Suppression of OCT2/MRP2 decreases kidney injury and enhances the chemosensitivity of co-administration of cisplatin and astragaloside IV / 药学学报

Kidney injury and decreased chemosensitivity of tumor cells are obstacles with cisplatin (CDDP) chemotherapy. Down-regulation of the organic cation transporter 2 (OCT2) and multidrug resistance-associated protein 2 (MRP2) is a key means to alleviate CDDP-induced kidney injury and increase chemosensitivity. Astragaloside IV (AS IV) is obtained from the well-known traditional Chinese herb Astragalus membranaceus. This study explored the role of AS IV in preventing kidney injury and enhancing the antitumor effect of CDDP by suppressing OCT2 expression in kidney and MRP2 in tumors. This project was reviewed and approved by the Animal Ethics Committee of the First Hospital of Jilin University. The effects of AS IV on CDDP inhibition of tumor growth and promotion of apoptosis were assessed in Lewis lung tumor (LLC)-bearing mice by H&E and TUNEL staining. Kidney injury was assessed by serum biochemical parameters and H&E staining. We used Western blotting and immunohistochemistry assays to detect OCT2 and MRP2 expression in kidney and tumor. The concentration of CDDP in kidney and tumor was measured by HPLC-MS/MS. AS IV enhanced CDDP chemosensitivity by increasing tumor cell apoptosis and slowing tumor growth, and decreased kidney injury as evidenced by lower blood creatinine (Cr) and blood urea nitrogen (BUN). Co-administration of AS IV suppressed MRP2 overexpression induced by CDDP in tumor tissues and may be an important mechanism for enhancing CDDP chemosensitivity. Moreover, AS IV reduced CDDP-induced kidney injury in mice along with suppression of OCT2 expression in kidney. The concentration of CDDP was increased in tumor but decreased in kidney. In total, AS IV not only enhanced the antitumor effect of CDDP by suppressing MRP2 expression in tumor cells, but also decreased kidney injury induced by CDDP. The results provide new insight into the combined use of a chemotherapy drug and natural ingredients to treat cancer.

XingNaoJing injections protect against cerebral ischemia/reperfusion injury and alleviate blood-brain barrier disruption in rats, through an underlying mechanism of NLRP3 inflammasomes suppression / 中国天然药物

The aim of this study was to explore the neuroprotective effect and mechanism of XingNaoJing injections (XNJ) on cerebral ischemia injury and blood-brain barrier (BBB) disruption. Middle cerebral artery occlusion (MCAO) method was applicated to establish the model of cerebral ischemia/reperfusion (I/R) injury in rats. BBB permeability after I/R injury was assessed with the leaking amount of Evans Blue and the expression of occludin and ZO-1. The expression of NOD-like receptor family, pyrin domain containing (NLRP3) was checked to explore the inhibition of inflammation by XNJ. The results showed that XNJ could significantly increase the survival percent, decrease the infarct area and ameliorate neurological deficits and brain damage after I/R injury. Leaking amount of Evans Blue was reduced by XNJ, and the expression of tight junction protein, occludin and ZO-1 was also up-regulated by XNJ, which showed a role of protection on BBB disruption. The expression of NLRP3 was inhibited after exposure of XNJ, which was associated with inhibition of the inflammatory response. In summary, XNJ could suppress NLRP3 inflammasomes and improve BBB disruption and brain damage in rats after cerebral I/R injury, which provided a beneficial insight to further explore XNJ.

Effect of preventive moxibustion on heat shock proteins and stress hormones in natural menopausal rats / 中国针灸

<p><b>OBJECTIVE</b>To investigate the effect of preventive moxibustion at the acupoint of 'Guanyuan" (CV 4) on the stress-related hormones, proteins and genes in natural menopausal rats, and explore its protective mechanism.</p><p><b>METHODS</b>One hundred and twenty eight healthy female SD rats were used in this study, in which 16 rats aged 4 months were used as normal control group, the rest 10-month-old rats with disorder of estrus cycle were randomly divided into 7 groups, including 4 control groups at the age of 10, 12, 14 and 16 months, and 3 preventive moxibustion groups at the age of 12, 14 and 16 months, 16 cases in each group. The 10-month-old rats were treated with preventive moxibustion at the acupoint of "Guanyuan" (CV 4), twice a week for 8 weeks consistently, then observed on the following 12, 14 and 16 months. Its effects on the level of heat shock protein 70 (HSP 70), heat shock protein 70 mRNA (HSP 70 mRNA), corticotropin-releasing hormone (CRH), beta-endorphin (beta-EP), adrenocorticotrophic hormone (ACTH) in the different nuclei of hypothalamus were examined with radio-immunity, immunohistochemistry or in situ hybridization methods.</p><p><b>RESULTS</b>In the control groups, the expression of HSP 70 and HSP 70 mRNA was increased in paraventricular, arcuate and supraoptic nucleus, the level of CRH, beta-EP was showed with declining trend in volatility, while the content of ACTH was increased. In comparison to the same-aged control groups, the preventive moxibustion groups were showed that the expression of HSP 70 in the 14-month-old group was lower and the expression of HSP 70 mRNA in the 12 and 16-month-old group was significantly higher in the paraventricular nucleus (all P < 0.05), the expression of HSP 70 in the 12 and 14-month-old groups and HSP 70 mRNA in the 12-month-old group was significantly increased in the arcuate nucleus (P < 0.05, P < 0.01), while the expression of HSP 70 in the 14-month-old group and HSP 70 mRNA in the 12 and 16-month-old group was significantly decreased in the supraoptic nucleus (all P < 0.05), the content of CRH and ACTH decreased significantly in 14-month group (P < 0.05, P < 0.01), but the content of beta-EP obviously went up in the 12-month-old group (P < 0.05).</p><p><b>CONCLUSION</b>Preventive moxibustion at the acupoint of "Guanyuan" (CV 4) can regulate the expression of stress proteins, genes and hormones in the hypothalamus for the natural menopausal rats, which might be playing a protective role.</p>

Experimental study on changes of expressions of ER-alpha and ER-alpha mRNA in different hypothalamic nuclei and the effect of "preventive acupuncture and moxibustion" in ovariectomy rats / 中国针灸

<p><b>OBJECTIVE</b>To explore the mechanism of "preventive acupuncture and moxibustion" for regulating hypothalamic function in ovariectomy rats.</p><p><b>METHODS</b>Thirty female SD rats, aged 3.5 months, were randomly divided into normal group, sham operation group, ovariectomy model group, preventive acupuncture group and preventive moxibustion group. After "preventive acupuncture and moxibustion" were previously given to the preventive acupuncture group and the preventive moxibustion group for one month, respectively. At the same time, ovarietomy was made in the preventive acupuncture group, the preventive moxibustion group and the ovariectomy model group. For the sham operation group, only a little fat around the ovary was removed without ovariectomy, and nothing was not applied to the normal group. Immunohistochemical and in situs hybridization methods were used to investigate changes of expressions of ER-alpha and ER-alpha mRNA in paraventricular nucleus, supraoptic nucleus and arcuate nucleus.</p><p><b>RESULTS</b>In the model group the expressions of ER-alpha and ER-alpha mRNA in paraventricular nucleus and the expression of ER-alpha mRNA in supraoptic nucleus increased significantly (P<0.01), but the expression of ER-alpha dropped significantly in both supraoptic nucleus and arcuate nucleus (P<0.01). After preconditioning with acupuncture or moxibustion, the expression of ER-alpha mRNA in paraventricular nucleus significantly reduced (P<0.05), and the expression of ER-alpha had no significant change (P>0.05); the expression of ER-alpha in supraoptic nucleus and arcuate nucleus significantly increased (P<0.01 or P<0.05), and the expression of ER-alpha mRNA in paraventricular nucleus had no significant change (P>0.05).</p><p><b>CONCLUSION</b>"Preventive acupuncture and moxibustion" at "Guanyuan" (CV 4) have an effect on the expressions of ER-alpha and ER-alpha mRNA in different hypothalamic nuclei in ovariectomy rats, which possibly is one of the ways for modulating the hypothalamic activity.</p>

Effects of electroacupuncture on CRH, IL-2 and beta-EP contents in the hypothalamus in the rat of adjuvant arthritis / 中国针灸

<p><b>OBJECTIVE</b>To explore Mechanisms of electroacupuncture in anti-inflammation and immunoregulation, and to compare differences among "Dazhui" (GV 14), "Mingmen "(GV 4) and non-acupoint in these actions.</p><p><b>METHODS</b>Adjuvant arthritis rat model was made. The rats were divided into 5 groups: normal group, model group, "Dazhui" (GV 14) electroacupuncture group, "Mingmen" (GV 4) electroacupuncture group and non-acupoint electroacupuncture group. Effects of electroacupuncture on local joint inflammation and corticotropin-releasing hormone (CRH), beta-endorphin (betaEP) and interleukin-2 (IL-2) contents in the hypothalamus were observed and differences of the actions among different points were compared.</p><p><b>RESULTS</b>CRH content in the hypothalamus in the "Dazhui" (GV 14) electroacupuncture group decreased as compared with the model group (P < 0.05); there was no significant change in beta-EP and IL-2 contents of the hypothalamus in the 3 electroacupuncture groups as compared with the model group (P > 0.05); there was positive correlation between CRH and IL-2 contents, and between IL-2 and beta-EP contents in the hypothalamus. The swelling rate of the toe in the "Dazhui" (GV 14) group and the "Mingmen" (GV 4) group was lower than that in the non-acupoint group (P < 0 05).</p><p><b>CONCLUSION</b>Electroacupuncture exerts anti-inflammation and immunoregulation possibly via regulation of CRH, IL-2 and beta-EP each other, and the anti-inflammation action of "Dazhui" (GV 14) and "Mingmen" (GV 4) is stronger than that of non-acupoint.</p>