Acute and repeated dose 26-week oral toxicity study of 20(S)-ginsenoside Rg3 in Kunming mice and Sprague-Dawley rats

Li, Chunmei,Wang, Zhezhe,Li, Guisheng,Wang, Zhenhua,Yang, Jianrong,Li, Yanshen,Wang, Hongtao,Jin, Haizhu,Qiao, Junhua,Wang, Hongbo,Tian, Jingwei,Lee, Albert W.,Gao, Yonglin The Korean Society of Ginseng 2020 Journal of Ginseng Research Vol.44 No.2

Background: 20(S)-ginsenoside-Rg3 (C₄₂H₇₂O₁₃), a natural triterpenoid saponin, is extracted from red ginseng. The increasing use of 20(S)-ginsenoside Rg3 has raised product safety concerns. Methods: In acute toxicity, 20(S)-ginsenoside Rg3 was singly and orally administrated to Kunming mice and Sprague-Dawley (SD) rats at the maximum doses of 1600 mg/kg and 800 mg/kg, respectively. In the 26-week toxicity study, we used repeated oral administration of 20(S)-ginsenoside Rg3 in SD rats over 26 weeks at doses of 0, 20, 60, or 180 mg/kg. Moreover, a 4-week recovery period was scheduled to observe the persistence, delayed occurrence, and reversibility of toxic effects. Results: The result of acute toxicity shows that oral administration of 20(S)-ginsenoside Rg3 to mice and rats did not induce mortality or toxicity up to 1600 and 800 mg/kg, respectively. During a 26-week administration period and a 4-week withdrawal period (recovery period), there were no significant differences in clinical signs, body weight, food consumption, urinalysis parameters, biochemical and hematological values, or histopathological findings. Conclusion: The mean oral lethal dose (LD₅₀) of 20(S)-ginsenoside Rg3, in acute toxicity, is above 1600 mg/kg and 800 mg/kg in mice and rats, respectively. In a repeated-dose 26-week oral toxicity study, the no-observed-adverse-effect level for female and male SD rats was 180 mg/kg.

Assessment of cutting time on nutrient values, in vitro fermentation and methane production among three ryegrass cultivars

Wang Chunmei,Hou Fujiang,Wanapat Metha,Yan Tianhai,김은중,Scollan Nigel David 아세아·태평양축산학회 2020 Animal Bioscience Vol.33 No.8

Objective: The 3×3 factorial arrangement was used to investigate if either high water-soluble carbohydrates (WSC) cultivars or suitable time of day that the grass cut could improve nutrient values and in vitro fermentation characteristics. Methods: The 3 cultivars were mowed at 3 diurnal time points and included a benchmark WSC ryegrass cultivar ‘Premium’, and 2 high WSC cultivars AberAvon and AberMagic, which contained, on average, 157, 173, and 193 g/kg dry matter (DM) of WSC, and 36.0, 36.5, and 34.1 g/kg DM of N during 7th regrowth stage, respectively. The fermentation jars were run at 39°C with gas production recorded and sampled at 2, 5, 8, 11, 14, 17, 22, 28, 36, and 48 h. The rumen liquid was collected from 3 rumen fistulated cows grazing on ryegrass pasture. Results: High WSC cultivars had significantly greater WSC content, in vitro DM digestibility (IVDMD) and total gas production (TGP), and lower lag time than Premium cultivar. Methane production for AberMagic cultivar containing lower N concentration was marginally lower than that for AberAvon and Premium cultivars. Grass cut at Noon or PM contained greater WSC concentration, IVDMD and TGP, and lower N and neutral detergent fiber (NDF) contents, but CH4 production was also increased, compared to grass cut in AM. Meanwhile, the effects of diurnal cutting time were influenced by cultivars, such as in vitro CH4 production for AberMagic was not affected by cutting time. The IVDMD and gas production per unit of DM incubated were positively related to WSC concentration, WSC/N and WSC/NDF, respectively, and negatively related to N and NDF concentrations. Conclusion: These results imply either grass cut in Noon or PM or high WSC cultivars could improve nutrient values, IVDMD and in vitro TGP, and that AberMagic cultivar has a slightly lower CH4 production compared to AberAvon and Premium. Further study is necessary to determine whether the increase of CH4 production response incurred by shifting from AM cutting to Noon and/or PM cutting could be compensated for by high daily gain from increased WSC concentration and DM digestibility.

Acute and repeated dose 26-week oral toxicity study of 20(S)-ginsenoside Rg3 in Kunming mice and Sprague – Dawley rats

Chunmei Li,ZhezheWang,Guisheng Li,ZhenhuaWang,Jianrong Yang,Yanshen Li,Hongtao Wang,Haizhu Jin,Junhua Qiao,Hongbo Wang,Jingwei Tian,Albert W. Lee,Yonglin Gao 고려인삼학회 2020 Journal of Ginseng Research Vol.44 No.2

Background: 20(S)-ginsenoside-Rg3 (C42H72O13), a natural triterpenoid saponin, is extracted from redginseng. The increasing use of 20(S)-ginsenoside Rg3 has raised product safety concerns. Methods: In acute toxicity, 20(S)-ginsenoside Rg3 was singly and orally administrated to Kunming miceand SpragueeDawley (SD) rats at the maximum doses of 1600 mg/kg and 800 mg/kg, respectively. In the26-week toxicity study, we used repeated oral administration of 20(S)-ginsenoside Rg3 in SD rats over 26weeks at doses of 0, 20, 60, or 180 mg/kg. Moreover, a 4-week recovery period was scheduled to observethe persistence, delayed occurrence, and reversibility of toxic effects. Results: The result of acute toxicity shows that oral administration of 20(S)-ginsenoside Rg3 to mice andrats did not induce mortality or toxicity up to 1600 and 800 mg/kg, respectively. During a 26-weekadministration period and a 4-week withdrawal period (recovery period), there were no significantdifferences in clinical signs, body weight, food consumption, urinalysis parameters, biochemical andhematological values, or histopathological findings. Conclusion: The mean oral lethal dose (LD50) of 20(S)-ginsenoside Rg3, in acute toxicity, is above 1600mg/kg and 800 mg/kg in mice and rats, respectively. In a repeated-dose 26-week oral toxicity study, theno-observed-adverse-effect level for female and male SD rats was 180 mg/kg.

Two-stage Active Disturbance Rejection Control for Coupled Permanent Magnet Synchronous Motors System With Mismatched Disturbance

Chunmei Pu,Zhanshan Wang,Shuran Wang 제어·로봇·시스템학회 2024 International Journal of Control, Automation, and Vol.22 No.6

In this paper, the design method of active disturbance reject control (ADRC) is revisited for coupled permanent magnet synchronous motors (CPMSMs) system with mismatched disturbance conditions. The traditional ADRC is not applicable in the case of mismatched disturbances, because it requires the controlled object have a strict integral chain form. In addition, the coupled permanent magnet synchronous motors is exactly one of the model with mismatch disturbance. Therefore, the idea of dividing the control law into two-stage is proposed, which is to make the disturbance and control input appear in the same channel, so that establish a matched disturbance form model of CPMSMs. An important contribution of this article is to overcome the disturbance which is not in the same equation as the control input voltage (that is ud and uq). Then, design a linear extended state observer (LESO) and a control law to estimate and compensate the mismatched disturbance. Finally, the proposed control strategy is verified by simulation via Matlab/Simulink program. The simulation results show that the proposed control method has a better control performance.

Tizoxanide induces autophagy by inhibiting PI3K/Akt/ mTOR pathway in RAW264.7 macrophage cells

Jiaoqin Shou,Mi Wang,Xiaolei Cheng,Xiaoyang Wang,Lifang Zhang,Yingchun Liu,Chenzhong Fei,Chunmei Wang,Feng Gu,Feiqun Xue,Juan Li,Keyu Zhang 대한약학회 2020 Archives of Pharmacal Research Vol.43 No.2

As the main metabolite of nitazoxanide, tizoxanide(TIZ) has a broad-spectrum anti-infective effect againstparasites, bacteria, and virus. In this study, we investigatedthe effects of TIZ on autophagy by regulating the PI3K/Akt/mTOR signaling pathway. RAW264.7 macrophage cellswere treated with various TIZ concentrations. Cell viabilityassay, transmission electron microscope, and immunofluorescencestaining were used to detect the biological functionof the macrophage cells, and the expression levels of theautophagy pathway-related proteins were measured by Westernblot. Results revealed that TIZ promoted the conversionof LC3-I to LC3-II, the formation of autophagy vacuoles,and the degradation of SQSTM1/p62 in a concentration- andtime-dependent manner in RAW264.7 cells. Treatment withTIZ increased the Beclin-1 expression level and inhibitedPI3K, Akt, mTOR, and ULK1 activation. These effects wereenhanced by pretreatment with rapamycin but attenuated bypretreatment with LY294002. In addition, the conversion ofLC3-I to LC3-II was observed in Vero, 293T, and HepG2cells treated with TIZ. These data suggested that TIZ mayinduce autophagy by inhibiting the Akt/mTOR/ULK1 signalingpathway in macrophages and other cells.

Protective Effect of Schisandra chinensis Polysaccharides Against the Immunological Liver Injury in Mice Based on Nrf2/ARE and TLR4/NF-κB Signaling Pathway

Yingying Shan,Bin Jiang,Jiahui Yu,Jiaye Wang,Xiaoli Wang,He Li,Chunmei Wang,JianGuang Chen,Jinghui Sun 한국식품영양과학회 2019 Journal of medicinal food Vol.22 No.9

We have previously demonstrated the hepatoprotective effect of Schisandra chinensis polysaccharides (SCP) against the liver injury induced by alcohol, high-fat diet, and carbon tetrachloride in mice. In this study, we investigated the effect of SCP against the immunological liver injury induced by concanavalin A (Con A) in mice. The results showed that SCP could significantly reduce the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in the serum of mice with immunological liver injury. SCP could significantly decrease the content of malondialdehyde (MDA) and nitric oxide (NO) and increase the activity of superoxide dismutase (SOD) and glutathione (GSH) in the liver tissue. SCP could significantly increase the number of CD4+ and decrease the number of CD8+ in the peripheral blood, and elevate the ratio of CD4+/CD8+. SCP could significantly downregulate the expression of Kelch-like ECH-associated protein 1 (Keap1) and upregulate the expression of nuclear factor-erythroid 2-related factor2 (Nrf2) and downstream gene heme oxygenase-1 (HO-1), and downregulate the expression of toll-like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (MyD88), and nuclear factor-kappa B (NF-κB) proteins. This study indicates that SCP can reduce the release of a large number of inflammatory factors to inhibit the oxidative stress in mice with the immunological liver injury induced by Con A, and its mechanism is closely related to the regulation of Nrf2/antioxidant response element and TLR4/NF-κB signaling pathways.

In vitro biological evaluation of 100 selected methanol extracts from the traditional medicinal plants of Asia

Chunmei Li,Myeong-Hyeon Wang 한국영양학회 2014 Nutrition Research and Practice Vol.8 No.2

BACKGROUND/OBJECTIVES: In Asia, various medicinal plants have been used as the primary sources in the health care regimen for thousands of years. In recent decades, various studies have investigated the biological activity and potential medicinal value of the medicinal plants. In this study, 100 methanol extracts from 98 plant species were evaluated for their biological activities. MATERIALS/METHODS: The research properties, including 1,1-diphenyl-2-pic-rylhydrazyl (DPPH) radical scavenging activity, α-glucosidase and α-tyrosinase inhibitory effects, anti-inflammatory activity, and anticancer activity were evaluated for the selected extracts. RESULTS: Fifteen of the extracts scavenged more than 90% of the DPPH radical. Among the extracts, approximately 20 extracts showed a strong inhibitory effect on α-glucosidase, while most had no effect on α-tyrosinase. In addition, 52% of the extracts showed low toxicity to normal cells, and parts of the extracts exhibited high anti-inflammatory and anticancer activities on the murine macrophage cell (RAW 264.7) and human colon cancer cell (HT-29) lines, respectively. CONCLUSIONS: Our findings may contribute to further nutrition and pharmacological studies. Detailed investigations of the outstanding samples are currently underway.

Ginsenoside Rh2 reduces m6A RNA methylation in cancer via the KIF26B-SRF positive feedback loop

Chunmei Hu,Linhan Yang,Yi Wang,Shijie Zhou,Jing Luo,Yi Gu 고려인삼학회 2021 Journal of Ginseng Research Vol.45 No.6

Background: The underlying mechanisms of the potential tumor-suppressive effects of ginsenoside Rh2are complex. N6-methyladenosine (m6A) RNA methylation is usually dysregulated in cancer. This studyexplored the regulatory effect of ginsenoside Rh2 on m6A RNA methylation in cancer. Methods: m6A RNA quantification and gene-specific m6A RIP-qPCR assays were applied to assess totaland gene-specific m6A RNA levels. Co-immunoprecipitation, fractionation western blotting, andimmunofluorescence staining were performed to detect protein interactions and distribution. QRT-PCR,dual-luciferase, and ChIP-qPCR assays were conducted to check the transcriptional regulation. Results: Ginsenoside Rh2 reduces m6A RNA methylation and KIF26B expression in a dose-dependentmanner in some cancers. KIF26B interacts with ZC3H13 and CBLL1 in the cytoplasm of cancer cellsand enhances their nuclear distribution. KIF26B inhibition reduces m6A RNA methylation level in cancercells. SRF bound to the KIF26B promoter and activated its transcription. SRF mRNA m6A abundancesignificantly decreased upon KIF26B silencing. SRF knockdown suppressed cancer cell proliferation andgrowth both in vitro and in vivo, the effect of which was partly rescued by KIF26B overexpression. Conclusion: ginsenoside Rh2 reduces m6A RNA methylation via downregulating KIF26B expression insome cancer cells. KIF26B elevates m6A RNA methylation via enhancing ZC3H13/CBLL1 nuclear localization. KIF26B-SRF forms a positive feedback loop facilitating tumor growth.

Anti-inflammatory effect of the water fraction from hawthorn fruit on LPS-stimulated RAW 264.7 cells

Chunmei Li,Myeong-Hyeon Wang 한국영양학회 2011 Nutrition Research and Practice Vol.5 No.2

The hawthorn fruit (Crataegus pinnatifida Bunge var. typica Schneider) is used as a traditional medicine in Korea. The objective of this study was to understand the mechanisms of the anti-inflammatory effects of the water fractionated portion of hawthorn fruit on a lipopolysaccharide (LPS)-stimulated RAW 264.7 cellular model. The level of nitric oxide (NO) production in the water fraction and LPS-treated RAW 264.7 cells were determined with an ELISA. The cytotoxicity of the water fraction and LPS was measured with an MTT assay. Expression of nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF)-α, interleukin 6 (IL-6), and interleukin 1β (IL-1β) mRNA were analyzed with a reverse transcription polymerase chain reaction (RT-PCR). The water fraction of hawthorn fruit was determined to be safe and significantly inhibited NO production in LPS-stimulated RAW 264.7 cells and suppressed COX-2, TNF-α, IL-1β, and IL-6 expression. The observed anti-inflammatory effects of the water fraction of hawthorn fruit might be attributed to the down-regulation of COX-2, TNF-α, IL-1β, and IL-6 expression in LPS-stimulated RAW 264.7 cells.

Biological Activities of Water and Ethanolic Extracts from Allium victorialis L. Mature Leaves

Chunmei Li,Young-Mee Lee,Kyeong-Cheol Lee,Woong Han,Myeong-Hyeon Wang,Sang-Sup Han 한국식품영양과학회 2011 Preventive Nutrition and Food Science Vol.16 No.3

Allium victorialis L. (A. victorialis) is a very popular vegetable in Korea. The most commonly used parts of this vegetable are the bulbs and young leaves. To determine if the mature leaves have any beneficial properties, we investigated antioxidant, anti-α-glucosidase, anti-inflammatory, and anticancer activities of water and ethanol extracts from A. victorialis. Antioxidant activity was evaluated by measuring total phenolic content, DPPH and superoxide radicals scavenging activities. The water extract from A. victorialis (W·A. victorialis) exhibited higher antioxidant ability than the ethanol extract (E·A. victorialis). Moreover, the water extract showed strong inhibitory effect on α-glucosidase. On the other hand, the ethanol extract had greater anti-inflammatory activity on murine macrophage cells (RAW 264.7) and greater anticancer activities against human colon cancer cells (HT-29). These results suggest that mature leaves from E·A. victorialis may have health-enhancing effects.