cytotoxicity compared to the treatment on the cancer cells. This ability of the extract proved the anti-cancer property of the M. peregrina extract from the stem, tuber and leaves. The information provided in the present study enables further studies on the isolation and characterization of an anticancer molecule from the tubers of M. peregrina.