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Combination Therapy for the Treatment of Alzheimer's Disease: Recent Progress and Future Prospects

Shirbhate E, Patel VK, Tiwari P, Kore R, Veerasamy R, Mishra A, et al.

Curr Top Med Chem, 2022;22(22):1849-1867.
PMID: 36082857 DOI: 10.2174/1568026622666220907114443

BACKGROUND: The management of Alzheimer's disease is challenging due to its complexity. However, the currently approved and marketed treatments for this neurodegenerative disorder revolves around cholinesterase inhibitors, glutamate regulators, or the combination of these agents. Despite the prompt assurance of many new drugs, several agents were unsuccessful, especially in phase II or III trials, not meeting efficacy endpoints.
OBJECTIVE: The execution of effective treatment approaches through further trials investigating a rational combination of agents is necessitude for Alzheimer's disease.
METHODS: For this review, more than 248 relevant scientific papers were considered from a variety of databases (Scopus, Web of Science, Google Scholar, ScienceDirect, and PubMed) using the keywords Alzheimer's disease, amyloid-β, combination therapies, cholinesterase inhibitors, dementia, glutamate regulators, AD hypothesis.
RESULT AND DISCUSSION: The researcher's intent is to either develop a disease-modifying therapeutic means for aiming in the early phases of dementia and/or optimize the available symptomatic treatments principally committed to the more advanced stages of Alzheimer's. Since Alzheimer's possesses multifactorial pathogenesis, designing a multimodal therapeutic intervention for targeting different pathological processes of dementia may appear to be the most practical method to alter the course of disease progression.
CONCLUSION: The combination approach may even allow for providing individual agents in lower doses, with reducible costs and side effects. Numerous studies on combination therapy predicted better clinical efficacy than monotherapy. The literature review highlights the major clinical studies (both symptomatic and disease-modifying) conducted in the past decade on combination therapy to combat cognitive disorder.

Matched MeSH terms: Glutamates/therapeutic use
Prediction of tea theanine content using near-infrared spectroscopy and flower pollination algorithm

Ong P, Chen S, Tsai CY, Chuang YK

Spectrochim Acta A Mol Biomol Spectrosc, 2021 Jul 05;255:119657.
PMID: 33744842 DOI: 10.1016/j.saa.2021.119657

In this study, near-infrared (NIR) spectroscopy was exploited for non-destructive determination of theanine content of oolong tea. The NIR spectral data (400-2500 nm) were correlated with the theanine level of 161 tea samples using partial least squares regression (PLSR) with different wavelengths selection methods, including the regression coefficient-based selection, uninformative variable elimination, variable importance in projection, selectivity ratio and flower pollination algorithm (FPA). The potential of using the FPA to select the discriminative wavelengths for PLSR was examined for the first time. The analysis showed that the PLSR with FPA method achieved better predictive results than the PLSR with full spectrum (PLSR-full). The developed simplified model using on FPA based on 12 latent variables and 89 selected wavelengths produced R-squared (R2) value and root mean squared error (RMSE) of 0.9542, 0.8794 and 0.2045, 0.3219 for calibration and prediction, respectively. For PLSR-full, the R2 values of 0.9068, 0.8412 and RMSEs of 0.2916, 0.3693, were achieved for calibration and prediction. Also, the optimized model using FPA outperformed other wavelengths selection methods considered in this study. The obtained results indicated the feasibility of FPA to improve the predictability of the PLSR and reduce the model complexity. The nonlinear regression models of support vector machine regression and Gaussian process regression (GPR) were further utilized to evaluate the superiority of using the FPA in the wavelength selection. The results demonstrated that utilizing the wavelength selection method of FPA and nonlinear regression model of GPR could improve the predictive performance.

Matched MeSH terms: Glutamates
Fulltext Nutritional composition and amino acid profile of a sub-tropical red seaweed Gelidium pusillum collected from St. Martin’s Island, Bangladesh

Siddique, M.A.M., Khan, M.S.K., Bhuiyan, M.K.A.

International Food Research Journal, 2013;20(5):2287-2292.
MyJurnal

Nutritional fact study has prime importance to make the species edible and commercially viable to the food consumers. The proximate chemical composition and amino acid profile of Gelidium pusillum were studied to understand the nutritional status. The red seaweed Gelidium pusillum was rich in dietary fibre (24.74 ± 1.05%), lipid (2.16 ± 0.61%) and ash content (21.15 ± 0.74%). The mean protein content (11.31 ± 1.02% DW) was within the range of 10-47% for green and red seaweeds and this range was higher than Gracilaria cornea (5.47% DW), Gracilaria changgi (6.90% DW) and Eucheuma cottonii (9.76% DW). Gelidium pusillum was found to contained all the essential amino acids, which accounted for 52.08% of the total amino acids. Tyrosine (26.2 mg g-1 protein), methionine (15.8 mg g-1 protein) and Lysine (48.3 mg g-1 protein) were the limiting amino acid of Gelidium pusillum. However, the levels of other essential amino acids were above the FAO/WHO requirement pattern (EAA score ranged from 1.14 to 1.62). Aspartic and glutamic acids constituted a substantial amount of the total amino acids (24.68% of total amino acid). The result from this study suggested that Gelidium pusillum could be utilized as a healthy food item for human consumption.

Matched MeSH terms: Glutamates
Fulltext Characterisation of the ability of globulins from legume seeds to produce cocoa specific aroma

Rashidah, S., Jinap, S., Nazamid, S., Jamilah, B.

International Food Research Journal, 2007;14(2):103-114.
MyJurnal

This study was carried out to extract and compare the characteristic ability of globulins from cottonseed, alfalfa seed, pea seed, mung bean and French bean with cocoa seeds to produce cocoa-specific aroma precursors. The extracted globulins were compared through SDS PAGE, amino acid and oligopeptide profiles. A very low recovery was obtained during globulin extraction from different seeds ranging from 0.5% to 2.7%. Cottonseed produced the highest total protein (13.90 mg/g), followed by cocoa seed (11.91 mg/g), whereas alfalfa seed, mung bean, pea seed and French bean produced 7.86, 4.77, 4.59 and 3.89 mg/g respectively. Two distinctive bands of 51.1 and 33.0 kDa were observed for cocoa vicilin-class globulin (VCG) from SDS PAGE. More than three bands were shown for other seed globulins. Comparative HPLC analyses of the obtained peptide mixtures revealed different and complex patterns of predominantly hydrophobic peptides. A similar high content of amides (glutamic acids-glutamine, aspartic acid- asparagine and arginine) and low concentrations of lysine were observed in all seeds globulin.

Matched MeSH terms: Glutamates
Fulltext Antinociceptive activities of a novel diarylpentanoid analogue, 2-benzoyl-6-(3-bromo-4-hydroxybenzylidene)cyclohexen-1-ol, and its possible mechanisms of action in mice

Ong HM, Azmi AFA, Leong SW, Abas F, Perimal EK, Farouk AAO, et al.

Sci Rep, 2021 12 16;11(1):24121.
PMID: 34916536 DOI: 10.1038/s41598-021-02961-1

A novel synthetic compound from the 2-benzoyl-6-benzylidenecyclohexanone analogue, namely 2-benzoyl-6-(3-bromo-4-hydroxybenzylidene)cyclohexen-1-ol (BBHC), showed pronounced nitric oxide inhibition in IFN-γ/LPS-induced RAW 264.7 cells. Based on this previous finding, our present study aimed to investigate the antinociceptive effects of BBHC via chemical and thermal stimuli in vivo. The investigation of the antinociceptive activity of BBHC (0.1, 0.3, 1.0 and 3.0 mg/kg, i.p.) was initiated with 3 preliminary screening tests, then BBHC was subjected to investigate its possible involvement with excitatory neurotransmitters and opioid receptors. The potential acute toxicity of BBHC administration was also studied. Administration of BBHC significantly inhibited acetic acid-induced abdominal constrictions, formalin-induced paw licking activity and developed notable increment in the latency time. BBHC's ability to suppress capsaicin- and glutamate-induced paw licking activities, as well as to antagonise the effect of naloxone, had indicated the possible involvement of its antinociception with TRPV1, glutamate and opioid receptors, respectively. The antinociceptive activities of BBHC was not related to any sedative action and no evidence of acute toxic effect was detected. The present study showed that BBHC possessed significant peripheral and central antinociceptive activities via chemical- and thermal-induced nociceptive murine models without any locomotor alteration and acute toxicity.

Matched MeSH terms: Glutamates