Induction of heme oxygenase-1 by traditional Chinese medicine formulation ISF-1 and its ingredients as a cytoprotective mechanism against oxidative stress

Abstract

Abstract. Traditional medicines are clinically used to treat post-stroke disorders in China. In search of alternative medicines for post-stroke rehabilitation, we recently identified the heme oxygenase-1 (HO-1) pathway as a key mechanism underlying the biological activities of the ischemic stroke formulation ISF-1. This study was designed to further investigate ISF-1 for HO-1 induction in cultured human cells and corresponding cytoprotective effects against oxidative injury. A rat stroke model induced by middle cerebral artery occlusion was employed to verify the activity of ISF-1 in vivo. It was found that HO-1 expression was induced by ISF-1 in a dose-and time-dependent manner. Four ingredients from ISF-1 were identified to be responsible for HO-1 induction. The appropriate combinations of these active ingredients or purified compounds resulted in synergistic induction of HO-1 expression. A minimal HO-1-inducing formulation was prepared and showed significant cytoprotection against H 2 O 2 -induced oxidative stress. Collectively, the herbal formulation ISF-1 was capable of inducing HO-1 expression, in vitro and in vivo, offering a potential mechanism for post-stroke rehabilitation. This study may shed light on the development of mechanism-defined therapies based on traditional herbal remedies.

Combinative effects of Thanh Hao Miet Giap Thang (sweetwormwood and tortoise shell decoction) ingredients on antioxidative activity<i> in vitro</i>

“…High antioxidant activity of MC observed in this study was in agreement with previous reports (Matsuda et In a multi-component formula, curative effects result from interactions among different components (Rong et al, 2008;Wang et al, 2014). We generated a panel of all possible combinations of ingredients from THMGT and tested their anti-oxidative capacity in order to determine possible combinative effects of components on the overall activity of the whole formula.…”

Pharmacological induction of leukotriene B4-12-hydroxydehydrogenase suppresses the oncogenic transformation of human hepatoma HepG2 cells

“…We recently described a genome-wide biological response fingerprinting (BioReF) approach for simultaneous identification of the genes regulated by complex herbal formulations in human cells (28,46). By assaying the change of specific genes, we further developed a step-wise deletion strategy for the identification of the active ingredients in the formulation as described (30). As a result, we successfully characterized three active ingredients for the induction of heme oxygenase-1 expression.…”

“…Following the drug treatment, the cellular proteins were extracted and analyzed for protein expression as previously described (29,30). Briefly, 30 µg of the cellular proteins were resolved by electrophoresis in 10% SDS-polyacrylamide gel, and subsequently transferred to polyvinylidene difluoride (PVDF) membrane.…”

Botanical Drug Puerarin Attenuates 6-Hydroxydopamine (6-OHDA)-Induced Neurotoxicity via Upregulating Mitochondrial Enzyme Arginase-2

“…For the analysis at mRNA level, total RNAs were isolated from puerarin-treated and control cells, and arginase-1 and -2 mRNAs were then detected by reverse transcription polymerase chain reaction (RT-PCR) technique as described [37]. As shown in Fig.…”