Catalpol attenuates ischemic stroke by promoting neurogenesis and angiogenesis via the SDF-1α/CXCR4 pathway.

BACKGROUND: Stroke is a leading cause of disability and death worldwide. Currently, there is a lack of clinically effective treatments for the brain damage following ischemic stroke. Catalpol is a bioactive compound derived from the traditional Chinese medicine Rehmannia glutinosa and shown to be protective in various neurological diseases. However, the potential roles of catalpol against ischemic stroke are still not completely clear. PURPOSE: This study aimed to further elucidate the protective effects of catalpol against ischemic stroke. METHODS: A rat permanent middle cerebral artery occlusion (pMCAO) and oxygen-glucose deprivation (OGD) model was established to assess the effect of catalpol in vivo and in vitro, respectively. Behavioral tests were used to examine the effects of catalpol on neurological function of ischemic rats. Immunostaining was performed to evaluate the proliferation, migration and differentiation of neural stem cells (NSCs) as well as the angiogenesis in each group. The protein level of related molecules was detected by western-blot. The effects of catalpol on cultured NSCs as well as brain microvascular endothelial cells (BMECs) subjected to OGD in vitro were also examined by similar methods. RESULTS: Catalpol attenuated the neurological deficits and improved neurological function of ischemic rats. It stimulated the proliferation of NSCs in the subventricular zone (SVZ), promoted their migration to the ischemic cortex and differentiation into neurons or glial cells. At the same time, catalpol increased the cerebral vessels density and the number of proliferating cerebrovascular endothelial cells in the infracted cortex of ischemic rats. The level of SDF-1α and CXCR4 in the ischemic cortex was found to be enhanced by catalpol treatment. Catalpol was also shown to promote the proliferation and migration of cultured NSCs as well as the proliferation of BMECs subjected to OGD insult in vitro. Interestingly, the impact of catalpol on cultured cells was inhibited by CXCR4 inhibitor AMD3100. Moreover, the culture medium of BMECs containing catalpol promoted the proliferation of NSCs, which was also suppressed by AMD3100. CONCLUSION: Our data demonstrate that catalpol exerts neuroprotective effects by promoting neurogenesis and angiogenesis via the SDF-1α/CXCR4 pathway, suggesting the therapeutic potential of catalpol in treating cerebral ischemia.

Gastrodin alleviates cisplatin nephrotoxicity by inhibiting ferroptosis via the SIRT1/FOXO3A/GPX4 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Cisplatin (CP) results in acute kidney injury (AKI) and negatively affects patients' therapy and survival. The dried rhizome of Gastrodia elata Blume has been used to treat clinical kidney diseases. Gastrodin (GAS) is an active ingredient of the G. elata tuber. It is unknown whether GAS can alleviate CP-induced AKI. AIM OF THE STUDY: This study aimed to investigate whether GAS, an active ingredient of G. elata Blume, can alleviate CP-induced AKI and to explore its underlying mechanisms. MATERIALS AND METHODS: Experiments were conducted with a CP-induced AKI mouse model and an immortalized human renal tubular epithelial cell line (HK-2). Serum creatinine, Periodic acid-Schiff staining, tissue iron, glutathione, malondialdehyde, and 4-Hydroxynonenal were detected in serum and kidney samples to observe whether GAS inhibits CP-induced tubule ferroptosis. The drug target was verified by detecting the effects of GAS on sirtuin-1 (SIRT1) activity in vitro. Transcriptional regulation of glutathione peroxidase 4 (GPX4) by forkhead box O3A (FOXO3A) was verified by siRNA knockdown, overexpression, and chromatin immunoprecipitation. The effects of FOXO3A, SIRT1, and GAS on CP-induced ferroptosis were measured with propidium iodide, dihydroethidium, monobromobimane, and dipyrromethene boron difluoride staining in HK-2 cells. The relationship between GAS and the SIRT1/FOXO3A/GPX4 pathway was studied using Western blotting. RESULTS: GAS treatment inhibited CP-induced reactive oxygen species, lipid peroxidation, and tubule death in the cell and animal models. GAS activated SIRT1 in vitro. The SIRT1 inhibitor blocked the protective role of GAS in reducing lipid peroxidation in HK-2 cells. FOXO3A transcriptionally regulated GPX4 expression and inhibited CP-induced cell ferroptosis. Compared to CP-damaged mouse kidneys, GAS-treated mice demonstrated significantly increased SIRT1 and GPX4 expression levels, decreased CP-induced acetylation of FOXO3A, and inhibited lipid peroxidation and cell death. CONCLUSIONS: GAS alleviated CP-induced AKI by inhibiting ferroptosis via the SIRT1/FOXO3A/GPX4 signaling pathway. The results offer new insights into the development of new anti-AKI drugs from traditional Chinese medicine.

[Protective effect of catalpolon destruction of tight junctions of high glucose induced BMECs].

This paper aimed to observe the protective effect of catalpol on the high glucose induced destruction of tight junctions of rat primary brain microvascular endothelial cells (BMECs). Catalpol co-administrated with high glucose increased BMECs survival, decreased its ET-1 secretion, and improved transmembrane electrical resistance in a time-dependent manner. Furthermore, transmission electron microscopy was used to observe catalpol's protective effect on tight junction. Fluorescence staining displayed that catalpol reversed the rearrangement of the cytoskeleton protein F-actin and up-regulated the tight junction proteins claudin-5 and ZO-1, which were further demonstrated by the mRNA expression levels of claudin-5, occludin, ZO-1, ZO-2, ZO-3, α-actintin, vinculin and cateinins. This study indicated that catalpol reverses the disaggregation of cytoskeleton actin in BMECs and up-regulates the expression of tight junction proteins, such as claudin-5, occludin, and ZO-1, and finally alleviates the increase in high glucose-induced BMECs injury.

[Effects of Schisandrae Chinensis Fructus induced CYPs and Nrf2 activation on acute liver injury induced by acetaminophen].

Schisandra chinensis is a commonly used hepatoprotective medicine in clinic. Previous studies have showed that Schisandrae Chinensis Fructus has dual effects on the activity of CYPs. Short-term administration of Schisandrae Chinensis Fructus may inhibit CYP450s activity, while long-term administration may up-regulate CYP activity. High CYP450s activity level may increase the frequency of reactive metabolites-induced liver injury. It remains unclear how long-term administration of Schisandrae Chinensis Fructus may affect acetaminophen-induced acute hepatotoxicity. After oral administration of Schisandrae Chinensis Fructus extract (0.5-2.0 g·kg⁻¹) for 21 d, the activity of CYPs, Nrf2, HO-1, GST expressions, SOD and GST activity as well as glutathione level of SD rats were up-regulated. Besides, Schisandrae Chinensis Fructus extract ameliorated APAP (500 mg·kg⁻¹)-induced acute hepatotoxicity in a dose-dependent manner, as evidenced by decrease in ALT, AST, and MDA level and increase in GSH level (P<0.05). What's more, the liver histopathology was alleviated, and cleaved caspase-3 expression was decreased. Besides, the increase of N-acetyl-p-benzoquinoneimine-GSH (reactive metabolite of acetaminophen) formation was observed in Schisandrae Chinensis Fructus extract groups. In conclusion, the present study indicated that the effects of Schisandrae Chinensis Fructuson acetaminophen-induced hepatotoxicity may rely on the Nrf2 signal pathway activation, and less depends on the increase in CYP450s activity.

[Recent advances of Drynaria fortunei].

Drynaria fortunei (Kunze) is a common medicine in department of orthopaedics and traumaology, more researches about it recently, including basic theory, pharmaco and clinical study.

[Effects of Rehmannia root decoction serum on cell proliferation and EPO expression in cultured human umbilical vein endothelial cells].

OBJECTIVE: To explore the efficacy of the rehmannia root decoction containing serum in enhencing the proliferation of HUVECs-1 and EPO expression and to give libratory evidence for the tonifying blood and kidney therapy with rehmannia root. METHOD: Twenty-four male Sprague-Dawley rats were randomly devided into 4 group and administrered by gastrogavage rehmannia root decoction of 3, 6, 10 g x kg(-1) once a day for 1 weeks. Using serum pharmacologic method, the proliferation of HUVECs-1 cell was determined by MTT chromatometry at 48 h points by co-culturing with medicated serum containing different concentration of rehmannia root decoction. The expression of EPO on HUVECs-1 were observed by immunity cytochemistry and Western blot. NS serum was taken as control. RESULT: After the HUVECs-1 cultivating with medicated serum for 48 h, compared with NS serum, 20% serum containing rehmannia root (6 g x kg(-1)) could obviously increase proliferation of HUVEC-1 (P < 0.05) and increase the level of the expression of EPO on HUVECs-1 (P < 0.05). CONCLUSION: Rehmannia root extract has good actions of proliferation of HUVECs-1 and increase EPO expression, which is the mechanisms of nourishing yin and blood and tonifying essence of rehmannia root.

[Study of catalpol promoting axonal growth for cultured cortical neurons from rats].

OBJECTIVE: To explore the effects of different concentration of catalpol on the cell survival and axonal growth of cortical neurons cultured in vitro from 24 h newly born rat. METHOD: Primary cultured cortical neurons from 24 h newly born rat were dissociated and cultured. The different concentration of catalpol and 1 mg mL(-1) citicoline were added to the culture plates for 48 h, and the final of catalpol concentration were 0.25, 0.5, 1, 2.5, 5 mg mL(-1), respectively. The cortical neuron was identified by NF-200 antigen and its survival activity detected by MTT assay. The axonal growth of cultured cortical neuron were observed by inverted microscopy with micrometer. RESULT: Immunocytochemistry demonstrated more than 95% of the primary cultured cortical neurons were positive for NF-200 antigen, which indicated the cultured cells were neurons. Neurons survived growing on the concentration of 0.25, 0.5, 1, 2.5, 5 mg mL(-1). Compared with blank and 1 mg mL(-1) citicoline group,neurons survival rates were not statistical significant difference. However, it demonstrated that catalpol significantly promoted axonal growth from 1-5 mg mL(-1) (P <0.05). Interestedly, compared with the dose of 2.5 mg mL(-1), axonal growth was shorter at the dose of 5 mg mL(-1), and 2.5 mg mL(-1) catalpol showed the strongest promotion effect. CONCLUSION: The catalpol can enhance cortical neuron axonal growth, but not promote cortical neuron survival.