Tocotrienol-Rich Fraction Ameliorates the Aluminium Chloride-Induced Neurovascular Dysfunction-Associated Vascular Dementia in Rats.

Neurovascular dysfunction leads to the second most common type of dementia, i.e., vascular dementia (VaD). Toxic metals, such as aluminium, increase the risk of neurovascular dysfunction-associated VaD. Hence, we hypothesized that a natural antioxidant derived from palm oil, i.e., tocotrienol-rich fraction (TRF), can attenuate the aluminium chloride (AlCl3)-induced VaD in rats. Rats were induced with AlCl3 (150 mg/kg) intraperitoneally for seven days followed by TRF treatment for twenty-one days. The elevated plus maze test was performed for memory assessment. Serum nitrite and plasma myeloperoxidase (MPO) levels were measured as biomarkers for endothelial dysfunction and small vessel disease determination. Thiobarbituric acid reactive substance (TBARS) was determined as brain oxidative stress marker. Platelet-derived growth factor-C (PDGF-C) expression in the hippocampus was identified using immunohistochemistry for detecting the neovascularisation process. AlCl3 showed a significant decrease in memory and serum nitrite levels, while MPO and TBARS levels were increased; moreover, PDGF-C was not expressed in the hippocampus. However, TRF treatment significantly improved memory, increased serum nitrite, decreased MPO and TBARS, and expressed PDGF-C in hippocampus. Thus, the results imply that TRF reduces brain oxidative stress, improves endothelial function, facilitates hippocampus PDGF-C expression for neovascularisation process, protects neurons, and improves memory in neurovascular dysfunction-associated VaD rats.

Palm Oil Derived Tocotrienol-Rich Fraction Attenuates Vascular Dementia in Type 2 Diabetic Rats.

Vascular dementia (VaD) is a serious global health issue and type 2 diabetes mellitus (T2DM) patients are at higher risk. Palm oil tocotrienol-rich fraction (TRF) exhibits neuroprotective properties; however, its effect on VaD is not reported. Hence, we evaluated TRF effectiveness in T2DM-induced VaD rats. Rats were given a single dose of streptozotocin (STZ) and nicotinamide (NA) to develop T2DM. Seven days later, diabetic rats were given TRF doses of 30, 60, and 120 mg/kg orally for 21 days. The Morris water maze (MWM) test was performed for memory assessment. Biochemical parameters such as blood glucose, plasma homocysteine (HCY) level, acetylcholinesterase (AChE) activity, reduced glutathione (GSH), superoxide dismutase (SOD) level, and histopathological changes in brain hippocampus and immunohistochemistry for platelet-derived growth factor-C (PDGF-C) expression were evaluated. VaD rats had significantly reduced memory, higher plasma HCY, increased AChE activity, and decreased GSH and SOD levels. However, treatment with TRF significantly attenuated the biochemical parameters and prevented memory loss. Moreover, histopathological changes were attenuated and there was increased PDGF-C expression in the hippocampus of VaD rats treated with TRF, indicating neuroprotective action. In conclusion, this research paves the way for future studies and benefits in understanding the potential effects of TRF in VaD rats.

Physiological and Pathophysiological Role of Cysteine Metabolism in Human Metabolic Syndrome.

Cysteine is one of the major intermediate products of cellular amino-acid metabolism. It is a semi-essential amino acid for protein synthesis. Besides, it is also employed in the regulation of major endogenous anti-oxidant molecule i.e., reduced glutathione (GSH). Further, it is a precursor of multiple sulfur-containing molecules like hydrogen sulfide, lanthionine, taurine, coenzyme A and biotin. It is also one of the key molecules for post-translational modifications of various cellular proteins. In physiological conditions, it is employed in the sulfhydration process and plays a key role in the physiology modification of the inflammatory process in various organs, including the neurological system. The catabolism of cysteine is regulated by cysteine dioxygenase enzyme activity. The dysregulated conditions of cysteine and cysteine-associated hydrogen sulfide metabolism are widely employed in the acceleration of the neurodegenerative process. Moreover, the upregulation of cysteine and hydrogen sulfide synthesis occurs via the reverse trans-sulfuration process. This process helps to manage the worsening of a pathological condition of a cellular system. Moreover, it is also employed in the accumulation of homocysteine contents. Further, both cysteine and homocysteine molecules are widely accepted as biomarkers for various types of diseases. Therefore, the targets involved in the regulation of cysteine have been considered as valid targets to treat various disorders like cardiac disease, ischemic stroke, diabetes, cancer, and renal dysfunction.

Chemosensitivity assessments of curdlan-doped smart nanocomposites containing erlotinib HCl.

Curdlan (CN)-doped montmorillonite/poly(N-isopropylacrylamide-co-N,N'-methylene-bis-acrylamide) [CN/MT/P(NIPA-co-MBA)] smart nanocomposites (NCs) were developed for efficient erlotinib HCl (ERL) delivery to lung cancer cells. The placebo NCs demonstrated excellent biodegradability, pH/thermo-responsive swelling profiles and declined molar mass (M¯c) between the crosslinks with increasing temperature. The XRD, FTIR, DSC, TGA, and SEM analyses revealed the architectural chemistry of these NC scaffolds. The NCs loaded with ERL (F-1-F-3) displayed acceptable diameter (734-1120 nm) and zeta potential (+1.16 to -11.17 mV), outstanding drug entrapping capability (DEE, 78-99%) and sustained biphasic ERL elution patterns (Q8h, 53-91%). The ERL release kinetics of the optimal matrices (F-3) obeyed Higuchi model and their transport occurred through anomalous diffusion. The mucin adsorption behaviour of these matrices followed Freudlich isotherms. As compared to pure ERL, the formulation (F-3) displayed an improved anti-proliferative potential and induced apoptosis more effectively on A549 cells. Thus, the CN-doped smart NCs could be utilized as promising drug-cargoes for lung cancer therapy.

Actividad inmunomoduladora de la Bauhinia racemosa Lam / Immunomodulatory activity of Bauhinia Racemosa Lam

Objetivo: Evaluar la actividad del extracto metanólico de la corteza del tallo de la Bauhinia Racemosa Lam en ratones albinos suizos. Material y métodos: La inmunidad humoral específica fue evaluada mediante el ensayo de hemaglutinación de antincuerpos ( H.A. Titer) y la inmunidad no específica fue evaluada mediante el test de aclaramiento de carbono y el test de adhesión de neutrofilos. Resultados: se encontró que el extracto del tallo de Bauhinia racemosa (MEBR) era efectivo para el incremento del H.A Titer. La respuesta primaria y secundaria no mostró un ascenso significativo en el H.A Titer en el grupo con estado inmune normal al compararlo con el grupo control. Sin embargo, en el grupo de inmunodeprimidos donde la inmunidad estaba suprimida mediante ciclofosfamida se observó un aumento significativo en el H.A Titer (p<0.01) a dosis de 200mg/kg cuando se comparaba con la ciclofosfamida. El extracto del tallo de Bauhinia racemosa mostró un aumento significativo (p<0,05) en la actividad fagocítica a dosis de 200mg/kg (p.o) en el test de aclaramiento de carbón. En el test de adhesión de neutrófilos el extracto del tallo de Bauhinia racemosa mostró un aumento significativo (p<0,01) del porcentaje de adhesión de neutrófilos a dosis de 200mg/kg (p.o) Conclusión: El presente estudio sostiene al MEBR como un prometedor agente inmunomodulador(AU)

Aim: To evaluate immunomodulatory activity of methanolic extract of stem bark of Bauhinia racemosa Lam swiss albino mice. Material and Methods: The specific humoral immunity was assessed by performing hemagglutinating antibody titer (H.A.Titer) and the non-specific immunity was assessed by performing carbon clearance test and neutrophil adhesion test. Results: The methanolic extract of stem bark of Bauhinia Racemosa (MEBR) was found effective in increasing the H.A.Titer. Primary and secondary antibody response showed no significant rise in H.A.Titer in normal immune status group when compared with control group, whereas in immunosupressed group, where immunity was suppressed by cyclophosphamide, significant rise in H.A.Titer (p<0.01) was observed at dose of 200 mg/kg (p.o.) when compared with cyclophosphamide. MEBR showed significant increase (p<0.05) in phagocytic activity at dose of 200 mg/kg (p.o.) in carbon clearance test. In neutrophil adhesion test MEBR showed significant (p<0.01) rise in percentage neutrophil adhesion at dose of 200 mg/kg (p.o.). Conclusion: Present study, therefore, reveals that MEBR) holds promise as immunomodulatory agent(AU)