The herbal extract KCHO-1 exerts a neuroprotective effect by ameliorating oxidative stress via heme oxygenase-1 upregulation

Lee, Dong‐Sung; Ko, Wonmin; Song, Bong‐Keun; Son, Ilhong; Kim, Dong‐Woung; Kang, Dae‐Gil; Lee, Hosub; Oh, Hyuncheol; Jang, Jun‐Hyeog; Kim, Youn‐Chul; Kim, Sung‐Chul

doi:10.3892/mmr.2016.5129

Cited by 15 publications

(11 citation statements)

References 44 publications

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“…Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor which controls the redox state as the cell’s main defense mechanism against oxidative stress. 6 , 7 Nrf2 acts by activating the antioxidant response, which induces the transcription of a wide range of genes that are able to counteract the harmful effects of oxidative stress, thus restoring intracellular homeostasis. 8 Under basal conditions, Nrf2 is localized in the cytoplasm, anchored by the Kelch-like ECH-associated protein (Keap1), and degraded by the ubiquitin-26S proteasome pathway, with a half-life of 20 min.…”

Section: Introductionmentioning

confidence: 99%

Ketamine ameliorates oxidative stress-induced apoptosis in experimental traumatic brain injury via the Nrf2 pathway

Liang¹,

Wu²,

Xie³

et al. 2018

DDDT

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BackgroundKetamine can act as a multifunctional neuroprotective agent by inhibiting oxidative stress, cellular dysfunction, and apoptosis. Although it has been proven to be effective in various neurologic disorders, the mechanism of the treatment of traumatic brain injury (TBI) is not fully understood. The aim of this study was to investigate the neuroprotective function of ketamine in models of TBI and the potential role of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in this putative protective effect.Materials and methodsWild-type male mice were randomly assigned to five groups: Sham group, Sham + ketamine group, TBI group, TBI + vehicle group, and TBI + ketamine group. Marmarou’s weight drop model in mice was used to induce TBI, after which either ketamine or vehicle was administered via intraperitoneal injection. After 24 h, the brain samples were collected for analysis.ResultsKetamine significantly ameliorated secondary brain injury induced by TBI, including neurological deficits, brain water content, and neuronal apoptosis. In addition, the levels of malondialdehyde (MDA), glutathione peroxidase (GPx), and superoxide dismutase (SOD) were restored by the ketamine treatment. Western blotting and immunohistochemistry showed that ketamine significantly increased the level of Nrf2. Furthermore, administration of ketamine also induced the expression of Nrf2 pathway-related downstream factors, including hemeoxygenase-1 and quinine oxidoreductase-1, at the pre- and post-transcriptional levels.ConclusionKetamine exhibits neuroprotective effects by attenuating oxidative stress and apoptosis after TBI. Therefore, ketamine could be an effective therapeutic agent for the treatment of TBI.

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Section: Introductionmentioning

confidence: 99%

Ketamine ameliorates oxidative stress-induced apoptosis in experimental traumatic brain injury via the Nrf2 pathway

Liang¹,

Wu²,

Xie³

et al. 2018

DDDT

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“…Prior studies have shown that Mecasin, a herbal extract, has neuro-protective and anti-neuroinflammatory effects, and its safety has been proven in both in vitro and in vivo trials [ 8 – 14 ]; it has been shown to reduce the progression of ALS in Korean Medicine Clinics [ 6 , 7 ]. No previous randomized controlled trial has examined the effects of Mecasin for the treatment of ALS.…”

Section: Discussionmentioning

confidence: 99%

“…Another study showed that 30 days of the combined therapy led to a K-ALSFRS-R score increase from 28.42 ± 7.83 to 29.08 ± 7.99 [ 7 ]. Mecasin, also known as KCHO-1, a herbal extract from modified jakyakgamchobuja-tang , has shown neuro-protective and anti-neuroinflammatory effects and safety in both in vitro and in vivo trials [ 8 – 14 ]. The aim of this study was to develop a protocol to assess the optimal dosage of Mecasin, and to test whether Mecasin alleviates the functional decline in patients with ALS.…”

Section: Introductionmentioning

confidence: 99%

Mecasin treatment in patients with amyotrophic lateral sclerosis: study protocol for a randomized controlled trial

Kim

Son

et al. 2018

Trials

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BackgroundAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes paralysis of limb, swallowing, and breathing muscles. Riluzole, the Food and Drug Administration-approved drug for ALS, provides minimal benefit, prolonging patient life by only 2–3 months. Previous studies have found a neuro-protective and anti-neuroinflammatory effect of Mecasin, with retrospective studies providing suggestive evidence for a beneficial effect of Mecasin. The aim of this study was to develop a protocol to determine the proper dosage of Mecasin.MethodsThis is a phase II-A, multi-center, randomized study with three arms. Thirty-six patients with ALS will be randomly assigned to one of three groups, each receiving the standard treatment with 100 mg of riluzole in addition to one of 1.6 g of Mecasin, 2.4 g of Mecasin, or a placebo. The Primary outcome is the Korean version of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised result after 12 weeks of treatment. Secondary outcomes include results of the Short Form Health Survey-8, Medical Research Council Scale, Visual Analogue Scale for Pain, Hamilton Rating Scale for Depression, Fatigue Severity Scale, Patient Global Impression of Change, pulmonary function test, forced expiratory volume in 1 s and its ratio to forced vital capacity, creatine kinase, and body weight. The frequencies of total adverse events and serious adverse events will be described and documented. The trial protocol has been approved by the Institutional Review Board of the Wonkwang University Gwangju and Sanbon Hospital (2016–5-4 and 2016–34-01, respectively). An Investigational New Drug status (30731) was granted by the Korea Food and Drug Administration.DiscussionThis trial will aim to identify the optimal dosage of Mecasin. Additionally, it will test the efficacy and safety of Mecasin in conjunction with standard treatment, riluzole, for alleviating the functional decline in patients with ALS.Trial registrationKorean National Clinical Trial Registry CRIS; KCT0001984. Registered on 28 July 2016.Electronic supplementary materialThe online version of this article (10.1186/s13063-018-2557-z) contains supplementary material, which is available to authorized users.

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“…KCHO‐1 has been shown to reduce oxidative damage caused by glutamate and H 2 O 2 in nerve cells such as HT22 mouse hippocampal cells. KCHO‐1 can upregulate the translocation of Nrf2 and increase transcription and the expression of HO‐1 in these same cells (Lee et al, ). Another study has suggested that pretreatment of PC12 cells with the monoterpenes α‐pinene or eucalyptol prevented changes in cell morphology and viability caused by H 2 O 2 .…”

Section: Neurotoxicitymentioning

confidence: 99%

“…The exposure of astrocytes to MeHg can lead to changes in their morphology and to an increase in the rate of apoptosis. On the other hand, treatment with tea polyphenols significantly upregulated Nrf2 and its downstream genes like HO‐1 and ameliorated to a large degree the MeHg toxic effects (Lee et al, ).…”

Section: Neurotoxicitymentioning

confidence: 99%

The neuroprotective activities of natural products through the Nrf2 upregulation

Tavakkoli

Iranshahi

Hasheminezhad

et al. 2019

Phytotherapy Research

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Nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) is a basic‐region leucine zipper transcription factor that regulates the expression of many Phase II detoxifying/antioxidant enzymes. Many natural products act on the Nrf2 pathway and exhibit their preventive and/or therapeutic effects by activating Nrf2 and subsequently antioxidant enzymes. In this article, we reviewed the research literature that described Nrf2 activation as a mechanism for the neuroprotective effect of natural products. Our results showed that the inhibition of Kelch‐like ECH‐associated protein 1 and the activation of different intracellular kinases that lead to Nrf2 phosphorylation were the main mechanisms of Nrf2 upregulation suggested for these the natural products. Although some natural compounds such as terpenoids and alkaloids were reported to protect the nervous system by Nrf2 activating, flavonoids and phenolic compounds represent the majority of the reported neuroprotective natural substances that activate Nrf2. We also evaluated the physiochemical properties of some of the same substances to predict their oral bioavailability and central nervous system penetration. The results showed that sulforaphane and berberine have good oral bioavailability and would be predicted to cross through blood–brain barrier (BBB) easily, whereas the flavonoids in general would be predicted to be less effective in BBB transition because of their relatively high polar surface area.

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The herbal extract KCHO-1 exerts a neuroprotective effect by ameliorating oxidative stress via heme oxygenase-1 upregulation

Cited by 15 publications

References 44 publications

Ketamine ameliorates oxidative stress-induced apoptosis in experimental traumatic brain injury via the Nrf2 pathway

Ketamine ameliorates oxidative stress-induced apoptosis in experimental traumatic brain injury via the Nrf2 pathway

Mecasin treatment in patients with amyotrophic lateral sclerosis: study protocol for a randomized controlled trial

The neuroprotective activities of natural products through the Nrf2 upregulation

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