Baicalin attenuates fibrogenic process in human renal proximal tubular cells (HK-2) exposed to diabetic milieu.

AIMS: Baicalin, a flavonoid glycoside substance extracted from Scutellaria baicalensis Georgi, has been shown to exhibit multiple therapeutic properties owing to its anti-inflammatory effect. Diabetes is characterized by chronic hyperglycemia, inflammation and oxidative stress, which promote renal fibrosis and kidney failure. Although anti-fibrogenic effects of baicalin in lung and liver have been reported previously, no study has investigated its roles in renal fibrosis. Here, we demonstrated protective effects of baicalin against fibrogenic process in human kidney proximal tubular epithelial cells (HK-2) exposed to diabetic milieu. MAIN METHODS: To investigate the effects of baicalin on oxidative stress- and inflammation-induced fibrosis in HK-2 cells, protein and gene expressions of NF-κB- and STAT3-associated inflammatory molecules and TGFß-associated extracellular matrix proteins were examined by western blotting, immunocytochemistry and qRT-PCR. To determine physiological changes of HK-2 exposed to diabetic milieu in response to baicalin, production of cAMP and cGMP and Ca2+ influx were measured. KEY FINDINGS: Baicalin attenuated oxidative stress- and inflammation-inudced IκB and JAK2 phosphorylations and, subsequent, NF-κB nuclear translocation and STAT3 phosphorylation. Consequently, it markedly reduced transactivation of NF-κB- and STAT3-associated inflammatory genes such as ICAM1, VCAM1, TGFß, IL1ß and MCP1, and protein expression of TGFß-associated extracellular matrix proteins, such as fibronectin and collagen IV. These effects are, partially, attributed to its regulatory function of intracellular concentration of Ca2+ via interaction with type A γ-aminobutyric acid receptor. SIGNIFICANCE: This is the first study which investigated anti-fibrogenic effect of baicalin in human kidney cells, and our results highlight a potential therapeutic application of baicalin for diabetic nephropathy.

Ethanol extract of the seed of Zizyphus jujuba var. spinosa potentiates hippocampal synaptic transmission through mitogen-activated protein kinase, adenylyl cyclase, and protein kinase A pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: As the seed of Zizyphus jujuba var. spinosa (Bunge) Hu ex H.F. Chow (Rhamnaceae) has been used to sleep disturbances in traditional Chinese and Korean medicine, many previous studies have focused on its sedative effect. AIM OF THE STUDY: Recently, we reported the neuroprotective effect of the effect of Z. jujuba var. spinosa. However, its effects on synaptic function have not yet been studied. In this project, we examined the action of ethanol extract of the seed of Z. jujuba var. spinosa (DHP1401) on synaptic transmission in the hippocampus. MATERIALS AND METHODS: To investigate the effects of DHP1401, field recordings were conducted using hippocampal slices (400µm). Object recognition test was introduced to examine whether DHP1401 affect normal recognition memory. RESULTS: DHP1401 (50µg/ml) induced a significant increase in synaptic activity in Shaffer collateral pathway in a concentration-dependent manner. This increase of synaptic responses was blocked by NBQX, a broad spectrum α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, but not IEM-1460, a Ca2+-permeable AMPAR blocker. Moreover, U0126, a mitogen-activated protein kinase inhibitor, SQ22536, an adenylyl cyclase inhibitor, and PKI, a protein kinase A inhibitor, blocked DHP1401-induced increase in synaptic transmission. Finally, DHP1401 facilitated object recognition memory. CONCLUSIONS: These results suggest that DHP1401 increase synaptic transmission through increase of synaptic AMPAR transmission via MAPK, AC and PAK.