PMID: 

J Ginseng Res. 2019 Oct ;43(4):618-624. Epub 2018 Aug 30. PMID: 31695568

Abstract Title: 

Studies of the effects and mechanisms of ginsenoside Re and Rkon myelosuppression induced by cyclophosphamide.

Abstract: 

Background: Ginsenoside Re (Re) is one of the major components ofMeyer. Ginsenoside Rk(Rk) is a secondary metabolite of Re. The aim of this study was to investigate and compare the effects and underlying mechanisms of Re and Rkon cyclophosphamide-induced myelosuppression.Methods: The mice myelosuppression model was established by intraperitoneal (i.p.) injection of cyclophosphamide. Peripheral blood cells, bone marrow nucleated cells, and colony yield of hematopoietic progenitor cellswere counted. The levels of erythropoietin, thrombopoietin, and granulocyte macrophage colony-stimulating factor in plasma were measured by enzyme-linked immunosorbent assay. Bone marrow cell cycle was performed by flow cytometry. The expression of apoptotic protein bcl-2, bax, and caspase-3 was detected by Western blotting.Results: Both Re and Rkcould improve peripheral blood cells, bone marrow nucleated cell counts, thymus index, and spleen index. Furthermore, they could enhance the yield of colonies culturedand make the levels of granulocyte macrophage colony-stimulating factor, erythropoietin, and thrombopoietin normal, reduce the ratio of G/Gphase cells, and increase the proliferation index. Finally, Re and Rkcould upregulate the expression of bcl-2, whereas they could downregulate the expression of bax and caspase-3.Conclusion: Re and Rkcould improve the hematopoietic function of myelosuppressed mice. The effect of Rkwas superior to that of Re at any dose. Regulating the levels of cytokines, promoting cells enter the normal cell cycle, regulating the balance of bcl-2/bax, and inhibiting the expression of caspase-3 may be the effects of Re and Rkon myelosuppression.

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PMID: 

J Ginseng Res. 2019 Oct ;43(4):635-644. Epub 2019 Mar 7. PMID: 31695569

Abstract Title: 

Fermented red ginseng and ginsenoside Rd alleviate ovalbumin-induced allergic rhinitis in mice by suppressing IgE, interleukin-4, and interleukin-5 expression.

Abstract: 

Background: To increase the pharmacological effects of red ginseng (RG, the steamed root ofMeyer), RG products modified by heat process or fermentation have been developed. However, the antiallergic effects of RG and modified/fermented RG have not been simultaneously examined. Therefore, we examined the allergic rhinitis (AR)-inhibitory effects of water-extracted RG (wRG), 50% ethanol-extracted RG (eRG), and bifidobacteria-fermented eRG (fRG) in vivo.Methods: RBL-2H3 cells were stimulated with phorbol 12-myristate-13-acetate/A23187. Mice with AR were prepared by treatment with ovalbumin. Allergic markers IgE, tumor necrosis factor-α, interleukin (IL)-4, and IL-5 were assayed in the blood, bronchoalveolar lavage fluid, nasal mucosa, and colon using enzyme-linked immunosorbent assay. Mast cells, eosinophils, and Th2 cell populations were assayed using a flow cytometer.Results: RG products potently inhibited IL-4 expression in phorbol 12-myristate-13-acetate/A23187-stimulated RBL-2H3 cells. Of tested RG products, fRG most potently inhibited IL-4 expression. RG products also alleviated ovalbumin-induced AR in mice. Of these, fRG most potently reduced nasal allergy symptoms and blood IgE levels. fRG treatment also reduced IL-4 and IL-5 levels in bronchoalveolar lavage fluid, nasal mucosa, and reduced mast cells, eosinophils, and Th2 cell populations. Furthermore, treatment with fRG reduced IL-4, IL-5, and IL-13 levels in the colon and restored ovalbumin-suppressed Bacteroidetes and Actinobacteria populations and ovalbumin-induced Firmicutes population in gut microbiota. Treatment with ginsenoside Rd significantly alleviated ovalbumin-induced AR in mice.Conclusion: fRG and ginsenoside Rd may alleviate AR by suppressing IgE, IL-4, IL-5, and IL-13 expression and restoring the composition of gut microbiota.

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PMID: 

Life Sci. 2019 Dec 15 ;239:117083. Epub 2019 Nov 20. PMID: 31759043

Abstract Title: 

Analgesic effect and related amino acids regulation of ginsenoside Rg3 in mouse pain models.

Abstract: 

AIMS: The present study aims to evaluate the analgesic effect of ginsenoside Rg3 in different mouse pain models.MAIN METHODS: Formalin-, carrageenan- and S180 tumor cells induced mouse pain models were built in the study. The licking and biting time and PEG2 contents in the inflammatory sites were measured. The excitatory and inhibitory amino acids in the brains were determined by pre-column derivation FLD-HPLC method.KEY FINDING: We have found that ginsenoside Rg3 treated the pain phases and decreased the PGE2 in formalin and carrageenan induced models, respectively. It significantly increased the contents of EAAs (Asp and Glu) in the brains of S180 tumor inducing pain mice, meanwhile, the IAAs (Gly, Tau and GABA) decreased.SIGNIFICANCE: Our results revealed that ginsenoside Rg3 acted central and peripheral analgesic effect and regulated the inflammatory factors and pain-related amino acids. It could re-balance the abnormal EAAs/IAAs value when the pain occurred. The analgesic mechanism and the clinical application of ginsenoside Rg3 need be evaluated furtherly.

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PMID: 

Biochem Biophys Res Commun. 2019 Nov 23. Epub 2019 Nov 23. PMID: 31771882

Abstract Title: 

Ginsenoside Rh2 induces DNA damage and autophagy in vestibular schwannoma is dependent of LAMP2 transcriptional suppression.

Abstract: 

Ginsenoside Rh2 (G-Rh2), a component of ginseng extraction, exerted anti-tumor property in the occurrence and progress of human tumors. Vestibular schwannoma (VS) is a kind of benign tumor. Extraction of traditional Chinese herb has been applied to treat VS as adjuvant therapy. Nevertheless, G-Rh2-related molecular mechanisms in VS progress are not yet clear. The purpose of current study is to unveil the function and potential molecular mechanism of Rh2 in VS cellular functions. At first, the viability and apoptosis of VS cells treated with different concentrations of Rh2 were assessed. Autophagy and DNA damage response can be induced by multiple drugs. Here, we observed the changes of autophagy and DNA damage in Rh2-induced VS cells. Based on the experimental data, treatment with Rh2 contributed to cell apoptosis by inducing DNA damage and suppressing DNA damage. LAMP2 (lysosomal associated membrane protein 2), an autophagy inducer, was downregulated in Rh2-treated VS cells. Through mechanism study, we determined that Rh2 led to the transcriptional inactivation of LAMP2 by downregulating its transcription activator NR2F2 (nuclear receptor subfamily 2 group F member 2). In addition, NR2F2 overexpression recovered the role of Rh2 in cell functions, which was further rescued by the silence of LAMP2. Collectively, our study unveiled a novel NR2F2/LAMP2 axis in Rh2-mediated VS cells, which potentially contributes to the therapy for VS.

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PMID: 

J BUON. 2019 Sep-Oct;24(5):2056-2061. PMID: 31786875

Abstract Title: 

Targeted antitumor activity of Ginsenoside (Rg1) in paclitaxel-resistant human nasopharyngeal cancer cells are mediated through activation of autophagic cell death, cell apoptosis, endogenous ROS production

Abstract: 

PURPOSE: Nasopharyngeal carcinoma is one of common and vicious cancers of head and neck. The main purpose of this study was to examine the anticancer effects of the naturally occurring compound Ginsenoside (Rg1) against paclitaxel-resistant human nasopharyngeal cancer cells along with evaluation of its effects on cell autophagy, apoptosis, ROS production, cell cycle progression and m-TOR/PI3K/AKT signalling pathway.METHODS: The viability of SUNE1 cancer cell line and NP460 normal cell line was checked by CCK8 counting assay. Apoptosis-related studies were examined by fluorescent microscopy using acridine orange (AO)/ethidium bromide (EB) staining as well as flow cytometry using annexin V assay. Further, transmission electron microscopy (TEM) was used to study autophagic effects induced by Ginsenoside (Rg1). Western blot assay was used to study the effects of Ginsenoside on apoptosis and on autophagy-related protein expressions including Bax, Bcl-2, LC3-ll.RESULTS: The results indicated that Ginsenoside (Rg1) reduces the viability of the nasopharyngeal carcinoma cells in a dose-dependent manner, showing IC50 of 15µM in cancer cells and IC50 of 80 µM in normal cell lines. The AO/EB staining showed that Ginsenoside (Rg1) inhibits the viability of cancer cells via induction of apoptotic cell death which was correlated with increase in Bax and decrease in Bcl-2 levels. Electron microscopic analysis showed thatGinsenoside (Rg1) caused the development of autophagosomes in cancer cells. Similarly, Ginsenoside (Rg1) increased the expression of LC3-II protein, indicating autophagic cell death. Ginsenoside (Rg1) also induced dose-dependent S phase cell cycle arrest. Western blot analysis showed that Ginsenoside (Rg1) has the potential to block m-TOR/PI3K/AKT signalling pathway.CONCLUSIONS: In conclusion, the results of this study clearly indicate that Ginsenoside (Rg1) could be developed as a potent candidate drug against nasopharyngeal cancer provided further in vivo studies as well as toxicological studies are carried out.

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PMID: 

Nanomedicine (Lond). 2020 Jan ;15(1):41-54. PMID: 31868113

Abstract Title: 

A cocktail of betulinic acid, parthenolide, honokiol and ginsenoside Rh2 in liposome systems for lung cancer treatment.

Abstract: 

Lung cancer has a very high incidence rate, and thus, there is an urgent need for novel and effective therapies.In this study, we proposed a potential treatment option by combining four natural products in liposome systems.studies indicated that the combination of betulinic acid, parthenolide, honokiol and ginsenoside Rh2 exhibited a synergistic action. When these four natural products were loaded into liposome systems, we observed an increased effect. The relative action was also observed. The cisplatin group presented obvious kidney damage, whereas both cocktail therapy and cocktail liposome therapy were safer.Therefore, we propose cocktail liposome systems may provide a more efficient and safer treatment for lung cancer.

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PMID: 

Small. 2019 Dec 9:e1905233. Epub 2019 Dec 9. PMID: 31814271

Abstract Title: 

Nanoparticle Conjugation of Ginsenoside Rg3 Inhibits Hepatocellular Carcinoma Development and Metastasis.

Abstract: 

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. The prognosis of HCC remains very poor; thus, an effective treatment remains urgent. Herein, a type of nanomedicine is developed by conjugating Fe@FeOnanoparticles with ginsenoside Rg3 (NpRg3), which achieves an excellent coupling effect. In the dimethylnitrosamine-induced HCC model, NpRg3 application significantly prolongs the survival of HCC mice. Further research indicates that NpRg3 application significantly inhibits HCC development and eliminates HCC metastasis to the lung. Notably, NpRg3 application delays HCC-induced ileocecal morphology and gut microbial alterations more than 12 weeks during HCC progression. NpRg3 administration elevates the abundance of Bacteroidetes and Verrucomicrobia, but decreases Firmicutes. Twenty-nine predicted microbial gene functions are enriched, while seven gene functions are reduced after NpRg3 administration. Moreover, the metabolomics profile presents a significant progression during HCC development, but NpRg3 administration corrects tumor-dominant metabolomics. NpRg3 administration decreases 3-indolepropionic acid and urea, but elevates free fatty acids. Importantly, NpRg3 application remodels the unbalanced correlation networks between gut microbiota and metabolism during HCC therapy. In conclusion, nanoparticle conjugation of ginsenoside Rg3 inhibits HCC development and metastasis via the remodeling of unbalanced gut microbiota and metabolism in vivo, providing an antitumor therapy strategy.

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PMID: 

Anticancer Agents Med Chem. 2019 Dec 8. Epub 2019 Dec 8. PMID: 31814556

Abstract Title: 

Ginsenoside Rh2 improves the cisplatin anti-tumor effect in lung adenocarcinoma A549 cells via superoxide and PD-L1.

Abstract: 

BACKGROUND: Ginsenoside Rh2 (Rh2) is a major biological component of ginseng that exerts anti-tumor activities in multiply cancers including Non-Small Cell Lung Cancers (NSCLCs). Rh2 also enhance the anti-tumor effects of various chemotherapy drugs including cisplatin at relatively low concentrations. Here, the mechanistic role of Rh2 in chemotherapy-treated NSCLCs will be investigated.METHODS: In this study, FACS, western blot and siRNA addition were used to analyze the role of Rh2 in cisplatin-treated lung adenocarcinoma A549 and H1299 cells.RESULTS: Subsequent observations indicated that Rh2 enhanced cisplatin-induced NSCLCs A549 and H1299 cells apoptosis. Cisplatin-induced productive autophagy was repressed by Rh2 in A549 cells. Rh2 also enhanced cisplatin cytotoxicity by elevating superoxide dismutase activity and repressing cisplatin-induced superoxide generation. Conversely, Rh2 was found to repress cisplatin-induced phosphorylation of epidermal growth factor receptor, phosphoinositide 3-kinase, protein kinase B, and autophagy. Cisplatin-induced Programmed Death-Ligand 1 (PD-L1) expression was repressed by Rh2 via the superoxide.CONCLUSION: These findings suggest that Rh2 enhanced the function of cisplatin by repressing superoxide generation, PD-L1 expression, and autophagy in lung adenocarcinoma cells.

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PMID: 

Int J Mol Sci. 2019 Dec 4 ;20(24). Epub 2019 Dec 4. PMID: 31817146

Abstract Title: 

Ginsenoside Rh2 Ameliorates Atopic Dermatitis in NC/Nga Mice by Suppressing NF-kappaB-Mediated Thymic Stromal Lymphopoietin Expression and T Helper Type 2 Differentiation.

Abstract: 

Ginsenosides are known to have various highly pharmacological activities, such as anti-cancer and anti-inflammatory effects. However, the search for the most effective ginsenosides against the pathogenesis of atopic dermatitis (AD) and the study of the effects of ginsenosides on specific cytokines involved in AD remain unclear. In this study, ginsenoside Rh2 was shown to exert the most effective anti-inflammatory action on thymic stromal lymphopoietin (TSLP) and interleukin 8 in tumor necrosis factor-alpha and polyinosinic: polycytidylic acid induced normal human keratinocytes by inhibiting proinflammatory cytokines at both protein and transcriptional levels. Concomitantly, Rh2 also efficiently alleviated 2,4-dinitrochlorobenzene-induced AD-like skin symptoms when applied topically, including suppression of immune cell infiltration, cytokine expression, and serum immunoglobulin E levels in NC/Nga mice. In line with the in vitro results, Rh2 inhibited TSLP levels in AD mice via regulation of an underlying mechanism involving the nuclear factorκB pathways. In addition, in regard to immune cells, we showed that Rh2 suppressed not only the expression of TSLP but the differentiation of naïve CD4+ T-cells into T helper type 2 cells and their effector function in vitro. Collectively, our results indicated that Rh2 might be considered as a good therapeutic candidate for the alternative treatment of AD.

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CBD has gone from what seemed like a passing wellness trend to a legitimate product with incredible health benefits for millions. The industry could reach an estimated worth of $20 billion by 2024.

CBD shows no signs of slowing down. With new products and creative consumption methods popping up daily, the possibilities and benefits of CBD are endless. Industries like cosmetics, health products, skin care, and pharmaceuticals have seen the largest amount of growth, but more industries are using CBD in their products every year.

Here are a few industry expert-predicted trends for CBD in 2020.

Changing attitudes and more information

The legal aspect of CBD transformed throughout 2018 and is continuing to evolve today. This change and the CBD boom started at the end of 2018 when the Farm Bill was signed into law that decriminalized CBD oil on a federal level by redefining it as an agricultural product instead of a drug.

These changes and the increase of CBD has not been without some hiccups. Law enforcement agencies have had to familiarize themselves with CBD and laws that differ from state to state. This has led to arrests at airports where travelers are not aware of the laws.

After these arrests and the improved attitudes towards CBD, The TSA has stated on their websites that CBD oil is allowed on planes.

The FDA is also starting to come around and held recently held a public hearing to “determine whether the agency should rethink its stance on CBD oil.”

These changes will allow more people to use CBD with legal consequences.

More CBD-Enhanced Products

Other industries are jumping on the trend and adding CBD to their products.

The cosmetics industry has done this successfully with industry giants Sephora and Ulta now selling CDB products.

CBD is also starting to show up in our favorite beverages. Several breweries are brewing CBD-infused beers and corner coffee shops around the country are adding the cannabinoid to lattes and smoothies.

In 2020, look for more CBD-infused beverages like waters and seltzers.

More Studies

Until recently, there were only a few medical studies focusing on CBD. This lack of evidence led many away from using CBD feeling the product was the modern equivalent to a snake oil. With many proclaiming the health benefits of CBD, the medical community has started to notice.

The first comprehensive study on CBD explored the benefits of CBD in epilepsy patients. This year, more evidence came to light that CBD is an effective method in controlling seizures. One study found that children taking a 20mg dose of CBD daily experienced a 46% decrease in convulsive seizures.

Customer demographics

CBD has bridged the generation gap between baby boomers and millennials. Both generations make up a large part of the CBD customer base. A study conducted by Chicago firm CBD Marketing examined how baby boomers, Gen X and millennials discuss their experiences with CBD online.

CBD Marketing’s study analyzed 1.3 million U.S. social media posts and other public comments for the period Jan. 1, 2018 to Jan. 1, 2019. Monthly conversations about CBD oil increased steadily over this period and were generated about equally by men (48%) and women (52%).

Baby boomers (ages 54 to 72) and millennials (ages 22 to 37) each generated 41% of the posts, while Gen Xers (ages 38 to 53) represented 18%. Tracked conversations appeared on Twitter, Tumblr, YouTube, Instagram, blogs and forums. Facebook privacy regulations for personal accounts prevented its inclusion.

The conversations from all generations in the study focused on pain management, mental health, beauty, skincare, and pet care.

Understanding consumer demographics and their wants allows for CBD companies to focus their marketing efforts.