Effects of icariside II on brain tissue oxidative stress and Nrf2/HO-1 expression in rats with cerebral ischemia-reperfusion injury

Abstract Purpose: To investigate the effects of icariside II on brain tissue oxidative stress and Nrf2/HO-1 expression in rats with cerebral ischemia-reperfusion injury (CIRI). Methods: One hundred SD rats were randomly divided into sham-operated, model, and 5, 10 and 20 mg/kg icariside II groups, 20 rats in each group. The middle cerebral artery occlusion model (ischemia for 2 h followed by reperfusion for 24 h) was established in the later 4 groups. In later 3 groups, at reperfusion beginning, the rats were intragastrically administrated with 5, 10 and 20 mg/kg icariside II, respectively. After 24 h of reperfusion, the neurological severity score, cerebral water content and cerebral infarction volume, brain tissue oxidative stress indexes and Nrf2 and HO-1 protein expressions were determined. Results: Compared with model group, in 20 mg/kg icariside II group the neurological severity score, cerebral water content and cerebral infarction volume, brain tissue ROS content and MDA level were significantly decreased (P<0.05), and the brain tissue SOD, GSH-Px and catalase levels and Nrf2 and HO-1 protein levels were significantly increased (P<0.05). Conclusion: Icariside II can alleviate the CIRI in rats through reducing brain tissue oxidative stress and improving Nrf2/HO-1 expression.

Icariside II improves left ventricular function by improving endoplasmic reticulum stress and caspase 12 signaling in SHR / 中国药理学通报

Aim: To explore the mechanism of icariside II (ICS II) on improving left ventricular function based on endoplasmic reticulum stress and caspase-12 signaling in spontaneously hypertensive rats (SHRs). Methods: Thirty 14-week-old male SHRs were divided into model group, ICS II low, middle and high dose groups and positive drug group (n = 6). WKY was used as control group (n =6). ICS II groups were respectively given ICS 114, 8, 16 mg · kg-1(ig, qd), and positive drug group was given losartan (20 mg · kg-1). At the end of 26th weeks, anesthetized rats were measured by ultrasound for detection of the left ventricular function, RT-PCR was used to determine the level of GRP78 mR- NA in the left ventricle tissue, and Western blot was used to assess the levels of GRP78 and cleaved-caspase- 12/9/3 protein in the left ventricle tissues. Results: Compared with WKY group, the internal diameter and posterior wall thickness of the left ventricular end diastolic increased, while the ejection fraction and fractional shortening decreased in SHR group. GRP78 mRNA and protein levels were up-regulated, and the levels of cleaved-caspase-12/9/3 protein were raised in left ventricle (P < 0.05). Compared with SHR group, the internal diameter and posterior wall thickness of the left ventricular end diastolic increased in ICS II medium and high dose groups and positive drug group (P <0. 05), while the ejection fraction and fractional shortening decreased (P<0.05). GRP78 mRNA and protein levels were down-regulated, the levels of cleaved-caspase-12/ 9/3 protein declined in left ventricle (P <0.05). Conclusions: ICS II could improve left ventricular function in SHRs, and its mechanism may be related to improving left ventricular endoplasmic reticulum stress and down-regulating the elevated caspase-12 signaling.

Anticancer Properties of Icariside II in Human Oral Squamous Cell Carcinoma Cells

OSCC is currently the most common malignancy of the head and neck, affecting tens of thousands of patients per year worldwide. Natural flavonoids from plants are potential sources for novel anti-cancer drugs. Icariin is the active ingredient of flavonol glycoside, which is derived from the medical plant Herba Epimedii. A metabolite of icariin, icariside II exhibits a variety of pharmacological actions, including anti-rheumatic, anti-depressant, cardiovascular protective, and immunomodulatory functions. However, the exact mechanism causing the apoptosis-inducing effect of icariside II in OSCC is still not fully understood. In the present study, we assessed the anti-cancer effect of icariside II in OSCC cell lines by measuring its effect on cell viability, cell proliferation, and mitochondria membrane potential (MMP). Icariside II treatment of OSCC cells resulted in a dose- and time-dependent decrease in cell viability. Hoechst staining indicated apoptosis in icariside II-treated HSC cells. Icariside II inhibited cell proliferation and induced apoptosis in HSC cells, with significant increases in all present parameters in HSC-4 cells. The results clearly suggested that icariside II induced apoptosis via activation of intrinsic pathways and caspase cascades in HSC-4 cell lines. The collective findings of the study suggested that Icariside II is a potential treatment for OSCC; in addition, the data could provide a basis for the development of a novel anti-cancer strategy.

Determination of partition coefficients of icariside-II and icaritin based on the HPLC retention time / 中国药学杂志

OBJECTIVE: The aim of the study is to measure partition coefficients of two highly hydrophobic compounds, icariside-II and icaritin, based on their retention time on HPLC. METHODS: A series of compounds with similar structure were selected as the reference substances and their partition coefficients were determined by shake-flask method or obtained from the science finder database. The retention time of the above reference substances was determined under different concentrations of organic phase. Logkw was obtained by extrapolating to zero concentration of organic phase. A linear relationship between lgP and lgkw was established. Logkw of two substances for validation purpose (quercetin and formononetin) and two substances to be measured (icariside-II and icaritin) were obtained by the same method. LogP of above four compounds was calculated from the linear regression equation obtained from the reference substances and compared with the lgP of validation substances determined by shake-flask method. RESULTS: A linear regression equation between lgP and lgkw was established: lgP = (1.532 ± 0.091)lgkw - (1.805 ± 0.301), r2 = 0.9590. The lgP of validation substances determined by shake-flask method is within the range of lgP measured by HPLC method, indicating that the partition of the selected compounds in HPLC system is similar to that in octanol-water system. Therefore, the partition coefficient could be determined using their retention time on HPLC. The calculated lgP value of icariside-II and icaritin is (5.114 ± 0.712) and (6.074 ± 0.769), respectively. CONCLUSION: HPLC is an accurate, convenient and rapid method to determine the partition coefficient of highly hydrophobic compounds (lgP > 4). Copyright 2012 by the Chinese Pharmaceutical Association.