A Phase I, Open-label, Randomised, Single-centre, 2-way Crossover Bioequivalence Study Comparing 2 Formulations of Imeglimin After Single Oral Doses in Healthy Caucasian Subjects

This is an open-label assessment of the bioequivalence of two 500 mg-tablet formulations of imeglimin (Tablet A [reference product] and Tablet B [test product]), in at least 16 healthy Caucasian volunteers.

Start Date03 Sep 2018

Sponsor / Collaborator

Poxel SA

100 Clinical Results associated with SIRT1 x GSK-3β

100 Translational Medicine associated with SIRT1 x GSK-3β

0 Patents (Medical) associated with SIRT1 x GSK-3β

112

Literatures (Medical) associated with SIRT1 x GSK-3β

01 May 2025·International Journal of Biological Macromolecules

Functions of high glycemic index carbohydrates: Exploring the effect of amorphous rice starch digestibility on glycometabolism

Article

Author: Ha, Chuanzhi ; Sheng, Tao ; Zhu, Hui ; Wu, Yujie ; Yu, Zhenyu ; Mang, Lai ; Xiao, Shixun ; Zhou, Yibin

The digestive characteristics of amorphous starch in cooked rice have rarely been studied from a metabolic perspective. This study explores the effects of cooked rice starch on glycometabolism in rats to explore the role of high glycemic index (GI) carbohydrates in the daily diet. Utilizing X-ray diffraction and Fourier transform infrared spectroscopy allowed the structure of amorphous starch to be probed, while rats were subjected to a long-term pre-prandial gavage intervention (glucose as a positive control and normal saline as a negative control) to assess the effects of high GI carbohydrates on glucose tolerance, insulin sensitivity, and markers of glucose metabolism in skeletal muscle (SIRT1, PGC-1α, GSK-3β, GLUT4). Results showed that high-GI carbohydrates significantly enhanced systemic insulin sensitivity, glucose tolerance, and skeletal muscle glucose metabolism. Waxy rice starch (WRS), containing a high amylopectin content (98.57 %), was found to be particularly effective due to its high rapidly digestible starch (RDS) content (66.01 %) and a GI of 102 after cooked into an amorphous state. Consequently, it can be concluded that a long-term moderate intake of amorphous rice starch induces the body to increase insulin sensitivity and improve glycometabolism. These findings emphasize the functional characteristics of high-GI starchy foods, offering a more profound understanding of carbohydrate-based diets.

01 May 2025·Biomedicine & Pharmacotherapy

Combining vinpocetine or cocoa with levodopa, Coenzyme Q10 and vitamin B complex mitigates rotenone-induced Parkinson’s disease in rats: Impact on Nrf2/HO-1, NF-kB, AMPK/SIRT-1/Beclin-1, AKT/GSK-3β/CREB/BDNF and Apoptotic Pathways

Article

Author: Elsanhory, Heba M A ; Abbas, Ashwaq N ; Atwa, Ahmed M ; Hamdan, Amira M ; Abu-Elfotuh, Karema ; Alkhamali, Alanoud ; Gowifel, Ayah M H ; Abdelhakim, Khaled R ; Alharthi, Fatimah Ali ; Negm, Amira M ; Al-Rekabi, Mohammed D ; Hamdan, Ahmed M E ; Elshahat, Rehab M ; Darwish, Alshaymaa

There are no curative treatments for Parkinson's disease (PD), and current treatments focus on symptomatic management. This study aimed to investigate the beneficial effects of combining L-DOPA/Carbidopa with essential cofactors (vitamin (VIT) B complex and coenzyme Q10 (CoQ10)), alone or in conjunction with vinpocetine (VIN) or cocoa, as a potential strategy to enhance neuroprotection in rotenone (RT)-induced PD rat model, highlighting mechanistic insights into their underlying neuroprotective mechanisms and focusing on addressing oxidative stress, inflammation, autophagy, and apoptosis. These combinations were tested on adult male Wistar rats allocated into six groups. Group I received saline (normal control), while groups II-VI were injected with RT for 19 days to induce PD. Group II received RT alone, group III received daily oral L-DOPA/Carbidopa, and groups IV-VI received L-DOPA/Carbidopa with VIT B complex and CoQ10, either alone (Group IV) or combined with cocoa (Group V) or VIN (Group VI). These treatments markedly improved RT-induced perturbations in locomotor and cognitive outcomes; neurotransmitters' levels; oxidative stress (Nrf2/HO-1, MDA, INOS, SOD and TAC); inflammatory (NF-κB, TNF-α, IL-1β, GFAP and COX-2); neurotrophic (AKT/CREB/BDNF); apoptotic (BAX, caspase-3, AIF, and Bcl-2); and autophagic (AMPK/SIRT-1/Beclin-1) biomarkers; histopathological findings and tyrosine hydroxylase (TH) immunoexpression. Furthermore, the best outcomes were observed in cocoa and VIN combinations. These results indicated that combining L-DOPA with CoQ10 and VIT B complex in conjunction with either VIN or cocoa could provide a potential strategy for managing motor impairments and preventing neurodegeneration in PD. The interaction between key signaling pathways, including Nrf2/HO-1, NF-kB, AMPK/SIRT-1, and AKT/GSK-3β/CREB/BDNF, likely mediates this effect. However, further clinical validation is required to assess this approach's real-world applicability and therapeutic potential.

01 Mar 2025·Mitochondrion

Pyridoxal-5-phosphate mitigates age-related metabolic imbalances in the rat heart through the H2S/AKT/GSK3β signaling axis

Article

Author: Mys, Lidiia A ; Sagach, Vadym F ; Piven, Oksana O ; Balatskyi, Volodymyr V ; Denysova, Maiia V ; Strutynska, Nataliia A ; Luchkova, Alina Yu ; Dobrzyn, Pawel ; Strutynskyi, Vladyslav R ; Goshovska, Yulia V ; Korkach, Yuliia P ; B Strutynskyi, Ruslan

Pyridoxal-5-phosphate (PLP) enhances the synthesis of endogenous hydrogen sulfide, a potent regulator of cell metabolism. We used 24-month-old rats to investigate the PLP mitoprotective function in the aging heart. We demonstrated improvement of mitochondrial bioenergetic functions, inhibition of mPTP opening after PLP administration. Moreover, PLP treatment increased glucose consumption and utilization, decreased lipid transport into the cells, but increased fatty acid β-oxidation, providing sufficient energy. An ECG study showed a significant improvement in cardiac function in PLP-treated old rats. Our data suggest that PLP may exert its effect through the H₂S/AKT/GSK3β axis with further targeting of the Sirt1/PGC-1α signaling pathway.

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