Evaluation of In Vivo Efficacy of Aqueous Extract of Aerial Parts of Cynodon dactylon in Rats with Simultaneous Type 2 Diabetes and Hypertension

Bone marrow-derived multipotent stromal cells (BMMSCs) represent an attractive therapeutic modality for cell therapy in type 2 diabetes mellitus (T2DM)-associated complications. T2DM changes the bone marrow environment; however, its effects on BMMSC properties remain unclear. The present study aimed at investigating select functions and differentiation of BMMSCs harvested from the T2DM microenvironment as potential candidates for regenerative medicine. BMMSCs were obtained from Zucker diabetic fatty (ZDF; an obese-T2DM model) rats and their lean littermates (ZL; controls), and cultured under normoglycemic conditions. The BMMSCs derived from ZDF animals were fewer in number, with limited clonogenicity (by 2-fold), adhesion (by 2.9-fold), proliferation (by 50%), migration capability (by 25%), and increased apoptosis rate (by 2.5-fold) compared to their ZL counterparts. Compared to the cultured ZL-BMMSCs, the ZDF-BMMSCs exhibited (i) enhanced adipogenic differentiation (increased number of lipid droplets by 2-fold; upregulation of the Pparg, AdipoQ, and Fabp genes), possibly due to having been primed to undergo such differentiation in vivo prior to cell isolation, and (ii) different angiogenesis-related gene expression in vitro and decreased proangiogenic potential after transplantation in nude mice. These results provided evidence that the T2DM environment impairs BMMSC expansion and select functions pertinent to their efficacy when used in autologous cell therapies.

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In-vivo anti-inflammatory activity and safety assessment of the aqueous extract of Algerian Erica arborea L. (Ericaceae) aerial parts

Journal of Ethnopharmacology ◽

10.1016/j.jep.2021.113881 ◽

2021 ◽

Vol 271 ◽

pp. 113881

Author(s):

Djouher Amroun ◽

Meriem Hamoudi ◽

Seddik Khennouf ◽

Sabrina Boutefnouchet ◽

Daoud Harzallah ◽

...

Keyword(s):

Aqueous Extract ◽

Safety Assessment ◽

Inflammatory Activity ◽

Aerial Parts ◽

Erica Arborea ◽

Anti Inflammatory

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In silico network pharmacology and in vivo analysis of berberine-related mechanisms against type 2 diabetes mellitus and its complications

Journal of Ethnopharmacology ◽

10.1016/j.jep.2021.114180 ◽

2021 ◽

pp. 114180

Author(s):

Sha Di ◽

Lin Han ◽

Xuedong An ◽

Ran Kong ◽

Zezheng Gao ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

In Silico ◽

Network Pharmacology ◽

In Vivo Analysis

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PAR-4/Ca2+-calpain pathway activation stimulates platelet-derived microparticles in hyperglycemic type 2 diabetes

Cardiovascular Diabetology ◽

10.1186/s12933-021-01267-w ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Alessandra Giannella ◽

Giulio Ceolotto ◽

Claudia Maria Radu ◽

Arianna Cattelan ◽

Elisabetta Iori ◽

...

Keyword(s):

Type 2 Diabetes ◽

Normal Glucose Tolerance ◽

Calpain Inhibitor ◽

Pathway Activation ◽

Normal Glucose ◽

Circulating Levels ◽

Dependent Mechanism

Abstract Background Patients with type 2 diabetes (T2DM) have a prothrombotic state that needs to be fully clarified; microparticles (MPs) have emerged as mediators and markers of this condition. Thus, we investigate, in vivo, in T2DM either with good (HbA1c ≤ 7.0%; GGC) or poor (HbA1c > 7.0%; PGC) glycemic control, the circulating levels of MPs, and in vitro, the molecular pathways involved in the release of MPs from platelets (PMP) and tested their pro-inflammatory effects on THP-1 transformed macrophages. Methods In 59 T2DM, and 23 control subjects with normal glucose tolerance (NGT), circulating levels of CD62E+, CD62P+, CD142+, CD45+ MPs were determined by flow cytometry, while plasma levels of ICAM-1, VCAM-1, IL-6 by ELISA. In vitro, PMP release and activation of isolated platelets from GGC and PGC were investigated, along with their effect on IL-6 secretion in THP-1 transformed macrophages. Results We found that MPs CD62P+ (PMP) and CD142+ (tissue factor-bearing MP) were significantly higher in PGC T2DM than GGC T2DM and NGT. Among MPs, PMP were also correlated with HbA1c and IL-6. In vitro, we showed that acute thrombin exposure stimulated a significantly higher PMP release in PGC T2DM than GGC T2DM through a more robust activation of PAR-4 receptor than PAR-1 receptor. Treatment with PAR-4 agonist induced an increased release of PMP in PGC with a Ca2+-calpain dependent mechanism since this effect was blunted by calpain inhibitor. Finally, the uptake of PMP derived from PAR-4 treated PGC platelets into THP-1 transformed macrophages promoted a marked increase of IL-6 release compared to PMP derived from GGC through the activation of the NF-kB pathway. Conclusions These results identify PAR-4 as a mediator of platelet activation, microparticle release, and inflammation, in poorly controlled T2DM.

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Identifying potential PPARγ agonist/partial agonist from plant molecules to control type 2 diabetes using in silico and in vivo models

Medicinal Chemistry Research ◽

10.1007/s00044-016-1621-z ◽

2016 ◽

Vol 25 (9) ◽

pp. 1980-1992 ◽

Cited By ~ 4

Author(s):

Antony Stalin ◽

Santiagu Stephen Irudayaraj ◽

Dhandapani Ramesh Kumar ◽

Kedike Balakrishna ◽

Savarimuthu Ignacimuthu ◽

...

Keyword(s):

Type 2 Diabetes ◽

In Silico ◽

Partial Agonist ◽

In Vivo Models ◽

Pparγ Agonist

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Abstract 13373: Exercise Improves Angiogenic Function of Circulating Exosomes in Type 2 Diabetes: Role of Extracellular SOD

Circulation ◽

10.1161/circ.142.suppl_3.13373 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Kareem Abdelsaid ◽

Sudhahar Varadarajan ◽

Archita Das ◽

Yutao Liu ◽

Xuexiu Fang ◽

...

Keyword(s):

Type 2 Diabetes ◽

Wound Healing ◽

Endothelial Dysfunction ◽

Wound Repair ◽

Cell Communication ◽

Tube Formation ◽

Skin Wound ◽

Skin Wound Healing

Background: Exosomes, key mediators of cell-cell communication, derived from type 2 diabetes mellitus (T2DM) have detrimental effects. Exercise not only improves endothelial dysfunction and angiogenesis in T2DM but also induces secretion of exosomes into circulation. Extracellular superoxide dismutase (ecSOD) is a major secretory Cu containing antioxidant enzyme that catalyzes dismutation of O 2 •- to H 2 O 2 and its full activity requires Cu transporter ATP7A. We reported that ecSOD-derived H 2 O 2 in endothelial cells (ECs) enhances angiogenesis while impaired ATP7A-ecSOD axis in diabetes induces endothelial dysfunction. Here we examined whether exercise-derived exosomes (Exe-Exo) may have pro-angiogenic effects via regulating ATP7A-ecSOD axis in T2DM. Results: Two weeks of voluntary wheel exercise of control C57Bl6 mice increased plasma exosome levels (6.2-fold) characterized by Nanosight, TEM and exosome markers (CD63, CD81, Tsg101). Treatment of HUVECs with equal number of exosomes revealed that angiogenic responses such as EC migration (1.8-fold) and tube formation (1.7-fold) were significantly enhanced by Exe-Exo compared to sedentary-derived exosomes (Sed-Exo). This was associated with increased ATP7A (2.9-fold) and ecSOD (1.4-fold) expression in Exe-Exo. Sed-Exo from high fat-induced T2DM mice significantly decreased EC migration (40%) and tube formation (10%) as well as ATP7A expression (28%) compared to Sed-Exo from control mice, which were restored by T2DM Exe-Exo, but not by T2DM/ecSOD KO Exe-Exo. Furthermore, exosomes overexpressing ecSOD (ecSOD-Exo) which mimic exercise increased angiogenesis and H2O2 levels in ECs, which were inhibited by overexpression of catalase. In vivo, skin wound healing model showed that direct application of T2DM Sed-Exo delayed while T2DM Exe-Exo enhanced wound healing of control mice. Furthermore, defective wound healing in T2DM mice or ecSOD KO mice were rescued by ecSOD-Exo application. Conclusion: Exercise training improves pro-angiogenic function of circulating exosomes in T2DM via increasing ATP7A-ecSOD axis, which may provide an effective therapy for promoting angiogenesis and wound repair in metabolic and cardiovascular diseases.

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