Screening ginseng saponins in progenitor cells identifies 20(R)-ginsenoside Rh2 as an enhancer of skeletal and cardiac muscle regeneration

Kim, Ah Ra; Kim, Seon Wook; Lee, Ba-Wool; Kim, Kuk-Hwa; Kim, Woong‐Hee; Seok, Hong; Lee, Jihyung; Um, JungIn; Yim, Soon‐Ho; Ahn, Youngkeun; Jin, Suk‐Won; Jung, Dawoon; Oh, Won Keun; Williams, Darren R.

doi:10.1038/s41598-020-61491-4

Cited by 10 publications

(5 citation statements)

References 67 publications

(56 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…So, the anti-inflammatory effects alone may not be sufficient to address all of the efficacy of YH23537 in this model. YH23537 has various biologically known or unknown active compounds which result in anti-inflammatory, antimicrobial, tissue-regenerating, and antioxidative stress effects [ 27 , 30 , 31 , 33 , 37 , 38 ]. For example, ginsenoside Rg1 was found to stimulate the proliferation and differentiation of human periodontal ligament cells [ 39 ] while grape seed extracts, green tea extracts, and horse chestnut leaf extracts, containing various active compounds, have demonstrated to alleviate experimental periodontitis [ 40 – 42 ].…”

Section: Discussionmentioning

confidence: 99%

Novel Herbal Therapeutic YH23537 Improves Clinical Parameters in Ligature-Induced Periodontal Disease Model in Beagle Dogs

Shin

Lee

Noh

et al. 2023

International Journal of Dentistry

View full text Add to dashboard Cite

Currently, available medicine does not satisfy the clinical unmet needs of periodontal disease. Therefore, novel drugs with improved efficacy profiles are needed. We previously demonstrated that YH14642, water extracts of Notoginseng Radix and Rehmanniae Radix Preparata, improved probing depths in double-blind phase II clinical trial. However, it still has hurdles for commercialization due to the low efficiency of active compound extraction. To resolve this issue, we developed YH23537 through process optimization to extract active compounds efficiently while still achieving the chemical profile of YH14642. In this study, we investigated the therapeutic effects of YH23537 compared with YH14642 using a canine model of ligature-induced periodontitis. Human gingival fibroblast (hGF) cells were treated with various concentrations of YH23537 or YH14642 with lipopolysaccharide (LPS) for 24 hr. IL-6 and IL-8 levels in the conditioned media were determined using Luminex. Sixteen 3-year-old male beagle dogs had their teeth scaled and polished using a piezo-type ultrasonic scaler under general anesthesia and brushed once daily for the following 2 weeks. Two weeks after the scaling procedure, the left upper second premolar (PM2), third premolar (PM3), and fourth premolar (PM4) as well as the left lower PM3, PM4, and first molar (M1) were ligated with silk-wire twisted ligatures. The dogs were fed with soft moistened food to induce periodontitis for 8 weeks, and the ligatures were then removed. YH23537 and YH14642 were administered for 4 weeks, and clinical periodontal parameters such as plaque index (PI), gingival index (GI), probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BoP) were determined before and 1, 2, 3, and 4 weeks after treatment. YH23537 inhibited IL-6 and IL-8 secretion in a dose-dependent manner in hGF cells stimulated with LPS. The IC50 values for YH23537 were 43 and 54 μg/ml for IL-6 and IL-8, respectively, while the values for YH14642 were 104 and 117 μg/ml, respectively. In the animal study, clinical parameters including GI, PD, CAL, and BoP were significantly increased after 8 weeks of ligature-induced periodontitis. The YH23537 300 and YH23537 900 mg groups had significant improvements in CAL from 1 to 4 weeks after treatment in comparison to the placebo group. GR values in the YH23537 900 mg group were decreased throughout the treatment period. GI values were also reduced significantly after 4-week treatment with 300 and 900 mg of YH23537. YH23537 at 300 mg doses showed comparable efficacy for CAL and GR with 1,000 mg of YH14642. YH23537 showed therapeutic efficacy against periodontitis in dogs, mediated by anti-inflammatory effects. These findings indicate that YH23537 has the potential for further development as a new drug for patients suffering from periodontal disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Novel Herbal Therapeutic YH23537 Improves Clinical Parameters in Ligature-Induced Periodontal Disease Model in Beagle Dogs

Shin

Lee

Noh

et al. 2023

International Journal of Dentistry

View full text Add to dashboard Cite

show abstract

“…In a rat model of acute MI it was also observed how the continuous application of Rg1 enhances the number of peripheral blood CD34 + stem cells and stimulates the homing of stem cells to the infarcted area, leading to ventricular remodeling with reduction of infarct size and significant myocardial regeneration [ 243 ]. A detailed study recently published in Nature has identified the 20(R)-ginsenoside Rh 2 among several ginseng saponins, capable of increasing the proliferation of skeletal myoblasts in vitro [ 244 ]. The molecular mechanism underlying this important effect was identified in the activation of Akt signaling and in the inhibition of the cyclin-dependent kinases inhibitors (CDKIs), p27 Kip1 and p57 Kip2 which negatively regulate cell proliferation.…”

Section: Natural Compounds and Stem Cells Activation And Differentmentioning

confidence: 99%

“…Additionally, in the animal model of barium chloride-induced skeletal muscle degeneration, treatment with ginsenoside Rh 2 leads to a reduction in muscle scarring and fewer inflammatory cells. These features are associated with reduced tissue degeneration and a greater proportion of smaller diameter fibers, which increase in diameter as the muscle heals [ 244 ].…”

Section: Natural Compounds and Stem Cells Activation And Differentmentioning

confidence: 99%

The Potential Properties of Natural Compounds in Cardiac Stem Cell Activation: Their Role in Myocardial Regeneration

et al. 2021

View full text Add to dashboard Cite

Cardiovascular diseases (CVDs), which include congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, and many other cardiac disorders, cause about 30% of deaths globally; representing one of the main health problems worldwide. Among CVDs, ischemic heart diseases (IHDs) are one of the major causes of morbidity and mortality in the world. The onset of IHDs is essentially due to an unbalance between the metabolic demands of the myocardium and its supply of oxygen and nutrients, coupled with a low regenerative capacity of the heart, which leads to great cardiomyocyte (CM) loss; promoting heart failure (HF) and myocardial infarction (MI). To date, the first strategy recommended to avoid IHDs is prevention in order to reduce the underlying risk factors. In the management of IHDs, traditional therapeutic options are widely used to improve symptoms, attenuate adverse cardiac remodeling, and reduce early mortality rate. However, there are no available treatments that aim to improve cardiac performance by replacing the irreversible damaged cardiomyocytes (CMs). Currently, heart transplantation is the only treatment being carried out for irreversibly damaged CMs. Hence, the discovery of new therapeutic options seems to be necessary. Interestingly, recent experimental evidence suggests that regenerative stem cell medicine could be a useful therapeutic approach to counteract cardiac damage and promote tissue regeneration. To this end, researchers are tasked with answering one main question: how can myocardial regeneration be stimulated? In this regard, natural compounds from plant extracts seem to play a particularly promising role. The present review will summarize the recent advances in our knowledge of stem cell therapy in the management of CVDs; focusing on the main properties and potential mechanisms of natural compounds in stimulating and activating stem cells for myocardial regeneration.

show abstract

“…Cell culture was carried out as previously described 19,20 . C2C12 murine skeletal muscle precursor cells (myoblasts) were purchased from Koram Biotech Corp., Seoul, Republic of Korea, and maintained in growth media (GM), consisting of Dulbecco's Modi ed Eagle's Medium (DMEM) supplemented with 10% fetal bovine serum (FBS), 50 units/mL penicillin and 50 mg/mL streptomycin (PenStrep).…”

Section: Cell Culturementioning

confidence: 99%

“…The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetra -zolium bromide (MTT) assay was used for analyzing cell proliferation as previously described 19,22 . Myoblasts were seeded in a 96-well plate at a density of 1.5x10 3 cells per well.…”

Section: Mtt Assay For Cell Proliferationmentioning

confidence: 99%

Glycogen Synthase Kinase-3β Inhibitor Lithium Chloride Protects Against Inflammation-Mediated Skeletal Muscle Wasting

Lee

Kim

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Inflammation-mediated skeletal muscle wasting is induced by inflammatory cytokines. It occurs in critically ill patients with sepsis (termed intensive care unit acquired weakness) and patients with advanced metastasis (termed cancer cachexia). Both conditions severely impact on patient morbidity and mortality. Lithium chloride has been investigated as a drug repurposing candidate for numerous diseases. In this study, we assessed whether lithium chloride affects inflammation-mediated muscle wasting, using in vitro and in vivo models of cancer cachexia and sepsis. Lithium chloride prevented wasting in myotubes cultured with cancer cell conditioned media, maintained expression of the muscle fiber contractile protein, myosin heavy chain 2 and blocked upregulation of the E3 ubiquitin ligase, Atrogin-1. Glycogen synthase kinase-3β inhibition was indicated as the target mechanism, due to the following observations: 1) β-catenin was upregulated in the myotubes and 2) inhibition of IMPA1, the secondary biological target of lithium chloride, did not inhibit the effects of cancer conditioned media. Lithium chloride inhibited upregulation of the inflammation-associated cytokines Il-1β, Il-6 and inos in macrophages treated with lipopolysaccharide. Lithium chloride treatment in an animal model of sepsis improved body weight, increased muscle mass, preserved the survival of larger fibers and decreased expression of the wasting effector genes, Atrogin-1 and Murf-1. In a model of cancer cachexia, lithium chloride increased muscle mass, enhanced muscle strength and increased fiber cross sectional area, with no significant effect on tumorigenesis. These results indicate that lithium chloride could be repurposed as a drug to treat patients with inflammation-mediated skeletal muscle wasting.

show abstract

Screening ginseng saponins in progenitor cells identifies 20(R)-ginsenoside Rh2 as an enhancer of skeletal and cardiac muscle regeneration

Abstract: 48 hpf. EdU staining and confocal microscopy assessment indicated that CPP531 treatment enhanced cardiomyocyte proliferation in the zebrafish (Fig. 4F).

Cited by 10 publications

References 67 publications

Novel Herbal Therapeutic YH23537 Improves Clinical Parameters in Ligature-Induced Periodontal Disease Model in Beagle Dogs

Novel Herbal Therapeutic YH23537 Improves Clinical Parameters in Ligature-Induced Periodontal Disease Model in Beagle Dogs

The Potential Properties of Natural Compounds in Cardiac Stem Cell Activation: Their Role in Myocardial Regeneration

Glycogen Synthase Kinase-3β Inhibitor Lithium Chloride Protects Against Inflammation-Mediated Skeletal Muscle Wasting

Contact Info

Product

Resources

About