Baicalin, a Flavone, Induces the Differentiation of Cultured Osteoblasts

Abstract

Flavonoids, a group of natural compounds found in a variety of vegetables and herbal medicines, have been intensively reported on regarding their estrogen-like activities and particularly their ability to affect bone metabolism. Here, different subclasses of flavonoids were screened for their osteogenic properties by measuring alkaline phosphatase activity in cultured rat osteoblasts. The flavone baicalin derived mainly from the roots of Scutellaria baicalensis showed the strongest induction of alkaline phosphatase activity. In cultured osteoblasts, application of baicalin increased significantly the osteoblastic mineralization and the levels of mRNAs encoding the bone differentiation markers, including osteonectin, osteocalcin, and collagen type 1␣1. Interestingly, the osteogenic effect of baicalin was not mediated by its estrogenic activity. In contrast, baicalin promoted osteoblastic differentiation via the activation of the Wnt/ ␤-catenin signaling pathway; the activation resulted in the phosphorylation of glycogen synthase kinase 3␤ and, subsequently, induced the nuclear accumulation of the ␤-catenin, leading to the transcription activation of Wnt-targeted genes for osteogenesis. The baicalin-induced osteogenic effects were fully abolished by DKK-1, a blocker of Wnt/␤-catenin receptor. Moreover, baicalin also enhanced the mRNA expression of osteoprotegerin, which could regulate indirectly the activation of osteoclasts. Taken together, our results suggested that baicalin could act via Wnt/␤-catenin signaling to promote osteoblastic differentiation. The osteogenic flavonoids could be very useful in finding potential drugs, or food supplements, for treating post-menopausal osteoporosis.

Kaempferol as a flavonoid induces osteoblastic differentiation via estrogen receptor signaling

“…Taken together, these results suggested that the osteogenic effects mediated by flavonoids could be dependent or independent of their estrogenic properties. This idea is supported by our previous screening of different flavonoids, encompassing the major sub-classes, which showed that the estrogenic activities of selective flavonoids are not correlated with osteogenic activities [12]. Moreover, our results also implied that different flavonoids could promote bone differentiation via different signaling mechanisms and these mechanisms of action and signaling cascades should be further studied.…”

Potential Antiosteoporotic Agents from Plants: A Comprehensive Review

“…These compounds can be divided into 6 categories, including flavonoids: icariin (Figure 1) [23–26], genistein (Figure 2) [29], daidzein (Figure 2) [31, 32], kaempferol (Figure 11) [72], quercetin (Figure 11) [73, 74], naringin (Figure 8) [75–77], hesperidin (Figure 11) [78], linarin (Figure 11) [79], bavachalcone (Figure 3) [36], rutin (Figure 11) [80], (+)-catechin (Figure 11) [81], nobiletin (Figure 11) [82], luteolin (Figure 11) [83], baicalein (Figure 11) [84], baicalin (Figure 1) [85], xanthohumol (Figure 11) [86]; coumarins: psoralen (Figure 3) [35], osthole (Figure 11) [87]; lignans: honokiol (Figure 11) [88, 89], isotaxiresinol (Figure 11) [90], magnolol (Figure 11) [91]; polyphenol: resveratrol (Figure 11) [92–95], curcumin (Figure 11) [96–98], tea polyphenols (including epigallocatechin-3-gallate, epigallocatechin, epi-catechin, epicatechin-3-gallate, Figure 11) [99, 100]; anthraquinones: rubiadin (Figure 10), 2-hydroxy-1-methoxy-anthraquinone (Figure 10), 1,3,8-trihydroxy-2-methoxy-anthraquinone (Figure 10) [71]; alkaloids: harmine (Figure 11) [101], coptisine (Figure 11) [102], palmatine (Figure 11) [103], berberine (Figure 11) [104, 105]; and other compounds: curculigoside (Figure 11) [106, 107], asperosaponin VI (Figure 11) [108], limonoid 7-oxo-deacetoxygeduni...…”

Flavonoids Induce the Synthesis and Secretion of Neurotrophic Factors in Cultured Rat Astrocytes: A Signaling Response Mediated by Estrogen Receptor

“…In line to this notion, a study showed that ER α played a critical role in estrogen-induced glutamatergic synapse formation, including the expressions of presynaptic vesicular glutamate transporter protein (vGlut1) and postsynaptic NMDA receptor (NR1 subunit) [37]. Flavonoids are well-known phytoestrogens with multiple activities in different systems [38, 39]. Much attention has been focused on the neuronal beneficial effects of flavonoids, including the neuroprotection against neurotoxin stress [16] as well as the promotion of memory and learning and cognitive functions [15].…”