Andrographolide Promotes Neural Differentiation of Rat Adipose Tissue-Derived Stromal Cells through Wnt/β-Catenin Signaling Pathway

Abstract

Adipose tissue-derived stromal cells (ADSCs) are a high-yield source of pluripotent stem cells for use in cell-based therapies. We explored the effect of andrographolide (ANDRO, one of the ingredients of the medicinal herb extract) on the neural differentiation of rat ADSCs and associated molecular mechanisms. We observed that rat ADSCs were small and spindle-shaped and expressed multiple stem cell markers including nestin. They were multipotent as evidenced by adipogenic, osteogenic, chondrogenic, and neural differentiation under appropriate conditions. The proportion of cells exhibiting neural-like morphology was higher, and neurites developed faster in the ANDRO group than in the control group in the same neural differentiation medium. Expression levels of the neural lineage markers MAP2, tau, GFAP, and β-tubulin III were higher in the ANDRO group. ANDRO induced a concentration-dependent increase in Wnt/β-catenin signaling as evidenced by the enhanced expression of nuclear β-catenin and the inhibited form of GSK-3β (pSer9). Thus, this study shows for the first time how by enhancing the neural differentiation of ADSCs we expect that ANDRO pretreatment may increase the efficacy of adult stem cell transplantation in nervous system diseases, but more exploration is needed.

Wnt‐induced activation of glucose metabolism mediates the in vivo neuroprotective roles of Wnt signaling in Alzheimer disease

“…Both Wnt3a, ANDRO and Li are able to turn on the Wnt canonical pathway, constituting a potentially relevant therapeutic approach to up-regulate Wnt canonical signaling in vivo. Indeed, both molecules promote the accumulation of b-catenin by preventing the degradation of this protein through the inhibition of GSK-3b (Toledo and Inestrosa 2010;Tapia-rojas et al 2015;Liang et al 2017;Xia et al 2017;Rivera et al 2018). Relevantly, the canonical Wnt signaling has emerged as one of the more relevant pathways to be addressed when approaching to neurodegenerative disorders, overall because it has been related to several brain pathologies, such as AD, autism, schizophrenia and Parkinson disease.…”

<p>Andrographolide attenuates bupivacaine-induced cytotoxicity in SH-SY5Y cells through preserving Akt/mTOR activity</p>

“…A previous study indicated that Andro can stimulate neurogenesis in the adult hippocampus 13. Liang et al found that Andro may exhibit neuroprotective effects in nervous system diseases 14. Meanwhile, a recent study showed that Andro exerted strong neuroprotective effects in a mouse model of Parkinson’s disease 15.…”

Neurobiological Promises of the Bitter Diterpene Lactone Andrographolide

“…In a recent study, ANDRO (5–100 μ g/kg, i.p.) increased Wnt/ β -catenin signaling as evidenced by the enhanced nuclear β -catenin expression and inhibited GSK-3 β (pSer9) [ 70 ].…”

“…Furthermore, NOX2 and iNOS expression were reduced by impairing PI3K/protein kinase B-(AKT-) dependent NF-κB and HIF-1α activation in cerebral ischemia in mice [24]. [20], [44], [47], [26], [46]) 22], [94], [95], [52], [50], [51], [55], [56], [57], [54]) 16], [62], [61], [63], [57], [96]) [27], [68], [69], [97], [70])…”

“…In a recent study, ANDRO (5-100 μg/kg, i.p.) increased Wnt/β-catenin signaling as evidenced by the enhanced nuclear β-catenin expression and inhibited GSK-3β (pSer9) [70]. [71] and is a prime CNS health problem all over the world with high morbimortality rates.…”