Senkyunolides reduce hydrogen peroxide-induced oxidative damage in human liver HepG2 cells via induction of heme oxygenase-1

School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong.
Chemico-biological interactions (Impact Factor: 2.58). 12/2009; 183(3):380-9. DOI: 10.1016/j.cbi.2009.11.029
Source: PubMed


Rhizoma Chuanxiong is widely used as folk medicine to treat the diseases caused by oxidative stress and inflammation. To delineate the underlying molecular mechanisms, we recently found that Rhizoma Chuanxiong extract significantly induced heme oxygenase-1 (HO-1), an enzyme that degrades intracellular heme into three bioactive products: biliverdin, carbon monoxide and free iron. The anti-inflammatory, antiapoptotic and antiproliferative actions of these products highlight HO-1 as a key endogenous antioxidant and cytoprotective gene. This study was designed to further characterize HO-1 induction of Rhizoma Chuanxiong through bioactivity-guided fractionation. All isolated fractions were assayed for HO-1 induction in human HepG2 cell line at mRNA and protein levels. Based on chromatographic profiling, nuclear magnetic resonance (NMR) and mass spectrometric analysis, the active compounds were identified as senkyunolide-H and its stereoisomer senkyunolide-I. Both senkyunolide isomers inhibited the formation of reactive oxygen species and lipid peroxidation and enhanced the cellular resistance to hydrogen peroxide-induced oxidative damage. Notably, heme oxygenase inhibitor tin protoporphyrin IX (SnPP) significantly suppressed the antioxidant activity of senkyunolide stereoisomers. Thus, this study demonstrated that senkyunolide-H and -I attenuated oxidative damage via activation of HO-1 pathway.

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    • "The formulation consists of seven ingredients, including Radix Astragali (Huang Qi), Radix Angelicae Sinensis (Dang Gui), Radix Paeoniae Rubra (Chi Shao), Rhizoma Chuanxiong (Chuan Xiong), Flos Carthami (Hong Hua), Semen Persicae (Tao Ren), and Pheretima (Di Long) [20,21]. We previously profiled the cellular responses to formulation ISF-1 in human HepG2 cells by a genome-wide biological response fingerprinting (BioReF) approach [20], and developed a bioactivity-guided fractionation procedure involving liquid-liquid extraction, HPLC separation and RT-PCR detection to identify the active compounds involved in the induction of heme oxygenase-1 and leukotriene B4 12-hydroxydehydrogenase [22,23]. "
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    ABSTRACT: Background The Chinese medicine formulation ISF-1 (also known as Bu-Yang-Huan-Wu-Tang) for post-stroke rehabilitation could increase the expression of growth-regulating protein follistatin by approximately 4-fold. This study aims to identify the active compounds of ISF-1 for the induction of follistatin expression. Methods Active compounds in ISF-1 responsible for induction of follistatin were identified by a bioactivity-guided fractionation procedure involving liquid-liquid extraction, HPLC separation and RT-PCR detection. The aqueous extracts of seven ISF-1 ingredients including Semen Persicae (Tao Ren) and the S. Persicae-derived fractions were assayed for the induction of follistatin mRNA expression in human hepatocarcinoma HepG2 cells by RT-PCR. The concentrations of isolated compounds were proportionally normalized to the reported IC50 concentration (5.8 mg/mL) of the formulation ISF-1 in HepG2. The active fractions were characterized by reverse-phase HPLC on a C18 column and identified by mass spectrometry. Results Three ingredients of ISF-1, namely S. Persicae (Tao Ren), Pheretima (Di Long), and Flos Carthami (Hong Hua), induced the expression of follistatin mRNA. Among these, the ingredient S. Persicae were the most active, and amygdalin from S. Persicae extract was identified as a novel follistatin inducer. Amygdalin stimulated the growth of skeletal muscle cell line C2C12 cells in a concentration-dependent manner. Conclusions Amygdalin isolated from S. Persicae extract in ISF-1 through a bioactivity-guided fractionation procedure induced the expression of follistatin in HepG2 and C2C12 cell lines.
    Full-text · Article · Sep 2014 · Chinese Medicine
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    • "Compared with the single target-based bioactivity-guided fractionation, our BioReF-based strategy guarantees the high success rate for the identification of the active compounds from complex herbal medicines. For example, we have successfully identified the active compounds for inducing heme oxygenase-1 (HO-1) and leukotriene B4 12-hydroxydehydrogenase (LTB4DH) from the well-known poststroke rehabilitation formulation ISF-1 [22, 23]. In the present study, we investigated the activity of herbal medicine Semen Persicae in promoting neurite outgrowth in PC12 cells. "
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    ABSTRACT: Herbal medicine Semen Persicae is widely used to treat blood stasis in Chinese medicine and other oriental folk medicines. Although little is known about the effects of Semen Persicae and its active compounds on neuron differentiation, our pilot study showed that Semen Persicae extract promoted neurite outgrowth in rat dopaminergic PC12 cells. In the present study, we developed a bioactivity-guided fractionation procedure for the characterization of the neurotrophic activity of Semen Persicae extract. The resultant fractions were assayed for neurite outgrowth in PC12 cells based on microscopic assessment. Through liquid-liquid extraction and reverse phase HPLC separation, a botanical glycoside amygdalin was isolated as the active compound responsible for the neurotrophic activity of Semen Persicae extract. Moreover, we found that amygdalin rapidly induced the activation of extracellular-signal-regulated kinase 1/2 (ERK1/2). A specific ERK1/2 inhibitor PD98059 attenuated the stimulatory effect of amygdalin on neurite outgrowth. Taken together, amygdalin was identified as a potent neurotrophic agent from Semen Persicae extract through a bioactivity-guided fractional procedure. The neurotrophic activity of amygdalin may be mediated by the activation of ERK1/2 pathway.
    Full-text · Article · Jun 2014 · BioMed Research International
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    • "Protein expression was analyzed by western blotting as previously described [10, 12]. Briefly, thirty micrograms of the cellular proteins was resolved by electrophoresis in 10% SDS-polyacrylamide gel and subsequently transferred to polyvinylidene difluoride (PVDF) membrane. "
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    ABSTRACT: Chinese herbal medicine formula Tao Hong Si Wu decoction (THSWD) is traditionally used in China for cerebrovascular diseases. However, the molecular mechanisms of THSWD associated with the cerebral ischemia reperfusion injury are largely unknown. The current study applied the two-dimensional gel electrophoresis-based proteomics to investigate the different protein profiles in PC12 cells with and without the treatment of THSWD. Twenty-six proteins affected by THSWD were identified by MALDI-TOF mass spectrometry. Gene ontology analysis showed that those proteins participated in several important biological processes and exhibited diverse molecular functions. In particular, six of them were found to be phase II antioxidant enzymes, which were regulated by NF-E2-related factor-2 (Nrf2). Quantitative PCR further confirmed a dose-dependent induction of the six phase II enzymes by THSWD at the transcription level. Moreover, the individual ingredients of THSWD were discovered to synergistically contribute to the induction of phase II enzymes. Importantly, THSWD's protection against oxygen-glucose deprivation-reperfusion (OGD-Rep) induced cell death was significantly attenuated by antioxidant response element (ARE) decoy oligonucleotides, suggesting the protection of THSWD may be likely regulated at least in part by Nrf2-mediated phase II enzymes. Thus, our data will help to elucidate the molecular mechanisms underlying the neuroprotective effect of THSWD.
    Full-text · Article · May 2014 · Evidence-based Complementary and Alternative Medicine
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