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Background. Doxorubicin (DOX) is a commonly used chemotherapeutic drug but is limited in clinical applications by its cardiotoxicity. Neiguan acupoint (PC6) is a well-recognized acupoint for the treatment of cardiothoracic disease. However, whether acupuncture at PC6 could be effective in preventing DOX-induced cardiotoxicity is still unknown. Methods. A set of experiments were performed with myocardial cells, wild type, inducible nitric oxide synthase knockout (iNOS-/-), and myocardial-specific ablation arginase 2 (Myh6-ARG 2-/-) mice. We investigated the protective effect and the underlying mechanisms for electroacupuncture (EA) against DOX-induced cardiotoxicity by echocardiography, immunostaining, biochemical analysis, and molecular biotechnology in vivo and in vitro analysis. Results. We found that DOX-mediated nitric oxide (NO) production was positively correlated with the iNOS level but has a negative correlation with the arginase 2 (ARG 2) level in both myocardial cells and tissues. Meanwhile, EA at PC6 alleviated cardiac dysfunction and cardiac hypertrophy in DOX-treated mice. EA at PC6 blocked the upregulation of NO production in accompanied with the downregulated iNOS and upregulated ARG 2 levels in myocardial tissue induced by DOX. Furthermore, knockout iNOS prevented cardiotoxicity and EA treatment did not cause the further improvement of cardiac function in iNOS-/- mice treated by DOX. In contrast, deficiency of myocardial ARG 2 aggravated DOX-induced cardiotoxicity and reduced EA protective effect. Conclusion. These results suggest that EA treatment at PC6 can prevent DOX-induced cardiotoxicity through modulating NO production by modulating the iNOS/ARG 2 balance in myocardial cells.

Attenuating β amyloid- (Aβ-) induced microglial activation is considered to be effective in treating Alzheimer’s disease (AD). Berberine (BBR) can reduce microglial activation in Aβ-treated microglial cells; the mechanism, however, is still illusive. Silencing of cytokine signaling factor 1 (SOCS1) is the primary regulator of many cytokines involved in immune reactions, whose upregulation can reverse the activation of microglial cells. Microglia could be activated into two different statuses, classic activated state (M1 state) and alternative activated state (M2 state), and M1 state is harmful, but M2 is beneficial. In the present study, N9 microglial cells were exposed to Aβ to imitate microglial activation in AD. And Western blot and immunocytochemistry were taken to observe inducible nitric oxide synthase (iNOS), Arginase-1 (Arg-1), and SOCS1 expressions, and the enzyme-linked immunosorbent assay (ELISA) was used to measure inflammatory and neurotrophic factor release. Compared with the normal cultured control cells, Aβ exposure markedly increased the level of microglial M1 state markers ( P < 0.05 ), including iNOS protein expression, tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and IL-6 releases, and BBR administration upregulated SOSC1 expression and the level of microglial M2 state markers ( P < 0.05 ), such as Arg-1 expression, brain-derived neurotrophic factor (BDNF), and glial cell-derived neurotrophic factor (GDNF) releases, downregulating the SOCS1 expression by using siRNA, however, significantly reversed the BBR-induced effects on microglial M1 and M2 state markers and SOCS1 expression ( P < 0.05 ). These findings indicated that BBR can inhibit Aβ-induced microglial activation via modulating the microglial M1/M2 activated state, and SOCS1 mediates the process.

XBC microemulsion can enhance TMP oral bioavailability, brain targeting and tissue distribution, mainly through a synergistic action of Rhizoma ligustric Chuanxiong extracts and borneol.

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