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Effect of improving blood pressure in patients with high blood pressure and diabetes Announced at the 13th International Symposium on Ginseng 2022 SEOUL, South Korea, Oct. 31, 2022 /PRNewswire/ -- Experts who have conducted scientific studies on the effect of ginseng gathered in Seoul from all around the world. The Korean Society of Ginseng (chaired by Lee Man-hui) said that the 13th International Symposium on Ginseng took place from the 25th to the 28th at Lotte Hotel Seoul. Professor Seikwan Oh's team from College of Medicine, Ehwa Women's University verifies that red ginseng improves memory loss and learning ability Continue Reading The 13th International Symposium on Ginseng 2022 According to the findings of a research study in 2022, red ginseng improves the memory loss associated with post-traumatic stress disorder (PTSD) [1] Post-traumatic stress disorder is stress-induced memory impairment accompanying neuroinflammation. Professor Seikwan Oh's team (joint researcher: Bombi Lee from College of Oriental Medicine, Kyunghee University) conducted a passive avoidance test and Morris water maze test on 48 rats six to eight weeks old (experiment rats), divided in six groups, to verify their learning and spatial cognition abilities after giving a constant one-time stress and injecting red ginseng extract 20, 50, 100mg/kg/1day for 14 days. The results showed the stressed rats lagged when escaping from the maze, whereas the red ginseng-injected group escaped from the maze at a similar speed to the unstressed group. They also checked the figures of various stress-induced inflammatory cytokines. Red ginseng appeared to reduce interleukin-6 (IL-6) and interleukin-8 (IL-8), which are markers of stress-induced inflammation, while increasing interleukin-12 (IL-12), which is the marker of anti-inflammation that suppresses inflammation. In addition, the red ginseng-injected group showed no increase in NF-kB, which increased and caused inflammation in the hippocampus of stressed group, and the generation of mRNA, which is the growth factor of deteriorated cranial nerves, was recovered by 252.51% after injection of red ginseng (p < 0.05). The team also disclosed the effect of red ginseng on age-related memory impairment (2015). They injected red ginseng extract (approx. 200/kg/1 day) into 32 18-month-old mice divided in four groups for three months after inducing cognitive impairment, and then conducted the Y-maze test to assess the effect on the spatial cognition ability and Morris water maze test to assess the spatial cognition and learning abilities. The result showed red ginseng represses age-related learning and memory failure. The findings verified the anti-dementia effect using the aged experiment animals that had memory failure amid continuous increase in dementia among the aged. Professor Hyong Young Kwon's team from Soonchunhyang University verifies that ginseng (ginsenoside Rd) suppresses muscle loss Published in the Journal of Cachexia, Sarcopenia and Muscle (JCSM) [2] with IF of 12.91(as of 2022) Professor Hyong Young Kwon's team from Soonchunhyang University said they verified the impact of ginsenoside Rd on muscle cells and effect of strengthening muscles, and identified the action mechanism. The findings were published in the Journal of Cachexia, Sarcopenia and Muscle, 2022, which has an impact factor (IF) of 12.91. The IF is an index figure used to compare and assess the relative importance of journals. Researches published in a journal of IF 10 or higher are regarded highly reliable. Muscle atrophy is a general degenerative disease which is caused by muscle loss and hypofunction, and can cause various cardiovascular diseases, cancers, blood poisoning, obesity and depression. According to the results of research by professor Hyong Young Kwon's team, the muscle strength of aged mice injected with ginsenoside Rd improved with time to a level similar to that of the general adult mice. Also, their muscle cell C2C12 grew bigger than the control group and the number of nuclei per cell increased from 20% to 37% in over six nuclei. Such effects appeared the same in muscle atrophy caused by steroid administration as well. The team also identified the mechanism that ginsenoside Rd grows the size of muscle cells by reducing active oxygen within muscle cells increased by TNF-α, the gene that induces inflammation. Ginsenoside Rd grew the size of muscle cells and induced the cell fusion by activating pAKT, which is the pathway essential for protein synthesis of muscle cells and reducing MuRF1 which promotes proteolysis. In addition, they implied that ginsenoside Rd can be utilized to prevent and treat cancer cachexia-led muscle atrophy by showing that it reduces phosphorylation, atrogin-1 and MuRF-1* that cause inflammation and induce muscle loss activated by TNF-α and interferon-gamma (IFNg), which cause inflammation when cancer cells proliferate or spread. Such effect of ginsenoside Rd in suppressing muscle loss also appeared in a cell test using human skeletal muscle cells (HSkM), the same as in the animal cells. Professor Narayanan's team from University of Michigan verifies that red ginseng prevents bone loss by keeping balance in intestinal microorganisms [3] The intestinal microbiota is an important controller for bone health. Intestinal microorganisms unbalanced or reduced in variety and number by extensive antibiotic treatment can bring bone loss, and it is known that bones are healthy when the intestinal microorganisms vary in types. The professor's team injected a broad-spectrum antibiotic into 21 adult male mice divided into four groups for two weeks, and then for four weeks injected water into one group and red ginseng extract 500mg/kg/1day into another group. As a result, the variety of intestinal microorganisms of mice decreased significantly after the injection of antibiotic, but it was significantly suppressed in the red ginseng-injected group, along with suppression of barrier damage. In addition, bone loss occurred considerably in femur and spine of mice, but this was prevented in the red ginseng-injected group. Professor Vuksan's team from Canada verifies that ginseng improves blood pressure of patients with high blood pressure and diabetes, and is safe for consumption by the patients [4] Professor Vuksan's team from Canada conducted a clinical test on 80 patients with Type 2 diabetes and high blood pressure for 12 weeks, and found the center systolic blood pressure significantly reduced in the group administered with Korean red ginseng and American ginseng in parallel after 12 weeks (reduction by 3.98±2 mmHg, p=0.04). Above this, there was no significant change in the pulse wave velocity and reactive hyperemia index which are used to assess the function of blood vessels. Accordingly, it confirmed that ginseng can improve the center systolic blood pressure of diabetic patients when administered auxiliary, apart from medication, without directly affecting the function of blood vessels. Moreover, professor Seo Sang-hee's team from Chungnam University presented that ginseng improves immunity against the infection of COVID 19 and enhances immunity with time. Researchers from other countries also revealed their research findings on various effects of ginseng and red ginseng. Such as Professor Tianshi Wang's team from Shanghai Jiao Tong University, China. They unveiled the effect of ginsenoside Rh1, one of the active ingredients of red ginseng, in suppressing the risk of metastasis of breast cancer. [Reference] * STAT3 phosphorylation, atrogin-1, MuRF-1 STAT3 (signal transducer and activator of transcription-3), atrogin-1 and MuRF-1(muscle ring finger=1) are proteins that promote the generation of various genes within cells, and atrogin-1 and MuRF-1 are especially involved in muscle cell fusion and differentiation. SOURCE The Korean Society of Ginseng

导语：对动物而言，冬眠是通过减少体力活动和全身新陈代谢，从而在食物匮乏和寒冷的冬季环境中生存的关键生存策略。黑熊为冬眠动物，每年需冬眠5-7个月。尽管每年有持续半年时间不活动，但黑熊仍能维持较好的肌肉质量和力量。研究表明，冬眠期间，黑熊对骨骼肌萎缩的抵抗力和新陈代谢的维持可能是通过体液或全身因素来实现的。冬眠熊的血清或血浆中可能含有一些全身循环因子，这些因子会影响骨骼肌蛋白质代谢的调节，并有助于在冬眠期间维持骨骼肌质量。骨骼肌是人体中高度可塑的组织。通过体育锻炼增加收缩活动会触发骨骼肌肥大，转变为慢肌类型，并通过线粒体生物发生增加氧化能力。相比之下，长时间不活动或营养不良会导致人体代谢功能障碍，例如骨骼肌萎缩、转变为快肌类型以及能量代谢不足。由于骨骼肌质量的损失和代谢功能障碍与较短的健康寿命直接相关，因此良好的骨骼肌质量和代谢特征是人类健康生活的一大保证。黑熊血清中含有的物质恰好可以防止人类肌肉萎缩。2022年1月，日本北海道大学研究团队在PLOS ONE发表题为“Supplementing cultured human myotubes with hibernating bear serum results in increased protein content by modulating Akt/FOXO3a signaling”的研究成果（图1）[1]。结果表明冬眠熊血清培养的人骨骼肌细胞的总蛋白质含量显著增加，可通过抑制由Akt-FOXO3a信号传导介导的蛋白质降解系统抑制蛋白质降解。图1 研究成果（图源：[1]）本研究通过在体外培养的人骨骼肌细胞中添加冬眠熊血清（Hibernating bear serum，HBS），确定HBS是否会改变骨骼肌的蛋白质和能量代谢；分析了与非冬眠期血清（active period bear serum，ABS）相比，HBS是否会改变调节人类骨骼肌细胞中蛋白质和能量代谢的信号通路。结果发现： 1与ABS相比，HBS提高了人肌管中总蛋白质含量经黑熊血清培养24小时后，人肌管并没有任何明显的形态变化或分化细胞核数量的增加。与ABS相比，HBS培养显著增加了人肌管总蛋白含量。 2HBS诱导Akt/mTORC1通路的激活本研究中使用了完全分化的肌管，因此细胞蛋白质含量的变化基本上反映了蛋白质合成和降解的平衡。鉴于HBS增加了总蛋白质含量，接下来检查了Akt的激活状态和mTORC1（mechanistic target of rapamycin complex 1）途径的机械靶点，这些途径可调节骨骼肌中蛋白质的合成。与ABS相比，HBS培养的肌管中Akt在Thr308处的磷酸化（Akt激酶活性的指标）显著增加；此外，mTORC1活性的直接下游靶点S6K1磷酸化也在Thr389和Thr421/Ser424处显著增强；S6K1的总蛋白表达也增加；Ser473的Akt磷酸化和pan-Akt的表达水平没有改变；蛋白质合成的速率没有明显的变化。这些结果表明HBS处理会诱导Akt/mTORC1通路的激活，但并不直接诱导人骨骼肌细胞中蛋白质合成的激活。 3HBS抑制人类骨骼肌细胞中蛋白质的降解因为总蛋白质含量增加而蛋白质合成系统不受影响，研究人员探索了HBS对培养肌管中蛋白水解系统的影响。骨骼肌中存在两种主要的蛋白水解途径：自噬-溶酶体系统和泛素-蛋白酶体系统。微管相关蛋白1 LC3-II（light chain 3）是自噬体形成的标志物，在肌管中没有改变，表明培养的肌管中的自噬通量没有变化。相比之下，MuRF1（muscle RING-finger protein-1）（一种骨骼肌特异性E3泛素连接酶和已知的肌肉萎缩标志物）的表达在HBS处理后显著降低。Atrogin1蛋白表达没有改变。这些结果表明，HBS抑制人类骨骼肌细胞中通过泛素-蛋白酶体依赖性系统的蛋白质降解。4HBS增强Akt-FOXO轴Akt-FOXO轴可能是骨骼肌细胞中泛素-蛋白酶体系统的潜在调节机制，特别是通过调节atrogin1和murf1基因的转录激活。FOXO3a在Ser253和Ser318/321位点的磷酸化，被Akt直接和间接磷酸化，对于核输出到胞质溶胶和抑制FOXO3a转录因子活性很重要。与ABS相比，HBS处理后肌管中FOXO3a的磷酸化和总表达显著增加。此外，HBS处理后细胞溶质FOXO3a显著增加，而核FOXO3a没有变化。这些结果表明，HBS促进了FOXO3a蛋白在胞质部分的磷酸化和螯合增加，这可能导致FOXO3a的转录活性降低。5HBS提高了IGF-1浓度IGF-1是一种血清生长因子，可诱导骨骼肌中Akt-FOXO3a轴的激活。与ABS相比，HBS处理的骨骼肌细胞IGF-1含量显著更高。该结果表明，冬眠期间血清IGF-1量的增加会影响骨骼肌细胞中的Akt-FOXO3a途径，导致MuRF1表达降低，这是FOXO3a转录活性的潜在靶标。6HBS没有诱导培养的人骨骼肌细胞中的线粒体生物发生先前的研究表明，骨骼肌中的线粒体生物发生在冬眠期间增强，因此，研究人员检测了HBS处理后培养的肌管中OXPHOS亚基蛋白的表达。研究发现大多数因素没有统计学上的显著变化，HBS处理后复合物III的表达有所下降。此外，线粒体生物发生调节因子（过氧化物酶体增殖物激活受体γ共激活因子1-α：Pgc1a）的基因表达水平和其他线粒体相关因子（线粒体解偶联蛋白3、细胞色素c、细胞色素c氧化酶亚基4和肉碱棕榈酰转移酶-1b）没有显著改变，但Pgc1b表达上调。因此，HBS处理不太可能诱导培养的人骨骼肌细胞中线粒体生物发生。在本研究中，将HBS直接添加到培养的人骨骼肌细胞中，以分析全身体液因子对蛋白质代谢调节的影响。实验结果表明，HBS正向调节肌肉蛋白质代谢，可能是通过抑制由Akt-FOXO3a信号传导介导的蛋白质降解系统，从而导致总蛋白质含量的积累。研究中一个未解决的问题是除了IGF-1之外，HBS中的哪些成分会影响骨骼肌蛋白代谢。尽管在本研究中观察到IGF-1浓度增加，但在熊血清中总蛋白质含量正常化后发现这种情况无效。先前的研究报道，熊血清中的IGF-1浓度呈现出季节性变化，在活跃的夏季期间最高，在冬眠早期最低，然后在冬眠结束时再次升高。因此，如目前的结果所示，很难确定血清IGF-1是否起到维持培养的骨骼肌细胞中蛋白质含量的作用。近年来，利用组学方法对冬眠熊的血清或组织中可能有助于代谢特征的新因子进行了广泛的探索。对冬眠熊血清的脂质组学分析表明，内源性大麻素系统在冬眠期间发生了特异性改变，从而有助于调节脂肪和骨骼肌中的能量代谢。在一项涉及miRNA测序和转录组分析的联合研究中，冬眠期间特异性诱导的三种循环microRNA的表达有助于在冬眠期间长期不活动的情况下预防静脉血栓栓塞。对于人类而言，探索黑熊冬眠期间直接有助于抑制骨骼肌蛋白水解的循环因子有助于研发药物来预防与治疗治疗与长期不活动相关的骨骼肌萎缩。撰文|文竞择排版|乔维钧 End 参考资料：[1]Miyazaki M, Shimozuru M, Tsubota T. Supplementing cultured human myotubes with hibernating bear serum results in increased protein content by modulating Akt/FOXO3a signaling. PLoS One. 2022 Jan 25;17(1):e0263085. doi: 10.1371/journal.pone.0263085. PMID: 35077510; PMCID: 本文系生物探索原创，欢迎个人转发分享。 其他任何媒体、网站如需转载，须在正文前注明来源生物探索。 往期精选 围观 新冠疫苗致月经异常的中东/北非/南美数据：高达66.3%！包括辉瑞/国药/科兴… 热文 巧合？又是武汉海鲜市场！研究在牛蛙中发现霍乱弧菌，霍乱与水产品有何关联 热文 华人自述：感染新冠BA.5后咳血难忍，BA.5抗性是mRNA疫苗的4倍！迄今最糟糕的变异版本 热文 Science重磅！新一代纳米疫苗即将问世，可免疫8种冠状病毒，预防未来变体 热文 西班牙11家医院血液中心：新冠疫苗引发自身免疫性血液疾病？可能性极低 点击“阅读原文”，了解更多~